A causal relationship between irritability and cardiovascular diseases: a Mendelian randomization study

Dihui Cai; Yin Fu; Yongfei Song; Hui Lin; Yanna Ba; Jiangfang Lian

doi:10.3389/fcvm.2023.1174329

A causal relationship between irritability and cardiovascular diseases: a Mendelian randomization study

Front Cardiovasc Med. 2023 May 30:10:1174329. doi: 10.3389/fcvm.2023.1174329. eCollection 2023.

Authors

Dihui Cai^#¹, Yin Fu^#¹, Yongfei Song¹, Hui Lin¹, Yanna Ba¹, Jiangfang Lian¹

Affiliation

¹ Department of Cardiology, Lihuili Hospital Affiliated to Ningbo University, Ningbo University, Ningbo Institute of Innovation for Combined Medicine and Engineering, Ningbo, China.

^# Contributed equally.

Abstract

Background: Observational studies have suggested that irritability is associated with a higher risk of cardiovascular disease (CVD). However, the potential causal association is not clear. Therefore, we used Mendelian randomization (MR) analysis to assess the causal association of irritability with CVD risk.

Methods: A two-sample MR analysis was performed to confirm the causal association of irritability with the risk of several common CVDs. The exposure data were derived from the UK biobank involving 90,282 cases and 232,386 controls, and outcome data were collected from the published genome-wide association studies (GWAS) and FinnGen database. Inverse-variance weighted (IVW), MR-Egger, and weighted median methods were performed to assess the causal association. Furthermore, the mediating effect of smoking, insomnia, and depressed affect was explored by using a two-step MR.

Results: The MR analysis indicated that genetically predicted irritability increased the risk of CVD, including coronary artery disease (CAD) (Odds ratio, OR: 2.989; 95% confidence interval, CI: 1.521-5.874, p = 0.001), myocardial infarction (MI) (OR: 2.329, 95% CI: 1.145-4.737, p = 0.020), coronary angioplasty (OR: 5.989, 95% CI: 1.696-21.153, p = 0.005), atrial fibrillation (AF) (OR: 4.646, 95% CI: 1.268-17.026, p = 0.02), hypertensive heart disease (HHD) (OR: 8.203; 95% CI: 1.614-41.698, p = 0.011), non-ischemic cardiomyopathy (NIC) (OR: 5.186; 95% CI: 1.994-13.487, p = 0.001), heart failure (HF) (OR: 2.253; 95% CI: 1.327-3.828, p = 0.003), stroke (OR: 2.334; 95% CI: 1.270-4.292, p = 0.006), ischemic stroke (IS) (OR: 2.249; 95% CI: 1.156-4.374, p = 0.017), and ischemic stroke of large-artery atherosclerosis ISla (OR: 14.326; 95% CI: 2.750-74.540, p = 0.002). The analysis also indicated that smoking, insomnia, and depressed affect play an important role in the process of irritability leading to cardiovascular disease.

Conclusion: Our findings support the first genetic evidence of the causality of genetically predicted irritability with the risk of developing into CVDs. Our results deliver a viewpoint that more early active interventions to manage an individual's anger and related unhealthy lifestyle habits are needed to prevent the occurrence of adverse cardiovascular events.

Keywords: Mendelian randomization; cardiovascular disease; coronary artery disease; heart failure; irritability.

Grants and funding

This study was funded by the National Natural Science Foundation of China (grant no. 81870255), the Natural Science Foundation of the Zhejiang Province (grant no. LY21H020001), the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (grant no. 2021KY306), and the Natural Science Foundation of Ningbo Municipality (grant no. 2021J296).