Coronary Artery Calcification, Intima-Media Thickness, and Ankle-Brachial Index Are Complementary Stroke Predictors

Background and Purpose-Coronary artery calcification (CAC), a marker of coronary atherosclerosis, predicts stroke in addition to established risk factors. Whether CAC's predictive value can be improved by peripheral atherosclerosis markers, namely carotid intima-media thickness (CIMT) and ankle-brachial index (ABI), was unknown. Methods-A total of 3289 participants of the population-based Heinz Nixdorf Recall study (45-75 years; 48.8% men) without previous stroke or coronary heart disease were evaluated for incident stroke for 9.0 +/- 1.9 years. CAC, CIMT, and ABI were examined as stroke predictors. Results-Eighty-four strokes occurred during follow-up. In multivariable Cox proportional hazard regressions, CAC (hazard ratio, 1.45 [95% confidence interval, 1.11-1.88] per SD increase in ln(CAC+1); SD, 2.40), CIMT (1.34 [1.08-1.66] per SD increase; SD, 0.127 mm), and ABI (1.55 [1.32-1.82] per SD decrease; SD, 0.148) were associated with stroke in addition to established risk factors. When combined with each other, ln(CAC+1)'s hazard ratio remained similar when CIMT (1.41 [1.09-1.83]) was inserted into the multivariable model, but slightly decreased when ABI (1.31 [1.01-1.72]) or CIMT and ABI (1.29 [0.99-1.68]) were included. Although CAC alone did not significantly elevate the area under the curve in Harrell's c-statistics (by 0.009; P=0.379) in addition to established risk factors, the combination of CAC and ABI increased area under the curve (by 0.029; P=0.047), as did ABI (by 0.025; P=0.038) but not CIMT (by 0.002; P=0.795) alone. The combination of CAC and ABI also resulted in significant category-free net reclassification and integrated discrimination improvement. Conclusions-CAC, CIMT, and ABI provide complementary information about stroke risk. ABI, which is distinctive in a small subpopulation, had the highest and CIMT, which is distributed across a larger range of values, had the lowest predictive value.