A systematic review and study-level meta-analysis investigating the association between pre-endovascular intervention C-reactive protein levels and femoropopliteal artery restenosis

ABSTRACT Introduction Restenosis in previously treated femoral or popliteal arteries remains a clinical issue, leading to repeat procedures, and major adverse limb events. Elevated pre-endovascular intervention levels of C-reactive protein (CRP), a marker of systemic inflammation, have previously been associated with coronary restenosis, however, its association with femoropopliteal artery restenosis is unclear. We conducted a systematic review and study-level meta-analysis to assess the association between pre-endovascular intervention CRP levels and femoropopliteal artery restenosis. Methods Online databases of PubMed, EMBASE, MEDLINE (OVID), Scopus and Web of Science were searched for relevant articles published until September 30th, 2025. A Z-test using a random effects model was used to pool study-level results to obtain pooled standardized mean differences (SMD) and its 95% confidence intervals (CI). A p value of <0.05 indicated statistical significance. Results After screening a total of 331 unique articles, 14 studies, including 2,097 patients (562 restenosis cases/1,535 no-restenosis controls) were available for quantitative synthesis. Pooled results suggested a significant association between higher pre-endovascular intervention CRP levels and femoropopliteal artery restenosis. (SMD= 0.44, 95% Cl, 0.09-0.78, p=0.01). There was no evidence of publication bias, both visually via Begg's funnel plot and statistically via Egger's test results (p= 0.52). Leave-one-out sensitivity analysis supported the robustness of the pooled results. Conclusions This systematic review and study-level meta-analysis suggests a significant association between higher pre-endovascular intervention CRP levels and the subsequent development of femoropopliteal artery restenosis. Our findings should be interpreted with caution and further large-scale prospective investigations are warranted to substantiate our results.