Effect of renin‐angiotensin system antihypertensive medication use on cognitive function in diabetes mellitus with obesity or overweight: An ancillary study to the Action for Health in Diabetes (Look AHEAD ) trial

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Type 2 diabetes mellitus with overweight or obesity and hypertension (n=712). Intervention: Renin-angiotensin system antihypertensive medication (RAS-AHM: ACE inhibitors or AT1 receptor blockers) vs. Other antihypertensive medications (diuretics, beta-blockers, calcium channel blockers, alpha-1 receptor blockers). Primary outcome: Adjudicated cognitive impairment (mild cognitive impairment or probable dementia) (OR 0.62, 95% CI 0.29-1.31, p=0.21).

Whitney Wharton; Andrea Anderson; Kathleen M. Hayden; Owen Carmichael; Jeanne M. Clark; José A. Luchsinger; Mark A. Espeland; Sevil Yaşar

doi:10.1111/dom.14838

August 16, 2022Diabetes Obesity and MetabolismOpen Access

Effect of renin‐angiotensin system antihypertensive medication use on cognitive function in diabetes mellitus with obesity or overweight: An ancillary study to the Action for Health in Diabetes (Look AHEAD ) trial

View Full Paper

Ask AI

Bookmark

Share

Key result

Renin-angiotensin system antihypertensive use did not significantly reduce cognitive impairment (OR 0.62, p=0.21) compared to other antihypertensives, but slowed composite cognitive decline (p=0.008).

Why the study?

To determine whether antihypertensive medication acting through the renin-angiotensin system, compared with other antihypertensive medications, can mitigate effects on cognitive function and risk for impairment in type 2 diabetes mellitus.

Does the use of renin-angiotensin system antihypertensive medications reduce the risk of cognitive impairment or slow cognitive decline compared with other antihypertensive medications in adults with type 2 diabetes and overweight or obesity?

Key Points

To determine whether antihypertensive medications acting via the renin-angiotensin system (RAS-AHM) mitigate cognitive decline and lower the risk of cognitive impairment compared with other antihypertensive medications in adults with type 2 diabetes mellitus.
Secondary analysis of 712 community-dwelling participants with overweight or obesity and type 2 diabetes from the randomized controlled Look AHEAD trial, followed over an average of 14.8 years.
Participants were categorized as users of RAS-AHM (N=563) or other antihypertensive medications (N=149), with cognitive impairment adjudicated across up to four cognitive assessments.
Multivariable logistic regression evaluated cognitive impairment risk, and linear regression assessed domain-specific cognitive performance after adjusting for confounders.
Cognitive impairment occurred in 7.5% of RAS-AHM users and 10.1% of other-AHM users; fully adjusted models showed no significant risk reduction (OR=0.62, 95% CI 0.29–1.31; p=0.21).
RAS-AHM users showed significantly better executive function on Trail Making Test Part B (β=−16.4, p=0.004), processing speed on Digit Symbol Substitution Test (β=2.6, p=0.005), and verbal memory on Rey Auditory Verbal Learning Test delayed recall (β=2.3, p=0.005).
Overall composite cognitive scores were significantly higher in the RAS-AHM group compared to other antihypertensive users (β=0.17, p=0.008).

Study Design

Type

Cohort (n=712)

Blinding

Two masked adjudicators independently reviewed cognitive status

Multicenter

Yes

Structured PICO

Does the use of renin-angiotensin system antihypertensive medications reduce the risk of cognitive impairment or slow cognitive decline compared with other antihypertensive medications in adults with type 2 diabetes and overweight or obesity?

P

Population

712 community-dwelling adults aged 45-76 years with type 2 diabetes and overweight or obesity using antihypertensive medications in the Look AHEAD ancillary study, followed for a mean of 14.8 years.

E

Exposure

Renin-angiotensin system antihypertensive medications (RAS-AHM, n=563), consisting of angiotensin-converting enzyme inhibitors (benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, trandolapril) or angiotensin 1 receptor blockers (candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan), without concurrent or sequential use of other antihypertensive classes.

C

Comparator

Other antihypertensive medications (Other-AHM, n=149), including diuretics, beta-receptor blockers, calcium channel blockers, and alpha-1 receptor blockers, without concurrent or sequential use of RAS-AHM.

O

Outcome

Adjudicated cognitive impairment (composite of mild cognitive impairment or probable dementia) and standardized composite cognitive function z-score over a mean of 14.8 years of follow-up.composite

Main Result

Odds Ratio: 0.62 (95% CI 0.29–1.31)

Absolute Event Rate: 7.5% vs 10.1%

p-value: p=0.21

In adults with type 2 diabetes and overweight or obesity, renin-angiotensin system antihypertensives did not significantly reduce the incidence of mild cognitive impairment or dementia compared with other antihypertensives over 14.8 years, but were associated with slower decline across executive function, processing speed, verbal memory, and composite cognition.

Limitations

Unable to account for the history of hypertension, including length, severity, and prior antihypertensive medication use
Observational cohort design susceptible to residual confounding and unable to establish causality
Lack of baseline cognitive evaluation at trial enrollment
Study population was highly educated and predominantly white, limiting generalizability
Exclusion of participants using both RAS-AHM and other antihypertensive classes concurrently or at different visits
Potential survival bias with large intervals between cognitive assessments
Cannot account for prior history, duration, or severity of hypertension
Observational secondary analysis susceptible to unmeasured confounding and unable to establish causality
No baseline cognitive evaluation was performed at original trial enrollment
Excluded participants who used both RAS-AHM and other antihypertensive classes concurrently or at different visits
Study population was predominantly White and highly educated, limiting generalizability
Medication compliance was not determined despite visual inspection at visits
Potential survival bias across long intervals between cognitive assessments

Ask about this paper

Answers are grounded in this paper and cite their sources.

Implication

Does not support RAS antihypertensives to prevent cognitive impairment in T2D; leaves open slowed decline for prospective trials.

Abstract

AIM: To determine whether antihypertensive medication (AHM) acting through the renin angiotensin system (RAS-AHM), compared with other AHM, can mitigate effects on cognitive function and risk for impairment in a population with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This secondary analysis of the randomized controlled Action for Health in Diabetes (Look AHEAD) study included 712 community-dwelling participants who were followed over 15 years. Logistic regression was used to relate RAS-AHM use to cognitive impairment, and linear regression was used to relate RAS-AHM use to domain-specific cognitive function after adjusting for potential confounders. RESULTS: A total of 563 individuals reported RAS-AHM use and 149 reported other-AHM use during the study. RAS-AHM users have college or higher education (53%), had higher baseline glycated haemoglobin (57 mmol/mol), and reported higher diabetes medication use (86%), while other-AHM users were more likely to be White (72%), obese (25%) and to have cardiovascular history (19%). RAS-AHM use was not associated with a reduced risk of dementia compared with other-AHM use. We did observe better executive function (Trail Making Test, part B, P < 0.04), processing speed (Digit Symbol Substitution Test, P < 0.004), verbal memory (Rey Auditory Verbal Learning Test-delayed recall, P < 0.005), and composite score (P < 0.008) among RAS-AHM users compared with other-AHM users. CONCLUSION: In this sample of adults with T2DM, free of dementia at baseline, we observed a slower decline in processing speed, executive function, verbal memory, and composite score among RAS-AHM users.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Wharton et al. (2022) conducted a cohort in Type 2 diabetes mellitus with overweight or obesity and hypertension (n=712). Renin-angiotensin system antihypertensive medication (RAS-AHM: ACE inhibitors or AT1 receptor blockers) vs. Other antihypertensive medications (diuretics, beta-blockers, calcium channel blockers, alpha-1 receptor blockers) was evaluated on Adjudicated cognitive impairment (mild cognitive impairment or probable dementia) (OR 0.62, 95% CI 0.29-1.31, p=0.21). Renin-angiotensin system antihypertensive use did not significantly reduce cognitive impairment (OR 0.62, p=0.21) compared to other antihypertensives, but slowed composite cognitive decline (p=0.008).

synapsesocial.com/papers/6a7af57fb008f0cadf328c48 https://doi.org/10.1111/dom.14838

View Full Paper

Ask AI

Bookmark

Share

Effect of renin‐angiotensin system antihypertensive medication use on cognitive function in diabetes mellitus with obesity or overweight: An ancillary study to the Action for Health in Diabetes (Look AHEAD ) trial

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Effect of renin‐angiotensin system antihypertensive medication use on cognitive function in diabetes mellitus with obesity or overweight: An ancillary study to the Action for Health in Diabetes (Look AHEAD ) trial

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Keep reading

Keep reading