Mortality risk in patients with underweight or obesity with peripheral artery disease: a meta-analysis including 5,735,578 individuals

Abstract

Objectives: The "obesity paradox" - in which patients with obesity exhibit superior survival than normal-weight counterparts - has been reported for several diseases. However, obesity is a well-known risk factor for cardiovascular disease, and whether the obesity paradox is present in peripheral artery disease (PAD) is unknown.

Methods: A comprehensive search for studies that reported mortality in patients with PAD grouped by BMI identified 12 studies. We compared the survival of underweight patients with those who were not underweight, and patients with obesity against those without. Underweight was defined by a BMI value of <18.5 kg/m² in most studies and obesity by BMI ≥ 30 kg/m². Subgroup analyses were performed according to length of follow-up, presentation of PAD, and mode of revascularization. Meta-regression analyses were conducted, with covariates including age, sex, presence of coronary artery disease (CAD) and diabetes mellitus (DM).

Results: The mortality risk of underweight patients with PAD was significantly higher compared to those who are not underweight (HR 1.72, 95% CI 1.38-2.14; I² = 84.2%). In contrast, the mortality risk of patients with obesity with PAD was significantly lower than those without (HR 0.78, 95% CI 0.62-0.97; I² = 89.8%). These findings remained consistent regardless of the presentation of PAD, revascularization, age, sex, or presence of CAD. The risk of death in the short-term of underweight patients (HR 1.50, 95% CI 0.47-4.72) and patients with obesity (HR 0.86, 95% CI 0.66-1.13) were not significantly different from their counterparts. The meta-regression showed that of the association between obesity and better survival was more pronounced in studies with a greater proportion of patients with concomitant CAD (regression coefficient -0.029, 95% CI -0.054 to -0.004).

Conclusions: In patients with PAD, mortality is higher among underweight patients and lower among patients with obesity. The mechanisms underlying the obesity paradox in patients with PAD remain to be elucidated, and further evidence is required to guide optimal weight control strategies in these patients.