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

Study Questions:

Can carotid intima-media thickness (CIMT) and ankle-brachial index (ABI) add to the predictive value of coronary artery calcification (CAC) of stroke?


Data from the population-based Heinz Nixdorf Recall Study, a random sample of men and women ages 45-75 years enrolled between December 2000 and August 2003, were used for the present analysis. Participants were followed up for 9.0 ± 1.9 years. Participants with a prior history of previous stroke or coronary heart disease were excluded.


A total of 3,289 participants (48.8% men) were included and followed over 9.0 ± 1.9 years. Eighty-four strokes (75 ischemic, 9 hemorrhagic) occurred during follow-up among 84 subjects (2.55%; 48 men, 36 women). Compared with subjects not having a stroke, subjects exhibiting a stroke were older; had a higher waist circumference; more often revealed arterial hypertension, diabetes mellitus, and atrial fibrillation; and had higher triglycerides and a higher Framingham risk score. Subjects experiencing a stroke had higher CAC and CIMT values, and lower ABI values. They more frequently received medications for hypertension and diabetes. In multivariable Cox proportional hazard regression models, CAC (hazard ratio, 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, 0.127 mm), and ABI (1.55 [1.32–1.82] per SD decrease; SD, 0.148) were associated with stroke, with established risk factors included in the models. 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.


The investigators concluded that CAC, CIMT, and ABI provide complementary information about stroke risk. ABI, which is distinctive in a small subpopulation, had the highest, whereas CIMT, which is distributed across a larger range of values, had the lowest predictive value.


These data suggest that information on CAC, CIMT, and ABI provide useful predictive information on stroke risk. Determining the cost-benefit of such testing is warranted.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Noninvasive Imaging, Prevention, Hypertriglyceridemia, Lipid Metabolism, Echocardiography/Ultrasound, Hypertension

Keywords: Stroke, Follow-Up Studies, Brachial Artery, Carotid Intima-Media Thickness, Ankle Brachial Index, Coronary Disease, Risk Factors, Waist Circumference, Research Personnel, Vascular Calcification, Confidence Intervals, Triglycerides, Hypertension, Diabetes Mellitus

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