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

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.

• Authors: Jan Willem van Dalen, Zachary A Marcum, Shelly L Gray, Douglas Barthold, Eric P Moll van Charante, Willem A van Gool, Paul K Crane, Eric B Larson, Edo Richard
• Journal: Neurology (Neurology) Vol. 96 Issue 1 Pg. e67-e80 (01 05 2021) ISSN: 1526-632X [Electronic] United States
• PMID: 33154085 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Antihypertensive Agents
• Sodium Chloride Symporter Inhibitors
• Angiotensin II

Topics

• Aged
• Angiotensin II (drug effects)
• Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
• Antihypertensive Agents (therapeutic use)
• Dementia (epidemiology)
• Female
• Humans
• Hypertension (drug therapy)
• Incidence
• Male
• Sodium Chloride Symporter Inhibitors (therapeutic use)