Lowering systolic blood pressure via the protein targets of antihypertensive drugs did not significantly affect the risk of developing Alzheimer's disease (OR 1.14).
Observational
Mendelian randomization
Does lowering systolic blood pressure via antihypertensive drug targets reduce the risk of Alzheimer's disease?
Mendelian randomization analysis found no significant evidence that lowering systolic blood pressure via antihypertensive drug targets reduces the risk of Alzheimer's disease.
Effect estimate: OR 1.14 (95% CI 0.83 to 1.56)
p-value: p=0.41
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.
Walker et al. (Thu,) conducted a observational in Alzheimer's disease. Lowering systolic blood pressure via protein targets of antihypertensive drugs was evaluated on Alzheimer's disease risk (combining all protein targets) (OR 1.14, 95% CI 0.83 to 1.56, p=0.41). Lowering systolic blood pressure via the protein targets of antihypertensive drugs did not significantly affect the risk of developing Alzheimer's disease (OR 1.14).