BackgroundThere has been an increase in Acute Coronary Syndrome (ACS) patients without standard modifiable risk factors i.e. hypertension, diabetes, dyslipidemia, and tobacco use (SMuRFless) compared to the patients with ≥ 1 SMuRF but this has not been studied in South Asia despite them being a high-risk population. We conducted a comparative analysis of first episodes of ACS cases admitted to a tertiary cardiac center in Pakistan between SMuRFless and ≥ 1 SMuRF patients for clinical presentation, management, in-hospital, and 5-year mortality.MethodsWe undertook a retrospective study and data of 15,051 patients admitted at Tabba Heart Institute (THI) with the first episode of ACS was extracted from Chest Pain-MI™, and the CathPCI Registry® registry affiliated with the National Cardiovascular Data Registry (NCDR®), USA. Logistic regression and Cox proportional algorithm yielded odds ratio (OR) and hazard ratios (HR) with 95% confidence interval (CI) for associated factors of in-patient and 5-year mortality.ResultsThere were 15% SMuRFless cases and in-hospital mortality was 4.1% in SMuRFless vs. 3.9% in the ≥ 1 SMuRF group (p-0.59), the difference remained insignificant after adjusting for age, gender, Killip class, multivessel disease, type of ACS, percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) (Adjusted OR:1.1 [0.8, 1.3]. Unadjusted 5-year mortality was 40% lower in the SMuRFless group but the difference was insignificant after adjusting for age, gender, disease at presentation, its severity, and management (Adjusted HR 0.7 95% CI[0.5, 1.0]). STEMI, NSTEMI, Killip class, and multivessel disease increased the risk of overall 5-year mortality.ConclusionIn-hospital and 5-year mortality was not different between the SMuRFless and ≥ 1 SMuRF group, there is a need to understand mediators of immediate and long-term mortality risk in SMuRFless patients.