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. The study was published in the journal Nature Medicine.
Arterial 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, while 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 the CRHCP-3, an open-label, cluster-randomized, phase III trial with blinded endpoint assessment. They enrolled 33,995 people aged 40 years and older with uncontrolled hypertension. The study group included 17,407 residents (mean age 62.8 years; 60.8 percent women) from 163 Chinese villages, while the control group included 16,588 residents (mean age 63.3 years; 61.6 percent women) from another 163 Chinese villages, who were randomly assigned to groups.
In the active intervention, specially trained local paramedics (not physicians) taught patients how to measure their blood pressure at home, principles of lifestyle changes, and treatment adherence, and titrated antihypertensive therapy according to recommendations until blood pressure was less than 130/80 mmHg. The remaining patients received standard care—blood pressure measurements and treatment prescriptions at medical appointments. A total of 14,541 participants in the intervention group and 13,594 in the control group completed the 48-month trial, when the development of cognitive impairment and dementia was assessed (1,269 and 1,392, respectively, died; the rest withdrew for other reasons).
By the end of the second year of the trial, patients with the active intervention were taking an average of three antihypertensive medications versus 1.2 with standard care. Over the course of the trial, systolic and diastolic blood pressure in the intervention group decreased from an average of 157.0 to 127.6 and from 87.9 to 72.6 mmHg, respectively, 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). Blood pressure below 130/80 mmHg was recorded in 67.7 percent of participants versus 15.0 percent. By month 48, dementia of any etiology was confirmed in 4.59 percent of patients in the active intervention group and 5.40 percent in the usual care group. 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). Moreover, the incidence of serious adverse events 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 hypertension. Previously, a group of researchers from European countries analyzed data from nearly 4,000 participants in the UK Biobank study and found a possible mechanistic link between hypertension and dementia—changes in the structure of the putamen and white matter in the corona radiata, anterior thalamus, and anterior margin of the internal capsule.
