Background:The degree to which hypercholesterolemia plays a role in the onset, progression, and consequences of peripheral arterial disease (PAD), a worldwide health issue associated with atherosclerosis, must be further clarified.The purpose of this systematic review and meta-analysis was to assess the relationship between high cholesterol and the incidence, severity, and consequences of PAD.Methods: Following PRISMA standards, pertinent case-control studies, cohort studies, and randomized controlled trials were looked for using several databases between the years 2000 and 2025.Included were studies with PAD and cholesterol data from adults (≥18 years old).The Cochrane and ROBINS-E techniques were used to evaluate the risk of bias.Due to significant heterogeneity (I² = 96.49%),random-effects models were employed.From 2,117 screened records, 13 studies (259,536 participants) met the inclusion criteria.Results: Elevated LDL-C was consistently associated with an increased risk of PAD, with the strongest correlation observed in familial hypercholesterolemia (FH) populations (OR 3.0, 95% CI: 2.1-4.3).Subgroup analyses indicated variability based on study design and population, with intervention trials demonstrating more pronounced effects.Publication bias was minimal (Egger's test: p = 0.029). Conclusion:In summary, high LDL-C is an independent and modifiable risk factor for PAD, particularly in individuals with FH.Intensive lipid-lowering therapies, including statins and PCSK9 inhibitors, may help reduce PAD progression and related complications.These findings highlight the importance of personalized cholesterol management in high-risk groups to alleviate the PAD burden.Future studies should explore ethnic disparities and the long-term effects of lipid-targeted treatments.
Reddy et al. (Sat,) studied this question.