Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis

Abstract

Context: Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction.

Objective: To determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction.

Data sources: Relevant studies were identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) was conducted using common text words for the term ankle brachial index combined with text words and Medical Subject Headings to capture prospective cohort designs. Review of reference lists and conference proceedings, and correspondence with experts was conducted to identify additional published and unpublished studies.

Study selection: Studies were included if participants were derived from a general population, ABI was measured at baseline, and individuals were followed up to detect total and cardiovascular mortality.

Data extraction: Prespecified data on individuals in each selected study were extracted into a combined data set and an individual participant data meta-analysis was conducted on individuals who had no previous history of coronary heart disease.

Results: Sixteen population cohort studies fulfilling the inclusion criteria were included. During 480,325 person-years of follow-up of 24,955 men and 23,339 women, the risk of death by ABI had a reverse J-shaped distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year cardiovascular mortality in men with a low ABI (< or = 0.90) was 18.7% (95% confidence interval [CI], 13.3%-24.1%) and with normal ABI (1.11-1.40) was 4.4% (95% CI, 3.2%-5.7%) (hazard ratio [HR], 4.2; 95% CI, 3.3-5.4). Corresponding mortalities in women were 12.6% (95% CI, 6.2%-19.0%) and 4.1% (95% CI, 2.2%-6.1%) (HR, 3.5; 95% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS (2.9 [95% CI, 2.3-3.7] for men vs 3.0 [95% CI, 2.0-4.4] for women). A low ABI (< or = 0.90) was associated with approximately twice the 10-year total mortality, cardiovascular mortality, and major coronary event rate compared with the overall rate in each FRS category. Inclusion of the ABI in cardiovascular risk stratification using the FRS would result in reclassification of the risk category and modification of treatment recommendations in approximately 19% of men and 36% of women.

Conclusion: Measurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS.

Figure 1

Flow diagram of selection of studies for inclusion in meta-analysis.

Figure 2

Hazard ratios of total mortality in men and women by ankle brachial index at baseline for all studies combined in the ABI collaboration. (Hazard ratios are not adjusted for age or cardiovascular risk factors)

Figure 3

Hazard ratios of total mortality for low (≤0.90) compared with normal (1.11-1.40) ankle brachial index in men in studies in the ABI collaboration. (Hazard ratios are not adjusted for age or cardiovascular risk factors) (Area of each square is proportional to weight of the study in the meta-analysis). (Total deaths/population for ≤ 0.90 group is 957/1841 and for 1.11 to 1.40 group is 2379/14,193).

Figure 4

Hazard ratios of total mortality for low (≤0.90) compared with normal (1.11-1.40) ankle brachial index in women in studies in the ABI collaboration. (Hazard ratios are not adjusted for age or cardiovascular risk factors) (Area of each square is proportional to weight of the study in the meta-analysis). (Total deaths/population for ≤ 0.90 group is 844/1901 and for 1.11 to 1.40 group is 1613/11,157).