Antihypertensives that exclusively stimulate versus inhibit type 2 and 4 angiotensin II receptors were associated with lower rates of amnestic MCI or probable dementia (HR 0.76; 95% CI 0.66-0.87).
Cohort (n=8,685)
Does the use of exclusively antihypertensive medication regimens that stimulate type 2 and 4 angiotensin II receptors reduce the risk of amnestic mild cognitive impairment or probable dementia in older adults with hypertension compared to regimens that inhibit these receptors?
Antihypertensive regimens that stimulate type 2 and 4 angiotensin II receptors are associated with a significantly lower risk of incident cognitive impairment compared to regimens that inhibit these receptors.
Hazard Ratio: 0.76 (95% CI 0.66–0.87)
Absolute Event Rate: 45% vs 59%
Importance: Use of antihypertensive medications that stimulate type 2 and 4 angiotensin II receptors, compared with those that do not stimulate these receptors, has been associated with a lower risk of dementia. However, this association with cognitive outcomes in hypertension trials, with blood pressure levels in the range of current guidelines, has not been evaluated. Objective: To examine the association between use of exclusively antihypertensive medication regimens that stimulate vs inhibit type 2 and 4 angiotensin II receptors on mild cognitive impairment (MCI) or dementia. Design, Setting, and Participants: This cohort study is a secondary analysis (April 2011 to July 2018) of participants in the randomized Systolic Blood Pressure Intervention Trial (SPRINT), which recruited individuals 50 years or older with hypertension and increased cardiovascular risk but without a history of diabetes, stroke, or dementia. Data analysis was conducted from March 16 to July 6, 2021. Exposures: Prevalent use of angiotensin II receptor type 2 and 4-stimulating or -inhibiting antihypertensive medication regimens at the 6-month study visit. Main Outcomes and Measures: The primary outcome was a composite of adjudicated amnestic MCI or probable dementia. Results: Of the 8685 SPRINT participants who were prevalent users of antihypertensive medication regimens at the 6-month study visit (mean SD age, 67.7 11.2 years; 5586 64.3% male; and 935 10.8% Hispanic, 2605 30.0% non-Hispanic Black, 4983 57.4% non-Hispanic White, and 162 1.9% who responded as other race or ethnicity), 2644 (30.4%) were users of exclusively stimulating, 1536 (17.7%) inhibiting, and 4505 (51.9%) mixed antihypertensive medication regimens. During a median of 4.8 years of follow-up (95% CI, 4.7-4.8 years), there were 45 vs 59 cases per 1000 person-years of amnestic MCI or probable dementia among prevalent users of regimens that contained exclusively stimulating vs inhibiting antihypertensive medications (hazard ratio HR, 0.76; 95% CI, 0.66-0.87). When comparing stimulating-only vs inhibiting-only users, amnestic MCI occurred at rates of 40 vs 54 cases per 1000 person-years (HR, 0.74; 95% CI, 0.64-0.87) and probable dementia at rates of 8 vs 10 cases per 1000 person-years (HR, 0.80; 95% CI, 0.57-1.14). Negative control outcome analyses suggested the presence of residual confounding. Conclusions and Relevance: In this secondary analysis of SPRINT, prevalent users of regimens that contain exclusively antihypertensive medications that stimulate vs inhibit type 2 and 4 angiotensin II receptors had lower rates of incident cognitive impairment. Residual confounding cannot be ruled out. If these results are replicated in randomized clinical trials, certain antihypertensive medications could be prioritized to prevent cognitive decline.
Marcum et al. (Fri,) conducted a cohort in hypertension and increased cardiovascular risk (n=8,685). Antihypertensive medications that exclusively stimulate type 2 and 4 angiotensin II receptors vs. Antihypertensive medications that exclusively inhibit type 2 and 4 angiotensin II receptors was evaluated on composite of adjudicated amnestic MCI or probable dementia (HR 0.76, 95% CI 0.66-0.87). Antihypertensives that exclusively stimulate versus inhibit type 2 and 4 angiotensin II receptors were associated with lower rates of amnestic MCI or probable dementia (HR 0.76; 95% CI 0.66-0.87).