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(Hypertension. 2005;46:492.)
© 2005 American Heart Association, Inc.

Original Articles

Cardiovascular Morbidity and Mortality in Hypertensive Patients With Lower Versus Higher Risk

A LIFE Substudy

Stanley S. Franklin; Kristian Wachtell; Vasilios Papademetriou; Michael H. Olsen; Richard B. Devereux; Frej Fyhrquist; Hans Ibsen; Sverre E. Kjeldsen; Björn Dahlöf

From the Heart Disease Prevention Program, University of California, Irvine (S.S.F.); Copenhagen County University Hospital, Glostrup, Denmark (K.W., M.H.O., H.I.); VA Medical Center, Washington DC (V.P.); Weill Medical College of Cornell University, New York, NY (K.W., R.B.D.); Helsinki University Central Hospital, Finland (F.F.); Ullevål University Hospital, Oslo, Norway (S.E.K.); Sahlgrenska University Hospital-Östra, Gothenburg, Sweden (B.D.).

Correspondence to Dr Stanley S. Franklin, MD, Heart Disease Prevention Program, C240 Medical Sciences, University of California, Irvine, CA 92697. E-mail ssfranklinmd{at}earthlink.net

We hypothesized that losartan was superior to atenolol in reducing cardiovascular events in a lower-risk group (LRG) versus a higher-risk group (HRG) of patients in a Losartan Intervention For Endpoint reduction (LIFE) substudy, independently of blood pressure (BP) reduction. In a post hoc analysis, we designated 4282 patients as LRG on the basis of: (1) no previous cardiovascular disease (coronary, cerebral, peripheral vascular disease); (2) no diabetes; (3) no isolated systolic hypertension; and (4) inclusion of the lowest 3 quartiles of electrocardiographically documented left ventricular hypertrophy. The HRG consisted of 4911 remaining patients who did not qualify for the LRG. In the LRG, losartan was superior to atenolol in reducing stroke: hazard ratio (HR), 0.72 (95% confidence interval [CI], 0.53 to 0.98); new-onset diabetes (HR, 0.74 [95% CI, 0.58 to 0.93]; and new-onset atrial fibrillation: HR, 0.69 (95% CI, 0.51 to 0.92), all P<0.05 but not composite end points or cardiovascular mortality (both P=NS). In the HRG, losartan was superior to atenolol in reducing composite end points: HR, 0.82 (95% CI, 0.71 to 0.94), P<0.01; cardiovascular mortality: HR, 0.77 (95% CI, 0.62 to 0.95), P<0.05; stroke: HR, 0.75 (95% CI, 0.61 to 0.92), P<0.01; new-onset diabetes: HR, 0.76 (95% CI, 0.60 to 0.96), P<0.05; and new-onset atrial fibrillation: HR, 0.71 (95% CI, 0.58 to 88), P<0.05. Test for interaction of treatment with LRG versus HRG was not significant for composite end point, stroke, or atrial fibrillation, but was for cardiovascular mortality (P=0.018). Achieved systolic BP reduction favored losartan over atenolol by –1.8 mm Hg in LRG (P=NS) and –0.7 mm Hg (P=0.001) in HRG, but no significant differences occurred in diastolic or mean BP in either group. In conclusion, losartan compared with atenolol reduces the risk of stroke, new-onset diabetes, and new-onset atrial fibrillation in the LRG and the HRG.

Key Words: risk factors • stroke • hypertrophy, left ventricular • hypertension