A genetic predisposition to high blood pressure (BP), coupled with higher body mass index (BMI), may be strongly associated with a greater burden of cerebral small vessel disease (CSVD), a study published in Neurology suggests.

Factors that contribute to CSVD are not well understood. Previous observational studies have implicated the cause of CSVD to cardiovascular risk factors, but due to the possibility of reverse causation and cofounding in these studies, it’s unclear whether this link is casual. To overcome these biases in the current study, researchers used Mendelian randomization (MR) to determine the cardiovascular risk factors involved in the etiology of CSVD.

In the study, a team of UK and German researchers analyzed data from large scale genome-wide association studies (GWAS) to identify genetic proxies for BP, blood lipids, BMI, type 2 diabetes, smoking initiation and cigarettes per day, as well as alcohol consumption in individuals of European ancestry. MR was performed to examine the association of these variables with white matter hyperintensities (WMH), fractional anisotropy (FA), and mean diffusivity (MD) CSVD neuroimaging features with genetic summary data from the UK Biobank (n=31,855).


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According to the researchers, the MR analysis demonstrated “consistent associations” across each method for greater genetically proxied systolic and diastolic BP with WMH, FA, as well as MD. Additionally, the analysis showed consistent associations for higher genetically proxied BMI with WMH. There was strong evidence for a causal association between BMI and WMH (95% CI, 0.085-0.160; P =1.29E-10).

Weaker evidence was found for significant associations between total cholesterol, low-density lipoprotein cholesterol, smoking initiation, pulse pressure, and type 2 diabetes liability, as well as ≥1 CSVD imaging feature. These associations were unable to be reproduced across the used validation methods, the researchers explained. In the multivariable MR analysis for BP traits, they found that the effect of the association was predominantly through genetically proxied diastolic BP across all traits of CSVD.

Given that the study focused on only 3 aspects of CSVD neuroimaging, the researchers noted that they lacked other aspects that may have been clinically relevant, including lacunar infarcts or cerebral microbleeds.

Based on their findings, it may be possible “that optimal management of cardiovascular risk factors, particularly blood pressure and BMI, could reduce the burden of stroke and dementia, the primary consequences of CSVD,” the researchers concluded.

Disclosure: Multiple authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.

Reference

Taylor-Bateman V, Gill D, Georgakis M, et al. Cardiovascular risk factors and MRI markers of cerebral small vessel disease: A Mendelian randomization studyNeurology. Published online November 29, 2021. doi:10.1212/WNL.0000000000013120