title: Coronary artery calcification, intima-media thickness, and ankle-brachial index are complementary stroke predictors.
abstract: OBJECTIVE
  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.
authors.affiliation: From the Departments of Neurology (J.G., C.W., D.M.H.) and Cardiology (M.B., A.A.M., H.K., R.E.), University Hospital Essen, Essen, Germany; Institute of Medical Informatics, Biometry, and Epidemiology, University of Duisburg-Essen, Essen, Germany (N.L., S.M., K.-H.J.); and Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany (K.B.).
authors.forename: Janine
authors.initials: J
authors.lastname: Gronewold
authors.affiliation: From the Departments of Neurology (J.G., C.W., D.M.H.) and Cardiology (M.B., A.A.M., H.K., R.E.), University Hospital Essen, Essen, Germany; Institute of Medical Informatics, Biometry, and Epidemiology, University of Duisburg-Essen, Essen, Germany (N.L., S.M., K.-H.J.); and Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany (K.B.).
authors.forename: Marcus
authors.initials: M
authors.lastname: Bauer
authors.affiliation: From the Departments of Neurology (J.G., C.W., D.M.H.) and Cardiology (M.B., A.A.M., H.K., R.E.), University Hospital Essen, Essen, Germany; Institute of Medical Informatics, Biometry, and Epidemiology, University of Duisburg-Essen, Essen, Germany (N.L., S.M., K.-H.J.); and Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany (K.B.).
authors.forename: Nils
authors.initials: N
authors.lastname: Lehmann
authors.affiliation: From the Departments of Neurology (J.G., C.W., D.M.H.) and Cardiology (M.B., A.A.M., H.K., R.E.), University Hospital Essen, Essen, Germany; Institute of Medical Informatics, Biometry, and Epidemiology, University of Duisburg-Essen, Essen, Germany (N.L., S.M., K.-H.J.); and Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany (K.B.).
authors.forename: Amir A
authors.initials: AA
authors.lastname: Mahabadi
authors.affiliation: From the Departments of Neurology (J.G., C.W., D.M.H.) and Cardiology (M.B., A.A.M., H.K., R.E.), University Hospital Essen, Essen, Germany; Institute of Medical Informatics, Biometry, and Epidemiology, University of Duisburg-Essen, Essen, Germany (N.L., S.M., K.-H.J.); and Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany (K.B.).
authors.forename: Hagen
authors.initials: H
authors.lastname: Kälsch
authors.affiliation: From the Departments of Neurology (J.G., C.W., D.M.H.) and Cardiology (M.B., A.A.M., H.K., R.E.), University Hospital Essen, Essen, Germany; Institute of Medical Informatics, Biometry, and Epidemiology, University of Duisburg-Essen, Essen, Germany (N.L., S.M., K.-H.J.); and Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany (K.B.).
authors.forename: Christian
authors.initials: C
authors.lastname: Weimar
authors.affiliation: From the Departments of Neurology (J.G., C.W., D.M.H.) and Cardiology (M.B., A.A.M., H.K., R.E.), University Hospital Essen, Essen, Germany; Institute of Medical Informatics, Biometry, and Epidemiology, University of Duisburg-Essen, Essen, Germany (N.L., S.M., K.-H.J.); and Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany (K.B.).
authors.forename: Klaus
authors.initials: K
authors.lastname: Berger
authors.affiliation: From the Departments of Neurology (J.G., C.W., D.M.H.) and Cardiology (M.B., A.A.M., H.K., R.E.), University Hospital Essen, Essen, Germany; Institute of Medical Informatics, Biometry, and Epidemiology, University of Duisburg-Essen, Essen, Germany (N.L., S.M., K.-H.J.); and Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany (K.B.).
authors.forename: Susanne
authors.initials: S
authors.lastname: Moebus
authors.affiliation: From the Departments of Neurology (J.G., C.W., D.M.H.) and Cardiology (M.B., A.A.M., H.K., R.E.), University Hospital Essen, Essen, Germany; Institute of Medical Informatics, Biometry, and Epidemiology, University of Duisburg-Essen, Essen, Germany (N.L., S.M., K.-H.J.); and Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany (K.B.).
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Jöckel
authors.affiliation: From the Departments of Neurology (J.G., C.W., D.M.H.) and Cardiology (M.B., A.A.M., H.K., R.E.), University Hospital Essen, Essen, Germany; Institute of Medical Informatics, Biometry, and Epidemiology, University of Duisburg-Essen, Essen, Germany (N.L., S.M., K.-H.J.); and Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany (K.B.).
authors.forename: Raimund
authors.initials: R
authors.lastname: Erbel
authors.affiliation: From the Departments of Neurology (J.G., C.W., D.M.H.) and Cardiology (M.B., A.A.M., H.K., R.E.), University Hospital Essen, Essen, Germany; Institute of Medical Informatics, Biometry, and Epidemiology, University of Duisburg-Essen, Essen, Germany (N.L., S.M., K.-H.J.); and Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany (K.B.). dirk.hermann@uk-essen.de.
authors.forename: Dirk M
authors.initials: DM
authors.lastname: Hermann
mesh_terms: D000368:Aged; D055109:Ankle Brachial Index; D019540:Area Under Curve; D002114:Calcinosis / Q000000981:diagnostic imaging / Q000503:physiopathology*; D059168:Carotid Intima-Media Thickness; D003324:Coronary Artery Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000503:physiopathology*; D014057:Tomography, X-Ray Computed
keywords: carotid atherosclerosis; coronary artery disease; peripheral arterial disease