Abstract
Observational studies have reported an association of handgrip strength with risk of cardiovascular disease. However, residual confounding and reverse causation may have influenced these findings. A Mendelian randomization (MR) study was conducted to examine whether handgrip is causally associated with cardiovascular disease. Two single nucleotide polymorphisms (SNPs), rs3121278 and rs752045, were used as the genetic instruments for handgrip. The effect of each SNP on coronary artery disease/myocardial infarction (CAD/MI) was weighted by its effect on handgrip strength, and estimates were pooled to provide a summary measure for the effect of increased handgrip on risk of CAD/MI. MR analysis showed that higher grip strength reduces risk for CAD/MI, with 1-kilogram increase in genetically determined handgrip reduced odds of CAD by 6% (odds ratio (OR) = 0.94, 95% confidence interval (CI) 0.91–0.99, P = 0.01), and reduced odds of MI by 7% (OR = 0.93, 95% CI 0.89–0.98, P = 0.003). No association of grip strength with type 2 diabetes, body mass index, LDL- and HDL-cholesterol, triglycerides and fasting glucose was found. The inverse causal relationship between handgrip and the risk of CAD or MI suggests that promoting physical activity and resistance training to improve muscle strength may be important for cardiovascular health.
Highlights
Handgrip strength, a prognostic marker for healthy aging, has been associated with a number of chronic disease outcomes in observational studies
Each handgrip increasing allele was associated with 5–7% reduction in coronary artery disease (CAD) risk and 6–10% reduction in myocardial infarction (MI) risk
The current Mendelian randomization analysis using the most updated genome wide association study (GWAS) results on handgrip found that greater grip strength was significantly associated with lower risks of coronary artery disease and myocardial infarction
Summary
A prognostic marker for healthy aging, has been associated with a number of chronic disease outcomes in observational studies. Traditional observational studies cannot account for all possible confounders It is unclear whether grip strength, as a marker of muscle strength, causes the metabolic abnormalities or cardiovascular disease per se, or is only a predictor of underlying health conditions. Mendelian randomization (MR) studies make use of genetic variants as instrumental variables to investigate the effect of environmental exposures on health outcomes. Single nucleotide polymorphisms (SNPs) identified in a recent genome wide association study (GWAS)[7] were used as genetic instrumental variables, to examine the causal effect of handgrip on coronary artery disease (CAD) and cardiovascular risk factors
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