Key result
Higher CAD polygenic risk score is linked to ~63% higher sudden cardiac death risk per SD.
Why the study?
Sudden cardiac death is a major cause of mortality among patients with coronary artery disease, motivating this study to identify risk factors for CAD-related SCD through autopsy data and genetic screening with a particular emphasis on rare variants.
What environmental, pathological, and genetic risk factors (including polygenic risk scores and rare variants) are associated with coronary artery disease-related sudden cardiac death compared to silent coronary artery disease?
Case-Control (n=482)
No
What environmental, pathological, and genetic risk factors (including polygenic risk scores and rare variants) are associated with coronary artery disease-related sudden cardiac death compared to silent coronary artery disease?
Both acquired factors (nocturnal timing, winter season, multivessel disease, RCA stenosis, unstable plaque) and genetic factors (elevated CAD polygenic risk score and rare variants in MUC19 and CGN) are associated with sudden cardiac death in individuals with previously undiagnosed coronary artery disease.
Answers are grounded in this paper and cite their sources.
Polygenic risk scores may refine sudden cardiac death stratification in CAD; extends genetic associations but remains hypothesis-generating pending prospective validation.
Sudden cardiac death (SCD) is a major cause of mortality among patients with coronary artery disease (CAD). This study aimed to identify risk factors for CAD-related SCD (SCDCAD) through autopsy data and genetic screening with a particular emphasis on rare variants (minor allele frequency < 0.01). We included 241 SCDCAD cases (mean age 54.6 ± 12.8 years, 74.7% male) verified by medico-legal examination and 241 silent CAD controls (mean age 53.6 ± 15.2 years, 25.3% female) who died from severe craniocerebral trauma. Information about death characteristics was obtained from questionnaires, police reports and autopsy data. Whole-exome sequencing was performed on myocardial tissue samples. Polygenic risk score (PRS) from a previously validated model was applied and rare variant pathogenicity was predicted using in silico tools. SCDCAD victims predominantly died at night and showed higher mortality rates during summer and winter months, with more complex coronary disease. Nocturnal time (adjusted odds ratio [AOR] = 3.53, 95% CI: 2.37–5.25, p < 0.001), winter (AOR = 2.06, 95% CI: 1.33–3.20, p = 0.001), multiple vessel occlusion (AOR = 1.79, 95% CI: 1.16–2.77, p = 0.009), right coronary artery stenosis (AOR = 2.38, 95% CI: 1.54–3.68, p < 0.001) and unstable plaque (AOR = 2.17, 95% CI: 1.46–3.23, p < 0.001) were identified as risk factors of SCDCAD. The PRS score was associated with a 60% increased risk of SCDCAD (OR = 1.632 per SD, 95%CI: 1.631–1.633, p < 0.001). Genetic analysis identified MUC19 and CGN as being associated with SCDCAD. We identified both hereditary and acquired risk factors that may contribute to cardiac dysfunction and precipitate SCD in CAD patients, thereby facilitating the prevention and early recognition of high-risk individuals.
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He et al. (2025) conducted a case-control in Coronary artery disease-related sudden cardiac death (SCDCAD) (n=482). Coronary artery disease polygenic risk score (CAD-PRS) and clinical/autopsy risk factors (nocturnal time, winter, multivessel occlusion, RCA stenosis, unstable plaque) vs. Silent coronary artery disease controls dying from craniocerebral trauma was evaluated on Coronary artery disease-related sudden cardiac death (SCDCAD) (OR 1.632 per SD, 95% CI 1.631-1.633, p=<0.001). Higher CAD polygenic risk scores increased sudden cardiac death risk by 60% per SD, alongside nocturnal death, RCA stenosis, and unstable plaque.
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