Long-Term (7-Year) Clinical Implications of Newly Unveiled Asymptomatic Abnormal Ankle-Brachial Index in Patients With Coronary Artery Disease

Abstract

Background The long-term impact of newly discovered, asymptomatic abnormal ankle-brachial index (ABI) in patients with significant coronary artery disease is limited. Methods and Results Between January 2006 and December 2009, ABI was evaluated in 2424 consecutive patients with no history of claudication or peripheral artery disease who had significant coronary artery disease. We previously reported a 3-year result; therefore, the follow-up period was extended. The primary end point was a composite of all-cause death, myocardial infarction (MI), and stroke over 7 years. Of the 2424 patients with significant coronary artery disease, 385 had an abnormal ABI (ABI ≤0.9 or ≥1.4). During the follow-up period, the rate of the primary outcome was significantly higher in the abnormal ABI group than in the normal ABI group (P<0.001). The abnormal ABI group had a significantly higher risk of composite of all-cause death/MI/stroke than the normal ABI group, after adjustment with multivariable Cox proportional hazards regression analysis (hazard ratio [HR], 2.07; 95% CI, 1.67-2.57; P<0.001) and propensity score-matched analysis (HR, 1.97; 95% CI, 1.49-2.60; P<0.001). In addition, an abnormal ABI was associated with a higher risk of all-cause death, MI, and stroke, but not repeat revascularization. Conclusions Among patients with significant coronary artery disease, asymptomatic abnormal ABI was associated with sustained and increased incidence of composite of all-cause death/MI/stroke, all-cause death, MI, and stroke during extended follow-up over 7 years.

Keywords: ankle–brachial index; asymptomatic diseases; atherosclerosis; coronary artery disease.

Figure 1. Flow diagram illustrating the selection of the study population.

Of the 2543 patients, 390 (15.3%) had an abnormal ankle–brachial index (ABI). Of the 2424 patients with at least 1 significant stenosis (≥50%) in a major epicardial coronary artery, 385 (15.9%) had an abnormal ABI, including 348 (14.4%) with ABI ≤0.9 and 37 (1.5%) with ABI ≥1.4.

Figure 2. Kaplan‐Meier curves of the outcomes of the entire cohort of patients with normal and abnormal ankle–brachial index (ABI).

A, Outcomes for death, myocardial infarction, and stroke. B, Outcomes for event‐free survival. C, Myocardial infarction. D, Stroke. E, Repeat revascularization event‐free survival rates (at 7 years) were derived from paired Kaplan‐Meier curves.

Figure 3. Kaplan‐Meier curves of the outcomes of propensity‐score matched patients with normal and abnormal ankle–brachial index (ABI).

Propensity‐score matching of the entire cohort of patients yielded 359 matched pairs. A, Outcomes for all‐cause death, myocardial infarction, and stroke. B, Outcomes for event‐free survival C, Myocardial infarction. D, Stroke. E, Repeat revascularization event‐free survival rates (at 7 years) were derived from paired Kaplan–Meier curves.

Figure 4. Dose‐response gradient between ankle–brachial index (ABI) values and adverse events.

A, Kaplan‐Meier curves for all‐cause death, myocardial infarction, and stroke outcomes according to the ABI values at baseline (low, normal, and high groups). Event‐free survival rates (at 7 years) were derived from paired Kaplan‐Meier curves. B, Adjusted hazard ratios for all‐cause death, myocardial infarction, and stroke at the 7‐year follow‐up according to ABI values at baseline (low, normal, and high groups). Hazard ratios were derived from multivariate Cox proportional hazards analysis. C, Adjusted hazard ratios for all‐cause death, myocardial infarction, and stroke at the 7‐year follow‐up according to the ABI at baseline (low, middle, high tertials in low, normal, and high groups). Hazard ratios were derived from multivariate Cox proportional hazards analyses.