(non-aspirin) NSAIDs use and risk of cardiovascular diseases: A Mendelian randomization study

Abstract Objectives Non-steroidal anti-inflammatory drugs (NSAIDs) are currently the most common anti-inflammatory and analgesic drugs. Some clinical studies have reported that NSAIDs increase the incidence of several cardiovascular diseases (CVDs). However, a solid causal association has not been demonstrated. In this Mendelian randomization (MR) study, we investigated the causal association of NSAIDs use with the risk of CVDs. Methods A two-sample MR was utilized to determine whether there is a causal relationship between NSAIDs use and the risk of CVDs. Single-nucleotide polymorphisms(SNPs)associated with NSAIDs indices were used as instrumental variables to estimate the associations with the risk of CVDs. The dataset was obtained from genome-wide association studies (GWAS). Estimation of the causal effect was mainly performed using the random effects inverse-variance weighted method (IVW). Furthermore, Cochran’s Q test, MR-Egger intercept tests, MR-PRESSO, leave-one-out analyses, and funnel plot were used in the sensitivity analysis. Results NSAIDs use increase causally the risks of coronary heart disease [CHD; odds ratio(OR) = 1.005, 95% confidence interval(CI): 1.002–1.007, P < 0.05], heart failure(HF; OR = 1.091; 95% CI, 1.027–1.160; P < 0.05), atrial fibrillation(AF; OR = 1.087; 95% CI, 1.034–1.142; P < 0.05) with multiplicative random-effects IVW MR analysis. However, there was no suggestive evidence of a causal association between NSAIDs use and myocardial infarction (MI; OR = 1.001; 95% CI, 0.999–1.003; P = 0.23), or hypertension(OR = 1.001; 95% CI, 0.995–1.007; P = 0.72). The main results are kept stable in the sensitivity analysis. Conclusion This MR study provided support for a causal association of NSAIDs use with CHD, HF, and AF. However, it did not support an association of genetically predicted NSAIDs use on MI, and hypertension.