The SMuRF-less paradox in ST-segment-elevation myocardial infarction: a retrospective hospital-based two-cohort study

Background Patients with ST-segment-elevation myocardial infarction (STEMI) without standard modifiable cardiovascular risk factors (SMuRFs) exhibit paradoxically increased mortality. We aimed to characterize associations with adverse outcomes and identify potential drivers. Methods We included patients with STEMI from a hospital-based cohort in Lanzhou, China ( n = 6,892; 2014–2023) and the US Medical Information Mart for Intensive Care IV (MIMIC-IV; n = 4,480; 2008–2019). SMuRF-less status was defined as the absence of hypertension, diabetes, hyperlipidemia, and smoking, with obesity included in sensitivity analyses. Primary outcomes were 30- and 365-day all-cause mortality. Secondary outcomes were major adverse cardiac and cerebrovascular events (MACCEs), 7-day delirium and acute kidney injury (AKI). Associations were estimated using adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs), and Fine–Gray competing-risk analyses performed for 7-day delirium and AKI. Results SMuRF-less patients comprised 17.2% ( n = 1,182) of the Lanzhou cohort and 13.6% ( n = 608) of the MIMIC-IV cohort. SMuRF-less status was associated with higher 30-day mortality in both cohorts (Lanzhou: aHR, 1.37; 95% CI, 1.09–1.71; MIMIC-IV: 1.67, 1.39–2.01). In landmark analyses, SMuRF-less status was not significantly associated with mortality during days 31–365 in Lanzhou (1.68; 0.84–3.37) but was associated with higher mortality in MIMIC-IV (1.34; 1.02–1.77). SMuRF-less status was not significantly associated with MACCEs in Lanzhou. In MIMIC-IV, SMuRF-less status was associated with a higher risk of 7-day delirium (1.40; 1.17–1.67) but was not associated with 7-day AKI (1.05; 0.94–1.17). For both 7-day delirium and AKI, competing-risk analyses yielded consistent findings. In subgroup analyses, excess 30-day mortality was greater among patients in Lanzhou not receiving extracorporeal membrane oxygenation, those not receiving intra-aortic balloon pump, and those with Killip class I–III ( P for interaction <0.05). Sensitivity analyses incorporating obesity showed similar associations for 30-day mortality in Lanzhou (1.40; 1.12–1.76) and MIMIC-IV (1.63; 1.33–1.99), as well as for 7-day delirium (1.33; 1.09–1.62). Conclusions SMuRF-less status was independently associated with increased early mortality in both cohorts and a higher risk of delirium in the MIMIC-IV cohort. This excess risk was not fully explained by measured clinical and physiological markers, suggesting that residual risk may extend beyond conventional modifiable cardiovascular risk factors.