Clinical, SMuRF-related, and angiographic characteristics associated with long-term all-cause mortality in patients aged ≤ 40 years with acute coronary syndrome: a retrospective cohort study

Acute coronary syndrome (ACS) in adults aged ≤ 40 years is uncommon, and evidence on characteristics associated with long-term mortality in this age group remains limited. We evaluated clinical, angiographic, and standard modifiable cardiovascular risk factor (SMuRF)-related characteristics in relation to all-cause mortality in a large cohort of very young patients with ACS. This retrospective cohort study included 903 consecutive patients aged ≤ 40 years who were treated for ACS at a tertiary center between January 2011 and June 2024. ACS presentation, cardiovascular risk factors, SMuRF status, coronary angiographic findings, and mortality were assessed. SMuRFs were defined as hypertension, diabetes mellitus, hyperlipidemia, and current smoking, while obesity was analyzed separately. Survival was evaluated using Kaplan–Meier analysis and Cox proportional hazards regression. The principal multivariable analysis used 10-year administrative censoring and a parsimonious Cox model. The cohort included 528 patients with ST-segment elevation myocardial infarction, 293 with non-ST-segment elevation myocardial infarction, and 82 with unstable angina. During a median follow-up of 4.93 years [95% confidence interval (CI) 4.69–5.18], 51 deaths occurred. Obesity was present in 180 patients (19.9%), left anterior descending artery (LAD) involvement in 436 (48.3%), and multivessel disease in 190 (21.0%). In the principal 10-year multivariable Cox model, obesity [adjusted hazard ratio (HR) 2.547, 95% CI 1.367–4.746; p = 0.003] and LAD involvement [adjusted HR 3.805, 95% CI 1.883–7.690; p < 0.001] were associated with mortality. SMuRF-less patients comprised 10.6% of the cohort and had higher proportions of female sex, obesity, LAD involvement, and multivessel disease than SMuRF-positive patients, although mortality did not differ significantly between the groups. Kaplan–Meier analysis showed lower survival among patients with obesity and among those with LAD involvement. A time-varying obesity model improved fit ( p = 0.044). The full-follow-up secondary analysis supported the main findings. In patients aged ≤ 40 years with ACS, obesity and LAD involvement were associated with long-term all-cause mortality, whereas mortality did not differ significantly by SMuRF status. These findings support considering cardiometabolic burden and coronary anatomy in long-term assessment of very young patients with ACS.