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Clinical Research

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.

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Fig. 1: PRISMA flowchart for the identification, inclusion, and exclusion of studies.
Fig. 2: Forest plot of the meta-analysis examining mortality for patients who are underweight versus non-underweight.
Fig. 3: Forest plot of the meta-analysis examining mortality for patients with obesity versus those without.
Fig. 4: Meta-regression of CAD% for patients with obesity with peripheral artery disease.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank Alfred Hsing-Fen Lin and Zoe Ya-Zhu Syu for their assistance with the statistical analysis during the completion of this manuscript.

Funding

This research was supported by the Ministry of Science and Technology of Taiwan [MOST 108-2221-E-002-163-, MOST 109-2221-E-002 -083 -] and the National Taiwan University Hospital [107-EDN11, 108-N4406, 108EDN02, 109-O20, 109-S4579, 109-EDN11].

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All authors significantly contributed to the manuscript and approved the final version for publication. JKL contributed to the study design, data acquisition, interpretation of data and manuscript revision. DSHL contributed to manuscript drafting. HYL and ALY contributed to data acquisition. KLC contributed to data interpretation. JKL is the guarantor of this work.

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Correspondence to Jen-Kuang Lee.

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Lin, D.SH., Lo, HY., Yu, AL. et al. Mortality risk in patients with underweight or obesity with peripheral artery disease: a meta-analysis including 5,735,578 individuals. Int J Obes 46, 1425–1434 (2022). https://doi.org/10.1038/s41366-022-01143-x

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