School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
School of Nursing, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Hereditas. 2024 Sep 5;161(1):30. doi: 10.1186/s41065-024-00329-9.
The lipid-lowering effects of Omega-3 fatty acids have been widely reported, yet their impact on ischemic stroke remains controversial. Reports on the protective effects of unsaturated fatty acids, such as Omega-6 and Omega-7, as well as saturated fatty acids in cardiovascular diseases, including hypertension and ischemic stroke, are less frequent.
This study aims to identify fatty acids associated with blood pressure and ischemic stroke through Mendelian randomization. Besides, it seeks to determine whether specific fatty acids can prevent ischemic stroke by managing blood pressure and revealing the specific mechanisms of this action.
This research involved downloading relevant data from websites and extracting SNPs that met the standard criteria as instrumental variables. Simultaneously, the 'MR-PRESSO' package and 'Mendelian Randomization' package were used to eliminate confounding SNPs that could bias the study results. Then, inverse variance weighting and the weighted median were employed as primary analysis methods, accompanied by sensitivity analysis to assess the validity of the causal relationships. Initially, multivariable Mendelian randomization was used to identify fatty acids linked to blood pressure and the incidence of ischemic stroke. The causal link between certain fatty acids and the initiation of ischemic stroke was then investigated using bidirectional and mediator Mendelian randomization techniques. Stepwise Regression and the Product of Coefficients Method in mediator Mendelian randomization were utilized to ascertain whether specific fatty acids reduce ischemic stroke risk by lowering blood pressure.
Multivariable Mendelian randomization analysis indicated a potential inverse correlation between Omega-3 intake and both blood pressure and ischemic stroke. Consequently, Omega-3 was selected as the exposure, with blood pressure and ischemic stroke-related data as outcomes, for further bidirectional and mediation Mendelian Randomization analyses. Bidirectional Mendelian Randomization revealed that Omega-3 significantly influences DBP (P = 1.01e-04) and IS (P = 0.016). It also showed that DBP and SBP significantly affect LAS, SVS, CES, IS, and LS. Mediator Mendelian Randomization identified five established mediating pathways: Omega-3-Diastolic blood pressure-Small vessel stroke, Omega-3-Diastolic blood pressure-Cardioembolic stroke, Omega-3-Diastolic blood pressure-Lacunar stroke, Omega-3-Diastolic blood pressure-Large artery atherosclerosis stroke, and Omega-3-Diastolic blood pressure-Ischemic stroke. Of these, four pathways are complete mediation, and one pathway is partial mediation.
The findings suggest that Omega-3 may indirectly reduce the incidence of ischemic stroke by lowering blood pressure. Thus, blood pressure modulation might be one of the mechanisms through which Omega-3 prevents ischemic stroke. In summary, incorporating an increased intake of Omega-3 in the diet can serve as one of the dietary intervention strategies for patients with hypertension. Additionally, it can act as an adjunctive therapy for the prevention of ischemic strokes and their complications.
ω-3 脂肪酸的降脂作用已被广泛报道，但它们对缺血性中风的影响仍存在争议。关于不饱和脂肪酸（如 ω-6 和 ω-7）以及饱和脂肪酸在心血管疾病（包括高血压和缺血性中风）中的保护作用的报道较少。
本研究旨在通过孟德尔随机化确定与血压和缺血性中风相关的脂肪酸。此外，还旨在确定特定的脂肪酸是否可以通过控制血压和揭示这种作用的具体机制来预防缺血性中风。
本研究从网站下载相关数据，并提取符合标准的 SNP 作为工具变量。同时，使用“MR-PRESSO”包和“孟德尔随机化”包来消除可能会使研究结果产生偏差的混杂 SNP。然后，采用逆方差加权和加权中位数作为主要分析方法，并进行敏感性分析以评估因果关系的有效性。首先，使用多变量孟德尔随机化确定与血压和缺血性中风发生相关的脂肪酸。然后，使用双向和中介孟德尔随机化技术研究特定脂肪酸与缺血性中风发作之间的因果关系。中介孟德尔随机化中使用逐步回归和系数乘积法来确定特定脂肪酸是否通过降低血压来降低缺血性中风的风险。
多变量孟德尔随机化分析表明，ω-3 摄入量与血压和缺血性中风之间存在潜在的负相关关系。因此，选择 ω-3 作为暴露因素，以血压和缺血性中风相关数据作为结果，进一步进行双向和中介孟德尔随机化分析。双向孟德尔随机化显示，ω-3 显著影响 DBP（P = 1.01e-04）和 IS（P = 0.016）。它还表明 DBP 和 SBP 显著影响 LAS、SVS、CES、IS 和 LS。中介孟德尔随机化确定了五个已建立的中介途径：ω-3-舒张压-小血管中风、ω-3-舒张压-心源性中风、ω-3-舒张压-腔隙性中风、ω-3-舒张压-大动脉粥样硬化性中风和 ω-3-舒张压-缺血性中风。其中，四条途径是完全中介，一条途径是部分中介。
研究结果表明，ω-3 可能通过降低血压间接降低缺血性中风的发生率。因此，血压调节可能是 ω-3 预防缺血性中风的机制之一。总之，增加 ω-3 的摄入量可以作为高血压患者的饮食干预策略之一。此外，它可以作为预防缺血性中风及其并发症的辅助治疗。
