Sex differences in survival following acute coronary syndrome with and without standard modifiable risk factors.

Purpose: This meta-analysis investigates the sex differences in mortality risk between the acute coronary syndrome (ACS) population without standard modifiable risk factors (SMuRF-less) and those with at least one standard modifiable risk factor (SMuRF), and analyses mortality rates between males and females within the SMuRF-less cohort.

Methods: The MEDLINE and Embase databases were searched for cohort studies with sex-stratified outcomes for SMuRF-less versus SMuRF patients with ACS till 15 December 2023. The analysis of variables reported in proportions was carried out by utilizing a meta-analysis with a generalized linear mixed model while continuous variables were analyzed by a meta-analysis of means, using an inverse variance method.

Results: Eight studies were included in the current paper, with 82,395 SMuRF-less ACS patients and 607,558 SMuRF ACS patients. Excess in-hospital mortality found in SMuRF-less ACS, compared to those with SMuRFs, were only observed in females (RR 1.56, 95%CI 1.08-2.25, p = 0.029), but not in males (RR 1.59, 95%CI 0.90-2.80, p = 0.088). On longer follow-up, the 1- and 2-year post-ACS mortality rates were similar across the SMuRF-less and SMuRF cohorts, for both sexes. The subgroup analysis of SMuRF-less ACS individuals revealed that SMuRF-less females had higher in-hospital (RR 1.52, 95%CI 1.30-1.78, p = 0.002), 1-year (RR 1.51, 95%CI 1.34-1.71, p = 0.005) and 2-year mortality risks (RR 1.40, 95%CI 1.13-1.75, p = 0.016) compared to the SMuRF-less male counterparts.

Conclusion: Paradoxical excess mortality in SMuRF-less ACS, compared to those with SMuRFs, was only observed in females. Females without cardiovascular risk factors are at the highest risk of short- and medium-term mortality following ACS.