scholarly journals The Pharmacogenetics of Statin Therapy on Clinical Events: No Evidence that Genetic Variation Affects Statin Response on Myocardial Infarction

2022 ◽  
Vol 12 ◽  
Author(s):  
Stella Trompet ◽  
Iris Postmus ◽  
Helen R. Warren ◽  
Raymond Noordam ◽  
Roelof A. J. Smit ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Genetic Variation ◽  
Statin Therapy ◽  
Risk Reduction ◽  
Meta Analysis ◽  
Clinical Events ◽  
Genome Wide ◽  
Stage 1 ◽  
Statin Response

Background: The pharmacogenetic effect on cardiovascular disease reduction in response to statin treatment has only been assessed in small studies. In a pharmacogenetic genome wide association study (GWAS) analysis within the Genomic Investigation of Statin Therapy (GIST) consortium, we investigated whether genetic variation was associated with the response of statins on cardiovascular disease risk reduction.Methods: The investigated endpoint was incident myocardial infarction (MI) defined as coronary heart disease death and definite and suspect non-fatal MI. For imputed single nucleotide polymorphisms (SNPs), regression analysis was performed on expected allelic dosage and meta-analysed with a fixed-effects model, inverse variance weighted meta-analysis. All SNPs with p-values <5.0 × 10−4 in stage 1 GWAS meta-analysis were selected for further investigation in stage-2. As a secondary analysis, we extracted SNPs from the Stage-1 GWAS meta-analysis results based on predefined hypotheses to possibly modifying the effect of statin therapy on MI.Results: In stage-1 meta-analysis (eight studies, n = 10,769, 4,212 cases), we observed no genome-wide significant results (p < 5.0 × 10−8). A total of 144 genetic variants were followed-up in the second stage (three studies, n = 1,525, 180 cases). In the combined meta-analysis, no genome-wide significant hits were identified. Moreover, none of the look-ups of SNPs known to be associated with either CHD or with statin response to cholesterol levels reached Bonferroni level of significance within our stage-1 meta-analysis.Conclusion: This GWAS analysis did not provide evidence that genetic variation affects statin response on cardiovascular risk reduction. It does not appear likely that genetic testing for predicting effects of statins on clinical events will become a useful tool in clinical practice.

P5015Efficacy of lipid lowering therapy beyond statins to prevent cardiovascular events: A meta-analysis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
I Dykun ◽  
R Mincu ◽  
M Totzeck ◽  
T Rassaf ◽  
A A Mahabadi
Keyword(s):  
Myocardial Infarction ◽  
Relative Risk ◽  
Statin Therapy ◽  
Risk Reduction ◽  
Cardiovascular Events ◽  
Ldl Cholesterol ◽  
Meta Analysis ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy

Abstract Background Lipid lowering therapy is a key cornerstone in secondary prevention of patients with coronary artery disease. However, only a minority of patients with statin therapy reach LDL thresholds as suggested by the ESC. Ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors allow for reduction in LDL-cholesterol in addition to statin therapy. Purpose To perform a meta-analysis of existing trials, evaluating how lipid lowering therapy beyond statins impacts cardiovascular outcome. Methods We performed a systematic search using the Pubmed, Cochrane, SCOPUS, and Web of Science databases for studies, evaluating the impact of an intensified lipid lowering therapy via ezetimibe or PCSK-9 inhibitor in addition to statin therapy compared to statin therapy alone. Manuscript and congress presentations, published until 1st of November 2018, were included. We made our search specific and sensitive using Medical Subject Headings terms and free text and considered studies published in English language. Search terms used were “ezetimibe”, “evolocumab”, “alirocumab”, or “bococizumab” and “cardiovascular events”. Results A total of 100,610 patients from 9 randomized controlled trials (IMPROVE-IT, FOURIER, ODYSSEY Outcomes, SIPRE I, SPIRE II, ODYSSEY LONG TERM, OSLER-1 and OSLER-2, HIJ-PROPER) were included. Treatment with ezetimibe or a PCSK-9 inhibitor was associated with a 18% risk reduction in cardiovascular events (OR [95% CI]: 0.82 [0.75–0.89]). Effect sizes were similar for myocardial infarction (0.84 [0.76–0.92]) and even more pronounced for ischemic stroke (0.77 [0.67–0.83]). In contrast, all-cause mortality was not improved by the intensified lipid lowering therapy (0.94 [0.85–1.05]). No relevant heterogeneity and inconsistency between groups was present in all analyses (detailed data not shown). Comparing efficacy of LDL-reduction and relative risk redaction of cardiovascular events, a linear relationship was observed (figure). Figure 1. Correlation of reduction of LDL-cholesterol at one year with relative risk reduction (95% confidence interval) of cardiovascular events in included trials. Conclusion Intensified LDL-lowering therapy with ezetimibe or PCSK-9 inhibitors, in addition to statins, reduces the risk of myocardial infarction and stroke, however, does not impact overall mortality. There is a linear relationship between LDL reduction and cardiovascular risk reduction, confirming the beneficial effects of LDL lowering therapy beyond statins in secondary prevention.

scholarly journals 1462. The protective effect of pneumococcal vaccination on cardiovascular disease in adults: A systematic review and meta-analysis

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S733-S733
Author(s):  
Fawziah Marra ◽  
Angel Zhang ◽  
Emma Gillman ◽  
Katherine Bessai ◽  
Kamalpreet Parhar ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Protective Effect ◽  
Risk Reduction ◽  
Cardiovascular Event ◽  
Meta Analysis ◽  
Significant Risk ◽  
Pneumococcal Vaccination ◽  
The Impact ◽  
Research Grant

Abstract Background Epidemiological studies suggest a link between pneumococcal infection and an adverse cardiovascular outcome such as myocardial infarction. Therefore, studies have evaluated the protective effect of the 23-valent polysaccharide pneumococcal vaccination (PPV23), but results have varied. We conducted a meta-analysis to summarize the available evidence on the impact of PPV23 on cardiovascular disease Methods A literature search from January 1946 to September 2019 was conducted in Embase, Medline and Cochrane. All studies evaluating PPV23 compared to a control (placebo, no vaccine or another vaccine) for any cardiovascular events including myocardial infarction (MI), heart failure, cerebrovascular events were included. Risk ratios (RRs) were pooled using random effects models. Results Eighteen studies were included, with a total of 716,108 participants. Vaccination with PPV23 was associated with decreased risk of any cardiovascular event (RR: 0.91;95% CI: 0.84-0.99), and MI (RR of 0.88; 95% CI:0.79-0.98) in all age groups, with a significant effect in those 65 years and older, but not in the younger age group. Similarly, PPV23 vaccine was associated with significant risk reduction in all-cause mortality in all ages (RR: 0.78; 95%CI: 0.68-0.88), specifically in those aged 65 years and older (RR: 0.71; 95%CI: 0.60-0.84). A significant risk reduction in cerebrovascular disease was not observed following pneumococcal vaccination. Conclusion Polysaccharide pneumococcal vaccination decreases the risk of a cardiovascular event, specifically acute MI in the vaccinated population, particularly those 65 years of age and older. It would be highly beneficial to vaccinate the population who is at greater risk for cardiovascular diseases. Disclosures Fawziah Marra, BSc (Pharm), PharmD, Pfizer Inc (Research Grant or Support) Nirma Khatri Vadlamudi, BA, BS, MPH, Pfizer Inc (Research Grant or Support)

Genome-Wide Association Studies Identify Two Novel Loci Conferring Susceptibility to Diabetic Retinopathy in Japanese Patients with Type 2 Diabetes

2021 ◽  
Author(s):  
Minako Imamura ◽  
Atsushi Takahashi ◽  
Masatoshi Matsunami ◽  
Momoko Horikoshi ◽  
Minoru Iwata ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Association Studies ◽  
Meta Analysis ◽  
Japanese Patients ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Stage 1

Abstract Several reports have suggested that genetic susceptibility contributes to the development and progression of diabetic retinopathy. We aimed to identify genetic loci that confer susceptibility to diabetic retinopathy in Japanese patients with type 2 diabetes. We analysed 5 790 508 single nucleotide polymorphisms (SNPs) in 8880 Japanese patients with type 2 diabetes, 4839 retinopathy cases and 4041 controls, as well as 2217 independent Japanese patients with type 2 diabetes, 693 retinopathy cases, and 1524 controls. The results of these two genome-wide association studies (GWAS) were combined with an inverse variance meta-analysis (Stage-1), followed by de novo genotyping for the candidate SNP loci (p < 1.0 × 10−4) in an independent case–control study (Stage-2, 2260 cases and 723 controls). After combining the association data (Stage-1 and -2) using meta-analysis, the associations of two loci reached a genome-wide significance level: rs12630354 near STT3B on chromosome 3, p = 1.62 × 10−9, odds ratio (OR) = 1.17, 95% confidence interval (CI) 1.11–1.23, and rs140508424 within PALM2 on chromosome 9, p = 4.19 × 10−8, OR = 1.61, 95% CI 1.36–1.91. However, the association of these two loci were not replicated in Korean, European, or African American populations. Gene-based analysis using Stage-1 GWAS data identified a gene-level association of EHD3 with susceptibility to diabetic retinopathy (p = 2.17 × 10−6). In conclusion, we identified two novel SNP loci, STT3B and PALM2, and a novel gene, EHD3, that confers susceptibility to diabetic retinopathy; however, further replication studies are required to validate these associations.

Patients Living With HIV Are Less Likely to Receive Appropriate Statin Therapy for Cardiovascular Disease Risk Reduction

2021 ◽  
pp. 089719002199979
Author(s):  
Roshni P. Emmons ◽  
Nicholas V. Hastain ◽  
Todd A. Miano ◽  
Jason J. Schafer
Keyword(s):  
Cardiovascular Disease ◽  
Logistic Regression ◽  
Statin Therapy ◽  
Risk Reduction ◽  
Blood Cholesterol ◽  
Control Group ◽  
Atherosclerotic Cardiovascular Disease ◽  
Ascvd Risk ◽  
Living With Hiv ◽  
To Receive

Background: Recent studies suggest that statins are underprescribed in patients living with HIV (PLWH) at risk for atherosclerotic cardiovascular disease (ASCVD), but none have assessed if eligible patients receive the correct statin and intensity compared to uninfected controls. Objectives: The primary objective was to determine whether statin-eligible PLWH are less likely to receive appropriate statin therapy compared to patients without HIV. Methods: This retrospective study evaluated statin eligibility and prescribing among patients in both an HIV and internal medicine clinic at an urban, academic medical center from June-September 2018 using the American College of Cardiology/American Heart Association guideline on treating blood cholesterol to reduce ASCVD risk. Patients were assessed for eligibility and actual treatment with appropriate statin therapy. Characteristics of patients appropriately and not appropriately treated were compared with chi-square testing and predictors for receiving appropriate statin therapy were determined with logistic regression. Results: A total of 221/300 study subjects were statin-eligible. Fewer statin-eligible PLWH were receiving the correct statin intensity for their risk benefit group versus the uninfected control group (30.2% vs 67.0%, p < 0.001). In the multivariable logistic regression analysis, PLWH were significantly less likely to receive appropriate statin therapy, while those with polypharmacy were more likely to receive appropriate statin therapy. Conclusion: Our study reveals that PLWH may be at a disadvantage in receiving appropriate statin therapy for ASCVD risk reduction. This is important given the heightened risk for ASCVD in this population, and strategies that address this gap in care should be explored.

scholarly journals Genome-wide association of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) plasma levels in the ELSA-Brasil study

2020 ◽  
Author(s):  
Isabela Bensenor ◽  
Kallyandra Padilha ◽  
Isabella Ramos Lima ◽  
Raul Dias Santos ◽  
Gilles Lambert ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Genetic Variation ◽  
Disease Incidence ◽  
Plasma Concentrations ◽  
Genome Wide Association ◽  
Interindividual Variation ◽  
Lipid Lowering ◽  
Proprotein Convertase ◽  
Genome Wide ◽  
A Genome

AbstractPharmacological inhibition of PCSK9 (proprotein convertase subtilisin/kexin type 9) is an established therapeutic option to treat hypercholesterolemia and plasma PCSK9 levels have been implicated in cardiovascular disease incidence. A number of genetic variants within the PCSK9 gene locus have been shown to modulate PCSK9 levels, but these only explain a very small percentage of the overall PCSK9 interindividual variation. Here we present data on the genetic association structure between PCSK9 levels and genome-wide genetic variation in a healthy sample from the general population.We performed a genome-wide association study of plasma PCSK9 levels in a sample of Brazilian individuals enrolled in the ELSA-Brasil cohort (n=810). Enrolled individuals were free from cardiovascular disease, diabetes and were not under lipid-lowering medication. Genome-wide genotyping was conducted using the Axiom_PMRA.r3 array and imputation used the TOPMED multi-ancestry sample panel. Total PCSK9 plasma concentrations were determined using the Quantikine SPC900 ELISA kit.We observed two genome-wide significant loci and seven loci that reached the pre-defined p value threshold of 1 × 10−6. Significant variants were near KCNA5 and KCNA1, and LINC00353. Genetic variation at the PCSK9 locus was able to explain approximately 4% of the overall interindividual variation in PCSK9 levels. Colocalization analysis using eQTL data suggested RWDD3, ATXN7L1, KCNA1, and FAM177A1 to be potential mediators of some of the observed associations.Our results suggest that PCSK9 levels may be modulated by trans genetic variation outside of the PCSK9 gene and this may have clinical implications. Understanding both environmental and genetic predictors of PCSK9 levels may help identifying new targets for cardiovascular disease treatment and contribute to a better assessment of the benefits of long-term PCSK9 inhibition.

scholarly journals Migraine and cardiovascular disease

2011 ◽  
Vol 69 (1) ◽  
pp. 122-129 ◽  
Author(s):  
Marcelo E. Bigal
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Risk Factor ◽  
Diagnostic Criteria ◽  
Epidemiological Study ◽  
Cardiovascular Mortality ◽  
Coronary Revascularization ◽  
Meta Analysis ◽  
Established Risk Factor ◽  
The Brain

Migraine, especially migraine with aura is an established risk factor for ischemic lesions of the brain. Recent evidence has also linked migraine with and without aura to a broader range of ischemic vascular disorders including angina, myocardial infarction, coronary revascularization, claudication and cardiovascular mortality. The topic is therefore of considerable interest. Accordingly, herein we review the association between migraine and cardiovascular disease. We start by briefly presenting diagnostic criteria for migraine and revising its pathophysiology. We follow by summarizing the evidence on the topic. We then briefly present the results of a recent meta-analysis. We close by highlighting results of a large epidemiological study conducted after the publication of the meta-analysis.

Meta-analysis of genome-wide association studies to assess C-reactive protein response to statin therapy

The Lancet ◽  
2016 ◽  
Vol 387 ◽  
pp. S37 ◽  
Author(s):  
Harshal Deshmukh ◽  
Daniel Chasman ◽  
Stella Trompet ◽  
Xiaohui Li ◽  
Fangui Sun ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Genome Wide ◽  
Protein Response
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