Causal associations between premature ovarian insufficiency and cardiovascular diseases: a Mendelian randomization study

To date, there remains a paucity of prospective studies examining the association between premature ovarian insufficiency (POI) and cardiovascular diseases (CVD). The objective of this study was to investigate the potential association between POI and CVD utilizing the method of Mendelian randomization (MR). MR analyses utilized summary statistics from the most extensive genome-wide association studies (GWAS) on POI and CVD extracted from European ancestry cohorts and the FinnGen biobank. The inverse variance-weighted (IVW) method was the primary MR analysis technique. Supplementary analyses were performed using MR-Robust Adjusted Profile Score (MR-RAPS). Cochran's Q statistic, MR-Egger, and weighted median MR models were employed to further assess heterogeneity and horizontal pleiotropy. Causal effects of POI on coronary heart disease (odds ratio [OR] = 1.048, 95% confidence interval [CI]: 1.006-1.091; p = 0.023)] and ischemic stroke (OR = 1.010, 95% CI: 1.000-1.020; p = 0.0498) were found. However, we did not observe a significant correlation between POI and hypertension (OR = 0.999, 95% CI: 0.994-1.004, p = 0.691), heart failure (OR = 1.009, 95% CI: 0.999-1.020, p = 0.0725), atrial fibrillation (OR = 0.995, 95% CI: 0.986-1.004, p = 0.3035), and myocardial infarction (OR = 1.002, 95% CI: 0.991-1.013, p = 0.7061). POI was causally associated with coronary heart disease and ischemic stroke, with no apparent impact on hypertension, heart failure, atrial fibrillation, or myocardial infarction. The causal relationship between POI and CVD underscores the imperative for proactive cardiovascular risk management in individuals with POI.