Higher mortality in acute coronary syndrome patients without standard modifiable risk factors: Results from a global meta-analysis of 1,285,722 patients

Background: Standard modifiable cardiovascular risk factors (SMuRF), comprising diabetes, hyperlipidemia, hypertension, and smoking, are used for risk stratification in acute coronary syndrome (ACS). Recent studies showed an increasing proportion of SMuRF-less ACS patients. Methods: Embase, Medline and Pubmed were searched for studies comparing SMuRF-less and SMuRF patients with first presentation of ACS. We conducted single-arm analyses to determine the proportion of SMuRF-less patients in the ACS cohort, and compared the clinical presentation and outcomes of these patients. Results: Of 1,285,722 patients from 15 studies, 11.56% were SMuRF-less. A total of 7.44% of non-ST-segment -elevation ACS patients and 12.87% of ST-segment-elevation myocardial infarction (STEMI) patients were SMuRF-less. The proportion of SMuRF-less patients presenting with STEMI (60.71%) tended to be higher than those with SMuRFs (49.21%). Despite lower body mass index and fewer comorbidities such as chronic kidney disease, peripheral arterial disease, stroke and heart failure, SMuRF-less patients had increased in-hospital mortality (RR:1.57, 95%CI:1.38 to 1.80) and cardiogenic shock (RR:1.39, 95%CI:1.18 to 1.65), but lower risk of heart failure (RR:0.91, 95%CI:0.83 to 0.99). On discharge, SMuRF-less patients were prescribed less statins (RR:0.93, 95%CI:0.91 to 0.95), beta-blockers (RR:0.94, 95%CI:0.92 to 0.96), P2Y12 inhibitors (RR: 0.98, 95%CI: 0.96 to 0.99), and angiotensin-converting-enzyme inhibitor or angiotensin-receptor blocker (RR:0.92, 95% CI:0.75 to 0.91). Conclusion: In this study level meta-analysis, SMuRF-less ACS patients demonstrate higher mortality compared with patients with at least one traditional atherosclerotic risk factor. Underuse of guideline-directed medical therapy amongst SMuRF-less patients is concerning. Unraveling novel risk factors amongst SMuRF-less in-dividuals is the next important step. Summary: Standard modifiable cardiovascular risk factors (SMuRF), comprising diabetes mellitus, hyperlipid-emia, hypertension, and smoking, are often used for risk stratification in acute coronary syndrome (ACS). Recent studies showed an increasing proportion of SMuRF-less ACS patients. Of 1,285,722 ACS patients, 11.56% were SMuRF-less. Despite lower body mass index and fewer comorbidities, SMuRF-less patients had increased in -hospital mortality and cardiogenic shock. However, despite worse outcomes, SMuRF-less patients were pre-scribed less guideline-directed medical therapies on discharge.