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The Prevention of Dementia With Antihypertensive Treatment
New Evidence From the Systolic Hypertension in Europe (Syst-Eur) Study
Françoise Forette, MD;
Marie-Laure Seux, MD;
Jan A. Staessen, MD, PhD;
Lutgarde Thijs, MSc;
Marija-Ruta Babarskiene, MD;
Speranta Babeanu, MD;
Alfredo Bossini, MD;
Robert Fagard, MD;
Blas Gil-Extremera, MD;
Tovio Laks, MD;
Zhanna Kobalava, MD;
Cinzia Sarti, MD;
Jaakko Tuomilehto, MD;
Hannu Vanhanen, MD;
John Webster, MD;
Yair Yodfat, MD;
Willem H. Birkenhäger, MD;
for the Syst-Eur Investigators
Arch Intern Med. 2002;162:2046-2052.
Background After the double-blind, placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial ended in February 1997, randomized patients were offered active study medication for a further period of observation.
Objective To refine the estimates of the long-term effects of antihypertensive therapy on the incidence of dementia.
Methods Eligible patients had no dementia and were at least 60 years old. Their systolic blood pressure at entry was 160 to 219 mm Hg, with diastolic blood pressure below 95 mm Hg. Antihypertensive therapy was started immediately after randomization in the active treatment group, but only after termination of the double-blind trial in the control patients. Treatment consisted of nitrendipine (10-40 mg/d), with the possible addition of enalapril maleate (5-20 mg/d), hydrochlorothiazide (12.5-25 mg/d), or both add-on drugs.
Results Median follow-up increased from 2.0 years in the double-blind trial to 3.9 years overall. The incidence of dementia doubled from 32 to 64 cases, 41 of whom had Alzheimer disease. Throughout follow-up, systolic/diastolic blood pressure was 7.0/3.2 mm Hg higher in the 1417 control patients than in the 1485 subjects randomized to active treatment. At the last examination, the blood pressure difference was still 4.2/2.9 mm Hg; 48.1%, 26.4%, and 11.4% of the control patients were taking nitrendipine, enalapril, and/or hydrochlorothiazide, whereas in the active treatment group these proportions were 70.2%, 35.4%, and 18.4%, respectively. Compared with the controls, long-term antihypertensive therapy reduced the risk of dementia by 55%, from 7.4 to 3.3 cases per 1000 patient-years (43 vs 21 cases, P<.001). After adjustment for sex, age, education, and entry blood pressure, the relative hazard rate associated with the use of nitrendipine was 0.38 (95% confidence interval, 0.23-0.64; P<.001). Treatment of 1000 patients for 5 years can prevent 20 cases of dementia (95% confidence interval, 7-33).
Conclusion The extended follow-up of Syst-Eur patients reinforces the evidence that blood pressure–lowering therapy initiated with a long-acting dihydropyridine protects against dementia in older patients with systolic hypertension.
From the Department of Geriatrics, Hôpital Broca, University of Paris V, Paris, France (Drs Forette and Seux); Study Coordinating Centre, Department of Molecular and Cardiovascular Research, University of Leuven, Leuven, Belgium (Drs Staessen and Fagard and Ms Thijs); Institute of Cardiology, Kaunas, Lithuania (Dr Babarskiene); National Institute Ana Aslan, Bucharest, Romania (Dr Babeanu); Centro Ipertensione Policlinico Umberto I, Rome, Italy (Dr Bossini); Facultad de Medicina, Universidad de Granada, Granada, Spain (Dr Gil-Extremera); Tallinn Central Hospital, Tallinn, Estonia (Dr Laks); Department of Internal Diseases, Municipal Clinical Hospital, Moscow, Russian Federation (Dr Kobalava); Department of Epidemiology and Health Promotion, National Public Health Institute, and Department of Public Health, University of Helsinki, Helsinki, Finland (Drs Sarti and Tuomilehto); Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland (Dr Vanhanen); Aberdeen Royal Hospitals, University of Aberdeen, Aberdeen, Scotland (Dr Webster); Department of Family Medicine, Hadassah Medical School, Hebrew University of Jerusalem, Jerusalem, Israel (Dr Yodfat); and Erasmus University, Rotterdam, the Netherlands (Dr Birkenhäger).
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