scholarly journals Effects of copper and zinc on ischemic heart disease and myocardial infarction: a Mendelian randomization study

2018 ◽  
Vol 108 (2) ◽  
pp. 237-242 ◽  
Author(s):  
Hanish P Kodali ◽  
Brian T Pavilonis ◽  
C Mary Schooling
Keyword(s):  
Sensitivity Analysis ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Dietary Factors ◽  
Ischemic Heart ◽  
P Value ◽  
Copper And Zinc ◽  
A Genome

ABSTRACTBackgroundDespite great progress in prevention and control, ischemic heart disease (IHD) remains a leading cause of global morbidity and mortality. Diet plays a key role in IHD, but a comprehensive delineation of the role of dietary factors in IHD is not yet quite complete.ObjectiveThe aim of this study was to test the long-standing hypothesis that copper is protective and zinc harmful in IHD.DesignWe used separate-sample instrumental variable analysis with genetic instruments (Mendelian randomization). We obtained single nucleotide polymorphisms (SNPs) from a genome wide association study, strongly (P value < 5 × 10−8) and independently associated with erythrocyte copper and zinc. We applied these genetic predictors of copper and zinc to the largest, most extensively genotyped IHD case (n ≤ 76014)-control (n ≤ 264785) study, based largely on CARDIoGRAMplusC4D 1000 Genomes and the UK Biobank SOFT CAD, to obtain SNP-specific Wald estimates for the effects of copper and zinc on IHD, which were combined through the use of inverse variance weighting. Sensitivity analysis included use of the MR-Egger method, and reanalysis including SNPs independently associated with erythrocyte copper and zinc at P value < 5 × 10−6.ResultsGenetically instrumented copper was negatively associated with IHD (OR: 0.94; 95% CI: 0.90, 0.98). Genetically instrumented zinc was positively associated with IHD (OR: 1.06; 95% CI: 1.02, 1.11). Sensitivity analysis via MR-Egger gave no indication of unknown pleiotropy; less strongly associated SNPs gave similar results for copper.ConclusionGenetic validation of a long-standing hypothesis suggests that further investigation of the effects, particularly of copper, on IHD may provide a practical means of reducing the leading cause of mortality and morbidity.

scholarly journals Effect of glutamate and aspartate on ischemic heart disease, blood pressure, and diabetes: a Mendelian randomization study

2019 ◽  
Vol 109 (4) ◽  
pp. 1197-1206 ◽  
Author(s):  
Jie V Zhao ◽  
M K Kwok ◽  
C Mary Schooling
Keyword(s):  
Blood Pressure ◽  
Sensitivity Analysis ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Evolutionary Biology ◽  
Mendelian Randomization ◽  
Meta Analysis ◽  
Genetic Selection ◽  
Ischemic Heart ◽  
Uk Biobank

ABSTRACT Background Evolutionary biology suggests reproduction trades off against longevity. Genetic selection in favor of fertility and ischemic heart disease (IHD) exists in humans. Observationally, soy protects against IHD. Soy amino acids, glutamate and aspartate, may lower androgens. No large randomized controlled trials testing their health effects exist. Objective Using Mendelian randomization, we assessed how genetically predicted glutamate and aspartate affected IHD, blood pressure, and diabetes. Methods A separate sample instrumental variable analysis with genetic instruments was used to obtain unconfounded estimates using genetic variants strongly (P < 5 × 10−8) and solely associated with glutamate or aspartate applied to an IHD case (n ≤76,014)–control (n ≤ 264,785) study (based on a meta-analysis of CARDIoGRAMplusC4D 1000 Genomes, UK Biobank CAD SOFT GWAS and Myocardial Infarction Genetics and CARDIoGRAM Exome), blood pressure from the UK Biobank (n ≤ 361,194), and the DIAbetes Genetics Replication And Meta-analysis diabetes case (n = 26,676)–control (n = 132,532) study. A weighted median and MR-Egger were used for a sensitivity analysis. Results Glutamate was not associated with IHD, blood pressure, or diabetes after correction for multiple comparisons. Aspartate was inversely associated with IHD (odds ratio (OR) 0.92 per log-transformed standard deviation (SD); 95% confidence interval (CI) 0.88, 0.96) and diastolic blood pressure (−0.03; 95% CI −0.04, −0.02) using inverse variance weighting, but not diabetes (OR 1.00; 95% CI 0.91, 1.09). Associations were robust to the sensitivity analysis. Conclusions Our findings suggest aspartate may play a role in IHD and blood pressure, potentially underlying cardiovascular benefits of soy. Clarifying the mechanisms would be valuable for IHD prevention and for defining a healthy diet.

EXPRESS: Effect of genetic liability to visceral adiposity on stroke and its subtypes: a Mendelian randomization study

2021 ◽  
pp. 174749302110062
Author(s):  
Bin Yan ◽  
Jian Yang ◽  
Li Qian ◽  
Fengjie Gao ◽  
Ling Bai ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Ischemic Stroke ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Visceral Adiposity ◽  
Large Artery ◽  
Nucleotide Polymorphisms ◽  
Genetic Liability ◽  
A Genome ◽  
Increased Risk

Background: Observational studies have found an association between visceral adiposity and stroke. Aims: The purpose of this study was to investigate the role and genetic effect of visceral adipose tissue (VAT) accumulation on stroke and its subtypes. Methods: In this two-sample Mendelian randomization (MR) study, genetic variants (221 single nucleotide polymorphisms; P<5×10-8) using as instrumental variables for MR analysis was obtained from a genome-wide association study (GWAS) of VAT. The outcome datasets for stroke and its subtypes were obtained from the MEGASTROKE consortium (up to 67,162 cases and 453,702 controls). MR standard analysis (inverse variance weighted method) was conducted to investigate the effect of genetic liability to visceral adiposity on stroke and its subtypes. Sensitivity analysis (MR-Egger, weighted median, MR-PRESSO) were also utilized to assess horizontal pleiotropy and remove outliers. Multi-variable MR analysis was employed to adjust potential confounders. Results: In the standard MR analysis, genetically determined visceral adiposity (per 1 SD) was significantly associated with a higher risk of stroke (odds ratio [OR] 1.30; 95% confidence interval [CI] 1.21-1.41, P=1.48×10-11), ischemic stroke (OR 1.30; 95% CI 1.20-1.41, P=4.01×10-10), and large artery stroke (OR 1.49; 95% CI 1.22-1.83, P=1.16×10-4). The significant association was also found in sensitivity analysis and multi-variable MR analysis. Conclusions: Genetic liability to visceral adiposity was significantly associated with an increased risk of stroke, ischemic stroke, and large artery stroke. The effect of genetic susceptibility to visceral adiposity on the stroke warrants further investigation.

scholarly journals Comprehensive Study of Acute Myocardial Infarctions Triggers

2020 ◽  
Author(s):  
Kamal Khademvatani ◽  
Amin Sedokani ◽  
Sima Masudi ◽  
Parisa Nejati ◽  
Mir Hossein Seyed-Mohammadzad ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Health Care Systems ◽  
Ischemic Heart ◽  
Clinical Event ◽  
P Value ◽  
Cross Sectional

AbstractAimMyocardial infarction (MI) is one of the most important cardiovascular diseases. A trigger is an external stimulus, potential to create a pathological change leading to a clinical event. In addition to classic risk factors of ischemic heart disease and myocardial infarction, MI triggers play critical roles in the incidence of acute MI.Methods and ResultsThis is a cross-sectional study of 254 patients with the first acute myocardial infarction referring to Seyedoshohada heart center of Urmia, Iran were enrolled in the study within one year of study. After 48h of hospitalization and, treatment, and cardiac caring, the patients were provided with the questionnaire to collecting the history of the disease ad triggers. In addition to laboratory and paraclinical data, the analysis of the study was performed. Out of 220 (86.4%) patients with STEMI and 34 (13.6%) patients with NSTEMI, there were significant differences (P-value <0.05) in AMI triggers with LVEF (0.03), gender (0.027), residency and living area (0.039), occupation (0.002), smoking (0.008), abnormal serum TG levels (0.018) and the season of AMI occurrence (0.013). The mean age for AMI patients was 60.4±12.97 years old with a mean BMI of 26.65±4.35 kg/m2.ConclusionIn addition to classic risk factors of ischemic heart disease and myocardial infarction, health care systems and physicians must pay more attention to triggers that may induce an acute myocardial infarction in people with predisposing factors especially in the male sex, stressful and hand working jobs, and psychological and mental tension patients.

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