Causal atlas on comorbidities in cardiomyopathy: a Mendelian randomization study of European ancestry.

Background: Cardiomyopathy (CM) is often accompanied by comorbidities that increase the risk of death. Our aim is to explore the causal association between CM and its subtypes and various related comorbidities.

Methods: Bidirectional Mendelian randomization (MR) was used to explore the causal association between 39 comorbidities and CM, 13 comorbidities and hypertrophic cardiomyopathy (HCM), 25 comorbidities and dilated cardiomyopathy (DCM), and 13 comorbidities and restrictive cardiomyopathy (RCM). Besides, we explored the causal associations between systolic, diastolic, and pulse pressure with CM and DCM, respectively. MR Mediation analysis was used to explore whether atrial fibrillation (AF) or hypertension was as mediating variable mediating the causal association between each other and CM.

Results: By MR analysis, we found that AF (OR = 1.28) and hypertension (OR = 3.58) were associated with an increased risk of CM, and CM was causally associated with an increased risk of heart failure (OR = 1.40). In addition, hypertension was causally associated with a lower risk of DCM (OR = 0.22). The results of the causal association of systolic, diastolic, and pulse pressure with CM and DCM were consistent with the direction of the causal association of hypertension with CM and DCM. Through MR Mediation analysis, we found AF as a mediating factor mediates the causal association between hypertension and CM, with a mediating proportion of about 16.22%.

Conclusions: This study is the first to reveal the causal association between certain comorbidities and CM and DCM, and to find possible mediating effects among them.