Impact of Insomnia on Myocardial Infarction Risk and Coronary Plaque Vulnerability: Insights From Mendelian...

Insomnia is a prevalent sleep disorder increasingly recognized as a risk factor for cardiovascular diseases (CVDs). However, its causal relationship with myocardial infarction (MI) and its impact on coronary plaque vulnerability remain poorly understood.

We performed Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary data for insomnia (n = 462,341) and MI (n = 484,598) in populations of European descent. Additionally, 340 patients with coronary artery disease (CAD) underwent coronary angiography and optical coherence tomography (OCT) imaging. Insomnia was assessed by the Insomnia Severity Index (ISI), and OCT was used to evaluate plaque features including thin-cap fibroatheroma (TCFA), fibrous cap thickness, lipid arc, macrophage infiltration, and plaque rupture.

MR analysis showed a potential causal effect of genetically predicted insomnia on MI risk (OR = 1.015; 95% CI: 1.004-1.027; p = 0.007), with no evidence of pleiotropy or heterogeneity. Clinically patients with insomnia (ISI ≥ 8) had higher rates of hypertension (54.3% vs. 39.6%) and MI (32.4% vs. 21.7%), elevated CRP levels, and exhibited greater plaque vulnerability on OCT, including increased incidence of TCFA (29.5% vs. 17.0%), thinner fibrous caps, larger lipid arcs, and more frequent macrophage infiltration and plaque rupture. Logistic regression identified both insomnia (OR = 1.806; p = 0.037) and CRP (OR = 1.384; p = 0.034) as independent predictors of TCFA.

This study provides genetic and clinical evidence that insomnia contributes to MI risk and coronary plaque vulnerability, underscoring the importance of addressing sleep disturbances in CAD management.