Blood Pressure Lowering Reduces Dementia Risk

Results of a trial using an intensive, 4-year program aimed at blood pressure lowering showed that intervention reduced not only blood pressure (BP), but also significantly reduced the risk of total dementia over that period.

All-cause dementia, the primary outcome, was significantly reduced by 15% in the intervention group compared with usual care, and cognitive impairment no dementia (CIND), a secondary outcome, was also significantly reduced by 16%.

"Blood pressure reduction is effective in reducing the risk of dementia in patients with hypertension," concluded Jiang He, MD, PhD, professor of epidemiology and medicine and director of Tulane University's Translational Science Institute in New Orleans, Louisiana. "This proven, effective intervention should be widely scaled up to reduce the global burden of dementia."

He presented these results from the China Rural Hypertension Control Project (CRHCP) November 11 at the American Heart Association (AHA) Scientific Sessions 2023 in Philadelphia.

Target Organ Damage

Keith Ferdinand, MD, also from Tulane University, commented on the findings during a press conference at the meeting. This result "opens our opportunity to recognize that the target organ damage of hypertension also now includes dementia," he said.

The researchers were able to "rigorously lower blood pressure from 157 to 127.6 in the intervention, 155 to 147 in the controls — 22 mg Hg — and if you look at the P values for all the various outcomes, they were very robust," Ferdinand said.

Another interesting feature about the strategy used in this trial is that "this was true team-based care," he pointed out. The trained interventionists in the study, called village doctors, collaborated with primary care physicians and initiated medications. "They stayed on a simple treatment protocol, and they were able to assist patients to ensure they had free medications, health coaching for lifestyle, home blood pressure measurement, and ensuring adherence."

So, Ferdinand added, "one of the questions is whether this is a model we can use in other places around the globe, in places with low resources, and in the United States in disadvantaged populations."

Public Health Priority

It's estimated that the global number of those living with dementia will increase from 57.4 million in 2019 to 152.8 million by 2050, He said. "In the absence of curative treatment, the primary prevention of dementia through risk factor reduction, such as blood pressure lowering, becomes a public health priority."

Previous randomized trials have lacked sample size and duration but have reported a nonsignificant reduction in dementia associated with antihypertensive treatment in patients with hypertension or a history of stroke, He noted.

This new trial aimed to test the effectiveness of intensive BP intervention to reduce the risk of all-cause dementia and cognitive impairment over a 48-month intervention period vs usual care.

It was an open-label, blinded-endpoint, cluster-randomized trial, and included 33,995 individual patients from 325 villages in China. aged 40 years and older, who had untreated hypertension. The villages were randomly assigned to an intervention group or usual care, stratified by province, county, and township.

Patients were eligible if they had mean untreated systolic BP of > 140 mm Hg and/or diastolic BP > 90 mm Hg or mean treated systolic BP of > 130 and/or diastolic > 80 mm Hg. Patients with a history of cardiovascular disease, chronic kidney disease, or diabetes and a mean systolic BP of > 130 mm Hg and/or diastolic BP of > 80 mm Hg from six measures on two different days were also eligible.

All were enrolled in the China New Rural Cooperative Medical Scheme, which covers 99% of rural residents for healthcare services, He noted.

The intervention was a simple stepped-care protocol for hypertension treatment, aimed at achieving a target systolic BP of < 130 mm Hg and diastolic of < 80 mm Hg.

Village doctors started and titrated antihypertensive treatment based on a protocol and were able to deliver discounted and free medications to patients. They also did health coaching on lifestyle modification and adherence to medication, and instructed patients on home BP monitoring.

Patients were provided training, supervision, and consultation by primary care physicians and hypertension specialists.

At the month 48 follow-up visit, the participants were assessed by neurologists who were blinded to randomization assignments. Neurologists did a variety of tests and assessments including collecting data on the patient's medical and psychiatric history and risk factors for dementia, as well as neurologic assessment using the Mini-Mental State Examination, the Functional Activities Questionnaire, and the Quick Dementia Rating System.

The primary outcome was all-cause dementia, defined according to recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease.

Secondary outcomes included CIND, a composite outcome of dementia or CIND, and a composite of dementia or deaths.

The final diagnosis of all-cause dementia or CIND was made by an expert adjudication panel blinded to the intervention assignment.

At 48 months, 91.3% of patients completed the follow-up for clinical outcomes. Participants were an average of 63 years of age, 61% were female, and 23% had less than a primary school education, He noted.

The net group differences in systolic and diastolic BP reduction were 22 and 9.3 mm Hg, respectively (P < .0001).

Significant differences were also seen between the groups in the primary outcome of all-cause dementia, as well as secondary outcomes of CIND, dementia or cognitive impairment, or dementia or deaths.

Serious adverse events were more common in the usual care group, and there was no difference between groups in the occurrence of falls or syncope.

CRHCP: Primary, Secondary, and Safety Outcomes
Endpoint	Intensive BP Lowering		Usual Care		Relative Risk (95% CI)	P value
Endpoint	N	Rate Per Year (%)	N	Rate Per Year (%)	Relative Risk (95% CI)	P value
Primary Outcome	668	1.12	734	1.31	0.85 (0.76 - 0.95)	.0035
CIND	2506	4.19	2808	5.02	0.84 (0.80 - 0.87)	< .0001
Dementia or Cognitive Impairment	3174	5.31	3542	6.34	0.84 (0.81 - 0.87)	< .0001
Dementia or Deaths	1908	3.04	2092	3.54	0.86 (0.81 - 0.92)	< .0001
Serious Adverse Event	6201	9.16	6329	9.86	0.94 (0.91 - 0.98)	.0006
Falls Requiring Medical Care	166	0.25	157	0.24	1.01 (0.80 - 1.28)	.92
Syncope Requiring Medical Care	127	0.19	102	0.16	1.20 (0.87 - 1.66)	.27

The effect was consistent across subgroups, He said, including age, sex, education, cigarette smoking, body mass index, systolic BP, and fasting plasma glucose at baseline.

First Definitive Evidence

Invited discussant for the trial, Daniel W. Jones, MD, University of Mississippi Medical Center, Jackson, and past president of the AHA, pointed out that previous results from CRHCP on cardiovascular outcomes, reported earlier this year in The Lancet, showed that, similar to results of the large SPRINT trial, lowering systolic BP to a goal of less than 130 mm Hg reduced a composite endpoint of MI, stroke, heart failure requiring hospitalization, and cardiovascular disease death over the 36-month follow-up.

The SPRINT findings also suggested a possible reduction in dementia, Jones said.

Now, in these new CRHCP results, "there was a clear benefit for intensive BP control in reducing risk for dementia and cognitive dysfunction," he said. "This is, importantly, the first definitive evidence of dementia risk reduction demonstrated in a randomized controlled clinical trial. This outcome supports observational data that shows a strong relationship between BP and dementia."

Since it is the first of its kind though, replication of the results will be important, he noted.

The study also showed that the intervention, using minimally trained village doctors, sustained BP control for 48 months. "This model could be used in any setting with modifications, including in the United States," Jones said.

The study was supported by the Ministry of Science and Technology of China; US investigators did not receive financial support from this study. The researchers and Jones have disclosed no relevant financial relationships.

American Heart Association (AHA) Scientific Sessions 2023. Presented November 11, 2023.

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