Framingham Stroke Risk Function in a Large Population-Based Cohort of Elderly People The 3C Study Se ´bastien Bineau, MD, Msc; Carole Dufouil, PhD; Catherine Helmer, MD, PhD; Karen Ritchie, PhD; Jean-Philippe Empana, MD, PhD; Pierre Ducimetie `re, PhD; Annick Alpe ´rovitch, MD, Msc; Marie Germaine Bousser, MD; Christophe Tzourio, MD, PhD Background and Purpose—External validation of the Framingham stroke risk function has been rarely performed. We assessed its predictive ability in a population-based cohort of French elderly. Methods—The sample comprised 6913 subjects from the 3C Study, aged 65 to 84 at baseline, who were followed up to 6 years. Predictive accuracy of the original Framingham stroke risk function was assessed in a 3-step procedure: comparison between the Framingham and 3C cohorts of the prevalence of selected risk factors and the associated relative risks (RR) for stroke, comparison of the predicted to the observed number of stroke events (calibration), and ability to separate high-risk from low-risk participants (discrimination). We also compared predictive performances of the original Framingham, the recalibrated Framingham, and the local stroke risk functions. Results—During follow-up, 110 incident strokes occurred. For most risk factors, RRs were comparable between the 2 cohorts, except for age in women. The original Framingham stroke risk function applied to the 3C cohort overestimated the 6-year absolute risk for stroke by a factor of 3.7 for men and 4.4 for women. However, the recalibrated Framingham and 3C functions did not show any over- or underestimation of stroke risk. The 3 stroke risk functions (original, recalibrated, and 3C) provided acceptable discrimination with areas under the ROC curve ranging from 0.67 to 0.73. Conclusions—The original Framingham stroke risk function strongly overestimated the stroke risk for 3C participants. Derived Framingham stroke score sheets should not be directly used by physicians in the French elderly population. (Stroke. 2009; 40:1564-1570.) Key Words: stroke  risk  aging  cohort studies C erebrovascular disease is a major cause of death. 1 Al- most 90% of deaths attributed to stroke occur among people aged 65 years or older. 2 Stroke is an important public health problem, especially in the elderly, as population ageing has given rise to significant increases in stroke incidence. Epidemiological studies have identified numerous stroke risk factors such as age, blood pressure, atrial fibrillation, heart failure, and diabetes mellitus. 3,4 Prediction models have subsequently been developed to assess the individual absolute risk of developing stroke. 5–9 Several widely used risk func- tions for stroke have been drawn from the Framingham Heart Study (FHS), one of the well-known studies in this field. 5,6,9 Primary prevention based on such tool should help to de- crease stroke incidence, stroke-related mortality, and long- term disability among the elderly. However, the Framingham cohort has certain particulari- ties which may preclude generalization of these risk functions to other samples including the large proportion of white, middle-aged, suburban Americans included, and the low prevalence of subjects treated for classical cardiovascular risk factors. To apply FHS risk functions to other populations, external validation studies are therefore required. Implementation of the Framingham stroke risk functions has been rarely investigated in other geographic settings and in elderly populations taking multiple medications. 7,10,11 The aim of the present study was to assess the external validity of the Framingham stroke risk functions in a large cohort of French people aged 65 years and over, the Three-City (3C) Study. Materials and Methods Study Population The 3C Study is an ongoing French prospective multicenter population-based cohort study whose main objective is to estimate Received July 24, 2008; final revision received October 3, 2008; accepted November 13, 2008. From INSERM U708 “Neuroepidemiology” (S.B., C.D., A.A., C.T.), Paris; UPMC Univ Paris 06 (S.B., C.D., A.A., C.T.), Paris; INSERM U593 and Universite ´ Bordeaux 2 (C.H.), Bordeaux; INSERM U888 (K.R.), Montpellier; INSERM U909 (J.-P.E., P.D.), Villejuif; and the Department of Neurology (M.G.B., C.T.), Ho ˆpital Lariboisie `re, Paris, France. Correspondence to Dr Christophe Tzourio, INSERM U708, Ho ˆpital de la Salpe ˆtrie `re, 47, boulevard de l’Ho ˆpital, 75651 PARIS CEDEX 13, France. E-mail tzourio@chups.jussieu.fr © 2009 American Heart Association, Inc. Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.108.532325 1564 by guest on June 23, 2015 http://stroke.ahajournals.org/ Downloaded from