Genetic variants that predict higher systolic blood pressure (SBP) are associated with a higher probability of taking antihypertensive medication and with decreased risk of Alzheimer disease (AD), according to a study published this week in PLOS Medicine. The study, conducted by Robert Scott of the MRC Epidemiology Unit, University of Cambridge, UK, Soren Ostergaard, (Aarhus University Hospital, Risskov, Denmark) and Shubhabrata Mukherjee (University of Washington, Seattle, USA) and colleagues suggests that either higher blood pressure, or anti-hypertensive therapy, may play a protective role against the development of AD.
Epidemiological studies have identified several potential risk factors for AD, but the causative nature of these associations has not been established. Without knowledge of cause, it is unclear whether health interventions upon these risk factors can alter the risk of AD. Scott and colleagues used a "Mendelian randomization" technique to test whether certain modifiable risk factors, including blood pressure, smoking, and cholesterol levels, might play a causative role in the development of AD. In Mendelian randomization, causality is inferred from associations between genetic variants linked to a risk factor, and the outcome of interest. The use of gene variants, which are inherited randomly and fixed throughout life, mitigates the risk that an identified association is mediated by a third, confounding factor related to genetic history or lifestyle.
These findings suggest that higher blood pressure (odds ratio (OR) per-SD (15.4 mmHg) of SBP [95% CI]: 0.75[0.62-0.91]; p=3.4x10-3) is associated with lower AD risk, which may be related to the effect of greater exposure to anti-hypertensive medication. Like all Mendelian randomization studies, the reliability of these results depends on the ability of the genetic variants used in the analyses to predict blood pressure, and the assumption that these genetic variants do not affect other risk factors. Moreover, as the study included an exclusively European population, the causal association may not be valid for non-European ethnic groups. Given that hypertension is a risk factor for cardiovascular disease, the researchers do not advocate raising blood pressure as a measure to prevent AD. "However," the authors state, "since there is a strong association between higher SBP gene scores and exposure to antihypertensive treatments, there is a need to evaluate the possible protective role of some of these substances against AD, independent of their effects on blood pressure."