Causal relationship between hypertension and ischemic stroke: A two-sample Mendelian randomization study

Abstract: BACKGROUND: Ischemic stroke (IS) is a well-recognized risk factor for human health and has become a major cause of the global burden of disease over the past decades. Determining the correlation between hypertension and IS is important for the prevention of IS. In epidemiologic studies, researches have reported a strong association between hypertension and IS. However, there is a great deal of heterogeneity between these findings, and the strength of the two associations shows very different results in international studies. Here, we used genetic data to methodically assess the association between hypertension and the risk of IS using a Mendelian randomization (MR) framework. This study may provide a more comprehensive theoretical basis for the link between hypertension and IS. METHODS: We studied three hypertension traits including essential hypertension, gestational hypertension, and preexisting hypertension, in a two-sample MR method. Genetic susceptibility to each type of hypertension was explored for the association with the risk of small-vessel IS in data from the IEU-POENGWAS. RESULTS: We observed a strong association between essential hypertension with small-vessel IS. Our evidence from data-driven analyses further suggests that genetic susceptibility to gestational hypertension and preexisting hypertension are associated with the development of small-vessel IS. However, in multivariate analyses, these associations would be explained by congenital hypertension. CONCLUSIONS: Through our study, we further validated that hypertension is an individual risk factor for IS, with the risk of small-vessel IS increasing approximately 6-fold for every one standard deviation increase in essential hypertension.