Abstract

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: 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 over 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[HR]=1.45[95%-confidence interval=1.11-1.88] per standard deviation (SD) increase in ln(CAC+1); SD=2.40), CIMT (1.34[1.08-1.66] per SD increase; SD=0.127mm) 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 HR 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. While CAC alone did not significantly elevate the area-under-the-curve (AUC) in Harrell's c-statistics (by 0.009; p=0.379) in addition to established risk factors, the combination of CAC and ABI increased AUC (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.

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