Angiotensin receptor blockers may lower risk for progression to dementia
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Angiotensin receptor blockers may reduce progression from mild cognitive impairment to dementia in patients undergoing antihypertensive treatment, researchers wrote in Hypertension.
Compared with ACE inhibitors, beta-blockers, calcium channel blockers, diuretic and no treatment at all, antihypertensive treatment using angiotensin receptor blockers (ARBs) was associated with lower risk for progression to dementia during a median of 3 years follow-up among patients with mild cognitive impairment and hypertension, according to the retrospective cohort study.
“The angiotensin hypothesis has recently been proposed that the renin-angiotensin system plays a role in brain function. ... Medications that increase angiotensin-mediated activity at the angiotensin II and angiotensin IV receptors (eg, ARBs) may provide better brain protection compared with those decreasing activity at these receptors (eg, ACE inhibitors),” Zhenhong Deng, of the department of neurology at Sun Yat-sen Memorial Hospital, Sun Yat-sen University in Guangzhou, China, and colleagues wrote. “It remains unclear whether and to what extent ARBs are superior to ACE inhibitors in reducing progression to dementia in patients with mild cognitive impairment.”
Researchers investigated whether ARBs, compared with ACE inhibitors and other antihypertensive medications, may lower risk for progression from mild cognitive impairment to dementia in patients with hypertension.
Researchers used the Alzheimer’s Disease Neuroimaging Initiative, developed by the Laboratory of Neuro Imaging at University of Southern California, to identify 403 patients with hypertension and mild cognitive impairment at baseline (mean age, 74 years; 38% women). Data on antihypertensive medications received during a median follow-up of 3 years were self-reported.
During follow-up, 39.2% of participants progressed to dementia and the 3-year rate of progression-free survival was 67%.
In patients with hypertension and mild cognitive impairment, ARBs were associated with lower risk for progression to dementia compared with ACE inhibitors (adjusted HR = 0.45; 95% CI, 0.25-0.81; P = .023).
Compared with beta-blockers, calcium channel blockers and diuretics, ARB use was associated with lower risk for progression of mild cognitive impairment to dementia (aHR = 0.49; 95% CI, 0.27-0.89; P = .037).
Hypertension treatment with ARBs was also associated with lower risk for progression to dementia in patients with hypertension and mild cognitive impairment compared with no treatment (aHR = 0.31; 95% CI, 0.16-0.58; P = .001).
In adjusted analyses, treatment with ACE inhibitors did not affect progression of cognitive impairment compared with beta-blockers, calcium channel blockers and diuretics (P = .685) nor compared with no treatment (P = .179).
Moreover, antihypertensive treatment with beta-blockers, calcium channel blockers and diuretics did not prevent cognitive decline compared with no treatment in this cohort (P = .121).
“Overall, angiotensin II and IV may provide neuroprotection through angiotensin II and angiotensin IV receptors, although most evidence was based on experimental studies and the mechanisms were not fully understood,” the researchers wrote. “ARBs, which selectively block the angiotensin I receptors without inhibiting ACE and result in the relatively upregulated activities of angiotensin II and angiotensin IV receptors, and keep the pathway of amyloid beta degradation mediated by ACE intact, may offer superior protection than simultaneously lowering all the angiotensin receptors’ activities with ACE inhibitors.”
Perspective
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Hypertension is deleterious to cognitive functions, and it has been associated with mild cognitive impairment leading to dementia. Aggressive treatment of high BP, such as data from the SPRINT MIND trial, is associated with fewer people developing mild cognitive impairment or dementia. Therefore, it is critical to identify optimal antihypertensive medications for the control of progression of mild cognitive impairment and dementia. Most commonly used antihypertensives used in this situation act on inhibition of the renin-angiotensin system, such as ACE inhibitors and angiotensin receptor blockers. Previously, it has been shown that angiotensin receptor blockers are associated with lower incidence of dementia compared with ACE inhibitors. However, the extent of angiotensin receptor blockers’ superiority in reducing progression to dementia in patients with mild cognitive impairment was not explored.
The recent study by Deng et al addresses this issue in a retrospective cohort study from the Alzheimer’s Disease Neuroimaging Initiative database with 403 participants. They observed that angiotensin receptor blockers were associated with a lower risk of progression of mild cognitive impairment to dementia compared with ACE inhibitors in patients with hypertension and mild cognitive impairment. Longitudinal analysis of cognitive changes also showed a slower annual increase in CDR-SB and ADAs-Cog-13 scores and slower annual decline in Ray Auditory Verbal Learning Test and MMSE scores in the angiotensin receptor blocker group. This implicates their neuroprotective role by mechanisms involving attenuation of oxidative stress, neuroinflammation, etc. Further studies with other classes of antihypertensives need to be conducted to determine this unique superiority of angiotensin receptor blockers. Nonetheless, the study is likely to have a significant impact in the care of patients with mild cognitive impairment and hypertension.
Perspective
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I did not spend much time reading this manuscript because it's not of great value, in my opinion. The study conclusions are based on a relatively small comparison in a nonrandomized cohort study design. At best, it's a hypothesis-generating study and not one that should influence clinical decision-making. Also bear in mind that the vast majority of adults with hypertension require two or three antihypertensive agents to achieve control. There is a high probability that an ACE inhibitor or angiotensin receptor blocker will be used in combination with a diuretic or dihydropyridine calcium-channel blocker.
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