The smoker's paradox: early-onset ACS in active smokers

Smoking is one of the strongest modifiable risk factors for premature atherosclerosis and acute coronary syndrome (ACS). Active smokers typically experience their first coronary event at a younger age than non-smokers, reflecting accelerated vascular damage and prothrombotic effects. Understanding the clinical profile and outcomes of these patients may help clarify the impact of smoking on early-onset ACS and guide targeted preventive strategies.

To assess the influence of active smoking on the age of first ACS presentation and to compare clinical characteristics and in-hospital outcomes between smokers and non-smokers.

A single-centre study of patients admitted with a first ACS between October 2010 and June 2025. Patients were stratified by smoking status (active smoker vs. non-active smoker). Baseline clinical characteristics, ACS presentation, and in-hospital complications were analysed. Multivariate linear regression was performed to identify predictors of earlier ACS onset.

A total of 1,260 patients were included (mean age 66.6 ± 12.9 years; 28.7% female), of whom 25.5% were active smokers. Compared with non-smokers, active smokers presenting with a first ACS were more frequently male (86.0% vs. 66.3%, p <0.001) and significantly younger (55 vs. 71 years, p <0.001), with a lower body mass index (26 vs. 27 kg/m², p=0.002). They had lower prevalence of hypertension (33.8% vs. 74.4%, p <0.001), diabetes (10.4% vs. 34.9%, p <0.001), and dyslipidaemia (50.2% vs. 60.8%, p <0.001), but higher LDL cholesterol at admission (126 vs. 110 mg/dL, p <0.001) and more frequent family history of coronary artery disease (8.5% vs. 4.2%, p=0.003).

Smokers more often presented with ST-elevation myocardial infarction (62.0% vs. 46.6%, p <0.001) and a lower Killip class (Killip I: 92.8% vs. 85.0%, p <0.001), but had slightly lower left ventricular ejection fraction at discharge (49% vs. 52%, p=0.025). New-onset heart failure (11.2% vs. 20.9%, p <0.001) and atrial fibrillation (4.0% vs. 8.5%, p=0.008) were less frequent. Rates of reinfarction, cardiogenic shock, mechanical and arrhythmic complications, in-hospital mortality (0.6% vs. 2.1%, p=0.075), and one-year mortality (1.9% vs. 3.1%, p=0.250) were similar between groups.

In multivariate regression, active smoking was the strongest predictor of earlier ACS onset, associated with 11.5 years younger age at first event (adjusted R² = 0.39, p <0.001).

Active smoking is strongly associated with early-onset ACS, with smokers presenting 11 years earlier and more often with ST-elevation myocardial infarction. Despite this higher-risk presentation, in-hospital and one-year outcomes were similar to non-smokers. These findings underscore the "smoker’s paradox" and the need for targeted primary prevention and smoking cessation strategies in younger adults.