For the Syst-Eur Investigators. The Prevention of Dementia With Antihypertensive Treatment. New Evidence From the Systolic Hypertension in Europe (Syst-Eur) Study - Syst-Eur

Description:

The goal of this study was to assess the degree to which antihypertensive treatment is associated with a reduction in the frequency of vascular disease (VascD) and Alzheimer's dementia (AlzD).

Study Design

Study Design:

Drug/Procedures Used:

An extended observational study of the long-term incidence of dementia developing in participants of the Syst-Eur Study, a randomized placebo controlled trial assessing the effect of dihydropyridine / HCTZ / and or ACEi in the treatment of systolic hypertension (160-219 mmHg / <95 mmHg) on the subsequent risk of stroke and CVD. Patients randomized to placebo were treated with the active drugs and all subjects were followed or a total of 3.9 years. Dementia was determined by a Mini-Mental Status Exam. VascD and AlzD were differentiated by brain CT or the Hachinski score.

Principal Findings:

Of the initial 3,228 patients in Syst-Eur, 1,417 previously on placebo and 1,485 on active drug were enrolled in the dementia and follow-up study. The mean age was 68 years, about two thirds were women, and 25% had previous CVD and 1% of patients had sustained a CVA. The incidence of dementia increased from 32 to 64 cases (41 AlzD). The syst/dias BP was 7.0/3.2 mmHg higher in the control compared with the treatment patients throughout the follow-up. The majority of patients in both groups were on nitrendipine. Compared with controls, patients randomized to initial active treatment had a 55% reduced risk of dementia (7.4 to 3.3 cases per 1000 pt years, p < 0.001 (it should be noted that there were only 32 cases, however). After adjustment for sex, age, education, and entry BP, the RR associated with nitrendipine was 0.38 (95%CI 0.23-0.64, p 0.001).

Interpretation:

Among older patients with systolic hypertension, blood pressure lowering with a long acting dihydropyridine was associated with a reduction in the frequency of vascular (VascD) and Alzheimer's dementia. The initial hypothesis was that treatment would lower the incidence of vascular dementia, and in fact the dominant effect was on degenerative Alzheimer's disease. It is of interest that beta-blockers, ACEi, and diuretics reduce stroke rates among patients with hypertension, but have no effect on dementia or cognitive function. The authors speculate that calcium channel blockers may offer some neuroprotection via regulation of intracellular calcium and reduction in cell death.

References:

Forette F, Seux ML, Staessen JA et al. For the Syst-Eur Investigators. The Prevention of Dementia With Antihypertensive Treatment. New Evidence From the Systolic Hypertension in Europe (Syst-Eur) Study. Arch Intern Med. 2002;162:2046-52.

Presented at the European Society of Cardiology, Vienna, Austria, September 2003.

Clinical Topics: Prevention, Vascular Medicine, Statins, Hypertension, Sleep Apnea

Keywords: Dihydropyridines, Stroke, Cognition, Follow-Up Studies, Diuretics, Cell Death, Calcium Channel Blockers, Nitrendipine, Dementia, Vascular, Hydrochlorothiazide, Hypertension


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