Mendelian Randomization Study of Whole Blood Viscosity and Cardiovascular Diseases

Aims Association between whole blood viscosity (WBV) and an increased risk of cardiovascular disease (CVD) has been reported. However, the causal relationship between WBV and CVD remains not thoroughly investigated. The aim of this study was to investigate the causal relation between WBV and CVD. Methods Mendelian randomization was employed to investigate the casual relationship between WBV and CVD. Calculated WBV, derived polygenic risk score (PRS) for WBV, and medical records from 378,210 individuals participating in the UK biobank study were analyzed. Results The means of calculated WBVs were 16.9 (standard deviation: 0.8) and 55.1 (standard deviation: 17.2) for high shear rate (HSR) and low shear rate (LSR), respectively. 37,859 (10.0%) major cardiovascular event (MACE) consisted of 23,894 (6.3%) cases of myocardial infarction (MI), 9,245 (2.4%) cases of ischemic stroke, 10,377 (2.7%) cases of revascularization, and 5,703 (1.5%) cases of Coronary heart disease-related death. WBVs of individuals with PRS above median were significantly higher than the group that were below median for both low shear rate (P<0.001) and high shear rate (P<0.001). The odd ratios (95% confidence intervals) for MACE in the higher WBV group were 1.22 (1.19 - 1.25) and 1.14 (1.12 - 1.16), for HSR and LSR, respectively. The higher PRS group was insignificant with all outcomes, for both HSR and LSR. Conclusions The Mendelian randomization analysis conducted in this study does not support a causal relationship between calculated WBV and CVD. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This project was funded by the National Institute for Health Research (NIHR) Artificial Intelligence and Multimorbidity: Clustering in Individuals, Space and Clinical Context (AIM-CISC) grant NIHR202639. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: No I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Our data is available as a part of the UK Biobank project. Details of procedures for accessing the UK Biobank data can be found here: