Lu Chen1, Xingang Sun2, Zhen Wang3, Yunlong Lu4, Miao Chen5, Yuxian He6, Hongfei Xu7, Liangrong Zheng8. 1. Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China. Electronic address: rembercl@163.com. 2. Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China. Electronic address: 11918190@zju.edu.cn. 3. Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China. Electronic address: 873924224@qq.com. 4. Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China. Electronic address: luyl@zju.edu.cn. 5. Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China. Electronic address: yxschenmiao@163.com. 6. Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China. Electronic address: 1508027621@qq.com. 7. Department of Cardiothoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China. Electronic address: xuhongfei@zju.edu.cn. 8. Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China. Electronic address: 1191066@zju.edu.cn.
Abstract
BACKGROUND & AIMS: Previous observational studies have reported associations between plasma vitamin C levels, and cardiovascular diseases (CVDs) and Alzheimer's disease (AD); however, no conclusive results have been obtained. We conducted a Mendelian randomization (MR) study to investigate the causality of vitamin C on the risk of nine CVDs [including coronary artery disease (CAD), myocardial infarction (MI), atrial fibrillation (AF), heart failure (HF), stroke, ischemic stroke (IS), and IS subtypes] and Alzheimer's disease. METHODS: Eleven single-nucleotide polymorphisms (SNPs) identified in a recent genome-wide meta-analysis (N = 52,018) were used as the instrumental variables for plasma vitamin C levels. The summary-level data for CVDs and AD were extracted from consortia and genome-wide association studies (GWAS). We performed MR analyses using the fixed-effects inverse-variance-weighted (IVW) method, weighted median, and MR-Egger approaches. RESULTS: This MR study found suggestive evidence that genetic liability to higher vitamin C levels was associated with a lower risk of cardioembolic stroke [odds ratio (OR, presented per 1 standard deviation increase in plasma vitamin C levels) = 0.773; 95% confidence interval (CI), 0.623-0.959; P = 0.020] and AD (OR = 0.968; 95% CI, 0.946-0.991; P = 0.007) using the fixed-effects IVW method. Sensitivity analysis yielded directionally similar results. A null-association was observed between vitamin C and the other CVDs. CONCLUSION: Our MR study provided suggestive evidence that higher vitamin C levels were casually associated with a decreased risk of cardioembolic stroke and AD. No evidence was observed to suggest that vitamin C affected the risk of CAD, MI, AF, HF, stroke, IS, large artery stroke, or small vessel stroke. However, well-designed studies are warranted to confirm these results and determine the underlying mechanisms of the causal links.
BACKGROUND & AIMS: Previous observational studies have reported associations between plasma vitamin C levels, and cardiovascular diseases (CVDs) and Alzheimer's disease (AD); however, no conclusive results have been obtained. We conducted a Mendelian randomization (MR) study to investigate the causality of vitamin C on the risk of nine CVDs [including coronary artery disease (CAD), myocardial infarction (MI), atrial fibrillation (AF), heart failure (HF), stroke, ischemic stroke (IS), and IS subtypes] and Alzheimer's disease. METHODS: Eleven single-nucleotide polymorphisms (SNPs) identified in a recent genome-wide meta-analysis (N = 52,018) were used as the instrumental variables for plasma vitamin C levels. The summary-level data for CVDs and AD were extracted from consortia and genome-wide association studies (GWAS). We performed MR analyses using the fixed-effects inverse-variance-weighted (IVW) method, weighted median, and MR-Egger approaches. RESULTS: This MR study found suggestive evidence that genetic liability to higher vitamin C levels was associated with a lower risk of cardioembolic stroke [odds ratio (OR, presented per 1 standard deviation increase in plasma vitamin C levels) = 0.773; 95% confidence interval (CI), 0.623-0.959; P = 0.020] and AD (OR = 0.968; 95% CI, 0.946-0.991; P = 0.007) using the fixed-effects IVW method. Sensitivity analysis yielded directionally similar results. A null-association was observed between vitamin C and the other CVDs. CONCLUSION: Our MR study provided suggestive evidence that higher vitamin C levels were casually associated with a decreased risk of cardioembolic stroke and AD. No evidence was observed to suggest that vitamin C affected the risk of CAD, MI, AF, HF, stroke, IS, large artery stroke, or small vessel stroke. However, well-designed studies are warranted to confirm these results and determine the underlying mechanisms of the causal links.
Authors: Cristina Gallego-Fabrega; Elena Muiño; Jara Cárcel-Márquez; Laia Llucià-Carol; Miquel Lledós; Jesús M Martín-Campos; Natalia Cullell; Israel Fernández-Cadenas Journal: Int J Mol Sci Date: 2022-06-20 Impact factor: 6.208