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1
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Guo J, Jiang Z, Xia Y, Wang H, Tang Q, Meng B. The association between statin use and diabetic nephropathy in US adults: data from NHANES 2005 - 2018. Front Endocrinol (Lausanne) 2024; 15:1381746. [PMID: 38726340 PMCID: PMC11079199 DOI: 10.3389/fendo.2024.1381746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Accepted: 04/11/2024] [Indexed: 05/12/2024] Open
Abstract
Background A serious consequence of diabetes is diabetic nephropathy (DN), which is commonly treated by statins. Studies evaluating the effects of statin medication have yielded inconsistent results regarding the potential association with diabetic nephropathy. To manage diabetic nephropathy's onset and improve the quality of life of patients, it is imperative to gain a comprehensive understanding of its contributing factors. Data and methods Our study was conducted using the National Health and Nutrition Examination Survey (NHANES) as well as weighted multivariate logistic regression models to determine the odds ratio (OR) and 95% confidence intervals (95%CI) for diabetic nephropathy. We conducted stratified analyses to examine the impact of statins and the duration of their usage on diabetic nephropathy in different subgroups. A nomogram model and the receiver operating characteristic (ROC) curve were also developed to predict DN risk. Results Statin use significantly increased the incidence of DN (OR=1.405, 95%CI (1.199,1.647), p<0.001). Individuals who used statins for 5 to 7 years were more likely to develop diabetic nephropathy (OR=1.472, 95%CI (1.057,2.048), p=0.022) compared to those who used statins for 1-3 years (OR=1.334, 95%CI (1.058,1.682), p=0.015) or <1 year (OR=1.266, 95%CI (1.054,1.522), p = 0.012). Simvastatin has a greater incidence of diabetic nephropathy (OR=1.448, 95%CI(1.177, 1.78), P < 0.001). Conclusion Taking statins long-term increases the risk of DN. Statin use is associated with an increased risk of DN. Caution should be exercised when prescribing atorvastatin and simvastatin for long-term statin therapy.
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Affiliation(s)
| | | | | | | | - Qun Tang
- Medical School, Hunan University of Chinese Medicine, Changsha, Hunan, China
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2
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Caklili OT, Rizzo M, Cesur M. Efficacy and Safety of Bempedoic Acid in Patients with High Cardiovascular Risk: An Update. Curr Vasc Pharmacol 2024; 22:242-250. [PMID: 38323615 DOI: 10.2174/0115701611290763240126045433] [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: 11/04/2023] [Revised: 12/24/2023] [Accepted: 01/08/2024] [Indexed: 02/08/2024]
Abstract
Statins play a significant role in the prevention of cardiovascular (CV) diseases (CVDs); however, non-adherence with statin treatment or statin intolerance (mainly attributed to muscleassociated side effects) is not uncommon. New agents such as bempedoic acid (BA) can provide more treatment options. BA is administered orally, once daily, at a dose of 180 mg in current clinical practice. It can decrease circulating low-density lipoprotein cholesterol (LDL-C) levels by nearly 30% as monotherapy or by 20% as an add-on to statins. CV outcome studies have shown that BA decreases major adverse CV event risk in patients with established CVD or high CV risk by 13%. When patients with high CV risk were analyzed alone, the risk reduction was 30%. Its side effects include a rise in serum uric acid levels and liver enzyme activity, whereas it does not increase diabetes risk as statins do. BA can be used as adjunctive therapy to statins in patients at high CV risk in whom lipid targets cannot be achieved or as an alternative to statins in patients with statin intolerance.
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Affiliation(s)
- Ozge Telci Caklili
- Department of Endocrinology and Metabolism, Kocaeli City Hospital, Kocaeli, Türkiye
| | - Manfredi Rizzo
- School of Medicine, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (Promise), University of Palermo, Palermo, Italy
- College of Medicine, Mohammed Bin Rashid University (MBRU), Dubai, UAE
| | - Mustafa Cesur
- Department of Endocrinology and Metabolism, Ankara Guven Hospital, Ankara, Türkiye
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3
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Akbari A, Razmi M, Rafiee M, Watts GF, Sahebkar A. The Effect of Statin Therapy on Serum Uric Acid Levels: A Systematic Review and Meta-analysis. Curr Med Chem 2024; 31:1726-1739. [PMID: 36748810 DOI: 10.2174/0929867330666230207124516] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 11/17/2022] [Accepted: 11/23/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND Elevated concentrations of serum uric acid (SUA) are associated with several conditions, including cardiovascular disease. The present study aimed to estimate the impact of statin therapy on SUA levels through a systematic review and meta-analysis of clinical trials. METHODS PubMed, Embase, Web of Science, and Scopus were searched on January 14, 2022, to identify eligible clinical trials. The intervention group received statins as monotherapy or in combination with other drugs, and the control group received non-statins or placebo. Studies reporting SUA levels before and after treatment were selected for further analysis. Finally, the data were pooled, and the mean changes in SUA, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides were reported. RESULTS Out of 1269 identified studies, 23 were included in the review. A total of 3928 participants received statin therapy, and 1294 were included in control groups. We found a significant reduction in SUA levels following statin therapy (mean difference (MD) = -26.67 μmol/L with 95% confidence interval (CI) [-44.75, -8.60] (P =0.004)). Atorvastatin (MD = -37.93 μmol/L [-67.71, -8.15]; P < 0.0001), pravastatin (MD = -12.64 μmol/L [-18.64, -6.65]; P < 0.0001), and simvastatin (MD = -5.95 μmol/L [-6.14, -5.80]; P < 0.0001), but not rosuvastatin, were significantly associated with a reduction in SUA levels. An analysis comparing different types of statins showed that pravastatin 20-40 mg/day could significantly reduce SUA when compared to simvastatin 10-20 mg/day (-21.86 μmol/L [-36.33,-7.39]; P =0.003). CONCLUSION Statins were significantly associated with a decrease in SUA levels, particularly atorvastatin, which was found to be most effective in lowering SUA. Atorvastatin may be the most appropriate cholesterol-lowering agent for patients with or at risk of hyperuricemia.
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Affiliation(s)
- Abolfazl Akbari
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahya Razmi
- Student Research Committee, Faculty of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahdi Rafiee
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gerald F Watts
- Department of Cardiology, School of Medicine, Perth, Australia and Lipid Disorders Clinic, Cardiometabolic Services, Royal Perth Hospital, University of Western Australia, Perth, Australia
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- School of Medicine, The University of Western Australia, Perth, Australia
- Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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Elendu C, John Okah M, Fiemotongha KDJ, Adeyemo BI, Bassey BN, Omeludike EK, Obidigbo B. Comprehensive advancements in the prevention and treatment of diabetic nephropathy: A narrative review. Medicine (Baltimore) 2023; 102:e35397. [PMID: 37800812 PMCID: PMC10553077 DOI: 10.1097/md.0000000000035397] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 09/05/2023] [Indexed: 10/07/2023] Open
Abstract
Diabetic nephropathy (DN) is a common and severe complication of diabetes mellitus and is the leading cause of chronic kidney disease (CKD) worldwide. Despite current treatments, many individuals with DN progress to end-stage renal disease (ESRD), requiring dialysis or kidney transplantation. The advancement in our understanding of the pathogenesis of diabetic nephropathy has led to the development of new prevention and treatment strategies. We comprehensively reviewed the literature on advances in the prevention and treatment of DN. We searched PubMed, Scopus, and Web of Science databases for articles published between 2000 and 2023, using keywords such as "diabetic nephropathy," "prevention," "treatment," and "recent advances." The recent advances in the prevention and treatment of DN include novel approaches targeting inflammation and fibrosis, such as inhibitors of the nuclear factor kappa-B (NF-kB) pathway, inhibitors of the transforming growth factor-beta (TGF-beta) pathway, and anti-inflammatory cytokines. Other promising strategies include stem cell therapy, gene therapy, and artificial intelligence-based approaches, such as predictive models based on machine learning algorithms that can identify individuals at high risk of developing DN and guide personalized treatment strategies. Combination therapies targeting multiple disease pathways may also offer the most significant potential for improving outcomes for individuals with DN. Overall, the recent advances in the prevention and treatment of DN represent promising avenues for future research and clinical development. Novel therapies targeting inflammation and fibrosis, stem cell and gene therapies, and artificial intelligence-based approaches all show great potential for improving outcomes for individuals with DN.
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Njeim R, Alkhansa S, Fornoni A. Unraveling the Crosstalk between Lipids and NADPH Oxidases in Diabetic Kidney Disease. Pharmaceutics 2023; 15:pharmaceutics15051360. [PMID: 37242602 DOI: 10.3390/pharmaceutics15051360] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 04/25/2023] [Accepted: 04/25/2023] [Indexed: 05/28/2023] Open
Abstract
Diabetic kidney disease (DKD) is a serious complication of diabetes mellitus and a leading cause of end-stage renal disease. Abnormal lipid metabolism and intrarenal accumulation of lipids have been shown to be strongly correlated with the development and progression of diabetic kidney disease (DKD). Cholesterol, phospholipids, triglycerides, fatty acids, and sphingolipids are among the lipids that are altered in DKD, and their renal accumulation has been linked to the pathogenesis of the disease. In addition, NADPH oxidase-induced production of reactive oxygen species (ROS) plays a critical role in the development of DKD. Several types of lipids have been found to be tightly linked to NADPH oxidase-induced ROS production. This review aims to explore the interplay between lipids and NADPH oxidases in order to provide new insights into the pathogenesis of DKD and identify more effective targeted therapies for the disease.
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Affiliation(s)
- Rachel Njeim
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA
- Peggy and Harold Katz Family Drug Discovery Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Sahar Alkhansa
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut 1107-2020, Lebanon
- AUB Diabetes, American University of Beirut, Beirut 1107-2020, Lebanon
| | - Alessia Fornoni
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA
- Peggy and Harold Katz Family Drug Discovery Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA
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Kanai D, Fujii H, Nakai K, Kono K, Watanabe K, Goto S, Nishi S. Statin Use Influence on the Occurrence of Acute Kidney Injury in Patients with Peripheral Arterial Disease. J Atheroscler Thromb 2022; 29:1646-1654. [PMID: 35013022 PMCID: PMC9623082 DOI: 10.5551/jat.63265] [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: 09/20/2021] [Accepted: 12/03/2021] [Indexed: 11/11/2022] Open
Abstract
AIM Acute kidney injury (AKI) is an important clinical issue in the diagnosis and treatment of cardiovascular diseases. The association between pretreatment by statins and the occurrence of AKI in patients with peripheral arterial diseases (PAD) remains unclear. Therefore, we examined the association between statin therapy and the occurrence of AKI in patients with PAD. METHODS We retrospectively analyzed data from the endovascular treatment (EVT) database in our hospital. A total of 295 patients who underwent angiography and/or intervention for PAD between October 2011 and March 2016 were enrolled and divided into two groups: those without statins (control group; N=157) and those with statins (statin group; N=138) for at least 1 month before admission. We examined the occurrence of AKI and its related factors in these patients. RESULTS The serum creatinine levels, dose of contrast medium, use of a renin-angiotensin system inhibitor, smoking habit, and blood pressure were similar in both groups. The statin group had more diabetes patients, had patients who were significantly younger, had patients with a higher body mass index (BMI), and had patients with lower low-density lipoprotein cholesterol than the control group. With regard to the occurrence of AKI, there was a significantly lower incidence in the statin group compared with the control group (5% vs. 16%, p＜0.05). The result of the multivariate analysis indicated that statin therapy was significantly correlated with lower occurrence rates of AKI (p＜0.05). CONCLUSIONS Our study suggests that statin therapy might prevent the occurrence of AKI after angiography and/or intervention for PAD.
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Affiliation(s)
- Daisuke Kanai
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan
- Department of Nephrology and Kidney Center, Kakogawa Central City Hospital, Hyogo, Japan
| | - Hideki Fujii
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kentaro Nakai
- Department of Nephrology and Kidney Center, Kakogawa Central City Hospital, Hyogo, Japan
| | - Keiji Kono
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kentaro Watanabe
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Shunsuke Goto
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Shinichi Nishi
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan
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Lin L, Tan W, Pan X, Tian E, Wu Z, Yang J. Metabolic Syndrome-Related Kidney Injury: A Review and Update. Front Endocrinol (Lausanne) 2022; 13:904001. [PMID: 35813613 PMCID: PMC9261267 DOI: 10.3389/fendo.2022.904001] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 05/09/2022] [Indexed: 11/15/2022] Open
Abstract
Metabolic syndrome (MetS) includes visceral obesity, hyperglycemia, dyslipidemia, and hypertension. The prevalence of MetS is 20-25%, which is an important risk factor for chronic kidney disease (CKD). MetS causes effects on renal pathophysiology, including glomerular hyperfiltration, RAAS, microalbuminuria, profibrotic factors and podocyte injury. This review compares several criteria of MetS and analyzes their differences. MetS and the pathogenesis of CKD includes insulin resistance, obesity, dyslipidemia, inflammation, oxidative stress, and endothelial dysfunction. The intervention of MetS-related renal damage is the focus of this article and includes controlling body weight, hypertension, hyperglycemia, and hyperlipidemia, requiring all components to meet the criteria. In addition, interventions such as endoplasmic reticulum stress, oxidative stress, gut microbiota, body metabolism, appetite inhibition, podocyte apoptosis, and mesenchymal stem cells are reviewed.
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Affiliation(s)
- Lirong Lin
- Department of Nephrology, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing, China
| | - Wei Tan
- Department of Nephrology, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing, China
| | - Xianfeng Pan
- Department of Nephrology, Chongqing Kaizhou District People’s Hospital of Chongqing, Chongqing, China
| | - En Tian
- Department of Nephrology, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing, China
| | - Zhifeng Wu
- Department of Nephrology, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing, China
| | - Jurong Yang
- Department of Nephrology, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing, China
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De Luca L, Gulizia MM, Gabrielli D, Meessen J, Mattei L, D'Urbano M, Colivicchi F, Temporelli PL, Borghi C, Desideri G. Impact of serum uric acid levels on cardiovascular events and quality of life in patients with chronic coronary syndromes: Insights from a contemporary, prospective, nationwide registry. Nutr Metab Cardiovasc Dis 2022; 32:393-401. [PMID: 34893417 DOI: 10.1016/j.numecd.2021.09.034] [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: 06/01/2021] [Revised: 09/05/2021] [Accepted: 09/30/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND AND AIMS Hyperuricemia is a metabolic disorder that has been associated with adverse cardiovascular (CV) events. Using the data from a nationwide, prospective registry on patients with chronic coronary syndromes (CCS), we assessed the impact of serum uric acid (SUA) levels on quality of life (QoL) and major adverse CV events (MACE), a composite of CV death and hospitalization for myocardial infarction, heart failure (HF), angina or revascularization at 1-year. METHODS AND RESULTS Among the 5070 consecutive CCS patients enrolled in the registry, levels of SUA were available for 2394 (47.2%). Patients with SUA levels available at baseline were grouped as low tertile (n = 860; 4.3 [3.7-4.7] mg/dL), middle tertile (n = 739; 5.6 [5.3-5.9] mg/dL) and high tertile (n = 795; 7.1 [6.7-7.9] mg/dL). At 1 year, the incidence of MACE was 3.7%, 4.1% and 6.8% for low, middle and high tertiles, respectively (p = 0.005 for low vs high tertile). Patients in the high tertile of SUA had a significantly higher rate of CV mortality (1.4% vs 0.4%; p = 0.05) and hospital admission for HF (2.8% vs 1.6%; p = 0.03) compared to the low tertile. However, hyperuricemia did not result as an independent predictor of MACE at multivariable analysis [hazard ratio: 1.27; 95% confidence intervals: 0.81-2.00; p = 0.3]. CONCLUSIONS In this contemporary, large cohort of CCS, those in the high tertile of SUA had a greater burden of CV disease and worse QoL. However, SUA did not significantly influence the higher rate of CV mortality, hospitalization for HF and MACE observed in these patients during 1-year follow-up.
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Affiliation(s)
- Leonardo De Luca
- Department of Cardiosciences, Azienda Ospedaliera San Camillo-Forlanini, Roma, Italy.
| | | | - Domenico Gabrielli
- Department of Cardiosciences, Azienda Ospedaliera San Camillo-Forlanini, Roma, Italy
| | - Jennifer Meessen
- Department of Cardiovascular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy
| | - Luisa Mattei
- Division of Cardiology, Ospedale Monfalcone-Gorizia, Italy
| | | | | | - Pier L Temporelli
- Division of Cardiology, Istituti Clinici Scientifici Maugeri, IRCCS, Gattico-Veruno, Novara, Italy
| | - Claudio Borghi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Giovambattista Desideri
- Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
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9
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Chen Y, Ding C, Hu L, Ruan Y, Zou K, Dai C, Liao Y, Liao H, Xia Y, Zhao Y, Yang R. Association between baseline serum uric acid and development of LDL-C level in patients with first acute myocardial infarction. BMC Cardiovasc Disord 2021; 21:572. [PMID: 34847885 PMCID: PMC8638344 DOI: 10.1186/s12872-021-02383-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Accepted: 11/10/2021] [Indexed: 12/22/2022] Open
Abstract
Background Data on the relationship of baseline serum uric acid (SUA) with development of low-density lipoprotein cholesterol (LDL-C) level in patients with first acute myocardial infarction (AMI) are limited. The present study is to evaluate whether elevated SUA predicts the development of LDL-C in the first AMI. Methods This is a retrospective 6-month cohort study of 475 hospitalized Chinese patients who underwent first AMI between January 2015 and December 2019 and were reevaluated half a year later at the Department of Cardiology, the Second Affiliated Hospital of Nanchang University, Jiangxi Province, China. The associations of baseline SUA with the percentage decrease of LDL-C (%) and LDL-C control were analyzed by using logistic regression analyses, multivariate linear regression analyses and the restricted cubic spline. Results Over the 6-month follow-up, baseline SUA was independently and positively associated with the percentage decrease of LDL-C (%) and LDL-C control in a dose response fashion. After multivariable adjustment, per SD increment of baseline SUA (120.58 μmol/L) was associated with 3.96% higher percentage decrease of LDL-C(%). The adjusted OR (95% CI) for LDL-C control was 5.62 (2.05, 15.36) when comparing the highest tertile (SUA ≥ 437.0 μmol/L) to the lowest tertile (< 341.7 μmol/L) of baseline SUA. Conclusions Among Chinese patients with first AMI, higher baseline SUA was associated with higher LDL-C deduction percentage (%), and higher rate of LDL-C control in the short-term follow-up, respectively. SUA acquired when AMI occurred was prone to be profitable in predicting the risk stratification of uncontrolled LDL-C and dyslipidemia management. Supplementary Information The online version contains supplementary material available at 10.1186/s12872-021-02383-x.
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Affiliation(s)
- Yang Chen
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang of Jiangxi, 330006, China
| | - Congcong Ding
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang of Jiangxi, 330006, China
| | - Longlong Hu
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang of Jiangxi, 330006, China
| | - Yuehua Ruan
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang of Jiangxi, 330006, China
| | - Kai Zou
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang of Jiangxi, 330006, China
| | - Cong Dai
- Department of Cardiovascular Medicine, The First Affiliated Hospital of Nanchang University, Nanchang of Jiangxi, China
| | - Yanhui Liao
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang of Jiangxi, 330006, China
| | - Hanhui Liao
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang of Jiangxi, 330006, China
| | - Yi Xia
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang of Jiangxi, 330006, China
| | - Yuanbin Zhao
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang of Jiangxi, 330006, China
| | - Renqiang Yang
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang of Jiangxi, 330006, China.
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Sfikas G, Psallas M, Koumaras C, Imprialos K, Perdikakis E, Doumas M, Giouleme O, Karagiannis A, Athyros VG. Prevalence, Diagnosis, and Treatment with 3 Different Statins of Non-alcoholic Fatty Liver Disease/Non-alcoholic Steatohepatitis in Military Personnel. Do Genetics Play a Role? Curr Vasc Pharmacol 2021; 19:572-581. [DOI: 10.2174/1570161118666201015152921] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Revised: 09/15/2020] [Accepted: 09/17/2020] [Indexed: 12/18/2022]
Abstract
Background:
Non-alcoholic fatty liver disease (NAFLD) and its severe form, non-alcoholic
steatohepatitis (NASH), are major health problems worldwide. Genetics may play a role in
the pathogenesis of NAFLD/NASH.
Aim:
To investigate the prevalence of NAFLD/NASH in 5,400 military personnel and evaluate
the effect of treatment with 3 statins on NAFLD/NASH using 2 non-invasive scores [NAFLD Activity
Score (NAS); Fibrosis-4 score (FIB-4)].
Methods:
During the mandatory annual medical check-up, military personnel underwent a clinical
and laboratory evaluation. Participants with NAFLD/NASH were randomized into 4 groups
(n=151 each): diet-exercise, atorvastatin, rosuvastatin, or pitavastatin for 1 year (i.e., until the next
routine evaluation).
Results:
From all the participants, 613 had NAFLD/NASH (prevalence 11.3 vs 39.8% in the general
population, p<0.001), and a total of 604 consented to participate in the study. After a year of
treatment, the diet-exercise group showed no significant changes in both scores (NAS 4.98 baseline
vs. 5.62, p=0.07; FIB-4 3.42 vs. 3.52, p=0.7). For the atorvastatin group, both scores were reduced
(NAS 4.97 vs 1.95, p<0.001, FIB-4 3.56 vs 0.83, p<0.001), for rosuvastatin (NAS 5.55 vs
1.81, p<0.001, FIB-4 3.61 vs 0.79, p<0.001), and for pitavastatin (NAS 4.89 vs 1.99, p<0.001,
FIB-4 3.78 vs 0.87, p<0.001).
Conclusions:
Atorvastatin, rosuvastatin, and pitavastatin have a beneficial and safe effect in
NAFLD/NASH patients as recorded by the improvement in the NAS (representing NAFLD activity)
and FIB-4 (representing liver fibrosis) scores. Since both those with and without NAFLD/-
NASH shared several baseline characteristics, genetics may play a role in the pathogenesis of
NAFLD/NASH and its treatment with statins.
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Affiliation(s)
- Georgios Sfikas
- 1st Department of Internal Medicine, 424 General Military Training Hospital, Thessaloniki, Greece
| | - Michael Psallas
- 1st Department of Internal Medicine, 424 General Military Training Hospital, Thessaloniki, Greece
| | - Charalambos Koumaras
- 1st Department of Internal Medicine, 424 General Military Training Hospital, Thessaloniki, Greece
| | - Konstantinos Imprialos
- 2nd Propedeutic Department of Internal Medicine, Hippocration Hospital, Aristotle University School of Medicine, Thessaloniki, Greece
| | - Evangelos Perdikakis
- Department of Ultrasonography, 424 General Military Training Hospital, Thessaloniki, Greece
| | - Michael Doumas
- 2nd Propedeutic Department of Internal Medicine, Hippocration Hospital, Aristotle University School of Medicine, Thessaloniki, Greece
| | - Olga Giouleme
- 2nd Propedeutic Department of Internal Medicine, Hippocration Hospital, Aristotle University School of Medicine, Thessaloniki, Greece
| | - Asterios Karagiannis
- 2nd Propedeutic Department of Internal Medicine, Hippocration Hospital, Aristotle University School of Medicine, Thessaloniki, Greece
| | - Vasilios G. Athyros
- 2nd Propedeutic Department of Internal Medicine, Hippocration Hospital, Aristotle University School of Medicine, Thessaloniki, Greece
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Roumeliotis S, Roumeliotis A, Gorny X, Mertens PR. Could Antioxidant Supplementation Delay Progression of Cardiovascular Disease in End-Stage Renal Disease Patients? Curr Vasc Pharmacol 2021; 19:41-54. [PMID: 32183680 DOI: 10.2174/1570161118666200317151553] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Revised: 02/19/2020] [Accepted: 02/20/2020] [Indexed: 12/27/2022]
Abstract
In end-stage renal disease patients, the leading causes of mortality are of cardiovascular (CV) origin. The underlying mechanisms are complex, given that sudden heart failure is more common than acute myocardial infarction. A contributing role of oxidative stress is postulated, which is increased even at early stages of chronic kidney disease, is gradually augmented in parallel to progression to endstage renal disease and is further accelerated by renal replacement therapy. Oxidative stress ensues when there is an imbalance between reactive pro-oxidants and physiologically occurring electron donating antioxidant defence systems. During the last decade, a close association of oxidative stress with accelerated atherosclerosis and increased risk for CV and all-cause mortality has been established. Lipid peroxidation has been identified as a trigger for endothelial dysfunction, the first step towards atherogenesis. In order to counteract the deleterious effects of free radicals and thereby ameliorate, or delay, CV disease, exogenous administration of antioxidants has been proposed. Here, we attempt to summarize existing data from studies that test antioxidants for CV protection, such as vitamins E and C, statins, omega-3 fatty acids and N-acetylcysteine.
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Affiliation(s)
- Stefanos Roumeliotis
- Division of Nephrology and Hypertension, 1st Department of Internal Medicine, AHEPA Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Athanasios Roumeliotis
- Division of Nephrology and Hypertension, 1st Department of Internal Medicine, AHEPA Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Xenia Gorny
- Clinic of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University Magdeburg, Leipziger Str. 40, 39120, Magdeburg, Germany
| | - Peter R Mertens
- Clinic of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University Magdeburg, Leipziger Str. 40, 39120, Magdeburg, Germany
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12
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Athyros VG. Multifactorial treatment of diabetic patients with cardiovascular disease to maximize results. J Diabetes Complications 2021; 35:107904. [PMID: 33839008 DOI: 10.1016/j.jdiacomp.2021.107904] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 02/19/2021] [Accepted: 02/19/2021] [Indexed: 11/16/2022]
Affiliation(s)
- Vasilios Gabriel Athyros
- Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki 55132, Greece.
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13
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Demiray A, Afsar B, Covic A, Kuwabara M, Ferro CJ, Lanaspa MA, Johnson RJ, Kanbay M. The Role of Uric Acid in the Acute Myocardial Infarction: A Narrative Review. Angiology 2021; 73:9-17. [PMID: 33902350 DOI: 10.1177/00033197211012546] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Increased serum uric acid (SUA) levels have been associated with various pathologic processes such as increased oxidative stress, inflammation, and endothelial dysfunction. Thus, it is not surprising that increased SUA is associated with various adverse outcomes including cardiovascular (CV) diseases. Recent epidemiological evidence suggests that increased SUA may be related to acute myocardial infarction (AMI). Accumulating data also showed that elevated UA has pathophysiological role in the development of AMI. However, there are also studies showing that SUA is not related to the risk of AMI. In this narrative review, we summarized the recent literature data regarding SUA and AMI after providing some background information for the association between UA and coronary artery disease. Future studies will show whether decreasing SUA levels is beneficial for outcomes related to AMI and the optimum SUA levels for best outcomes in CV diseases.
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Affiliation(s)
- Atalay Demiray
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Baris Afsar
- Division of Nephrology, Department of Internal Medicine, Suleyman Demirel University School of Medicine, Isparta, Turkey
| | - Adrian Covic
- Department of Nephrology, Grigore T. Popa' University of Medicine, Iasi, Romania
| | - Masanari Kuwabara
- Intensive Care Unit and Department of Cardiology, Toranomon Hospital, Tokyo, Japan
| | - Charles J Ferro
- Department of Renal Medicine, University Hospitals Birmingham, Edgbaston, Birmingham, the United Kingdom
| | - Miguel A Lanaspa
- Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Richard J Johnson
- Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Mehmet Kanbay
- Department of Medicine, Division of Nephrology, Koc University School of Medicine, Istanbul, Turkey
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14
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Kou F, Yang S, Wang S, Liu M, He Y. Association between serum uric acid and major chronic diseases among centenarians in China: based on the CHCCS study. BMC Geriatr 2021; 21:231. [PMID: 33827437 PMCID: PMC8028058 DOI: 10.1186/s12877-021-02185-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 03/30/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND This study aims to analyze the distribution of serum uric acid (SUA) level based on more than 1000 centenarians and to explore the association with three common diseases including hypertension, diabetes and dyslipidemia. METHODS All the 1002 centenarians from the CHCCS were included. Household survey was conducted. RESULTS The mean SUA level of centenarians was 329.04 ± 97.75 μmol/L and the prevalence of hyperuricemia in centenarians was 26.5%. There was no statistical difference in the distribution of SUA levels among centenarians with or without hypertension/diabetes. For dyslipidemia, there was an independent positive association. The risk of dyslipidemia among those with hyperuricemia was 1.646 (95%CI: 1.078-2.298) compared with those who didn't have hyperuricemia. By comparing different subtypes of dyslipidemia, hyperuricemia was positively associated with hypertriglyceridemia and low-density lipoprotein cholesterolemia, with the corresponding ORs of 2.553 (95%CI: 1.282-5.083) and 1.927 (95%CI: 1.273-2.917) respectively, while there was no statistically significant association with hypercholesterolemia 0.998 (95%CI: 0.574-1.732). CONCLUSIONS There was no relation between SUA with hypertension or diabetes, while there was independently and positively association with hypertriglyceridemia and low-density lipoprotein cholesterolemia. The health benefits of controlling SUA in centenarians still require evidence based on prospective studies.
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Affiliation(s)
- Fuyin Kou
- Health Service Department, Chinese PLA General Hospital, Beijing, China
| | - Shanshan Yang
- Department of Disease Prevention and Control, The 1st Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Shengshu Wang
- Beijing Key Laboratory of Aging and Geriatrics, National Clinical Research Center for Geriatrics Diseases, State Key Laboratory of Kidney Diseases, Institute of Geriatrics, Second Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Miao Liu
- Graduate School of Chinese PLA General Hospital, Institute of Geriatrics, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China.
| | - Yao He
- Beijing Key Laboratory of Aging and Geriatrics, National Clinical Research Center for Geriatrics Diseases, State Key Laboratory of Kidney Diseases, Institute of Geriatrics, Second Medical Center of Chinese PLA General Hospital, Beijing, China.
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15
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Takeuchi S, Takahashi Y, Asai S. Comparison of pleiotropic effects of statins vs fibrates on laboratory parameters in patients with dyslipidemia: A retrospective cohort study. Medicine (Baltimore) 2020; 99:e23427. [PMID: 33327270 PMCID: PMC7738156 DOI: 10.1097/md.0000000000023427] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Differences in the mechanism of action and potential pleiotropic effects between statins and fibrates would potentially drive a different effect on various laboratory parameters, but this remains controversial because of a paucity of reports comparing them. Therefore, the aim of this study was to compare the effects of statins and fibrates on laboratory parameters in Japanese patients in routine clinical practice.This retrospective cohort study included patients with dyslipidemia who had been newly treated with statin or fibrate monotherapy between January 2005 and December 2017. Patients were randomly matched into two sets of pairs by sex, age, and baseline triglyceride (TG) or low-density lipoprotein (LDL) cholesterol level. The 830 patients in TG-matched pairs (415 fibrate users and 415 matched statin users) and 1172 patients in LDL cholesterol-matched pairs (586 fibrate users and 586 matched statin users) were included in this study. Generalized estimating equations were used to estimate the effects of the drugs on serum creatinine level, estimated glomerular filtration rate (eGFR), urea nitrogen, hemoglobin A1c, aspartate aminotransferase, and alanine aminotransferase (ALT), in addition to LDL cholesterol and TG levels, and red blood cell (RBC) and platelet (PLT) counts, up to 12 months after the start of study drug administration.In TG-matched pairs, the increases in creatinine and urea nitrogen levels (P = .010 and P < .001, respectively) and the decreases in eGFR, ALT level and RBC count (P < .001, P = .003, and P = .014, respectively) were greater in fibrate users than in statin users. The decrease in PLT count was greater in statin users than in fibrate users (P < .001). The mean changes in aspartate aminotransferase and hemoglobin A1c levels were not significantly different between statin users and fibrate users. In LDL cholesterol-matched pairs, the differences in changes of all laboratory parameter levels between statin users and fibrate users were similar to those in TG-matched pairs.We demonstrate here that fibrates have a greater effect of increasing creatinine and urea nitrogen levels and of reducing eGFR, ALT level, and RBC count than statins, and that the lowering effect on PLT count is greater with statins than with fibrates.
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Affiliation(s)
- Satoshi Takeuchi
- Division of Pharmacology, Department of Biomedical Sciences, Nihon University School of Medicine
| | - Yasuo Takahashi
- Division of Genomic Epidemiology and Clinical Trials, Clinical Trials Research Center, Nihon University School of Medicine, 30-1 Oyaguchi-Kami Machi, Itabashi-ku, Tokyo, Japan
| | - Satoshi Asai
- Division of Pharmacology, Department of Biomedical Sciences, Nihon University School of Medicine
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16
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Cao JY, Waldman B, O'Connell R, Sullivan DR, Scott RS, Aryal N, Gebski V, Marschner I, Taskinen MR, Simes JR, McGill N, Jenkins AJ, Keech AC. Uric acid predicts long-term cardiovascular risk in type 2 diabetes but does not mediate the benefits of fenofibrate: The FIELD study. Diabetes Obes Metab 2020; 22:1388-1396. [PMID: 32243036 DOI: 10.1111/dom.14046] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 03/28/2020] [Accepted: 03/28/2020] [Indexed: 01/17/2023]
Abstract
AIM To explore the relationship between baseline uric acid (UA) levels and long-term cardiovascular events in adults with type 2 diabetes (T2D) and to determine whether the cardioprotective effects of fenofibrate are partly mediated through its UA-lowering effects. METHODS Data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial were utilized, comprising 9795 adults with T2D randomly allocated to treatment with fenofibrate or matching placebo. Plasma UA was measured before and after a 6-week, active fenofibrate run-in phase in all participants. Cox proportional hazards models were used to explore the relationships between baseline UA, pre-to-post run-in reductions in UA and long-term cardiovascular outcomes. RESULTS Mean baseline plasma UA was 0.33 mmol/L (SD 0.08). Baseline UA was a significant predictor of long-term cardiovascular events, with every 0.1 mmol/L higher UA conferring a 21% increase in event rate (HR 1.21, 95% CI 1.13-1.29, P < .001). This remained significant after adjustment for treatment allocation, cardiovascular risk factors and renal function. The extent of UA reduction during fenofibrate run-in was also a significant predictor of long-term cardiovascular events, with every 0.1 mmol/L greater reduction conferring a 14% lower long-term risk (HR 0.86, 95% CI 0.76-0.97, P = .015). This effect was not modified by treatment allocation (Pinteraction = .77). CONCLUSIONS UA is a strong independent predictor of long-term cardiovascular risk in adults with T2D. Although greater reduction in UA on fenofibrate is predictive of lower cardiovascular risk, this does not appear to mediate the cardioprotective effects of fenofibrate.
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Affiliation(s)
- Jacob Y Cao
- National Health and Medical Research Council Clinical Trials Centre, Sydney, New South Wales, Australia
- Sydney Medical School, Sydney, New South Wales, Australia
| | - Boris Waldman
- National Health and Medical Research Council Clinical Trials Centre, Sydney, New South Wales, Australia
- Sydney Medical School, Sydney, New South Wales, Australia
| | - Rachel O'Connell
- National Health and Medical Research Council Clinical Trials Centre, Sydney, New South Wales, Australia
| | - David R Sullivan
- National Health and Medical Research Council Clinical Trials Centre, Sydney, New South Wales, Australia
- Sydney Medical School, Sydney, New South Wales, Australia
| | - Russell S Scott
- Lipid & Diabetes Research Group, Christchurch Hospital, Christchurch, New Zealand
| | - Nanda Aryal
- National Health and Medical Research Council Clinical Trials Centre, Sydney, New South Wales, Australia
| | - Val Gebski
- National Health and Medical Research Council Clinical Trials Centre, Sydney, New South Wales, Australia
| | - Ian Marschner
- National Health and Medical Research Council Clinical Trials Centre, Sydney, New South Wales, Australia
| | - Marja-Riitta Taskinen
- Heart and Lung Centre, Cardiovascular Research Unit, Helsinki University Central Hospital, Helsinki, Finland
| | - John R Simes
- National Health and Medical Research Council Clinical Trials Centre, Sydney, New South Wales, Australia
- Sydney Medical School, Sydney, New South Wales, Australia
| | - Neil McGill
- National Health and Medical Research Council Clinical Trials Centre, Sydney, New South Wales, Australia
- Sydney Medical School, Sydney, New South Wales, Australia
| | - Alicia J Jenkins
- National Health and Medical Research Council Clinical Trials Centre, Sydney, New South Wales, Australia
- Sydney Medical School, Sydney, New South Wales, Australia
| | - Anthony C Keech
- National Health and Medical Research Council Clinical Trials Centre, Sydney, New South Wales, Australia
- Sydney Medical School, Sydney, New South Wales, Australia
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17
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Li L, Zhu JX, Hou XH, Ma YH, Xu W, Tan CC, Sun FR, Li HQ, Dong Q, Tan L, Yu JT. Serum Uric Acid Levels and Risk of Intracranial Atherosclerotic Stenosis: A Cross-Sectional Study. Neurotox Res 2020; 37:936-943. [PMID: 32034694 DOI: 10.1007/s12640-020-00171-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Revised: 01/20/2020] [Accepted: 01/22/2020] [Indexed: 01/07/2023]
Abstract
Elevated serum uric acid (SUA) has been reported to be associated with an increased risk of cardiovascular diseases, but the role of SUA in intracranial atherosclerosis remains unclear. To investigate the association between SUA and intracranial atherosclerotic stenosis (ICAS), we evaluated 1522 subjects (305 with ICAS, 1217 without ICAS) with magnetic resonance angiography (MRA). Subjects were classified into ten groups according to the deciles of the SUA level. The rate of ICAS reached a minimum in the seventh decile (6.0-6.3 mg/dL; reference group). After adjusting for confounding factors, multivariate logistic regression analysis demonstrated that both low SUA level (≤ 3.8 mg/dL; OR, 2.34; 95% CI, 1.29-4.39; p = 0.006) and high SUA level (≥ 7.8 mg/dL; OR, 2.10; 95% CI, 1.15-3.92; p = 0.017) conferred greater risk for ICAS. In multivariable analysis with a quadratic model which used SUA as a continuous variable, a U-shaped association between SUA and the rate of ICAS was confirmed (α > 0; p < 0.001). The estimated SUA level associated with the lowest rate of ICAS was 6.2 mg/dL. In conclusion, our findings suggest a U-shaped association between ICAS and SUA.
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Affiliation(s)
- Lin Li
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266071, China
| | - Jun-Xia Zhu
- Department of Prevention and Health Protection, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xiao-He Hou
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266071, China
| | - Ya-Hui Ma
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266071, China
| | - Wei Xu
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266071, China
| | - Chen-Chen Tan
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266071, China
| | - Fu-Rong Sun
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266071, China
| | - Hong-Qi Li
- Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, 12th Wulumuqi Zhong Road, Shanghai, 200040, China
| | - Qiang Dong
- Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, 12th Wulumuqi Zhong Road, Shanghai, 200040, China.
| | - Lan Tan
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266071, China.
| | - Jin-Tai Yu
- Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, 12th Wulumuqi Zhong Road, Shanghai, 200040, China.
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18
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Taylor KS, Mclellan J, Verbakel JY, Aronson JK, Lasserson DS, Pidduck N, Roberts N, Fleming S, O'Callaghan CA, Bankhead CR, Banerjee A, Hobbs FR, Perera R. Effects of antihypertensives, lipid-modifying drugs, glycaemic control drugs and sodium bicarbonate on the progression of stages 3 and 4 chronic kidney disease in adults: a systematic review and meta-analysis. BMJ Open 2019; 9:e030596. [PMID: 31542753 PMCID: PMC6756484 DOI: 10.1136/bmjopen-2019-030596] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVE To evaluate the effects of drug interventions that may modify the progression of chronic kidney disease (CKD) in adults with CKD stages 3 and 4. DESIGN Systematic review and meta-analysis. METHODS Searching MEDLINE, EMBASE, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, International Clinical Trials Registry Platform, Health Technology Assessment, Science Citation Index, Social Sciences Citation Index, Conference Proceedings Citation Index and Clinical Trials Register, from March 1999 to July 2018, we identified randomised controlled trials (RCTs) of drugs for hypertension, lipid modification, glycaemic control and sodium bicarbonate, compared with placebo, no drug or a drug from another class, in ≥40 adults with CKD stages 3 and/or 4, with at least 2 years of follow-up and reporting renal function (primary outcome), proteinuria, adverse events, maintenance dialysis, transplantation, cardiovascular events, cardiovascular mortality or all-cause mortality. Two reviewers independently screened citations and extracted data. For continuous outcomes, we used the ratio of means (ROM) at the end of the trial in random-effects meta-analyses. We assessed methodological quality with the Cochrane Risk of Bias Tool and confidence in the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. RESULTS We included 35 RCTs and over 51 000 patients. Data were limited, and heterogeneity varied. Final renal function (estimated glomerular filtration rate) was 6% higher in those taking glycaemic control drugs (ROM 1.06, 95% CI 1.02 to 1.10, I2=0%, low GRADE confidence) and 4% higher in those taking lipid-modifying drugs (ROM 1.04, 95% CI 1.00 to 1.08, I2=88%, very low GRADE confidence). For RCTs of antihypertensive drugs, there were no significant differences in renal function. Treatment with lipid-modifying drugs led to a 36% reduction in cardiovascular disease and 26% reduction in all-cause mortality. CONCLUSIONS Glycaemic control and lipid-modifying drugs may slow the progression of CKD, but we found no pooled evidence of benefit nor harm from antihypertensive drugs. However, given the data limitations, further research is needed to confirm these findings. PROSPERO REGISTRATION NUMBER CRD42015017501.
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Affiliation(s)
- Kathryn S Taylor
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Julie Mclellan
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Jan Y Verbakel
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
- Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium
| | - Jeffrey K Aronson
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Daniel S Lasserson
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Nicola Pidduck
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Nia Roberts
- Bodleian Health Care Libraries, University of Oxford, Oxford, UK
| | - Susannah Fleming
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | | | - Clare R Bankhead
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Amitava Banerjee
- Farr Institute of Health Informatics Research, University College London, London, UK
| | - Fd Richard Hobbs
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Rafael Perera
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
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19
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Yim K, Bindayi A, McKay R, Mehrazin R, Raheem OA, Field C, Bloch A, Wake R, Ryan S, Patterson A, Derweesh IH. Rising Serum Uric Acid Level Is Negatively Associated with Survival in Renal Cell Carcinoma. Cancers (Basel) 2019; 11:cancers11040536. [PMID: 30991671 PMCID: PMC6520981 DOI: 10.3390/cancers11040536] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 04/11/2019] [Accepted: 04/11/2019] [Indexed: 12/31/2022] Open
Abstract
Aim and Background: To investigate the association of serum uric acid (SUA) levels along with statin use in Renal Cell Carcinoma (RCC), as statins may be associated with improved outcomes in RCC and SUA elevation is associated with increased risk of chronic kidney disease (CKD). Methods: Retrospective study of patients undergoing surgery for RCC with preoperative/postoperative SUA levels between 8/2005–8/2018. Analysis was carried out between patients with increased postoperative SUA vs. patients with decreased/stable postoperative SUA. Kaplan-Meier analysis (KMA) calculated overall survival (OS) and recurrence free survival (RFS). Multivariable analysis (MVA) was performed to identify factors associated with increased SUA levels and all-cause mortality. The prognostic significance of variables for OS and RFS was analyzed by cox regression analysis. Results: Decreased/stable SUA levels were noted in 675 (74.6%) and increased SUA levels were noted in 230 (25.4%). A higher proportion of patients with decreased/stable SUA levels took statins (27.9% vs. 18.3%, p = 0.0039). KMA demonstrated improved 5- and 10-year OS (89% vs. 47% and 65% vs. 9%, p < 0.001) and RFS (94% vs. 45% and 93% vs. 34%, p < 0.001), favoring patients with decreased/stable SUA levels. MVA revealed that statin use (Odds ratio (OR) 0.106, p < 0.001), dyslipidemia (OR 2.661, p = 0.004), stage III and IV disease compared to stage I (OR 1.887, p = 0.015 and 10.779, p < 0.001, respectively), and postoperative de novo CKD stage III (OR 5.952, p < 0.001) were predictors for increased postoperative SUA levels. MVA for all-cause mortality showed that increasing BMI (OR 1.085, p = 0.002), increasing ASA score (OR 1.578, p = 0.014), increased SUA levels (OR 4.698, p < 0.001), stage IV disease compared to stage I (OR 7.702, p < 0.001), radical nephrectomy (RN) compared to partial nephrectomy (PN) (OR 1.620, p = 0.019), and de novo CKD stage III (OR 7.068, p < 0.001) were significant factors. Cox proportional hazard analysis for OS revealed that increasing age (HR 1.017, p = 0.004), increasing BMI (Hazard Ratio (HR) 1.099, p < 0.001), increasing SUA (HR 4.708, p < 0.001), stage III and IV compared to stage I (HR 1.537, p = 0.013 and 3.299, p < 0.001), RN vs. PN (HR 1.497, p = 0.029), and de novo CKD stage III (HR 1.684, p < 0.001) were significant factors. Cox proportional hazard analysis for RFS demonstrated that increasing ASA score (HR 1.239, p < 0.001, increasing SUA (HR 9.782, p < 0.001), and stage II, III, and IV disease compared to stage I (HR 2.497, p < 0.001 and 3.195, p < 0.001 and 6.911, p < 0.001) were significant factors. Conclusions: Increasing SUA was associated with poorer outcomes. Decreased SUA levels were associated with statin intake and lower stage disease as well as lack of progression to CKD and anemia. Further investigation is requisite.
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Affiliation(s)
- Kendrick Yim
- Department of Urology, University of California at San Diego, La Jolla, CA, 92093, USA.
| | - Ahmet Bindayi
- Department of Urology, University of California at San Diego, La Jolla, CA, 92093, USA.
| | - Rana McKay
- Department of Urology, University of California at San Diego, La Jolla, CA, 92093, USA.
| | - Reza Mehrazin
- Department of Urology, University of Tennessee Health Sciences Center, Memphis, TN 38163, USA.
| | - Omer A Raheem
- Department of Urology, University of California at San Diego, La Jolla, CA, 92093, USA.
| | - Charles Field
- Department of Urology, University of California at San Diego, La Jolla, CA, 92093, USA.
| | - Aaron Bloch
- Department of Urology, University of California at San Diego, La Jolla, CA, 92093, USA.
| | - Robert Wake
- Department of Urology, University of Tennessee Health Sciences Center, Memphis, TN 38163, USA.
| | - Stephen Ryan
- Department of Urology, University of California at San Diego, La Jolla, CA, 92093, USA.
| | - Anthony Patterson
- Department of Urology, University of Tennessee Health Sciences Center, Memphis, TN 38163, USA.
| | - Ithaar H Derweesh
- Department of Urology, University of California at San Diego, La Jolla, CA, 92093, USA.
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20
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Calza L, Colangeli V, Borderi M, Manfredi R, Marconi L, Bon I, Re MC, Viale P. Rosuvastatin and atorvastatin preserve renal function in HIV-1-infected patients with chronic kidney disease and hyperlipidaemia. HIV CLINICAL TRIALS 2019; 19:120-128. [PMID: 29770749 DOI: 10.1080/15284336.2018.1468676] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
BACKGROUND Hyperlipidaemia is a risk factor for the progression of chronic kidney disease (CKD), which is a frequent comorbidity in patients with HIV-1 infection, but the renal effects of statins remain unclear. METHODS We performed an observational, prospective study of HIV-infected patients on suppressive antiretroviral therapy, with CKD and hyperlipidaemia, and starting a lipid-lowering treatment with rosuvastatin, atorvastatin or omega-3 fatty acids. CKD was defined as an estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m2 for >3 months. RESULTS As a whole, 69 patients (53 men, 58 Caucasian, median age 56.2 years) were enrolled. Overall, 25 patients started rosuvastatin (10 mg daily, group A), 23 patients atorvastatin (20 mg daily, group B), and 21 started omega-3 fatty acids (3 g daily, group C). At baseline, median eGFR was 54.4 mL/min/1.73 m2, and the eGFR ranged between 50 and 60 mL/min/1.73 m2 in 87% of patients. After 12 months, the median eGFR decline was significantly lower in group A (-0.84 mL/min/1.73 m2) and in group B (-0.91 mL/min/1.73 m2) in comparison with the group C (-1.53 mL/min/1.73 m2; p < 0.001 for both comparisons). The median decrease in prevalence of proteinuria and high-sensitivity C-reactive protein was also significantly greater in groups A and B than in group C, while the incidence of treatment discontinuations was comparable across the three groups. CONCLUSION In our study, rosuvastatin and atorvastatin showed a significant protective effect on the renal function compared to omega-3 fatty acids in HIV-1-infected patients with CKD and dyslipidaemia.
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Affiliation(s)
- Leonardo Calza
- a Department of Medical and Surgical Sciences, Clinic of Infectious Diseases , "Alma Mater Studiorum" University of Bologna, S. Orsola-Malpighi Hospital , Bologna , Italy
| | - Vincenzo Colangeli
- a Department of Medical and Surgical Sciences, Clinic of Infectious Diseases , "Alma Mater Studiorum" University of Bologna, S. Orsola-Malpighi Hospital , Bologna , Italy
| | - Marco Borderi
- a Department of Medical and Surgical Sciences, Clinic of Infectious Diseases , "Alma Mater Studiorum" University of Bologna, S. Orsola-Malpighi Hospital , Bologna , Italy
| | - Roberto Manfredi
- a Department of Medical and Surgical Sciences, Clinic of Infectious Diseases , "Alma Mater Studiorum" University of Bologna, S. Orsola-Malpighi Hospital , Bologna , Italy
| | - Lorenzo Marconi
- a Department of Medical and Surgical Sciences, Clinic of Infectious Diseases , "Alma Mater Studiorum" University of Bologna, S. Orsola-Malpighi Hospital , Bologna , Italy
| | - Isabella Bon
- b Unit of Microbiology , "Alma Mater Studiorum" University of Bologna, S. Orsola-Malpighi Hospital , Bologna , Italy
| | - Maria Carla Re
- b Unit of Microbiology , "Alma Mater Studiorum" University of Bologna, S. Orsola-Malpighi Hospital , Bologna , Italy
| | - Pierluigi Viale
- a Department of Medical and Surgical Sciences, Clinic of Infectious Diseases , "Alma Mater Studiorum" University of Bologna, S. Orsola-Malpighi Hospital , Bologna , Italy
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Zhang C, Jiang L, Xu L, Tian J, Liu J, Zhao X, Feng X, Wang D, Zhang Y, Sun K, Xu B, Zhao W, Hui R, Gao R, Song L, Yuan J. Implications of Hyperuricemia in Severe Coronary Artery Disease. Am J Cardiol 2019; 123:558-564. [PMID: 30527777 DOI: 10.1016/j.amjcard.2018.11.027] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Revised: 11/11/2018] [Accepted: 11/15/2018] [Indexed: 12/19/2022]
Abstract
Hyperuricemia has been associated with mortality in patients with coronary artery disease (CAD). However, its prognostic value remains unknown in the context of severe CAD with heavy atherosclerotic burden in all 3 vessels. We used data from a large cohort of consecutive patients with severe CAD. The primary end point was all-cause death. Propensity score matching was used to identify 2 cohorts of patients with similar baseline characteristics. A total of 8,529 patients with available serum uric acid data were included in the study. Hyperuricemia was present in 1,207 (14.2%) patients. At baseline, hyperuricemic patients had more co-morbidities, and more often received medical therapy alone. During the median follow-up of 7.5 years, significantly more deaths occurred in hyperuricemic patients compared with normouricemic patients (22.5% vs 13.7%; p < 0.001). Multivariable analyses showed that hyperuricemia was associated with an increased risk of mortality (hazard ratio 1.33; 95% confidence interval 1.15 to 1.53; p < 0.001). Propensity score matching yielded similar results (hazard ratio 1.33; 95% confidence interval 1.11 to 1.61; p = 0.003). The association was relatively consistent across subgroups, except for an interaction between age and hyperuricemia. Addition of uric acid to SYNTAX score II provided significant improvements of reclassification and discrimination for mortality prediction. In conclusion, hyperuricemia is relatively common among patients with severe CAD and is independently associated with mortality. Moreover, uric acid can improve the predictability of a well-established risk score.
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Venishetty S, Bhat R, Rajagopal KV. Serum Uric Acid Levels in Type 2 Diabetes Mellitus: Is There a Linear Relationship with Severity of Carotid Atherosclerosis? Indian J Endocrinol Metab 2018; 22:678-682. [PMID: 30294580 PMCID: PMC6166567 DOI: 10.4103/ijem.ijem_641_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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
AIMS The aim of this study was to correlate serum uric acid (SUA) levels and carotid intima-media thickness (CIMT) in patients with type 2 diabetes mellitus (DM). SETTINGS AND DESIGN This study was a cross-sectional observational study on 103 diabetic patients conducted from September 2015 to May 2017. SUBJECTS AND METHODS We screened 103 patients with type 2 DM between the ages of 30-65 years. SUA levels and the CIMT were measured. The patients were divided into quartiles based on uric acid level. The CIMT of the quartiles is compared and analyzed. STATISTICAL ANALYSIS USED Chi-squared test, Analysis of Variance, and Pearson's correlation. RESULTS Uric acid levels were positively associated with CIMT (P = 0.001). The association remained significant after further adjustment for potential confounders. Strong correlation was found among them as depicted by correlation coefficient (r = 0.779). CONCLUSIONS Carotid atherosclerosis as measured by IMT is associated with SUA levels in patients with type 2 DM.
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Affiliation(s)
| | - Rama Bhat
- Department of Medicine, Kasturba Hospital, Manipal, Karnataka, India
| | - K. V. Rajagopal
- Department of Radiodiagnosis, Kasturba Hospital, Manipal, Karnataka, India
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Katsiki N, Giannoukas AD, Athyros VG, Mikhailidis DP. Lipid-lowering treatment in peripheral artery disease. Curr Opin Pharmacol 2018; 39:19-26. [PMID: 29413998 DOI: 10.1016/j.coph.2018.01.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2017] [Revised: 01/14/2018] [Accepted: 01/19/2018] [Indexed: 12/19/2022]
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Xu Q, Zhang M, Abeysekera IR, Wang X. High serum uric acid levels may increase mortality and major adverse cardiovascular events in patients with acute myocardial infarction. Saudi Med J 2018; 38:577-585. [PMID: 28578435 PMCID: PMC5541179 DOI: 10.15537/smj.2017.6.17190] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Objectives: To determine the validity of uric acid as a potential prognostic marker for long-term outcomes of patients with acute myocardial infarction (AMI) and those with AMI undergoing percutaneous coronary intervention (PCI). Methods: Systematic review and meta-analysis were performed. We retrieved data from retrospective and prospective cohort studies that investigated whether serum uric acid (SUA) level affects the prognosis of patients with AMI. Results: Thirteen studies involving 9371 patients were included. High serum uric acid (HSUA) level increased mid/long-term mortality (risk ratio (RR)=2.32, 95% confidence intervals (CI): 2.00–2.70) and had higher short-term mortality (RR=3.09, 95% CI: 2.58–3.71), higher mid/long-term major adverse cardiovascular events (MACE) risk (RR=1.70, 95% CI: 1.54–1.88), and higher short-term MACE risk (RR=2.47, 95% CI: 2.08–2.92) for patients with AMI. In the PCI subgroup, the HSUA level also increased mid/long-term mortality (RR=2.33, 95% CI: 1.89 to 2.87) and had higher mid/long-term MACE risk (RR=1.64, 95% CI: 1.48–1.82), and higher short-term MACE risk (RR 2.43, 95% CI: 2.02–2.93) for patients who were treated with PCI after AMI. Particularly in the PCI subgroup, a higher short-term mortality (RR=6.70, 95% CI: 3.14–14.31) was presented in the group with lower HSUA cut-off level, and the mortality was higher than the group with higher HSUA cut-off level (RR=2.69, 95% CI: 2.09–3.46). Conclusion: The HSUA level significantly increased the mortality and MACE risk of patients with AMI. Mild elevation of SUA levels (normal range) have started to have a significant impact on the short-term mortality of patients who underwent PCI, and has not received the attention of previous studies. However, this condition should be further investigated.
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Affiliation(s)
- Qiyao Xu
- Cardiology Center, the Affiliated Hospital of Logistics University of PAP, Tianjin,China. E-mail.
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Al Zarzour RH, Ahmad M, Asmawi MZ, Kaur G, Saeed MAA, Al-Mansoub MA, Saghir SAM, Usman NS, Al-Dulaimi DW, Yam MF. Phyllanthus Niruri Standardized Extract Alleviates the Progression of Non-Alcoholic Fatty Liver Disease and Decreases Atherosclerotic Risk in Sprague-Dawley Rats. Nutrients 2017; 9:E766. [PMID: 28718838 PMCID: PMC5537880 DOI: 10.3390/nu9070766] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2017] [Revised: 06/19/2017] [Accepted: 07/12/2017] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the major global health issues, strongly correlated with insulin resistance, obesity and oxidative stress. The current study aimed to evaluate anti-NAFLD effects of three different extracts of Phyllanthus niruri (P. niruri). NAFLD was induced in male Sprague-Dawley rats using a special high-fat diet (HFD). A 50% methanolic extract (50% ME) exhibited the highest inhibitory effect against NAFLD progression. It significantly reduced hepatomegaly (16%) and visceral fat weight (22%), decreased NAFLD score, prevented fibrosis, and reduced serum total cholesterol (TC) (48%), low-density lipoprotein (LDL) (65%), free fatty acids (FFAs) (25%), alanine aminotransferase (ALT) (45%), alkaline phosphatase (ALP) (38%), insulin concentration (67%), homeostatic model assessment of insulin resistance (HOMA-IR) (73%), serum atherogenic ratios TC/high-density lipoprotein (HDL) (29%), LDL/HDL (66%) and (TC-HDL)/HDL (64%), hepatic content of cholesterol (43%), triglyceride (29%) and malondialdehyde (MDA) (40%) compared to a non-treated HFD group. In vitro, 50% ME of P. niruri inhibited α-glucosidase, pancreatic lipase enzymes and cholesterol micellization. It also had higher total phenolic and total flavonoid contents compared to other extracts. Ellagic acid and phyllanthin were identified as major compounds. These results suggest that P. niruri could be further developed as a novel natural hepatoprotective agent against NAFLD and atherosclerosis.
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Affiliation(s)
- Raghdaa Hamdan Al Zarzour
- Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia.
| | - Mariam Ahmad
- Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia.
| | - Mohd Zaini Asmawi
- Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia.
| | - Gurjeet Kaur
- Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Penang 11800, Malaysia.
| | - Mohammed Ali Ahmed Saeed
- Discipline of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia.
| | - Majed Ahmed Al-Mansoub
- Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia.
| | - Sultan Ayesh Mohammed Saghir
- Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia.
| | - Nasiba Salisu Usman
- Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia.
| | - Dhamraa W Al-Dulaimi
- Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia.
| | - Mun Fei Yam
- Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia.
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Kimura G, Kasahara M, Ueshima K, Tanaka S, Yasuno S, Fujimoto A, Sato T, Imamoto M, Kosugi S, Nakao K. Effects of atorvastatin on renal function in patients with dyslipidemia and chronic kidney disease: assessment of clinical usefulness in CKD patients with atorvastatin (ASUCA) trial. Clin Exp Nephrol 2017; 21:417-424. [PMID: 27392909 PMCID: PMC5486454 DOI: 10.1007/s10157-016-1304-6] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2016] [Accepted: 06/27/2016] [Indexed: 11/28/2022]
Abstract
BACKGROUND Dyslipidemia is a risk factor for the progression of chronic kidney disease (CKD). While conventional lipid lowering therapy provides a benefit to CKD management, the effect of statins on eGFR remains unclear. METHODS A prospective, multi-center, open-labeled, randomized trial. Total of 349 CKD patients with hyperlipidemia were randomized into 2 groups, and followed for 2 years. Group A included patients who were treated with atorvastatin. Group C were treated with conventional lipid lowering drugs other than statin. Primary endpoint was changes in eGFR. Secondary endpoints included changes in urinary albumin excretion, serum LDL-C, serum triglyceride, cardio-vascular events and all-cause mortality. RESULTS As the primary endpoint, eGFR decreased by 2.3 ml/min/1.73 m2 in Group A and by 2.6 ml/min/1.73 m2 in Group C, indicating that there was no difference in change of eGFR between the two groups. As secondary endpoints, atorvastatin succeeded to reduce serum LDL-C level significantly and rapidly, but conventional therapy did not. In fact, mean LDL-C level did not reach the target level of 100 mg/dl in Group C. Serum triglyceride was lowered only by atorvastatin, but not conventional drugs. The number of cardiovascular events and all-cause mortality did not differ between in two groups. CONCLUSION The ASUCA (Assessment of Clinical Usefulness in CKD Patients with Atorvastatin) trial demonstrated that atorvastatin failed to exhibit reno-protections compared to conventional therapy in Japanese patients with dyslipidemia and CKD. It would be due in part to the ability of atorvastatin to more potently reduce serum LDL and triglycerides compared to conventional therapy.
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Affiliation(s)
| | - Masato Kasahara
- Department of EBM Research, Institute of Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan.
- Institute for Clinical and Translational Science, Nara Medical University Hospital, 840 Shijo-cho, Kashihara, Nara, Japan.
| | - Kenji Ueshima
- Department of EBM Research, Institute of Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan
| | - Sachiko Tanaka
- Department of EBM Research, Institute of Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan
| | - Shinji Yasuno
- Department of EBM Research, Institute of Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan
| | - Akira Fujimoto
- Department of EBM Research, Institute of Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan
| | - Toshiya Sato
- Department of Biostatistics, Kyoto University School of Public Health, Kyoto, Japan
| | - Miyuki Imamoto
- Department of Food and Nutritional Science, Kobe Women's Junior College, Kobe, Japan
| | - Shinji Kosugi
- Department of Medical Ethics/Medical Genetics, Kyoto University School of Public Health, Kyoto, Japan
| | - Kazuwa Nakao
- Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan
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Shen X, Zhang Z, Zhang X, Zhao J, Zhou X, Xu Q, Shang H, Dong J, Liao L. Efficacy of statins in patients with diabetic nephropathy: a meta-analysis of randomized controlled trials. Lipids Health Dis 2016; 15:179. [PMID: 27733168 PMCID: PMC5062823 DOI: 10.1186/s12944-016-0350-0] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2016] [Accepted: 10/07/2016] [Indexed: 01/13/2023] Open
Abstract
Background The effects of statins in patients with diabetic nephropathy are controversial. With increasing interest in the potential therapeutic role of statins in diabetic nephropathy, it is essential to evaluate its real effects. Methods PubMed, EMBASE, Web of Science databases, Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure were systematically searched for randomized controlled trials (RCTs) of statins in patients with diabetic nephropathy. Results Fourteen trials with 2866 participants were included in our meta-analysis. Compared with placebo, albuminuria and urinary albumin excretion rates in the statin group were reduced by 0.46 [95 % confidence interval (CI),−0.68 to −0.25, P < 0.0001] and 1.68 (95 % CI, −3.23 to −0.12, P = 0.03), respectively. The reduction of albuminuria was greater in patients of type 2 diabetes mellitus with diabetic nephropathy [standardized mean difference (SMD), −0.56; 95 % CI, −0.80 to −0.32, P < 0.00001] and the decrease was significant during the 1 to 3 years period of statin therapy (SMD, −0.57; 95 % CI, −0.95 to −0.19, P = 0.003). Subgroup analysis demonstrated the effects of statins were much stronger in subjects with pathologic albuminuria: change of −0.71 (95 % CI, −1.09 to −0.33, P = 0.0003) for those with urinary protein excretion 30 to 300 mg/day, −0.37 (95 % CI, −0.67 to −0.06, P = 0.02) for those with excretion more than 300 mg/day and −0.29 (95 % CI, −0.78 to 0.21, P = 0.26) for those with excretion less than 30 mg/day. In contrast, statins did not significantly reduce estimated glomerular filtration rate, serum creatinine and blood urea nitrogen levels. Conclusions Statins decrease the albuminuria and urinary albumin excretion rates significantly. The efficacy of statins on renal function is time dependent and better in type 2 diabetic patients with nephropathy.
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Affiliation(s)
- Xue Shen
- Department of Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Zhongwen Zhang
- Department of Medicine, Division of Endocrinology, Shandong Provincial Qianfoshan Hospital, Shandong University, No.16766, Jingshi Road, Lixia District, Jinan, 250014, Shandong Province, China
| | - Xiaoqian Zhang
- Department of Medicine, Division of Endocrinology, Shandong Provincial Qianfoshan Hospital, Shandong University, No.16766, Jingshi Road, Lixia District, Jinan, 250014, Shandong Province, China
| | - Junyu Zhao
- Department of Medicine, Division of Endocrinology, Shandong Provincial Qianfoshan Hospital, Shandong University, No.16766, Jingshi Road, Lixia District, Jinan, 250014, Shandong Province, China
| | - Xiaojun Zhou
- Department of Medicine, Division of Endocrinology, Shandong Provincial Qianfoshan Hospital, Shandong University, No.16766, Jingshi Road, Lixia District, Jinan, 250014, Shandong Province, China
| | - Qinglei Xu
- Department of Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Hongxia Shang
- Department of Medicine, Division of Endocrinology, Shandong Provincial Qianfoshan Hospital, Shandong University, No.16766, Jingshi Road, Lixia District, Jinan, 250014, Shandong Province, China
| | - Jianjun Dong
- Department of Medicine, Division of Endocrinology, Qilu Hospital of Shandong University, Jinan, 250012, China
| | - Lin Liao
- Department of Medicine, Division of Endocrinology, Shandong Provincial Qianfoshan Hospital, Shandong University, No.16766, Jingshi Road, Lixia District, Jinan, 250014, Shandong Province, China.
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Herrington W, Emberson J, Mihaylova B, Blackwell L, Reith C, Solbu M, Mark P, Fellström B, Jardine A, Wanner C, Holdaas H, Fulcher J, Haynes R, Landray M, Keech A, Simes J, Collins R, Baigent C. Impact of renal function on the effects of LDL cholesterol lowering with statin-based regimens: a meta-analysis of individual participant data from 28 randomised trials. Lancet Diabetes Endocrinol 2016; 4:829-39. [PMID: 27477773 DOI: 10.1016/s2213-8587(16)30156-5] [Citation(s) in RCA: 208] [Impact Index Per Article: 23.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2016] [Revised: 06/23/2016] [Accepted: 06/23/2016] [Indexed: 12/30/2022]
Abstract
BACKGROUND Statin therapy is effective for the prevention of coronary heart disease and stroke in patients with mild-to-moderate chronic kidney disease, but its effects in individuals with more advanced disease, particularly those undergoing dialysis, are uncertain. METHODS We did a meta-analysis of individual participant data from 28 trials (n=183 419), examining effects of statin-based therapy on major vascular events (major coronary event [non-fatal myocardial infarction or coronary death], stroke, or coronary revascularisation) and cause-specific mortality. Participants were subdivided into categories of estimated glomerular filtration rate (eGFR) at baseline. Treatment effects were estimated with rate ratio (RR) per mmol/L reduction in LDL cholesterol. FINDINGS Overall, statin-based therapy reduced the risk of a first major vascular event by 21% (RR 0·79, 95% CI 0·77-0·81; p<0·0001) per mmol/L reduction in LDL cholesterol. Smaller relative effects on major vascular events were observed as eGFR declined (p=0·008 for trend; RR 0·78, 99% CI 0·75-0·82 for eGFR ≥60 mL/min per 1·73 m(2); 0·76, 0·70-0·81 for eGFR 45 to <60 mL/min per 1·73 m(2); 0·85, 0·75-0·96 for eGFR 30 to <45 mL/min per 1·73 m(2); 0·85, 0·71-1·02 for eGFR <30 mL/min per 1·73 m(2) and not on dialysis; and 0·94, 0·79-1·11 for patients on dialysis). Analogous trends by baseline renal function were seen for major coronary events (p=0·01 for trend) and vascular mortality (p=0·03 for trend), but there was no significant trend for coronary revascularisation (p=0·90). Reducing LDL cholesterol with statin-based therapy had no effect on non-vascular mortality, irrespective of eGFR. INTERPRETATION Even after allowing for the smaller reductions in LDL cholesterol achieved by patients with more advanced chronic kidney disease, and for differences in outcome definitions between dialysis trials, the relative reductions in major vascular events observed with statin-based treatment became smaller as eGFR declined, with little evidence of benefit in patients on dialysis. In patients with chronic kidney disease, statin-based regimens should be chosen to maximise the absolute reduction in LDL cholesterol to achieve the largest treatment benefits. FUNDING UK Medical Research Council, British Heart Foundation, Cancer Research UK, European Community Biomed Programme, Australian National Health and Medical Research Council, Australian National Heart Foundation.
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Renoprotective Effects of Atorvastatin in Diabetic Mice: Downregulation of RhoA and Upregulation of Akt/GSK3. PLoS One 2016; 11:e0162731. [PMID: 27649495 PMCID: PMC5029810 DOI: 10.1371/journal.pone.0162731] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2016] [Accepted: 08/26/2016] [Indexed: 12/25/2022] Open
Abstract
Potential benefits of statins in the treatment of chronic kidney disease beyond lipid-lowering effects have been described. However, molecular mechanisms involved in renoprotective actions of statins have not been fully elucidated. We questioned whether statins influence development of diabetic nephropathy through reactive oxygen species, RhoA and Akt/GSK3 pathway, known to be important in renal pathology. Diabetic mice (db/db) and their control counterparts (db/+) were treated with atorvastatin (10 mg/Kg/day, p.o., for 2 weeks). Diabetes-associated renal injury was characterized by albuminuria (albumin:creatinine ratio, db/+: 3.2 ± 0.6 vs. db/db: 12.5 ± 3.1*; *P<0.05), increased glomerular/mesangial surface area, and kidney hypertrophy. Renal injury was attenuated in atorvastatin-treated db/db mice. Increased ROS generation in the renal cortex of db/db mice was also inhibited by atorvastatin. ERK1/2 phosphorylation was increased in the renal cortex of db/db mice. Increased renal expression of Nox4 and proliferating cell nuclear antigen, observed in db/db mice, were abrogated by statin treatment. Atorvastatin also upregulated Akt/GSK3β phosphorylation in the renal cortex of db/db mice. Our findings suggest that atorvastatin attenuates diabetes-associated renal injury by reducing ROS generation, RhoA activity and normalizing Akt/GSK3β signaling pathways. The present study provides some new insights into molecular mechanisms whereby statins may protect against renal injury in diabetes.
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Jamshed H, Gilani AUH, Sultan FAT, Amin F, Arslan J, Ghani S, Masroor M. Almond supplementation reduces serum uric acid in coronary artery disease patients: a randomized controlled trial. Nutr J 2016; 15:77. [PMID: 27543277 PMCID: PMC4991057 DOI: 10.1186/s12937-016-0195-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2016] [Accepted: 08/02/2016] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVE Elevated serum uric acid (UA), a biomarker of renal insufficiency, is also an independent prognostic marker for morbidity in coronary artery disease (CAD) and poses serious health risks. This study reports the effect of almond consumption on UA in CAD patients. STUDY DESIGN A randomized controlled clinical trial was conducted with three groups: no-intervention (NI), Pakistani almonds (PA) or American almonds (AA). Patients were recruited from the Cardiology Clinics, Aga Khan University Hospital. Two follow-ups were scheduled at week-6 and week-12. 150 patients were randomly divided in three groups (50 per group). NI was not given almonds, whereas the PA and AA were given Pakistani and American almond varieties (10 g/day), respectively; with instruction to soak overnight and eat before breakfast. RESULTS Almonds supplementation significantly reduced (p < 0.05) serum UA among groups, and over time. At week-6, UA concentrations were -13 to -16 % less in PA and AA; at week-12 the concentrations were -14 to -18 % less, compared to NI. Systolic and diastolic blood pressure and body weights of the participants remained fairly constant among all the groups. CONCLUSION Almonds (10 g/day), eaten before breakfast, reduces serum UA in CAD patients. Prevention of hyperuricemia can confer protection from kidney and vascular damage and if extrapolated for general population, dietary almonds can offer grander health benefit. Trial is registered at Australian New Zealand Clinical trial registry as ACTRN12614000036617.
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Affiliation(s)
- Humaira Jamshed
- Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan
| | - Anwar-ul-Hassan Gilani
- Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan
- Pakistan Council for Science and Technology, Government of Pakistan, Shahara-i-Jamhuriat, G-5/2, Islamabad, Pakistan
| | | | - Faridah Amin
- Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan
| | - Jamshed Arslan
- Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan
| | - Sumaira Ghani
- Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan
| | - Madiha Masroor
- Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan
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Athyros VG, Katsiki N, Mikhailidis DP. Statins, renal function and homocysteine. Pharmacol Rep 2016; 68:1093. [PMID: 27229182 DOI: 10.1016/j.pharep.2016.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2016] [Accepted: 04/07/2016] [Indexed: 10/21/2022]
Affiliation(s)
- Vasilios G Athyros
- Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece
| | - Niki Katsiki
- Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece
| | - Dimitri P Mikhailidis
- Department of Clinical Biochemistry (Vascular Disease Prevention Clinics), Royal Free Hospital Campus, University College London Medical School, University College London (UCL), London, UK.
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Relationship between serum uric acid, metabolic syndrome and resting heart rate in Chinese elderly. Obes Res Clin Pract 2016; 10:159-68. [DOI: 10.1016/j.orcp.2015.04.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2014] [Revised: 04/09/2015] [Accepted: 04/15/2015] [Indexed: 11/20/2022]
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Abstract
PURPOSE OF REVIEW Chronic kidney disease (CKD) is a well-known risk factor for cardiovascular disease (CVD). Renal biomarkers might be valuable in predicting CVD. Investigation of these biomarkers may uncover some of the poorly understood mechanisms that link renal and CVD as well as aid in the modification of disease and serve as a useful tool in diagnosing early disease and monitoring therapeutic responses. In this review we discuss the clinical utility of emerging and known renal biomarkers in predicting CVD. RECENT FINDINGS Prior to adopting a biomarker into routine clinical practice, evidence-based laboratory medicine requires optimal technical and analytical performance, which is a prerequisite to have confidence in the result. Furthermore, an ideal biomarker should have evidence of its utility in predicting clinical, therapeutic and other health outcomes as well as proving its organizational impact and cost-effectiveness. The renal biomarkers that have been associated with CVD include cystatin C as a better marker of glomerular filtration than creatinine, albuminuria, neutrophil gelatinase associated lipocalin, a marker of acute kidney injury, fibroblast growth factor-23 and parathyroid hormone. Only urine albumin has been adopted into routine clinical practice. SUMMARY Of all the renal biomarkers, only albumin is clearly associated with CVD. The other biomarkers are earlier in clinical development and the evidence base for their clinical utility needs to be expanded substantially before they can be adopted into routine practice.
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Athyros VG, Mikhailidis DP. High incidence of metabolic syndrome further increases cardiovascular risk in patients with type 2 diabetes. Implications for everyday practice. J Diabetes Complications 2016; 30:9-11. [PMID: 26275865 DOI: 10.1016/j.jdiacomp.2015.07.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Vasilios G Athyros
- Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece.
| | - Dimitri P Mikhailidis
- Department of Clinical Biochemistry, Vascular Prevention Clinics, Royal Free Hospital Campus, University College Medical School, University College London, London, UK
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Zhao J, Huang Y. Salivary uric acid as a noninvasive biomarker for monitoring the efficacy of urate-lowering therapy in a patient with chronic gouty arthropathy. Clin Chim Acta 2015; 450:115-20. [PMID: 26276048 DOI: 10.1016/j.cca.2015.08.005] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2015] [Revised: 08/07/2015] [Accepted: 08/09/2015] [Indexed: 01/02/2023]
Abstract
BACKGROUND Monitoring blood uric acid (UA) is important in all patients on urate-lowering therapy so that the selection of the effective drugs and dosage adjustments could be made until the target level is reached. The issue is that frequent needle jabs are unacceptable. Reported mean levels of salivary UA were 185-240 μmol/l in healthy adults. A linear correlation was demonstrated between UA concentrations in saliva and plasma. We monitored salivary UA instead of plasmatic UA in a patient with gout. METHODS Allopurinol and benzbromarone were used as the therapeutic drugs. Salivary UA; urinary UA and creatinine; and plasmatic UA, creatinine, kynurenine and tryptophan were measured by HPLC. RESULTS Salivary UA indicated the efficacy of therapy accurately and conveniently. After eight weeks therapy, the weekly mean levels of salivary UA were reduced and maintained to <300 μmol/l, which was equivalent to <360 μmol/l of plasmatic UA according to the salivary UA/plasmatic UA ratio of this patient. CONCLUSION Measurement of salivary UA is a noninvasive and useful way for monitoring the status of hyperuricemia and the therapeutic efficacy of urate-lowering therapy. It has value for the management of hyperuricemia and gout.
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Affiliation(s)
- Jianxing Zhao
- Ruijin Hospital, Shanghai Jiao Tong University School of Medicine and Shanghai Institute of Hypertension, Shanghai, China.
| | - Ying Huang
- Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Athyros VG, Tziomalos K, Karagiannis A. Treatment options for dyslipidemia in chronic kidney disease and for protection from contrast-induced nephropathy. Expert Rev Cardiovasc Ther 2015; 13:1059-1066. [PMID: 26206619 DOI: 10.1586/14779072.2015.1072047] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Chronic kidney disease (CKD) is highly prevalent worldwide and represents a major cardiovascular risk factor. Dyslipidemia is present in most patients with CKD and further worsens CKD, creating a vicious cycle. The treatment of CKD-related dyslipidemia has been a controversial topic. The use of statins is recommended in all stages of CKD, but it appears to reduce cardiovascular and renal events only in the early CKD stages, up to stage 3. The use of atorvastatin has proven very beneficial; thus, the earliest we start statin treatment, the better for the patient. Atorvastatin and pitavastatin do not need dose adjustments at any level of renal function. Fibrates can be administered in mixed hyperlipidemia, combined with statins in early CKD stages. Omega-3 fatty acids are useful for treating hypertriglyceridemia in CKD. Antibodies against proprotein convertase subtilisin/kexin type 9 hold promise for a better control of dyslipidemia and a greater reduction of cardiovascular risk.
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Affiliation(s)
- Vasilios G Athyros
- a 1 Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece
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Kargiotis K, Athyros VG, Giouleme O, Katsiki N, Katsiki E, Anagnostis P, Boutari C, Doumas M, Karagiannis A, Mikhailidis DP. Resolution of non-alcoholic steatohepatitis by rosuvastatin monotherapy in patients with metabolic syndrome. World J Gastroenterol 2015; 21:7860-7868. [PMID: 26167086 PMCID: PMC4491973 DOI: 10.3748/wjg.v21.i25.7860] [Citation(s) in RCA: 110] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2014] [Accepted: 05/27/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effect of rosuvastatin monotherapy on non-alcoholic steatohepatitis (NASH). At present there is no effective treatment for non-alcoholic fatty liver disease or its advanced form NASH.
METHODS: This prospective study included 20 biopsy proven patients with NASH, metabolic syndrome (MetS) and dyslipidaemia. Biochemical parameters of the blood of the patients and an ultrasonography of the liver were performed at baseline. Then patients received lifestyle advice and were treated for a 12 mo period with rosuvastatin (10 mg/d) monotherapy. Patients were re-evaluated during the study at 3 mo intervals, during which biochemical parameters of the blood were measured including liver enzymes. A repeat biopsy and ultrasonography of the liver were performed at the end of the study in all 20 patients. Changes in liver enzymes, fasting plasma glucose, serum creatinine, serum uric acid (SUA), high sensitivity C reactive protein (hsCRP) and lipid profile were assessed every 3 mo. The primary endpoint was the resolution of NASH and the secondary endpoints were the changes in liver enzyme and lipid values.
RESULTS: The repeat liver biopsy and ultrasonography showed complete resolution of NASH in 19 patients, while the 20th, which had no improvement but no deterioration either, developed arterial hypertension and substantial rise in triglyceride levels during the study, probably due to changes in lifestyle including alcohol abuse. Serum alanine transaminase, aspartate transaminase, and γ-glutamyl transpeptidase were normalised by the 3rd treatment month (ANOVA P < 0.001), while alkaline phosphatase activities by the 6th treatment month (ANOVA, P = 0.01). Fasting plasma glucose and glycated haemoglobin were significantly reduced (P < 0.001). Lipid values were normalised by the 3rd treatment month. No patient had MetS by the 9th treatment month. Body mass index and waist circumference remained unchanged during the study. Thus, changes in liver pathology and function should be attributed solely to rosuvastatin treatment. A limitation of the study is the absence of a control group.
CONCLUSION: These findings suggest that rosuvastatin monotherapy could ameliorate biopsy proven NASH and resolve MetS within 12 mo. These effects and the reduction of fasting plasma glucose and SUA levels may reduce the risk of vascular and liver morbidity and mortality in NASH patients. These findings need confirmation in larger studies.
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Athyros VG, Tziomalos K, Katsiki N, Doumas M, Karagiannis A, Mikhailidis DP. Cardiovascular risk across the histological spectrum and the clinical manifestations of non-alcoholic fatty liver disease: An update. World J Gastroenterol 2015; 21:6820-6834. [PMID: 26078558 PMCID: PMC4462722 DOI: 10.3748/wjg.v21.i22.6820] [Citation(s) in RCA: 103] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2015] [Revised: 03/31/2015] [Accepted: 05/07/2015] [Indexed: 02/07/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is considered to be an independent cardiovascular disease (CVD) risk factor. However, simple steatosis has a benign clinical course without excess mortality. In contrast, the advanced form of NAFLD, non-alcoholic steatohepatitis (NASH) with liver fibrosis increases mortality by approximately 70%, due to an increase in CVD mortality by approximately 300%. Chronic kidney disease (CKD) may be caused by NAFLD/NASH and it substantially increases CVD risk, especially in the presence of type 2 diabetes mellitus. Moreover, CKD may trigger NAFLD/NASH deterioration in a vicious cycle. NAFLD/NASH is also related to increased arterial stiffness (AS), an independent CVD risk factor that further raises CVD risk. Diagnosis of advanced liver fibrosis (mainly by simple non-invasive tests), CKD, and increased AS should be made early in the course of NAFLD and treated appropriately. Lifestyle measures and statin treatment may help resolve NAFLD/NASH and beneficially affect the CVD risk factors mentioned above.
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Athyros VG, Katsiki N, Karagiannis A, Mikhailidis DP. Statins can improve proteinuria and glomerular filtration rate loss in chronic kidney disease patients, further reducing cardiovascular risk. Fact or fiction? Expert Opin Pharmacother 2015; 16:1449-1461. [PMID: 26037614 DOI: 10.1517/14656566.2015.1053464] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
INTRODUCTION The prevalence of chronic kidney disease (CKD), a risk factor for cardiovascular disease (CVD), is increasing worldwide. Statin treatment, the cornerstone of prevention or treatment of CVD, might have beneficial effects on urine protein excretion and renal function as determined by the glomerular filtration rate, whereas it might protect from acute kidney injury (AKI), mainly due to contrast-induced AKI. These beneficial effects on CKD may not be drug class effects; specific statins at specific doses may help prevent CKD deterioration and reduce CVD risk. We analysed all statin studies that had renal and CVD endpoints as main outcome measures. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched up to February 2015. AREAS COVERED We consider the effects of statins on microalbuminuria, proteinuria, glomerular filtration rate, AKI associated with angiography or percutaneous coronary intervention and on CVD event rates in patients with CKD. EXPERT OPINION Current evidence points towards the need to prescribe high-potency statins in patients with CKD, before a major decline in kidney function occurs. This may reduce CVD risk and delay the progress of CKD. Administration of either atorvastatin or rosuvastatin can prevent contrast-induced AKI before angiography or percutaneous coronary intervention. The combination of simvastatin + ezetimibe may decrease vascular events in patients with advanced CKD.
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Affiliation(s)
- Vasilios G Athyros
- Aristotle University of Thessaloniki, Hippocration Hospital, Medical School, Second Propedeutic Department of Internal Medicine , Thessaloniki , Greece +30 2310 892606 ; +30 2310 835955 ;
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Barkas F, Liberopoulos E, Klouras E, Liontos A, Elisaf M. Attainment of multifactorial treatment targets among the elderly in a lipid clinic. J Geriatr Cardiol 2015; 12:239-45. [PMID: 26089847 PMCID: PMC4460166 DOI: 10.11909/j.issn.1671-5411.2015.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2014] [Revised: 01/21/2015] [Accepted: 03/02/2015] [Indexed: 11/21/2022] Open
Abstract
OBJECTIVE To examine target attainment of lipid-lowering, antihypertensive and antidiabetic treatment in the elderly in a specialist setting of a University Hospital in Greece. METHODS This was a retrospective study including consecutive subjects ≥ 65 years old (n = 465) with a follow-up ≥ 3 years. Low-density lipoprotein cholesterol (LDL-C), blood pressure (BP) and glycated hemoglobin (HbA1c) goal achievement were recorded according to European Society of Cardiology/European Atherosclerosis Society (ESC/EAS), European Society of Hypertension (ESH)/ESC and European Association for the Study of Diabetes (EASD) guidelines. RESULTS The LDL-C targets were attained by 27%, 48% and 62% of very high, high and moderate risk patients, respectively. Those receiving statin + ezetimibe achieved higher rates of LDL-C goal achievement compared with those receiving statin monotherapy (48% vs. 33%, P < 0.05). Of the diabetic subjects, 71% had BP < 140/85 mmHg, while 78% of those without diabetes had BP < 140/90 mmHg. A higher proportion of the non-diabetic individuals (86%) had BP < 150/90 mmHg. Also, a higher proportion of those with diabetes had HbA1c < 8% rather than < 7% (88% and 47%, respectively). Of note, almost one out of three non-diabetic individuals and one out of ten diabetic individuals had achieved all three treatment targets. CONCLUSIONS Even in a specialist setting of a University Hospital, a high proportion of the elderly remain at suboptimal LDL-C, BP and HbA1c levels. The use of drug combinations could improve multifactorial treatment target attainment, while less strict targets could be more easily achieved in this population.
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Affiliation(s)
- Fotios Barkas
- Department of Internal Medicine, University of Ioannina Medical School, Ioannina, Greece
| | - Evangelos Liberopoulos
- Department of Internal Medicine, University of Ioannina Medical School, Ioannina, Greece
| | - Eleftherios Klouras
- Department of Internal Medicine, University of Ioannina Medical School, Ioannina, Greece
| | - Angelos Liontos
- Department of Internal Medicine, University of Ioannina Medical School, Ioannina, Greece
| | - Moses Elisaf
- Department of Internal Medicine, University of Ioannina Medical School, Ioannina, Greece
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Barkas F, Liberopoulos EN, Kostapanos MS, Liamis G, Tziallas D, Elisaf M. Lipid target achievement among patients with very high and high cardiovascular risk in a lipid clinic. Angiology 2015; 66:346-353. [PMID: 24830420 DOI: 10.1177/0003319714535073] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
This was a retrospective study that assessed achievement of lipid-lowering treatment targets in the setting of a University Hospital Lipid Clinic. Low-density lipoprotein cholesterol (LDL-C) goal attainment according to National Cholesterol Education Program-Adult Treatment Panel III (NCEP ATP III) and European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines was recorded in 1000 consecutive adult patients followed for ≥3 years (mean 8 years). The LDL-C targets according to the NCEP ATP III were attained by 66% and 86% of patients with "very high" (n = 477) and "high" (n = 408) cardiovascular risk, respectively. Fewer patients were within LDL-C goals according to the ESC/EAS guidelines: 25% and 42%. Overall, 92% of the patients were on statins: 67% were on statin monotherapy, while 33% were on combinations with ezetimibe (25%), ω-3 fatty acids (5%), fibrates (4%), or colesevelam (2%). Even in a specialist lipid clinic, a large proportion of patients are not at goal according to the recent ESC/EAS guidelines.
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Affiliation(s)
- Fotios Barkas
- Department of Internal Medicine, University of Ioannina Medical School, Ioannina, Greece
| | | | - Michael S Kostapanos
- Department of Internal Medicine, University of Ioannina Medical School, Ioannina, Greece
| | - George Liamis
- Department of Internal Medicine, University of Ioannina Medical School, Ioannina, Greece
| | - Dimitrios Tziallas
- Department of Internal Medicine, University of Ioannina Medical School, Ioannina, Greece
| | - Moses Elisaf
- Department of Internal Medicine, University of Ioannina Medical School, Ioannina, Greece
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Bonfrate L, Procino G, Wang DQH, Svelto M, Portincasa P. A novel therapeutic effect of statins on nephrogenic diabetes insipidus. J Cell Mol Med 2015; 19:265-282. [PMID: 25594563 PMCID: PMC4407600 DOI: 10.1111/jcmm.12422] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2014] [Accepted: 08/01/2014] [Indexed: 12/12/2022] Open
Abstract
Statins competitively inhibit hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase, resulting in reduced plasma total and low-density lipoprotein cholesterol levels. Recently, it has been shown that statins exert additional 'pleiotropic' effects by increasing expression levels of the membrane water channels aquaporin 2 (AQP2). AQP2 is localized mainly in the kidney and plays a critical role in determining cellular water content. This additional effect is independent of cholesterol homoeostasis, and depends on depletion of mevalonate-derived intermediates of sterol synthetic pathways, i.e. farnesylpyrophosphate and geranylgeranylpyrophosphate. By up-regulating the expression levels of AQP2, statins increase water reabsorption by the kidney, thus opening up a new avenue in treating patients with nephrogenic diabetes insipidus (NDI), a hereditary disease that yet lacks high-powered and limited side effects therapy. Aspects related to water balance determined by AQP2 in the kidney, as well as standard and novel therapeutic strategies of NDI are discussed.
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Affiliation(s)
- Leonilde Bonfrate
- Department of Biomedical Sciences and Human Oncology, Internal Medicine, University Medical SchoolBari, Italy
| | - Giuseppe Procino
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo MoroBari, Italy
| | - David Q-H Wang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of MedicineSt. Louis, MO, USA
| | - Maria Svelto
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo MoroBari, Italy
| | - Piero Portincasa
- Department of Biomedical Sciences and Human Oncology, Internal Medicine, University Medical SchoolBari, Italy
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Fabbian F, De Giorgi A, Monesi M, Pala M, Tiseo R, Misurati E, Parisi C, Volpi R, Graziani R, Mikhailidis DP, Manfredini R. All-cause mortality and estimated renal function in type 2 diabetes mellitus outpatients: Is there a relationship with the equation used? Diab Vasc Dis Res 2015; 12:46-52. [PMID: 25344129 DOI: 10.1177/1479164114552656] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND We investigated the relationship between serum creatinine (SCr) and estimated glomerular filtration rate (eGFR), evaluated by different formulae, and all-cause mortality (ACM) in type 2 diabetes mellitus (T2DM) outpatients. METHODS This observational cohort study considered 1365 T2DM outpatients, who had been followed up for a period of up to 11 years. eGFR was estimated using several equations. RESULTS Seventy subjects (5.1%) died after a follow-up of 9.8 ± 3 years. Univariate analysis showed that diagnosis of nephropathy (odds ratio (OR): 2.554, 95% confidence interval (CI): 1.616-4.038, p < 0.001) and microvascular complications (OR: 2.281, 95% CI: 1.449-3.593, p < 0.001) were associated with ACM. Receiving operating characteristic (ROC) curves showed that the areas under the curve for ACM were similar using the different eGFR equations. eGFR values were predictors of ACM, and the hazard ratios (HRs) of the different equations for eGFR estimation were similar. CONCLUSION In our cohort of T2DM outpatients, different eGFR equations perform similarly in predicting ACM, whereas SCr did not.
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Affiliation(s)
- Fabio Fabbian
- Operative Unit of Clinica Medica, Department of Medical Sciences, University Hospital St. Anna, Ferrara, Italy
| | - Alfredo De Giorgi
- Operative Unit of Clinica Medica, Department of Medical Sciences, University Hospital St. Anna, Ferrara, Italy
| | - Marcello Monesi
- Diabetes and Clinical Nutrition, University Hospital St. Anna, Ferrara, Italy
| | - Marco Pala
- Operative Unit of Clinica Medica, Department of Medical Sciences, University Hospital St. Anna, Ferrara, Italy
| | - Ruana Tiseo
- Operative Unit of Clinica Medica, Department of Medical Sciences, University Hospital St. Anna, Ferrara, Italy
| | - Elisa Misurati
- Operative Unit of Clinica Medica, Department of Medical Sciences, University Hospital St. Anna, Ferrara, Italy
| | - Claudia Parisi
- Operative Unit of Clinica Medica, Department of Medical Sciences, University Hospital St. Anna, Ferrara, Italy
| | - Riccardo Volpi
- Department of Internal Medicine and Biomedical Science, University of Parma, Parma, Italy
| | - Roberto Graziani
- Diabetes and Clinical Nutrition, University Hospital St. Anna, Ferrara, Italy
| | - Dimitri P Mikhailidis
- Department of Clinical Biochemistry (Vascular Disease Prevention Clinics), University College London Medical School, University College London (UCL), London, UK
| | - Roberto Manfredini
- Operative Unit of Clinica Medica, Department of Medical Sciences, University Hospital St. Anna, Ferrara, Italy
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Prasad GVR. Metabolic syndrome and chronic kidney disease: Current status and future directions. World J Nephrol 2014; 3:210-219. [PMID: 25374814 PMCID: PMC4220353 DOI: 10.5527/wjn.v3.i4.210] [Citation(s) in RCA: 102] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2014] [Revised: 08/26/2014] [Accepted: 09/24/2014] [Indexed: 02/06/2023] Open
Abstract
Metabolic syndrome (MetS) is a term used to denote a combination of selected, widely prevalent cardiovascular disease (CVD)-related risk factors. Despite the ambiguous definition of MetS, it has been clearly associated with chronic kidney disease markers including reduced glomerular filtration rate, proteinuria and/or microalbuminuria, and histopathological markers such as tubular atrophy and interstitial fibrosis. However, the etiological role of MetS in chronic kidney disease (CKD) is less clear. The relationship between MetS and CKD is complex and bidirectional, and so is best understood when CKD is viewed as a common progressive illness along the course of which MetS, another common disease, may intervene and contribute. Possible mechanisms of renal injury include insulin resistance and oxidative stress, increased proinflammatory cytokine production, increased connective tissue growth and profibrotic factor production, increased microvascular injury, and renal ischemia. MetS also portends a higher CVD risk at all stages of CKD from early renal insufficiency to end-stage renal disease. Clinical interventions for MetS in the presence of CKD should include a combination of weight reduction, appropriate dietary modification and increase physical activity, plus targeting of individual CVD-related risk factors such as dysglycemia, hypertension, and dyslipidemia while conforming to relevant national societal guidelines.
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Katsiki N, Mikhailidis DP, Nair DR. The effects of antiepileptic drugs on vascular risk factors: A narrative review. Seizure 2014; 23:677-84. [DOI: 10.1016/j.seizure.2014.05.011] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2013] [Revised: 05/21/2014] [Accepted: 05/24/2014] [Indexed: 12/13/2022] Open
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Abstract
Achieving low-density lipoprotein cholesterol (LDL-C) goals in clinical practice is still unsatisfactory. Furthermore, a significant residual risk remains, even after reaching LDL-C targets, in terms of both fasting and postprandial triglycerides, high-density lipoprotein cholesterol (quantity and quality) and small dense LDL particles. Statins are the first choice for treating lipid abnormalities. Other lipid-lowering agents can be administered when statins are not tolerated and if LDL-C targets are not reached. Furthermore, multifactorial treatment, including a statin, exerts several beneficial effects on cardiovascular and residual risk reduction. The role of novel developing lipid therapies in clinical practice remains to be established.
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Affiliation(s)
- Niki Katsiki
- 2nd Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital , Thessaloniki , Greece
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Zhang JW, He LJ, Cao SJ, Yang Q, Yang SW, Zhou YJ. Association of serum uric acid and coronary artery disease in premenopausal women. PLoS One 2014; 9:e106130. [PMID: 25184207 PMCID: PMC4153543 DOI: 10.1371/journal.pone.0106130] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2013] [Accepted: 08/02/2014] [Indexed: 02/07/2023] Open
Abstract
Objective To date, no study in the published literature has investigated the role of various serum uric acid (SUA) concentrations in the development of angiographically-proven coronary artery disease (CAD) in premenopausal women. Therefore, the aim of this study was to investigate the role SUA levels may play in the prevalence, severity, and prognosis of CAD in premenopausal women. Methods This cross-sectional retrospective study included 607 premenopausal women who had undergone coronary angiography. The CAD diagnosis was based upon stenosis affecting ≥50% of the luminal diameter. Association of the SUA levels with CAD prevalence, severity, and clinical outcomes were assessed by statistical analysis. Results In total, 369 (60.8%) of the patients were diagnosed with CAD. The CAD patients had significantly higher SUA levels than those without CAD (5.3±1.9 vs. 4.8±1.7 mg/dL, P = 0.001). The SUA levels were found to be significantly associated with CAD prevalence (P = 0.013). Patients with higher levels of SUA also showed increased rates of multivessel disease and composite end-points, such as major adverse cardiac events. Furthermore, multivariate analysis identified abnormally high levels of uric acid (hyperuricemia) as an independent risk factor for CAD (OR 1.51 (1.11–2.53), P<0.05). Conclusions The SUA levels are significantly associated with the prevalence of CAD. The SUA levels may be a predictor for incidence of major cardiovascular events in premenopausal women.
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Affiliation(s)
- Jian-wei Zhang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, The Key Laboratory of Remodeling-related Cardiovascular Disease, Ministry of Education, Beijing, China
| | - Ling-jie He
- Department of Emergency, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Shu-jun Cao
- Department of Cardiology, Beijing Daxing Hospital, Capital Medical University, Beijing, China
| | - Qing Yang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, The Key Laboratory of Remodeling-related Cardiovascular Disease, Ministry of Education, Beijing, China
| | - Shi-wei Yang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, The Key Laboratory of Remodeling-related Cardiovascular Disease, Ministry of Education, Beijing, China
| | - Yu-jie Zhou
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, The Key Laboratory of Remodeling-related Cardiovascular Disease, Ministry of Education, Beijing, China
- * E-mail:
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Sun Y, Yu X, Zhi Y, Geng S, Li H, Liu T, Xu K, Chen L, Wu C, Qi G. A cross-sectional analysis of the relationship between uric acid and coronary atherosclerosis in patients with suspected coronary artery disease in China. BMC Cardiovasc Disord 2014; 14:101. [PMID: 25128201 PMCID: PMC4236559 DOI: 10.1186/1471-2261-14-101] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2013] [Accepted: 07/31/2014] [Indexed: 01/07/2023] Open
Abstract
Background Although many studies have examined the relationship between uric acid (UA) and coronary artery disease (CAD), whether UA is an independent risk factor contributing to progression of CAD is still controversial. Whether UA plays a different role in different sexes is also unclear. Methods A total of 1116 individuals with suspected CAD were stratified into four groups according to their serum UA quartiles in total (men and women combined), in men, and in women. The association of UA with coronary atherosclerosis was assessed by univariable and multivariable logistic regression. Results In total and in women, the prevalence of any plaques and significant/severe stenosis was significantly increased with an increase in quartiles of UA (all P < 0.05). The proportion of triple-vessel disease and left main artery lesion was highest in the fourth quartile (both p < 0.05). Increasing quartiles of UA were significantly associated with a coronary artery calcium score (CACS) >10 (all P < 0.01). As UA levels increased in women, the incidence of double-vessel lesions (p = 0.017) and the proportion of mixed plaques (p = 0.022) were significantly increased. The proportion of a CACS of 0 in total, in men and women was highest in the first quartile (all P < 0.01). UA was the strongest predictor of significant stenosis, multivessel disease, and mixed plaques in women (all p < 0.05). UA was the only risk factor for mixed plaques in total (P = 0.046). Conclusion The level of UA was significantly associated with coronary atherosclerosis in women, but not men.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Guoxian Qi
- Department of Cardiology of Aging, Department of Cardiology, The First Affiliated Hospital of China Medical University, NO,155 Nanjing North Street, Heping Ward, Shenyang 110001, China.
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Shakib MC, Gabrial S, Gabrial G. Rice Bran Oil Compared to Atorvastatin for Treatment of Dyslipidemia in Patients with Type 2 Diabetes. Open Access Maced J Med Sci 2014. [DOI: 10.3889/oamjms.2014.017] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Objective: To compare the effect of rice bran oil versus statins (atorvastatin drug) on blood glucose, glycosylated hemoglobin (HbA1C) and serum lipid profiles in patients with type 2 diabetes. The safety of the tested rice bran oil and atorvastatin were investigated. Fatty acids contents of RBO, olive and sesame oil were also assessed.Materials and Methods: Forty four eligible patients with type 2 diabetes and moderately hyperlipidemic were randomly and equally allocated into two groups, rice bran oil (RBO) group and atorvastatin group. The RBO group received a low-calorie diet and consumed 30Â g / day RBO oil as salad dressing and for use as main cooking oil for 6 months. The Atorvastatin group received a low-calorie diet and 40 mg/day of atorvastatin drug for 6 months. At baseline and after 6 months of study intervention, blood glucose, glycosylated hemoglobin (HbA1c), serum lipid profiles; hepatic, renal and inflammatory biomarkers were estimated.Results: Results showed significant increase in fasting and postprandial blood glucose, HbA1C and liver transaminases (alanine transaminase ALT and aspartate transaminase AST) in the atorvastatin group while a significant reduction was shown in RBO group. Moreover, significant reductions in lipid profile levels, blood urea, serum uric acid and erythrocyte sedimentation rate (ESR) were observed in both RBO and atorvastatin groups after 6 months of the study intervention.Conclusion: The use of rice bran oil together with dietary modifications may have implications in lowering fasting and postprandial blood glucose, suppressing serum lipid levels, reduce the TC/HDL-C ratio and therefore reducing the risk of cardiovascular disease. Moreover, RBO exerts a hypouricemic action and anti-inflammatory effects. The findings obtained from the current study reinforce the use of RBO as an alternative natural potent hypolipidemic agent safer than atorvastatin drug that may induce side effects in some cases in patients intolerant to statins.
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Kim WJ, Kim SS, Bae MJ, Yi YS, Jeon YK, Kim BH, Song SH, Kim IJ, Kim YK. High-normal serum uric acid predicts the development of chronic kidney disease in patients with type 2 diabetes mellitus and preserved kidney function. J Diabetes Complications 2014; 28:130-4. [PMID: 24438886 DOI: 10.1016/j.jdiacomp.2013.11.006] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2013] [Revised: 11/12/2013] [Accepted: 11/13/2013] [Indexed: 02/06/2023]
Abstract
AIMS We evaluated whether high-normal serum uric acid (SUA) levels can predict the development of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus and preserved kidney function at baseline. METHODS This was a retrospective observational longitudinal study of patients presenting at the Department of Endocrinology and Metabolism, Pusan National University Hospital. A total of 512 patients with type 2 diabetes mellitus and preserved kidney function (estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m(2)) and normouricemia were included. The main outcome was development of CKD of stage 3 or greater. The patients were divided into four groups according to quartiles of SUA levels. RESULTS During the follow-up period, 62 (12.1%) patients had progressed to CKD 3 or greater. The group with the highest-normal range of SUA (Q4) showed a higher cumulative incidence of CKD stage 3 or greater than that of the other lower quartiles (Q4 vs. Q3; P = 0.037, Q4 vs. Q2; P<0.001, Q4 vs. Q1; P<0.001). In a univariate analysis, Q4 was significantly associated with the development of CKD 3 or greater (log-rank statistic, 31.93; P<0.001). In a multivariate analysis, Q4 (hazard ratio, 2.97; 95% confidence interval, 1.15-7.71; P = 0.025) showed a significant association with CKD 3 or greater. CONCLUSIONS High-normal SUA may predict the occurrence of CKD stage 3 or greater in patients with type 2 diabetes mellitus and preserved kidney function.
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Affiliation(s)
- Won Jin Kim
- Department of Internal Medicine, Pusan National University Hospital, Busan, Korea; Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Sang Soo Kim
- Department of Internal Medicine, Pusan National University Hospital, Busan, Korea; Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Min Jung Bae
- Kim Yong Ki Internal Medicine Clinic, Busan, Korea
| | | | - Yun Kyung Jeon
- Department of Internal Medicine, Pusan National University Hospital, Busan, Korea; Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Bo Hyun Kim
- Department of Internal Medicine, Pusan National University Hospital, Busan, Korea; Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Sang Heon Song
- Department of Internal Medicine, Pusan National University Hospital, Busan, Korea; Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - In Joo Kim
- Department of Internal Medicine, Pusan National University Hospital, Busan, Korea; Biomedical Research Institute, Pusan National University Hospital, Busan, Korea.
| | - Yong Ki Kim
- Kim Yong Ki Internal Medicine Clinic, Busan, Korea
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