饱和和不饱和脂肪酸（FA）与心血管疾病（CVD）的关系仍然存在争议。因此，我们的目的是研究客观测量的 FA 与 CVD 的前瞻性关联，包括冠心病 (CHD) 和中风，以及 CVD 死亡率。对 172,891 名既往无血管病史的参与者进行了循环 FA 浓度的分析，以总 FA 的百分比表示。欧洲癌症和营养-CVD 前瞻性调查 (EPIC-CVD)（7,343 例 CHD；6,499 例中风）、英国生物库（1,825；1,474）和 INTERVAL（285；209）队列研究的基线疾病。使用 Cox 回归模型估算每 1 个标准差 (SD) 较高 FA 浓度的风险比 (HR)，并通过随机效应荟萃分析进行汇总。系统地搜索了 2023 年 5 月 6 日发表的关于 FA 和 CVD 之间关联的系统综述和荟萃分析，并使用随机效应模型进行了更新的荟萃分析。还总结了随机对照试验 (RCT) 的证据。在综合分析中，总饱和 FA (SFA) 浓度较高与较高的心血管风险相关，在仅限于 EPIC-CVD 的进一步分析中指出了 SFA 亚型的差异结果：正相关对于偶数链 SFA [CHD 的 HR 1.24 (95% CI: 1.18-1.32)；中风 1.23 (1.10-1.38)] 和奇数链的负关联 [0.82 (0.76-0.87)； 0.73（0.67-0.78）]和长链[0.95（0.80-1.12）； 0.84 (0.72-0.99)] SFA。在综合分析中，总 n-3 多不饱和 FA (PUFA) [0.91 (0.85-0.97)]，包括二十二碳六烯酸 (DHA) [0.91 (0.84-0.98)]，与 CHD 风险呈负相关。同样，总 n-6 PUFA [0.94 (0.91-0.98)]，包括亚油酸 (LA) [0.89 (0.83-0.95)]，与中风风险呈负相关。相比之下，EPIC-CVD 中更详细的分析表明，LA 的几种下游 n-6 PUFA 与 CHD 风险呈正相关。对 37 项 FA 的更新荟萃分析（包括 49 项非重叠研究，涉及 7,787 至 22,802 例 CHD 和 6,499 至 14,221 例中风病例）显示与我们的综合实证分析大致相似的结果，并进一步表明个体长链 n-3 之间存在显着的负相关性PUFA 和 LA 对 CHD 和中风都有作用。尽管单一疗法的证据不足，但长链 n-3 PUFA 的研究结果与已发表的关于 CHD 的 RCT 的结果一致，而对于其余探索的 FA 的 RCT 证据仍不清楚。我们的研究概述了有关 CHD 的最新证据。客观测量的 FA 与 CVD 结果之间的关联。总的来说，这些数据揭示了 SFA 亚型之间的显着差异，并呼吁进一步研究，尤其是随机对照试验，来探索这些联系。© 作者 2024。由牛津大学出版社代表欧洲心脏病学会出版。

Associations of saturated and unsaturated fatty acids (FAs) with cardiovascular disease (CVD) remain controversial. We therefore aimed to investigate the prospective associations of objectively measured FAs with CVD, including incident coronary heart disease (CHD) and stroke, as well as CVD mortality.Circulating FA concentrations expressed as the percentage of total FAs were assayed in 172,891 participants without prior vascular disease at baseline from the European Prospective Investigation into Cancer and Nutrition-CVD (EPIC-CVD) (7,343 CHD; 6,499 stroke), UK Biobank (1,825; 1,474), and INTERVAL (285; 209) cohort studies. Hazard ratio (HR) per 1-standard deviation (SD) higher FA concentrations was estimated using Cox regression models and pooled by random-effects meta-analysis. Systematic reviews with meta-analysis published by 6 May 2023 on associations between FAs and CVDs were systematically searched and updated meta-analyses using random-effects model were conducted. Evidence from randomized controlled trials (RCTs) was also summarized.Higher concentrations of total saturated FAs (SFAs) were associated with higher cardiovascular risks in the combined analysis, with differential findings noted for SFA subtypes in further analysis restricted to EPIC-CVD: positive associations for even-chain SFA [HR for CHD 1.24 (95% CI: 1.18-1.32); stroke 1.23 (1.10-1.38)] and negative associations for odd-chain [0.82 (0.76-0.87); 0.73 (0.67-0.78)] and longer-chain [0.95 (0.80-1.12); 0.84 (0.72-0.99)] SFA. In the combined analysis, total n-3 polyunsaturated FA (PUFA) [0.91 (0.85-0.97)], including docosahexaenoic acid (DHA) [0.91 (0.84-0.98)], was negatively associated with incident CHD risk. Similarly, total n-6 PUFA [0.94 (0.91-0.98)], including linoleic acid (LA) [0.89 (0.83-0.95)], was negatively associated with incident stroke risk. By contrast, more detailed analyses in EPIC-CVD revealed that several downstream n-6 PUFAs of LA were positively associated with CHD risk. Updated meta-analyses of 37 FAs including 49 non-overlapping studies, involving between 7,787 to 22,802 CHD and 6,499 to 14,221 stroke cases, showed broadly similar results as our combined empirical analysis and further suggested significant inverse associations of individual long-chain n-3 PUFAs and LA on both CHD and stroke. The findings of long-chain n-3 PUFAs were consistent with those from published RCTs on CHD despite insufficient evidence in monotherapy, while RCT evidence remained unclear for the rest of the explored FAs.Our study provides an overview of the most recent evidence on the associations between objectively measured FAs and CVD outcomes. Collectively, the data reveals notable differences in associations by SFA subtypes and calls for further studies, especially RCTs, to explore these links.© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.