Evidence map›Paper›PMID 33154085›Full record

Trial reportNeurology2021

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

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

Open access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.

  1. Pooled it
  2. Effect of Initiation and Continuous Adherence to ARBs Versus ACEIs on Risk of Adjudicated Mild Cognitive Impairment or Dementia.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025
    Trial
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  17. Studying and learning.Journal of diabetes · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 2 countries.

Jan Willem van DalenFrom 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.ORCID 0000-0002-3439-8841
Zachary A MarcumFrom 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.
Shelly L GrayFrom 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.
Douglas BartholdFrom 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.
Eric P Moll van CharanteFrom 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.
Willem A van GoolFrom 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.
Paul K CraneFrom 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.
Eric B LarsonFrom 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.
Edo RichardFrom 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.
Radboud University Nijmegen · NL

Funding

UW Patient-Centered Outcomes Research Career Development Program K12 2014 2019K12HS022982 · AHRQ · UNIVERSITY OF WASHINGTON · PI SULLIVAN, SEAN D · 2014 to 2018
$3.8M
Antihypertensives and the Aging BrainK76AG059929 · NIA · UNIVERSITY OF WASHINGTON · PI MARCUM, ZACHARY ADAM · 2019 to 2021
$694k
AHRQ HHS K12 HS022982NIA NIH HHS K76 AG059929
6 · The paper itself

Abstract

objectiveTo 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."

methodsWe 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.

resultsAfter 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.

conclusionsUsers 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.

Indexed as

AgedAngiotensin-Converting Enzyme InhibitorsAngiotensin IIAntihypertensive AgentsDementiaFemaleHumansHypertensionIncidenceMaleSodium Chloride Symporter InhibitorsAngiotensin-Converting Enzyme InhibitorsAngiotensin IIAntihypertensive AgentsSodium Chloride Symporter Inhibitors

Identifiers

PMID33154085
PMCPMC7884979
OpenAlexW3097116649

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.