7-013 Exploring the causal relevance of genetically predicted endometriosis on cardiac structure, function and cardiovascular outcomes: a endelian randomisation study

Introduction Endometriosis is a chronic condition affecting 5–10% of women of reproductive age, characterised by ectopic endometrial tissue. Although its symptoms, such as chronic pain, anxiety, and depression, are well-documented, the disease9s complex pathophysiology and its association with cardiovascular disease (CVD) remain unclear. Possible theories include hormonal changes and release of pro-inflammatory mediators leading to systemic inflammation. Cohort studies have shown a potential link, but findings remain inconsistent. In addition, a major limitation to causal inference in observational studies is the potential for bias and residual confounding. Methods Using Mendelian randomisation (MR), we investigate the causal relationship between genetically predicted endometriosis and CVD, using data from a genome-wide association study. Sex-specific, uncorrelated (r2 < 0.05) single nucleotide polymorphisms associated with each exposure at genome-wide significance (P < 5 × 10−8) were selected as instrumental variants. Instrumental variables were extracted from a GWAS meta-analysis on 60,674 endometriosis cases and 701,926 controls which identified multiple genetic risk loci associated with endometriosis. For the primary analysis, inverse-variance weighted MR was used to examine associations with CVD outcomes, including atrial fibrillation, heart failure, ischaemic stroke and coronary artery disease, as well as cardiac magnetic resonance (CMR) measures of cardiac structure and function. Results No significant association was found between genetically predicted endometriosis and coronary artery disease (OR=1.00, 95%CI 0.93 to 1.07, p=0.933), heart failure (OR=1.00, 95%CI 0.94 to 1.05, p=0.920), ischaemic stroke (OR=0.97, 95%CI 0.91 to 1.03, p=0.342), and atrial fibrillation (OR=1.06, 95%CI 1.00 to 1.12, p=0.059), as well as CMR measures of cardiac structure and function in the left and right heart. Genetically predicted endometriosis was not associated with aorta measurements including proximal pulmonary artery diameter and ascending aorta diameter. Sensitivity analyses indicated potential pleiotropic effects between genetically predicted endometriosis and ascending aorta diameter (MR-Egger intercept test p=0.03, MR-Egger β=0.15 [0.08 to 0.21], p=0.04). Further potential direction pleiotropy was seen between genetically predicted endometriosis and proximal pulmonary artery diameter (MR-Egger intercept test p=0.021, MR-Egger β=0.13 [0.07 to 0.19], p=0.05). The minimum relative risk increase that we had 80% power to detect was 5.3% for AF, 11.5% for CAD, 3.9% for HF and 7.1% for ischaemic stroke. Conclusion MR analyses do not identify any direct evidence to support a causal role of genetically predicted endometriosis on CVD or measures of adverse cardiac structure and function. There was a trend toward an association of genetically predicted endometriosis with higher risk of AF. Further research is warranted when larger data sources become available.