American and Chinese researchers conducted large-scale clinical trials and found that intensive detection and treatment of uncontrolled hypertension significantly reduces the risk of dementia and cognitive impairment. A report on the work was published in the journal Nature Medicine.
Hypertension is the leading modifiable risk factor for cardiovascular disease and premature death worldwide. Its association with dementia risk is less well established: observational cohort studies have shown that it is elevated in people with uncontrolled hypertension, and randomized controlled trials of hypertension therapy have not yet provided clear and sufficient evidence of its preventive effect.
Jiang He from the University of Texas Southwestern Medical Center and colleagues from China and the United States conducted open-label, cluster-randomized, phase III trials with blinded assessment of endpoints CRHCP-3. They involved 33,995 people aged 40 years and older with uncontrolled hypertension. The main group included 17,407 residents (mean age 62.8 years; 60.8 percent women) of 163 Chinese villages, and the control group included 16,588 residents (mean age 63.3 years; 61.6 percent women) of another 163 Chinese villages, who were randomly assigned to groups.
In the active intervention, trained local paramedics (not doctors) taught patients how to measure their blood pressure at home, the principles of lifestyle changes and adherence to treatment, and titrated antihypertensive therapy according to the given recommendations to achieve blood pressure less than 130/80 mmHg. The remaining patients received standard care - their blood pressure was measured and treatment prescribed at medical appointments. A total of 14,541 participants in the main group and 13,594 participants in the control group reached 48 months of the trial, when the development of cognitive impairment and dementia was assessed (1,269 and 1,392, respectively, died, the rest dropped out for other reasons).
By the end of the second year of the trial, patients with active intervention were taking an average of three antihypertensive drugs versus 1.2 with standard care. During the trial, systolic and diastolic pressures in the main group decreased from an average of 157.0 to 127.6 and from 87.9 to 72.6 mmHg, and in the control group from 155.4 to 147.7 and from 87.2 to 81.0 mmHg; the difference in reduction between the groups was -22.0 and -9.3 mmHg (p < 0.0001). Pressures below 130/80 mmHg were reached by 67.7 versus 15.0 percent of the participants. By month 48, dementia of any etiology was confirmed in 4.59 percent of patients with active intervention and 5.40 percent with usual care. The risk of its development in the main group was 15 percent lower than in the control group (p = 0.0035). The risk of cognitive impairment without dementia was lower by 16 percent (p < 0.0001), the combined indicator of dementia or cognitive impairment was also lower by 16 percent (p < 0.0001), and the combined indicator of dementia or death from all causes was lower by 14 percent (p < 0.0001). At the same time, the frequency of serious side effects was lower by six percent (p = 0.0006). Analysis of the obtained results with the addition of data from four more previously conducted randomized trials also revealed a 15 percent reduction in the risk of dementia (p < 0.0001). Results of large-scale cluster-randomized clinical trials have confirmed that intensive blood pressure reduction is an effective method for preventing dementia of any etiology in people with arterial hypertension. Previously, a group of researchers from European countries analyzed data from almost four thousand participants in the UK Biobank study and found a possible mechanistic link between arterial hypertension and dementia — it changed the structure of the putamen and white matter in the corona radiata, anterior thalamus, and anterior margin of the internal capsule.