Cardiovascular risk factors modulate the effect of brain imaging-derived phenotypes on ischemic stroke risk

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 Cardiovascular risk factors modulate the effect of brain imaging-derived phenotypes on ischemic stroke risk

Short title: CRF Affect IS Risk

Yuan-yuan Liang1, Meng-jie Li1,5, Dong-rui Ma1, Meng-nan Guo1, Xiao-yan Hao1,5,

Shuang-jie Li1, Chun-yan Zuo1, Chen-wei Hao1, Zhi-yun Wang1, Yan-mei Feng1,

Chenyuan Mao1, Chan zhang1, Bo Song1,2,3,4, Yuming Xu1,2,3,4, Changhe Shi, MD,

PhD1,2,3,4

1 Department of Neurology, The First Affiliated Hospital of Zhengzhou University,

Zhengzhou University, Zhengzhou, 450000, Henan, China.

2 NHC Key Laboratory of Prevention and treatment of Cerebrovascular Diseases, The

First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou,

450000, Henan, China.

3 Henan Key Laboratory of Cerebrovascular Diseases, The First Affiliated Hospital of

Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.

4 Institute of Neuroscience, Zhengzhou University, Zhengzhou, 450000, Henan, China.

5 Academy of Medical Sciences of Zhengzhou University, Zhengzhou, 450000, Henan,

China.

Abstract

Studies have shown that cardiovascular risk factors are closely related to the occurrence

of stroke, especially ischemic stroke, as they can lead to changes in brain structure and

function. However, the role of cardiovascular risk factors - induced changes in brain

structure and function in the development of ischemic stroke has not been studied. The

aim of this study is thus to explore the causal association among cardiovascular risk

factors, brain phenotypes and ischemic stroke by assessing mendelian randomization.

We used univariate mendelian randomization to sequentially investigate the causal

effects of the 12 most common cardiovascular risk factors on brain structure and 3,935

brain imaging-derived phenotypes in the development of ischemic stroke. We also

examined the mediating effect of brain structure on blood pressure - induced ischemic

stroke using a multivariable mendelian randomization test. We tested the reliability of

our results using the Steiger test, heterogeneity test, horizontal pleiotropy test and leave-

one-out method.

We found that 8 of the 12 examined cardiovascular risk factors were associated with

538 brain imaging-derived phenotypes, and 9 of the 12 cardiovascular risk factors were

associated with IS. The main cardiovascular risk factors associated with brain imaging-

derived phenotypes and ischemic stroke was blood pressure (systolic and diastolic),

which can affect the occurrence of ischemic stroke through 6 types of brain imaging-

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