Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands; Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands; Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands.
J Am Coll Cardiol. 2021 Jan 5;77(1):45-54. doi: 10.1016/j.jacc.2020.10.048.
Previously, observational studies have identified associations between higher levels of dietary-derived antioxidants and lower risk of coronary heart disease (CHD), whereas randomized clinical trials showed no reduction in CHD risk following antioxidant supplementation.
The purpose of this study was to investigate possible causal associations between dietary-derived circulating antioxidants and primary CHD risk using 2-sample Mendelian randomization (MR).
Single-nucleotide polymorphisms for circulating antioxidants (vitamins E and C, retinol, β-carotene, and lycopene), assessed as absolute levels and metabolites, were retrieved from the published data and were used as genetic instrumental variables. Summary statistics for gene-CHD associations were obtained from 3 databases: the CARDIoGRAMplusC4D consortium (60,801 cases; 123,504 control subjects), UK Biobank (25,306 cases; 462,011 control subjects), and FinnGen study (7,123 cases; 89,376 control subjects). For each exposure, MR analyses were performed per outcome database and were subsequently meta-analyzed.
Among an analytic sample of 768,121 individuals (93,230 cases), genetically predicted circulating antioxidants were not causally associated with CHD risk. For absolute antioxidants, the odds ratio for CHD ranged between 0.94 (95% confidence interval [CI]: 0.63 to 1.41) for retinol and 1.03 (95% CI: 0.97 to 1.10) for β-carotene per unit increase in ln-transformed antioxidant values. For metabolites, the odds ratio ranged between 0.93 (95% CI: 0.82 to 1.06) for γ-tocopherol and 1.01 (95% CI: 0.95 to 1.08) for ascorbate per 10-fold increase in metabolite levels.
Evidence from our study did not support a protective effect of genetic predisposition to high dietary-derived antioxidant levels on CHD risk. Therefore, it is unlikely that taking antioxidants to increase blood antioxidants levels will have a clinical benefit for the prevention of primary CHD.
先前的观察性研究已经确定了饮食中抗氧化剂水平与冠心病（CHD）风险降低之间存在关联，而随机临床试验则表明抗氧化剂补充并不能降低 CHD 风险。
本研究旨在使用双样本 Mendelian 随机化（MR）方法，探究饮食中循环抗氧化剂与原发性 CHD 风险之间的因果关联。
从已发表的数据中检索到循环抗氧化剂（维生素 E 和 C、视黄醇、β-胡萝卜素和番茄红素）的单核苷酸多态性，作为绝对水平和代谢物进行评估，并将其用作遗传工具变量。从三个数据库中获取基因-CHD 关联的汇总统计数据：CARDIOGRAMplusC4D 联盟（60801 例病例；123504 例对照）、英国生物银行（25306 例病例；462011 例对照）和 FinnGen 研究（7123 例病例；89376 例对照）。对于每种暴露，在每个结果数据库中进行 MR 分析，并随后进行荟萃分析。
在一个包含 768121 人的分析样本中（93230 例病例），遗传预测的循环抗氧化剂与 CHD 风险无因果关系。对于绝对抗氧化剂，视黄醇的 CHD 比值比（OR）范围为 0.94（95%置信区间 [CI]：0.63 至 1.41），β-胡萝卜素为 1.03（95%CI：0.97 至 1.10），每增加 ln 转换的抗氧化剂值一个单位。对于代谢物，γ-生育酚的 OR 范围为 0.93（95%CI：0.82 至 1.06），抗坏血酸为 1.01（95%CI：0.95 至 1.08），每增加 10 倍代谢物水平。
我们的研究结果并未支持遗传易感性高的饮食抗氧化剂水平对 CHD 风险具有保护作用的证据。因此，增加血液抗氧化剂水平以服用抗氧化剂来预防原发性 CHD 不太可能具有临床获益。
