Association of lower extremity performance with cardiovascular and all-cause mortality in patients with peripheral artery disease: a systematic review and meta-analysis

Abstract

Background: Peripheral artery disease (PAD) is associated with impaired mobility and a high rate of mortality. The aim of this systematic review was to investigate whether reduced lower extremity performance was associated with an increased incidence of cardiovascular and all-cause mortality in people with PAD.

Methods and results: A systematic search of the MEDLINE, EMBASE, SCOPUS, Web of Science, and Cochrane Library databases was conducted. Studies assessing the association between measures of lower extremity performance and cardiovascular or all-cause mortality in PAD patients were included. A meta-analysis was conducted combining data from commonly assessed performance tests. The 10 identified studies assessed lower extremity performance by strength tests, treadmill walking performance, 6-minute walk, walking velocity, and walking impairment questionnaire (WIQ). A meta-analysis revealed that shorter maximum walking distance was associated with increased 5-year cardiovascular (unadjusted RR=2.54, 95% CI 1.86 to 3.47, P<10(-5), n=1577, fixed effects) and all-cause mortality (unadjusted RR=2.23 95% CI 1.85 to 2.69, P<10(-5), n=1710, fixed effects). Slower 4-metre walking velocity, a lower WIQ stair-climbing score, and poor hip extension, knee flexion, and plantar flexion strength were also associated with increased mortality. No significant associations were found for hip flexion strength, WIQ distance score, or WIQ speed score with mortality.

Conclusions: A number of lower extremity performance measures are prognostic markers for mortality in PAD and may be useful clinical tools for identifying patients at higher risk of death. Further studies are needed to determine whether interventions that improve measures of lower extremity performance reduce mortality.

Keywords: lower extremity performance; mortality; peripheral artery disease.

Figure 1.

Outline of the study. One hundred and seventeen published studies assessing the association of lower extremity performance measures with mortality in peripheral artery disease (PAD) patients were identified by searching the EMBASE, MEDLINE, SCOPUS, Web of Science, and Cochrane Library databases. Appraisal of the abstracts identified 12 studies eligible for full‐text appraisal. From these, a further 2 articles were excluded, yielding a total of 10 studies included in the review.

Figure 2.

Meta‐analysis of the association between maximum walking distance and 5‐year cardiovascular and all‐cause mortality. Forest plot illustrating unadjusted risk ratios (RRs) and 95% CIs for the association of shorter walking distance with cardiovascular and all‐cause mortality. The diamond represents an overall RR calculated in the current meta‐analysis. The number n represents the sum of patients in the highest and lowest quantiles for each study. P<10⁻⁵ under both fixed‐effects and random‐effects models. *Comparison of lowest‐ performance quartile to highest‐performance quartile.^, †Comparison of patients with performance below set value compared to patients with performance above and including set value.

Figure 3.

Meta‐analysis of maximally adjusted risk ratios (RRs) for the association between maximum walking distance and mortality in peripheral artery disease. Forest plot illustrating maximally adjusted RRs and 95% CIs for the association of shorter walking distance with cardiovascular and all‐cause mortality. Covariates included in multivariate analyses for individual studies are listed in Table 4. The diamond represents an overall RR calculated in the current meta‐analysis. The number n represents the combined sum of patients in each study. *P value calculated according to fixed‐effects model. †P value calculated according to random‐effects model.