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Observational Study
. 2024 Feb 16;19(1):19.
doi: 10.5334/gh.1302. eCollection 2024.

Heartache and Heartbreak: An Observational and Mendelian Randomization Study

Dihui Cai  1 , Mengming Xia  2 , Xuhui Chen  2 , Kunimasa Yagi  3 , Liang Xu  4 , Bingyu Wang  1 , Yanyi Wang  5 , Yujie Zhou  5 , Jianhui Liu  1
Affiliations
Observational Study

Heartache and Heartbreak: An Observational and Mendelian Randomization Study

Dihui Cai et al. Glob Heart. .

Abstract

Background: Depression has a significant effect on cardiovascular disease (CVD), but uncertainties persist regarding which modifiable risk factors mediate the causal effects. We aim to determine whether depression is causally linked to CVD and which modifiable risk factors play potential mediating roles.

Methods: We used a two-sample Mendelian randomization (MR) approach and NHANES 2007-2018 data to estimate the effects of depression on various CVD cases and investigated 28 potential mediators of the association between depression and CVD.

Results: The results of our MR analysis indicated that genetically determined depression was associated with increased risk of several CVD, including coronary heart disease (odds ratio (OR) = 1.14; 95% confidence interval (CI): 1.05,1.22), myocardial infarction (OR = 1.19; 95% CI, 1.09,1.31), atrial fibrillation (OR = 1.14; 95% CI, 1.06,1.22), and stroke (OR = 1.13; 95% CI, 1.05,1.22). However, there was no causal association between depression and heart failure. Four out of 28 cardiometabolic risk factors, including hyperlipidemia, hypertension, diabetes, and prescription opioid use, were identified as mediators of the association between depression and various CVDs. Observational association analyses from NHANES data yielded consistent results.

Conclusion: Our findings demonstrated that depression has a causal detrimental effect on various CVDs. Four causal mediators (hyperlipidemia, hypertension, diabetes, and prescription opioid use) were screened to explain the causal effect. Implementing targeted management strategies for these risk factors may be warranted to mitigate the public health burden of CVD among individuals with depression.

Keywords: Mendelian randomization; cardiovascular diseases; depression.

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Conflict of interest statement

The authors have no competing interests to declare.

Figures

A. Study design. B. Mediator screening process
Figure 1
A. Study design. B. Mediator screening process. HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TDI, Townsend deprivation index; TV, television.
A. Mendelian randomization (MR) estimates of the causal associations of depression on cardiovascular diseases. B. MR estimates of proportions mediated by mediators in the causal association between depression on cardiovascular diseases
Figure 2
A. Mendelian randomization (MR) estimates of the causal associations of depression on cardiovascular diseases. B. MR estimates of proportions mediated by mediators in the causal association between depression on cardiovascular diseases. OR, odds ratio; CI, confidence interval; HTN, hypertension; HPL, hyperlipidemia; DM2, type 2 diabetes; POU, prescription opioid use; CHD, coronary heart disease; MI, myocardial infarction; TS, total stroke, AF, atrial fibrillation.
See this image and copyright information in PMC

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