Why is this important?
Hypertension is one of the main modifiable risk factors for Alzheimer’s disease and related dementia (ARDD). Several observational studies have suggested that antihypertensive treatments that activate angiotensin 2 and 4 receptors are associated with a lower incidence of mild cognitive impairment and dementia, compared to treatments that do not stimulate these receptors. But their methodological quality did not allow these results to be affirmed with certainty. An American study therefore wished to re-examine this association between recent initiation of an anti-hypertensive stimulating these angiotensin receptors and the incidence of ADD, compared to anti-hypertensives inhibiting them, within a population of Medicare health insurance beneficiaries.
Methodology
This retrospective cohort study involved hypertensive subjects aged 65 or older with Medicare membership. They were included if they had initiated antihypertensive treatment that stimulated angiotensin 2 and 4 receptors (angiotensin type 1 receptor antagonists, dihydropyridine calcium channel blockers, or thiazide diuretics) and/or inhibited them (angiotensin converting enzyme inhibitors, beta-blockers, non-dihydropyridine calcium channel blocker), between January 2007 and December 2014. The primary endpoint was time to onset of MADA.
Principle results
In total, the analyzes focused on 57,773 participants: nearly 63% women, average age of 74, the vast majority of Caucasian origin (87%).
Over a median follow-up of approximately 7 years, the unadjusted incidence density of MADA was 2.2 per 100 person-years [2,1-2,4] in the group that received antihypertensives that stimulate angiotensin 2 and 4 receptors, compared with 3.1 person-years [3,0-3,2] for those who received antihypertensive drugs that inhibit these receptors, with an intermediate result (2.7 person-years [2,6-2,9]) for those who received mixed treatment.
After adjusting for socio-demographic and clinical factors, Cox regression revealed an association between treatments stimulating these receptors and a 16% reduction in the risk of ADD compared to treatments inhibiting these same receptors (HR 0.84 [2,6-2,9]). Mixed treatments were also associated with a reduction in these pathologies (-10%), but to a lesser extent (HR 0.90 [0,84-0,96]).
Treatments stimulating angiotensin receptors 2 and 4 could also be associated with a lower risk of vascular dementia (HR 0.82 [0,69-0,96]), as well as the mixed treatments (HR 0.83 [0,70-0,98]).