Sex-specific risk of smoking for abdominal aortic aneurysm and exploration of potential mechanism: meta-analysis and prospective cohort study

Abstract

Objective: Smoking is the strongest modifiable risk factor for abdominal aortic aneurysm (AAA). This study aims to confirm whether smoking is a stronger risk factor in women than men and identify contributory reasons, including inflammation, for any sex-specific difference observed. Methods: Systematic review and meta-analysis, conducted according to PRISMA guidance (Prospero registration (CRD2024586609)). Data sources were Medline, Embase, and CENTRAL. Population-based studies reporting risk of AAA, adjusted for age and cardiovascular risk factors, for women versus men, were included. These were complemented by data from the UK Biobank (UKB) cohort, which also were assessed for sex-specific effects of smoking on incident atherosclerotic cardiovascular disease (ASCVD). Results: Meta-analysis of 6 studies (including UKB), 2001-2024) showed that the relative risk ratio of current versus never-smokers for incident AAA in women versus men was 1.78 [95%CI 1.32, 2.38]. Comparison of the sex-specific relative risks of current smoking and number of cigarettes/day were similar in the UKB cohort and these risks were much higher for AAA than for ASCVD, but the risks of pack-years were similar. Sex-specific risks of current smoking for AAA were not significantly modified by inflammatory markers (including C-reactive protein, alkaline phosphatase and white blood cell count), lung function or physical activity. Stopping smoking reduced the risk of AAA by almost half in both sexes. Conclusion: The risk of developing AAA by current smokers is almost twice as high in women versus men. Inflammation was not a major modifier and other reasons for the disparity must be sought.