番茄社区

Blood pressure treatment, regardless of medication class, was tied to lower dementia and Alzheimer's disease risk in hypertensive people, a meta-analysis showed.

Among people with high blood pressure -- defined as systolic pressure of ≥140 mm Hg, or diastolic pressure ≥90 mm Hg -- those who used any of five major classes of antihypertensive drugs, singly or in combination, had 12% less risk for dementia and 16% less risk for Alzheimer's disease than those not using blood pressure medication, reported Lenore Launer, PhD, of the National Institute on Aging at the NIH in Baltimore, and colleagues.

There were no differences between one drug class versus all others on the risk of dementia, they reported in . And in people with normal blood pressure (systolic pressure <140 mm Hg and diastolic pressure <90 mm Hg), there was no association between antihypertensive medication use and incident dementia or Alzheimer's.

"Dementia is a major health concern and prevention and treatment strategies remain elusive. Lowering high blood pressure, a known strategy to prevent cardiovascular disease, has been considered as candidate intervention to reduce the risk for dementia," Launer said. "It has also been suggested by experimental and observational studies that specific classes of anti-hypertensive medications may have a direct effect on reducing dementia-related brain pathology."

Earlier research showed that angiotensin-converting enzyme and angiotensin receptor blockers () may have protective effects against dementia and Alzheimer's disease. The SPRINT MIND trial found that aggressively lowering blood pressure in hypertensive older adults reduced mild cognitive impairment by 19%, but did not significantly reduce dementia risk.

This meta-analysis "extends findings of the recent SPRINT MIND trial that showed lowering blood pressure levels reduced the risk for a combined dementia and mild cognitive impairment outcome," Launer told 番茄社区.

"We were able to study the effects of specific medications in a group of people who did not have elevated blood pressure levels, which has not been investigated in previous clinical trials," she noted. "Also, not possible in a trial, we had long-term follow-up data on the participants, which given the time it takes to develop clinical dementia, is essential to understanding prevention of the condition." The meta-analysis included people with multiple co-morbidities and "their characteristics better reflect the typical person seen in general medical practices," she added.

In their analysis, Launer and colleagues looked at six large, longitudinal community-based studies of 31,090 dementia-free adults (age >55) that had baseline data collected from 1987 to 2008. Mean participant ages ranged from 59 to 77 and median follow ups ranged from 7 to 22 years.

The researchers stratified participants into two groups: 15,553 people with high (systolic ≥140 mm Hg, or diastolic ≥90 mm Hg), and 15,537 people with normal blood pressure (systolic <140 mm Hg and diastolic <90 mm Hg). Both groups included people on antihypertensive drugs and people who were not.

The researchers performed a meta-analysis by drug class using individual participant data, looking at five major classes: ACE inhibitors, ARBs, beta blockers, calcium channel blockers, and diuretics. Other drug classes, such as vasodilators or aldosterone blockers, were not included. Participants were classified as users if they took medication with or without other antihypertensive drugs.

Throughout the studies, there were 3,728 incident cases of dementia, including 1,741 incident Alzheimer's disease diagnoses. In fully adjusted models of the high blood pressure group, people using any antihypertensive drug had a reduced risk for developing dementia (HR 0.88, 95% CI 0.79-0.98, P=0.019) and Alzheimer's disease (HR 0.84, 0.73-0.97, P=0.021), compared with people not using drugs.

In the high blood pressure group, there were no significant differences between one drug class versus others on dementia risk, but beta blockers and diuretics showed a potentially protective effect compared with no drug use. Also in this group, APOE ε4 carriers using any antihypertensive medication showed a decreased risk of incident dementia (HR 0.77, 95% CI 0.64-0.93).

In the normal blood pressure group, incident dementia and Alzheimer's risks were similar in people regardless of whether people were using antihypertensive drugs. No evidence suggested any single drug class differed in its association with the outcomes.

Although this meta-analysis could not account for duration of drug treatment, its findings are supported by a parallel meta-analysis not yet published, noted Craig Anderson, MD, PhD, and Ruth Peters, PhD, both of the University of New South Wales in Sydney, Australia, in an .

In the parallel study, which required a minimum drug class exposure of 12 months, "a similar neutral effect for specific drug classes was found for both dementia and cognitive decline, consistent in subgroup analyses in which individuals with only a few years of follow-up were excluded to minimize reverse causality," they wrote. "A similar signal for a protective effect of diuretic-based blood pressure lowering was also seen in some of the analyses."

This research had other limitations, the investigators noted. Some subgroups contained few cases, such as the ARBs users in the high blood pressure group. The analysis could not evaluate the effect of change in blood pressure and dementia risk. Misclassification may have occurred "in the grey area between mild cognitive impairment and mild dementia," the authors pointed out, as well as residual confounding.

Comment