A systematic review and meta-analysis of gender differences in long-term mortality and cardiovascular events in peripheral artery disease

Objective: Individual studies of peripheral artery disease (PAD) have indicated that gender discrepancies exist in the symptoms, functional status, and treatment usage. It remains uncertain whether these discrepancies result in different long-term outcomes. We examined the potential gender differences in mortality and major adverse cardiovascular events (MACE) in patients with symptomatic PAD. Methods: The PubMed and Embase databases were searched for studies from 2000 to January 2019. After a review of 13,582 citations, 14 articles were analyzed. The reported age-adjusted hazard ratios (HRs) for gender differences in mortality and MACE were included in the meta-analysis. The mortality outcomes were stratified according to the clinical presentation and study context. Results: Male gender was associated with a greater risk of all-cause mortality (HR, 1.13; 95% confidence interval [CI], 1.10-1.16; P <.001) and MACE (HR, 1.10; 95% CI, 1.06-1.14; P <.001). In a stratified analysis, male gender was associated with a higher mortality risk for patients presenting with either critical limb ischemia (HR, 1.08; 95% CI, 1.05-1.10; P <.001) or mixed clinical presentations (HR, 1.16; 95% CI, 1.11-1.21; P <.001) but not for those with intermittent claudication (HR, 1.13; 95% CI, 0.98-1.30; P =.09). Elevated mortality risk was evident after revascularization (HR, 1.11; 95% CI, 1.04-1.19; P =.003), hospitalization (HR, 1.15; 95% CI, 1.08-1.22; P <.001), and amputation (HR, 1.09; 95% CI, 1.08-1.10; P <.001), although not in outpatient clinics (HR, 1.13; 95% CI, 0.97-1.32; P =.13), in men compared with women. Conclusions: Greater mortality and MACE rates in men with PAD occurred despite other accepted gender disparities. The mechanisms underlying these gender differences in the outcomes for PAD patients require further investigation.