School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
School of Public Health and Health Policy, City University of New York, New York, NY 10027, USA.
Nutrients. 2021 Apr 28;13(5):1489. doi: 10.3390/nu13051489.
Arachidonic acid (AA), a major long-chain omega-6 polyunsaturated fatty acid, is associated with ischemic heart disease (IHD) and stroke. We assessed bi-directional associations of AA synthesis reflected by plasma phospholipid AA with CVD risk factors, and identified mediators of associations of AA with IHD and stroke using Mendelian randomization (MR). We used two-sample MR to assess bi-directional associations of AA synthesis with lipids, blood pressure, adiposity, and markers of inflammation and coagulation. We used multivariable MR to assess mediators of associations of AA with IHD and stroke. Genetically predicted AA (% of total fatty acids increase) was positively associated with apolipoprotein B (ApoB, 0.022 standard deviations (SD), 95% confidence interval (CI) 0.010, 0.034), high-density (0.030 SD, 95% CI 0.012, 0.049) and low-density lipoprotein cholesterol (LDL-C, 0.016 SD, 95% CI 0.004, 0.027) and lower triglycerides (-0.031 SD, 95% CI -0.049, -0.012) but not with other traits. Genetically predicted these traits gave no association with AA. The association of AA with IHD was attenuated adjusting for ApoB or LDL-C. Genetically predicted AA was associated with lipids but not other traits. Given ApoB is thought to be the key lipid in IHD, the association of AA with IHD is likely mediated by ApoB.
花生四烯酸（AA）是一种主要的长链ω-6 多不饱和脂肪酸，与缺血性心脏病（IHD）和中风有关。我们评估了反映血浆磷脂 AA 的 AA 合成的双向关联与 CVD 危险因素的关系，并使用孟德尔随机化（MR）鉴定了 AA 与 IHD 和中风关联的中介物。我们使用两样本 MR 来评估 AA 合成与脂质、血压、肥胖、炎症和凝血标志物的双向关联。我们使用多变量 MR 来评估 AA 与 IHD 和中风关联的中介物。遗传预测的 AA（总脂肪酸的百分比增加）与载脂蛋白 B（ApoB）呈正相关（0.022 个标准差（SD），95%置信区间（CI）为 0.010，0.034），高密度脂蛋白（0.030 SD，95%CI 为 0.012，0.049）和低密度脂蛋白胆固醇（LDL-C，0.016 SD，95%CI 为 0.004，0.027）升高，甘油三酯降低（-0.031 SD，95%CI 为-0.049，-0.012），但与其他特征无关。遗传预测这些特征与 AA 无关。在调整 ApoB 或 LDL-C 后，AA 与 IHD 的关联减弱。遗传预测的 AA 与脂质相关，但与其他特征无关。鉴于 ApoB 被认为是 IHD 的关键脂质，AA 与 IHD 的关联可能是由 ApoB 介导的。
