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Post-exercise ankle–brachial index decline and risk of all-cause mortality: A meta-analysis

The ankle–brachial index (ABI), calculated as the ratio of ankle and brachial systolic blood pressure, is widely used for detection of peripheral arterial disease (PAD). Conventional ABI value is determined in the rest state. However, a considerable portion of patients with normal resting ABI have abnormal post-exercise ABI. When ABI is normal at rest in patients with suspected PAD, post-exercise ABI is recommended to improve the sensitivity for diagnosis of PAD. In addition to diagnosis and exclusion of PAD, the ABI test also has prognostic implications in risk stratification of mortality. An abnormal resting ABI was associated with an increased risk of future cardiovascular and all-cause mortality. However, there is controversy regarding the prognostic utility of post-exercise ABI for predicting all-cause mortality in patients with suspected or known PAD. These conflicting results may be partly attributed to the different resting ABI status. No previous meta-analysis has assessed the association between exercise ABI and all-cause mortality risk. We therefore conducted this meta-analysis to assess the prognostic utility of post-exercise ABI decline for predicting all-cause mortality in patients with suspected or known PAD. A comprehensive search of articles was conducted on PubMed and Embase databases from their inceptions to 15 March 2019. The following search keywords were applied: ‘ankle–brachial index’ OR ‘ankle brachial pressure index’ OR ‘ABI’ AND ‘exercise’ OR ‘postexercise’ AND ‘mortality’ OR ‘death’ AND ‘followup’. Studies satisfying the following inclusion criteria were eligible: 1) longitudinal observational design; 2) study population comprised patients with suspected or known PAD; 3) post-exercise ABI decline as exposure; 4) all-cause mortality as outcome measures; and 5) reported multivariate adjusted risk estimate (risk ratio, hazard ratio or odds ratio with their corresponding 95% confidence intervals (CIs)) of all-cause mortality comparing the post-exercise ABI decline with the reference normal exercise ABI. When multiple articles from the same population were identified, only the study with the longest follow-up time was selected. Methodological quality of the included studies was evaluated by the Newcastle–Ottawa Scale (NOS). A study with a score of 7 points was deemed to be of good quality. All meta-analyses were performed by STATA 12.0. Four studies involving 14,884 participants were finally included in this meta-analysis. Characteristics of the included studies are summarized in Supplemental Table 1 online. The mean age of patients varied from 55.6 to 72.5 years. The percentage of male gender ranged from 28.9% to 59.2%. The length of followup ranged from 3.8 years to 8.0 years. All the included studies were grouped as high quality with NOS scores ranging from seven to eight points. The meta-analysis showed that post-exercise ABI decline was associated with an increased risk of allcause mortality (risk ratio 1.46; 95% CI 1.19–1.80; I1⁄4 68.8%, p1⁄4 0.004) in a random effect model (Figure 1). The possibility of publication bias was low based on Begg’s test (p1⁄4 0.764) and Egger’s test (p1⁄4 0.857). A leave-out-one-study sensitivity analysis showed that the pooled risk ratio ranged from 1.33 (95% CI 1.06–1.67) to 1.60 (95% CI 1.28–1.99). Subgroup analysis according to the resting ABI status showed that post-exercise ABI decline significantly increased all-cause mortality (risk ratio 1.70; 95% CI 1.43–2.01) among those with abnormal resting ABI but not in the individuals with normal ABI (risk ratio 1.30; 95% CI 0.94–1.80). This meta-analysis suggests that post-exercise ABI decline is associated with an increased risk of allcause mortality among patients with abnormal resting