Comparison of traditional cardiovascular risk factors and polygenic risk score between younger and older patients with first-ever myocardial infarction

Background The incidence of early-onset myocardial infarction (MI) is increasing. Risk profiles differ between younger and older patients, underscoring the need to better define age-specific determinants, including genetic susceptibility, to improve identification of high-risk young individuals and optimize primary prevention strategies.1 Purpose To compare traditional cardiovascular risk factors and a polygenic risk score for coronary artery disease (PRSCAD) between younger (men ≤55y, women ≤60y) and older patients with incident MI and to identify risk factors that differentially contribute to MI risk across the two age groups. Methods Data on incident MI cases from 2012–2023 were retrospectively obtained through linkage of the Estonian Biobank (EstB, n= ~210000) with the Estonian Myocardial Infarction Registry (EMIR, n= ~30000). Patients identified in both databases (n=3031) were included in the analysis. Clinical characteristics were obtained from EMIR, and the PRS from EstB. The two age groups (young and old) used in the analysis were defined according to the European Society of Cardiology definition of premature cardiovascular disease, with cutoffs of 55 years for men and 60 years for women. The multi-ancestry coronary artery disease PRS developed by Patel et al.2 and validated in the EstB by Puusepp et al.3 was used. Multivariable logistic regression was used to estimate adjusted odds ratios (aOR) for individual risk factors, assessing their differential association with MI across two age groups. A p-value <0.05 was considered statistically significant. Results Among 3031 participants, 780 were classified as young and 2251 as old. The baseline characteristics of study participants are shown in Table 1. In the multivariable analysis comparing younger and older MI patients, current smoking demonstrated the strongest association with MI at younger age (aOR 3.84, 95%CI 3.14–4.70). A high polygenic risk score and obesity were also independently linked to younger onset of MI (aOR 1.85, 95%CI 1.51–2.27; aOR 1.92, 95%CI 1.49–2.46, respectively), while male sex showed a modest association (aOR 1.28, 95%CI 1.05–1.56). Overweight status, former smoking, and dyslipidemia were not significantly different between age groups. In contrast, diabetes and hypertension were more strongly associated with MI occurring at older age (aOR 0.62, 95%CI 0.47–0.79; aOR 0.40, 95%CI 0.33–0.49, respectively) (Figure 1). Conclusions Findings suggest that polygenic risk and modifiable lifestyle factors may play a prominent role in early-onset MI, while cumulative cardiometabolic burden characterizes older patients with MI.Table 1.Baseline characteristicsFigure 1.