No causal association between plasma cystatin C and cardiovascular diseases: Mendelian randomization analyses in UK biobank

Jingjing Tu; Ying Xu; Xu Guo; Jiayu Zhang; Duo Xu; Liyuan Han; Yue Wang; Boya Zhang; Hongpeng Sun

doi:10.3389/fmed.2023.1191675

No causal association between plasma cystatin C and cardiovascular diseases: Mendelian randomization analyses in UK biobank

Front Med (Lausanne). 2023 Aug 17:10:1191675. doi: 10.3389/fmed.2023.1191675. eCollection 2023.

Authors

Jingjing Tu¹, Ying Xu², Xu Guo¹, Jiayu Zhang², Duo Xu³, Liyuan Han³, Yue Wang³, Boya Zhang², Hongpeng Sun³

Affiliations

¹ Department of Rehabilitation Medicine, Ningbo No.2 Hospital, Ningbo, China.
² School of Public Health, Medical College of Soochow University, Suzhou, China.
³ Department of Global Health, Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China.

Abstract

Background: We aimed to determine whether the plasma cystatin C is a causal risk factor for cardiovascular events, stroke, myocardial infarction (MI), and cardiovascular disease (CVD) mortality by conducting Mendelian randomization (MR) designs.

Methods: Our study included 277,057 individuals free of CVDs or cancer at baseline in the UK Biobank. The genetic scores of plasma cystatin C comprising 67 single-nucleotide polymorphisms were calculated on the basis of data from a large genome-wide association study. By stratifying the genetic score, we conducted cox regression to assess the relationship between plasma cystatin C and CVDs. In this study, linear MR analysis was used to estimate the causal association between plasma cystatin C and CVDs.

Results: Observational analyses showed that plasma cystatin C concentrations were associated with the risk of CVDs [hazard ratios (HR) per standard deviation (SD) 1.09, 95% confidence interval (CI); 1.07-1.10] and CVD mortality (1.14, 1.11-1.17). Among CVDs, plasma cystatin C were associated with stroke (1.10, 1.08-1.11) and MI (1.08, 1.07-1.10). Linear MR analysis did not provide evidence of a causal association between plasma cystatin C and the risk of CVDs [odds ratio (OR) per SD 0.96, 95% CI;0.90-1.03], stroke (0.96, 0.93-1.01), MI (0.97, 0.91-1.03), and CVD mortality (0.98, 0.96-1.01), with consistent estimates from sensitivity analyses.

Conclusion: Observational findings indicated that higher plasma cystatin C is associated with a higher risk of CVDs; According to MR studies, there is no causal association between plasma cystatin C and the risk of CVDs and CVD mortality.

Keywords: Mendelian randomization; cardiovascular disease; genetic risk; myocardial infarction; plasma cystatin C; stroke.