Standard modifiable cardiovascular risk factors and acute coronary syndrome free survival

Background and aims Recent studies suggest that patients without standard modifiable cardiovascular risk factors (SMuRFs), hypertension, hypercholesterolemia, diabetes, or smoking, may experience higher short-term mortality after acute coronary syndrome (ACS) than those with risk factors. This study examined the relationship between SMuRF burden, ACS-free survival, and short-term outcomes, and explored potential mechanisms including index-event and dilution bias. Methods We analyzed data from 70,953 Caucasian patients with first-time ACS enrolled between 2005 and 2021 in the ISACS-TC Registry (NCT04008173). Patients with prior coronary heart disease were excluded. Traditional SMuRFs were identified from clinical history. The primary outcome was 30-day all-cause mortality; secondary measures included age at ACS onset and early death from hospital admission (≤1 day). Inverse probability weighting models adjusted for baseline imbalance. Results At least one SMuRF was present in 84 % of patients. Increasing SMuRF number was associated with progressively younger age at ACS (women: 67.1 vs 61.9 years; men: 62.8 vs 58.9 years; both P < 0.001). Conversely, 30-day mortality showed an inverse pattern, being highest in SMuRF-less patients and lowest among those with multiple SMuRFs (women: 16.3 % vs 7.7 %; men: 11.5 % vs 4.8 %). Diabetes alone conferred excess mortality (RR 1.29 [95 % CI 1.06–1.57] in women; 1.40 [1.16–1.69] in men), whereas isolated smoking, hypertension, or hypercholesterolemia were associated with lower risk. Early deaths at admission (≤1 day) were more frequent in SMuRF-less patients (36.8 % vs 31.7 %), suggesting arrhythmic mechanisms. Conclusions SMuRFs remain strong determinants of earlier ACS onset and shorter ACS-free survival. The apparent paradox of higher mortality in SMuRF-less patients likely reflects index-event and dilution bias. Prevention strategies targeting smoking, hypercholesterolemia, and diabetes remain crucial to extend ACS-free life expectancy.