Le Viet T, Knight Stacey, Watrous Jeramie D, Najhawan Mahan, Dao Khoi, McCubrey Raymond O, Bair Tami L, Horne Benjamin D, May Heidi T, Muhlestein Joseph B, Nelson John R, Carlquist John F, Knowlton Kirk U, Jain Mohit, Anderson Jeffrey L
Intermountain Medical Center, Intermountain Heart Institute, Salt Lake City, UT, United States.
Department of Physician Assistant Studies, Rocky Mountain University of Health Professions, Provo, UT, United States.
Front Cardiovasc Med. 2023 Aug 23;10:1229130. doi: 10.3389/fcvm.2023.1229130. eCollection 2023.
Long-chain omega-3 polyunsaturated fatty acids (OM3 PUFA) are commonly used for cardiovascular disease prevention. High-dose eicosapentaenoic acid (EPA) is reported to reduce major adverse cardiovascular events (MACE); however, a combined EPA and docosahexaenoic acid (DHA) supplementation has not been proven to do so. This study aimed to evaluate the potential interaction between EPA and DHA levels on long-term MACE.
We studied a cohort of 987 randomly selected subjects enrolled in the INSPIRE biobank registry who underwent coronary angiography. We used rapid throughput liquid chromatography-mass spectrometry to quantify the EPA and DHA plasma levels and examined their impact unadjusted, adjusted for one another, and fully adjusted for comorbidities, EPA + DHA, and the EPA/DHA ratio on long-term (10-year) MACE (all-cause death, myocardial infarction, stroke, heart failure hospitalization).
The average subject age was 61.5 ± 12.2 years, 57% were male, 41% were obese, 42% had severe coronary artery disease (CAD), and 311 (31.5%) had a MACE. The 10-year MACE unadjusted hazard ratio (HR) for the highest (fourth) vs. lowest (first) quartile (Q) of EPA was HR = 0.48 (95% CI: 0.35, 0.67). The adjustment for DHA changed the HR to 0.30 (CI: 0.19, 0.49), and an additional adjustment for baseline differences changed the HR to 0.36 (CI: 0.22, 0.58). Conversely, unadjusted DHA did not significantly predict MACE, but adjustment for EPA resulted in a 1.81-fold higher risk of MACE (CI: 1.14, 2.90) for Q4 vs. Q1. However, after the adjustment for baseline differences, the risk of MACE was not significant for DHA (HR = 1.37; CI: 0.85, 2.20). An EPA/DHA ratio ≥1 resulted in a lower rate of 10-year MACE outcomes (27% vs. 37%, adjusted -value = 0.013).
Higher levels of EPA, but not DHA, are associated with a lower risk of MACE. When combined with EPA, higher DHA blunts the benefit of EPA and is associated with a higher risk of MACE in the presence of low EPA. These findings can help explain the discrepant results of EPA-only and EPA/DHA mixed clinical supplementation trials.
长链ω-3多不饱和脂肪酸（OM3 PUFA）常用于预防心血管疾病。据报道，高剂量二十碳五烯酸（EPA）可减少主要不良心血管事件（MACE）；然而，补充EPA和二十二碳六烯酸（DHA）的组合尚未被证实有此效果。本研究旨在评估EPA和DHA水平对长期MACE的潜在相互作用。
我们研究了987名随机选取的纳入INSPIRE生物样本库登记系统并接受冠状动脉造影的受试者队列。我们使用快速通量液相色谱 - 质谱法对血浆中EPA和DHA水平进行定量，并检查它们在未调整、相互调整以及针对合并症、EPA + DHA和EPA/DHA比值进行完全调整的情况下对长期（10年）MACE（全因死亡、心肌梗死、中风、心力衰竭住院）的影响。
受试者平均年龄为61.5±12.2岁，57%为男性，41%为肥胖者，42%患有严重冠状动脉疾病（CAD），311人（31.5%）发生了MACE。EPA最高（第四）四分位数（Q）与最低（第一）四分位数相比，未调整的10年MACE风险比（HR）为HR = 0.48（95%CI：0.35，0.67）。对DHA进行调整后，HR变为0.30（CI：0.19，0.49），对基线差异进行额外调整后，HR变为0.36（CI：0.22，0.58）。相反，未调整的DHA对MACE无显著预测作用，但对EPA进行调整后，第四四分位数与第一四分位数相比，MACE风险高1.81倍（CI：1.14，2.90）。然而，在对基线差异进行调整后，DHA的MACE风险不显著（HR = 1.37；CI：0.85，2.20）。EPA/DHA比值≥1导致10年MACE结局发生率较低（27%对37%，调整后P值 = 0.013）。
较高水平的EPA而非DHA与较低的MACE风险相关。当与EPA联合时，较高的DHA会削弱EPA的益处，并且在EPA水平较低时与较高的MACE风险相关。这些发现有助于解释仅使用EPA和EPA/DHA混合的临床补充试验结果的差异。
