Abstract
OBJECTIVE: To assess the association between the blood pressure (BP) reduction mediated by BP-lowering agents and the risks of peripheral arterial disease (PAD) in patients with cardiometabolic risk factors. METHODS: PubMed, EMBASE, the Cochrane Centre Register of Controlled Trials for Studies, the Scopus, Web of Science and Clinicaltrial.gov were searched from January 1980 to October 2023. Randomized controlled trials (RCTs) with statistically significant BP reduction in intensive BP-lowering treatments group compared with control treatment group, reporting the incidence of PAD were included. Regular and dose-response meta-analyses were both conducted. RESULTS: In all, 15 RCTs involving 94482 participants were included. The standardized analysis based on systolic blood pressure (SBP) reduction revealed that each 10 mmHg reduction in SBP mediated by BP-lowering agents was associated with a 37% increase in the risk of PAD in patients with cardiometabolic risk factors (RR = 1.37, 95% CI 1.08 to 1.74). The difference of the SBP reduction from baseline between the intensive anti-hypertensive treatment group and the control group was associated with the increased risk of PAD (β=-0.1107, 95%CI, -0.219 to -0.002, p = 0.047). Dose-response analysis further confirmed a linear association between SBP reduction and the risk of PAD in patients with cardiometabolic risk factors, with a 3.22% increase in risk for every 1 mmHg decrease in SBP (RR = 1.032, 95% CI 1.008 to 1.057, p = 0.009). CONCLUSION: Our meta-analysis revealed that intensive reductions in SBP mediated by BP-lowering agents conferred increase the risk of PAD in patients with cardiometabolic risk factors. A gradual and moderate BP reduction as well as regular BP monitoring should be recommended for patients at high risk of PAD.