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The association of GATM polymorphism with statin-induced myopathy: a systematic review and meta-analysis.
Liu, M, Fan, F, Zhang, Y, Li, J
European journal of clinical pharmacology. 2021;(3):349-357
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Abstract
PURPOSE Statin-induced myopathy (SIM) is the commonest reason for discontinuation of statin therapy. The aim of this present meta-analysis is to assess the relationship between glycine amidinotransferase gene (GATM) polymorphism and risk of SIM. METHODS MEDLINE, EMBASE, Web of Science, and Cochrane Library databases were searched systematically for case-control studies investigating the relationship between GATM polymorphism and SIM. Retrieved articles were carefully reviewed and assessed according to the inclusion criteria. Associations were assessed in pooled data by calculating odds ratio with 95% confidence intervals. Subgroup analysis was performed according to comedications and severity of SIM. RESULTS Six studies with 707 cases and 2321 controls were included in this meta-analysis. GATM rs9806699 G>A was associated with decreased risk of SIM (OR = 0.80, 95% CI 0.68-0.94, P = 0.006). This association remained significant in the subgroup with fibrates or niacin excluded. However, the association of rs9806699 G>A with severe SIM was not significant. In addition, another two variations at GATM, rs1719247 C>T, and rs1346268 T>C were also associated with declined risk of SIM. CONCLUSIONS GATM polymorphism including rs9806699 G>A, rs1719247 C>T, and rs1346268 T>C may be protective factors of SIM. GATM rs9806699 G>A may only exert protective effect on mild SIM cases. Our meta-analysis indicates that GATM polymorphism may represent a pharmacogenomics biomarker for predicting incidence of SIM, which contributes to risk stratification and optimizing statin adherence.
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A Mendelian Randomization Approach Using 3-HMG-Coenzyme-A Reductase Gene Variation to Evaluate the Association of Statin-Induced Low-Density Lipoprotein Cholesterol Lowering With Noncardiovascular Disease Phenotypes.
Liu, G, Shi, M, Mosley, JD, Weng, C, Zhang, Y, Lee, MTM, Jarvik, GP, Hakonarson, H, Namjou-Khales, B, Sleiman, P, et al
JAMA network open. 2021;(6):e2112820
Abstract
IMPORTANCE Observational studies suggest that statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, may be associated with beneficial effects in many noncardiovascular diseases. OBJECTIVE To construct a weighted HMG-CoA reductase (HMGCR) gene genetic risk score (GRS) using variants in the HMGCR gene affecting low-density lipoprotein cholesterol as an instrumental variable for mendelian randomization analyses to test associations with candidate noncardiovascular phenotypes previously associated with statin use in observational studies. DESIGN, SETTING, AND PARTICIPANTS This cohort study included 53 385 unrelated adults of European ancestry with genome-wide genotypes available from BioVU (a practice-based biobank, used for discovery) and 30 444 unrelated adults with European ancestry available in the Electronic Medical Records and Genomics (eMERGE; a research consortium that conducts genetic research using electronic medical records, used for replication). The study was conducted from February 6, 2015, through April 31, 2019; data analysis was performed from August 26, 2019, through December 22, 2020. INTERVENTIONS An HMGCR GRS was calculated. MAIN OUTCOMES AND MEASURES The association between the HMGCR GRS and the presence or absence of 22 noncardiovascular phenotypes previously associated with statin use in clinical studies. RESULTS Of the 53 385 individuals in BioVU, 29 958 (56.1%) were women; mean (SD) age was 59.9 (15.6) years. The finding between the HMGCR GRS and the noncardiovascular phenotypes of interest in this cohort was significant only for type 2 diabetes. An HMGCR GRS equivalent to a 10-mg/dL decrease in the low-density lipoprotein cholesterol level was associated with an increased risk of type 2 diabetes (odds ratio [OR], 1.09; 95% CI, 1.04-1.15; P = 5.58 × 10-4). The HMGCR GRS was not associated with other phenotypes; the closest were increased risk of Parkinson disease (OR, 1.30; 95% CI, 1.07-1.58; P = .007) and kidney failure (OR, 1.18; 95% CI, 1.05-1.34; P = .008). Of the 30 444 individuals in eMERGE, 16 736 (55.0%) were women; mean (SD) age was 68.7 (15.4) years. The association between the HMGCR GRS and type 2 diabetes was replicated in this cohort (OR, 1.09; 95% CI, 1.01-1.17; P = .02); however, the HMGCR GRS was not associated with Parkinson disease (OR, 0.93; 95% CI, 0.75-1.16; P = .53) and kidney failure (OR, 1.18; 95% CI, 0.98-1.41; P = .08) in the eMERGE cohort. CONCLUSIONS AND RELEVANCE A mendelian randomization approach using variants in the HMGCR gene replicated the association between statin use and increased type 2 diabetes risk but provided no strong evidence for pleiotropic effects of statin-induced decrease of the low-density lipoprotein cholesterol level on other diseases.
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Comparison of Percutaneous Coronary Intervention, Coronary Artery Bypass Grafting and Medical Therapy in Non-ST Elevation Acute Coronary Syndrome Patients With 3-Vessel Disease.
Jia, S, Zhang, C, Jiang, L, Xu, L, Tian, J, Zhao, X, Feng, X, Wang, D, Zhang, Y, Sun, K, et al
Circulation journal : official journal of the Japanese Circulation Society. 2020;(10):1718-1727
Abstract
BACKGROUND The aim of this study is to compare the long-term prognosis of non-ST elevation acute coronary syndrome (NSTE-ACS) patients with 3-vessel disease (3VD) who underwent percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) or medical therapy (MT).Methods and Results:Overall, 3,928 NSTE-ACS patients with 3VD were consecutively enrolled from April 2004 to February 2011 at Fu Wai Hospital. Patients were followed up for a median of 7.5 years, and were divided into PCI, CABG or MT groups according to their treatment. Compared with patients undergoing PCI, CABG patients had lower rates of myocardial infarction (MI), unplanned revascularization, major adverse cardiovascular and cerebrovascular events (MACCE) and a higher rate of stroke (all P<0.05). Compared with MT, PCI and CABG had lower incidences of all adverse outcomes (all P<0.05), except for a similar rate of stroke between PCI and MT. Kaplan-Meier analysis showed similar results. After adjusting for confounders, CABG was independently associated with a lower risk of cardiac death, revascularization and MACCE compared with PCI (all P<0.05). Compared with MT, PCI reduced long-term risk of death, whereas CABG reduced long-term risk of death, revascularization and MACCE events (all P<0.05). CONCLUSIONS In NSTE-ACS patients with 3VD, CABG is independently associated with a lower risk of long-term cardiac death, revascularization and MACCE compared with PCI. Patients who received MT alone had the highest risk of long-term MACCE.
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Effects of Statins on Lipid Profile of Kidney Transplant Recipients: A Meta-Analysis of Randomized Controlled Trials.
Huang, X, Jia, Y, Zhu, X, Zhang, Y, Jiang, L, Wei, X, Zhao, D, Zhao, X, Du, Y
BioMed research international. 2020;:9094543
Abstract
OBJECTIVE To assess the benefits of statins on lipid profile in kidney transplant recipients via a meta-analysis. METHODS We systematically identified peer-reviewed clinical trials, review articles, and treatment guidelines from PubMed, Embase, the Cochrane Library, Wanfang, Chinese National Knowledge Infrastructure (CNKI), SinoMed (CBM), and Chongqing VIP databases from inception to April 2019. In the analysis, only randomized controlled clinical trials performed in human were included. RESULTS Eight articles were included in the analysis, involving 335 kidney transplant recipients who received statins and 350 kidney transplant patients as the control group. Results revealed that statins improved the lipid profile of kidney transplant recipients. Specifically, statin therapy significantly reduced total cholesterol and low-density lipoprotein cholesterol. However, it had no effects on high-density lipoprotein cholesterol and triglyceride levels. CONCLUSIONS The present study provides valuable knowledge on the potential benefits of statins in kidney transplant recipients. This meta-analysis shows that statin therapy modifies the lipid profile in this patient population.
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An evaluation of pitavastatin for the treatment of hypercholesterolemia.
Chan, P, Shao, L, Tomlinson, B, Zhang, Y, Liu, ZM
Expert opinion on pharmacotherapy. 2019;(1):103-113
Abstract
Statins are the first line of therapy to reduce low-density lipoprotein cholesterol (LDL-C) in order to decrease cardiovascular events. Pitavastatin is the latest statin to be introduced to the market. Areas covered: In this article, the authors review the efficacy, safety, and tolerability of pitavastatin. The authors also review a recent cardiovascular outcome study. Expert opinion: Pitavastatin produces dose-dependent reductions in LDL-C at lower doses than other statins. The maximum approved dose of 4 mg reduces LDL-C by about 40-49% in different patient groups and is equivalent to atorvastatin 20 mg in this effect. Pitavastatin undergoes minimal metabolism so drug-drug interactions are less likely than with many other statins, but it can interact with some drugs that inhibit drug transporters. Compared with other statins, it has been associated with greater increases in high-density lipoprotein cholesterol and it was found to be less likely to cause new onset diabetes. In a recent study in Japanese patients with stable coronary artery disease, pitavastatin 4 mg was more effective than pitavastatin 1 mg in reducing cardiovascular events. Therefore, the highest dose may be preferred in high-risk patients.
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Effect of Statins on COPD: A Meta-Analysis of Randomized Controlled Trials.
Zhang, W, Zhang, Y, Li, CW, Jones, P, Wang, C, Fan, Y
Chest. 2017;(6):1159-1168
Abstract
BACKGROUND Much controversy persists regarding the place of statin drugs in the treatment of patients with COPD. This systematic review and meta-analysis sought to determine the clinical efficacy of statin therapy in COPD. METHODS We searched MEDLINE, EMBASE, the Cochrane Database, and PubMed for relevant clinical studies. Randomized controlled trials (RCTs) comparing the effects of statin drugs with placebo in COPD populations were included. Pooled estimates were calculated using a random-effects model. Heterogeneity was determined using the I2 statistic. RESULTS Ten trials with a total of 1,471 patients were included. Statin treatment was associated with a larger improvement in exercise capacity, lung function, and St. George's Respiratory Questionnaire score compared with placebo, but there were no statistically significant differences in inflammatory markers, all-cause mortality, and safety outcomes; however, subgroup analysis indicated that statin drugs improved clinical outcomes in the subjects from trials enrolling patients with overt cardiovascular disease (CVD), elevated baseline C-reactive protein levels, or a high cholesterol level. CONCLUSIONS The findings from this systematic review suggest a role for statin drugs in patients with COPD and coexisting CVD, evidence of increased systemic inflammation, or hyperlipidemia with respect to improving exercise tolerance and pulmonary function. These findings need to be confirmed by RCTs specifically designed to test this hypothesis and identify appropriate patients for statin use. TRIAL REGISTRY PROSPERO CRD42017060594; https://www.crd.york.ac.uk/PROSPERO/.
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Association between statin usage and prostate cancer prevention: a refined meta-analysis based on literature from the years 2005-2010.
Zhang, Y, Zang, T
Urologia internationalis. 2013;(3):259-62
Abstract
INTRODUCTION Statins are cholesterol-lowering drugs that are widely used to prevent and treat atherosclerotic cardiovascular disease. It was found that statins can be associated with the occurrence of prostate cancer. However, no consensus has been concluded. MATERIALS AND METHODS In the present study, we provide a refined meta-analysis on the association between statins and prostate cancers. Our objective is to offer a congruent recognition of the impact of statins on prostate cancer. RESULTS Our refined analysis has included seven previous publications from the years 2005 to 2010. CONCLUSIONS Based on the results, we concluded that there were associations for statin usage in preventing prostate cancer (OR 1.195, 95% CI 1.018-1.403, p = 0.029). Different from previous meta-analyses, our positive conclusion is primarily based on the recent new published literature, which supported the efficiency of statin use to control prostate cancer. More specific efforts for excluding the influence of other factors are crucial in further assessment of the efficiency of statin use.
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Reduction in arterial wall strain with aggressive lipid-lowering therapy in patients with carotid artery disease.
Li, ZY, Tang, TY, Jiang, F, Zhang, Y, Gillard, JH
Circulation journal : official journal of the Japanese Circulation Society. 2011;(6):1486-92
Abstract
BACKGROUND Inflammation and biomechanical factors have been associated with the development of vulnerable atherosclerotic plaques. Lipid-lowering therapy has been shown to be effective in stabilizing them by reducing plaque inflammation. Its effect on arterial wall strain, however, remains unknown. The aim of the present study was to investigate the role of high- and low-dose lipid-lowering therapy using an HMG-CoA reductase inhibitor, atorvastatin, on arterial wall strain. METHODS AND RESULTS Forty patients with carotid stenosis >40% were successfully followed up during the Atorvastatin Therapy: Effects on Reduction Of Macrophage Activity (ATHEROMA; ISRCTN64894118) Trial. All patients had plaque inflammation as shown by intraplaque accumulation of ultrasmall super paramagnetic particles of iron oxide on magnetic resonance imaging at baseline. Structural analysis was performed and change of strain was compared between high- and low-dose statin at 0 and 12 weeks. There was no significant difference in strain between the 2 groups at baseline (P = 0.6). At 12 weeks, the maximum strain was significantly lower in the 80-mg group than in the 10-mg group (0.0850.033 vs. 0.1690.084; P = 0.001). A significant reduction (26%) of maximum strain was observed in the 80-mg group at 12 weeks (0.0180.02; P = 0.01). CONCLUSIONS Aggressive lipid-lowering therapy is associated with a significant reduction in arterial wall strain. The reduction in biomechanical strain may be associated with reductions in plaque inflammatory burden.
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Effect of atorvastatin versus rosuvastatin on levels of serum lipids, inflammatory markers and adiponectin in patients with hypercholesterolemia.
Qu, HY, Xiao, YW, Jiang, GH, Wang, ZY, Zhang, Y, Zhang, M
Pharmaceutical research. 2009;(4):958-64
Abstract
PURPOSE To compare the short-term effect of treatment with atorvastatin and rosuvastatin on levels of serum lipids, inflammatory markers and adiponectin in patients with hypercholesterolemia. METHODS Sixty-nine patients with hypercholesterolemia were randomly assigned to receive 10 mg/day of atorvastatin or rosuvastatin for 12 weeks. Inflammatory biomarkers, including highsensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-alpha, matrix metalloproteinase-9 (MMP-9), and endothelin (ET-1), plasminogen activator inhibitor type 1 (PAI-1) and plasma tissue plasminogen activator (tPA), adiponectin, and lipid profiles were measured before and after statin therapy. RESULTS Atorvastatin and rosuvastatin both lowered levels of hs-CRP, MMP-9, PAI-1, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) from baseline values, with rosuvastatin lowering TC and LDL-C to a greater extent than atorvastatin (P < 0.05). Adiponectin level increase was 15% higher than that at baseline with atorvastatin (P > 0.05) but 67% higher with rosuvastatin (P < 0.05). CONCLUSIONS Therapy with both statins not only significantly improved lipid profiles but also decreased levels of vascular biomarkers hs-CRP, MMP-9, and PAI-1; however, only rosuvastatin increased serum adiponectin levels significantly in patients with hypercholesterolemia, which could imply a beneficial effect in coronary artery disease.