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Patel S, Fung M, Prasai S, Butalia S, Anderson TJ. Emergency department visits and hospitalizations after a diagnosis of angina with no obstructive coronary artery disease (ANOCA). Am Heart J 2025; 285:82-92. [PMID: 40032042 DOI: 10.1016/j.ahj.2025.02.021] [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: 11/12/2023] [Revised: 02/24/2025] [Accepted: 02/27/2025] [Indexed: 03/05/2025]
Abstract
BACKGROUND Angina with no obstructive coronary artery disease (ANOCA) presents diagnostic and treatment challenges, significantly burdening healthcare resources. This study assessed emergency department (ED) visits and hospitalizations and factors associated with these outcomes following ANOCA and stable angina (SA) with obstructive coronary artery disease (CAD) diagnoses. METHODS A retrospective cohort of individuals who had their first invasive cardiac catheterization for chest pain in Alberta from 2002 to 2017 was extracted retrospectively from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) database. Incidence rates (IRs) were calculated for ED visits and hospitalizations, while factors associated with these outcomes were analyzed using Cox models. RESULTS Our analysis included 28,881 individuals (ANOCA, 36%). Two-year postcatheterization IRs of ED visits were 100.3-119.3 per 1,000 person-years for ANOCA and increased over time (unstandardized beta coefficient [b] = 2.19 per biennium [95% CI 0.83-3.55]; P = .008); for SA with obstructive CAD the IRs were 209.3-240.2 per 1,000 person-years and remained stable (b = -1.83 per biennium [95% CI -5.73 to 1.70]; P = .25). IRs of hospitalizations were 12.4-25.8 per 1,000 person-years and stable for ANOCA (b = -0.93 per biennium [95% CI -2.49 to 0.64]; P = .20); for SA with obstructive CAD, they were 106.4-171.4 per 1,000 person-years and decreased over time (b = -9.02 per biennium [95% CI -13.27 to -4.77; P = .002). A previous history of heart failure was most associated with ED visits (HR = 1.74 [95% CI 1.41-2.14]; P < .001) and hospitalizations (HR = 2.40 [95% CI 1.82-3.18]; P < .001) for ANOCA. CONCLUSIONS ED visits for ANOCA have risen over time while hospitalizations remain stable, indicating a growing burden despite generally lower rates than SA with obstructive CAD. These findings underscore the need for more effective management strategies to address the significant morbidity and resource utilization in ANOCA.
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Affiliation(s)
- Shubh Patel
- Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Cardiac Sciences and Libin Cardiovascular Institute of Alberta, Cumming, School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Marinda Fung
- Department of Cardiac Sciences and Libin Cardiovascular Institute of Alberta, Cumming, School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Shuvam Prasai
- Department of Medicine and Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Sonia Butalia
- Department of Medicine and Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Todd J Anderson
- Department of Cardiac Sciences and Libin Cardiovascular Institute of Alberta, Cumming, School of Medicine, University of Calgary, Calgary, Alberta, Canada.
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Baratta F, Moscucci F, Lospinuso I, Cocomello N, Colantoni A, Di Costanzo A, Tramontano D, D'Erasmo L, Pastori D, Ettorre E, Del Ben M, Arca M, Desideri G. Lipid-Lowering Therapy and Cardiovascular Prevention in Elderly. Drugs 2025; 85:801-812. [PMID: 40338434 PMCID: PMC12098413 DOI: 10.1007/s40265-025-02182-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/28/2025] [Indexed: 05/09/2025]
Abstract
The global population aged 80 years and older will reach approximately half a billion in the coming years, and cardiovascular prevention in this group of patients will become a global health challenge. In the era of evidence-based medicine, the use of lipid-lowering therapies (LLTs) in the elderly, particularly in primary and secondary cardiovascular prevention, remains an area of active research. Although there is broad consensus on the use of LLTs in the elderly to prevent recurrent cardiovascular events in secondary prevention, there is considerable debate about their use in primary prevention. Many efforts have been made to improve cardiovascular risk stratification in patients over 75 years of age in primary prevention. In recent years, some specific risk scores have been developed, including the Systematic Coronary Risk Evaluation 2 for Older Persons (SCORE2-OP). While there are very few specific warnings to consider for LLTs in the elderly, an important challenge in this patient population is to identify the turning point at which the disutility risk outweighs the potential benefits. However, despite the widespread recognition of the importance of this issue, there is a lack of guidance on how to identify patients who should be withdrawn from therapy. The aim of this narrative review is to examine the current state of knowledge regarding the indications for LLT in elderly patients, identify outstanding issues, and discuss future developments.
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Affiliation(s)
- Francesco Baratta
- Geriatric Unit, Department of Internal Medicine and Medical Specialties, AOU Policlinico Umberto I, Rome, Italy.
| | - Federica Moscucci
- Geriatric Unit, Department of Internal Medicine and Medical Specialties, AOU Policlinico Umberto I, Rome, Italy
| | - Ilaria Lospinuso
- Geriatric Unit, Department of Internal Medicine and Medical Specialties, AOU Policlinico Umberto I, Rome, Italy
| | - Nicholas Cocomello
- Department of Anatomical Sciences, Histological, Legal Medical and Locomotor, Sapienza University of Rome, Rome, Italy
- Department of Clinical, Internal Medicine, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Alessandra Colantoni
- Department of Clinical, Internal Medicine, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Alessia Di Costanzo
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Daniele Tramontano
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Laura D'Erasmo
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Daniele Pastori
- Department of Clinical, Internal Medicine, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Evaristo Ettorre
- Department of Clinical, Internal Medicine, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Maria Del Ben
- Department of Clinical, Internal Medicine, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Marcello Arca
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Giovambattista Desideri
- Department of Clinical, Internal Medicine, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.
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Bass R, Stalvey M, Solomon G, Rowe S, Nichols D, Schwarzenberg SJ, Freedman S, Walega R, Kelly A. Cholesterol and triglyceride concentrations following 12-18 months of clinically prescribed elexacaftor-tezacaftor-ivacaftor-PROMISE sub-study. J Clin Transl Endocrinol 2025; 40:100391. [PMID: 40248170 PMCID: PMC12005328 DOI: 10.1016/j.jcte.2025.100391] [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: 01/10/2025] [Revised: 03/06/2025] [Accepted: 04/01/2025] [Indexed: 04/19/2025] Open
Abstract
Background/Aims People with CF (PwCF) have low total, high, and low density lipoprotein cholesterol (TC, HDL-C and LDL-C) and historically have had low prevalence of cardiovascular disease. More recently, cases of acute myocardial infarction are reported in PwCF. The impact of elexacaftor-tezacaftor-ivacaftor (ETI) on cholesterol and triglyceride (TG) concentrations, traditional cardiometabolic risk factors, is unknown. Methods/Results TC, LDL-C, HDL-C, and TG concentrations were analyzed from participants enrolled in the observational PROMISE study of clinically prescribed ETI prior to and 12-18 months after initiation. Pre-ETI and follow-up concentrations were compared, and relationships between TC, LDL-C, HDL-C and TG and clinical factors were tested using linear mixed-effect models.Fasting samples were available for 51 participants (25 M/26F, median age 17.4 y) with pancreatic exocrine insufficiency at baseline and 12-18 months after ETI initiation. TC and HDL-C were higher after 12-18 mo ETI in an unadjusted model, but with adjustment for BMI-Z, only HDL-C remained significantly higher at follow up (p < 0.05). Low HDL-C was the most common abnormality (>50 %), but prevalence of participants meeting criteria for low HDL-C did not differ between timepoints. Conclusions In a population of youth and young adults with CF, TC and HDL-C were higher after 12-18 months of ETI, but differences in TC were attenuated with adjustment for BMI-Z. Prevalence of low HDL-C was high at both timepoints.
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Affiliation(s)
- Rosara Bass
- Ohio State University and Nationwide Children’s Hospital, Columbus, OH, USA
| | | | - George Solomon
- University of Alabama at Birmingham, Birmingham, AL, USA
| | - Steven Rowe
- University of Alabama at Birmingham, Birmingham, AL, USA
| | | | | | - Steven Freedman
- Harvard University, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Rachel Walega
- University of Pennsylvania and Children’s Hospital of Philadelphia, Philadelphia, PA, USA
| | - Andrea Kelly
- University of Pennsylvania and Children’s Hospital of Philadelphia, Philadelphia, PA, USA
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Alwagdani MS, Alshoaibi N, Elghetany HM, Algrigri AH, Bahurmuz RA, Alqahtani AA, Olfat ZT, Halawani H. Lipid-Lowering Therapy in Post-Acute Coronary Syndrome Patients: An Observational Study. Cardiol Res 2025; 16:250-258. [PMID: 40370629 PMCID: PMC12074677 DOI: 10.14740/cr2063] [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] [Received: 03/17/2025] [Accepted: 04/12/2025] [Indexed: 05/16/2025] Open
Abstract
Background Cardiovascular disease remains a major cause of morbidity and mortality globally. International guidelines recommend aggressive lipid-lowering therapy (LLT) in patients with atherosclerotic cardiovascular disease (ASCVD), targeting a low-density lipoprotein cholesterol (LDL-C) level of < 55 mg/dL and a ≥ 50% reduction from baseline. However, real-world studies continue to show suboptimal LDL-C target achievement. This study aimed to assess the proportion of post-acute coronary syndrome (ACS) patients achieving both LDL-C < 55 mg/dL and a ≥ 50% reduction from baseline at 6 months. A secondary objective was to evaluate target achievement after 1 year and analyze outcomes across different LLT regimens. Methods We conducted a retrospective cohort study at a single tertiary center, including patients aged ≥ 18 years who presented with ACS between January 2021 and January 2022, underwent percutaneous coronary intervention (PCI), and had documented LDL-C levels at baseline and at least one follow-up within 12 months. Patients with baseline LDL-C ≤ 55 mg/dL or on ongoing LLT were excluded. Results A total of 122 patients were included (mean age 63.5 years; 59.8% had both diabetes and hypertension). At 6 months, only 13/82 patients (15.9%) achieved the primary LDL-C target. The highest achievement was seen in the rosuvastatin + ezetimibe group (30.0%), followed by rosuvastatin (17.9%), atorvastatin + ezetimibe (14.3%), and atorvastatin monotherapy (14.0%). A ≥ 50% LDL-C reduction without meeting the < 55 mg/dL threshold was observed in 24/82 patients (29.3%). Conclusions LDL-C target achievement remains low among post-ACS patients despite high-intensity statin use. Combination therapy with rosuvastatin + ezetimibe showed more favorable outcomes, particularly in older adults. These findings underscore the need for structured follow-up, treatment intensification, and broader use of advanced therapies such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to close the real-world treatment gap.
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Affiliation(s)
- Meshari S. Alwagdani
- Department of Cardiology, Doctor Soliman Fakeeh Hospital, Jeddah 23434, Saudi Arabia
| | - Naeem Alshoaibi
- Department of Cardiology, King Abdulaziz University Hospital, Jeddah 22252, Saudi Arabia
| | | | | | - Razan A. Bahurmuz
- Department of Cardiology, Doctor Soliman Fakeeh Hospital, Jeddah 23434, Saudi Arabia
| | | | - Zeyad T. Olfat
- Department of Cardiology, Doctor Soliman Fakeeh Hospital, Jeddah 23434, Saudi Arabia
| | - Hatun Halawani
- Department of Cardiology, Doctor Soliman Fakeeh Hospital, Jeddah 23434, Saudi Arabia
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Suwal R, Pant V, Shrestha SR, Poudel P, Shrestha S, Pradhan S, Bhandary S. The low-density lipoprotein debate: indirect methods vs direct measurement in the Nepalese population. Lab Med 2025:lmaf016. [PMID: 40424557 DOI: 10.1093/labmed/lmaf016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/29/2025] Open
Abstract
INTRODUCTION Many clinical laboratories use indirect estimation methods for low-density lipoprotein cholesterol (LDL-C) because of cost and practicality. This study compared the accuracy of indirect LDL-C estimates derived from the Friedewald, Puavilai, Hatta, and Martin equations in a Nepalese population. METHODS This retrospective analysis included 7750 patients who underwent lipid profile testing at the Norvic International Hospital, Kathmandu, from February 1 to July 31, 2021. Participants were categorized based on triglyceride levels (<400 mg/dL and ≥400 mg/dL). Pearson correlation, paired t tests, and analysis of variance were employed to assess relationships and differences between directly measured and estimated LDL-C values. RESULTS The Puavilai equation demonstrated the highest concordance with directly measured LDL-C (92%), followed by the Martin (89%), Friedewald (88%), and Hatta (81%) equations. The Puavilai equation exhibited the smallest discrepancies (mean difference = 8.9 mg/dL) for triglyceride values below 150 mg/dL. The Martin equation was most accurate for triglyceride values above 150 mg/dL (mean difference = 10.0 mg/dL) and remained reliable, even for triglyceride values above 400 mg/dL. The Hatta equation showed the largest estimation errors. DISCUSSION The Puavilai equation is recommended for estimating LDL-C when triglyceride levels are below 150 mg/dL, while the Martin equation is preferred for levels above this threshold in the Nepalese population.
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Affiliation(s)
- Ranjan Suwal
- Department of Biochemistry, Patan Academy of Health Sciences, Kathmandu, Nepal
| | - Vivek Pant
- Department of Biochemistry, Samyak Diagnostic Pvt Ltd, Kathmandu, Nepal
| | | | - Prakash Poudel
- Department of Pathology, Norvic International Hospital, Kathmandu, Nepal
| | - Sujan Shrestha
- Department of Pathology, National Academy of Medical Sciences, Kathmandu, Nepal
| | - Santosh Pradhan
- Department of Biochemistry, Samyak Diagnostic Pvt Ltd, Kathmandu, Nepal
| | - Shital Bhandary
- School of Public Health, Patan Academy of Health Sciences, Kathmandu, Nepal
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Langlois MR. The Friedewald formula strikes back. Clin Chem Lab Med 2025; 63:1043-1045. [PMID: 40009481 DOI: 10.1515/cclm-2025-0211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/28/2025]
Affiliation(s)
- Michel R Langlois
- Department of Laboratory Medicine, 60208 AZ St.-Jan Hospital , Bruges, Belgium
- Chair of Division: Science, European Federation of Clinical Chemistry and Laboratory Medicine (EFLM), Brussels, Belgium
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7
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Drobnik S, Scharnagl H, Samani NJ, Braund PS, Nelson CP, Hollstein T, Kassner U, Dressel A, Drobnik W, März W. Evaluation of current indirect methods for measuring LDL-cholesterol. Clin Chem Lab Med 2025; 63:1099-1108. [PMID: 39964360 DOI: 10.1515/cclm-2025-0024] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Accepted: 01/29/2025] [Indexed: 04/26/2025]
Abstract
OBJECTIVES Accurately quantifying low-density lipoprotein cholesterol (LDL-C) is crucial for precise cardiovascular disease risk assessment and treatment decisions. The commonly used Friedewald equation (LDL-CFW) has faced criticism for its tendency to underestimate LDL-C, particularly at high triglycerides (TG) or low LDL-C, potentially leading to undertreatment. Newer equations, such as those by Martin and Hopkins (LDL-CMH) or Sampson (LDL-CSN), have been proposed as alternatives. Our study aimed to assess the validity of LDL-CFW, LDL-CMH, and LDL-CSN compared to ß-quantification (LDL-CUC), the reference method recommended by the Lipid Research Clinics. METHODS Using data from three studies comprising 5,738 datasets, LDL-C was determined with the four methods in samples with TG up to 5.65 mmol/L. We calculated median and mean differences, correlations, and used the Passing and Bablok regression for comparisons. Concordance/discordance analyses were conducted. RESULTS All equations provided generally accurate LDL-C estimations with slight differences among them. At TG<1.69 mmol/L, no clinically significant divergences were observed. As TG values increased, LDL-CFW offered the most accurate estimation, followed by LDL-CSN, while LDL-CMH exhibited increasingly strong positive bias. LDL-CFW was not inferior to LDL-CSN and LDL-CMH in terms of concordance/discordance. CONCLUSIONS LDL-CFW generally provided reliable estimates of LDL-C in most samples, showing non-inferiority to LDL-CSN or LDL-CMH, thereby confirming its legitimacy for routine use. Since current treatment recommendations are based on studies employing LDL-CFW, its replacement by alternatives is not justified.
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Affiliation(s)
- Sophia Drobnik
- Medical Clinic I, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | - Hubert Scharnagl
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - Nilesh J Samani
- Department of Cardiovascular Sciences, University of Leicester, and NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK
| | - Peter S Braund
- Department of Cardiovascular Sciences, University of Leicester, and NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK
| | - Christopher P Nelson
- Department of Cardiovascular Sciences, University of Leicester, and NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK
| | - Tim Hollstein
- Department of Endocrinology, Campus Virchow-Klinikum, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Ursula Kassner
- Department of Endocrinology, Campus Virchow-Klinikum, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Alexander Dressel
- D•A•CH-Gesellschaft Prävention von Herz-Kreislauf-Erkrankungen e.V., Hamburg, Germany
- Dr.Dressel Consulting, Mannheim, Germany
| | | | - Winfried März
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
- SYNLAB Academy, SYNLAB Holding Deutschland GmbH, Mannheim and Augsburg, Germany
- Department of Internal Medicine III (Cardiology, Angiology, Pneumology), Medical Faculty Heidelberg, University of Heidelberg, Mannheim, Germany
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Jha M, Agrawal SP, Maheta D, Bhattacharjee P, Jain H, Zacks J, Frishman WH, Aronow WS. Efficacy and safety of evolocumab in statin-treated patients with cardiovascular risk factors: a systematic review and meta-analysis. Expert Opin Biol Ther 2025:1-11. [PMID: 40402652 DOI: 10.1080/14712598.2025.2511063] [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: 01/23/2025] [Revised: 04/25/2025] [Accepted: 05/21/2025] [Indexed: 05/24/2025]
Abstract
INTRODUCTION This systematic review and meta-analysis evaluated the lipid-lowering efficacy and safety of evolocumab in statin-treated patients at high cardiovascular risk, focusing on changes in LDL-C, TG, ApoB, HDL-C, and Lp(a) after 12 weeks. METHODS A comprehensive search identified randomized controlled trials comparing evolocumab to placebo in adults on statin therapy. Studies reporting baseline and 12-week lipid and safety data were included. Risk of bias was assessed using the Cochrane tool. Random-effects models were used to calculate mean differences (MD) or odds ratios (OR) with 95% confidence intervals (CI). RESULTS Five trials with 4,009 participants were analyzed. Evolocumab significantly reduced LDL-C (MD: -64.67; 95% CI: -66.72 to -62.61), TG, ApoB, and Lp(a), and increased HDL-C. No significant difference was observed in total TEAEs (OR: 0.97; 95% CI: 0.84 to 1.14) or serious TEAEs (OR: 1.23; 95% CI: 0.80 to 1.89) versus placebo. CONCLUSIONS Evolocumab offers robust lipid-lowering benefits with a safety profile comparable to placebo in statin-treated patients. Limitations include short follow-up and variable statin regimens. Further long-term studies are needed to confirm cardiovascular outcome benefits. PROTOCOL REGISTRATION www.crd.york.ac.uk/prospero identifier is CRD42024543525.
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Affiliation(s)
- Mayank Jha
- Department of Internal Medicine, Government Medical College and New Civil Hospital, Surat, India
| | - Siddharth Pravin Agrawal
- Department of Internal Medicine, New York Medical College/Landmark Medical Center, Woonsocket, RI, USA
| | | | | | - Hritvik Jain
- Department of Internal Medicine, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Jerome Zacks
- Department of Cardiology, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
| | | | - Wilbert S Aronow
- Departments of Cardiology and Medicine, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
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Hernández-Negrín H, Bernal-López MR, López-Sampalo A, Rubio-Rivas M, Aguilar-García JA, Gómez-Uranga A, Carnevali M, Taboada-Martínez ML, Ramos-Rincón JM, Gómez-Huelgas R, Hernández-Negrín H, Bernal-López MR, López-Sampalo A, Rubio-Rivas M, Aguilar-García JA, Gómez-Uranga A, Carnevali M, Taboada-Martínez ML, Muiño-Miguez A, Beato-Perez JL, Torres-Peña JD, Martín-Oterino JÁ, Loureiro-Amigo J, Casas-Rojo JM, Gil-Sánchez R, López-Reboiro ML, Román-Bernal B, Fernandez-Sola J, Amorós-Martínez F, Vicente-López N, Valle-Bernad R, Pérez-González A, Ramos-Rincón JM, Gómez-Huelgas R. Cardiovascular profile of systemic lupus erythematosus patients hospitalized for COVID-19 in Spain: Analysis of the SEMI-COVID-19 Registry. Med Clin (Barc) 2025; 164:106889. [PMID: 39818450 DOI: 10.1016/j.medcli.2024.11.022] [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: 07/28/2024] [Revised: 11/15/2024] [Accepted: 11/21/2024] [Indexed: 01/18/2025]
Abstract
BACKGROUND Despite advancements in understanding the interplay between systemic lupus erythematosus (SLE), cardiovascular disease and COVID-19, challenges and knowledge gaps persist. This study aimed to characterize the cardiovascular profiles of SLE patients hospitalized with COVID-19 and to evaluate the influence of SLE on the development of cardiovascular complications. METHODS This was a multicentre, nationwide observational study in which data were sourced from the SEMI-COVID-19 Registry between March 1, 2020, and March 31, 2021, involving 150 Spanish hospitals. SLE patients were matched with non-SLE patients based on sex, age, and hospitalization date. RESULTS Of the 20,970 patients included in the SEMI-COVID-19 Registry, 38 were previously diagnosed with SLE. The non-SLE group was composed of 103 patients. The mean age of the SLE patients was 63 years, with 81.6% females and 21.1% non-European patients. SLE patients exhibited a significantly higher frequency of chronic kidney disease (14.4% vs 2.9%; p=0.004), stroke (23.7% vs 2.9%; p<0.001), and increased use of cardiovascular medications. SLE demonstrated an independent association with the occurrence of major cardiovascular events (MACE) (OR: 3.934; 95% CI: 1.247-12.432). CONCLUSIONS SLE patients hospitalized for COVID-19 are at high risk of having an unfavorable baseline cardiovascular profile and are more prone to MACEs and adverse noncardiovascular outcomes during hospitalization.
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Affiliation(s)
- Halbert Hernández-Negrín
- Internal Medicine Clinical Management Unit, Hospital Regional Universitario de Málaga, Instituto de Investgación Biomédica de Málaga (IBIMA-Plataforma BIONAND), Avenida Carlos Haya S/N, 29010 Málaga, Spain; Faculty of Medicine, Universidad de Málaga, Campus Teatinos, 29010 Málaga, Spain
| | - María Rosa Bernal-López
- Internal Medicine Clinical Management Unit, Hospital Regional Universitario de Málaga, Instituto de Investgación Biomédica de Málaga (IBIMA-Plataforma BIONAND), Avenida Carlos Haya S/N, 29010 Málaga, Spain; Faculty of Medicine, Universidad de Málaga, Campus Teatinos, 29010 Málaga, Spain; Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Almudena López-Sampalo
- Internal Medicine Clinical Management Unit, Hospital Regional Universitario de Málaga, Instituto de Investgación Biomédica de Málaga (IBIMA-Plataforma BIONAND), Avenida Carlos Haya S/N, 29010 Málaga, Spain; Faculty of Medicine, Universidad de Málaga, Campus Teatinos, 29010 Málaga, Spain
| | - Manuel Rubio-Rivas
- Internal Medicine Department, Hospital Universitario de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain
| | | | - Angie Gómez-Uranga
- Internal Medicine Department, Hospital Universitario de San Juan, Alicante, Spain
| | - María Carnevali
- Internal Medicine Department, 12 de Octubre University Hospital, Madrid, Spain
| | | | | | - Ricardo Gómez-Huelgas
- Internal Medicine Clinical Management Unit, Hospital Regional Universitario de Málaga, Instituto de Investgación Biomédica de Málaga (IBIMA-Plataforma BIONAND), Avenida Carlos Haya S/N, 29010 Málaga, Spain; Faculty of Medicine, Universidad de Málaga, Campus Teatinos, 29010 Málaga, Spain; Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain.
| | - Halbert Hernández-Negrín
- Internal Medicine Clinical Management Unit, Hospital Regional Universitario de Málaga, Instituto de Investgación Biomédica de Málaga (IBIMA-Plataforma BIONAND), Avenida Carlos Haya S/N, 29010 Málaga, Spain; Faculty of Medicine, Universidad de Málaga, Campus Teatinos, 29010 Málaga, Spain
| | - María Rosa Bernal-López
- Internal Medicine Clinical Management Unit, Hospital Regional Universitario de Málaga, Instituto de Investgación Biomédica de Málaga (IBIMA-Plataforma BIONAND), Avenida Carlos Haya S/N, 29010 Málaga, Spain; Faculty of Medicine, Universidad de Málaga, Campus Teatinos, 29010 Málaga, Spain; Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Almudena López-Sampalo
- Internal Medicine Clinical Management Unit, Hospital Regional Universitario de Málaga, Instituto de Investgación Biomédica de Málaga (IBIMA-Plataforma BIONAND), Avenida Carlos Haya S/N, 29010 Málaga, Spain; Faculty of Medicine, Universidad de Málaga, Campus Teatinos, 29010 Málaga, Spain
| | - Manuel Rubio-Rivas
- Internal Medicine Department, Hospital Universitario de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain
| | | | - Angie Gómez-Uranga
- Internal Medicine Department, Hospital Universitario de San Juan, Alicante, Spain
| | - María Carnevali
- Internal Medicine Department, 12 de Octubre University Hospital, Madrid, Spain
| | | | - Antonio Muiño-Miguez
- Internal Medicine Department, Hospital Universitario Gregorio Marañón, Madrid, Spain
| | - José Luis Beato-Perez
- Internal Medicine Department, Complejo Hospitalario Universitario de Albacete, Albacete, Spain
| | - José David Torres-Peña
- Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain; Lipids and Atherosclerosis Unit, Department of Internal Medicine, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain
| | | | - José Loureiro-Amigo
- Internal Medicine Department, Moisès Broggi Hospital, Sant Joan Despí, Barcelona, Spain
| | - José Manuel Casas-Rojo
- Internal Medicine Department, Hospital Universitario Infanta Cristina, Parla, Madrid, Spain
| | | | | | - Berta Román-Bernal
- Internal Medicine Department, Hospital Dr. José Molina Orosa, Lanzarote, Spain
| | | | | | - Natalia Vicente-López
- Internal Medicine Department, Hospital Universitario del Sureste, Arganda del Rey, Madrid, Spain
| | - Reina Valle-Bernad
- Internal Medicine Department, Hospital Sierrallana, Torrelavega, Cantabria, Spain
| | | | | | - Ricardo Gómez-Huelgas
- Internal Medicine Clinical Management Unit, Hospital Regional Universitario de Málaga, Instituto de Investgación Biomédica de Málaga (IBIMA-Plataforma BIONAND), Avenida Carlos Haya S/N, 29010 Málaga, Spain; Faculty of Medicine, Universidad de Málaga, Campus Teatinos, 29010 Málaga, Spain; Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain
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10
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Li G, Yang W, Kuang Z, Cai Y, You J. Association of the estimated glucose disposal rate with and mortality risk in patients with atherosclerotic cardiovascular disease: A cohort study from the NHANES 1999-2018. Diabetes Res Clin Pract 2025:112263. [PMID: 40409724 DOI: 10.1016/j.diabres.2025.112263] [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: 02/16/2025] [Revised: 05/01/2025] [Accepted: 05/17/2025] [Indexed: 05/25/2025]
Abstract
AIM To investigate the association between estimated glucose disposal rate (eGDR) and mortality risk among patients with atherosclerotic cardiovascular disease (ASCVD). METHODS NHANES (1999-2018) data were analyzed using weighted Cox regression and restricted cubic splines (RCS) to assess the association between eGDR and mortality. Improvement in predictive performance was evaluated. Subgroup, mediation, and sensitivity analyses were conducted. RESULTS Among 4,425 ASCVD patients (67.40 % ≥60 years, 44.66 % female), 1,815 deaths (35.62 %) and 751 CVD deaths (18.48 %) occurred over 7.7 years. Compared to the highest quartile, the lowest eGDR quartile had HRs of 2.13 and 2.06 for CVD and all-cause mortality, respectively. RCS demonstrated linearity (P-nonlinear > 0.05). Addition of eGDR improved the predictive performance for both CVD and all-cause mortality (P < 0.001), whereas other insulin resistance indicators did not yield comparable improvements. Diabetes status modified its association with CVD mortality (P-interaction = 0.029). Neutrophil-to-lymphocyte ratio and estimated pulse wave velocity were key mediators. CONCLUSIONS Lower eGDR was associated with increased mortality risk in ASCVD, particularly among patients without diabetes. eGDR enhances mortality prediction, supporting its role as a prognostic marker in ASCVD.
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Affiliation(s)
- Guoming Li
- Cerebrovascular Disease Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Dade Road No. 111, Guangzhou, Guangdong 510120, China; Guangdong Provincial Chinese Emergency Key Laboratory, Guangzhou, Guangdong 510120, China.
| | - Weilin Yang
- Cerebrovascular Disease Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Dade Road No. 111, Guangzhou, Guangdong 510120, China.
| | - Zhuoran Kuang
- Cerebrovascular Disease Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Dade Road No. 111, Guangzhou, Guangdong 510120, China.
| | - Yefeng Cai
- Encephalopathy Center, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Dade Road No. 111, Guangzhou, Guangdong 510120, China.
| | - Jingsong You
- Cerebrovascular Disease Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Dade Road No. 111, Guangzhou, Guangdong 510120, China; Guangdong Provincial Chinese Emergency Key Laboratory, Guangzhou, Guangdong 510120, China.
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11
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Nordestgaard AT, Tybjærg-Hansen A, Mansbach H, Kersten S, Nordestgaard BG, Rosenson RS. Target Populations for Novel Triglyceride-Lowering Therapies. J Am Coll Cardiol 2025; 85:1876-1897. [PMID: 40368577 DOI: 10.1016/j.jacc.2025.02.035] [Citation(s) in RCA: 1] [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: 10/17/2024] [Revised: 02/10/2025] [Accepted: 02/20/2025] [Indexed: 05/16/2025]
Abstract
Lipoprotein lipase regulates triglyceride hydrolysis and contributes to cellular uptake of triglyceride-rich lipoprotein remnants. Multiple pathways modulate lipoprotein lipase activity, which has prompted interest in the development of drugs that increase lipoprotein lipase activity as means to reduce risk for acute pancreatitis, atherosclerotic cardiovascular disease, and metabolic dysfunction-associated steatohepatitis through reduction of circulating triglycerides and remnant cholesterol. The authors provide an overview of the target populations for agents that lower triglycerides and remnant cholesterol through increased lipoprotein lipase activity, the drugs being developed for these indications, including apolipoprotein C-III and angiopoietin-like protein 3, 3/8, and 4 inhibitors, and the epidemiologic and genetic evidence supporting the use of these drugs for the prevention of atherosclerotic cardiovascular disease and acute pancreatitis. In addition, the authors provide a corresponding overview of fibroblast growth factor-21 analogues that share many characteristics with these novel triglyceride-lowering drugs. Apolipoprotein C-III inhibitors, angiopoietin-like protein 3, 3/8, and 4 inhibitors, and fibroblast growth factor-21 analogues have pronounced triglyceride-lowering and remnant cholesterol-lowering effects. In clinical trials, apolipoprotein C-III inhibitors have been shown to lower risk for acute pancreatitis in patients with severe hypertriglyceridemia and are approved for this indication, while fibroblast growth factor-21 analogues reduce hepatic steatosis and fibrosis in patients with metabolic dysfunction-associated steatohepatitis. It remains to be seen whether these novel drugs may lower risk for atherosclerotic cardiovascular disease as well.
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Affiliation(s)
- Ask T Nordestgaard
- Center for Cardiovascular Disease Prevention, Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Department of Clinical Biochemistry and the Copenhagen General Population Study, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark.
| | - Anne Tybjærg-Hansen
- Department of Clinical Biochemistry, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | | | - Sander Kersten
- Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA
| | - Børge G Nordestgaard
- Department of Clinical Biochemistry and the Copenhagen General Population Study, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Robert S Rosenson
- Metabolism and Lipids Unit, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, New York, USA
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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; 110:1740-1755. [PMID: 39797609 DOI: 10.1210/clinem/dgaf018] [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: 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 high-density lipoprotein cholesterol and the presence of small, dense low-density lipoprotein 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 type 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 and individualized treatment selection and the need to avoid therapy inertia to mitigate cardiovascular risk. We also address lipid-related effects of glycemic-lowering therapies.
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Affiliation(s)
- Stephanie Kim
- Assistant Professor of Clinical Practice Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA 98109, USA
| | - Savitha Subramanian
- Professor of Medicine Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA 98109, USA
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13
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Kazibwe R, Jehopio J, Schaich CL, Rikhi R, Mirzai S, Chevli PA, Namutebi JH, Chebrolu S, O'Connor S, Yeboah J, Shapiro MD. Atherogenic dyslipidemia and incident cardiovascular events in high-risk hypertension. Prog Cardiovasc Dis 2025:S0033-0620(25)00069-6. [PMID: 40393568 DOI: 10.1016/j.pcad.2025.05.006] [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: 03/28/2025] [Revised: 04/25/2025] [Accepted: 05/12/2025] [Indexed: 05/22/2025]
Abstract
BACKGROUND Atherogenic dyslipidemia (AD), characterized by low high-density lipoprotein cholesterol (HDL-C) and elevated triglycerides (TG), is associated with increased cardiovascular disease (CVD) risk. This study evaluates the association between AD and CVD in hypertension treated to systolic blood pressure (SBP) targets of <120 mmHg (intensive) or < 140 mmHg (standard). METHODS We included 9361 participants from the Systolic Blood Pressure Intervention Trial (SPRINT). Based on baseline lipid profiles, low HDL-C was defined as <40 mg/dL in men or < 50 mg/dL in women, and high TG as ≥150 mg/dL. Participants were classified into four lipid categories according to these cutoffs. AD was defined as the combination of low HDL-C and high TG. We used multivariable Cox regression to evaluate the association between lipid categories and the primary SPRINT outcome, a composite of major CVD events. RESULTS Over a median 3.8-year follow-up, 726 primary outcome events occurred. The incidence of the primary outcome was 9.5% (n = 104) in those with AD and 7.4% (n = 434) with normal HDL-C and TG. Compared to the reference group (normal HDL-C with normal TG), the hazard ratios (HRs) for primary outcome were 1.07 (95 % CI: 0.85-1.35) for high TG alone, 1.20 (95 % CI: 0.95-1.52) for low HDL-C alone, and 1.41 (95 % CI: 1.12-1.77) for AD. Similarly, HRs for the primary outcome associated with AD were 1.38 (95 % CI: 1.02-1.87) and 1.44 (95 % CI: 1.01-2.05) in the standard and intensive SBP-lowering arms, respectively. CONCLUSION Among SPRINT participants, AD was associated with a higher CVD risk. Early detection of AD in hypertensive patients, even without diabetes, may prompt greater therapeutic effort to reduce long-term CVD risk.
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Affiliation(s)
- Richard Kazibwe
- Department of Internal Medicine, Wake Forest University School of Medicine, 1 Medical Center Medical Center Boulevard, Winston-Salem, NC 27157, USA.
| | - Jeshuah Jehopio
- Uganda Christian University, School of Medicine, P.O. Box 4, Mukono, Uganda.
| | - Christopher L Schaich
- Hypertension and Vascular Research Center, Wake Forest University School of Medicine, 1 Medical Center Medical Center Boulevard, Winston-Salem, NC 27157, USA.
| | - Rishi Rikhi
- Division of Cardiology, Wake Forest University School of Medicine, 1 Medical Center Medical Center Boulevard, Winston-Salem, NC 27157, USA.
| | - Saeid Mirzai
- Division of Cardiology, Wake Forest University School of Medicine, 1 Medical Center Medical Center Boulevard, Winston-Salem, NC 27157, USA.
| | - Parag A Chevli
- Division of Cardiology, Wake Forest University School of Medicine, 1 Medical Center Medical Center Boulevard, Winston-Salem, NC 27157, USA.
| | - Juliana H Namutebi
- Wake Forest University, School of Biomedical Graduate Studies, 1 Medical Center Medical Center Boulevard, Winston-Salem, NC 27157, USA.
| | - Sneha Chebrolu
- Department of Internal Medicine, Wake Forest University School of Medicine, 1 Medical Center Medical Center Boulevard, Winston-Salem, NC 27157, USA.
| | - Shannon O'Connor
- Department of Internal Medicine, Wake Forest University School of Medicine, 1 Medical Center Medical Center Boulevard, Winston-Salem, NC 27157, USA.
| | - Joseph Yeboah
- Division of Cardiology, Wake Forest University School of Medicine, 1 Medical Center Medical Center Boulevard, Winston-Salem, NC 27157, USA.
| | - Michael D Shapiro
- Center for the Prevention of Cardiovascular Disease, Section on Cardiovascular Medicine, Wake Forest University School of Medicine, 1 Medical Center Medical Center Boulevard, Winston-Salem, NC 27157, USA.
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14
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Ratrout BM, Katamesh BE, Vincent A, Hurt RT, Bonnes S, Adusumalli J, Lawson DK, Schroeder D, VerNess CD, Croghan I. Evaluating atherosclerosis prevalence via coronary calcium in executives with normal LDL levels in the US: a cohort study-the clear protocol. BMJ Open 2025; 15:e094899. [PMID: 40379338 PMCID: PMC12083267 DOI: 10.1136/bmjopen-2024-094899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Accepted: 05/01/2025] [Indexed: 05/19/2025] Open
Abstract
INTRODUCTION The coronary artery calcium (CAC) scan serves as a crucial tool in assessing the risk of coronary atherosclerosis in patients with hyperlipidaemia, particularly when there is ambiguity surrounding pharmacotherapy decisions. In addition to CAC, advanced glycation end products (AGEs), glycated proteins and lipids involved in ageing are emerging as markers for atherosclerosis. However, the relationship between AGEs score and CAC scores has not been evaluated to date. Our primary objective is to evaluate abnormal CAC scores in patients with low and borderline ASCVD risk and normal low-density lipoprotein cholesterol (LDL-C) levels ≤100 mg/dL. The secondary objective is to explore potential associations between CAC and AGEs scores. METHODS AND ANALYSIS We will retrospectively review health records of adult patients seen at the General Internal Medicine Executive Health Program (Mayo Clinic; Rochester, Minnesota) between 1 September 2023 and 31 March 2024, where all patients were offered the option of a baseline CAC scan. For our primary aim, we will determine the percentage of patients with low and borderline 10-year Atherosclerotic Cardiovascular Disease (ASCVD) risk, not receiving pharmacotherapy for hyperlipidaemia, who have LDL-C levels ≤100 mg/dL and have an abnormal CAC score. For our secondary aim, we will examine potential associations between CAC and AGEs scores. ETHICS AND DISSEMINATION This study was determined to be exempt from institutional review board approval (ID 24-0 03 921; 45 CFR 46.104d, category/subcategory 4(iii)) at the Mayo Clinic, Rochester. The findings of this study will be published in a peer-reviewed journal.
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Affiliation(s)
| | | | - Ann Vincent
- Division of General Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | | | | | | | | | | | | | - Ivana Croghan
- General Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
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15
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Nordestgaard AT, Pradhan AD, Everett BM, MacFadyen JG, Bhatt DL, Visseren FLJ, Libby P, Santos RD, Nissen SE, Nordestgaard BG, Ridker PM. Expanding the triglyceride range in clinical trials: therapeutic opportunities. Eur Heart J 2025; 46:1835-1848. [PMID: 39950981 DOI: 10.1093/eurheartj/ehaf074] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 09/25/2024] [Accepted: 01/29/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND AND AIMS Guidelines focus on individuals with triglycerides between 2.3 and 5.6 mmol/L (200 and 499 mg/dL). The hypotheses that triglycerides across the full biological range and within this constrained range associated with cardiovascular risk were re-assessed. METHODS Multivariable-adjusted hazard ratios for major cardiovascular events and death according to baseline triglycerides among 119 573 individuals with triglycerides across the full biological range from the Copenhagen General Population Study, among 27 757 individuals with baseline triglycerides between 2.3 and 5.6 mmol/L from the Copenhagen General Population Study and the Women's Health Study cohorts, and among 31 272 individuals with mild-to-moderate hypertriglyceridaemia from the PROMINENT, REDUCE-IT, and STRENGTH trials were calculated. RESULTS Increasing triglycerides across the full range (0.3 to 11.2 mmol/L) were associated with an increasing risk of major cardiovascular events (N = 12 241). In the cohorts, combined hazard ratios [95% confidence interval (triglyceride range in mmol/L)] for major cardiovascular events (N = 3928) from lowest to highest triglyceride quartile were 1.0 [referent (range: < 2.5)], 0.95 [0.87-1.04 (range: 2.5 to <3.0)], 1.04 [0.95-1.13 (range: 3.0 to <3.6)], and 1.13 [1.04-1.23 (range: ≥ 3.6)]. In the three contemporary trials, the corresponding hazard ratios (N = 4265 cardiovascular events) from lowest to highest quartile were 1.0 [referent (ranges for PROMINENT/REDUCE-IT/STRENGTH: < 2.6/2.0/2.2)], 1.01 [0.93-1.10 (ranges: 2.6 to <3.1/2.0 to <2.5/2.2 to <2.7)], 1.05 [0.96-1.14 (ranges: 3.1 to <3.9/2.5 to <3.1/2.7 to < 3.5)] and 1.09 [1.00-1.19 (ranges: ≥ 3.9/3.1/3.5)]. In neither cohorts nor trials were triglycerides across this range strongly associated with risk of cardiovascular or all-cause death. CONCLUSIONS Individuals with mild-to-moderate hypertriglyceridaemia may not express the same magnitude of cardiovascular risk as that observed across the full range of plasma triglycerides. Future triglyceride-lowering therapy trials may want to consider enrolment across a wider range of triglyceride levels if there is no prior history of pancreatitis nor excessive alcohol intake.
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Affiliation(s)
- Ask T Nordestgaard
- Center for Cardiovascular Disease Prevention, Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA
- Department of Clinical Biochemistry and the Copenhagen General Population Study, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark
| | - Aruna D Pradhan
- Center for Cardiovascular Disease Prevention, Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Brendan M Everett
- Center for Cardiovascular Disease Prevention, Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Jean G MacFadyen
- Center for Cardiovascular Disease Prevention, Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Deepak L Bhatt
- Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Frank L J Visseren
- Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Peter Libby
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Raul D Santos
- Academic Research Organization, Hospital Israelita Albert Einstein & Lipid Clinic Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo SP, Brazil
| | - Steven E Nissen
- Cleveland Clinic Coordinating Center for Clinical Research, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Børge G Nordestgaard
- Department of Clinical Biochemistry and the Copenhagen General Population Study, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Paul M Ridker
- Center for Cardiovascular Disease Prevention, Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA
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16
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Tasdighi E, Dardari Z, Whelton SP, Patel J, Kanaya AM, Budoff MJ, Javaid A, Kulkarni S, Ma TW, Butler J, Shah NS, Blaha MJ, Agarwala A. Sex-Specific Coronary Artery Calcium Percentiles Across South Asian Adults: Combined Analyses From MASALA and DILWALE. JACC. ADVANCES 2025:101779. [PMID: 40402122 DOI: 10.1016/j.jacadv.2025.101779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/24/2024] [Revised: 03/26/2025] [Accepted: 03/30/2025] [Indexed: 05/23/2025]
Abstract
BACKGROUND Coronary artery calcium (CAC) testing is guideline-recommended to enhance atherosclerotic cardiovascular disease (ASCVD) risk prediction, yet there are no sex-specific CAC reference data for South Asians in the United States (SAUS) across their adult lives. OBJECTIVES The purpose of this study was to determine the sex-specific distribution of CAC scores across the adult lifespan of SAUS. METHODS We studied 2743 SAUS adults (ages 33-75 years old) free of known ASCVD from the MASALA (Mediators of Atherosclerosis in South Asians Living in America), a community-based cohort study, and the DILWALE (DIL Wellness and Arterial health Longitudinal Evaluation), a clinic-based study. We estimated the likelihood of CAC >0 and calculated sex-specific CAC percentiles as a function of age, employing nonparametric methods. RESULTS Participants had a mean age of 52 ± 9 years, with 37.8% women. The probability of CAC >0 for women and men was 20% and 45% at age 50 years, 40% and 70% at age 60 years, and 70% and 90% at 70 years old, respectively. The 75th and the 90th percentiles of CAC at age 60 years were 26 and 115 for SAUS women and 186 and 580 for SAUS men. A CAC score of 100 was at approximately the 75th percentile for a 55-year-old man or a 65-year-old woman. CONCLUSIONS These data address the current knowledge gap regarding the distribution of CAC scores among SAUS adults. Utilizing these CAC percentiles in the clinical assessment of ASCVD risk may enhance personalized interpretation of CAC scoring and guide ASCVD prevention efforts in SAUS.
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Affiliation(s)
- Erfan Tasdighi
- Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Baltimore, Maryland, USA; Department of Internal Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA
| | - Zeina Dardari
- Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Baltimore, Maryland, USA
| | - Seamus P Whelton
- Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Baltimore, Maryland, USA
| | - Jaideep Patel
- Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Baltimore, Maryland, USA
| | - Alka M Kanaya
- Department of Medicine, University of California-San Francisco, San Francisco, California, USA
| | - Matthew J Budoff
- Division of Cardiology, Lundquist Institute at Harbor-UCLA, Torrance, California, USA
| | - Aamir Javaid
- Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Baltimore, Maryland, USA
| | - Saneel Kulkarni
- Center for Cardiovascular Disease Prevention, Cardiovascular Division, Baylor Scott and White Health Heart Hospital Baylor Plano, Plano, Texas, USA
| | - Tsung-Wei Ma
- Baylor Scott and White Research Institute, Dallas, Texas, USA
| | - Javed Butler
- Baylor Scott and White Research Institute, Dallas, Texas, USA; University of Mississippi, Jackson, Mississippi, USA
| | - Nilay S Shah
- Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Michael J Blaha
- Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Baltimore, Maryland, USA
| | - Anandita Agarwala
- Center for Cardiovascular Disease Prevention, Cardiovascular Division, Baylor Scott and White Health Heart Hospital Baylor Plano, Plano, Texas, USA.
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17
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Lin H, Dong X, Yin Y, Gao Q, Peng S, Zhao Z, Li S, Huang R, Tao Y, Wen S, Li B, Wu Q, Lin T, Dai H, Wen F, Li Z, Xu L, Ma J, Feng Z, Liu S. Exploring the influencing factors of abdominal aortic calcification events in chronic kidney disease (CKD) and non-CKD patients based on interpretable machine learning methods. Int Urol Nephrol 2025:10.1007/s11255-025-04564-5. [PMID: 40348897 DOI: 10.1007/s11255-025-04564-5] [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: 03/12/2025] [Accepted: 05/01/2025] [Indexed: 05/14/2025]
Abstract
BACKGROUND Calcification is prevalent in CKD patients, with abdominal aortic calcification (AAC) being a strong predictor of coronary calcification. We aimed to identify key calcification factors in CKD and non-CKD populations using machine learning models. METHODS Data from the National Health and Nutrition Examination Survey (NHANES), including demographics, blood and urine tests, and AAC scores, were analyzed using machine learning models. The Shapley additive explanations (SHAP) analysis was applied to interpret the models. RESULTS Among 505 CKD and 2,582 non-CKD participants, common key factors for calcification included age, estimated glomerular filtration rate (eGFR), smoking history, blood glucose levels (Glu), Ca*P and the urine albumin-to-creatinine ratio (UACR). Age, smoking history and eGFR were the top-ranking features in the model for both two groups. Inflammatory markers such as monocyte-to-lymphocyte ratio (MHR), monocyte-to-high-density lipoprotein ratio (MLR) and neutrophil-to-lymphocyte ratio (NLR) were more significant in CKD group. Trigger points for AAC events were identified: in CKD, eGFR of 90 mL/min/1.73 m2, MHR values of 0.5 and 0.75, MLR values of 0.25, and SP of 120 mmHg; in non-CKD, eGFR of 105 mL/min/1.73 m2, Ca*P values of 40, UACR values of 10, and TG of 200 mg/dL. CONCLUSIONS Regardless of CKD status, age, smoking history, and eGFR are key determinants of calcification. In the CKD population, inflammatory markers are more significant than in the non-CKD group.
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Affiliation(s)
- Haowen Lin
- Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong, 510000, China
| | - Xiaoying Dong
- School of Medicine South, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), China University of Technology, Southern Medical University, Guangdong, 510000, China
| | - Yuhe Yin
- Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangdong, 510000, China
| | - Qingqing Gao
- Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangdong, 510000, China
| | - Siqi Peng
- Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangdong, 510000, China
| | - Zewen Zhao
- Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangdong, 510000, China
| | - Sijia Li
- Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangdong, 510000, China
| | - Renwei Huang
- Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangdong, 510000, China
| | - Yiming Tao
- Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangdong, 510000, China
| | - Sichun Wen
- Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangdong, 510000, China
| | - Bohou Li
- Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangdong, 510000, China
| | - Qiong Wu
- Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangdong, 510000, China
| | - Ting Lin
- Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangdong, 510000, China
| | - Hao Dai
- Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangdong, 510000, China
| | - Feng Wen
- Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangdong, 510000, China
| | - Zhuo Li
- Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangdong, 510000, China
| | - Lixia Xu
- Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangdong, 510000, China
| | - Jianchao Ma
- Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangdong, 510000, China
| | - Zhonglin Feng
- Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangdong, 510000, China
| | - Shuangxin Liu
- Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong, 510000, China.
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18
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Nicholls SJ, Nelson AJ, Ditmarsch M, Kastelein JJP, Ballantyne CM, Ray KK, Navar AM, Nissen SE, Harada-Shiba M, Curcio DL, Neild A, Kling D, Hsieh A, Butters J, Ference BA, Laufs U, Banach M, Mehran R, Catapano AL, Huo Y, Szarek M, Balinskaite V, Davidson MH. Safety and Efficacy of Obicetrapib in Patients at High Cardiovascular Risk. N Engl J Med 2025. [PMID: 40337982 DOI: 10.1056/nejmoa2415820] [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] [Indexed: 05/09/2025]
Abstract
BACKGROUND Obicetrapib is a highly selective cholesteryl ester transfer protein inhibitor that reduces low-density lipoprotein (LDL) cholesterol levels. The efficacy and safety of obicetrapib have not been fully characterized among patients at high risk for cardiovascular events. METHODS We conducted a multinational, randomized, placebo-controlled trial involving patients with heterozygous familial hypercholesterolemia or a history of atherosclerotic cardiovascular disease who were receiving maximum tolerated doses of lipid-lowering therapy. Patients with an LDL cholesterol level of 100 mg per deciliter or higher or a non-high-density lipoprotein (HDL) cholesterol level of 130 mg per deciliter or higher, as well as those with an LDL cholesterol level of 55 to 100 mg per deciliter or a non-HDL cholesterol level of 85 to 130 mg per deciliter and at least one additional cardiovascular risk factor, were eligible for inclusion. The patients were randomly assigned in a 2:1 ratio to receive either 10 mg of obicetrapib once daily or matching placebo for 365 days. The primary end point was the percent change in the LDL cholesterol level from baseline to day 84. RESULTS A total of 2530 patients underwent randomization; 1686 patients were assigned to receive obicetrapib and 844 to receive placebo. The mean age of the patients was 65 years, 34% were women, and the mean baseline LDL cholesterol level was 98 mg per deciliter. The least-squares mean percent change from baseline to day 84 in the LDL cholesterol level was -29.9% (95% confidence interval [CI], -32.1 to -27.8) in the obicetrapib group, as compared with 2.7% (95% CI, -0.4 to 5.8) in the placebo group, for a between-group difference of -32.6 percentage points (95% CI, -35.8 to -29.5; P<0.001). The incidence of adverse events appeared to be similar in the two groups. CONCLUSIONS Among patients with atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia who were receiving maximum tolerated doses of lipid-lowering therapy and were at high risk for cardiovascular events, obicetrapib reduced LDL cholesterol levels by 29.9%. (Funded by NewAmsterdam Pharma; BROADWAY ClinicalTrials.gov number, NCT05142722.).
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Affiliation(s)
| | - Adam J Nelson
- Victorian Heart Institute, Monash University, Clayton, VIC, Australia
| | | | - John J P Kastelein
- NewAmsterdam Pharma, Amsterdam
- Department of Vascular Medicine, University of Amsterdam, Amsterdam
| | | | | | | | | | - Mariko Harada-Shiba
- Cardiovascular Center, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | | | | | | | | | - Julie Butters
- Victorian Heart Institute, Monash University, Clayton, VIC, Australia
| | - Brian A Ference
- Centre for Naturally Randomized Trials, University of Cambridge, Cambridge, United Kingdom
| | - Ulrich Laufs
- Klinik und Poliklinik für Kardiologie, Leipzig University, Leipzig, Germany
| | - Maciej Banach
- Department of Preventive Cardiology and Lipidology, Medical University of Lodz, Lodz, Poland
| | - Roxana Mehran
- Mount Sinai Fuster Heart Hospital, Icahn School of Medicine, Mount Sinai, New York
| | | | - Yong Huo
- Peking University First Hospital, Beijing
| | - Michael Szarek
- Mount Sinai Fuster Heart Hospital, Icahn School of Medicine, Mount Sinai, New York
- University of Colorado Anschutz Medical Campus, Aurora
- State University of New York Downstate School of Public Health, New York
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19
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Krzowski J, Weir-McCall J, D'Errico L, Costopoulos C, Costanzo P. Aortic Valve Calcium: A Narrative Review of its Role in the Assessment of Aortic Stenosis and as a Predictor of Post-transcatheter Aortic Valve Implantation Outcomes. Interv Cardiol 2025; 20:e16. [PMID: 40396184 PMCID: PMC12090074 DOI: 10.15420/icr.2024.17] [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] [Received: 04/24/2024] [Accepted: 12/24/2024] [Indexed: 05/22/2025] Open
Abstract
Degenerative aortic valve disease is the third most common cause of heart disease in the developed world. Calcific deposits accrue in the valve endothelium causing progressive stenosis of the orifice. Increasingly, transcatheter aortic valve implantation is being used in place of surgery as treatment for aortic stenosis, particularly for patients who are considered high surgical risk. Although echocardiography remains the gold standard for the diagnosis and grading of aortic valve stenosis, there is an increasing interest in the role that aortic valve calcification scoring may play in these areas. In this review, the authors evaluate the current evidence for aortic valve calcium scoring as an adjunct to echocardiography in grading, and as a prognostic marker in challenging cases. They also explore the ability of calcium scoring to predict outcomes following transcatheter aortic valve implantation.
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Affiliation(s)
- James Krzowski
- Royal Papworth Hospital, Royal Papworth Hospital NHS Foundation Trust Cambridge, UK
| | - Jonathan Weir-McCall
- Royal Papworth Hospital, Royal Papworth Hospital NHS Foundation Trust Cambridge, UK
| | - Luigia D'Errico
- Royal Papworth Hospital, Royal Papworth Hospital NHS Foundation Trust Cambridge, UK
| | - Charis Costopoulos
- Royal Papworth Hospital, Royal Papworth Hospital NHS Foundation Trust Cambridge, UK
| | - Pierluigi Costanzo
- Royal Papworth Hospital, Royal Papworth Hospital NHS Foundation Trust Cambridge, UK
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20
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He J, Lin Z, Song C, Yuan S, Bian X, Li B, Ma W, Dou K. J-shaped association between apolipoprotein B and CV outcomes in statin-treated patients with chronic coronary syndrome. REVISTA ESPANOLA DE CARDIOLOGIA (ENGLISH ED.) 2025; 78:404-413. [PMID: 39270776 DOI: 10.1016/j.rec.2024.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 08/27/2024] [Indexed: 09/15/2024]
Abstract
INTRODUCTION AND OBJECTIVES The association between apolipoprotein B (apoB) and residual cardiovascular (CV) risk in patients with chronic coronary syndrome (CCS) remains unclear. We aimed to investigate the association between apoB levels and CV outcomes in statin-treated CCS patients. METHODS We enrolled 8641 statin-treated CCS patients at Fuwai Hospital. The patients were divided into 5 groups based on to apoB quintiles (Q1 to Q5). The primary endpoint was 3-year CV events, including CV death, nonfatal myocardial infarction, and nonfatal stroke. RESULTS During a median follow-up of 3.17 years, there were 232 (2.7%) CV events. After multivariable adjustment, a restricted cubic spline illustrated a J-shaped relationship between apoB levels and 3-year CV events, with the risk remaining flat until apoB levels exceeded 0.73g/L, after which the risk increased (nonlinear P <.05). Kaplan-Meier curves showed the lowest CV event rate in the Q3 group (0.68-0.78g/L). Compared with the Q3 group, multivariable Cox regression models revealed that both low (Q1, ≤0.57g/L) and high (Q5, >0.93g/L) apoB levels were associated with an increased risk of major adverse cardiac events (all P <.05). Notably, patients with low apoB levels (Q1) had the highest risk of CV death (HR, 2.44; 95%CI, 1.17-5.08). CONCLUSIONS Our analysis indicates that both low and high levels of apoB are associated with elevated CV risk, with the risk being particularly pronounced at higher levels (> 0.73g/L).
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Affiliation(s)
- Jining He
- State Key Laboratory of Cardiovascular Disease, Beijing, China; Cardiometabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhangyu Lin
- State Key Laboratory of Cardiovascular Disease, Beijing, China; Cardiometabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chenxi Song
- State Key Laboratory of Cardiovascular Disease, Beijing, China; Cardiometabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Sheng Yuan
- State Key Laboratory of Cardiovascular Disease, Beijing, China; Cardiometabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaohui Bian
- State Key Laboratory of Cardiovascular Disease, Beijing, China; Cardiometabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bowen Li
- State Key Laboratory of Cardiovascular Disease, Beijing, China; Cardiometabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wenjun Ma
- State Key Laboratory of Cardiovascular Disease, Beijing, China; Hypertension Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Kefei Dou
- State Key Laboratory of Cardiovascular Disease, Beijing, China; Cardiometabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; National Clinical Research Center for Cardiovascular Diseases, Beijing, China.
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21
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Cheng FWT, Xu W, Tang SCW, Wan EYF. Long-Term Benefits and Safety of Statins in Patients with Kidney Failure: A Target Trial Emulation Study. J Am Soc Nephrol 2025; 36:882-889. [PMID: 39480503 PMCID: PMC12059101 DOI: 10.1681/asn.0000000554] [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: 06/12/2024] [Accepted: 10/28/2024] [Indexed: 11/02/2024] Open
Abstract
Key Points Patients with kidney failure are at a higher risk of cardiovascular diseases, but the evidence for statin therapy remains inconclusive. The long-term benefits and risks of statin therapy in patients with kidney failure were analyzed using public electronic health records in Hong Kong. Statin therapy was associated with a lower risk of major cardiovascular diseases and all-cause mortality without a higher risk of major adverse events. Background Patients with kidney failure are at elevated risk of cardiovascular diseases. Although statins are commonly used to mitigate cardiovascular risk among the population with high risk, the evidence for initiating statin therapy among patients with kidney failure remains inconclusive. This study aimed to investigate the long-term benefits and risks associated with statin therapy in patients with kidney failure. Methods Using territory-wide public electronic health records in Hong Kong, 3019 statin-eligible individuals with kidney failure and elevated LDL cholesterol ≥100 mg/dl from January 2008 to December 2015 were included for analysis. The framework of target trial emulation was adopted to investigate the risk of the major cardiovascular diseases (i.e ., a composite of myocardial infarction, heart failure, and stroke), all-cause mortality, and major adverse events (i.e ., myopathies and liver dysfunction) between statin initiators and statin noninitiators. The pooled logistic model was used to obtain the hazard ratio for the outcomes of interest in both intention-to-treat (ITT) analysis and per-protocol (PP) analysis. Results Significant risk reduction associated with statin therapy (hazard ratio [95% confidence interval]) was observed for major cardiovascular diseases (ITT: 0.78 [0.62 to 0.98]; PP: 0.66 [0.50 to 0.87]) and all-cause mortality (ITT: 0.80 [0.68 to 0.95]; PP: 0.60 [0.48 to 0.76]). The standardized 5- and 10-year absolute risk reduction in PP analysis was 7% (3% to 11%) and 11% (4% to 18%), respectively. No significant risks for the major adverse events were observed. Conclusions Statin therapy was associated with lower risks of cardiovascular diseases and all-cause mortality in patients with kidney failure without a higher risk of major adverse events.
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Affiliation(s)
- Franco Wing Tak Cheng
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Pharmacy Department, Gleneagles Hong Kong Hospital, Hong Kong SAR, China
| | - Wanchun Xu
- Department of Family Medicine and Primary Care, LKS Faculty of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Sydney Chi Wai Tang
- Department of Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Eric Yuk Fai Wan
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Department of Family Medicine and Primary Care, LKS Faculty of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China
- Laboratory of Data Discovery for Health (D4H), Hong Kong Science and Technology Park, Hong Kong SAR, China
- The Institute of Cardiovascular Science and Medicine (ICSM), Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
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22
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Dayer N, Ciocca N, Antiochos P, Lu H, Auberson D, Meier D, Monney P, Gräni C, Rotzinger D, Leipsic J, Tzimas G. Comparison of cardiac computed tomography recommendations in recent ESC vs. ACC/AHA guidelines. Int J Cardiovasc Imaging 2025; 41:933-941. [PMID: 40085283 PMCID: PMC12075283 DOI: 10.1007/s10554-025-03375-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Accepted: 02/28/2025] [Indexed: 03/16/2025]
Abstract
Cardiac computed tomography (CCT) continues to expand with increasing applications and technological advancements. Growing evidence on the clinical utility of CCT necessitates evaluating how this knowledge is incorporated into European Society of Cardiology (ESC) and American College of Cardiology (ACC)/American Heart Association (AHA) guidelines. We aimed to provide a comprehensive comparison of CCT indications between ESC and ACC/AHA guidelines to identify areas of consensus and divergence in the current landscape of CCT utilization. ESC and ACC/AHA guidelines were systematically reviewed for CCT recommendations. The class of recommendation (COR) and level of evidence (LOE) were compared using χ2 or Fisher exact tests. The latest ESC guidelines included 40 recommendations regarding CCT: 18 (45%) COR-I, 14 (35%) COR-IIa, 6 (15%) COR-IIb, and 2 (5%) COR-III. Two (5%) recommendation had LOE-A, 20 (50%) had LOE-B, and 18 (45%) had LOE-C. The latest ACC/AHA guidelines consisted of 54 recommendations: 18 (33.3%) COR-I, 28 (51.9%) COR-IIa, 6 (11.1%) COR-IIb, and 2 (3.7%) COR-III. Two recommendations were assigned LOE-A (3.7%), 30 (55.6%) were classified as LOE-B, and 22 (40.7%) as LOE-C. ACC/AHA guidelines had a significantly higher proportion of COR-IIa recommendations (P = 0.04) and similar proportions of COR-I and COR-IIb recommendations (P = 0.28; P = 0.76), compared to ESC guidelines. The proportion of LOE-B and LOE-C recommendations weren't statistically different (P = 0.54; P = 0.84). ACC/AHA guidelines included more CCT recommendations with a higher COR and LOE than ESC guidelines. These findings highlight the need for continued research and consensus-building to establish standardized, evidence-based CCT recommendations in clinical practice.
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Affiliation(s)
- Nicolas Dayer
- Department of Cardiology, Lausanne University Hospital and University of Lausanne, 1011, Lausanne, Switzerland
| | - Nicola Ciocca
- Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Panagiotis Antiochos
- Department of Cardiology, Lausanne University Hospital and University of Lausanne, 1011, Lausanne, Switzerland
| | - Henri Lu
- Department of Cardiology, Lausanne University Hospital and University of Lausanne, 1011, Lausanne, Switzerland
| | - Denise Auberson
- Department of Cardiology, Lausanne University Hospital and University of Lausanne, 1011, Lausanne, Switzerland
| | - David Meier
- Department of Cardiology, Lausanne University Hospital and University of Lausanne, 1011, Lausanne, Switzerland
| | - Pierre Monney
- Department of Cardiology, Lausanne University Hospital and University of Lausanne, 1011, Lausanne, Switzerland
| | - Christoph Gräni
- Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - David Rotzinger
- Department of Diagnostic and Interventional Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Jonathon Leipsic
- Department of Medicine and Radiology, University of British Columbia, Vancouver, BC, Canada
| | - Georgios Tzimas
- Department of Cardiology, Lausanne University Hospital and University of Lausanne, 1011, Lausanne, Switzerland.
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23
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Chen CH, Sawamura T, Akhmedov A, Tsai MH, Akyol O, Kakino A, Chiang HH, Kraler S, Lüscher TF. Evolving concepts of low-density lipoprotein: From structure to function. Eur J Clin Invest 2025; 55:e70019. [PMID: 40045739 DOI: 10.1111/eci.70019] [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: 12/03/2024] [Accepted: 02/17/2025] [Indexed: 04/23/2025]
Abstract
BACKGROUND Low-density lipoprotein (LDL) is a central player in atherogenesis and has long been referred to as 'bad cholesterol.' However, emerging evidence indicates that LDL functions in multifaceted ways beyond cholesterol transport that include roles in inflammation, immunity, and cellular signaling. Understanding LDL's structure, metabolism and function is essential for advancing cardiovascular disease research and therapeutic strategies. METHODS This narrative review examines the history, structural properties, metabolism and functions of LDL in cardiovascular health and disease. We analyze key milestones in LDL research, from its early identification to recent advancements in molecular biology and omics-based investigations. Structural and functional insights are explored through imaging, proteomic analyses and lipidomic profiling, providing a deeper understanding of LDL heterogeneity. RESULTS Low-density lipoprotein metabolism, from biosynthesis to receptor-mediated clearance, plays a crucial role in lipid homeostasis and atherogenesis. Beyond cholesterol transport, LDL contributes to plaque inflammation, modulates adaptive immunity and regulates cellular signaling pathways. Structural studies reveal its heterogeneous composition, which influences its pathogenic potential. Evolving perspectives on LDL redefine its clinical significance, affecting cardiovascular risk assessment and therapeutic interventions. CONCLUSIONS A holistic understanding of LDL biology challenges traditional perspectives and underscores its complexity in cardiovascular health. Future research should focus on further elucidating LDL's structural and functional diversity to refine risk prediction models and therapeutic strategies, ultimately improving cardiovascular outcomes.
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Affiliation(s)
- Chu-Huang Chen
- Molecular Cardiology Research Laboratories, Vascular and Medicinal Research, The Texas Heart Institute, Houston, Texas, USA
| | - Tatsuya Sawamura
- Department of Molecular Pathophysiology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
| | - Alexander Akhmedov
- Center for Molecular Cardiology, University of Zurich, Zurich, Switzerland
| | - Ming-Hsien Tsai
- Department of Child Care, College of Humanities and Social Sciences, National Pingtung University of Science and Technology, Pingtung, Taiwan
| | - Omer Akyol
- Molecular Cardiology Research Laboratories, Vascular and Medicinal Research, The Texas Heart Institute, Houston, Texas, USA
| | - Akemi Kakino
- Department of Molecular Pathophysiology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
| | - Huan-Hsing Chiang
- Molecular Cardiology Research Laboratories, Vascular and Medicinal Research, The Texas Heart Institute, Houston, Texas, USA
| | - Simon Kraler
- Center for Molecular Cardiology, University of Zurich, Zurich, Switzerland
- Department of Internal Medicine and Cardiology, Cantonal Hospital Baden, Baden, Switzerland
| | - Thomas F Lüscher
- Center for Molecular Cardiology, University of Zurich, Zurich, Switzerland
- Heart Division, Royal Brompton and Harefield Hospitals, GSTT and King's College, London, UK
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24
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Marín-Jiménez I, Carpio D, Hernández V, Muñoz F, Zatarain-Nicolás E, Zabana Y, Mañosa M, Rodríguez-Moranta F, Barreiro-de Acosta M, Gutiérrez Casbas A. Spanish Working Group in Crohn's Disease and Ulcerative Colitis (GETECCU) position paper on cardiovascular disease in patients with inflammatory bowel disease. GASTROENTEROLOGIA Y HEPATOLOGIA 2025; 48:502314. [PMID: 39615874 DOI: 10.1016/j.gastrohep.2024.502314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 11/24/2024] [Indexed: 01/12/2025]
Abstract
Cardiovascular diseases (CVD) are the leading cause of death worldwide. Therefore, it is essential to understand their relationship and prevalence in different diseases that may present specific risk factors for them. The objective of this document is to analyze the specific prevalence of CVD in patients with inflammatory bowel disease (IBD), describing the presence of classical and non-classical cardiovascular risk factors in these patients. Additionally, we will detail the pathophysiology of atherosclerosis in this patient group and the different methods used to assess cardiovascular risk, including the use of risk calculators in clinical practice and different ways to assess subclinical atherosclerosis and endothelial dysfunction. Furthermore, we will describe the potential influence of medication used for managing patients with IBD on cardiovascular risk, as well as the potential influence of commonly used drugs for managing CVD on the course of IBD. The document provides comments and evidence-based recommendations based on available evidence and expert opinion. An interdisciplinary group of gastroenterologists specialized in IBD management, along with a consulting cardiologist for this type of patients, participated in the development of these recommendations by the Spanish Group of Work on Crohn's Disease and Ulcerative Colitis (GETECCU).
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Affiliation(s)
- Ignacio Marín-Jiménez
- Sección de Gastroenterología, Servicio de Aparato Digestivo, Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, España.
| | - Daniel Carpio
- Servicio de Aparato Digestivo, Complexo Hospitalario Universitario de Pontevedra, Pontevedra, España; Grupo de Investigación en Hepatología-Enfermedades Inflamatorias Intestinales, Instituto de Investigación Sanitaria Galicia Sur (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Pontevedra, España
| | - Vicent Hernández
- Servicio de Aparato Digestivo, Complexo Hospitalario Universitario de Vigo (CHUVI), SERGAS, Vigo, Pontevedra, España; Grupo de Investigación en Patología Digestiva, Instituto de Investigación Sanitaria Galicia Sur (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Pontevedra, España
| | - Fernando Muñoz
- Servicio de Digestivo. Complejo Asistencial Universitario de Salamanca, Salamanca, España
| | - Eduardo Zatarain-Nicolás
- Servicio de Cardiología, Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid; CIBERCV, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Universidad Complutense de Madrid, Madrid, España
| | - Yamile Zabana
- Servicio de Aparato Digestivo, Hospital Universitari Mútua Terrassa; Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), Terrasa, Barcelona, España
| | - Míriam Mañosa
- Servicio de Aparato Digestivo, Hospital Universitari Germans Trias; Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), Badalona, Barcelona, España
| | - Francisco Rodríguez-Moranta
- Servicio de Aparato Digestivo, Hospital Universitario de Bellvitge, IDIBELL, L'Hospitalet de Llobregat, Barcelona, España
| | - Manuel Barreiro-de Acosta
- Servicio de Gastroenterología, Hospital Clínico Universitario de Santiago, A Coruña, España; Fundación Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, A Coruña, España
| | - Ana Gutiérrez Casbas
- Servicio Medicina Digestiva, Hospital General Universitario Dr Balmis de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), CIBERehd, Alicante, España
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25
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Kearley J, Lissaman R, Laugier A, Rajah MN. Association between CAIDE risk score and episodic memory in middle-aged females: The impact of spontaneous menopause. Horm Behav 2025; 171:105739. [PMID: 40250164 DOI: 10.1016/j.yhbeh.2025.105739] [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: 09/23/2024] [Revised: 01/31/2025] [Accepted: 03/30/2025] [Indexed: 04/20/2025]
Abstract
There is growing evidence that postmenopause is associated with episodic memory decline in some females. Although midlife vascular risk factors are established predictors of brain health, it is unclear whether episodic memory decline at postmenopause is related to vascular risk, and whether such effects affect specific mnemonic functions (e.g. recollective processing vs. novelty detection). This study investigated whether vascular risk, measured by the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) score, predicts episodic memory in middle-aged females at pre- and post-menopause. Eighty-five cognitively unimpaired females (42 premenopausal, 43 postmenopausal) aged 39.5 to 65.1 years completed easy (low encoding load) and hard (high encoding load) versions of a face-location episodic memory task. Outcome measures were spatial source retrieval (correct source accuracy; CS) and detection of novel stimuli (correct rejections; CR). Linear-mixed models (LMMs) tested menopause group effects on CS and CR, while separate LMMs stratified by menopause status assessed whether CAIDE score predicted memory performance in each group. Results indicated that postmenopausal females performed worse than premenopausal females in both CS (β = 0.08, p < 0.001) and CR (β = 0.05, p = 0.011), with postmenopausal females more sensitive to task difficulty in CS. Higher CAIDE scores were associated with poorer CS accuracy in postmenopausal females only (β = -0.14, p = 0.009), with no effect on CR. These findings highlight the significance of vascular risk in episodic memory decline and emphasize the role of reproductive status in midlife cognition.
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Affiliation(s)
- Julia Kearley
- Department of Psychology, McGill University, Montréal, QC, Canada
| | - Rikki Lissaman
- Department of Psychiatry, McGill University, Montréal, QC, Canada
| | - Alix Laugier
- Department of Psychology, McGill University, Montréal, QC, Canada
| | - M Natasha Rajah
- Department of Psychiatry, McGill University, Montréal, QC, Canada; Department of Psychology, Toronto Metropolitan University, Toronto, ON, Canada.
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26
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Tsushima Y, Hatipoglu B. Diabetes and Lipids: A Review and Update on Lipid Biomarkers and Cardiovascular Risk. Endocr Pract 2025; 31:677-685. [PMID: 40158888 DOI: 10.1016/j.eprac.2025.03.011] [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: 02/26/2025] [Revised: 03/21/2025] [Accepted: 03/24/2025] [Indexed: 04/02/2025]
Abstract
OBJECTIVE To review existing and new evidence regarding the relationship between diabetes and dyslipidemia and to provide an update of the lipid biomarkers used to assess cardiovascular risk and the current guidelines reflecting these changes. METHODS We conducted a literature review pertaining to diabetes and lipids using the MEDLINE/PubMed database. We reviewed articles in English and primarily published between 1994 and early 2025. Also included are guidelines published by professional organizations who are recognized nationally or internationally in the fields of diabetes, lipids, and cardiovascular disease. RESULTS Studies evaluating the relationship between diabetes and hypertriglyceridemia have provided practice-changing evidence. Lipid markers such as apolipoprotein B, non-high-density lipoprotein cholesterol, and lipoprotein (a), as well as the concept of lipid variability have emerged as treatment targets. CONCLUSION Over the past 30 years, non-low-density lipoprotein cholesterol lipid markers have been identified to further stratify individuals with diabetes who are at risk for future cardiovascular events. Treatment targets and pharmacological therapy have been studied and continue to be updated.
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Affiliation(s)
- Yumiko Tsushima
- University Hospitals Cleveland Medical Center, Department of Medicine, Diabetes & Obesity Center, Mayfield Heights, Ohio; Case Western Reserve University School of Medicine, Mayfield Heights, Ohio
| | - Betul Hatipoglu
- University Hospitals Cleveland Medical Center, Department of Medicine, Diabetes & Obesity Center, Cleveland, Ohio; Case Western Reserve University School of Medicine, Cleveland, Ohio.
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Navar AM, Electricwala B, Multani JK, Zhou Z, Chen CC, Agatep BC, Petrilla AA, Schwartz TT, N'dri L, Cristino J, Rodriguez F. Lipid Management in United States Commercial and Medicare Enrollees With Atherosclerotic Cardiovascular Disease: Treatment Patterns and Low-Density Lipoprotein Cholesterol Control. Am J Cardiol 2025; 242:1-9. [PMID: 39826880 DOI: 10.1016/j.amjcard.2024.12.029] [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: 10/21/2024] [Revised: 12/09/2024] [Accepted: 12/19/2024] [Indexed: 01/22/2025]
Abstract
Lipid-lowering therapy (LLT) is the cornerstone for secondary prevention of atherosclerotic cardiovascular disease (ASCVD); however, many patients exhibit low adherence to therapy and fail to achieve low-density lipoprotein cholesterol (LDL-C) goals. This retrospective cohort study used 2 nationally representative closed administrative claims databases (PharMetrics Plus and Medicare Fee-for-Service Research Identifiable Files) to identify commercial and Medicare enrollees with ASCVD between 2014 and 2019. Patients were stratified by exposure to statin therapy, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibodies (PCSK9i mAb) regimens. Outcomes included LLT adherence (proportion of days covered ≥0.8), persistence, and discontinuation at 12 months. For patients with LDL-C test results, the percentage of patients achieving LDL-C <70 mg/100 ml during follow-up was evaluated. We identified 4.6 million patients with ASCVD (commercial: 945,704; Medicare: 3,659,011), with the majority having ischemic or coronary heart disease. Of these, 66.4% commercial and 71.4% Medicare patients were on at least 1 LLT, including 69.8% commercial and 71.4% Medicare patients on statin therapy, 2.7% commercial and 1.7% Medicare patients on ezetimibe, and 0.2% commercial and 0.04% Medicare patients on a PCSK9i mAb. By 12 months, medication discontinuation was as follows: 30.4% commercial and 34.1% Medicare for statin therapy, 35.5% commercial and 46.1% Medicare for ezetimibe, and 41.5% commercial and 55.8% Medicare for PCSK9i mAb. Approximately half of the treated patients remained adherent after 12 months. Of patients with LDL-C data available (n = 381,160), <20% achieved an LDL-C <70 mg/100 ml. In conclusion, medication discontinuation and low adherence to statin, ezetimibe, and PCSK9i mAb therapies were observed in both populations. Increased efforts are needed to ensure persistence and adherence to LLT in patients with ASCVD to attain LDL-C targets.
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Affiliation(s)
- Ann Marie Navar
- Division of Cardiology, Department of Medicine, University of Texas Southwestern Medical Center, 2001 Inwood Rd, Dallas TX.
| | - Batul Electricwala
- Health Economics & Outcomes Research, Novartis Pharmaceuticals Corporation, East Hanover, NJ
| | - Jasjit K Multani
- Health Economics & Outcomes Research, Real-World Evidence, IQVIA, Falls Church, VA
| | - Zifan Zhou
- Health Economics & Outcomes Research, Real-World Evidence, IQVIA, Falls Church, VA
| | - Chi-Chang Chen
- Health Economics & Outcomes Research, Real-World Evidence, IQVIA, Falls Church, VA
| | | | | | | | - Laetitia N'dri
- Health Economics & Outcomes Research, Novartis Pharmaceuticals Corporation, East Hanover, NJ
| | - Joaquim Cristino
- Health Economics & Outcomes Research, Novartis Pharmaceuticals Corporation, East Hanover, NJ
| | - Fatima Rodriguez
- Division of Cardiovascular Medicine and the Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA
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28
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Cai B, Zhou Y, Yang X, Wang Z, Huang C, Xiao Q, Jiang H, Zhao Y, Tian X, Wang Q, Li G, Li M, Zeng X, Zhao J. Remnant cholesterol predicts risk of recurrent thrombosis beyond LDL-cholesterol in patients with antiphospholipid syndrome. BMC Med 2025; 23:233. [PMID: 40264203 PMCID: PMC12016284 DOI: 10.1186/s12916-025-04063-5] [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: 09/26/2024] [Accepted: 04/10/2025] [Indexed: 04/24/2025] Open
Abstract
BACKGROUND Antiphospholipid syndrome (APS) is notably linked to thrombotic events, particularly cardiovascular disease (CVD). The role of remnant cholesterol (RC) in predicting CVD risk is established, yet its relationship with thrombotic risk in APS patients remains to be elucidated. This study aims to assess the association between RC and recurrent thrombotic risk in patients with APS. METHODS A prospective analysis was conducted based on a cohort of APS patients who met the 2006 Sydney revised classification criteria. Thrombotic risks associated with varying levels of RC were evaluated using Kaplan-Meier survival analysis and Cox proportional hazards regression models. Mendelian randomization (MR) was applied to examine the causal link between RC and different types of thrombotic events. RESULTS A total of 325 patients with APS were enrolled in this study. Over a median follow-up of 35 months, 51 patients experienced thrombotic events, including 24 venous, 19 arterial, and 16 microvascular incidents. Patients with RC levels above 0.60 mmol/L exhibited significantly higher risks, with multivariable-adjusted hazard ratio (and 95% confidence interval) for all-cause, venous, arterial thrombosis, and microvascular disease being 5.05 (2.23-11.41), 6.34 (1.71-23.54), 3.79 (1.00-14.32), and 4.36 (1.08-17.58), respectively. Notably, elevated RC remained a significant thrombotic risk factor even in patients with normal conventional lipid profiles. MR analysis revealed a significant causal association between RC and arterial thrombosis, but not venous thrombosis. CONCLUSIONS Elevated RC is linked to a substantial increase in the risk of thrombotic events in APS patients. These findings suggest that RC could be a valuable marker for thrombotic risk in this population and a potential target for therapeutic intervention.
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Affiliation(s)
- Bin Cai
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing Ave, Beijing, 100730, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China
- Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China
| | - Yangzhong Zhou
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing Ave, Beijing, 100730, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China
- Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China
| | - Xinzhuang Yang
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing Ave, Beijing, 100730, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China
- Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China
- Center for Bioinformatics, National Infrastructures for Translational Medicine, Institute of Clinical Medicine & Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhaoqing Wang
- Vanke School of Public Health, Tsinghua University, Beijing, China
- Institute for Healthy China, Tsinghua University, Beijing, China
| | - Can Huang
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing Ave, Beijing, 100730, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China
- Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China
| | - Qingqing Xiao
- Department of Cardiology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Hui Jiang
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing Ave, Beijing, 100730, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China
- Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China
| | - Yuan Zhao
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing Ave, Beijing, 100730, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China
- Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China
| | - Xinping Tian
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing Ave, Beijing, 100730, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China
- Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China
| | - Qian Wang
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing Ave, Beijing, 100730, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China
- Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China
| | - Guanqiao Li
- Vanke School of Public Health, Tsinghua University, Beijing, China
- Institute for Healthy China, Tsinghua University, Beijing, China
| | - Mengtao Li
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing Ave, Beijing, 100730, China.
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China.
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China.
- Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China.
| | - Xiaofeng Zeng
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing Ave, Beijing, 100730, China.
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China.
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China.
- Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China.
| | - Jiuliang Zhao
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing Ave, Beijing, 100730, China.
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China.
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China.
- Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China.
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Leosdottir M, Schubert J, Brandts J, Gustafsson S, Cars T, Sundström J, Jernberg T, Ray KK, Hagström E. Early Ezetimibe Initiation After Myocardial Infarction Protects Against Later Cardiovascular Outcomes in the SWEDEHEART Registry. J Am Coll Cardiol 2025; 85:1550-1564. [PMID: 40240093 DOI: 10.1016/j.jacc.2025.02.007] [Citation(s) in RCA: 1] [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: 11/30/2024] [Revised: 01/30/2025] [Accepted: 02/07/2025] [Indexed: 04/18/2025]
Abstract
BACKGROUND Combination lipid-lowering therapy (LLT) after myocardial infarction (MI) achieves lower low-density lipoprotein cholesterol (LDL-C) levels and better cardiovascular outcomes vs statin monotherapy. As a result, global guidelines recommend lower LDL-C but, paradoxically, advise treatment through a stepwise approach. Yet the need for combination therapy is inevitable as <20% of patients achieve goals with statins alone. Whether combining ezetimibe with a statin early vs late after MI results in better outcomes is unknown. OBJECTIVES In this study, the authors sought to assess the impact of delayed treatment escalation on outcomes by comparing early vs late oral combination LLT (statins plus ezetimibe) in patients with MI. METHODS LLT-naïve patients (SWEDEHEART registry) hospitalized for MI (2015-2022) and discharged on statins were included. Using clone-censor-weight and Cox proportional hazards models, we compared differences in risks of MACE (death, MI, stroke), components of MACE, and cardiovascular death between patients with ezetimibe added to statins ≤12 weeks after discharge as reference (early combination therapy), from 13 weeks to 16 months (late combination therapy), or not at all. RESULTS Of 35,826 patients (median age 65.1 years, 26.0% women), 6,040 (16.9%) received ezetimibe early, 6,495 (18.1%) ezetimibe late, and 23,291 (65.0%) received no ezetimibe. High-intensity statin use was ≥98% in all groups. Over a median 3.96 years (Q1-Q3: 2.15-5.81 years), 2,570 patients had MACE (440 cardiovascular deaths). One-year MACE incidences were 1.79 (early), 2.58 (late), and 4.03 (none) per 100 patient-years. Compared with early combination therapy, weighted risk differences in MACE for late combination therapy at 1, 2, and 3 years were 0.6% (95% CI: 0.1%-1.1%; P < 0.01), 1.1% (95% CI: 0.3%-2.0%; P < 0.01), and 0.7% (95% CI: -0.2% to 1.3%; P = 0.18), and 3-year HR was 1.14 (95% CI: 0.95-1.41). For those receiving no ezetimibe, risk differences were 0.7% (95% CI: 0.2%-1.3%), 1.6% (95% CI: 0.8%-2.5%), and 1.9% (95% CI: 0.8%-3.1%; P for all <0.01; 3-year HR: 1.29 [95% CI: 1.12-1.55]). Similar differences in risk of cardiovascular death at 3 years were observed (HRs vs early: late: 1.64 [95% CI: 1.15-2.63]; none: 1.83 [95% CI: 1.35-2.69]). CONCLUSIONS MI care pathways should implement early combination therapy with statins and ezetimibe as standard care, because delaying use of combination LLT or using high-intensity statin monotherapy is associated with avoidable harm.
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Affiliation(s)
- Margret Leosdottir
- Department of Cardiology, Skåne University Hospital, Malmö, Sweden; Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
| | - Jessica Schubert
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Julia Brandts
- Department of Primary Care and Public Health, Imperial Centre for Cardiovascular Disease Prevention, School of Public Health, Imperial College London, London, United Kingdom; Department of Internal Medicine, University Hospital RWTH Aachen, Aachen, Germany
| | | | | | - Johan Sundström
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Tomas Jernberg
- Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden
| | - Kausik K Ray
- Department of Primary Care and Public Health, Imperial Centre for Cardiovascular Disease Prevention, School of Public Health, Imperial College London, London, United Kingdom; Imperial Clinical Trials Unit, Imperial College London, London, United Kingdom
| | - Emil Hagström
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala, Sweden
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Nasir K, Blankstein R. Transforming the Cardiovascular Disease Prevention Paradigm: See Disease, Treat Disease. JAMA 2025; 333:1398-1400. [PMID: 40042944 DOI: 10.1001/jama.2025.2323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/23/2025]
Affiliation(s)
- Khurram Nasir
- Division of Cardiovascular Prevention & Wellness Program, DeBakey Heart & Vascular Center, Houston Methodist, Houston, Texas
- Houston Methodist-Rice Digital Health Institute, Houston, Texas
- Center for Cardiovascular Computational & Precision Health, DeBakey Heart & Vascular Center, Houston Methodist, Houston, Texas
| | - Ron Blankstein
- Departments of Medicine (Cardiovascular Division) and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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Williams MS, Levine GN, Kalra D, Agarwala A, Baptiste D, Cigarroa JE, Diekemper RL, Foster MV, Gulati M, Henry TD, Itchhaporia D, Lawton JS, Newby LK, Rogers KC, Soni K, Tamis-Holland JE. 2025 AHA/ACC Clinical Performance and Quality Measures for Patients With Chronic Coronary Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Performance Measures. J Am Coll Cardiol 2025:S0735-1097(25)00282-7. [PMID: 40310322 DOI: 10.1016/j.jacc.2025.02.001] [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] [Indexed: 05/02/2025]
Abstract
Chronic coronary disease (CCD) is the leading cause of death in the United States. There is an ongoing imperative to disseminate evidence-based and patient-centered care recommendations that further align the management of patients with CCD to updated evidence-based guidelines. The writing committee developed a comprehensive CCD measure set comprising 10 performance measures and 3 quality measures, the focus of which is to include practical steps to specifically advance care in the CCD population. The measure set begins with an assessment of tobacco use and evidence-based cessation interventions. Also included are topics such as antiplatelet therapy, lipid assessment and low-density lipoprotein cholesterol goals, and guideline-directed management and therapy for hypertension and reduced left ventricular dysfunction in patients with CCD. The measure set concludes with an emphasis on the importance of cardiac rehabilitation referral and patient education, including symptom management and lifestyle modification.
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Zheutlin AR, Jacobs JA, Bress AP. High-Density Lipoprotein Cholesterol and Statin Use Among U.S. Adults With Intermediate 10-Year Predicted ASCVD Risk. JACC. ADVANCES 2025:101725. [PMID: 40310328 DOI: 10.1016/j.jacadv.2025.101725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 02/18/2025] [Accepted: 03/12/2025] [Indexed: 05/02/2025]
Affiliation(s)
- Alexander R Zheutlin
- Division of Cardiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
| | - Joshua A Jacobs
- Intermountain Healthcare Department of Population Health Sciences, University of Utah, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah, USA
| | - Adam P Bress
- Intermountain Healthcare Department of Population Health Sciences, University of Utah, Spencer Fox Eccles School of Medicine, Salt Lake City, Utah, USA; Informatics, Decision-Enhancement, and Analytic Sciences (IDEAS) Center, Veterans Affairs, Salt Lake City Health Care System, Salt Lake City, Utah, USA
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Qi Q, Wu X, Cui X, Han Q, Yu J, Deng J, Zhang X, Jiang Y, Wang N, Wu S, Li K. Triglyceride/high-density lipoprotein cholesterol ratio associates major adverse cardiac and cerebrovascular events: a 13-year prospective cohort study. Acta Cardiol 2025:1-9. [PMID: 40223656 DOI: 10.1080/00015385.2025.2484855] [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: 12/05/2024] [Revised: 03/14/2025] [Accepted: 03/21/2025] [Indexed: 04/15/2025]
Abstract
BACKGROUND Few studies have been conducted to investigate the association between the triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and major adverse cardiac and cerebrovascular events (MACCEs) in a predominantly male cohort from China. METHODS A prospective cohort study was conducted on a total 95,837 individuals (males account for 79.67) extracted from the Kailuan study. All individuals were grouped according to the TG/HDL-C ratio quartile. The endpoints of this study were composite MACCEs and its subtypes [non-fatal myocardial (MI), non-fatal stroke and all-cause mortality]. The Kaplan-Meier method was employed to illustrate the cumulative incidence curve. The incidence rate was reported as per 1000 person-years. To explore the impact of varying quartiles of the TG/HDL-C ratio on the risk of MACCEs, Cox proportional hazard regression analysis was conducted. Furthermore, multivariate adjusted spline regression models were applied to examine the relationship between the TG/HDL-C ratio and the risk of MACCEs. RESULTS A total of 18,430 cases of composite MACCEs occurred during a 13.97-year follow-up. In brief, 1762 cases of MI, 6653 cases of stroke, and 12,524 cases of all-cause mortality were reported, respectively. The cumulative incidence and incidence rate of composite MACCEs, MI, and stroke increased with increment in the TG/HDL-C ratio (p < 0.001). In comparison to quartile 1, the hazard ratios of quartile 4 for composite MACCEs, MI, stroke, and all-cause mortality were 1.13 (95% CI 1.07-1.19), 1.55 (95% CI 1.30-1.84), 1.21 (95% CI 1.12-1.31), and 1.12 (95% CI 1.05-1.20), respectively. Multivariate adjusted spline regression models showed a nonlinear relationship between baseline TG/HDL-C ratio and risk of composite MACCEs (p for non-linearity < 0.01), MI (p for non-linearity < 0.01), stroke (p for non-linearity < 0.01), and all-cause mortality (p for non-linearity = 0.029). CONCLUSIONS The TG/HDL-C ratio is significantly associated with an increased risk of MACCEs in a predominantly male cohort from northern China.
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Affiliation(s)
- Qi Qi
- Department of Cardiology, Tangshan Gongren Hospital, Tangshan, China
- Hebei Medical University, Shijiazhuang, China
| | - Xinyu Wu
- Department of Cardiology, Tangshan Gongren Hospital, Tangshan, China
- Hebei Medical University, Shijiazhuang, China
| | - Xinyu Cui
- Department of Cardiology, Tangshan Gongren Hospital, Tangshan, China
| | - Quanle Han
- Department of Cardiology, Tangshan Gongren Hospital, Tangshan, China
| | - Jie Yu
- Department of Cardiology, Tangshan Gongren Hospital, Tangshan, China
| | - Jie Deng
- Department of Cardiology, Tangshan Gongren Hospital, Tangshan, China
| | - Xuechao Zhang
- Department of Cardiology, Tangshan Gongren Hospital, Tangshan, China
| | - Yue Jiang
- Catheterization Unit, Tangshan Gongren Hospital, Tangshan, China
| | - Nan Wang
- Catheterization Unit, Tangshan Gongren Hospital, Tangshan, China
| | - Shouling Wu
- Department of Cardiology, Kailuan General Hospital, Tangshan, China
| | - Kangbo Li
- School of Clinical Medicine, North China University of Science and Technology, Tangshan, China
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Worledge EA, Billups SJ, Titus OJ, Saseen JJ. Achievement of low-density lipoprotein cholesterol thresholds in very high-risk atherosclerotic cardiovascular disease. J Clin Lipidol 2025:S1933-2874(25)00263-6. [PMID: 40360376 DOI: 10.1016/j.jacl.2025.04.186] [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: 01/15/2025] [Revised: 04/03/2025] [Accepted: 04/07/2025] [Indexed: 05/15/2025]
Abstract
BACKGROUND The 2022 American College of Cardiology Expert Consensus Decision Pathway on the Role of Nonstatin Therapies recommended more aggressive management of low-density lipoprotein cholesterol (LDL-C) compared to the 2018 American Heart Association/American College of Cardiology/Multisociety Guideline. In congruence with European guidelines, a target LDL-C threshold of 55 mg/dL is recommended for patients with very high-risk atherosclerotic cardiovascular disease (ASCVD). Real-world status of the early implementation of this recommendation remains uncertain. OBJECTIVE To determine the proportion of patients with very high-risk ASCVD achieving an LDL-C <55 mg/dL and characterize differences between patients who did and did not achieve this LDL-C value. METHODS This retrospective cohort study evaluated patients between January 1, 2023, and December 31, 2023, who were ≥ 18 years old with very high-risk ASCVD from the University of Colorado Health system primary care practices. Very high-risk ASCVD was defined as a history of a major ASCVD event with at least 2 high-risk conditions. RESULTS A total of 8974 patients met inclusion criteria for very high-risk ASCVD. Of these, only 21.0% achieved an LDL-C <55 mg/dL, while 39.5% of patients achieved the previously recommended LDL-C threshold of <70 mg/dL. More than half of patients were prescribed a high-intensity statin-based regimen. CONCLUSION Within a large, academic health-system, achievement of LDL-C threshold among patients with very high-risk ASCVD was low. Recommendations from the 2022 ACC Expert Consensus Decision Pathway that endorse more aggressive LDL-C lowering and emphasize nonstatin therapies as an adjunct to statins are not fully implemented in real-world clinical practice.
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Affiliation(s)
- Elisa A Worledge
- Department of Clinical Pharmacy, University of Colorado Anschutz Medical Campus Skaggs School of Pharmacy, Aurora, CO (Drs Worledge, Billups and Saseen, and Mr. Titus)
| | - Sarah J Billups
- Department of Clinical Pharmacy, University of Colorado Anschutz Medical Campus Skaggs School of Pharmacy, Aurora, CO (Drs Worledge, Billups and Saseen, and Mr. Titus)
| | - Oliver J Titus
- Department of Clinical Pharmacy, University of Colorado Anschutz Medical Campus Skaggs School of Pharmacy, Aurora, CO (Drs Worledge, Billups and Saseen, and Mr. Titus)
| | - Joseph J Saseen
- Department of Clinical Pharmacy, University of Colorado Anschutz Medical Campus Skaggs School of Pharmacy, Aurora, CO (Drs Worledge, Billups and Saseen, and Mr. Titus); Department of Family Medicine, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, CO (Dr Saseen).
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Mesa A, Puig-Jové C, Pané A, Vinagre I, López-Quesada E, Meler E, Alonso-Carril N, Quirós C, Amor AJ, Perea V. Preeclampsia as an independent predictor of atherosclerosis progression in women with type 1 diabetes: a 5-year prospective study. Cardiovasc Diabetol 2025; 24:160. [PMID: 40205402 PMCID: PMC11983752 DOI: 10.1186/s12933-025-02719-3] [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: 01/09/2025] [Accepted: 03/29/2025] [Indexed: 04/11/2025] Open
Abstract
BACKGROUND Preeclampsia (PE) and type 1 diabetes (T1D) are significant risk factors for cardiovascular disease (CVD), but their combined effect on atherosclerosis progression has not been fully explored. This study aimed to evaluate the impact of T1D and PE on the progression of atherosclerosis. METHODS Prospective cohort study of 112 women divided into four groups: T1D + /PE + (n = 28), T1D + /PE- (n = 28), T1D-/PE + (n = 28), and T1D-/PE- (n = 28). Participants underwent an initial assessment and a follow-up visit five years later, which included anthropometric evaluation, blood tests, and carotid ultrasound. Atherosclerosis progression was defined as an increase in carotid plaque number or the occurrence of a cardiovascular event (CVE) during follow-up (fatal or non-fatal ischemic heart disease, fatal or non-fatal stroke, and/or heart failure). RESULTS A total of 104 women (92.9%) completed the follow-up (54 with T1D, mean age at inclusion 45.2 ± 7.6 years, mean follow-up 5.3 ± 1.2 years). An increase in carotid plaques was identified in 34 women (32.7%), and 3 CVEs (2.9%) occurred. In women with T1D, a history of PE was associated with a twofold increase in atherosclerosis progression (57.7% vs 25.0%, p = 0.015). In multivariate models adjusted for age, T1D and cardiovascular risk factors, PE [OR 4.97 (1.61-15.29), p = 0.005] and PE + T1D [OR 7.69 (1.25-47.29), p = 0.028] were independently associated with atherosclerosis progression. CONCLUSIONS PE was a strong independent predictor of atherosclerosis progression over a 5-year follow-up period, with an additive effect in T1D. These findings highlight preeclampsia as a significant CVD risk enhancer in young women with T1D.
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Affiliation(s)
- Alex Mesa
- Endocrinology and Nutrition Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- Diabetes Unit, Endocrinology and Nutrition Department, ICMDM, Hospital Clínic de Barcelona, Carrer de Villarroel, 170, 08036, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Carlos Puig-Jové
- Endocrinology and Nutrition Department, Hospital Universitari Mútua Terrassa, Doctor Robert Sq, 08221, Terrassa, Barcelona, Spain
| | - Adriana Pané
- Diabetes Unit, Endocrinology and Nutrition Department, ICMDM, Hospital Clínic de Barcelona, Carrer de Villarroel, 170, 08036, Barcelona, Spain
- Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Irene Vinagre
- Diabetes Unit, Endocrinology and Nutrition Department, ICMDM, Hospital Clínic de Barcelona, Carrer de Villarroel, 170, 08036, Barcelona, Spain
- Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Eva López-Quesada
- Obstetrics and Gynecology Department, Hospital Universitari Mútua Terrassa, Terrassa, Spain
| | - Eva Meler
- Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine, Hospital Clínic and Hospital Sant Joan de Déu., Barcelona, Spain
| | - Núria Alonso-Carril
- Endocrinology and Nutrition Department, Hospital Universitari Mútua Terrassa, Doctor Robert Sq, 08221, Terrassa, Barcelona, Spain
| | - Carmen Quirós
- Endocrinology and Nutrition Department, Hospital Universitari Mútua Terrassa, Doctor Robert Sq, 08221, Terrassa, Barcelona, Spain
| | - Antonio J Amor
- Diabetes Unit, Endocrinology and Nutrition Department, ICMDM, Hospital Clínic de Barcelona, Carrer de Villarroel, 170, 08036, Barcelona, Spain.
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
- Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
| | - Verónica Perea
- Endocrinology and Nutrition Department, Hospital Universitari Mútua Terrassa, Doctor Robert Sq, 08221, Terrassa, Barcelona, Spain.
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Revankar S, Shakra N, DiMaio JM, Agarwala A. Key Concepts in Cardiovascular Secondary Prevention: A Case-Based Review. Am J Cardiol 2025; 248:32-40. [PMID: 40188902 DOI: 10.1016/j.amjcard.2025.03.035] [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: 02/05/2025] [Revised: 03/12/2025] [Accepted: 03/30/2025] [Indexed: 04/26/2025]
Abstract
Atherosclerotic cardiovascular disease (ASCVD) continues to be a growing global health concern with ischemic heart disease and stroke as leading causes of years of life lost. While aging is a major ASCVD risk factor, recent trends show a concerning rise in its incidence among younger adults driven, in part, by increased rates of risk factors such as hypertension and diabetes. These individuals with ASCVD are at elevated risk of recurrence years following their initial event, further underscoring the need for aggressive implementation of secondary prevention strategies to reduce morbidity and mortality. This case-based review discusses evidence-based pharmacological approaches to ASCVD secondary prevention-focusing on the roles of antiplatelets, lipid lowering therapies, antihypertensive medications, and glucose lowering treatments, in practical clinical settings.
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Affiliation(s)
- Shruti Revankar
- Department of Internal Medicine, Baylor College of Medicine, Houston, Texas
| | - Nezar Shakra
- Center for Cardiovascular Disease Prevention, Baylor Scott and White Health The Heart Hospital, Plano, Texas
| | - John Michael DiMaio
- Cardiovascular Department, Baylor Scott and White Health The Heart Hospital, Plano, Texas; Texas A & M Department of Biomedical Engineering, College Station, Texas; Cardiovascular Department, Baylor Scott and White Research Institute, Dallas, Texas
| | - Anandita Agarwala
- Center for Cardiovascular Disease Prevention, Baylor Scott and White Health The Heart Hospital, Plano, Texas.
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Tremblay F, Xiong Q, Shah SS, Ko CW, Kelly K, Morrison MS, Giancarlo C, Ramirez RN, Hildebrand EM, Voytek SB, El Sebae GK, Wright SH, Lofgren L, Clarkson S, Waters C, Linder SJ, Liu S, Eom T, Parikh S, Weber Y, Martinez S, Malyala P, Abubucker S, Friedland AE, Maeder ML, Lombardo A, Myer VE, Jaffe AB. A potent epigenetic editor targeting human PCSK9 for durable reduction of low-density lipoprotein cholesterol levels. Nat Med 2025; 31:1329-1338. [PMID: 39930141 PMCID: PMC12003160 DOI: 10.1038/s41591-025-03508-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: 09/13/2024] [Accepted: 01/13/2025] [Indexed: 02/27/2025]
Abstract
Epigenetic editing holds the promise of durable therapeutic effects by silencing disease-causing genes without changing the underlying DNA sequence. In this study, we designed an epigenetic editor to target human PCSK9 and thereby induce DNA methylation at this locus. A single administration of lipid nanoparticles encapsulating mRNA encoding this epigenetic editor was sufficient to drive near-complete silencing of human PCSK9 in transgenic mice. Silencing was durable for at least 1 year and was fully maintained after partial hepatectomy-induced liver regeneration. In addition, we showed reversibility of epigenetic editing in mice with previously silenced PCSK9 upon treatment with a targeted epigenetic activator designed to demethylate the PCSK9 locus. Notably, in cynomolgus monkeys, a single administration of the epigenetic editor potently and durably decreased circulating PCSK9 protein levels by approximately 90% with concomitant reduction in low-density lipoprotein cholesterol levels by approximately 70%. These findings demonstrate the therapeutic potential of durable and reversible epigenetic editing in vivo and support the development of epigenetic editor-based treatment for hypercholesterolemia.
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Affiliation(s)
| | - Qiang Xiong
- Chroma Medicine, Boston, MA, USA
- nChromaBio, Boston, MA, USA
| | - Shrijal S Shah
- Chroma Medicine, Boston, MA, USA
- nChromaBio, Boston, MA, USA
| | - Chih-Wei Ko
- Chroma Medicine, Boston, MA, USA
- nChromaBio, Boston, MA, USA
| | | | | | | | | | | | - Sarah B Voytek
- Chroma Medicine, Boston, MA, USA
- nChromaBio, Boston, MA, USA
| | | | - Shane H Wright
- Chroma Medicine, Boston, MA, USA
- nChromaBio, Boston, MA, USA
| | | | | | | | | | - Songlei Liu
- Chroma Medicine, Boston, MA, USA
- nChromaBio, Boston, MA, USA
| | - Taesun Eom
- Chroma Medicine, Boston, MA, USA
- nChromaBio, Boston, MA, USA
| | - Shefal Parikh
- Chroma Medicine, Boston, MA, USA
- nChromaBio, Boston, MA, USA
| | - Yuki Weber
- Chroma Medicine, Boston, MA, USA
- nChromaBio, Boston, MA, USA
| | | | - Padma Malyala
- Chroma Medicine, Boston, MA, USA
- nChromaBio, Boston, MA, USA
| | | | | | | | - Angelo Lombardo
- San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | | | - Aron B Jaffe
- Chroma Medicine, Boston, MA, USA
- Curie.Bio, Cambridge, MA, USA
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Jones DW, Egan BM, Lackland DT. Dietary Sodium- and Potassium-Enriched Salt Substitutes-The Tipping Point? JAMA Cardiol 2025; 10:309-311. [PMID: 39908031 DOI: 10.1001/jamacardio.2024.5430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2025]
Affiliation(s)
- Daniel W Jones
- Department of Medicine, University of Mississippi Medical Center, Jackson
| | - Brent M Egan
- Cardiovascular Health, American Medical Association, Chicago, Illinois
- Medical University of South Carolina, Charleston
| | - Daniel Thomas Lackland
- Division of Translational Neurosciences and Population Studies, Department of Neurology, Medical University of South Carolina, Charleston
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Pavlović J, Bos D, Ikram MK, Ikram MA, Kavousi M, Leening MJG. Guideline-Directed Application of Coronary Artery Calcium Scores for Primary Prevention of Atherosclerotic Cardiovascular Disease. JACC Cardiovasc Imaging 2025; 18:465-475. [PMID: 40047745 DOI: 10.1016/j.jcmg.2024.12.008] [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: 09/09/2024] [Revised: 11/18/2024] [Accepted: 12/13/2024] [Indexed: 04/11/2025]
Abstract
BACKGROUND The 2018 ACC (American College of Cardiology)/AHA (American Heart Association) and 2021 ESC (European Society of Cardiology)/EAS (European Atherosclerosis Society) guidelines recommend coronary artery calcium (CAC) score for risk refinement in primary prevention of atherosclerotic cardiovascular disease (ASCVD). OBJECTIVES This study sought to compare CAC utility as a risk-refining tool following the ACC/AHA guideline using pooled cohort equations (PCE) or PREVENT (Predicting Risk of cardiovascular disease EVENTs) equations and ESC/EAS guideline using SCORE2 (Systematic COronary Risk Evaluation 2). METHODS A total of 1,903 statin-naive participants 55 to 75 years of age, free of ASCVD and diabetes, with low-density lipoprotein cholesterol <190 mg/dL from the prospective population-based Rotterdam Study were included. Per the guidelines, we determined proportions of CAC scan-eligible and reclassified men and women, ASCVD incidence rates, and numbers needed to treat for 10 years (NNT10y). RESULTS By the ACC/AHA (PCE), 18.3% of men and 11.9% of women, and by ACC/AHA (PREVENT), 13.4% of men and 3.4% of women were eligible for a CAC scan. By the ESC/EAS, 46.6% of men and 44.9% of women were CAC eligible. Proportions of uprisked and derisked individuals varied per guideline. Among ACC/AHA and ESC/EAS CAC-eligible individuals, incidence rates ranged from 9.3 to 23.8 per 1,000 person-years, and the estimated NNT10y to prevent 1 ASCVD event, based on high-intensity statin use, varied from 11 to 26. CONCLUSIONS The ACC/AHA and ESC/EAS guidelines differ in the selection and application of the CAC score for primary prevention of ASCVD. Guideline-directed application of CAC score in a middle-aged apparently healthy population improved risk stratification at an acceptable NNT10y for both guidelines.
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Affiliation(s)
- Jelena Pavlović
- Department of Epidemiology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands
| | - Daniel Bos
- Department of Epidemiology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands; Department of Radiology and Nuclear Medicine, Erasmus MC-University Medical Center, Rotterdam, the Netherlands; Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium; Department of Clinical Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - M Kamran Ikram
- Department of Epidemiology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands; Department of Neurology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands
| | - M Arfan Ikram
- Department of Epidemiology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands; Department of Neurology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands
| | - Maryam Kavousi
- Department of Epidemiology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands
| | - Maarten J G Leening
- Department of Epidemiology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands; Department of Radiology and Nuclear Medicine, Erasmus MC-University Medical Center, Rotterdam, the Netherlands; Department of Cardiology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands.
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40
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Gallo Ruelas M, Queiroz I, Pimentel T, Tavares AH, Defante MLR, Barbosa LM, Eckert I. Effects of seal oil supplementation on lipid profile biomarkers: A systematic review and meta-analysis of randomized controlled trials. Prostaglandins Leukot Essent Fatty Acids 2025; 204:102666. [PMID: 39914123 DOI: 10.1016/j.plefa.2025.102666] [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: 12/15/2024] [Revised: 01/26/2025] [Accepted: 01/27/2025] [Indexed: 03/14/2025]
Abstract
BACKGROUND Seal oil (SO) supplementation has been purported to have cardiovascular health benefits due to its content of omega-3 fatty acids; however, the clinical evidence base for this intervention has yet to be comprehensively assessed. OBJECTIVE We aimed to evaluate the effects of oral SO supplementation on lipid profile biomarkers. METHODS A systematic search was performed on Pubmed, Embase, Web of Science and Cochrane Library, from inception to August 2024. Only randomized controlled trials (RCTs) assessing the effect of SO on lipid profile biomarkers were included. A random-effects meta-analysis was applied to determine the overall effect estimate. The certainty of evidence (CoE) was evaluated using the GRADE approach. RESULTS Nine RCTs were included in the review after the screening of 242 studies, comprising a total of 626 patients. Supplementation of SO resulted in no statistically significant effects on LDL-C (MD -0.07 mmol/L; 95 % CI [-0.19, 0.05]; CoE: Low) and total cholesterol (MD -0.12 mmol/L; 95 % CI [-0.30, 0.06]; CoE: Very low). There were statistically significant results of modest-to-trivial clinical importance on triglycerides (MD -0.19 mmol/L, 95 % CI [-0.30, -0.08]; CoE: Low) and trivial importance on HDL-C (MD 0.07 mmol/L, 95 % CI [0.003, 0.13]; CoE: Very low). CONCLUSION There is no sufficiently certain evidence to determine the effects of SO on cardiovascular lipid biomarkers. Our analyses may suggest a modest-to-trivial, clinically uncertain beneficial effect on triglyceride levels; and little to no effect on LDL-C. Effect estimates for HDL-C and total cholesterol levels were highly uncertain. Further evidence is required to conclusively determine the effects of oral SO on lipid biomarkers. PROTOCOL REGISTRATION NUMBER CRD42024583739.
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Affiliation(s)
| | - Ivo Queiroz
- Catholic University of Pernambuco, Medicine Department, Brazil
| | - Túlio Pimentel
- Federal University of Pernambuco, Medicine Department, Brazil
| | | | - Maria L R Defante
- Redentor University Center, Medicine Department, Itaperuna, Rio de Janeiro, Brazil
| | | | - Igor Eckert
- Independent Researcher, Porto Alegre, Brazil
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Grigore M, Balaban DV, Jinga M, Ioniță-Radu F, Costache RS, Dumitru AL, Maniu I, Badea M, Gaman L, Bucurică S. Hypertriglyceridemia-Induced and Alcohol-Induced Acute Pancreatitis-A Severity Comparative Study. Diagnostics (Basel) 2025; 15:882. [PMID: 40218233 PMCID: PMC11988868 DOI: 10.3390/diagnostics15070882] [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: 02/05/2025] [Revised: 03/27/2025] [Accepted: 03/30/2025] [Indexed: 04/14/2025] Open
Abstract
Background: Alcohol use and hypertriglyceridemia are the second and third common causes of acute pancreatitis after choledocholithiasis. Still, few studies directly compare the severity and outcomes of these two groups, which share pathophysiology pathways. Methods: In our study, we compared the biologic profile, severity according to the Atlanta classification and Balthazar index, intensive care unit admissions, and mortality between patients with hypertriglyceridemia-induced pancreatitis (HTGP) and alcohol-induced acute pancreatitis (AAP). A total of 78 patients were included in this study, 37.17% of which had HTGP, and 62.82% had AAP. Results: HTGP was more severe in terms of the Atlanta revised classification severity assessment (82.76% vs. 46%, p = 0.014), led to more extended hospitalizations (p = 0.024), and resulted in similar serum CRP levels among patients, with a significant difference regarding median serum fibrinogen values (739 vs. 563 mg/dL, p = 0.030) and necrotizing forms (24.13% vs. 10.20%). Hyponatremia was more significant in HTGP patients compared with AAP patients (130 vs. 137 mmol/L, p < 0.000). No differences were found in other inflammation indexes such as NLR (neutrophil count/lymphocyte count), PLR (platelet count/lymphocyte count), MLR (monocyte/lymphocyte count), SII (systemic immune-inflammation index), or SIRI (systemic inflammation response index). Conclusions: The pattern of acute pancreatitis is related to its etiology and may have different grades of severity. In our study, we found that hypertriglyceridemia-induced pancreatitis required twice as many admissions to the intensive care unit and was associated with lower serum sodium levels, and almost twice as many patients with HTGP had moderate or severe forms of acute pancreatitis compared to alcohol-induced pancreatitis cases.
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Affiliation(s)
- Monica Grigore
- Department of Gastroenterology, Buzau County Emergency Hospital, 120140 Buzau, Romania;
| | - Daniel Vasile Balaban
- Department of Internal Medicine and Gastroenterology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania; (D.V.B.); (M.J.); (F.I.-R.); (R.S.C.)
- Department of Gastroenterology, University Emergency Central Military Hospital “Dr. Carol Davila, 010825 Bucharest, Romania
| | - Mariana Jinga
- Department of Internal Medicine and Gastroenterology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania; (D.V.B.); (M.J.); (F.I.-R.); (R.S.C.)
- Department of Gastroenterology, University Emergency Central Military Hospital “Dr. Carol Davila, 010825 Bucharest, Romania
| | - Florentina Ioniță-Radu
- Department of Internal Medicine and Gastroenterology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania; (D.V.B.); (M.J.); (F.I.-R.); (R.S.C.)
- Department of Gastroenterology, University Emergency Central Military Hospital “Dr. Carol Davila, 010825 Bucharest, Romania
| | - Raluca Simona Costache
- Department of Internal Medicine and Gastroenterology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania; (D.V.B.); (M.J.); (F.I.-R.); (R.S.C.)
- Department of Gastroenterology, University Emergency Central Military Hospital “Dr. Carol Davila, 010825 Bucharest, Romania
| | - Andrada Loredana Dumitru
- Department of Internal Medicine and Gastroenterology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania; (D.V.B.); (M.J.); (F.I.-R.); (R.S.C.)
- Department of Gastroenterology, University Emergency Central Military Hospital “Dr. Carol Davila, 010825 Bucharest, Romania
| | - Ionela Maniu
- Department of Mathematics and Informatics, Faculty of Sciences, Lucian Blaga University Sibiu, 550012 Sibiu, Romania;
- Research Team, Pediatric Clinical Hospital Sibiu, 550166 Sibiu, Romania
| | - Mihaela Badea
- Faculty of Medicine, Transilvania University of Brasov, 500019 Brasov, Romania;
- Research Center for Fundamental Research and Prevention Strategies in Medicine, Research and Development Institute, Transilvania University of Brasov, 500484 Brasov, Romania
| | - Laura Gaman
- Biochemistry Department, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania;
| | - Săndica Bucurică
- Department of Internal Medicine and Gastroenterology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania; (D.V.B.); (M.J.); (F.I.-R.); (R.S.C.)
- Department of Gastroenterology, University Emergency Central Military Hospital “Dr. Carol Davila, 010825 Bucharest, Romania
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Corsini A, Ginsberg HN, Chapman MJ. Therapeutic PCSK9 targeting: Inside versus outside the hepatocyte? Pharmacol Ther 2025; 268:108812. [PMID: 39947256 DOI: 10.1016/j.pharmthera.2025.108812] [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: 11/16/2024] [Revised: 01/13/2025] [Accepted: 01/29/2025] [Indexed: 02/27/2025]
Abstract
As a major regulator of LDL receptor (LDLR) activity and thus of LDL-cholesterol (LDL-C) levels, proprotein convertase subtilisin/kexin type 9 (PCSK9) represents an obvious therapeutic target for lipid lowering. The PCSK9 inhibitors, alirocumab and evolocumab, are human monoclonal antibodies (mAbs) that act outside the cell by complexing circulating PCSK9 and thus preventing its binding to the LDLR. In contrast, inclisiran, a small interfering RNA (siRNA), inhibits hepatic synthesis of PCSK9, thereby resulting in reduced amounts of the protein inside and outside the cell. Both approaches result in decreased plasma LDL-C concentrations and improved cardiovascular outcomes. Marginally superior LDL-C reduction (≈ 60 %) is achieved with mAbs as compared to the siRNA (≈ 50 %); head-to-head comparisons are required to confirm between-class differences in efficacy. Both drug classes have shown variability in LDL-C lowering response between individuals in waterfall analyses. Whereas mAb-mediated inhibition leads to a compensatory increase in plasma PCSK9 levels, siRNA treatment reduces them. These agents differ in their pharmacokinetic and pharmacodynamic features, which may translate into distinct clinical opportunities under acute (e.g. acute coronary syndromes) as compared to chronic conditions. Both drug classes provide additional reduction in LDL-C levels (up to 50 %) beyond those achieved with statin therapy, facilitating attainment of guideline-recommended LDL-C goals in high and very high-risk patients. Additional PCSK9 inhibitors, including an oral macrocyclic peptide, a small PCSK9 binding protein and a novel small molecule, plus hepatic gene editing of PCSK9, are under development. This review critically appraises pharmacological strategies to target PCSK9 either inside or outside the cell.
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Affiliation(s)
- Alberto Corsini
- Department of Pharmacological and Biomolecular Sciences "Rodolfo Paoletti", University of Milan, Milan, Italy
| | - Henry N Ginsberg
- Irving Institute for Clinical and Translational Research, Columbia University, New York, USA
| | - M John Chapman
- Sorbonne University Medical Faculty, Lipidology and Cardiovascular Prevention Unit, Pitie-Salpetriere University Hospital, Paris, France.
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Greenland P, Williams KA. Number Needed to Defeat?: Overcoming Barriers to Optimal Coronary Disease Screening With CT Calcium Scoring. JACC Cardiovasc Imaging 2025; 18:476-477. [PMID: 40204417 DOI: 10.1016/j.jcmg.2025.01.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Accepted: 01/16/2025] [Indexed: 04/11/2025]
Affiliation(s)
- Philip Greenland
- Departments of Preventive Medicine and Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
| | - Kim A Williams
- Department of Internal Medicine, University of Louisville School of Medicine, Louisville, Kentucky, USA
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Cameron NA, Begna H, Schwarz EB. Blood Pressure Monitoring and Knowledge in the First Year after a Hypertensive Disorder of Pregnancy. J Womens Health (Larchmt) 2025; 34:485-490. [PMID: 39648739 DOI: 10.1089/jwh.2024.0798] [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] [Indexed: 12/10/2024] Open
Abstract
Introduction: In the first year postpartum, hypertension is a leading cause of morbidity and mortality, particularly for those with hypertensive disorders of pregnancy (HDPs). Given that timely recognition of hypertension is key to reducing short- and long-term cardiovascular risk, we assessed knowledge of when to seek medical attention for blood pressure (BP) elevations and rates of BP measurement in the first year postpartum. Methods: This was a secondary analysis of a cohort of 405 primiparas who enrolled in a randomized trial during pregnancy. We calculated the proportion who stated they would contact a clinician for a systolic BP above 140 and a diastolic BP above 90 at 3 months postpartum, and the frequency and location of BP checks reported from 2 to 12 months postpartum by HDP status. Results: HDPs were reported by 16% of participants. Mean age was 32 ± 5 years; 40% identified as non-White, and 25% had public insurance. At 3 months postpartum, 44.6% with HDPs and 23.5% without identified a systolic BP of 140 as the threshold above which to contact a clinician (p < 0.01); 52.4% with HDPs and 28.5% without identified a diastolic BP threshold of 90 (p < 0.01). From 3 to 12 months postpartum, people with HDPs were more likely to report a BP check (83.1% versus 59.4%, p < 0.01) and home BP monitoring (41.6% versus9.7%, p < 0.01). Home monitoring was not associated with awareness of when to seek help for hypertension among those with HDPs. Conclusions: Efforts are needed to improve awareness of when to seek medical attention for postpartum hypertension.
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Affiliation(s)
- Natalie A Cameron
- Division of General Internal Medicine, Department of Medicine, and Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Hannah Begna
- Division of General Internal Medicine, Department of Medicine, University of California San Francisco, San Francisco, California, USA
| | - Eleanor B Schwarz
- Division of General Internal Medicine, Department of Medicine, University of California San Francisco, San Francisco, California, USA
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Li B, Khan H, Shaikh F, Zamzam A, Abdin R, Qadura M. Prediction of Major Adverse Limb Events in Females with Peripheral Artery Disease using Blood-Based Biomarkers and Clinical Features. J Cardiovasc Transl Res 2025; 18:316-330. [PMID: 39643751 DOI: 10.1007/s12265-024-10574-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: 02/23/2024] [Accepted: 11/13/2024] [Indexed: 12/09/2024]
Abstract
The objective of this study was to identify a female-specific prognostic biomarker for peripheral artery disease (PAD) and develop a prediction model for 2-year major adverse limb events (MALE). Patients with/without PAD were recruited (n=461). Plasma concentrations of 68 circulating proteins were measured and patients were followed for 2 years. The primary outcome was MALE (composite of vascular intervention, major amputation, or acute/chronic limb threatening ischemia). We trained a random forest model using: 1) clinical characteristics, 2) female-specific PAD biomarker, and 3) clinical characteristics and female-specific PAD biomarker. Galectin-9 was the only protein to be significantly elevated in females compared to males in the discovery/validation analyses. The random forest model achieved the following AUROC's: 0.72 (clinical features), 0.83 (Galectin-9), and 0.86 (clinical features + Galectin-9). We identified Galectin-9 as a female-specific PAD biomarker and developed an accurate prognostic model for 2-year MALE using a combination of clinical features and plasma Galectin-9 levels.
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Affiliation(s)
- Ben Li
- Department of Surgery, University of Toronto, Toronto, Canada
- Division of Vascular Surgery, St. Michael's Hospital, Unity Health Toronto, University of Toronto, 30 Bond Street, Suite 7-076, Toronto, Ontario, M5B 1W8, Canada
- Institute of Medical Science, University of Toronto, Toronto, Canada
- Temerty Centre for Artificial Intelligence Research and Education in Medicine (T-CAIREM), University of Toronto, Toronto, Canada
| | - Hamzah Khan
- Division of Vascular Surgery, St. Michael's Hospital, Unity Health Toronto, University of Toronto, 30 Bond Street, Suite 7-076, Toronto, Ontario, M5B 1W8, Canada
- Institute of Medical Science, University of Toronto, Toronto, Canada
| | - Farah Shaikh
- Division of Vascular Surgery, St. Michael's Hospital, Unity Health Toronto, University of Toronto, 30 Bond Street, Suite 7-076, Toronto, Ontario, M5B 1W8, Canada
| | - Abdelrahman Zamzam
- Division of Vascular Surgery, St. Michael's Hospital, Unity Health Toronto, University of Toronto, 30 Bond Street, Suite 7-076, Toronto, Ontario, M5B 1W8, Canada
| | - Rawand Abdin
- Department of Medicine, McMaster University, Hamilton, Canada
| | - Mohammad Qadura
- Department of Surgery, University of Toronto, Toronto, Canada.
- Division of Vascular Surgery, St. Michael's Hospital, Unity Health Toronto, University of Toronto, 30 Bond Street, Suite 7-076, Toronto, Ontario, M5B 1W8, Canada.
- Institute of Medical Science, University of Toronto, Toronto, Canada.
- Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, Canada.
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Kawaguchi YO, Fujimoto S, Nozaki YO, Tomizawa N, Daida H, Minamino T. Current status and future perspective of coronary artery calcium score in asymptomatic individuals. J Cardiol 2025; 85:275-282. [PMID: 39631694 DOI: 10.1016/j.jjcc.2024.11.008] [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: 10/24/2024] [Accepted: 11/03/2024] [Indexed: 12/07/2024]
Abstract
Atherosclerotic cardiovascular disease remains a major cause of death, and it is important to accurately estimate the cardiovascular events risk stratification even in asymptomatic patients. The coronary artery calcium score (CACS), which is quantitatively evaluated by electrocardiogram (ECG)-gated non-contrast chest computed tomography (CT) imaging, has been reported to be useful for cardiovascular event risk stratification in large studies. In the USA and Europe, guidelines recommend the use of the CACS in borderline or intermediate-risk asymptomatic individuals based on a high level of evidence. In Japan, however, the use of CACS in clinical practice is currently limited. Although it has been reported that the prevalence and distribution of coronary artery calcification (CAC) may differ by race and ethnicity, there are few data on its usefulness in stratifying the risk of cardiovascular events in asymptomatic Japanese individuals. While it is important to establish evidence for the usefulness of CACS in the Japanese population, for widespread clinical dissemination it would be beneficial to evaluate CAC and to perform accurate cardiovascular event risk stratification from non-ECG-gated non-contrast chest CT imaging performed during medical check-up and routine clinical practice. There have been reports on the usefulness of CAC assessed by non-ECG-gated chest CT imaging and on the relationship of CAC between ECG-gated and non-ECG-gated chest CT imaging. In recent years, a more accurate method of evaluating CACS from non-ECG-gated chest CT imaging has been developed using artificial intelligence, and further development is expected in the future.
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Affiliation(s)
- Yuko O Kawaguchi
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Shinichiro Fujimoto
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
| | - Yui O Nozaki
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Nobuo Tomizawa
- Department of Radiology, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Hiroyuki Daida
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Radiological Technology, Juntendo University, Graduate School of Health Science, Tokyo, Japan
| | - Tohru Minamino
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
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Cha JJ, Kim JH, Hong SJ, Lim S, Joo HJ, Park JH, Yu CW, Lee PH, Lee SW, Lee CW, Moon JY, Lee JY, Kim JS, Park JS, Lim DS. Safety and efficacy of moderate-intensity statin with ezetimibe in elderly patients with atherosclerotic cardiovascular disease. J Intern Med 2025; 297:400-408. [PMID: 39709592 DOI: 10.1111/joim.20029] [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] [Indexed: 12/23/2024]
Abstract
BACKGROUND High-intensity statin therapy significantly reduces mortality and cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD). However, moderate-intensity statins are often preferred for elderly patients due to their higher risk of intolerance to high-intensity statins. OBJECTIVE To compare the incidence of statin-associated muscle symptoms (SAMS) and the effect on low-density lipoprotein cholesterol (LDL-C) levels between elderly ASCVD patients receiving high-intensity statin monotherapy and those receiving moderate-intensity statin with ezetimibe in a combination therapy. METHOD In a prospective, multicenter, open-label trial conducted in South Korea, 561 patients aged 70 years or above with ASCVD were randomly assigned to receive either moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 5 mg with ezetimibe 10 mg) or high-intensity statin monotherapy (rosuvastatin 20 mg) over 6 months. The primary endpoint was the incidence of SAMS, and the key secondary endpoint was the achievement of target LDL-C levels (<70 mg/dL) within 6 months. RESULTS The primary endpoint showed a lower incidence of SAMS in the combination therapy group (0.7%) compared to the high-intensity statin monotherapy group (5.7%, p = 0.005). Both groups achieved similar LDL-C levels, with 75.4% in the combination therapy group and 68.7% in the monotherapy group reaching target levels. CONCLUSION Moderate-intensity statin with ezetimibe combination therapy offers a lower risk of SAMS and similar LDL-C reduction in elderly patients with ASCVD, compared to high-intensity statin monotherapy.
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Affiliation(s)
- Jung-Joon Cha
- Division of Cardiology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea
| | - Ju Hyeon Kim
- Division of Cardiology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea
| | - Soon Jun Hong
- Division of Cardiology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea
| | - Subin Lim
- Division of Cardiology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea
| | - Hyung Joon Joo
- Division of Cardiology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea
| | - Jae Hyoung Park
- Division of Cardiology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea
| | - Cheol Woong Yu
- Division of Cardiology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea
| | - Pil Hyung Lee
- Department of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Seung Whan Lee
- Department of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Cheol Whan Lee
- Department of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jae Youn Moon
- Department of Cardiology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea
| | - Jong-Young Lee
- Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jung-Sun Kim
- Division of Cardiology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Jae Suk Park
- Division of Cardiology, Incheon Sejong Hospital, Incheon, South Korea
| | - Do-Sun Lim
- Division of Cardiology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea
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Zhang Y, Li K, Bo X, Zhang Y, Xiao T, Liu H, Villamil OIRC, Chen K, Ding J. Effects of residual inflammatory and cholesterol risks on cardiovascular events with evolocumab in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Lipids Health Dis 2025; 24:123. [PMID: 40165297 PMCID: PMC11956451 DOI: 10.1186/s12944-025-02537-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Accepted: 03/17/2025] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND Evolocumab has shown significant reductions in low-density lipoprotein cholesterol (LDL-C) levels and incident cardiovascular events among acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Nonetheless, the potential modification of evolocumab's effectiveness by baseline inflammatory risk remains unclear. We aimed to assess evolocumab's effectiveness based on baseline neutrophil-to-lymphocyte ratio (NLR) and evaluate residual inflammatory and cholesterol-related risks across varying on-treatment NLR and LDL-C levels. METHODS This multicentric, retrospective analysis enrolled consecutive patients with ACS undergoing PCI and exhibiting elevated LDL-C at the First Affiliated Hospital of Zhengzhou University and Zhongda Hospital Southeast University between March 2019 and August 2021. Patients were categorized into evolocumab and standard-of-care treatment groups based on evolocumab administration. Hazard ratios for the primary composite outcome-including myocardial infarction, ischemic stroke, cardiac death, unplanned coronary revascularization, and hospitalization due to unstable angina-comparing baseline NLR quartiles were computed using multivariable Cox regression. We assessed evolocumab's impact on the primary outcome across median-based NLR dichotomization and evaluated the outcome across 1-month NLR and LDL-C levels. RESULTS The median baseline NLR was 2.99 (IQR: 2.14-4.69), remaining stable following evolocumab therapy. Each NLR quartile increase heightened the risk of primary outcome by 29% (95% CI, 17-42%; P < 0.01). The relative risk reductions with evolocumab were consistent across NLR categories (P-interaction > 0.05), but absolute risk reductions were higher in high-NLR patients (2.9% vs. 6.2%). Residual inflammatory and cholesterol risks, indicated by on-treatment NLR and LDL-C, independently correlated with the primary outcome (P < 0.001). CONCLUSIONS Higher baseline NLR is associated with increased cardiovascular risk in ACS/PCI patients. Relative risk reductions with evolocumab were consistent across NLR categories, while absolute risk reductions were more significant in high-NLR patients. Minimized risk is observed in patients with the lowest on-treatment NLR and LDL-C levels.
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Affiliation(s)
- Yahao Zhang
- Department of Cardiology, National Key Clinical Specialty, Zhongda Hospital, Southeast University, 87 Dingjiaqiao, Nanjing, 210009, China
| | - Kairu Li
- Department of Cardiology, Tinghu People's Hospital of Yancheng City, Yancheng, 224000, China
| | - Xiangwei Bo
- Department of Cardiology, National Key Clinical Specialty, Zhongda Hospital, Southeast University, 87 Dingjiaqiao, Nanjing, 210009, China
| | - Yanghui Zhang
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Tingting Xiao
- Department of Cardiology, National Key Clinical Specialty, Zhongda Hospital, Southeast University, 87 Dingjiaqiao, Nanjing, 210009, China
| | - Huan Liu
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Orion I R Chiara Villamil
- Department of Cardiology, National Key Clinical Specialty, Zhongda Hospital, Southeast University, 87 Dingjiaqiao, Nanjing, 210009, China
| | - Kui Chen
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Jiandong Ding
- Department of Cardiology, National Key Clinical Specialty, Zhongda Hospital, Southeast University, 87 Dingjiaqiao, Nanjing, 210009, China.
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Schwartz JK, Zhang X, Peterson AL. Changes in Youth Cholesterol Screening Rates in an Academic Center During the COVID-19 Pandemic. Pediatr Cardiol 2025:10.1007/s00246-025-03831-7. [PMID: 40116884 DOI: 10.1007/s00246-025-03831-7] [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: 01/22/2025] [Accepted: 03/12/2025] [Indexed: 03/23/2025]
Abstract
Screening youth for hypercholesterolemia allows for detection of familial hypercholesterolemia that can predispose to premature heart disease, however guidelines provide conflicting recommendations regarding universal cholesterol screening. The COVID-19 pandemic and the perception of conflicting guideline recommendations (2011 National Heart, Lung, and Blood Institute guidelines and United States Preventive Services Task Force recommendations in 2016 and 2023) may have adversely affected youth cholesterol screening rates. This study examines screening rates during and after the COVID-19 pandemic and the most recent guideline update. Electronic health record data from a single academic institution was used to calculate Order Placement Rates (OPRs) for subjects aged 8 years 9 months-21 years from 3/18/2019 to 12/31/2023. Demographic data included subject sex, age, zip code, and primary provider's specialty. Zip codes were categorized as rural/urban and underserved/middle/advantaged. The study period was divided into five stages (pre-pandemic, mid-pandemic, late-pandemic, post-pandemic, and post-guideline). Relative to baseline OPR prior to 3/18/2019, study period OPRs decreased slightly in pre-pandemic (73.3%), mid-pandemic (70.9%), and late-pandemic (65.4%) stages, with sharper declines during post-pandemic (47.6%) and post-guideline stages (35.2%). OPR decreased more significantly for youth 9-11 years than 17-21 years (post-guideline OPR: 35.1% versus 46.9%). Urban underserved and urban advantaged had higher OPRs. OPRs for family medicine and pediatrics declined (p < 0.01), more significantly in pediatrics (post-guideline versus pre-pandemic OPR adjusted odds ratio [95% CI] = 0.03 [0.02-0.04] for pediatrics, 0.35 [0.30-0.40] for family medicine). Our institution showed decreases in cholesterol screening OPRs after both the COVID-19 pandemic and guideline update. OPRs dropped most significantly among youth aged 9-11 years and among pediatric providers. Urban youth were more likely to be screened than rural youth. Discrepancies persist among access to youth cholesterol screening.
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Affiliation(s)
- Jessica K Schwartz
- Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Xiao Zhang
- Division of Pediatric Cardiology, Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, CSC H6/528 MC 4108, 600 Highland Ave., Madison, WI, 53792, USA
| | - Amy L Peterson
- Division of Pediatric Cardiology, Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, CSC H6/528 MC 4108, 600 Highland Ave., Madison, WI, 53792, USA.
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50
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Dressel A, Fath F, Krämer BK, Klose G, März W. Statins for primary prevention of cardiovascular disease in Germany: benefits and costs. Clin Res Cardiol 2025:10.1007/s00392-025-02608-5. [PMID: 40095039 DOI: 10.1007/s00392-025-02608-5] [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: 11/13/2024] [Accepted: 01/16/2025] [Indexed: 03/19/2025]
Abstract
BACKGROUND The reduction of LDL cholesterol lowers the risk of coronary and cerebrovascular events in individuals without manifest cardiovascular diseases. In Germany, statins at the expense of statutory health insurance had only been permitted for patients with atherosclerosis-related diseases or those at high cardiovascular risk (over 20 percent event probability within the next 10 years, calculated using one of the "available risk calculators"). However, international guidelines recommend lower risk thresholds for the use of statins. METHODS The health and economic impacts of different risk thresholds for statin use in primary prevention within the German population are estimated for thresholds of 7.5, 10, and 15 percent over 10 years, based on the US Pooled Cohort Equation (PCE) which is valid for Germany, using Markov models. FINDINGS Cost-effectiveness increases with a rising risk threshold, while individual benefit decreases with age at the start of treatment. The use of statins at a risk of 7.5 percent or more is cost-effective at any age (cost per QALY between 410 and 2100 Euros). In none of the examined scenarios does the proportion of the population qualifying for statin therapy exceed 25 percent. INTERPRETATION Lowering the threshold for statin therapy to a risk of 7.5 percent of either non-fatal myocardial infarction, coronary heart disease death, non-fatal or fatal stroke would align statin prescription in Germany with international standards. There is no urgent rationale for applying age-stratified risk thresholds.
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Affiliation(s)
- Alexander Dressel
- D-A-CH-Society for Prevention of Cardiovascular Diseases e. V., Hamburg, Germany
| | - Felix Fath
- D-A-CH-Society for Prevention of Cardiovascular Diseases e. V., Hamburg, Germany.
- Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
| | - Bernhard K Krämer
- European Center for Angioscience, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany
| | - Gerald Klose
- Drs. T. Beckenbauer and S. Maierhof, Bremen, Germany
- Drs. I. van de Loo, K. Spieker and C. Otte, Bremen, Germany
| | - Winfried März
- D-A-CH-Society for Prevention of Cardiovascular Diseases e. V., Hamburg, Germany
- SYNLAB Holding Deutschland GmbH, SYNLAB Academy, Mannheim, Germany
- Clinical Institute for Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
- Department of Internal Medicine III (Cardiology, Angiology and Pneumology), Heidelberg University Hospital, Heidelberg, Germany
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