The SMuRF-less paradox in ST-segment-elevation myocardial infarction: a retrospective hospital-based two-cohort study
5 affiliations
- 1The First School of Clinical Medicine, Lanzhou University
- 2Department of Cardiology, The First Hospital of Lanzhou University
- 3Gansu Province Clinical Research Centre for Cardiovascular Diseases, The First Hospital of Lanzhou University
- 4Shanghai-MOST Key Laboratory of Health and Disease Genomics, Shanghai Institute for Biomedical and Pharmaceutical Technologies
- 5Clinical Research Center, The First Affiliated Hospital of Jinan University
Abstract
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.
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BibTeX
@article{zhao2026smurfless,
title = {{The SMuRF-less paradox in ST-segment-elevation myocardial infarction: a retrospective hospital-based two-cohort study}},
author = {Jing Zhao and Junchu Wei and Chenliang Pan and Yu Peng and Peng Lei and Qiguo Lian and Jun Lyu and Ming Bai and Zheng Zhang},
journal = {Frontiers in Cardiovascular Medicine},
year = {2026},
month = oct,
doi = {10.3389/fcvm.2026.1955087},
url = {https://www.frontiersin.org/articles/10.3389/fcvm.2026.1955087/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The SMuRF-less paradox in ST-segment-elevation myocardial infarction: a retrospective hospital-based two-cohort study
AU - Jing Zhao
AU - Junchu Wei
AU - Chenliang Pan
AU - Yu Peng
AU - Peng Lei
AU - Qiguo Lian
AU - Jun Lyu
AU - Ming Bai
AU - Zheng Zhang
PY - 2026
DA - 2026/10/30
JO - Frontiers in Cardiovascular Medicine
DO - 10.3389/fcvm.2026.1955087
UR - https://www.frontiersin.org/articles/10.3389/fcvm.2026.1955087/full
AB - 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.
SN - 2297-055X
ER -