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[Preprint]. 2024 Aug 29:2024.08.28.24312754.
doi: 10.1101/2024.08.28.24312754.

Antihypertensive medications and dementia in older adults with hypertension

Suzanne G Orchard  1 , Zhen Zhou  1   2 , Michelle Fravel  3 , Joanne Ryan  1 , Robyn L Woods  1 , Rory Wolfe  1 , Raj C Shah  4 , Anne Murray  5 , Ajay Sood  6 , Christopher M Reid  7 , Mark R Nelson  2 , Lawrie Bellin  8 , Kevan R Polkinghorne  1   9   10 , Nigel Stocks  11 , Michael E Ernst  3   12
Affiliations

Antihypertensive medications and dementia in older adults with hypertension

Suzanne G Orchard et al. medRxiv. .

Abstract

Background: Studies on middle-aged or individuals with cognitive or cardiovascular impairments, have established that intensive blood pressure (BP) control reduces cognitive decline risk. However, uncertainty exists on differential effects between antihypertensive medications (AHM) classes on this risk, independent of BP-lowering efficacy, particularly in community-dwelling hypertensive older adults.

Methods: A post-hoc analysis of the ASPREE study, a randomized trial of low-dose aspirin in adults aged 70+ years (65+ if US minorities) without baseline dementia, and followed for two years post-trial. Cox proportional-hazards regression models were used to estimate associations between baseline and time-varying AHM exposure and incident dementia (an adjudicated primary trial endpoint), in participants with baseline hypertension. Subgroup analyses included prespecified factors, APO ε4 carrier status and monotherapy AHM use.

Results: Most hypertensive participants (9,843/13,916; 70.7%) used AHMs. Overall, 'any' AHM use was not associated with lower incident dementia risk, compared with untreated participants (HR 0.84, 95%CI 0.70-1.02, p=0.08), but risk was decreased when angiotensin receptor blockers (ARBs) were included (HR 0.73, 95%CI 0.59-0.92, p=0.007). ARBs and β-blockers decreased dementia risk, whereas angiotensin-converting enzyme inhibitors (ACEIs) and diuretics increased risk. There was no association with RAS modulating or blood-brain-barrier crossing AHMs on dementia risk.

Conclusions: Overall, AHM exposure in hypertensive older adults was not associated with decreased dementia risk, however, specific AHM classes were with risk direction determined by class; ARBs and β-blockers were superior to ACEIs and other classes in decreasing risk. Our findings emphasize the importance of considering effects beyond BP-lowering efficacy when choosing AHM in older adults.

Keywords: Angiotensin II receptor blocker; Angiotensin-converting enzyme inhibitor; Antihypertensive medication; aged; cognition; dementia; older adults.

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Conflict of interest statement

DISCLOSURES Dr. Shah reports being the site principal investigator or sub-investigator for Alzheimer’s disease clinical trials for which his institution (Rush University Medical Center) is compensated [Amylyx Pharmaceuticals, Inc., Athira Pharma, Inc., Edgewater NEXT, Eli Lilly & Co., Inc., Genentech, Inc.]. The remaining authors declare that they have no conflict of interests.

Figures

Figure 1.
Figure 1.
Risk of incident dementia between specific AHM treated groups (time-varying) over median 6.4 years of follow-up.
See this image and copyright information in PMC

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References

    1. World Health Organization. Geneva, Switzerland: World Health Organization; 2021. Fact sheets of dementia [Internet] [cited 2022 Apr 13]. Available from: https://www.who.int/news-room/fact-sheets/detail/dementia.
    1. Lucca U, Tettamanti M, Tiraboschi P, Logroscino G, Landi C, Sacco L, Garrì M, Ammesso S, Biotti A, Gargantini E, et al. Incidence of dementia in the oldest-old and its relationship with age: The Monzino 80-plus population-based study. Alzheimers Dement. 2020;16(3):472–481. doi: 10.1016/j.jalz.2019.09.083 - DOI - PubMed
    1. Abell JG, Kivimäki M, Dugravot A, Tabak AG, Fayosse A, Shipley M, Sabia S, Singh-Manoux A. Association between systolic blood pressure and dementia in the Whitehall II cohort study: role of age, duration, and threshold used to define hypertension. Eur Heart J. 2018;1;39(33):3119–3125. doi: 10.1093/eurheartj/ehy288 - DOI - PMC - PubMed
    1. Cheng W, Du Y, Zhang Q, Wang X, He C, He J, Jing F, Ren H, Guo M, Tian J, Xu Z. Age-related changes in the risk of high blood pressure. Front Cardiovasc Med. 2022;15;9:939103. doi: 10.3389/fcvm.2022.939103 - DOI - PMC - PubMed
    1. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Despres JP, Fullerton HJ, Howard VJ, et al., American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation. 2015;131:e29–322 - PubMed

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