A causal relationship between irritability and cardiovascular diseases: a Mendelian randomization study
Dihui Cai1, Yin Fu1, Yongfei Song1
1Department of Cardiology, Lihuili Hospital Affiliated to Ningbo University, Ningbo University, Ningbo Institute of Innovation for Combined Medicine and Engineering, Ningbo, China.
Frontiers in Cardiovascular Medicine
|June 16, 2023
Summary
Genetically predicted irritability significantly increases the risk of cardiovascular diseases (CVDs), including heart attack and stroke. Managing anger and unhealthy lifestyle habits may help prevent adverse cardiovascular events.
Area of Science:
- Genetics
- Cardiovascular Medicine
- Psychiatry
Background:
- Observational studies suggest a link between irritability and increased cardiovascular disease (CVD) risk.
- The causal relationship between irritability and CVD remains unclear.
- Mendelian randomization (MR) analysis is employed to investigate this potential causal association.
Purpose of the Study:
- To assess the causal association between genetically predicted irritability and the risk of developing various cardiovascular diseases.
- To explore potential mediating factors, such as smoking, insomnia, and depressed affect, in the pathway from irritability to CVD.
Main Methods:
- A two-sample Mendelian randomization (MR) analysis was conducted.
- Exposure data originated from the UK Biobank (90,282 cases, 232,386 controls).
- Outcome data were sourced from published genome-wide association studies (GWAS) and the FinnGen database.
- Standard MR methods (IVW, MR-Egger, weighted median) and two-step MR for mediation analysis were utilized.
Main Results:
- Genetically predicted irritability was found to significantly increase the risk of multiple CVDs, including coronary artery disease, myocardial infarction, atrial fibrillation, heart failure, and stroke.
- Specific increased risks were observed for coronary angioplasty, hypertensive heart disease, non-ischemic cardiomyopathy, and ischemic stroke subtypes.
- Smoking, insomnia, and depressed affect were identified as important mediators in the link between irritability and CVD.
Conclusions:
- This study provides the first genetic evidence supporting a causal role of irritability in the development of CVDs.
- Findings highlight the need for early interventions targeting anger management and associated unhealthy lifestyle habits to prevent cardiovascular events.
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