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Association of Angiotensin II-Stimulating Antihypertensive Use and Dementia Risk: Post Hoc Analysis of the PreDIVA Trial.

From the Departments of Neurology (J.W.v.D., W.A.v.G., E.R.) and General Practice (E.P.M.v.C.), Amsterdam UMC, University of Amsterdam; Department of Neurology (J.W.v.D., E.R.), Donders Institute for Brain, Behaviour and Cognition, Radboud University Medical Centre, Nijmegen, the Netherlands; Schools of Pharmacy (Z.A.M., S.L.G., D.B.) and Medicine (P.K.C.), University of Washington; and Kaiser Permanente Washington Health Research Institute (E.B.L.), Seattle. j.vandalen@amc.nl. From the Departments of Neurology (J.W.v.D., W.A.v.G., E.R.) and General Practice (E.P.M.v.C.), Amsterdam UMC, University of Amsterdam; Department of Neurology (J.W.v.D., E.R.), Donders Institute for Brain, Behaviour and Cognition, Radboud University Medical Centre, Nijmegen, the Netherlands; Schools of Pharmacy (Z.A.M., S.L.G., D.B.) and Medicine (P.K.C.), University of Washington; and Kaiser Permanente Washington Health Research Institute (E.B.L.), Seattle.

Neurology. 2021;(1):e67-e80
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Abstract

OBJECTIVE To assess whether angiotensin II-stimulating antihypertensives (thiazides, dihydropyridine calcium channel blockers, and angiotensin I receptor blockers) convey a lower risk of incident dementia compared to angiotensin II-inhibiting antihypertensives (angiotensin-converting enzyme inhibitors, β-blockers, and nondihydropyridine calcium channel blockers), in accordance with the "angiotensin hypothesis." METHODS We performed Cox regression analyses of incident dementia (or mortality as competing risk) during 6-8 years of follow-up in a population sample of 1,909 community-dwelling individuals (54% women) without dementia, aged 70-78 (mean 74.5 ± 2.5) years. RESULTS After a median of 6.7 years of follow-up, dementia status was available for 1,870 (98%) and mortality for 1,904 (>99%) participants. Dementia incidence was 5.6% (27/480) in angiotensin II-stimulating, 8.2% (59/721) in angiotensin II-inhibiting, and 6.9% (46/669) in both antihypertensive type users. Adjusted for dementia risk factors including blood pressure and medical history, angiotensin II-stimulating antihypertensive users had a 45% lower incident dementia rate (hazard ratio [HR], 0.55; 95% CI, 0.34-0.89) without excess mortality (HR, 0.86; 95% CI, 0.64-1.16), and individuals using both types had a nonsignificant 20% lower dementia rate (HR, 0.80; 95% CI,0.53-1.20) without excess mortality (HR, 0.97; 95% CI, 0.76-1.24), compared to angiotensin II-inhibiting antihypertensive users. Results were consistent for subgroups based on diabetes and stroke history, but may be specific for individuals without a history of cardiovascular disease. CONCLUSIONS Users of angiotensin II-stimulating antihypertensives had lower dementia rates compared to angiotensin II-inhibiting antihypertensive users, supporting the angiotensin hypothesis. Confounding by indication must be examined further, although subanalyses suggest this did not influence results. If replicated, dementia prevention could become a compelling indication for older individuals receiving antihypertensive treatment.

Methodological quality

Publication Type : Randomized Controlled Trial

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