Association of Sex and Cardiovascular Risk Factors with Atherosclerosis Distribution Pattern in Lower Extremity Peripheral Artery Disease

Background: Atherosclerosis expression varies across coronary, cerebrovascular and peripheral arteries, but also within the peripheral vascular tree. The underlying pathomechanisms of distinct atherosclerosis phenotypes in lower extremity peripheral artery disease (LEAD) is poorly understood. We investigated the association of cardiovascular risk factors (CVRF) and atherosclerosis distribution in a targeted approach analysing symptomatic patients with extreme anatomic phenotypes of LEAD. Methods: In a cross-sectional analysis of >15.000 patients undergoing first-time endovascular recanalisation for symptomatic LEAD, data of patients with extreme anatomic phenotypes of either proximal (iliac) or distal (infrageniculate) atherosclerosis were extracted. We performed a multivariate logistic regression model with backward elimination to investigate the association of proximal and distal LEAD with CVRFs. Findings: Of 637 patients (29% women) with endovascular recanalisation, 351 (55%) had proximal, 286 (45%) distal atherosclerosis. Female sex (OR 0·33, 95%CI 0·20 to 0·54), P=0·01), active smoking (OR 0·16, 95%CI 0·09 to 0·28), P <0·001, and former smoking (OR 0·33, 95%CI 0·20 to 0·57, P <0·001) were associated with proximal disease. Diabetes mellitus (DM) (OR 0·33, 95%CI 1·06 to 1·61 P=0·01), chronic kidney disease (CKD) (OR 1·18, 95%CI 1·08 to 1·28), p<0·001), and older age (OR 1·31, 95%CI 1·06 to1·61), P=0·01) were associated with distal disease. Interpretation: Female sex, particularly in the context of smoking, is associated with clinically relevant, proximal atherosclerosis expression. Our additional findings that distal atherosclerosis expression is associated with DM, CKD and older age suggest that LEAD has at least two distinct atherosclerotic phenotypes with sex-specific and individual susceptibility to atherogenic risk factors. Funding: None. Declaration of Interest: None to declare Ethical Approval: The study protocol conforms to the ethical guidelines of the 1975 declaration of Helsinki and has been approved by the institution’s Ethics Committee on research involving human data waiving the need for individual patient consent prior the year 2015 (approval 2018-00679).