Circulating N-Terminal Probrain Natriuretic Peptide Levels in Relation to Ischemic Stroke and Its Subtypes: A Mendelian Randomization Study.

Ming Li,Chuanjie Wu,Jiaqi Wu,Yi Xu,Xunming Ji,Ang Li

doi:10.3389/fgene.2022.795479

Abstract

Mendelian randomization was used to evaluate the potential causal association between N-terminal probrain natriuretic peptide (NT-proBNP) and ischemic stroke based on summary statistics data from large-scale genome-wide association studies. Three single-nucleotide polymorphisms (SNPs) rs198389, rs13107325, and rs11105306 associated with NT-proBNP levels found in large general populations and in patients with acute heart disease were used as instrumental variables. The results of genetic association analysis of each single SNP show that there is no significant association between NT-proBNP levels and ischemic stroke or its subtypes, whereas rs198389 alone has a suggestive association with large-artery atherosclerosis stroke. The MR analysis of three SNPs shows that NT-proBNP levels may reduce the risk of small-vessel occlusion stroke suggestively. This genetic analysis provides insights into the pathophysiology and treatment of ischemic stroke.

Highlights

Stroke is the second major cause of global death with a mortality rate of approximately 5.5 million/ year and poses a huge financial burden to family members and public health (Donkor, 2018)
The genetic association analysis evaluating the association between single NT-proBNP-associated Singlenucleotide polymorphism (SNP) and ischemic stroke and its three subtypes shows that neither of those SNPs have significant association with ischemic stroke and subtypes, whereas only rs198389 has a suggestive association with Large-artery atherosclerosis stroke (LAS) (Table 2)
The genetic association analysis shows that rs198389 has a suggestive association with LAS, and the Mendelian randomization (MR) analysis shows that NT-proBNP levels suggestively reduce the risk of small-vessel occlusion stroke (SVS)

Summary

Introduction

Stroke is the second major cause of global death with a mortality rate of approximately 5.5 million/ year and poses a huge financial burden to family members and public health (Donkor, 2018). The study of INTERSTROKE presents 10 potentially modifiable risk factors that are associated with around 90% of acute strokes (O’Donnell et al, 2016), and according to the data from the INTERHEART study, those factors account for the great majority of the risk of myocardial infarction (Yusuf et al, 2004). N-terminal probrain natriuretic peptide (NT-proBNP) is an N-terminal fragment of brain natriuretic peptide (BNP), released from the heart muscle in response to the blood pressure and volume overload (Daniels and Maisel, 2007). This factor is widely used in the clinic as a prognostic biomarker to predict mortality in patients with coronary artery disease (CAD), atrial fibrillation, and heart failure (Johansson et al, 2016). Due to the connections between cardiac dysfunction and stroke, NTproBNP is supposed to be a potential predictor for the risk of ischemic stroke (Zhao et al, 2020a)

Methods

Results

Conclusion