Repurposing antihypertensive drugs for the prevention of Alzheimer’s disease: a Mendelian randomization study
Year: 2019
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Evidence concerning the potential repurposing of antihypertensives for Alzheimer's disease prevention is inconclusive. We used Mendelian randomization, which can be more robust to confounding by indication and patient characteristics, to investigate the effects of lowering systolic blood pressure, via the protein targets of different antihypertensive drug classes, on Alzheimer's disease. METHODS: We used summary statistics from genome-wide association studies of systolic blood pressure and Alzheimer's disease in a two-sample Mendelian randomization analysis. We identified single-nucleotide polymorphisms (SNPs) that mimic the action of antihypertensive protein targets and estimated the effect of lowering systolic blood pressure on Alzheimer's disease in three ways: (i) combining the protein targets of antihypertensive drug classes, (ii) combining all protein targets and (iii) without consideration of the protein targets. RESULTS: There was limited evidence that lowering systolic blood pressure, via the protein targets of antihypertensive drug classes, affected Alzheimer's disease risk. For example, the protein targets of calcium channel blockers had an odds ratio (OR) per 10 mmHg lower systolic blood pressure of 1.53 [95% confidence interval (CI): 0.94 to 2.49; p = 0.09; SNPs = 17]. We also found limited evidence for an effect when combining all protein targets (OR per 10 mmHg lower systolic blood pressure: 1.14; 95% CI: 0.83 to 1.56; p = 0.41; SNPs = 59) and without consideration of the protein targets (OR per 10 mmHg lower systolic blood pressure: 1.04; 95% CI: 0.95 to 1.13; p = 0.45; SNPs = 153). CONCLUSIONS: Mendelian randomization suggests that lowering systolic blood pressure via the protein targets of antihypertensive drugs is unlikely to affect the risk of developing Alzheimer's disease. Consequently, if specific antihypertensive drug classes do affect the risk of Alzheimer's disease, they may not do so via systolic blood pressure.
DOI: 10.1093/ije/dyz155
Institutions: University of Bristol, MRC Integrative Epidemiology Unit
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,514
OpenAlex ID: W2951397190