Abstract
BackgroundObservational studies have suggested a close but controversial relationship between blood pressure (BP) and amyotrophic lateral sclerosis (ALS). It remains unclear whether this association is causal. The authors employed a bidirectional two-sample Mendelian randomization (MR) approach to evaluate the causal relationship between BP and ALS. Genetic proxies for systolic blood pressure (SBP), diastolic blood pressure (DBP), antihypertensive drugs (AHDs), ALS, and their corresponding genome-wide association study (GWAS) summary datasets were obtained from the most recent studies with the largest sample sizes. The inverse variance weighted (IVW) method was adopted as the main approach to examine the effect of BP on ALS and four other MR methods were used for sensitivity analyses. To exclude the interference between SBP and DBP, a multivariable MR approach was used.ResultsWe found that genetically determined increased DBP was a protective factor for ALS (OR = 0.978, 95% CI 0.960–0.996, P = 0.017) and that increased SBP was an independent risk factor for ALS (OR = 1.014, 95% CI 1.003–1.025, P = 0.015), which is supported by sensitivity analyses. The use of calcium channel blocker (CCB) showed a causal relationship with ALS (OR = 0.985, 95% CI 0.971–1.000, P = 0.049). No evidence was revealed that ALS caused changes in BP.ConclusionsThis study provides genetic support for a causal effect of BP and ALS that increased DBP has a protective effect on ALS, and increased SBP is a risk factor for ALS, which may be related to sympathetic excitability. Blood pressure management is essential in ALS, and CCB may be a promising candidate.
Highlights
Observational studies have suggested a close but controversial relationship between blood pressure (BP) and amyotrophic lateral sclerosis (ALS)
In our study, proxies related to systolic blood pressure (SBP), diastolic blood pressure (DBP), calcium channel blocker (CCB), and ALS were utilized to investigate the relationship between blood pressure and ALS using five Mendelian randomization (MR) methods
We found that increased DBP had a potential protective effect on ALS (IVW-odds ratio (OR) = 0.991, 95% confidence interval (CI) 0.982–1.001, P = 0.074) (Table 1, Fig. 2)
Summary
Observational studies have suggested a close but controversial relationship between blood pressure (BP) and amyotrophic lateral sclerosis (ALS). It remains unclear whether this association is causal. Some studies suggested that hypertension was associated with a delay in the age of ALS onset and identified hypertension as a protective factor for ALS risk [10, 11]. Due to these inconsistent observational studies being susceptible to the influence of confounders, selection biases, and reverse causality, the true association between blood pressure and ALS remains largely ambiguous. Interventions targeting hypertension could be a promising option for ALS prevention
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