Angiotensin -II stimulating antihypertensives users had lower dementia rates compared to angiotensin-II inhibiting antihypertensive users, suggests the findings of a recent study. The interesting findings have recently been published in the Neurology.
Accumulating evidence suggests that some antihypertensive drug subclasses may reduce incident dementia beyond their effect on BP. The mechanisms underlying these differential effects are currently unclear. They may be related to the renin-angiotensin system . In the RAS, angiotensin-II lowers BP, mainly via activity at angiotensin type 1 (AT1) receptors. It also activates AT2 receptors and AT4 receptors, which have a number of associated effects (vasodilation, apoptosis). Hypothetically, the RAS also helps maintaining brain function. Angiotensin-II and -IV seem to protect against ischemia, especially through AT2, and preserve memory through AT4. Furthermore, angiotensin converting enzyme mediates amyloid-beta degradation in the brain.
Researchers undertook the preDIVA trial to assess whether angiotensin-II stimulating antihypertensives (thiazides, dihydropyridine calcium channel blockers, and angiotensin-1 receptor blockers) convey a lower risk of incident dementia compared to angiotensin-II inhibiting antihypertensives (angiotensin-converting enzyme inhibitors, beta blockers, and non-dihydropyridine calcium channel blockers), in accordance with the 'angiotensin hypothesis'.
For the study design, data were derived from the Prevention of Dementia by Intensive Vascular Care (preDIVA) trial . This RCT tested the efficacy of four-monthly visits to a practice nurse for cardiovascular risk management, compared to usual care by the general practitioner, on the prevention of dementia.
Antihypertensive use was based on prescription records cross-checked with participants during the baseline assessment. Individuals using ARB, DiCCB and/or thiazide(-like) diuretics were categorized as angiotensin-II-stimulating antihypertensive users. Individuals using non-DiCCB, BB, and ACEI were categorized as angiotensin-II-inhibiting antihypertensive users.
On analysis, the following facts emerged.
After a median of 6.7 years of follow-up, dementia status was available for 1870 (98%) and mortality for 1904 (>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 (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 non-significant 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.
"This study found that individuals using angiotensin - II - stimulating antihypertensives had approximately 40% lower dementia rates compared to those using angiotensin-II-inhibiting antihypertensives. This association was not due to increased mortality and was independent of cardiovascular risk factors and comorbidity, but it may be specific for individuals without CVD."concluded the team.
For full article follow the link: https://doi.org/10.1212/WNL.0000000000010996
Primary source: Neurology