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Schwartz GG, Szarek M, Jukema JW, Cobbaert CM, Reijnders E, Bittner VA, Schwertfeger M, Bhatt DL, Fazio S, Garon G, Goodman SG, Harrington RA, White HD, Steg PG. Risk of Incident Diabetes Related to Lipoprotein(a), LDL Cholesterol, and Their Changes With Alirocumab: Post Hoc Analyses of the ODYSSEY OUTCOMES Randomized Trial. Diabetes Care 2025; 48:596-604. [PMID: 39913634 PMCID: PMC11932820 DOI: 10.2337/dc24-2110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 01/13/2025] [Indexed: 03/23/2025]
Abstract
OBJECTIVE Previous genetic and clinical analyses have associated lower lipoprotein(a) and LDL cholesterol (LDL-C) with greater risk of new-onset type 2 diabetes (NOD). However, PCSK9 inhibitors such as alirocumab lower both lipoprotein(a) and LDL-C without effect on NOD. RESEARCH DESIGN AND METHODS In a post hoc analysis of the ODYSSEY OUTCOMES trial (NCT01663402), we examined the joint prediction of NOD by baseline lipoprotein(a), LDL-C, and insulin (or HOMA-insulin resistance [HOMA-IR]) and their changes with alirocumab treatment. Analyses included 8,107 patients with recent acute coronary syndrome on optimized statin therapy, without diabetes at baseline, assigned to alirocumab or placebo with median follow-up 2.4 years. Splines were estimated from logistic regression models. RESULTS Lower baseline lipoprotein(a) and higher baseline insulin or HOMA-IR independently predicted 782 cases of NOD; baseline LDL-C did not predict NOD. Alirocumab reduced lipoprotein(a) and LDL-C without affecting insulin or NOD risk (odds ratio [OR] vs. placebo 0.998; 95% CI 0.860-1.158). However, in logistic regression, decreased lipoprotein(a) and LDL-C on alirocumab were independent, opposite predictors of NOD. OR for NOD for 25% and 50% lipoprotein(a) reductions on alirocumab were 1.12 (95% CI 1.01-1.23) and 1.24 (1.02-1.52). OR for NOD for 25% and 50% LDL-C reductions on alirocumab were 0.88 (95% CI 0.80-0.97) and 0.77 (0.64-0.94). CONCLUSIONS Baseline lipoprotein(a) was inversely associated with risk of NOD. Alirocumab-induced reductions of lipoprotein(a) and LDL-C were associated with increased and decreased risk of NOD, respectively, without net effect on NOD. Ongoing trials will determine the impact of larger and longer lipoprotein(a) reductions on NOD.
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Affiliation(s)
- Gregory G. Schwartz
- Division of Cardiology, University of Colorado School of Medicine, Aurora, CO
| | - Michael Szarek
- Division of Cardiology, University of Colorado School of Medicine, Aurora, CO
- CPC Clinical Research, Aurora, CO
- State University of New York Downstate Health Sciences University, Brooklyn, NY
| | - J. Wouter Jukema
- Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands
- Netherlands Heart Institute, Utrecht, the Netherlands
| | - Christa M. Cobbaert
- Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands
| | - Esther Reijnders
- Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands
| | - Vera A. Bittner
- Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL
| | | | - Deepak L. Bhatt
- Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY
| | | | | | - Shaun G. Goodman
- Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada
- St. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada
| | | | - Harvey D. White
- Green Lane Cardiovascular Research Unit, Te Whatu Ora–Health New Zealand and University of Auckland, Te Toka Tumai, New Zealand
| | - Philippe Gabriel Steg
- Université Paris-Cité, INSERM-UMR1148, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, French Alliance for Cardiovascular Trials, Institut Universitaire de France, Paris, France
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Avogaro A, Buzzetti R, Candido R, Cosmo SD, Notarianni L, Consolo E, Luciano M. Exploring the benefits of alirocumab as lipid-lowering therapy in people with diabetes and very high cardiovascular risk. Diabetes Res Clin Pract 2025; 222:112055. [PMID: 40020784 DOI: 10.1016/j.diabres.2025.112055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 02/07/2025] [Accepted: 02/17/2025] [Indexed: 03/03/2025]
Abstract
People with diabetes mellitus (DM) are at a higher risk (2-4 times) for cardiovascular (CV) death and atherosclerotic CV disease (ASCVD) than the general population. A multifactorial approach is recommended to reduce CV risk. Since low-density lipoprotein cholesterol (LDL-C) is a major causal and cumulative risk factor for ASCVD, the management of lipids is a fundamental element in global risk reduction. Intensive lipid lowering therapy (LLT), such as the addition of a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i), to achieve LDL-C goals and reduce the risk of first or recurrent CV events in people with DM at very high CV risk (VHCVR) of ASCVD (i.e. acute coronary syndrome, coronary artery disease, peripheral artery disease) is often required. Alirocumab, a monoclonal antibody against PCSK9, as lipid-lowering therapy offers significant CV benefits and a favourable safety profile in people with DM and a VHCVR, with or without previous CV events. This review highlights the role of LDL-C in the complex pathogenesis of atherosclerosis, summarises the guidelines for CV risk reduction related to LDL-C in patients with DM and a VHCVR, and focuses on the role of alirocumab in managing LDL-C and consequent CV risk reduction in these patients.
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Affiliation(s)
- Angelo Avogaro
- Department of Medicine, Section of Diabetes and Metabolic Diseases, University of Padua Metabolic Diseases Division, University Hospital of Padova, Padua, Italy.
| | - Raffaella Buzzetti
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Riccardo Candido
- Diabetes Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Trieste, Italy
| | - Salvatore De Cosmo
- Department of Medical Sciences, Unit of Internal Medicine, IRCCS "Casa Sollievo della Sofferenza" San Giovanni Rotondo (FG), Italy
| | | | | | - Myriam Luciano
- Medical and Scientific Department, Sanofi S.r.l., Milan, Italy
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Banach M, Jaiswal V, Ang SP, Sawhney A, Deb N, Amarenco P, Gaita D, Reiner Z, Pećin I, Lavie CJ, Penson PE, Toth PP. Impact of Lipid-Lowering Combination Therapy With Statins and Ezetimibe vs Statin Monotherapy on the Reduction of Cardiovascular Outcomes: A Meta-analysis. Mayo Clin Proc 2025:S0025-6196(25)00075-8. [PMID: 40126455 DOI: 10.1016/j.mayocp.2025.01.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 01/06/2025] [Accepted: 01/28/2025] [Indexed: 03/25/2025]
Abstract
OBJECTIVE To evaluate the efficacy of combination lipid-lowering therapy (LLT) compared with statin monotherapy for low-density lipoprotein cholesterol (LDL-C) reduction, associated adverse events, and outcomes. METHODS A systematic literature search was conducted using PubMed, Embase, and ClinicalTrials.gov to identify relevant articles published from inception until the end of June 2024. The outcomes were assessed using pooled odds ratios (ORs) for categorical data and mean difference for continuous data, with corresponding 95% CIs. RESULTS A total of 14 studies (11 randomized controlled trials and 3 cohort studies) with 108,373 very high-risk patients were included in the final analysis. The mean age of the patients in the combination LLT group and the statin monotherapy group was 67.31 and 67.89 years, respectively. Pooled analysis revealed that combination LLT significantly more effectively reduced the LDL-C level from baseline (mean difference, -12.96 mg/dL; 95% CI, -17.27 to -8.65; P<.001) and significantly reduced all-cause mortality (OR, 0.81; 95% CI, 0.67 to 0.97; P=.02), major adverse cardiovascular events (OR, 0.82; 95% CI, 0.69 to 0.97; P=.02), and stroke incidence (OR, 0.83; 95% CI, 0.75 to 0.91; P<.001), with an insignificant effect on cardiovascular mortality (OR, 0.86; 95% CI, 0.65 to 1.12; P=.26) when compared with statin monotherapy. The risk of adverse events and the therapy discontinuation rate were comparable between groups. CONCLUSION Combination LLT was associated with an overall greater reduction in LDL-C, the same risk of adverse effects, and significantly lower risk of all-cause mortality, major adverse cardiovascular events, and stroke compared with statin monotherapy. Forthcoming guidelines should consider the lipid-lowering combination therapy as early as possible, preferably up-front, for more effective LDL-C goal achievement and significant reduction of cardiovascular disease outcomes and mortality in high- and very high-risk patients.
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Affiliation(s)
- Maciej Banach
- Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Lodz, Poland; Faculty of Medicine, John Paul II Catholic University of Lublin, Lublin, Poland; Department of Cardiology and Adult Congenital Heart Diseases, Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland; Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD; Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool, UK.
| | - Vikash Jaiswal
- Department of Cardiovascular Research, Larkin Community Hospital, South Miami, FL
| | - Song Peng Ang
- Department of Internal Medicine, Rutgers Health/Community Medical Center, Toms River, NJ
| | - Aanchal Sawhney
- Department of Internal Medicine, Crozer-Chester Medical Center, Upland, PA
| | - Novonil Deb
- North Bengal Medical College, West Bengal, India
| | - Pierre Amarenco
- Department of Neurology and Stroke Center, Bichat University Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France
| | - Dan Gaita
- Institute for Cardiovascular Diseases, Research Center IBCVTIM, Timisoara, Romania
| | - Zeljko Reiner
- Department of Cardiology and Adult Congenital Heart Diseases, Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland; University Hospital Center Zagreb, Zagreb, Croatia
| | - Ivan Pećin
- Department of Internal Medicine, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Carl J Lavie
- John Ochsner Heart and Vascular Institute, Ochsner Clinical School-University of Queensland School of Medicine, New Orleans, LA
| | - Peter E Penson
- School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University and Liverpool Centre for Cardiovascular Science, Liverpool, UK
| | - Peter P Toth
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Preventive Cardiology, CGH Medical Center, Sterling, IL
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Wang Y, Courcelles E, Peyronnet E, Porte S, Diatchenko A, Jacob E, Angoulvant D, Amarenco P, Boccara F, Cariou B, Mahé G, Steg PG, Bastien A, Portal L, Boissel JP, Granjeon-Noriot S, Bechet E. Credibility assessment of a mechanistic model of atherosclerosis to predict cardiovascular outcomes under lipid-lowering therapy. NPJ Digit Med 2025; 8:171. [PMID: 40108310 PMCID: PMC11923190 DOI: 10.1038/s41746-025-01557-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Accepted: 03/09/2025] [Indexed: 03/22/2025] Open
Abstract
Demonstrating cardiovascular (CV) benefits with lipid-lowering therapy (LLT) requires long-term randomized clinical trials (RCTs) with thousands of patients. Innovative approaches such as in silico trials applying a disease computational model to virtual patients receiving multiple treatments offer a complementary approach to rapidly generate comparative effectiveness data. A mechanistic computational model of atherosclerotic cardiovascular disease (ASCVD) was built from knowledge, describing lipoprotein homeostasis, LLT effects, and the progression of atherosclerotic plaques leading to myocardial infarction, ischemic stroke, major acute limb event and CV death. The ASCVD model was successfully calibrated and validated, and reproduced LLT effects observed in selected RCTs (ORION-10 and FOURIER for calibration; ORION-11, ODYSSEY-OUTCOMES and FOURIER-OLE for validation) on lipoproteins and ASCVD event incidence at both population and subgroup levels. This enables the future use of the model to conduct the SIRIUS programme, which intends to predict CV event reduction with inclisiran, an siRNA targeting hepatic PCSK9 mRNA.
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Affiliation(s)
| | | | | | | | | | | | - Denis Angoulvant
- Cardiology department, Hôpital Trousseau, CHRU de Tours & UMR Inserm 1327 ISCHEMIA "Membrane Signaling and Inflammation in Reperfusion Injuries" Université de Tours, F37000, Tours, France
| | - Pierre Amarenco
- Department of Neurology and Stroke center, APHP, Bichat Hospital, Université Paris-Cité, Paris, France and McMaster University, Population Health Research Institute, Hamilton, ON, Canada
| | - Franck Boccara
- Sorbonne Université, GRC n°22, C2MV-Complications Cardiovasculaires et Métaboliques chez les patients vivant avec le Virus de l'immunodéficience humaine, Inserm UMR_S 938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-métabolisme et Nutrition (ICAN), Cardiologie, Hôpital Saint Antoine AP-HP, Paris, France
| | - Bertrand Cariou
- Nantes Université, CHU Nantes, CNRS, Inserm, l'institut du thorax, F-44000, Nantes, France
| | - Guillaume Mahé
- Vascular Medicine Unit, CHU Rennes, Univ Rennes, CIC1414, M2S-EA 7470, Rennes, France
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Li CY, Wang WT, Ma SH, Lo LW, Wu CY, Chang WC, Chen YJ, Chen TL. Association of proprotein convertase subtilisin/kexin type-9 inhibitors with risk of nonmelanoma skin cancer: a retrospective cohort study. Br J Dermatol 2025; 192:697-705. [PMID: 39585798 DOI: 10.1093/bjd/ljae438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 11/03/2024] [Accepted: 11/03/2024] [Indexed: 11/27/2024]
Abstract
BACKGROUND Growing evidence has shown that cholesterol metabolism abnormalities involve carcinogenesis. Proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors have been reported to inhibit tumour progression and prevent ultraviolet-related skin damage. OBJECTIVES To investigate the association of PCSK9 inhibitors with the risk of nonmelanoma skin cancer (NMSC). METHODS This retrospective cohort study analysed data from the US Collaborative Network in the TriNetX database. Adults aged ≥ 40 years with atherosclerotic cardiovascular disease (ASCVD) under statin therapy between 2016 and 2022 were identified. A target trial design was used to compare the risk of NMSC, including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), in patients also treated with PCSK9 inhibitors or continuing statin treatment (the control group). Each head-to-head comparison involved propensity score matching. Hazard ratios (HRs) were estimated using Cox proportional hazard models. Stratified analyses based on age, sex, Fitzpatrick skin type and immune status were also performed. RESULTS A total of 73 636 patients with ASCVD were analysed. Compared with the control group, patients with ASCVD initiating PCSK9 inhibitors had lower risks of developing NMSC [HR 0.78, 95% confidence interval (CI) 0.71-0.87], BCC (HR 0.78, 95% CI 0.69-0.89) and cSCC (HR 0.79, 95% CI 0.67-0.93). Subanalyses revealed a reduced risk of NMSC with each PCSK9 inhibitor, namely evolocumab and alirocumab. Stratified analyses showed similar results in patients aged 65-79 years, those older than 80 years and in men. CONCLUSIONS Our study indicated that patients with ASCVD taking PCSK9 inhibitors have a lower risk of incident NMSC than those not taking PCSK9 inhibitors.
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Affiliation(s)
- Cheng-Yuan Li
- Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, National Yang Ming Chao Tung University, Taipei, Taiwan
- Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Wei-Ting Wang
- School of Medicine, National Yang Ming Chao Tung University, Taipei, Taiwan
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taiwan
| | - Sheng-Hsiang Ma
- Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, National Yang Ming Chao Tung University, Taipei, Taiwan
- Department of Public Health, Institute of Public Health, National Yang Ming Chao Tung University, Taipei, Taiwan
| | - Li-Wei Lo
- Cardiovascular Center, Department of Internal Medicine, Taipei Veterans General Hospital, Taiwan
- Institute of Clinical Medicine, and Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chen-Yi Wu
- Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, National Yang Ming Chao Tung University, Taipei, Taiwan
- Department of Public Health, Institute of Public Health, National Yang Ming Chao Tung University, Taipei, Taiwan
| | - Wei-Chuan Chang
- Epidemiology and Biostatistics Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Yi-Ju Chen
- Department of Dermatology, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Tai-Li Chen
- Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, National Yang Ming Chao Tung University, Taipei, Taiwan
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Da Dalt L, Baragetti A, Norata GD. Targeting PCSK9 beyond the liver: evidence from experimental and clinical studies. Expert Opin Ther Targets 2025; 29:137-157. [PMID: 40110803 DOI: 10.1080/14728222.2025.2482545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2024] [Revised: 03/06/2025] [Accepted: 03/18/2025] [Indexed: 03/22/2025]
Abstract
INTRODUCTION PCSK9 has been widely studied as a target for lipid-lowering as its inhibition increases LDLR recycling on the surface of hepatocytes, which promotes the catabolism of LDL particles. PCSK9 can be synthesized in extra-hepatic tissues, including in the brain, the pancreas, and the heart, and in immune cells. It is of interest to understand whether the extra-hepatic effects observed when PCSK9 is genetically inhibited by naturally occurring mutations are also recapitulated by pharmacology. AREA COVERED Genetics studies reported an increased risk of developing new-onset diabetes, ectopic adiposity, and reduced immune-inflammatory responses with PCSK9 deficiency. However, these aspects were not observed in clinical trials and data from real-world medicine with monoclonal antibodies (mAbs) and gene silencing approaches targeting PCSK9. EXPERT OPINION It is possible that the biological adaptations occurring when PCSK9 is inhibited lifelong, as in the case of genetic studies, could explain the discrepancy with the data obtained by clinical studies testing the pharmacological inhibition of PCSK9. Also, PCSK9 mAbs have been in use for 12 years; thus, probably, in this time window, a pharmacological reduction of circulating PCSK9 up to 80-90% does not lead to changes other than the impressive reduction in LDL-C and in CVD events.
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Affiliation(s)
- Lorenzo Da Dalt
- Department of Pharmacological Sciences 'Rodolfo Paoletti', University of Milan, Milano, Italy
| | - Andrea Baragetti
- Department of Pharmacological Sciences 'Rodolfo Paoletti', University of Milan, Milano, Italy
| | - Giuseppe Danilo Norata
- Department of Pharmacological Sciences 'Rodolfo Paoletti', University of Milan, Milano, Italy
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Moura FA, Kamanu FK, Wiviott SD, Giugliano RP, Udler MS, Florez JC, Ellinor PT, Sabatine MS, Ruff CT, Marston NA. Type 2 diabetes genetic risk and incident diabetes across diabetes risk enhancers. Diabetes Obes Metab 2025; 27:1287-1295. [PMID: 39696834 DOI: 10.1111/dom.16123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 11/22/2024] [Accepted: 11/25/2024] [Indexed: 12/20/2024]
Abstract
AIMS To evaluate the predictive value of a contemporary type 2 diabetes (T2D) polygenic score (PGS) in detecting incident diabetes across a range of diabetes risk factors. MATERIALS AND METHODS We analysed participants in the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial (ClinicalTrials.gov, number NCT0176463), which compared the efficacy of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab versus placebo in lowering cardiovascular outcomes in participants with stable atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg/dL (1.8 mmol/L) or higher who were receiving statin therapy. Genetic risk was characterized using a previously validated T2D PGS based on ~1.2 million single-nucleotide polymorphisms. PGS was analysed continuously and categorically as high (top 20% of the PGS) and low to intermediate (lower 80% of the PGS). The effect of evolocumab on incident diabetes in patients without diabetes at baseline was also assessed. HbA1c was measured at baseline and every 24 weeks thereafter, while FPG was measured at baseline, week 12, week 24 and every 24 weeks thereafter. Potential cases of incident diabetes were adjudicated centrally. Hazards ratios (HRs) for incident diabetes were adjusted for baseline characteristics and ancestry. RESULTS Among 9388 participants, the mean age was 63 ± 9 years and 22.7% were women, with median HbA1c 39 mmol/mol (36 mmol/mol - 41 mmol/mol; 5.7% [5.4%-5.9%]) and mean body mass index (BMI) 28.7 ± 5 kg/m2. Diabetes developed in 690 participants (7.3%) during 2.3 years of median follow-up. T2D PGS predicted incident T2D (HR per 1-SD 1.22, 95% CI 1.14-1.32, p < 0.001). The rates of incident T2D in the high and low to intermediate genetic risk categories were 12.1% versus 6.8%, respectively (HR 1.43 95% CI 1.20-1.70, p < 0.001). Notably, high T2D genetic risk had greater predictive strength among individuals with lower HbA1c (P-int = 0.0499) and lower BMI (P-int = 0.004). CONCLUSIONS The T2D polygenic score serves as an independent predictor of incident diabetes, particularly among individuals with lower distribution of traditional risk factors.
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Affiliation(s)
- Filipe A Moura
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
- VA Connecticut Healthcare System, West Haven, Connecticut, USA
| | - Frederick K Kamanu
- TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Stephen D Wiviott
- TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Robert P Giugliano
- TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Miriam S Udler
- Center for Genomic Medicine and Diabetes Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
- Programs in Metabolism and Medical & Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | - Jose C Florez
- Center for Genomic Medicine and Diabetes Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
- Programs in Metabolism and Medical & Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | - Patrick T Ellinor
- Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
- Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Marc S Sabatine
- TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Christian T Ruff
- TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Nicholas A Marston
- TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
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Savulescu-Fiedler I, Dorobantu-Lungu LR, Dragosloveanu S, Benea SN, Dragosloveanu CDM, Caruntu A, Scheau AE, Caruntu C, Scheau C. The Cross-Talk Between the Peripheral and Brain Cholesterol Metabolisms. Curr Issues Mol Biol 2025; 47:115. [PMID: 39996836 PMCID: PMC11853762 DOI: 10.3390/cimb47020115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Revised: 01/30/2025] [Accepted: 02/07/2025] [Indexed: 02/26/2025] Open
Abstract
Cholesterol is an essential element for the development and normal function of the central nervous system. While peripheral cholesterol is influenced by liver metabolism and diet, brain cholesterol metabolism takes place in an isolated system due to the impermeability of the blood-brain barrier (BBB). However, cross-talk occurs between the brain and periphery, specifically through metabolites such as oxysterols that play key roles in regulating cholesterol balance. Several neurodegenerative conditions such as Alzheimer's disease or Parkinson's disease are considered to be affected by the loss of this balance. Also, the treatment of hypercholesterolemia needs to consider these discrete interferences between brain and peripheral cholesterol and the possible implications of each therapeutic approach. This is particularly important because of 27-hydroxycholesterol and 24-hydroxycholesterol, which can cross the BBB and are involved in cholesterol metabolism. This paper examines the metabolic pathways of cholesterol metabolism in the brain and periphery and focuses on the complex cross-talk between these metabolisms. Also, we emphasize the regulatory role of the BBB and the need for an integrated approach to cholesterol management.
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Affiliation(s)
- Ilinca Savulescu-Fiedler
- Department of Internal Medicine, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Internal Medicine and Cardiology, Coltea Clinical Hospital, 030167 Bucharest, Romania
| | - Luiza-Roxana Dorobantu-Lungu
- Department of Cardiology, Emergency Institute for Cardiovascular Diseases “C.C. Iliescu”, 022328 Bucharest, Romania
| | - Serban Dragosloveanu
- Department of Orthopaedics, “Foisor” Clinical Hospital of Orthopaedics, Traumatology and Osteoarticular TB, 021382 Bucharest, Romania
- Department of Orthopaedics and Traumatology, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Serban Nicolae Benea
- Department of Infectious Diseases, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Departament of Infectious Diseases, National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, 021105 Bucharest, Romania
| | - Christiana Diana Maria Dragosloveanu
- Department of Ophthalmology, Faculty of Dentistry, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Ophthalmology, Clinical Hospital for Ophthalmological Emergencies, 010464 Bucharest, Romania
| | - Ana Caruntu
- Department of Oral and Maxillofacial Surgery, “Carol Davila” Central Military Emergency Hospital, 010825 Bucharest, Romania
- Department of Oral and Maxillofacial Surgery, Faculty of Dental Medicine, “Titu Maiorescu” University, 031593 Bucharest, Romania
| | - Andreea-Elena Scheau
- Department of Radiology and Medical Imaging, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Constantin Caruntu
- Department of Physiology, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Dermatology, “Prof. N.C. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, 011233 Bucharest, Romania
| | - Cristian Scheau
- Department of Physiology, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Radiology and Medical Imaging, “Foisor” Clinical Hospital of Orthopaedics, Traumatology and Osteoarticular TB, 021382 Bucharest, Romania
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Dogan Z, Senyigit A, Durmus S, Duvarcı C, Gelişgen R, Uzun H, Tabak O. The relationship between oxLDL, sLOX-1, PCSK9 and carotid intima-media thickness in patients with prediabetes and type 2 diabetes. Sci Rep 2025; 15:4554. [PMID: 39915665 PMCID: PMC11802860 DOI: 10.1038/s41598-025-89220-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2024] [Accepted: 02/04/2025] [Indexed: 02/09/2025] Open
Abstract
Affection of vascular structures is a known complication in diabetes and prediabetes. Subclinical atherosclerosis begins to develop years before both cardiovascular and cerebrovascular diseases become symptomatic. The aim of this study was to evaluate the relationship between circulating oxidized LDL (oxLDL), soluble lectin-like oxidized LDL (sLOX)-1 and proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and carotid intima-media thickness (CIMT) in patients with prediabetes and T2DM. We recruited 50 T2DM patients with macrovascular complications, 50 T2DM patients with uncomplicated, 50 prediabetes patients, and 50 healthy participants. The common carotid arteries were visualized by high-resolution B-mode carotid artery ultrasonography. Measurement of serum oxLDL, sLOX-1 and PCSK9 levels were assessed by using a commercially available human enzyme-linked immunosorbent assay (ELISA) method. Homeostasis model assessment for insulin resistance (HOMA-IR) was also calculated. Circulating LDL-C, oxLDL, sLOX-1 and PCSK9 levels were significantly higher in T2DM patients with macrovascular complications compared to control group, prediabetes and uncomplicated diabetes. There was significant difference, especially between the controls and the T2DM patients with macrovascular complications. The CIMT increased progressively from control through to T2DM. Both right and left CIMT also showed significant differences between the groups of prediabetes versus uncomplicated diabetes at p < 0.001 showing progressive increase in vascular involvement with progression of disease. There was a positive correlation between PCSK9 levels with LDL-C, oxLDL, sLOX-1, and CIMT. ROC curve analyses showed that PCSK9, as well as oxLDL and LOX-1, was a strong predictor of T2DM with high sensitivity and specificity. In this study, we found that oxLDL, sLOX-1 and PCSK9 levels were significantly associated with carotid intima-media thickness. Our findings suggest that these biomarkers may be used as potential markers for the assessment of cardiovascular risk in patients with prediabetes and type 2 diabetes.
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Affiliation(s)
- Zeki Dogan
- Department of Cardiology, Faculty of Medicine, Istanbul Atlas University, Istanbul, Turkey.
| | - Abdulhalim Senyigit
- Department of Internal Medicine, Faculty of Medicine, Istanbul Atlas University, Istanbul, Turkey
| | - Sinem Durmus
- Department of Medical Biochemistry, Faculty of Medicine, Katip Celebi University, Izmir, Turkey
| | - Canan Duvarcı
- Department of Medical Biochemistry, Cerrahpasa Faculty of Medicine, Istanbul University- Cerrahpasa, Istanbul, Turkey
| | - Remise Gelişgen
- Department of Medical Biochemistry, Cerrahpasa Faculty of Medicine, Istanbul University- Cerrahpasa, Istanbul, Turkey
| | - Hafize Uzun
- Department of Medical Biochemistry, Faculty of Medicine, Istanbul Atlas University, Istanbul, Turkey
| | - Omur Tabak
- Department of Internal Medicine, Kanuni Sultan Suleyman Training and Research Hospital, Health Sciences University, Istanbul, Turkey
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10
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Tomlinson B, Chan P. Exploring emerging pharmacotherapies for type 2 diabetes patients with hypertriglyceridemia. Expert Opin Pharmacother 2025; 26:279-289. [PMID: 39794291 DOI: 10.1080/14656566.2025.2451752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Accepted: 01/07/2025] [Indexed: 01/13/2025]
Abstract
INTRODUCTION Atherogenic dyslipidemia with increased triglycerides, low high-density lipoprotein cholesterol levels and increased small dense low-density lipoprotein (LDL) particles is a major risk factor contributing to the increased cardiovascular (CV) risk in patients with type 2 diabetes (T2D). This is regarded as a residual risk after achieving target levels of LDL cholesterol. AREAS COVERED This article reviews the novel therapies to reduce triglycerides in patients with T2D. These were identified by a PubMed search and mainly focus on pemafibrate and the drugs targeting apolipoprotein C3 (apoC3) and angiopoietin-like 3 (ANGPTL3). EXPERT OPINION Current therapies to reduce triglycerides in patients with T2D include fibrates and omega-3 fatty acids but these are often not sufficient and the evidence for CV benefits is limited. Pemafibrate was effective in reducing triglycerides in patients with T2D but did not reduce CV events in the PROMINENT study. Inhibitors of apoC3 are effective in reducing triglycerides even in familial chylomicronaemia syndrome and olezarsen and plozasiran in this group are being studied in patients with combined hyperlipidemia. The ANGPTL3 inhibitor evinacumab has been approved for homozygous familial hypercholesterolemia, and other ANGPTL3 inhibitors may prove to be useful to reduce triglycerides in T2D.
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Affiliation(s)
- Brian Tomlinson
- Faculty of Medicine, Macau University of Science & Technology, Macau, China
| | - Paul Chan
- Division of Cardiology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
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11
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Pedro-Botet J, Arrieta F, Botana M, Gimeno-Orna JA, Martínez-Montoro JI, Ortega-Martínez de Victoria E, Ribalta J, Sánchez-Margalet V, Pérez-Pérez A. Lipid-lowering drug therapy for reducing cardiovascular risk in diabetes. A clinical view of the Cardiovascular Disease Working Group of the Spanish Diabetes Society. ENDOCRINOL DIAB NUTR 2025; 72:101523. [PMID: 39924389 DOI: 10.1016/j.endien.2025.101523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 08/21/2024] [Accepted: 09/03/2024] [Indexed: 02/11/2025]
Abstract
Patients with type 2 diabetes mellitus (T2DM) managed in both hospital and out-ofhospital settings usually have a high/very high cardiovascular risk, with a high burden of cardiovascular disease. All this justifies that the reduction of low-density lipoprotein cholesterol is the main therapeutic goal in T2DM. However, residual cardiovascular risk is very prevalent in T2DM, and is usually associated with atherogenic dyslipidemia and hyperlipoproteinemia(a); therefore, it is also necessary to reverse these lipoprotein abnormalities to achieve effective cardiovascular prevention. Given the considerable armamentarium of lipid-lowering drugs currently available, the Cardiovascular Disease Working Group of the Spanish Diabetes Society has considered it appropriate to carry out a narrative review and update of the effectiveness of these lipid-lowering drugs in the population with T2DM taking into account their effect on the lipoprotein profile and their potential impact on glycemic control.
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Affiliation(s)
- Juan Pedro-Botet
- Unidad de Lípidos y Riesgo Vascular, Hospital del Mar, Barcelona, Spain; Departamento de Medicina, Universidad Autónoma de Barcelona, Barcelona, Spain.
| | - Francisco Arrieta
- Servicio de Endocrinología y Nutrición, Hospital Universitario Rey Juan Carlos, Madrid, Spain
| | - Manuel Botana
- Sección de Endocrinología, Hospital Universitario Lucus Augusti, Lugo, Spain
| | - José A Gimeno-Orna
- Servicio de Endocrinología y Nutrición, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
| | - José I Martínez-Montoro
- Servicio de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Málaga, Spain; Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma Bionand, Málaga, Spain
| | - Emilio Ortega-Martínez de Victoria
- Servicio de Endocrinología y Nutrición, Hospital Clínic, Madrid, Spain; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain
| | - Josep Ribalta
- Departament de Medicina i Cirurgia, Unitat de Recerca en Lípids i Arteriosclerosi (URLA), Universitat Rovira i Virgili, Reus, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Víctor Sánchez-Margalet
- Departamento de Bioquímica Médica y Biología Molecular, e Inmunología, Facultad de Medicina, Hospital Universitario Virgen Macarena, Universidad de Sevilla, Sevilla, Spain
| | - Antonio Pérez-Pérez
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Servicio de Endocrinología y Nutrición, Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
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12
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Kim S, Subramanian S. Approach to Lipid Management in the Patient with Diabetes. J Clin Endocrinol Metab 2025:dgaf018. [PMID: 39797609 DOI: 10.1210/clinem/dgaf018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Revised: 12/13/2024] [Accepted: 01/09/2025] [Indexed: 01/13/2025]
Abstract
Diabetes is associated with increased atherosclerotic cardiovascular disease (ASCVD) risk, a leading cause of morbidity and mortality. Disordered lipid metabolism is a major contributor to ASCVD risk in diabetes. Dyslipidemia in type 2 diabetes is characterized by hypertriglyceridemia, low HDL cholesterol and the presence of small, dense LDL particles. Statins have demonstrated longstanding benefit for reducing ASCVD risk in individuals with diabetes. Newer agents for add-on therapies to statins are now available for additional cardiovascular risk reduction. In this clinical overview, we review the pathogenesis of dyslipidemia in both types 1 and 2 diabetes and provide an update on the management of lipids in the individual with diabetes. We discuss the importance of appropriate risk stratification, individualized treatment selection, and the need to avoid therapy inertia to mitigate cardiovascular risk. We will also address lipid-related effects of glycemic lowering therapies.
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Affiliation(s)
- Stephanie Kim
- Clinical Assistant Professor, Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle WA
| | - Savitha Subramanian
- Professor of Medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle WA
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13
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ElSayed NA, McCoy RG, Aleppo G, Balapattabi K, Beverly EA, Briggs Early K, Bruemmer D, Das SR, Echouffo-Tcheugui JB, Ekhlaspour L, Garg R, Khunti K, Kosiborod MN, Lal R, Lingvay I, Matfin G, Pandya N, Pekas EJ, Pilla SJ, Polsky S, Segal AR, Seley JJ, Stanton RC, Bannuru RR. 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes-2025. Diabetes Care 2025; 48:S207-S238. [PMID: 39651970 PMCID: PMC11635050 DOI: 10.2337/dc25-s010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2024]
Abstract
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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14
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ElSayed NA, McCoy RG, Aleppo G, Balapattabi K, Beverly EA, Briggs Early K, Bruemmer D, Ebekozien O, Echouffo-Tcheugui JB, Ekhlaspour L, Gaglia JL, Garg R, Khunti K, Lal R, Lingvay I, Matfin G, Pandya N, Pekas EJ, Pilla SJ, Polsky S, Segal AR, Seley JJ, Stanton RC, Bannuru RR. 3. Prevention or Delay of Diabetes and Associated Comorbidities: Standards of Care in Diabetes-2025. Diabetes Care 2025; 48:S50-S58. [PMID: 39651971 PMCID: PMC11635039 DOI: 10.2337/dc25-s003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2024]
Abstract
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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15
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Lan NSR, Dwivedi G, Fegan PG, Game F, Hamilton EJ. Unravelling the cardio-renal-metabolic-foot connection in people with diabetes-related foot ulceration: a narrative review. Cardiovasc Diabetol 2024; 23:437. [PMID: 39696281 PMCID: PMC11657306 DOI: 10.1186/s12933-024-02527-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Accepted: 11/26/2024] [Indexed: 12/20/2024] Open
Abstract
Diabetes-related foot ulceration (DFU), a serious but preventable complication of diabetes, is a leading cause of hospitalisation, lower extremity amputation and disability worldwide. People with DFU have a greater burden of cardiovascular risk factors, heart failure and chronic kidney disease, resulting in over two-fold higher risk of cardiovascular death compared with people with diabetes without DFU. Here, we propose a "cardio-renal-metabolic-foot" connection in people with diabetes based on shared pathophysiological mechanisms linking DFU with cardiovascular and renal disease. Whilst these mechanistic links remain to be fully elucidated, systemic inflammation and infection in the context of DFU are postulated as key mediators in the development, and progression of, cardiovascular and renal disease. However, cardiovascular and renal disease are also implicated in the pathogenesis of DFU, highlighting the multi-directional interplay between conditions. The impact of screening, prevention, and early management of cardiovascular complications associated with DFU requires further research. Multi-modality cardiac imaging could play a role in unravelling disease mechanisms leading to novel therapeutic strategies, as well as facilitating personalised risk assessment and management. Recent clinical trials have transformed the therapeutic landscape for people with type 2 diabetes, by demonstrating that sodium glucose co-transporter 2 inhibitors, glucagon-like peptide-1 agonists and non-steroidal mineralocorticoid receptor antagonists improve cardiovascular and renal outcomes. Although dedicated research in people with DFU is warranted, these therapies could target multiple facets of the "cardio-renal-metabolic-foot" connection. The holistic, person-centred approach to managing DFU should incorporate new multidisciplinary models of care focusing on the prevention and management of cardiovascular and kidney disease.
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Affiliation(s)
- Nick S R Lan
- Centre of Excellence for Cardiometabolic Health, Fiona Stanley Hospital, Perth, Australia
- Department of Cardiology, Fiona Stanley Hospital, Perth, Australia
- Medical School, The University of Western Australia, Perth, Australia
- Harry Perkins Institute of Medical Research, Perth, Australia
| | - Girish Dwivedi
- Centre of Excellence for Cardiometabolic Health, Fiona Stanley Hospital, Perth, Australia
- Department of Cardiology, Fiona Stanley Hospital, Perth, Australia
- Medical School, The University of Western Australia, Perth, Australia
- Harry Perkins Institute of Medical Research, Perth, Australia
| | - P Gerry Fegan
- Centre of Excellence for Cardiometabolic Health, Fiona Stanley Hospital, Perth, Australia
- Medical School, Curtin University, Perth, Australia
- Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Australia
| | - Fran Game
- Department of Diabetes and Endocrinology, University Hospitals of Derby and Burton NHS Foundation Trust, Derby, UK
| | - Emma J Hamilton
- Medical School, The University of Western Australia, Perth, Australia.
- Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Australia.
- Centre of Excellence Multidisciplinary Diabetes Foot Ulcer Service, Fiona Stanley and Fremantle Hospitals Group, 11 Robin Warren Drive, Murdoch, Perth, Australia.
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16
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Zendjebil S, Steg PG. PCSK9 Monoclonal Antibodies Have Come a Long Way. Curr Atheroscler Rep 2024; 26:721-732. [PMID: 39384735 DOI: 10.1007/s11883-024-01243-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/22/2024] [Indexed: 10/11/2024]
Abstract
PURPOSE OF THE REVIEW This review examines the pivotal role of monoclonal antibodies against PCSK9 in lipid-lowering therapy, emphasizing their biological and clinical impact. RECENT FINDINGS Randomized controlled trials have validated that PCSK9 monoclonal antibodies (Mabs) effectively reduce LDL-c levels by approximately 50%, even when added to maximal statin therapy. They moreover produce a notable 15-20% relative decrease in major cardiovascular events, with a greater reduction among high-risk patients and no evidence for serious adverse effects, assuaging previous concerns. This review highlights the benefits of PCSK9 Mabs in high cardiovascular risk patients. Despite their efficacy and safety, these therapies are hindered by limited access, and require broader integration into clinical practice to optimize therapeutic outcomes.
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Affiliation(s)
- Sandra Zendjebil
- Université Paris-Cité, Paris, France
- French Alliance for Cardiovascular Trials (FACT), INSERM U_1148/LVTS, AP-HP, Hôpital Bichat, Paris, France
- Département de Cardiologie, Hôpital Bichat, AP-HP 46 Rue Henri Huchard, 75018, Paris, France
| | - Philippe Gabriel Steg
- Université Paris-Cité, Paris, France.
- French Alliance for Cardiovascular Trials (FACT), INSERM U_1148/LVTS, AP-HP, Hôpital Bichat, Paris, France.
- Département de Cardiologie, Hôpital Bichat, AP-HP 46 Rue Henri Huchard, 75018, Paris, France.
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17
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Planchat A, Gencer B, Degrauwe S, Musayeb Y, Roffi M, Iglesias JF. Secondary prevention therapies following percutaneous coronary intervention or acute coronary syndrome in patients with diabetes mellitus. Front Cardiovasc Med 2024; 11:1436332. [PMID: 39650149 PMCID: PMC11621092 DOI: 10.3389/fcvm.2024.1436332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Accepted: 11/04/2024] [Indexed: 12/11/2024] Open
Abstract
Diabetes mellitus (DM) promotes atherosclerosis, leading to increased risk for cardiovascular morbidity and mortality. Diabetics represent a challenging subset of patients undergoing percutaneous coronary intervention (PCI) or who have experienced an acute coronary syndrome (ACS), a subset characterized by higher rates of recurrent ischemic events compared with non-diabetics. These events are caused by both patient-related accelerated atherosclerotic disease progression and worse stent-related adverse clinical outcomes translating into a higher risk for repeat revascularization. In addition, DM is paradoxically associated with an increased risk of major bleeding following PCI or an ACS. Secondary prevention therapies following PCI or an ACS in diabetic patients are therefore of paramount importance. This mini review focuses on the currently available evidence regarding short- and long-term secondary prevention treatments for diabetic patients undergoing PCI or who have experienced an ACS.
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Affiliation(s)
- Arnaud Planchat
- Department of Cardiology, Geneva University Hospitals, Geneva, Switzerland
| | - Baris Gencer
- Department of Cardiology, Lausanne University Hospital, Lausanne, Switzerland
| | - Sophie Degrauwe
- Department of Cardiology, Geneva University Hospitals, Geneva, Switzerland
| | - Yazan Musayeb
- Department of Cardiology, Geneva University Hospitals, Geneva, Switzerland
| | - Marco Roffi
- Department of Cardiology, Geneva University Hospitals, Geneva, Switzerland
| | - Juan F. Iglesias
- Department of Cardiology, Geneva University Hospitals, Geneva, Switzerland
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18
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Elshorbagy A, Lyons AR, Vallejo-Vaz AJ, Stevens CA, Dharmayat KI, Brandts J, Catapano AL, Freiberger T, Hovingh GK, Mata P, Raal FJ, Santos RD, Soran H, Watts GF, Abifadel M, Aguilar-Salinas CA, Alhabib KF, Alkhnifsawi M, Almahmeed W, Alonso R, Al-Rasadi K, Al-Sarraf A, Ashavaid TF, Banach M, Binder CJ, Bourbon M, Brunham LR, Chlebus K, Corral P, Cruz D, Davletov K, Descamps OS, Ezhov M, Gaita D, Groselj U, Harada-Shiba M, Holven KB, Kayikcioglu M, Khovidhunkit W, Lalic K, Latkovskis G, Laufs U, Liberopoulos E, Lima-Martinez MM, Lin J, Maher V, Marais AD, März W, Mirrakhimov E, Miserez AR, Mitchenko O, Nawawi H, Nordestgaard BG, Panayiotou AG, Paragh G, Petrulioniene Z, Pojskic B, Postadzhiyan A, Reda A, Reiner Ž, Reyes X, Sadiq F, Sadoh WE, Schunkert H, Shek AB, Stroes E, Su TC, Subramaniam T, Susekov AV, Tilney M, Tomlinson B, Truong TH, Tselepis AD, Tybjærg-Hansen A, Vázquez AC, Viigimaa M, Vohnout B, Wang L, Yamashita S, Arca M, Averna M, Schreier L, Pang J, Ebenbichler C, Dieplinger H, Innerhofer R, Winhofer-Stöckl Y, Greber-Platzer S, Krychtiuk K, Speidl W, Toplak H, Widhalm K, Stulnig T, Huber K, Höllerl F, Rega-Kaun G, Kleemann L, Mäser M, Scholl-Bürgi S, Säly C, Mayer FJ, Sperone A, Tanghe C, Gérard AC, Pojskic L, Sisic I, Durak Nalbantic A, Ejubovic M, Jannes CE, Pereira AC, Krieger JE, Petrov I, Goudev A, Nikolov F, Tisheva S, Yotov Y, Tzvetkov I, Baass A, Bergeron J, Bernard S, Brisson D, Brunham LR, Cermakova L, Couture P, Francis GA, Gaudet D, Hegele RA, Khoury E, Mancini GJ, McCrindle BW, Paquette M, Ruel I, Iatan I, Cuevas A, Wang X, Meng K, Song X, Yong Q, Jiang T, Liu Z, Duan Y, Hong J, Ye P, Chen Y, Qi J, Liu Z, Li Y, Zhang C, Peng J, Yang Y, Yu W, Wang Q, Yuan H, Cheng S, Jiang L, Chong M, Jiao J, Wu Y, Wen W, Xu L, Zhang R, Qu Y, He J, Fan X, Wang Z, Chow E, Pećin I, Perica D, Symeonides P, Vrablik M, Ceska R, Soska V, Tichy L, Adamkova V, Franekova J, Cifkova R, Kraml P, Vonaskova K, Cepova J, Dusejovska M, Pavlickova L, Blaha V, Rosolova H, Nussbaumerova B, Cibulka R, Vaverkova H, Cibickova L, Krejsova Z, Rehouskova K, Malina P, Budikova M, Palanova V, Solcova L, Lubasova A, Podzimkova H, Bujdak J, Vesely J, Jordanova M, Salek T, Urbanek R, Zemek S, Lacko J, Halamkova H, Machacova S, Mala S, Cubova E, Valoskova K, Burda L, Benn M, Bendary A, Daoud I, Emil S, Elbahry A, Rafla S, Sanad O, Kazamel G, Ashraf DM, Sobhy M, El-Hadidy A, Shafy MA, Kamal S, Bendary M, Talviste G, Christmann J, Dressel A, Fath F, Ferraro C, Frenzke L, Gopon A, Klein I, Pienkowska D, Sietmann T, Sonntag A, Adjan O, Bahrmann P, Baessler A, Barkowski R, Beckerdjian R, Berr C, Birkenfeld A, Böll G, Carstensen A, Demuth I, Finkernagel H, Gouni-Berthold I, Hahmann H, Hamerle M, Halder J, Heide M, Julius U, Kassner U, Katzmann JL, Kirschbaum A, Klose G, Könemann S, König C, König W, Krämer B, Kuprat G, Koschker AC, Krämer B, Kilic Ö, Laufs U, Lindenmeier G, Van de Loo I, Lorenz B, Lorenz E, Löhr B, McChord J, Maslarska M, Methe H, Merkel M, Moussaoui Z, Müller-Kozarez I, Olivier CB, Ong P, Otte B, Parhofer K, Partsch CJ, Paulus M, Pehlivanli S, Pflederer T, Pusl T, Richter V, Rosner S, Sanin V, Schäfer S, Schäfer C, Schatz U, Schirmer S, Schmidt C, Seeger W, Sisovic S, Spens A, Jablonski KS, Stadelmann A, Steinhagen-Thiessen E, Stürzebecher P, Tafelmeier M, Tillack D, Tselmin S, Tünnemann-Tarr A, Vogt A, Beckerath JV, Wilke A, Wolf U, Zemmrich C, Rizos CV, Skoumas I, Tziomalos K, Rallidis L, Kotsis V, Doumas M, Athyros V, Skalidis E, Kolovou G, Kolovou V, Garoufi A, Bilianou E, Koutagiar I, Kiouri E, Antza C, Zacharis E, Attilakos A, Sfikas G, Koumaras C, Anagnostis P, Anastasiou G, Liamis G, Koutsogianni AD, Petkou E, Milionis H, Koulouri A, Prodromiadou E, Karányi Z, Harangi M, Bajnok L, Audikovszky M, Márk L, Benczúr B, Reiber I, Nagy G, Nagy A, Reddy LL, Shah SAV, Ponde CK, Dalal JJ, Sawhney JP, Verma IC, Altaey M, Al-Jumaily K, Rasul D, Abdalsahib AF, Jabbar AA, Al-ageedi M, Abdalsahib AF, Al-ageedi M, Dhamin M, AlFil S, Khadhim F, Miahy S, Agar R, Catapano AL, Arca M, Averna M, Calandra S, Tarugi P, Casula M, Galimberti F, Olmastroni E, Sarzani R, Ferri C, Repetti E, Piro S, Suppressa P, Meregalli G, Borghi C, Muntoni S, Calabrò P, Cipollone F, Purrello F, Pujia A, Passaro A, Marcucci R, Pecchioli V, Pisciotta L, Mandraffino G, Pellegatta F, Mombelli G, Branchi A, Fiorenza AM, Pederiva C, Werba JP, Parati G, Carubbi F, Iughetti L, Fortunato G, Iannuzzi A, Iannuzzo G, Cefalù AB, Biasucci G, Zambon S, Pirro M, Sbrana F, Trenti C, D'Erasmo L, Federici M, Ben MD, Bartuli A, Giaccari A, Pipolo A, Citroni N, Guardamagna O, Lia S, Benso A, Biolo G, Maroni L, Lupi A, Bonanni L, Rinaldi E, Zenti MG, Matsuki K, Hori M, Ogura M, Masuda D, Kobayashi T, Nagahama K, Al-Jarallah M, Radovic M, Lunegova O, Bektasheva E, Abilova S, Erglis A, Gilis D, Nesterovics G, Saripo V, Meiere R, Skudrina G, Terauda E, Jambart S, Ayoub C, Ghaleb Y, Aliosaitiene U, Kutkiene S, Abdul Kadir SHS, Kasim NAM, Nor NSM, Abdul Hamid H, Abdul Razak S, Al-Khateeb A, Abd Muid S, Abdul Rahman T, Kasim SS, Radzi ABM, Ibrahim KS, Rosli MM, Razali R, Chua YA, Razman AZ, Nazli SA, Aziz N, Rosman A, Abdul Murad N, Jalaludin MA, Abdul Latif AZ, Azzopardi C, Mehta R, Martagon AJ, Ramirez GAG, Villa NEA, Vazquez AV, Elias-Lopez D, Retana GG, Rodriguez B, Macías JJC, Zazueta AR, Alvarado RM, Portano JDM, Lopez HA, Sauque-Reyna L, Herrera LGG, Mendia LES, Aguilar HG, Cooremans ER, Aparicio BP, Zubieta VM, Gonzalez PAC, Ferreira-Hermosillo A, Portilla NC, Dominguez GJ, Garcia AYR, Cazares HEA, Gonzalez JR, Valencia CVM, Padilla FG, Prado RM, Ibarra MODLR, Villicaña RDA, Rivera KJA, Carrera RA, Alvarez JA, Martinez JCA, Bustillo MDLRB, Vargas GC, Chacon RC, Andrade MHF, Ortega AF, Alcala HG, de Leon LEG, Guzman BG, Garcia JJG, Cuellar JCG, Cruz JRG, Garcia AH, Almada JRH, Herrera UJ, Sobrevilla FL, Rodriguez EM, Sibaja CM, Rodriguez ABM, Oyervides JCM, Vazquez DIP, Rodriguez EAR, Osorio MLR, Saucedo JR, Tamayo MT, Talavera LAV, Arroyo LEV, Carrillo EAZ, Stroes ES, Defesche J, Zuurbier L, Reeskamp L, Ibrahim S, Roeters van Lennep J, Wiegman A, Isara A, Obaseki DE, Al-Waili K, Al-Zadjali F, Al-Zakwani I, Al-Kindi M, Al-Mukhaini S, Al-Barwani H, Rana A, Shah LSU, Al-Nouri F, Starostecka E, Konopka A, Bielecka-Dabrowa A, Lewek J, Sosnowska B, Gąsior M, Dyrbuś K, Jóźwiak J, Pajkowski M, Romanowska-Kocejko M, Żarczyńska-Buchowiecka M, Chmara M, Wasąg B, Stróżyk A, Michalska-Grzonkowska A, Medeiros AM, Alves AC, Silva F, Lobarinhas G, Palma I, de Moura JP, Rico MT, Rato Q, Pais P, Correia S, Moldovan O, Virtuoso MJ, Araujo F, Salgado JM, Colaço I, Dumitrescu A, Lengher C, Mosteoru S, Meshkov A, Ershova A, Rozhkova T, Korneva V, Yu KT, Zafiraki V, Voevoda M, Gurevich V, Duplyakov D, Ragino Y, Chubykina U, Shaposhnik I, Alkaf F, Khudari A, Rwaili N, Al-Allaf F, Alghamdi M, Batais MA, Almigbal TH, Kinsara A, AlQudaimi AHA, Awan Z, Elamin OA, Altaradi H, Popovic L, Singh S, Rasulic I, Petakov A, Lalic NM, Lam C, Le TJ, Siang ELT, Dissanayake S, I-Shing JT, Shyong TE, Jin TCS, Ting SPL, Ming JHK, Drum CL, Nastar FA, Jia LW, Ya NKS, Jie MCW, Dalan R, Wei YQ, sian TY, Keong YK, Rong SK, Jin DSE, Ming IKJ, Chang TH, Peng FYK, Vasanwala RF, Raslova K, Balinth K, Buganova I, Fabryova L, Kadurova M, Klabnik A, Kozárová M, Sirotiakova J, Battelino T, Cevc M, Debeljak M, Torkar AD, Fras Z, Jug B, Cugalj BK, Kovac J, Mlinaric M, Sikonja J, Pilcher GJ, Blom DJ, Wolmarans KH, Brice BC, Muñiz-Grijalvo O, Díaz-Díaz JL, de Isla LP, Fuentes F, Badimon L, Martin F, Miserez EB, Shipton JL, Ganokroj P, Chattranukulchai P, Jiamjarasrungsi W, Thongtang N, Krittayaphong R, Vathesatogkit P, Sriphrapradang C, Phimphilai M, Leelawattana R, Anthanont P, Suraamornkul S, Deerochanawong C, Senthong V, Torpongpun A, Suteerayongprasert P, Pengpong N, Sathavarodom N, Sunanta U, Porntharukchareon T, Kiatpanabhikul P, Kaewkrasaesin C, Kongkit J, Umphonsathien M, Akbulut M, Alici G, Bayram F, Can LH, Celik A, Ceyhan C, Coskun FY, Demir M, Demircan S, Dogan V, Durakoglugil E, Dural İE, Gedikli O, Hacioglu A, Ildizli M, Kilic S, Kirilmaz B, Kutlu M, Oguz A, Ozdogan O, Onrat E, Ozer S, Sabuncu T, Sahin T, Sivri F, Sonmez A, Temizhan A, Topcu S, Tokgozoglu L, Tuncez A, Vural M, Yenercag M, Yesilbursa D, Yigit Z, Yildirim AB, Yildirir A, Yilmaz MB, Atallah B, Traina M, Sabbour H, Abdul Hay D, Luqman N, Elfatih A, Abdulrasheed A, Manla Y, Kwok S, DellOca N, Alieva RB, Fozilov KG, Hoshimov SU, Nizamov UI, Kan LE, Kim AR, Abdullaeva GJ, Abdullaev AA, Do DL, Nguyen MNT, Kim NT, Le TT, Le HA, Ray KK. Association of BMI, lipid-lowering medication, and age with prevalence of type 2 diabetes in adults with heterozygous familial hypercholesterolaemia: a worldwide cross-sectional study. Lancet Diabetes Endocrinol 2024; 12:811-823. [PMID: 39374602 DOI: 10.1016/s2213-8587(24)00221-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 07/05/2024] [Accepted: 07/15/2024] [Indexed: 10/09/2024]
Abstract
BACKGROUND Statins are the cornerstone treatment for patients with heterozygous familial hypercholesterolaemia but research suggests it could increase the risk of type 2 diabetes in the general population. A low prevalence of type 2 diabetes was reported in some familial hypercholesterolaemia cohorts, raising the question of whether these patients are protected against type 2 diabetes. Obesity is a well known risk factor for the development of type 2 diabetes. We aimed to investigate the associations of known key determinants of type 2 diabetes with its prevalence in people with heterozygous familial hypercholesterolaemia. METHODS This worldwide cross-sectional study used individual-level data from the EAS FHSC registry and included adults older than 18 years with a clinical or genetic diagnosis of heterozygous familial hypercholesterolaemia who had data available on age, BMI, and diabetes status. Those with known or suspected homozygous familial hypercholesterolaemia and type 1 diabetes were excluded. The main outcome was prevalence of type 2 diabetes overall and by WHO region, and in relation to obesity (BMI ≥30·0 kg/m2) and lipid-lowering medication as predictors. The study population was divided into 12 risk categories based on age (tertiles), obesity, and receiving statins, and the risk of type 2 diabetes was investigated using logistic regression. FINDINGS Among 46 683 adults with individual-level data in the FHSC registry, 24 784 with heterozygous familial hypercholesterolaemia were included in the analysis from 44 countries. 19 818 (80%) had a genetically confirmed diagnosis of heterozygous familial hypercholesterolaemia. Type 2 diabetes prevalence in the total population was 5·7% (1415 of 24 784), with 4·1% (817 of 19 818) in the genetically diagnosed cohort. Higher prevalence of type 2 diabetes was observed in the Eastern Mediterranean (58 [29·9%] of 194), South-East Asia and Western Pacific (214 [12·0%] of 1785), and the Americas (166 [8·5%] of 1955) than in Europe (excluding the Netherlands; 527 [8·0%] of 6579). Advancing age, a higher BMI category (obesity and overweight), and use of lipid-lowering medication were associated with a higher risk of type 2 diabetes, independent of sex and LDL cholesterol. Among the 12 risk categories, the probability of developing type 2 diabetes was higher in people in the highest risk category (aged 55-98 years, with obesity, and receiving statins; OR 74·42 [95% CI 47·04-117·73]) than in those in the lowest risk category (aged 18-38 years, without obesity, and not receiving statins). Those who did not have obesity, even if they were in the upper age tertile and receiving statins, had lower risk of type 2 diabetes (OR 24·42 [15·57-38·31]). The corresponding results in the genetically diagnosed cohort were OR 65·04 (40·67-104·02) for those with obesity in the highest risk category and OR 20·07 (12·73-31·65) for those without obesity. INTERPRETATION Adults with heterozygous familial hypercholesterolaemia in most WHO regions have a higher type 2 diabetes prevalence than in Europe. Obesity markedly increases the risk of diabetes associated with age and use of statins in these patients. Our results suggest that heterozygous familial hypercholesterolaemia does not protect against type 2 diabetes, hence managing obesity is essential to reduce type 2 diabetes in this patient population. FUNDING Pfizer, Amgen, MSD, Sanofi-Aventis, Daiichi-Sankyo, and Regeneron.
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Prentza V, Pavlidis G, Ikonomidis I, Pililis S, Lampsas S, Kountouri A, Pliouta L, Korakas E, Thymis J, Palaiodimou L, Tsegka A, Markakis K, Halvatsiotis P, Tsivgoulis G, Lambadiari V. Antidiabetic Treatment and Prevention of Ischemic Stroke: A Systematic Review. J Clin Med 2024; 13:5786. [PMID: 39407846 PMCID: PMC11476433 DOI: 10.3390/jcm13195786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Revised: 09/19/2024] [Accepted: 09/23/2024] [Indexed: 10/20/2024] Open
Abstract
Background: Diabetes mellitus (DM) is a prevalent disease in the general population and also a well-established risk factor for the development of ischemic stroke. Patients who have been diagnosed with diabetes have a 20% higher risk for developing ischemic stroke in comparison to non-diabetic individuals. The aim of the current systematic review is to provide the latest evidence regarding the association between antidiabetic treatment and the prevention of ischemic stroke. Methods: A comprehensive search in scientific literature databases PUBMED, COCHRANE, and SCOPUS was conducted. The studies that were deemed as eligible for this review were those that examined the clinical benefits of therapeutic strategies in terms of preventing ischemic strokes. Results: A total of 32 studies met the established selection criteria. The included studies showed that pioglitazone treatment significantly reduced the risk for recurrent stroke in patients with DM. Furthermore, in the context of primary prevention, the improvement in glycemic control after treatment with the glucagon-like peptide-1 receptor agonists (GLP-1RA) semaglutide and dulaglutide was associated with a reduction in the risk of ischemic stroke in diabetic subjects. Metformin monotherapy may reduce stroke risk, while dipeptidyl peptidase 4 inhibitors, sodium-glucose co-transporter 2 inhibitors, and insulin do not seem to affect the incidence of stroke. Conclusions: The findings of the present systematic review suggest that pioglitazone and GLP-1RA may decrease the risk of stroke. Further studies are needed to provide additional data regarding the preventive effect of novel antidiabetic drugs, such as dual glucose-dependent insulinotropic polypeptide/GLP-1RA agents, on stroke.
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Affiliation(s)
- Vasiliki Prentza
- 2nd Department of Cardiology, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (V.P.); (I.I.); (S.L.); (J.T.)
| | - George Pavlidis
- 2nd Department of Cardiology, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (V.P.); (I.I.); (S.L.); (J.T.)
| | - Ignatios Ikonomidis
- 2nd Department of Cardiology, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (V.P.); (I.I.); (S.L.); (J.T.)
| | - Sotirios Pililis
- Research Unit and Diabetes Center, 2nd Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (S.P.); (A.K.); (L.P.); (E.K.); (A.T.); (K.M.); (P.H.); (V.L.)
| | - Stamatios Lampsas
- 2nd Department of Cardiology, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (V.P.); (I.I.); (S.L.); (J.T.)
| | - Aikaterini Kountouri
- Research Unit and Diabetes Center, 2nd Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (S.P.); (A.K.); (L.P.); (E.K.); (A.T.); (K.M.); (P.H.); (V.L.)
| | - Loukia Pliouta
- Research Unit and Diabetes Center, 2nd Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (S.P.); (A.K.); (L.P.); (E.K.); (A.T.); (K.M.); (P.H.); (V.L.)
| | - Emmanouil Korakas
- Research Unit and Diabetes Center, 2nd Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (S.P.); (A.K.); (L.P.); (E.K.); (A.T.); (K.M.); (P.H.); (V.L.)
| | - John Thymis
- 2nd Department of Cardiology, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (V.P.); (I.I.); (S.L.); (J.T.)
| | - Lina Palaiodimou
- 2nd Department of Neurology, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece (G.T.)
| | - Aikaterini Tsegka
- Research Unit and Diabetes Center, 2nd Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (S.P.); (A.K.); (L.P.); (E.K.); (A.T.); (K.M.); (P.H.); (V.L.)
| | - Konstantinos Markakis
- Research Unit and Diabetes Center, 2nd Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (S.P.); (A.K.); (L.P.); (E.K.); (A.T.); (K.M.); (P.H.); (V.L.)
| | - Panagiotis Halvatsiotis
- Research Unit and Diabetes Center, 2nd Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (S.P.); (A.K.); (L.P.); (E.K.); (A.T.); (K.M.); (P.H.); (V.L.)
| | - Georgios Tsivgoulis
- 2nd Department of Neurology, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece (G.T.)
| | - Vaia Lambadiari
- Research Unit and Diabetes Center, 2nd Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (S.P.); (A.K.); (L.P.); (E.K.); (A.T.); (K.M.); (P.H.); (V.L.)
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Marco-Benedí V, Sánchez-Hernández RM, Díaz JL, Jarauta E, Suárez-Tembra M, Pintó X, Morillas C, Plana N, Pedro-Botet J, Civeira F. PCSK9 inhibitors on the management of primary and secondary cardiovascular prevention. Lipids Health Dis 2024; 23:290. [PMID: 39256734 PMCID: PMC11386113 DOI: 10.1186/s12944-024-02283-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Accepted: 09/01/2024] [Indexed: 09/12/2024] Open
Abstract
BACKGROUND Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have represented an important change in the management of hypercholesterolemia, although, until now, they have barely been used. Without PCSK9i, many patients with atherosclerotic cardiovascular disease (CVD) or those at very high risk do not reach their therapeutic LDLc objectives. OBJECTIVE The analysis aimed to examine the clinical and biochemical characteristics of subjects receiving PCSK9i treatment in the Dyslipidemia Registry of the Spanish Atherosclerosis Society. METHODS All consecutive subjects aged ≥ 18 years from different Lipid Units included in the Dyslipidemia Registry of the SEA were analyzed. Inclusion criteria consisted of unrelated patients aged ≥ 18 at the time of inclusion with hypercholesterolemia (LDL-C ≥ 130 mg/dL or non-HDL-C ≥ 160 mg/dL after the exclusion of secondary causes) who were studied for at least two years after inclusion. Participants' baseline and final visit clinical and biochemical characteristics were analyzed based on whether they were on primary or secondary prevention and whether they were taking PCSK9i at the end of follow-up. RESULTS Eight hundred twenty-nine patients were analyzed, 7014 patients in primary prevention and 1281 in secondary prevention at baseline. 4127 subjects completed the required follow-up for the final analysis. The median follow-up duration was 7 years (IQR 3.0-10.0). Five hundred patients (12.1%) were taking PCSK9i at the end of the follow-up. The percentage of PCSK9i use reached 35.6% (n = 201) and 8.7% (n = 318) in subjects with and without CVD, respectively. Subjects on PCSK9i and oral lipid-lowering agents with and without CVD achieved LDLc reductions of 80.3% and 75.1%, respectively, concerning concentrations without lipid-lowering drugs. Factors associated with PCSK9i use included increasing age, LDLc without lipid-lowering drugs and the Dutch Lipid Clinic Network (DLCN) score. However, hypertension, diabetes, smoking, and LDLc after oral lipid-lowering drugs were not independent factors associated with PCSK9i prescription. In subjects with CVD, the use of PCSK9i was higher in men than in women (an odds ratio of 1.613, P = 0.048). CONCLUSIONS Approximately one-third of CVD patients received PCSK9i at the end of follow-up. The use of PCSK9i was more focused on baseline LDLc concentrations rather than on CVD risk. Women received less PCSK9i in secondary prevention compared to men.
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Affiliation(s)
- Victoria Marco-Benedí
- Hospital Universitario Miguel Servet, IIS Aragón, CIBERCV, Saragossa, Spain.
- Unidad de Lípidos, Hospital Universitario Miguel Servet, Avda Isabel La Católica 1-3, 50009, Saragossa, Spain.
| | - Rosa M Sánchez-Hernández
- Sección de Endocrinología y Nutrición, Complejo Hospitalario Universitario Insular Materno-Infantil, Instituto Universitario de Investigaciones Biomédicas y Sanitarias de La Universidad de Las Palmas de Gran Canaria, de Las Palmas de Gran Canaria, Spain
| | - José Luis Díaz
- Unidad de Lípidos y Riesgo Cardiovascular, Medicina Interna, Hospital Universitario A Coruña, A Coruña, Spain
| | - Estíbaliz Jarauta
- Hospital Universitario Miguel Servet, IIS Aragón, CIBERCV, Saragossa, Spain
- Unidad de Lípidos, Hospital Universitario Miguel Servet, Avda Isabel La Católica 1-3, 50009, Saragossa, Spain
| | | | - Xavier Pintó
- Unidad de Lípidos y Riesgo Cardiovascular, Servicio de Medicina Interna, Hospital Universitario de Bellvitge, CIBEROBN, Barcelona, Spain
| | - Carlos Morillas
- Unidad de Lípidos Clínico-Epidemiológica, Hospital Universitario Dr. Peset, Valencia, Spain
| | - Núria Plana
- Unitat de Medicina Vascular I Metabolisme, Hospital Sant Joan de Reus, IISPV, CIBERDEM, Universitat Rovira I Virgili, Reus, Spain
| | - Juan Pedro-Botet
- Unidad de Lípidos y Riesgo Vascular, Servicio de Endocrinología y Nutrición, Hospital del Mar, Universidad Autónoma de Barcelona, Barcelona, Spain
| | - Fernando Civeira
- Hospital Universitario Miguel Servet, IIS Aragón, CIBERCV, Saragossa, Spain.
- Unidad de Lípidos, Hospital Universitario Miguel Servet, Avda Isabel La Católica 1-3, 50009, Saragossa, Spain.
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Xiao Y, Yu B, Chao C, Wang S, Hu D, Wu C, Luo Y, Xie L, Li C, Peng D, Zhou Z. Chinese expert consensus on blood lipid management in patients with diabetes (2024 edition). J Transl Int Med 2024; 12:325-343. [PMID: 39360162 PMCID: PMC11444477 DOI: 10.2478/jtim-2024-0014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/04/2024] Open
Abstract
Diabetes is a significant independent risk factor for atherosclerotic cardiovascular disease (ASCVD), with dyslipidemia playing a critical role in the initiation and progression of ASCVD in diabetic patients. In China, the current prevalence of dyslipidemia in diabetes is high, but the control rate remains low. Therefore, to enhance lipid management in patients with diabetes, the Endocrinology and Metabolism Physician Branch of the Chinese Medical Doctor Association, in collaboration with the Experts' Committee of the National Society of Cardiometabolic Medicine, has convened experts to develop a consensus on the management of dyslipidemia in patients with type 1 or type 2 diabetes. The development of this consensus is informed by existing practices in lipid management among Chinese diabetic patients, incorporating contemporary evidence-based findings and guidelines from national and international sources. The consensus encompasses lipid profile characteristics, the current epidemiological status of dyslipidemia, ASCVD risk stratification, and lipid management procedures in diabetic patients. For the first time, both low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol have been recommended as primary targets for lipid intervention in diabetic patients. The consensus also includes a summary and recommendations for lipid management strategies in special diabetic populations, including children and adolescents, individuals aged 75 years and older, patients with chronic kidney disease, metabolic-associated fatty liver disease, and those who are pregnant. This comprehensive consensus aims to improve cardiovascular outcomes in diabetic patients by contributing to the dissemination of key clinical advancements and guiding clinical practice.
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Affiliation(s)
- Yang Xiao
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha410011, Hunan Province, China
| | - Bilian Yu
- Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha410011, Hunan Province, China
| | - Chen Chao
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha410011, Hunan Province, China
| | - Shuai Wang
- Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha410011, Hunan Province, China
| | - Die Hu
- Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha410011, Hunan Province, China
| | - Chao Wu
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha410011, Hunan Province, China
| | - Yonghong Luo
- Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha410011, Hunan Province, China
| | - Lingxiang Xie
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha410011, Hunan Province, China
| | - Chenyu Li
- Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha410011, Hunan Province, China
| | - Daoquan Peng
- Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha410011, Hunan Province, China
| | - Zhiguang Zhou
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha410011, Hunan Province, China
| | - Endocrinology and Metabolism Physician Branch of the Chinese Medical Doctor Association
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha410011, Hunan Province, China
- Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha410011, Hunan Province, China
| | - National Society of Cardiometabolic Medicine
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha410011, Hunan Province, China
- Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha410011, Hunan Province, China
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Mousavi I, Nambi V, Abushamat LA, Al-Kindi SG, Shapiro MD, Sperling L, Virani SS, Minhas AMK. Bempedoic Acid in Secondary Prevention. Am J Prev Cardiol 2024; 19:100715. [PMID: 39224771 PMCID: PMC11367048 DOI: 10.1016/j.ajpc.2024.100715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Revised: 07/18/2024] [Accepted: 08/02/2024] [Indexed: 09/04/2024] Open
Abstract
•Bempedoic acid has been shown to reduce major adverse cardiovascular outcomes in patients unable to take statins due to statin-associated side effects.•Analysis of CLEAR Outcomes trial data reveals possible differences in baseline characteristics between the primary and secondary prevention subgroups.•Further research is needed to optimize use of bempedoic acid and clarify its impact on cardiovascular outcomes in diverse patient populations.
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Affiliation(s)
- Idine Mousavi
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Vijay Nambi
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
- Division of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
- Section of Cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Layla A. Abushamat
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
- Division of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | | | - Michael D. Shapiro
- Section on Cardiovascular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Laurence Sperling
- Division of Cardiology, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA, USA
| | - Salim S. Virani
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
- Aga Khan University, Karachi, Pakistan
- Baylor College of Medicine and Texas Heart Institute, Houston, TX, USA
| | - Abdul Mannan Khan Minhas
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
- Division of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
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Leiter LA, Raal FJ, Schwartz GG, Koenig W, Ray KK, Landmesser U, Han J, Conde LG, Wright RS. Inclisiran in individuals with diabetes or obesity: Post hoc pooled analyses of the ORION-9, ORION-10 and ORION-11 Phase 3 randomized trials. Diabetes Obes Metab 2024; 26:3223-3237. [PMID: 38757725 DOI: 10.1111/dom.15650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 04/26/2024] [Accepted: 04/26/2024] [Indexed: 05/18/2024]
Abstract
AIMS To conduct a pooled analysis of Phase 3 trials investigating the efficacy and safety of inclisiran across glycaemic and body mass index (BMI) strata. MATERIALS AND METHODS Participants were randomized 1:1 to receive 300 mg inclisiran sodium or placebo twice yearly, after initial and 3-month doses up to 18 months, with background oral lipid-lowering therapy. Analyses were stratified by glycaemic status (normoglycaemia, prediabetes, and diabetes) or BMI (<25, ≥25 to <30, ≥30 to <35, and ≥35 kg/m2). Co-primary endpoints were percentage and time-adjusted percentage change in low-density lipoprotein (LDL) cholesterol from baseline. Safety was also assessed. RESULTS Baseline characteristics were balanced between treatment arms and across strata. Percent LDL cholesterol change (placebo-corrected) with inclisiran from baseline to Day 510 ranged from -47.6% to -51.9% and from -48.8% to -54.4% across glycaemic/BMI strata, respectively. Similarly, time-adjusted percentage changes after Day 90 and up to Day 540 ranged from -46.8% to -52.0% and from -48.6% to -53.3% across glycaemic/BMI strata, respectively. Inclisiran led to significant reductions in proprotein convertase subtilisin/kexin type 9 and other atherogenic lipids and lipoproteins versus placebo across the glycaemic/BMI strata. The proportions of individuals achieving LDL cholesterol thresholds of <1.8 mmol/L and <1.4 mmol/L with inclisiran increased with increasing glycaemic and BMI strata. Across the glycaemic/BMI strata, a higher proportion of individuals had mild/moderate treatment-emergent adverse events (TEAEs) at the injection site with inclisiran (2.8%-7.7%) versus placebo (0.2%-2.1%). CONCLUSION Inclisiran provided substantial and sustained LDL cholesterol lowering across glycaemic/BMI strata, with a modest excess of transient mild-to-moderate TEAEs at the injection site.
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Affiliation(s)
- Lawrence A Leiter
- Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, Canada
| | - Frederick J Raal
- Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Gregory G Schwartz
- Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Wolfgang Koenig
- Deutsches Herzzentrum München, Technische Universität München, Munich, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
- Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany
| | - Kausik K Ray
- Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College, London, UK
| | - Ulf Landmesser
- Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Charité University Medicine Berlin, Friede Springer Cardiovascular Prevention Center od Charité, Berlin Institute of Health, DZHK, Partner Site Berlin, Berlin, Germany
| | - Jackie Han
- Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA
| | | | - R Scott Wright
- Division of Preventive Cardiology and Department of Cardiology, Mayo Clinic, Rochester, Minnesota, USA
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24
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Chen T, Liu N. How safe are proprotein convertase subtilisinekexin type 9 inhibitors in diabetes? Curr Opin Lipidol 2024; 35:187-194. [PMID: 38527426 DOI: 10.1097/mol.0000000000000934] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/27/2024]
Abstract
PURPOSE OF REVIEW To examine the safety of proprotein convertase subtilisinekexin type 9 (PCSK9) inhibitors in patients with diabetes, specifically focusing on their impact on glucose metabolism. RECENT FINDINGS Patients with diabetes often require intensified lipid-lowering therapy. PCSK9 inhibitors can reduce low-density lipoprotein cholesterol (LDL-C) concentrations by approximately 60%, and significantly reduce cardiovascular risk when added to statin therapy. Some studies have suggested an association between low LDL-C levels and an increased risk of new-onset diabetes, and genetics has almost consistently shown an increased glucose concentration and risk of diabetes. Most clinical trials have not demonstrated a deterioration in glycaemic control in patients with diabetes after the use of PCSK9 inhibitors, and they do not lead to other significant treatment-emergent adverse events. SUMMARY Although the majority of patients with diabetes are undergoing background statin therapy, which may mask potential adverse effects of PCSK9 inhibitors on glycaemic control, current data suggest that the benefits outweigh the risks for diabetic patients using PCSK9 inhibitors. Considering the different nature of genetic studies and of clinical trials, close monitoring of glucose parameters is necessary, especially in individuals with prediabetes.
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Affiliation(s)
- Tian Chen
- Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China
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25
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Goodman SG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, Harrington RA, Jukema JW, White HD, Zeiher AM, Manvelian G, Pordy R, Poulouin Y, Stipek W, Garon G, Schwartz GG. Safety of the PCSK9 inhibitor alirocumab: insights from 47 296 patient-years of observation. EUROPEAN HEART JOURNAL. CARDIOVASCULAR PHARMACOTHERAPY 2024; 10:342-352. [PMID: 38658193 PMCID: PMC11249957 DOI: 10.1093/ehjcvp/pvae025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 03/25/2024] [Accepted: 04/23/2024] [Indexed: 04/26/2024]
Abstract
The ODYSSEY OUTCOMES trial, comprising over 47 000 patient-years of placebo-controlled observation, demonstrated important reductions in the risk of recurrent ischaemic cardiovascular events with the monoclonal antibody to proprotein convertase subtilisin/kexin type 9 alirocumab, as well as lower all-cause death. These benefits were observed in the context of substantial and persistent lowering of low-density lipoprotein cholesterol with alirocumab compared with that achieved with placebo. The safety profile of alirocumab was indistinguishable from matching placebo except for a ∼1.7% absolute increase in local injection site reactions. Further, the safety of alirocumab compared with placebo was evident in vulnerable groups identified before randomization, such as the elderly and those with diabetes mellitus, previous ischaemic stroke, or chronic kidney disease. The frequency of adverse events and laboratory-based abnormalities was generally similar to that in placebo-treated patients. Thus, alirocumab appears to be a safe and effective lipid-modifying treatment over a duration of at least 5 years.
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Affiliation(s)
- Shaun G Goodman
- Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada
- St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Philippe Gabriel Steg
- Université Paris-Cité, Institut Universitaire de France, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, FACT (French Alliance for Cardiovascular Trials), and INSERM U1148, F-75018 Paris, France
| | - Michael Szarek
- CPC Clinical Research and Division of Cardiology, University of Colorado School of Medicine, Aurora, 80045 CO, USA
- State University of New York, Downstate Health Sciences University, Brooklyn, NY 11203, USA
| | - Deepak L Bhatt
- Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Vera A Bittner
- Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL 35233, USA
| | - Rafael Diaz
- Estudios Cardiológicos Latinoamérica, Instituto Cardiovascular de Rosario, S2000 Rosario, Argentina
| | | | - J Wouter Jukema
- Department of Cardiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
- Netherlands Heart Institute, 3511 EP Utrecht, The Netherlands
| | - Harvey D White
- Green Lane Cardiovascular Research Unit, Te Whatu Ora—Health New Zealand, Te Toka Tumai, and University of Auckland, Auckland 1030, New Zealand
| | - Andreas M Zeiher
- Department of Medicine III, Goethe University, 60596 Frankfurt am Main, Germany
| | | | - Robert Pordy
- Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA
| | | | - Wanda Stipek
- Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA
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26
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Wright RS, Ray KK, Landmesser U, Koenig W, Raal FJ, Leiter LA, Conde LG, Han J, Schwartz GG. Effects of Inclisiran in Patients With Atherosclerotic Cardiovascular Disease: A Pooled Analysis of the ORION-10 and ORION-11 Randomized Trials. Mayo Clin Proc 2024; 99:S0025-6196(24)00167-8. [PMID: 39093262 DOI: 10.1016/j.mayocp.2024.03.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 03/22/2024] [Accepted: 03/26/2024] [Indexed: 08/04/2024]
Abstract
OBJECTIVE To evaluate the efficacy, safety, and tolerability of inclisiran in participants with atherosclerotic cardiovascular disease (ASCVD) from ORION-10 and ORION-11 stratified by key patient characteristics. PATIENTS AND METHODS Participants were randomized 1:1 to receive 300 mg inclisiran sodium (284 mg inclisiran) or placebo on days 1, 90, 270, and 450, alongside background lipid-lowering therapy. This pooled, post hoc analysis stratified participants with ASCVD by sex, age, race, kidney function, body mass index, and glycemic status. Co-primary endpoints were percentage changes in low-density lipoprotein cholesterol (LDL-C) from baseline to day 510, and after day 90 and up to day 540 (time-adjusted). LDL-C goal attainment and safety were also assessed. RESULTS This analysis of 2975 participants included: female, n=827; Black, n=213; 75 years of age or older, n=458; obese, n=1474; diabetes, n=1182; and moderate-to-severe chronic kidney disease, n=538. Mean baseline LDL-C levels in the total ASCVD population were balanced between treatment arms (inclisiran, 103.4 mg/dL; placebo, 102.0 mg/dL). With inclisiran, mean placebo-corrected percentage changes in LDL-C from baseline were -51.5% (95% CI, -54.0% to -49.0%) and -52.1% (95% CI, -53.9% to -50.4%) to day 510 and day 540 (time-adjusted), respectively; this was consistent across subgroups. LDL-C less than 55 mg/dL at 1 or more visits was reached by 87.6% of participants receiving inclisiran. The inclisiran safety profile was consistent across subgroups. CONCLUSION Twice-yearly inclisiran (after initial and 3-month doses) was well-tolerated and provided significant, consistent LDL-C reductions for up to 18 months in participants with ASCVD independent of key patient characteristics (ORION-10 [Inclisiran for Participants With Atherosclerotic Cardiovascular Disease and Elevated Low-density Lipoprotein Cholesterol]; NCT03399370 and ORION-11 [Inclisiran for Subjects With ASCVD or ASCVD-Risk Equivalents and Elevated Low-density Lipoprotein Cholesterol]; NCT03400800).
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Affiliation(s)
- R Scott Wright
- Division of Preventive Cardiology and the Department of Cardiology, Mayo Clinic, Rochester, MN, USA.
| | - Kausik K Ray
- Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College London, London, UK
| | - Ulf Landmesser
- Department of Cardiology, Angiology, and Intensive Care Medicine, Deutsches Herzzentrum Charité; Charité Universitätsmedizin Berlin, Berlin Institute of Health, DZHK, Partner Site Berlin, Berlin, Germany
| | - Wolfgang Koenig
- Deutsches Herzzentrum München, Technische Universität München, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany and Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany
| | - Frederick J Raal
- Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Lawrence A Leiter
- Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto, Toronto, ON, Canada
| | | | - Jackie Han
- Novartis Pharmaceuticals Corp, East Hanover, NJ, USA
| | - Gregory G Schwartz
- Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA
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Darroudi S, Mahdavizadeh V, Mirzaei AH, Esparham A, Ahmadyar S, Esmaily H, Ferns GA, Moohebati M. Triglyceride glucose index and triglyceride HDL ratio as predictors of coronary artery stenosis in diabetic and non-diabetic patients. Nutr Metab Cardiovasc Dis 2024; 34:1692-1695. [PMID: 38772847 DOI: 10.1016/j.numecd.2023.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 11/18/2023] [Accepted: 12/01/2023] [Indexed: 05/23/2024]
Abstract
BACKGROUND AND AIM The current study investigated the association between triglyceride-glucose index (TyG) and triglyceride/HDL-C indices and coronary atherosclerosis extent in diabetic and non-diabetic patients. METHODS AND RESULTS In this case-control study, 1538 individuals were classified into two groups: diabetic and non-diabetic subjects. Each group was further grouped as follows: (1) angiography+ (2) angiography-and (3) subjects without a history of cardiovascular diseases. The TyG and TG/HDL-C indices were compared between the subgroups of the diabetic (n = 407) and non-diabetic (n = 1131) groups. In both diabetic and non-diabetic patients, there was no significant association in TG/HDL-C; and diabetic subjects, angiography+ and angiography-groups had significantly higher TyG (p < 0.05). A high TyG index was associated with a higher risk of angiography+ (OR: 1.883 (1.410-2.514)). CONCLUSIONS The TyG index, but not the TG/HDL-C, was an independent marker for predicting the severity of coronary stenosis in non-diabetic patients.
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Affiliation(s)
- Susan Darroudi
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Vahid Mahdavizadeh
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran; Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Hossain Mirzaei
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran; Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ali Esparham
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran; Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Soheil Ahmadyar
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran; Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Habibollah Esmaily
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran; Social Determinants of Health Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon A Ferns
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran; Brighton & Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex BN1 9PH, UK
| | - Mohsen Moohebati
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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Rivera FB, Cha SW, Magalong JV, Bantayan NRB, Cruz LLA, Arias-Aguirre E, Aguirre Z, Varona MC, Co EMF, Lumbang GNO, Enkhmaa B. Safety profile of proprotein convertase subtilisin/kexin type 9 inhibitors alirocumab and evolocumab: an updated meta-analysis and meta-regression. Curr Med Res Opin 2024; 40:1103-1121. [PMID: 38836510 DOI: 10.1080/03007995.2024.2363971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Accepted: 05/31/2024] [Indexed: 06/06/2024]
Abstract
BACKGROUND The use of alirocumab and evolocumab is generally safe and well-tolerated. However, concerns remain about their long-term safety, especially with regard to new-onset or worsening diabetes mellitus (DM). We aim to assess the safety profile of alirocumab and evolocumab compared to comparator. METHODS Studies were retrieved comparing the safety of PCSK9i vs. comparator (placebo or statin with or without ezetimibe). The primary outcome was adverse events leading to death. Secondary outcomes included serious adverse events, new onset diabetes mellitus (DM), worsening of DM, neurocognitive dysfunction, creatine kinase (CK) elevation, elevation of liver enzymes and local injection site reaction. Factors associated with the treatment effect were determined by meta-regression analysis. Subgroup analyses were done to explore potential treatment effect differences based on PCSK9i type and treatment duration. RESULTS We identified 56 studies with 85,123 adults (29.14% females). PCSK9i was not associated with adverse events that lead to death (OR 0.94, 95% CI 0.84 to 1.04, p = 0.22). Between the two PCSK9i, alirocumab decreased adverse events leading to death (OR 0.79, 95% CI, 0.67 to 0.94, p = 0.008). PCSK9i was associated with less serious events compared to the comparator (OR 0.93, 95% CI 0.89 to 0.98, p < 0.001). This reduction was driven mainly by alirocumab (OR 0.89, 95% CI, 0.85 to 0.93, p < 0.001). Evolocumab worsened DM (OR 2.3, 95% CI 1.26 to 4.2, p = 0.041). Subgroup analysis showed worsening of DM in the first 24 weeks of treatment with odds being highest in the first 12 weeks of treatment (<12 weeks: OR 3.82, 95% CI 1.13 to 12.99, p = 0.03; 12-24 weeks OR 2.12, 95% CI 1.20 to 3.73, p = 0.01. On the other hand, therapy >24 weeks reduced the odds of worsening DM (OR 0.89, 95% CI 0.79 to 0.99, p = 0.04). PCSK9i did not increase cognitive dysfunction, (OR 1.02, 95% CI 0.88 to 1.18, p = 0.76), or cause elevations in liver enzyme (OR 0.91, 95% CI 0.81 to 1.03, p = 0.14), or CK (OR 0.82, 95% CI 0.65 to 1.04, p = 0.10). However, PCSK9i was associated with local injection site reaction (OR 1.54, 95% CI 1.37 to 1.73, p < 0.01). CONCLUSION Alirocumab decreased adverse events leading to death. Alirocumab and Evolocumab both decreased serious adverse events. PCSK9i did not increase new onset DM however evolocumab worsened DM in the first 24 weeks of treatment. PCSK9i did not increase neurologic dysfunction, and did not elevate liver enzymes and CK, however it was associated with local injection site reaction.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Byambaa Enkhmaa
- Division of Endocrinology, Diabetes & Metabolism, UC Davis Health, Davis, CA, USA
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Liu H, Wang L, Wang H, Hao X, Du Z, Li C, Hou X. The association of triglyceride-glucose index with major adverse cardiovascular and cerebrovascular events after acute myocardial infarction: a meta-analysis of cohort studies. Nutr Diabetes 2024; 14:39. [PMID: 38844442 PMCID: PMC11156940 DOI: 10.1038/s41387-024-00295-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 05/02/2024] [Accepted: 05/15/2024] [Indexed: 06/09/2024] Open
Abstract
BACKGROUND Insulin resistance (IR) is indicated to be linked with adverse outcomes of acute myocardial infarction (AMI), for its pro-inflammatory and pro-thromboplastic function. The triglyceride-glucose (TyG) index is a newly developed substitute marker for IR. The aim of this pooled analysis was to provide a summary of the relationship of TyG index with occurrences of major adverse cardiovascular and cerebrovascular events (MACCEs) among populations suffering from AMI. METHODS Cohorts reporting multivariate-adjusted hazard ratios of TyG index with MACCEs or its independent events were identified through systematically searching PubMed, MEDLINE, Web of science, Embase and Cochrane databases. Results were combined using a random-effects model. RESULTS 21 cohorts comprising 20403 individuals were included. Compared to individuals in the lowest TyG category, patients in the highest TyG category exhibited elevated risks of both MACCEs (P < 0.00001) and all-cause death (P < 0.00001). These findings were in line with the results as TyG analyzed as continuous variables (MACCEs: P = 0.006; all-cause death: P < 0.00001). Subgroup analysis demonstrated that diabetic status, type of AMI, nor the reperfusion therapy did not destruct this correlation (for subgroups, all P < 0.05). CONCLUSION All these indicated that higher TyG index could potentially predict MACCEs and all-cause death in patients with AMI as an independent indicator.
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Affiliation(s)
- Huiruo Liu
- Centre for Cardiac Intensive Care, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Liangshan Wang
- Centre for Cardiac Intensive Care, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Hong Wang
- Centre for Cardiac Intensive Care, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Xing Hao
- Centre for Cardiac Intensive Care, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Zhongtao Du
- Centre for Cardiac Intensive Care, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Chenglong Li
- Centre for Cardiac Intensive Care, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Xiaotong Hou
- Centre for Cardiac Intensive Care, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
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Béliard S, Mourre F, Valéro R. Hyperlipidaemia in diabetes: are there particular considerations for next-generation therapies? Diabetologia 2024; 67:974-984. [PMID: 38376536 PMCID: PMC11058750 DOI: 10.1007/s00125-024-06100-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Accepted: 12/07/2023] [Indexed: 02/21/2024]
Abstract
Dyslipidaemias are major cardiovascular risk factors, especially in people with diabetes. In this area, next-generation therapies targeting circulating lipoparticle metabolism (LDL, VLDL, chylomicrons, HDL) have recently been approved by the European and US medical agencies, including anti- proprotein convertase subtilisin/kexin 9 (PCSK9) antibodies; an siRNA targeting PCSK9; bempedoic acid, which targets ATP citrate lyase; an antisense oligonucleotide targeting apolipoprotein C-III; an anti-angiopoietin-like 3 antibody; and a purified omega-3 fatty acid, icosapent ethyl. Other therapies are in different phases of development. There are several important considerations concerning the link between these new lipid-lowering therapies and diabetes. First, since concerns were first raised in 2008 about an increased risk of new-onset diabetes mellitus (NODM) with intensive statin treatment, each new lipid-lowering therapy is being evaluated for its associated risk of NODM, particularly in individuals with prediabetes (impaired fasting glucose and/or impaired glucose tolerance). Second, people with diabetes represent a large proportion of those at high or very high cardiovascular risk in whom these lipid-lowering drugs are currently, or will be, prescribed. Thus, the efficacy of these drugs in subgroups with diabetes should also be closely considered, as well as any potential effects on glycaemic control. In this review, we describe the efficacy of next-generation therapies targeting lipoprotein metabolism in subgroups of people with diabetes and their effects on glycaemic control in individuals with diabetes and prediabetes and in normoglycaemic individuals.
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Affiliation(s)
- Sophie Béliard
- APHM (Assistance Publique-Hôpitaux de Marseille), Department of Nutrition, Metabolic Diseases, Endocrinology, La Conception Hospital, Marseille, France.
- Inserm, INRAE (Institut National de Recherche pour l'agriculture, l'Alimentation et l'Environnement), C2VN (Centre de recherche en CardioVasculaire et Nutrition), Aix Marseille University, Marseille, France.
| | - Florian Mourre
- APHM (Assistance Publique-Hôpitaux de Marseille), Department of Nutrition, Metabolic Diseases, Endocrinology, La Conception Hospital, Marseille, France
- Inserm, INRAE (Institut National de Recherche pour l'agriculture, l'Alimentation et l'Environnement), C2VN (Centre de recherche en CardioVasculaire et Nutrition), Aix Marseille University, Marseille, France
| | - René Valéro
- APHM (Assistance Publique-Hôpitaux de Marseille), Department of Nutrition, Metabolic Diseases, Endocrinology, La Conception Hospital, Marseille, France
- Inserm, INRAE (Institut National de Recherche pour l'agriculture, l'Alimentation et l'Environnement), C2VN (Centre de recherche en CardioVasculaire et Nutrition), Aix Marseille University, Marseille, France
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Cheng Q, Sun J, Zhong H, Wang Z, Liu C, Zhou S, Deng J. Research trends in lipid-lowering therapies for coronary heart disease combined with hyperlipidemia: a bibliometric study and visual analysis. Front Pharmacol 2024; 15:1393333. [PMID: 38828451 PMCID: PMC11140088 DOI: 10.3389/fphar.2024.1393333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 05/03/2024] [Indexed: 06/05/2024] Open
Abstract
Background Cardiovascular disease (CVD) poses a significant global health and economic challenge, with atherosclerosis being a primary cause. Over the past 40 years, substantial research has been conducted into the prevention and reversal of atherosclerosis, resulting in the development of lipid-lowering agents such as statins and fibrates. Despite the extensive literature and formulation of numerous therapeutic guidelines in this domain, a comprehensive bibliometric analysis of the current research landscape and trends has not been performed. This study aimed to elucidate the evolution and milestones of research into lipid-lowering treatments for coronary heart disease (CHD) in conjunction with hyperlipidemia through bibliometric analysis, offering insights into future directions for treatment strategies. Methods This study examined publications from 1986 to 2023 retrieved from the Web of Science database (Core Collection). Utilizing tools such as VOSviewer, Pajek, and CiteSpace, we analyzed publication and citation numbers, H-indexes, contributions by countries and institutions, authorship, journal sources, and keyword usage to uncover research trajectories and areas of focus. Results Our analysis of 587 publications revealed a recent surge in research output, particularly post-2003. The American Journal of Cardiology published the highest number of studies, with 40 articles, whereas Circulation received the highest number of citations (6,266). Key contributors included the United States, Japan, and China, with the United States leading in citation numbers and the H-index. Harvard University and Leiden University emerged as pivotal institutions, and Professors J. Wouter Jukema and Robert P. Giugliano were identified as leading experts. Keyword analysis disclosed five thematic clusters, indicating a shift in research towards new drug combinations and strategies, signaling future research directions. Conclusion The last 4 decades have seen a notable rise in publications on lipid-lowering therapies for CHD and hyperlipidemia, with the United States retaining world-leading status. The increase in international collaboration aids the shift towards research into innovative lipid-lowering agents and therapeutic approaches. PCSK9 inhibitors and innovative combination therapies, including antisense oligonucleotides and angiopoietin-like protein 3 inhibitors, provide avenues for future research, intending to maximize the safety and efficacy of treatment approaches.
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Affiliation(s)
- Quankai Cheng
- Department of Cardiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Jingjing Sun
- Department of Cardiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Haicheng Zhong
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Ziming Wang
- Department of Cardiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Chang Liu
- Department of Cardiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Sheng Zhou
- Department of Cardiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Jie Deng
- Department of Cardiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
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Fularski P, Czarnik W, Dąbek B, Lisińska W, Radzioch E, Witkowska A, Młynarska E, Rysz J, Franczyk B. Broader Perspective on Atherosclerosis-Selected Risk Factors, Biomarkers, and Therapeutic Approach. Int J Mol Sci 2024; 25:5212. [PMID: 38791250 PMCID: PMC11121693 DOI: 10.3390/ijms25105212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Revised: 05/01/2024] [Accepted: 05/07/2024] [Indexed: 05/26/2024] Open
Abstract
Atherosclerotic cardiovascular disease (ASCVD) stands as the leading cause of mortality worldwide. At its core lies a progressive process of atherosclerosis, influenced by multiple factors. Among them, lifestyle-related factors are highlighted, with inadequate diet being one of the foremost, alongside factors such as cigarette smoking, low physical activity, and sleep deprivation. Another substantial group of risk factors comprises comorbidities. Amongst others, conditions such as hypertension, diabetes mellitus (DM), chronic kidney disease (CKD), or familial hypercholesterolemia (FH) are included here. Extremely significant in the context of halting progression is counteracting the mentioned risk factors, including through treatment of the underlying disease. What is more, in recent years, there has been increasing attention paid to perceiving atherosclerosis as an inflammation-related disease. Consequently, efforts are directed towards exploring new anti-inflammatory medications to limit ASCVD progression. Simultaneously, research is underway to identify biomarkers capable of providing insights into the ongoing process of atherosclerotic plaque formation. The aim of this study is to provide a broader perspective on ASCVD, particularly focusing on its characteristics, traditional and novel treatment methods, and biomarkers that can facilitate its early detection.
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Affiliation(s)
- Piotr Fularski
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Witold Czarnik
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Bartłomiej Dąbek
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Wiktoria Lisińska
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Ewa Radzioch
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Alicja Witkowska
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Ewelina Młynarska
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Beata Franczyk
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
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Shou Y, Li X, Fang Q, Xie A, Zhang Y, Fu X, Wang M, Gong W, Zhang X, Yang D. Progress in the treatment of diabetic cardiomyopathy, a systematic review. Pharmacol Res Perspect 2024; 12:e1177. [PMID: 38407563 PMCID: PMC10895687 DOI: 10.1002/prp2.1177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 12/29/2023] [Accepted: 01/19/2024] [Indexed: 02/27/2024] Open
Abstract
Diabetic cardiomyopathy (DCM) is a condition characterized by myocardial dysfunction that occurs in individuals with diabetes, in the absence of coronary artery disease, valve disease, and other conventional cardiovascular risk factors such as hypertension and dyslipidemia. It is considered a significant and consequential complication of diabetes in the field of cardiovascular medicine. The primary pathological manifestations include myocardial hypertrophy, myocardial fibrosis, and impaired ventricular function, which can lead to widespread myocardial necrosis. Ultimately, this can progress to the development of heart failure, arrhythmias, and cardiogenic shock, with severe cases even resulting in sudden cardiac death. Despite several decades of both fundamental and clinical research conducted globally, there are currently no specific targeted therapies available for DCM in clinical practice, and the incidence and mortality rates of heart failure remain persistently high. Thus, this article provides an overview of the current treatment modalities and novel techniques pertaining to DCM, aiming to offer valuable insights and support to researchers dedicated to investigating this complex condition.
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Affiliation(s)
- Yiyi Shou
- Department of Clinical MedicineAffiliated Hospital of Hangzhou Normal University, Hangzhou Normal UniversityHangzhouChina
| | - Xingyu Li
- Department of Clinical MedicineAffiliated Hospital of Hangzhou Normal University, Hangzhou Normal UniversityHangzhouChina
| | - Quan Fang
- Department of Clinical MedicineAffiliated Hospital of Hangzhou Normal University, Hangzhou Normal UniversityHangzhouChina
| | - Aqiong Xie
- Department of Clinical MedicineAffiliated Hospital of Hangzhou Normal University, Hangzhou Normal UniversityHangzhouChina
| | - Yinghong Zhang
- Department of ImmunologyAffiliated Hospital of Hangzhou Normal UniversityHangzhouChina
| | - Xinyan Fu
- Department of CardiologyAffiliated Hospital of Hangzhou Normal UniversityHangzhouChina
| | - Mingwei Wang
- Department of CardiologyAffiliated Hospital of Hangzhou Normal UniversityHangzhouChina
| | - Wenyan Gong
- Department of Clinical MedicineAffiliated Hospital of Hangzhou Normal University, Hangzhou Normal UniversityHangzhouChina
- Department of CardiologyAffiliated Hospital of Hangzhou Normal UniversityHangzhouChina
| | - Xingwei Zhang
- Department of Clinical MedicineAffiliated Hospital of Hangzhou Normal University, Hangzhou Normal UniversityHangzhouChina
- Department of CardiologyAffiliated Hospital of Hangzhou Normal UniversityHangzhouChina
| | - Dong Yang
- Department of Clinical MedicineAffiliated Hospital of Hangzhou Normal University, Hangzhou Normal UniversityHangzhouChina
- Department of CardiologyAffiliated Hospital of Hangzhou Normal UniversityHangzhouChina
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Ma J, Wang M, Wu P, Ma X, Chen D, Jia S, Yan N. Predictive effect of triglyceride-glucose index on No-Reflow Phenomenon in patients with type 2 diabetes mellitus and acute myocardial infarction undergoing primary percutaneous coronary intervention. Diabetol Metab Syndr 2024; 16:67. [PMID: 38481310 PMCID: PMC10938834 DOI: 10.1186/s13098-024-01306-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 03/05/2024] [Indexed: 03/17/2024] Open
Abstract
OBJECTIVE Triglyceride glucose (TyG) index is considered as a new alternative marker of insulin resistance and a clinical predictor of type 2 diabetes mellitus (T2DM) combined with coronary artery disease. However, the prognostic value of TyG index on No-Reflow (NR) Phenomenon in T2DM patients with acute myocardial infarction (AMI) remains unclear. METHODS In this retrospective study, 1683 patients with T2DM and AMI underwent primary percutaneous coronary intervention (PCI) were consecutively included between January 2014 and December 2019. The study population was divided into two groups as follows: Reflow (n = 1277) and No-reflow (n = 406) group. The TyG index was calculated as the ln [fasting triglycerides (mg/dL)×fasting plasma glucose (mg/dL)/2].Multivariable logistic regression models and receiver-operating characteristic curve analysis were conducted to predict the possible risk of no-reflow. Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) were calculated to determine the ability of the TyG index to contribute to the baseline risk model. RESULTS Multivariable logistic regression models revealed that the TyG index was positively associated with NR[OR,95%CI:5.03,(2.72,9.28),p<0.001] in patients with T2DM and AMI. The area under the curve (AUC) of the TyG index predicting the occurrence of NR was 0.645 (95% CI 0.615-0.673; p < 0.001)], with the cut-off value of 8.98. The addition of TyG index to a baseline risk model had an incremental effect on the predictive value for NR [net reclassification improvement (NRI): 0.077(0.043to 0.111), integrated discrimination improvement (IDI): 0.070 (0.031to 0.108), all p < 0.001]. CONCLUSIONS High TyG index was associated with an increased risk of no-reflow after PCI in AMI patients with T2DM. The TyG index may be a valid predictor of NR phenomenon of patients with T2DM and AMI. Early recognition of NR is critical to improve outcomes with AMI and T2DM patients.
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Affiliation(s)
- Juan Ma
- School of Clinical Medicine, Ningxia Medical University, 750004, Yinchuan, People's Republic of China
| | - Mohan Wang
- School of Clinical Medicine, Ningxia Medical University, 750004, Yinchuan, People's Republic of China
| | - Peng Wu
- School of Clinical Medicine, Ningxia Medical University, 750004, Yinchuan, People's Republic of China
| | - Xueping Ma
- Heart Centre, Department of Cardiovascular Diseases, General Hospital of Ningxia Medical University, 750004, Yinchuan, Ningxia, People's Republic of China
| | - Dapeng Chen
- Heart Centre, Department of Cardiovascular Diseases, General Hospital of Ningxia Medical University, 750004, Yinchuan, Ningxia, People's Republic of China
| | - Shaobin Jia
- Heart Centre, Department of Cardiovascular Diseases, General Hospital of Ningxia Medical University, 750004, Yinchuan, Ningxia, People's Republic of China.
| | - Ning Yan
- Heart Centre, Department of Cardiovascular Diseases, General Hospital of Ningxia Medical University, 750004, Yinchuan, Ningxia, People's Republic of China.
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Xu X, Qi Z, Han X, Wang Y, Yu M, Geng Z. Combined-task deep network based on LassoNet feature selection for predicting the comorbidities of acute coronary syndrome. Comput Biol Med 2024; 170:107992. [PMID: 38242014 DOI: 10.1016/j.compbiomed.2024.107992] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 01/03/2024] [Accepted: 01/13/2024] [Indexed: 01/21/2024]
Abstract
Acute coronary syndrome (ACS) is a multifaceted cardiovascular condition frequently accompanied by multiple comorbidities, which can have significant implications for patient outcomes and treatment approaches. Precisely predicting these comorbidities is crucial for providing personalized care and making well-informed clinical decisions. However, there is a shortage of research investigating the identification of risk factors associated with ACS comorbidities and accurately predicting their likelihood of occurrence beyond heart failure. In this study, an approach called Combined-task Deep Network based on LassoNet feature selection (CDNL) is presented for predicting ACS comorbidities, including hypertension, diabetes, hyperlipidemia, and heart failure. In order to identify crucial biomarkers associated with ACS comorbidities, the proposed framework first incorporates LassoNet, which extends Lasso regression to the deep network by adding a skip (residual) layer. Additionally, a correlation score calculation method across tasks is introduced based on measuring the overlap of identified biomarkers and their assigned importance. This method enables the development of an optimal combined-task prediction model for each ACS comorbidity, addressing the challenge of limited representations in traditional multi-task learning. Our evaluation, conducted through a meticulous cross-sectional study at a tertiary hospital in China, involved a dataset of 2941 samples with 42 clinical features. The results demonstrate that CDNL facilitates the identification of significant biomarkers and achieves an average improvement in AUC of 4.93% and 8.58% compared to deep learning multi-layer neural network (DNN) and SVM, respectively. Additionally, it shows an average improvement of 2.64% and 1.92% compared to two state-of-the-art multi-task models.
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Affiliation(s)
- Xiaolu Xu
- School of Computer and Artificial Intelligence, Liaoning Normal University, Dalian 116029, China
| | - Zitong Qi
- Department of Statistics, University of Washington, Seattle, WA 98195, USA
| | - Xiumei Han
- College of Artificial Intelligence, Dalian Maritime University, Dalian 116026, China
| | - Yuxing Wang
- Department of Cardiology, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China
| | - Ming Yu
- Department of Cardiology, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China
| | - Zhaohong Geng
- Department of Cardiology, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China.
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Mackinnon ES, Leiter LA, Wani RJ, Burke N, Shaw E, Witges K, Goodman SG. Real-World Risk of Recurrent Cardiovascular Events in Atherosclerotic Cardiovascular Disease Patients with LDL-C Above Guideline-Recommended Threshold: A Retrospective Observational Study. Cardiol Ther 2024; 13:205-220. [PMID: 38285331 PMCID: PMC10899549 DOI: 10.1007/s40119-024-00349-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 01/09/2024] [Indexed: 01/30/2024] Open
Abstract
INTRODUCTION The 2021 Canadian Cardiovascular Society (CCS) guidelines recommend intensive low-density lipoprotein cholesterol (LDL-C) reduction for patients with atherosclerotic cardiovascular disease (ASCVD). For patients above LDL-C threshold on maximally tolerated statins, adding ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) is recommended. This population-based, real-world study examined cardiovascular (CV) events in patients with ASCVD who are on statins and above current guideline threshold LDL-C levels. METHODS Using administrative health data in Alberta, Canada, we identified patients with myocardial infarction (MI), ischemic stroke (IS), or peripheral artery disease with LDL-C > 1.8 mmol/L on statins between April 1, 2010 and March 31, 2016. Exploratory subgroups included very high-risk patients with ASCVD shown to derive the most benefit from PCSK9i intensification as identified by the CCS guidelines, including those with acute coronary syndrome (ACS) or recent MI. Frequencies and rates of individual and composite CV events (primary outcome: MI, IS, hospitalization for unstable angina, coronary revascularization, cardiovascular death; secondary outcome: MI, IS, CV death) were calculated over follow-up. RESULTS The study included 32,984 patients with a mean (standard deviation) follow-up of 40.8 (21.0) months. Overall, 17.7% and 15.6% experienced a primary and secondary outcome, respectively, with rates of 5.58 and 4.83 per 100 patient-years, respectively. CV death and MI were the most common events. Subgroups with recurrent MI and comorbid diabetes exhibited higher CV event rates (23.6% and 22.2% had a primary outcome, respectively). Rates of CV events were notably high in patients with ACS or recent MI (49.4% and 54.0% had a primary outcome, respectively). CONCLUSION This real-world study confirms that statin-treated high-risk patients with ASCVD and above-threshold LDL-C levels have substantial incidence of recurrent CV events. These findings reinforce the opportunity for lipid-lowering therapy intensification in high-risk patients to levels below guideline-recommended threshold in order to reduce CV risk.
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Affiliation(s)
- Erin S Mackinnon
- Amgen Canada Inc., 6775 Financial Dr #300, Mississauga, ON, L5N 0A4, Canada.
| | - Lawrence A Leiter
- Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada
- Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Rajvi J Wani
- Amgen Canada Inc., 6775 Financial Dr #300, Mississauga, ON, L5N 0A4, Canada
| | - Natasha Burke
- Amgen Canada Inc., 6775 Financial Dr #300, Mississauga, ON, L5N 0A4, Canada
| | - Eileen Shaw
- Medlior Health Outcomes Research Ltd., Calgary, AB, Canada
| | - Kelcie Witges
- Medlior Health Outcomes Research Ltd., Calgary, AB, Canada
| | - Shaun G Goodman
- Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada
- Department of Medicine, University of Toronto, Toronto, ON, Canada
- Canadian VIGOUR Centre, University of Alberta, Edmonton, AB, Canada
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Chen L, Qiu W, Sun X, Gao M, Zhao Y, Li M, Fan Z, Lv G. Novel insights into causal effects of serum lipids and lipid-modifying targets on cholelithiasis. Gut 2024; 73:521-532. [PMID: 37945330 DOI: 10.1136/gutjnl-2023-330784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Accepted: 10/29/2023] [Indexed: 11/12/2023]
Abstract
OBJECTIVE Different serum lipids and lipid-modifying targets should affect the risk of cholelithiasis differently, however, whether such effects are causal is still controversial and we aimed to answer this question. DESIGN We prospectively estimated the associations of four serum lipids with cholelithiasis in UK Biobank using the Cox proportional hazard model, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). Furthermore, we estimated the causal associations of the genetically predicted serum lipids with cholelithiasis in Europeans using the Mendelian randomisation (MR) design. Finally, both drug-target MR and colocalisation analyses were performed to estimate the lipid-modifying targets' effects on cholelithiasis, including HMGCR, NPC1L1, PCSK9, APOB, LDLR, ACLY, ANGPTL3, MTTP, PPARA, PPARD and PPARG. RESULTS We found that serum levels of LDL-C and HDL-C were inversely associated with cholelithiasis risk and such associations were linear. However, the serum level of TC was non-linearly associated with cholelithiasis risk where lower TC was associated with higher risk of cholelithiasis, and the serum TG should be in an inverted 'U-shaped' relationship with it. The MR analyses supported that lower TC and higher TG levels were two independent causal risk factors. The drug-target MR analysis suggested that HMGCR inhibition should reduce the risk of cholelithiasis, which was corroborated by colocalisation analysis. CONCLUSION Lower serum TC can causally increase the risk of cholelithiasis. The cholelithiasis risk would increase with the elevation of serum TG but would decrease when exceeding 2.57 mmol/L. The use of HMGCR inhibitors should prevent its risk.
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Affiliation(s)
- Lanlan Chen
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Wei Qiu
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Xiaodong Sun
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Menghan Gao
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Yuexuan Zhao
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Mingyue Li
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Zhongqi Fan
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Guoyue Lv
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China
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Schonck WAM, Stroes ESG, Hovingh GK, Reeskamp LF. Long-Term Efficacy and Tolerability of PCSK9 Targeted Therapy: A Review of the Literature. Drugs 2024; 84:165-178. [PMID: 38267805 PMCID: PMC10981656 DOI: 10.1007/s40265-024-01995-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/08/2024] [Indexed: 01/26/2024]
Abstract
Increased plasma levels of low-density lipoprotein cholesterol (LDL-C) are causally associated with atherosclerotic cardiovascular disease (ASCVD), and statins that lower LDL-C have been the cornerstone of ASCVD prevention for decades. However, guideline-recommended LDL-C targets are not achieved in about 60% of statin users. Proprotein convertase subtilisin/kexin type 9 (PCSK9)-targeted therapy effectively lowers LDL-C levels and has been shown to reduce ASCVD risk. A growing body of scientific and clinical evidence shows that PCSK9-targeted therapy offers an excellent safety and tolerability profile with a low incidence of side effects in the short term. In this review, we present and discuss the current clinical and scientific evidence pertaining to the long-term efficacy and tolerability of PCSK9-targeted therapy.
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Affiliation(s)
- Willemijn A M Schonck
- Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
| | - Erik S G Stroes
- Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
| | - G Kees Hovingh
- Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
- Global Chief Medical Office, Novo Nordisk, Copenhagen, Denmark
| | - Laurens F Reeskamp
- Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
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Sun S, Wang Y, Pang S, Wu X. Combination of the glycated hemoglobin levels and prognostic nutritional index as a prognostic marker in patients with acute coronary syndrome and type 2 diabetes mellitus. Lipids Health Dis 2024; 23:12. [PMID: 38212760 PMCID: PMC10782571 DOI: 10.1186/s12944-023-01992-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Accepted: 12/26/2023] [Indexed: 01/13/2024] Open
Abstract
BACKGROUND Increased susceptibility to malnutrition and inadequate glycemic control are frequently observed in diabetic patients with coronary artery disease. The assessment of malnutrition is performed using the prognosis nutritional index (PNI). The inadequate glycemic control is measured using glycated hemoglobin (HbA1c). However, the combined effect of PNI and HbA1c on the prognosis in diabetic patients with coronary artery disease remains unknown. METHODS A study was conducted at Beijing Anzhen Hospital and included 2,005 patients diagnosed with type 2 diabetes mellitus (T2DM) accompanied by acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) from September 2021 to January 2022. Based on the median PNI and HbA1c, we categorized the patients into four groups including high (H)-PNI/low (L)-HbA1c, H-PNI/H-HbA1c, L-PNI/L-HbA1c, and L-PNI/H-HbA1c. Major adverse cardiac and cerebrovascular events (MACCE) were the primary outcome, including all-cause mortality, nonfatal myocardial infarction (MI), and nonfatal strokes. RESULTS Throughout a median follow-up of 16.3 months, 73 patients had MACCE, which comprised 36 cases of all-cause mortality. In comparison to the H-PNI, the L-PNI showed an obvious rise in MACCE and all-cause mortality (log-rank P = 0.048 and 0.021, respectively) among the H-HbA1c group. Compared to the other groups, the L-PNI/H-HbA1c group exhibited the greatest risk of MACCE (adjusted hazard ratio [aHR]: 2.50, 95% confidence interval [CI] 1.20-5.23, P = 0.014) and all-cause mortality (HR: 3.20, 95% CI 1.04-9.82, P = 0.042). With the addition of PNI, MACCE and all-cause mortality prediction models performed significantly better in patients with ACS and T2DM after PCI, particularly in those with H-HbA1c levels. CONCLUSIONS The combination of L-PNI and H-HbA1c is a prognostic marker for MACCE and all-cause mortality in patients diagnosed with ACS and T2DM who underwent PCI. The PNI can serve as an assessment tool of malnutrition in patients with ACS and T2DM accompanied by H-HbA1c who underwent PCI. Therefore, monitoring the long-term change of the PNI deserves attention in clinical practice.
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Affiliation(s)
- Shuaifeng Sun
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, 2nd Anzhen Road, Chaoyang District, Beijing, 100029, China
| | - Yue Wang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, 2nd Anzhen Road, Chaoyang District, Beijing, 100029, China
| | - Shuo Pang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, 2nd Anzhen Road, Chaoyang District, Beijing, 100029, China
| | - Xiaofan Wu
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, 2nd Anzhen Road, Chaoyang District, Beijing, 100029, China.
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González-Lleó AM, Sánchez-Hernández RM, Plana N, Ibarretxe D, Rehues P, Ribalta J, Llop D, Wägner AM, Masana L, Boronat M. Impact of PCSK9 inhibitors in glycaemic control and new-onset diabetes. Cardiovasc Diabetol 2024; 23:4. [PMID: 38172901 PMCID: PMC10765818 DOI: 10.1186/s12933-023-02077-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Accepted: 11/27/2023] [Indexed: 01/05/2024] Open
Abstract
BACKGROUND The diabetogenic effect of statins has been well established by clinical trials, Mendelian randomisation studies and meta-analyses. According to large clinical trials, PCSK9 inhibitors (PCSK9i) have no deleterious impact on glucose metabolism. However, few real-life studies have yet evaluated the long-term effects of these drugs on glucose homeostasis and their impact on new-onset diabetes (NODM). METHODS We studied 218 patients treated with either alirocumab or evolocumab (70% with familial hypercholesterolemia) for at least three years (PCSK9iG). We studied the NODM rate in the nondiabetic group at baseline (168) and overall glucose metabolism control in the whole group. Incidental DM was compared with two groups. The first was a propensity score matching (PSM)-selected group (n = 168) from the database of patients attending the Reus lipid unit (Metbank, n = 745) who were not on PCSK9i (PSMG). The second was a subgroup with a similar age range (n = 563) of the Di@bet.es study (Spanish prospective study on diabetes development n = 5072) (D@G). The incidence was reported as the percentage of NODM cases per year. RESULTS The fasting glucose (FG) level of the subjects with normoglycaemia at baseline increased from 91 (86-95.5) to 93 (87-101) mg/dL (p = 0.014). There were 14 NODM cases in the PCSK9i group (2.6%/y), all among people with prediabetes at baseline. The incidence of NODM in PSMG and D@G was 1.8%/y (p = 0.69 compared with the PCSK9iG). The incidence among the subjects with prediabetes was 5.1%/y in the PCSK9iG, 4.8%/y in the PSMG and 3.9%/y in the D@G (p = 0.922 and p = 0.682, respectively). In the multivariate analysis, only the FG level was associated with the development of NODM in the PCSK9iG (OR 1.1; 95% CI: 1.0-1.3; p = 0.027). Neither FG nor A1c levels changed significantly in patients with DM at baseline. CONCLUSION A nonsignificant increase in NODM occurred in the PCSK9iG, particularly in patients with prediabetes, compared with the PSMG and D@G groups. Baseline FG levels were the main variable associated with the development of DM. In the subjects who had DM at baseline, glucose control did not change. The impact of PCSK9i on glucose metabolism should not be of concern when prescribing these therapies.
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Affiliation(s)
- Ana M González-Lleó
- Sección de Endocrinología y Nutrición. Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria (CHUIMI), Las Palmas de Gran Canaria, España.
- Instituto Universitario de Investigaciones Biomédicas y Sanitarias (IUIBS), Universidad de Las Palmas de Gran Canaria (ULPGC), Las Palmas de Gran Canaria, España.
| | - Rosa M Sánchez-Hernández
- Sección de Endocrinología y Nutrición. Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria (CHUIMI), Las Palmas de Gran Canaria, España
- Instituto Universitario de Investigaciones Biomédicas y Sanitarias (IUIBS), Universidad de Las Palmas de Gran Canaria (ULPGC), Las Palmas de Gran Canaria, España
| | - Núria Plana
- Universitat Rovira i Virgili. Unidad de Medicina Vascular y Metabolismo. Unitat de Recerca Lipids i Arteriosclerosi. Hospital Universitari Sant Joan, IISPV: CIBERDEM., Reus, España
| | - Daiana Ibarretxe
- Universitat Rovira i Virgili. Unidad de Medicina Vascular y Metabolismo. Unitat de Recerca Lipids i Arteriosclerosi. Hospital Universitari Sant Joan, IISPV: CIBERDEM., Reus, España
| | - Pere Rehues
- Universitat Rovira i Virgili. Unidad de Medicina Vascular y Metabolismo. Unitat de Recerca Lipids i Arteriosclerosi. Hospital Universitari Sant Joan, IISPV: CIBERDEM., Reus, España
| | - Josep Ribalta
- Universitat Rovira i Virgili. Unidad de Medicina Vascular y Metabolismo. Unitat de Recerca Lipids i Arteriosclerosi. Hospital Universitari Sant Joan, IISPV: CIBERDEM., Reus, España
| | - Dídac Llop
- Universitat Rovira i Virgili. Unidad de Medicina Vascular y Metabolismo. Unitat de Recerca Lipids i Arteriosclerosi. Hospital Universitari Sant Joan, IISPV: CIBERDEM., Reus, España
| | - Ana M Wägner
- Sección de Endocrinología y Nutrición. Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria (CHUIMI), Las Palmas de Gran Canaria, España
- Instituto Universitario de Investigaciones Biomédicas y Sanitarias (IUIBS), Universidad de Las Palmas de Gran Canaria (ULPGC), Las Palmas de Gran Canaria, España
| | - Lluís Masana
- Universitat Rovira i Virgili. Unidad de Medicina Vascular y Metabolismo. Unitat de Recerca Lipids i Arteriosclerosi. Hospital Universitari Sant Joan, IISPV: CIBERDEM., Reus, España
| | - Mauro Boronat
- Sección de Endocrinología y Nutrición. Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria (CHUIMI), Las Palmas de Gran Canaria, España
- Instituto Universitario de Investigaciones Biomédicas y Sanitarias (IUIBS), Universidad de Las Palmas de Gran Canaria (ULPGC), Las Palmas de Gran Canaria, España
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ElSayed NA, Aleppo G, Bannuru RR, Bruemmer D, Collins BS, Das SR, Ekhlaspour L, Hilliard ME, Johnson EL, Khunti K, Kosiborod MN, Lingvay I, Matfin G, McCoy RG, Perry ML, Pilla SJ, Polsky S, Prahalad P, Pratley RE, Segal AR, Seley JJ, Stanton RC, Gabbay RA. 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes-2024. Diabetes Care 2024; 47:S179-S218. [PMID: 38078592 PMCID: PMC10725811 DOI: 10.2337/dc24-s010] [Citation(s) in RCA: 142] [Impact Index Per Article: 142.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2023]
Abstract
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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ElSayed NA, Aleppo G, Bannuru RR, Bruemmer D, Collins BS, Ekhlaspour L, Gaglia JL, Hilliard ME, Johnson EL, Khunti K, Lingvay I, Matfin G, McCoy RG, Perry ML, Pilla SJ, Polsky S, Prahalad P, Pratley RE, Segal AR, Seley JJ, Selvin E, Stanton RC, Gabbay RA. 3. Prevention or Delay of Diabetes and Associated Comorbidities: Standards of Care in Diabetes-2024. Diabetes Care 2024; 47:S43-S51. [PMID: 38078581 PMCID: PMC10725807 DOI: 10.2337/dc24-s003] [Citation(s) in RCA: 31] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2023]
Abstract
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Ray KK, Nicholls SJ, Li N, Louie MJ, Brennan D, Lincoff AM, Nissen SE. Efficacy and safety of bempedoic acid among patients with and without diabetes: prespecified analysis of the CLEAR Outcomes randomised trial. Lancet Diabetes Endocrinol 2024; 12:19-28. [PMID: 38061370 DOI: 10.1016/s2213-8587(23)00316-9] [Citation(s) in RCA: 35] [Impact Index Per Article: 35.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 10/06/2023] [Accepted: 10/13/2023] [Indexed: 12/23/2023]
Abstract
BACKGROUND Statins reduce LDL cholesterol and cardiovascular events among those with or without diabetes but have been reported to increase new-onset diabetes. The CLEAR Outcomes trial demonstrated that bempedoic acid reduced the risk of major adverse cardiovascular events among statin-intolerant patients at high cardiovascular risk. In this prespecified analysis, our dual aims were to evaluate the cardiovascular benefits of bempedoic acid, an ATP-citrate lyase inhibitor, in individuals with diabetes, and to evaluate the risk of new-onset diabetes and HbA1c among those without diabetes in the CLEAR Outcomes trial. METHODS CLEAR Outcomes was a randomised, double-blind, placebo-controlled trial conducted across 1250 primary care and outpatient sites in 32 countries. Patients with or without cardiovascular disease who were unwilling or unable to take guideline-recommended doses of statins and an LDL cholesterol of 2·59 mmol/L or more were randomly assigned (1:1) in a double-blinded manner to either bempedoic acid 180 mg once per day or placebo. In this prespecified analysis, the efficacy endpoint was a time-to-event analysis of four-component major adverse cardiovascular event (MACE-4), which is the composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularisation, using the intention-to-treat population stratified by baseline glycaemia status. The prespecified analysis of risk of new-onset diabetes and HbA1c increase was evaluated in patients without diabetes at baseline. The CLEAR Outcomes trial was completed on Nov 7, 2022, and is registered with ClinicalTrials.gov (NCT02993406). FINDINGS Between Dec 22, 2016, and Nov 7, 2022, 13 970 patients were screened and randomly assigned; 6373 (45·6%) with diabetes, 5796 (41·5%) with prediabetes, and 1801 (12·9%) with normoglycaemia. Over a median of 3·4 years follow up, patients with diabetes had significant relative and absolute cardiovascular risk reductions in MACE-4 endpoints with bempedoic acid (HR 0·83; 95% CI 0·72-0·95; absolute risk reduction of 2·4%) compared to placebo, with no statistical evidence of effect modification across glycaemic strata (interaction p=0·42). The proportion of patients who developed new-onset diabetes were similar between the bempedoic acid and placebo groups, with 429 of 3848 (11·1%) with bempedoic acid versus 433 of 3749 (11·5%) with placebo (HR 0·95; 95% CI 0·83-1·09). HbA1c concentrations at month 12 and the end of the study were similar between randomised groups in patients who had prediabetes and normoglycaemia. Placebo-corrected LDL cholesterol concentrations and high-sensitivity C-reactive protein at 6 months were reduced in each glycaemic stratum (diabetes, prediabtes, and normoglycaemia) for patients randomly assigned to bempedoic acid (all p<0·001). INTERPRETATION Among patients with diabetes, bempedoic acid reduces LDL cholesterol and high-sensitivity C-reactive protein and risk of cardiovascular events. Patients without diabetes had no increase in new-onset diabetes or worsening HbA1c with bempedoic acid. The efficacy and cardiometabolic safety profile of bempedoic acid makes it a clinical option for those with and without diabetes. FUNDING Esperion Therapeutics.
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Affiliation(s)
- Kausik K Ray
- Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College London, London, UK.
| | | | - Na Li
- Esperion Therapeutics, Ann Arbor, MI, USA
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Huang J, Gu JX, Wang K, Zhang AM, Hong TT, Li SS, Yao XQ, Yang M, Yin Y, Zhang N, Su M, Hu JJ, Zhang XZ, Jia M. Association between serum PCSK9 and coronary heart disease in patients with type 2 diabetes mellitus. Diabetol Metab Syndr 2023; 15:260. [PMID: 38115042 PMCID: PMC10731704 DOI: 10.1186/s13098-023-01238-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 12/09/2023] [Indexed: 12/21/2023] Open
Abstract
BACKGROUND AND AIMS Proprotein convertase subtilisin/kexin type 9 (PCSK9) is considered a new biomarker for atherosclerosis, but its ability to predict cardiovascular outcomes has been controversial. This study aimed to address the lack of data on PCSK9, coronary heart disease (CHD) severity, and major cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM). METHODS A total of 2984 T2DM patients underwent selective coronary angiography, and their serum PCSK9 levels were measured using enzyme-linked immunosorbent assay. Correlation and logistic regression analyses were performed to investigate the association between PCSK9 expression and CHD severity. This study used Cox regression analysis to assess the association between circulating PCSK9 levels and the risk of MACEs. RESULTS Circulating PCSK9 levels were significantly higher in the CHD group than in the non-CHD group [554.62 (265.11) ng/mL vs. 496.86 (129.05) ng/mL, p < 0.001]. Circulating PCSK9 levels positively correlated with CHD severity (diseased vessels: r = 0.35, p < 0.001; Gensini score: r = 0.46, p < 0.001). Elevated PCSK9 levels are an independent risk factor for CHD risk and severity (CHD group vs. non-CHD group: OR = 2.829, 95% CI: 1.771-4.520, p < 0.001; three vessel disease group vs. one vessel disease group: OR = 4.800, 95% CI: 2.387-9.652, p < 0.001; high GS group vs. low GS group: OR = 5.534, 95% CI: 2.733-11.208, p < 0.001). Through a six-year follow-up and multivariate Cox regression analysis, elevated circulating PCSK9 levels were found to be independently associated with MACEs in all participants (HR: 3.416, 5% CI: 2.485-4.697, p < 0.001; adjusted HR: 2.780, 95% CI: 1.930-4.004, p < 0.001). CONCLUSIONS Serum PCSK9 levels were positively correlated with multi-vessel CHD and Gensini score. Elevated circulating PCSK9 levels are an independent risk factor for CHD and increased incidence of MACEs in T2DM.
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Affiliation(s)
- Juan Huang
- Department of traditional Chinese medicine, Peking University International Hospital, No. 1 Shengmingyuan Road, Zhongguancun Life Science Park, Changping District, Beijing, 102206, P.R. China
| | - Jun-Xu Gu
- Department of Clinical Laboratory, Peking University People's Hospital, No. 11 Xizhimen South Street, Beijing, 100044, P.R. China
| | - Kun Wang
- Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, P.R. China
| | - Ai-Min Zhang
- Department of Clinical Laboratory, Peking University People's Hospital, No. 11 Xizhimen South Street, Beijing, 100044, P.R. China
| | - Ting-Ting Hong
- Department of Clinical Laboratory, Peking University People's Hospital, No. 11 Xizhimen South Street, Beijing, 100044, P.R. China
| | - Shan-Shan Li
- Department of Clinical Laboratory, Peking University People's Hospital, No. 11 Xizhimen South Street, Beijing, 100044, P.R. China
| | - Xiao-Qin Yao
- Department of traditional Chinese medicine, Peking University International Hospital, No. 1 Shengmingyuan Road, Zhongguancun Life Science Park, Changping District, Beijing, 102206, P.R. China
| | - Ming Yang
- Department of Clinical Laboratory, Peking University International Hospital, Beijing, P.R. China
| | - Yue Yin
- Department of Clinical Laboratory, Peking University People's Hospital, No. 11 Xizhimen South Street, Beijing, 100044, P.R. China
| | - Na Zhang
- Department of Clinical Laboratory, Peking University People's Hospital, No. 11 Xizhimen South Street, Beijing, 100044, P.R. China
| | - Ming Su
- Department of Clinical Laboratory, Peking University People's Hospital, No. 11 Xizhimen South Street, Beijing, 100044, P.R. China
| | - Jia-Jia Hu
- Department of Clinical Laboratory, Peking University People's Hospital, No. 11 Xizhimen South Street, Beijing, 100044, P.R. China.
| | - Xue-Zhi Zhang
- Department of traditional Chinese medicine, Peking University International Hospital, No. 1 Shengmingyuan Road, Zhongguancun Life Science Park, Changping District, Beijing, 102206, P.R. China.
| | - Mei Jia
- Department of Clinical Laboratory, Peking University People's Hospital, No. 11 Xizhimen South Street, Beijing, 100044, P.R. China.
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Wadström BN, Pedersen KM, Wulff AB, Nordestgaard BG. Elevated remnant cholesterol and atherosclerotic cardiovascular disease in diabetes: a population-based prospective cohort study. Diabetologia 2023; 66:2238-2249. [PMID: 37776347 PMCID: PMC10627991 DOI: 10.1007/s00125-023-06016-0] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 08/08/2023] [Indexed: 10/02/2023]
Abstract
AIMS/HYPOTHESIS Elevated remnant cholesterol is observationally and causally associated with increased risk of atherosclerotic cardiovascular disease (ASCVD) in the general population. This association is not well studied in individuals with diabetes, who are often included in clinical trials of remnant cholesterol-lowering therapy. We tested the hypothesis that elevated remnant cholesterol is associated with increased risk of ASCVD in individuals with diabetes. We also explored the fraction of excess risk conferred by diabetes which can be explained by elevated remnant cholesterol. METHODS We included 4569 white Danish individuals with diabetes (58% statin users) nested within the Copenhagen General Population Study (2003-2015). The ASCVDs peripheral artery disease, myocardial infarction and ischaemic stroke were extracted from national Danish health registries without losses to follow-up. Remnant cholesterol was calculated from a standard lipid profile. RESULTS During up to 15 years of follow-up, 236 individuals were diagnosed with peripheral artery disease, 234 with myocardial infarction, 226 with ischaemic stroke and 498 with any ASCVD. Multivariable adjusted HR (95% CI) per doubling of remnant cholesterol was 1.6 (1.1, 2.3; p=0.01) for peripheral artery disease, 1.8 (1.2, 2.5; p=0.002) for myocardial infarction, 1.5 (1.0, 2.1; p=0.04) for ischaemic stroke, and 1.6 (1.2, 2.0; p=0.0003) for any ASCVD. Excess risk conferred by diabetes was 2.5-fold for peripheral artery disease, 1.6-fold for myocardial infarction, 1.4-fold for ischaemic stroke and 1.6-fold for any ASCVD. Excess risk explained by elevated remnant cholesterol and low-grade inflammation was 14% and 8% for peripheral artery disease, 26% and 16% for myocardial infarction, 34% and 34% for ischaemic stroke, and 24% and 18% for any ASCVD, respectively. LDL-cholesterol did not explain excess risk, as it was not higher in individuals with diabetes. We also explored the fraction of excess risk conferred by diabetes which can be explained by elevated remnant cholesterol. CONCLUSIONS/INTERPRETATION Elevated remnant cholesterol was associated with increased risk of ASCVD in individuals with diabetes. Remnant cholesterol and low-grade inflammation explained substantial excess risk of ASCVD conferred by diabetes. Whether remnant cholesterol should be used as a treatment target remains to be determined in randomised controlled trials.
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Affiliation(s)
- Benjamin N Wadström
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
- The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Kasper M Pedersen
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
- The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Anders B Wulff
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
- The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Børge G Nordestgaard
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
- The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
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Gill PK, Hegele RA. New Biological Therapies for Low-Density Lipoprotein Cholesterol. Can J Cardiol 2023; 39:1913-1930. [PMID: 37562541 DOI: 10.1016/j.cjca.2023.08.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Revised: 08/01/2023] [Accepted: 08/03/2023] [Indexed: 08/12/2023] Open
Abstract
Depressed low-density lipoprotein cholesterol concentration protects against atherosclerotic cardiovascular disease. Natural hypocholesterolemia states can have a monogenic etiology, caused by pathogenic loss of function variants in the PCSK9, ANGPTL3, MTTP, or APOB genes. In this focused review, we discuss development and clinical use of several new therapeutics that inhibit these gene products to target elevated levels of low-density lipoprotein cholesterol. In particular, inhibitors of proprotein convertase subtilisin kexin type 9 (PCSK9) have notably affected clinical practice, followed recently by inhibition of angiopoietin-like 3 (ANGPTL3). Currently used in the clinic are alirocumab and evolocumab, two anti-PCSK9 monoclonal antibodies, inclisiran, a small interfering RNA that prevents PCSK9 translation, evinacumab, an anti-ANGPTL3 monoclonal antibody, and lomitapide, a small-molecule inhibitor of microsomal triglyceride transfer protein. Additional therapies are in preclinical or clinical trial stages of development. These consist of other monoclonal antibodies, antisense oligonucleotides, small-molecule inhibitors, mimetic peptides, adnectins, vaccines, and gene-editing therapies. Vaccines and gene-editing therapies in particular hold great potential to confer active long-term attenuation or provide single-treatment life-long knock-down of PCSK9 or ANGPTL3 activity. Biologic therapies inspired by monogenic hypocholesterolemia states are becoming valuable tools to help protect against atherosclerotic cardiovascular disease.
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Affiliation(s)
- Praneet K Gill
- Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
| | - Robert A Hegele
- Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
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Solnica B, Sniderman AD, Wyszomirski A, Rutkowski M, Chlebus K, Bandosz P, Pencina MJ, Zdrojewski T. Concordance/discordance between serum apolipoprotein B, low density lipoprotein cholesterol and non-high density lipoprotein cholesterol in NATPOL 2011 participants - An epidemiological perspective. Int J Cardiol 2023; 390:131150. [PMID: 37429441 DOI: 10.1016/j.ijcard.2023.131150] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 05/20/2023] [Accepted: 07/05/2023] [Indexed: 07/12/2023]
Abstract
BACKGROUND The study compared the distribution of serum LDL-C, non-HDL-C, and apolipoprotein B (apoB) among participants of the NATPOL 2011 survey and analysed concordance/discordance of results in the context of the risk for atherosclerotic cardiovascular disease (ASCVD). METHODS Serum levels of apoB, LDL-C, non-HDL-C and small dense LDL-C were measured/calculated in 2067-2098 survey participants. The results were compared between women and men, age groups and in relation to body mass index (BMI), fasting glucose and TG levels, and the presence of CVD. Percentile distribution of lipid levels and concordance/discordance analysis were based on medians and ESC/EAS 2019 target thresholds for ASCVD risk and on comparison of measured apoB levels and levels calculated from linear regression equations with serum LDL- C and non-HDL-C as independent variables. RESULTS Serum apoB, LDL-C and non-HDL-C were similarly related to sex, age, BMI, visceral obesity, cardiovascular disease, and fasting glucose and triglyceride levels. Serum apoB, LDL-C and non-HDL-C very high- and moderate- target thresholds were exceeded in 83%, 99% and 96.9% and in 41%, 75% and 63.7% of subjects, respectively. The incidence of the discordances between the results depended on the dividing values used and ranged from 0.2% to 45.2% of the respondents. Subjects with high apoB / low LDL-C/non-HDL-C discordance had features of metabolic syndrome. CONCLUSIONS Diagnostic discordances between apoB and LDL-C/non-HDL-C indicate limitations of serum LDL-C/non-HDL-C in ASCVD risk management. Due to the high apoB/low LDL-C/non-HDL-C discordance, obese/metabolic syndrome patients may benefit from replacing LDL-C/non-HDL-C by apoB in ASCVD risk assessment and lipid-lowering therapy.
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Affiliation(s)
- Bogdan Solnica
- Department of Clinical Biochemistry, Jagiellonian University Medical College, Kraków, Poland.
| | - Allan D Sniderman
- Mie and Valeria Centre for Cardiovascular Prevention, McGill University Health Centre, Montreal, Canada
| | - Adam Wyszomirski
- Department of Adult Neurology, Medical University of Gdańsk, Gdańsk, Poland
| | - Marcin Rutkowski
- Department of Preventive Medicine and Education, Medical University of Gdansk, Gdansk, Poland
| | - Krzysztof Chlebus
- I(st) Department of Cardiology, Medical University of Gdansk, Gdańsk, Poland
| | - Piotr Bandosz
- Department of Preventive Medicine and Education, Medical University of Gdansk, Gdansk, Poland
| | - Michael J Pencina
- Duke University, DCRI, Biostatistics and Bioinformatics, Durham, USA; Framingham Heart Study, USA
| | - Tomasz Zdrojewski
- Department of Preventive Medicine and Education, Medical University of Gdansk, Gdansk, Poland
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Alieva R, Shek A, Abdullaev A, Fozilov K, Khoshimov S, Abdullaeva G, Zakirova D, Kurbanova R, Kan L, Kim A. E670G PCSK9 polymorphism in HeFH & CAD with diabetes: is the bridge to personalized therapy within reach? FRONTIERS IN CLINICAL DIABETES AND HEALTHCARE 2023; 4:1277288. [PMID: 38028979 PMCID: PMC10646404 DOI: 10.3389/fcdhc.2023.1277288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Accepted: 10/11/2023] [Indexed: 12/01/2023]
Abstract
Objective To assess the distribution of PCSK9 E670G genetic polymorphism and PCSK9 levels in patients with Coronary Artery Disease (CAD) and Heterozygous Familial Hypercholesterolemia (HeFH), based on the presence of type 2 Diabetes Mellitus (T2DM). Methods The study included 201 patients with chronic CAD, including those with HeFH (n=57, group I) and without it (n=144, group II). DLCN was used to diagnose HeFH. The PCSK9 E670G (rs505151) polymorphism was genetically typed using the PCR-RFLP procedure. In both the patient and control groups, the genotype frequency matched the Hardy-Weinberg equilibrium distribution (P>0.05). Results There were twice more G alleles in group I (13, 11.4%) than in group II (17, 6.0%), and thrice more (1, 3.0%) than in the healthy control group; nevertheless, these differences weren't statistically significant. Simultaneously, PCSK9 levels were higher in HeFH patients (P<0.05) compared to non-HeFH patients not taking statins (n=63). T2DM was equally represented in groups I and II (31.6% vs. 33.3%). But carriers of AG+GG genotypes in group I had a higher chance of having a history of T2DM (RR 4.18; 95%CI 2.19-8.0; P<0.001), myocardial infarction (RR 1.79; 95%CI 1.18-2.73; P<0.05), and revascularization (RR 12.6; 95%CI 4.06-38.8; P<0.01), than AA carriers. T2DM was also more common among G allele carriers (RR 1.85; 95% CI 1.11-3.06; P<0.05) in patients with non-HeFH. Conclusion T2DM in patients with CAD, both with HeFH and non-HeFH, in the Uzbek population was significantly more often associated with the presence of the "gain-of-function" G allele of the PCSK9 E670G genetic polymorphism.
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Affiliation(s)
- Rano Alieva
- CAD & Atherosclerosis Department, Republican Specialized Center of Cardiology, Tashkent, Uzbekistan
| | - Aleksandr Shek
- CAD & Atherosclerosis Department, Republican Specialized Center of Cardiology, Tashkent, Uzbekistan
| | - Alisher Abdullaev
- Center for Advanced Technologies, Ministry of Innovative Development of Uzbekistan, Tashkent, Uzbekistan
| | - Khurshid Fozilov
- CAD & Atherosclerosis Department, Republican Specialized Center of Cardiology, Tashkent, Uzbekistan
| | - Shovkat Khoshimov
- CAD & Atherosclerosis Department, Republican Specialized Center of Cardiology, Tashkent, Uzbekistan
| | - Guzal Abdullaeva
- CAD & Atherosclerosis Department, Republican Specialized Center of Cardiology, Tashkent, Uzbekistan
| | - Dariya Zakirova
- Center for Advanced Technologies, Ministry of Innovative Development of Uzbekistan, Tashkent, Uzbekistan
| | - Rano Kurbanova
- CAD & Atherosclerosis Department, Republican Specialized Center of Cardiology, Tashkent, Uzbekistan
| | - Lilia Kan
- CAD & Atherosclerosis Department, Republican Specialized Center of Cardiology, Tashkent, Uzbekistan
| | - Andrey Kim
- CAD & Atherosclerosis Department, Republican Specialized Center of Cardiology, Tashkent, Uzbekistan
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Maïmoun L, Bourgeois E, Serrand C, Mura T, Cristol JP, Myzia J, Avignon A, Mariano-Goulart D, Sultan A. Relationship between Lean Tissue Mass and Muscle Function in Women with Obesity. Nutrients 2023; 15:4517. [PMID: 37960170 PMCID: PMC10649051 DOI: 10.3390/nu15214517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 10/16/2023] [Accepted: 10/19/2023] [Indexed: 11/15/2023] Open
Abstract
It is well documented that lean tissue mass (LTM) decreases with aging in patients with obesity, but there is no information available regarding muscle strength changes, a parameter that may be better associated with sarcopenic obesity (SO). The objectives of this study were to analyze the changes in LTM and fat mass (FM), muscle strength and muscle function with aging in women with obesity and to determine the prevalence of SO. LTM and FM were determined by DXA, muscle strength with the hand-grip test and muscle function with the 6 min walk test (6MWT) in 383 women with obesity. A redistribution of the LTM and FM occurred with age, characterized by a gain at the trunk to the detriment of the lower limbs, thus reducting in appendicular LTM indices. The physical performances evaluated by the muscle strength and muscle function decreased concomitantly, and the prevalence of low values for both these parameters was 22.8% and 13.4%, respectively, in the older patients. In summary, although a reduction in appendicular LTM and muscle performances occurred with age and resulted in an increase in the prevalence of SO, the number of women with obesity affected by SO remained low (n ≤ 15), even in those older than 60 years.
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Affiliation(s)
- Laurent Maïmoun
- Depatment of Nuclear Medicine, CHU Montpellier, 34295 Montpellier, France;
- Physiology and Experimental Medicine of the Heart and Muscles (PhyMedExp), University of Montpellier, 34295 Montpellier, France; (E.B.); (J.-P.C.); (A.S.)
| | - Elise Bourgeois
- Physiology and Experimental Medicine of the Heart and Muscles (PhyMedExp), University of Montpellier, 34295 Montpellier, France; (E.B.); (J.-P.C.); (A.S.)
- Department of Endocrinology, Nutrition and Diabetes, Team Nutrition, Diabetes, CHU Montpellier, 34295 Montpellier, France;
| | - Chris Serrand
- Department of Biostatistics, Epidemiology, Public Health and Innovation in Methodology, CHU Nîmes, 30029 Nîmes, France; (C.S.); (T.M.)
| | - Thibault Mura
- Department of Biostatistics, Epidemiology, Public Health and Innovation in Methodology, CHU Nîmes, 30029 Nîmes, France; (C.S.); (T.M.)
| | - Jean-Paul Cristol
- Physiology and Experimental Medicine of the Heart and Muscles (PhyMedExp), University of Montpellier, 34295 Montpellier, France; (E.B.); (J.-P.C.); (A.S.)
- Departement of Biochimy, Chu Montpellier, 34295 Montpellier, France
| | - Justine Myzia
- Department of Clinical Physiology, CHU Montpellier, 34295 Montpellier, France;
| | - Antoine Avignon
- Department of Endocrinology, Nutrition and Diabetes, Team Nutrition, Diabetes, CHU Montpellier, 34295 Montpellier, France;
- Desbrest Institute of Epidemiology and Public Health, IDESP UMR UA11 INSERM, University of Montpellier, 34295 Montpellier, France
| | - Denis Mariano-Goulart
- Depatment of Nuclear Medicine, CHU Montpellier, 34295 Montpellier, France;
- Physiology and Experimental Medicine of the Heart and Muscles (PhyMedExp), University of Montpellier, 34295 Montpellier, France; (E.B.); (J.-P.C.); (A.S.)
| | - Ariane Sultan
- Physiology and Experimental Medicine of the Heart and Muscles (PhyMedExp), University of Montpellier, 34295 Montpellier, France; (E.B.); (J.-P.C.); (A.S.)
- Department of Endocrinology, Nutrition and Diabetes, Team Nutrition, Diabetes, CHU Montpellier, 34295 Montpellier, France;
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50
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Marx N, Federici M, Schütt K, Müller-Wieland D, Ajjan RA, Antunes MJ, Christodorescu RM, Crawford C, Di Angelantonio E, Eliasson B, Espinola-Klein C, Fauchier L, Halle M, Herrington WG, Kautzky-Willer A, Lambrinou E, Lesiak M, Lettino M, McGuire DK, Mullens W, Rocca B, Sattar N. 2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J 2023; 44:4043-4140. [PMID: 37622663 DOI: 10.1093/eurheartj/ehad192] [Citation(s) in RCA: 486] [Impact Index Per Article: 243.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/26/2023] Open
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