Circulating vitamin C and the risk of cardiovascular diseases: A Mendelian randomization study
Section snippets
Background
Globally, deaths from cardiovascular disease (CVD) increased by 14.5% from 2006 to 2016, ranking the first leading cause of death [1]. Dietary factors such as high levels of fruit and vegetable intake have been reported to be related to a lower risk of CVD incidence and mortality [2,3]. Circulation levels of vitamin C are considered good biomarkers of fruit and vegetable intake for its antioxidation effects and anti-inflammatory functions [[4], [5], [6]]. Vitamin C may protect low-density
Study design
In this study, we employed a two-sample MR design (Fig. 1), in which summary statistics for exposure (i.e., plasma vitamin C levels) and outcome (i.e., CVDs and their risk factors) were derived from a different sample. There are three core assumptions for MR analysis: (1) the genetic variants must be robustly associated with the exposure of interest; (2) the genetic variants should not be related to potential confounders of the exposure-outcome association; (3) the genetic variants should only
Statistical power
With a type 1 error rate of 0.003, when the expected odds ratio (OR) was ≤0.85, our study had >99% power to detect it for coronary artery disease, >99% power for atrial fibrillation, >96% power for heart failure, and >90% power for ischemic stroke. In the analysis of the association between vitamin C and CVD risk factors, our study is also sufficiently powered to investigate very weak associations. Detailed information on a priori power calculation is presented in the Supplementary Table S4.
Vitamin C and four CVD events
As
Discussion
In the present study, we examined the causal association between genetically predicted plasma vitamin C concentration with a risk of four CVD outcomes (i.e., coronary artery disease, atrial fibrillation, heart failure, and ischemic stroke) and 11 CVD risk factors (i.e., HDL-cholesterol, LDL-cholesterol, total cholesterol, triglycerides, systolic blood pressure, diastolic blood pressure, BMI, waist circumference, WHR, fat mass, and fat-free mass) using the two-sample MR analysis. Our principal
Conclusions
Using comprehensive two-sample MR analyses, our finding provided little evidence for linear causal associations between genetically predicted plasma vitamin C concentrations and risk of coronary artery disease, atrial fibrillation, heart failure, and ischemic stroke. Additionally, no evidence was revealed for the associations between vitamin C and CVD risk factors, including higher blood lipids, higher blood pressure, and abnormal body composition. In combination with previous RCT results, our
Declaration of competing interest
The authors declare that they have no competing interests.
Acknowledgments
The authors thank all the relevant consortiums and investigators for the management and sharing of summary-level data.
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