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(Circulation. 1999;100:e88-e94.)
© 1999 American Heart Association, Inc.

Circulation Electronic Pages

Identification of Risk Factors in Hypertensive Patients

Contribution of Randomized Controlled Trials Through an Individual Patient Database

François Gueyffier, MD, PhD; Jean-Pierre Boissel, MD; Stuart Pocock, PhD; Florent Boutitie, MSc; John Coope, MD; Jeffrey Cutler, MD; Tord Ekbom, MD; Robert Fagard, MD; Lawrence Friedman, MD; Karla Kerlikowske, MD; Mitchell Perry, MD; Ronald Prineas, MD; Eleanor Schron, RN, MS

From the Clinical Pharmacology Department (F.G., J.-P.B., F.B.), Claude Bernard University, Lyon Hospitals, Lyon, France; the National Heart, Lung, and Blood Institute (J.C., L.F., E.S.), National Institutes of Health, Bethesda, Md; the Department of Community Health Sciences (T.E.), Dalby/Lund, Sweden; Veterans Administration Medical Center (K.K.), San Francisco, Calif; the Hypertension and Cardiovascular Rehabilitation Unit (R.F.), Leuven, Belgium; Washington University School of Medicine (M.P.), St Louis, Mo; London School of Hygiene and Tropical Medicine (S.P.), London, UK; and the Division of Epidemiology (R.P.), University of Minnesota, Minneapolis. Dr Coope is in general practice, Bollington, UK.

Correspondence to Dr François Gueyffier, Service de Pharmacologie Clinique, Faculté RTH Laënnec, Rue 6, Paradin BP8071, 69376 Lyon, France. E-mail fg{at}upcl.univ-lyon1.fr

Background—Predicting individual risk is needed to target preventive interventions toward people with the highest probability of benefit over a given time period. We assessed which prognostic factors should be used in predicting risk for hypertensive patients and in searching for treatment modifiers.

Methods and Results—Data from 24 390 hypertensive participants who constituted the control groups from 8 controlled trials (1726 deaths over 5 years) were analyzed in multivariate survival models. Outcomes were coronary heart disease death, stroke death, and cardiovascular death. We explored systematically the heterogeneity of results between trials. Left ventricular hypertrophy was electrocardiographically confirmed to be a powerful risk factor and should be included in risk scoring. Height, glomerular filtration rate, and serum uric acid deserve further exploration. Body mass index and heart rate were not confirmed as independent cardiovascular risk factors in this population. The association between male sex and coronary heart disease death was significantly stronger in British cohorts. The lack of prognostic value of diastolic blood pressure was explained by an interaction with age, with a positive association before 65 years and a negative association thereafter. Previous antihypertensive treatment was a significant risk factor.

Conclusions—Clinical trials provide valuable information for risk prediction. Carefully exploring the heterogeneity among trials is a way to assess the generalizability of findings. This approach, if systematically performed, should increase the ability to identify risk modifiers and to predict individual therapeutic benefit.

Key Words: hypertension • trials • epidemiology • stroke • coronary disease

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