The causal association between primary aldosteronism and cardiovascular diseases: a bidirectional two-sample Mendelian randomization study

Abstract

Background Many previous observational studies have shown that primary aldosteronism (PA) can increase the risk of cardiovascular diseases (CVDs), but the causal relationship is unclear. Methods We performed a bidirectional two-sample Mendelian randomization (MR) analysis to explore the causal association between PA and CVDs using summary statistics from the large publicly accessible genome-wide association study (GWAS) of PA (Ncases=1,724, Ncontrols=4,246) as well as six types of CVDs. Moreover, the inverse variance weighted (IVW) was used as the main method in MR analysis, and sensitivity analysis was further performed. Results Our results from the IVW analysis showed that genetically predicated PA conferred an increased risk of heart failure [odds ratio (OR) = 1.027, 95% confidence interval (CI): 1.013–1.041, p = 1.452×10− 4], atrial fibrillation (OR = 1.066, 95%CI: 1.051–1.082, p = 2.835×10− 17), hypertension (OR = 1.163, 95%CI: 1.105–1.223, p = 4.752×10− 9), coronary artery disease (OR = 1.032, 95%CI: 1.022–1.043, p = 1.664×10− 9), stroke (OR = 1.060, 95%CI: 1.044–1.075, p = 2.270×10− 15), myocardial infarction (OR = 1.020, 95%CI: 1.001–1.039, p = 0.044). However, with the exception of hypertension (OR = 3.316, 95%CI: 1.347–8.159, p = 0.009), CVDs leading to PA were not confirmed in reverse causality analysis. The sensitivity analysis showed the robustness of the results. Conclusion It is confirmed from the genetic level that there is a causal relationship between PA and CVDs and also confirmed that PA and hypertension are mutually causal. Our work highlights the necessity of routine screening, diagnosis and treatment of PA.