Triglycerides play a crucial role in the pathway from depression to cardiomyopathy: A mediation Mendelian randomization study

The causal relationships among depression, hypertriglyceridemia, and cardiomyopathy remain undefined. Cardiomyopathy encompasses both ischemic heart disease (IHD) and dilated cardiomyopathy (DCM). Inverse variance weighted random-effect, inverse variance weighted fixed-effect, maximum likelihood estimation, MR-Egger, weighted median, and penalized weighted median were employed to evaluate the causal relationship between exposure and outcome. Stepwise testing and multivariable Mendelian randomization analyses were employed in the mediation analysis. The onset of depression precipitates an increase in triglyceride levels, which in turn escalates the risk of developing DCM. The onset of depression not only directly escalates the risk of developing IHD but also indirectly amplifies this risk by elevating triglyceride levels. Exacerbation of depression was observed to lead to an elevation in triglyceride levels (odds ratio [OR]: 1.093, 95% confidence interval [CI]: 1.041-1.149, P < .001). There was no direct causal link established between depression and DCM (P = .392). The incidence of depression was associated with an increased risk of developing IHD (OR: 1.019, 95% CI: 1.011-1.026, P < .001). Elevated triglyceride levels were found to augment the risk of both IHD (OR: 1.019, 95% CI: 1.015-1.023, P < .001) and DCM (OR: 1.240, 95% CI: 1.047-1.469, P = .013). In the causal pathway between depression and DCM, triglycerides were found to mediate 100% of the effect. In the relationship between depression and IHD, triglycerides accounted for a mediation proportion of 8.4%.