Peripheral Artery Disease and Gender: Systematic Review with ☸️SAIMSARA.

• Generated: 2026-01-27 19:40:20 CET
• Plan: Pro (expanded craft tokens; source: Semantic Scholar)
• Source: Semantic Scholar
• Scope: All fields
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• Total Abstracts/Papers: 1648
• Downloaded Abstracts/Papers: 1000
• Included original Abstracts/Papers: 313
• Total study participants (naïve ΣN): 2050605

• Bias: Qualitatively inferred from study design fields. Retrospective cohort and cross-sectional studies are prevalent, introducing potential for selection and recall bias. Many studies did not specify directionality or follow-up, limiting causal inference. Small sample sizes in some studies and reliance on specific populations (e.g., diabetic patients, surgical inpatients) may limit generalizability.

• Prevalence and Burden: While males may bear a heavier absolute PAD burden, females often exhibit elevated age-standardized rates globally and in specific populations [14, 152, 167, 174]. Age-adjusted PAD mortality rates were higher in males (25.6 vs 19.4) but the gap is decreasing [8, 130].
• Risk Factors and Associations: The association between metabolic syndrome components and PAD is stronger in females [1]. TyG Index (TyGI) shows a linear correlation with PAD in males, but a non-linear relationship with a threshold in females [2]. Baseline coronary artery calcium score (CACs) is associated with incident PAD in males (1.11-fold higher odds per unit increase), but not in females [10]. Male gender is a significant contributor to PAD risk factors like age, smoking, and hyperlipidemia [12, 150].
• Clinical Presentation and Disease Severity: Women with PAD are often older, have a higher mean BMI, and more frequently present with hypercholesterolemia, obesity, cerebrovascular disease, and chronic kidney disease, while men are more frequent smokers and have more coronary artery disease [3, 144]. Women undergoing endovascular interventions for PAD present with more severe disease [11]. Male gender is associated with increased PAD severity (OR: 6.0, 95% CI: 1.1–32.2) [123].
• Treatment and Management Disparities: Optimal medical treatment (OMT) for PAD, including statins and renin-angiotensin-aldosterone system inhibitors, is insufficiently prescribed, particularly in women [6]. Female patients undergoing endovascular lower extremity (LE) interventions for PAD have higher rates of clinically driven target lesion revascularization (TLR) [50, 231] and are less likely to be taking statins (73% vs 78%) [11]. Female gender is also associated with lower initiation rates of cardioprotective glucose-lowering drugs in T2DM patients with CVD [43].
• Post-operative Outcomes and Complications: Females exhibit a significantly higher risk of post-operative stroke (p < 0.001), all-cause morbidity (p = 0.004), mortality (p < 0.001), and major adverse cardiovascular events (p < 0.001) in PAD surgery [4]. Women undergoing LE endovascular interventions also have higher adjusted rates of in-hospital mortality (OR 1.25, 95% CI 1.09-1.44) [11]. Conversely, male gender is an independent predictor of re-PTA [30], amputation [3, 41, 88, 97, 119, 159, 158], and death after amputation [140], and is associated with higher in-hospital mortality in acute myocardial infarction (AMI) patients with PAD [35]. Female gender was associated with significantly worse amputation-free survival in acute limb ischemia (ALI) patients treated with aspiration mechanical thrombectomy (OR 2.71, 1.03–7.17) [226].
• Functional Status and Quality of Life: Women with PAD report poorer physical (PCS: 37±10 vs 40±10, P=0.004) and mental (MCS: 47±12 vs 49±11, P=0.005) health status at diagnosis and follow-up compared to men [34, 44]. However, female gender was a protective factor for high quality of life in patients with in-stent restenosis after interventional therapy [20].
• Biological Markers and Pathophysiology: Gender differences exist in Elabela expression, with males generally showing higher levels [22]. Lp(a) levels are higher in women than in men [56, 209]. Male gender is associated with higher coronary artery calcium score (CACS) values [145] and greater total plaque burden in non-calcified plaque groups [271]. Atherosclerosis is higher in males, while thrombosis is more prevalent in females with T2DM and PAD [48].

• Tailored Risk Assessment: Clinicians should recognize that risk factor associations (e.g., MetS, TyGI, CACs) and their predictive power for PAD can differ significantly by gender, necessitating gender-specific risk stratification [1, 2, 10].
• Enhanced Monitoring for Women: Given the higher risk of post-operative stroke, overall morbidity, and mortality in females undergoing PAD surgery [4], and higher rates of reintervention post-endovascular therapy [50, 231], women may require more intensive post-procedural monitoring and follow-up.
• Addressing Treatment Disparities: The under-prescription of optimal medical treatment (OMT), including statins and cardioprotective glucose-lowering drugs, in women with PAD [6, 11, 43] highlights a critical need for interventions to ensure equitable care.
• Focus on Amputation Risk in Men: The consistent identification of male gender as a predictor for amputation and reamputation in PAD patients, particularly those with diabetes [3, 41, 88, 97, 119, 159], suggests a need for targeted amputation prevention strategies in men.
• Holistic Patient Support: Poorer physical and mental health status observed in women with PAD [34, 44] indicates a need for comprehensive support systems that address both physical and psychological well-being.

• Standardized Gender-Stratified Outcomes: Future studies need to standardize outcome definitions (e.g., PAD prevalence, amputation, mortality) and consistently report gender-stratified analyses to allow for more robust comparisons and meta-analyses [8, 174].
• Mechanistic Studies on Biological Markers: Research is needed to elucidate the underlying biological mechanisms driving gender differences in markers like Elabela [22], Lp(a) [56], and CACs [10, 145], and how these contribute to PAD pathogenesis and progression.
• Prospective Studies on Treatment Efficacy: There is a gap in prospective studies evaluating the gender-specific efficacy and safety of various PAD interventions (e.g., exercise programs, endovascular therapies, surgical revascularization) to inform tailored treatment guidelines [5, 50, 69].
• Impact of Socioeconomic and Psychosocial Factors: Further research should explore how socioeconomic status, access to care, and psychosocial factors (e.g., depression, health literacy) interact with gender to influence PAD burden and outcomes [39, 19, 24].
• Longitudinal Quality of Life Assessment: Longitudinal studies are needed to understand the long-term trajectory of physical and mental quality of life in PAD patients, with detailed gender stratification and identification of modifiable factors [34, 44].

• Heterogeneous Study Designs — The diverse range of study designs (cohort, cross-sectional, mixed, retrospective) limits the ability to draw definitive causal conclusions or directly compare outcomes across all studies.
• Varying Population Samples — Studies were conducted in diverse populations (e.g., T2DM patients, surgical inpatients, general population, specific ethnicities), making it challenging to generalize findings broadly.
• Inconsistent Outcome Definitions — Different studies used varying definitions for PAD, its severity, and associated complications, which can lead to discrepancies in reported prevalence and risk factors.
• Lack of Standardized Metrics — The absence of a single, consistently reported quantitative metric for gender-specific PAD burden or outcomes prevented a direct numerical synthesis across all studies.
• Qualitative Bias Inference — Bias was inferred qualitatively from study designs, and a formal quantitative assessment of bias was not performed, which could affect the interpretation of the strength of evidence.

• Standardize Reporting Guidelines — Implement standardized reporting guidelines for gender-specific PAD outcomes and risk factors in all cardiovascular research.
• Large-scale Prospective Cohorts — Conduct large-scale, prospective cohort studies with balanced gender representation and long-term follow-up across diverse populations.
• Investigate Biological Pathways — Explore specific biological and hormonal pathways that contribute to observed gender differences in PAD susceptibility and progression.
• Develop Gender-specific Guidelines — Create and test gender-specific clinical guidelines for PAD screening, diagnosis, and management based on robust evidence.
• Assess Healthcare Access Disparities — Research the impact of healthcare access, health literacy, and socioeconomic factors on gender disparities in PAD care and outcomes.