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

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.