循环脂肪酸与心血管疾病风险的关联：三个大型前瞻性队列和更新的荟萃分析的个体数据分析

饱和和不饱和脂肪酸（FAS）与心血管疾病（CVD）的关联仍然存在争议。因此，我们的目的是研究客观测量的FA与CVD的前瞻性关联，包括事件冠状动脉疾病（CHD）和中风和CVD死亡率，以及CVD死亡率。在172 891名参与者中分析了欧洲疾病的FA浓度为总FAS的百分比，该浓度在172 891名参与者中，来自欧洲前瞻性研究的3. EPVD和Nutiention-CVD（Nuttion-CVD）（Nuttion-CVD）（Nuttion-CVD）（Nuttion-CVD）（Nuttion-CVD（Nut）3） 6499中风），英国生物银行（1825; 1474）和间隔（285; 209）同类研究。使用COX回归模型估算每个1-标准偏差（SD）较高FA浓度的危险比（HR），并通过随机效应荟萃分析汇总。使用随机效应模型对2023年5月6日发表的有关FAS和CVD之间关联的荟萃分析进行了系统评价。还总结了随机对照试验（RCT）的证据。在组合分析中，较高浓度的总饱和FA（SFA）与较高的心血管风险有关，在进一步分析中，SFA子类型的差异结果仅限于Epic-CVD：均匀的CHAIN SFA [HR的阳性关联[HR的HR [chd 1.24（95％CI：1.18-18-1.32）;中风1.23（1.10-1.38）]和奇数链的负相关[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。在组合分析中，包括docosahexaenoic Acid（DHA）[0.91（0.84-0.98）]在内的总N-3多不饱和FA（PUFA）[0.91（0.85-0.97）]与入射CHD风险有负相关。同样，总N-6 PUFA [0.94（0.91-0.98）]，包括亚油酸（LA）[0.89（0.83-0.95）]，与入射冲程风险有负相关。相比之下，EPIC-CVD中更详细的分析表明，LA的几个下游N-6 PUFA与CHD风险呈正相关。更新的37个FA的荟萃分析，包括49项非重叠研究，涉及7787和22 802 CHD病例以及6499和14 221个中风病例，显示出与我们的合并经验分析的广泛相似结果，并进一步提出了在CHD和CHD上的单个长链N-3 Pufas和La的显着逆相关。长链N-3 PUFA的发现与单一疗法的证据不足，而RCT的证据不清楚，但对于其他探索的FAS仍不清楚CHD上已发表的RCT的发现。总体而言，数据揭示了SFA子类型在关联方面的显着差异，并呼吁进行进一步的研究，尤其是RCT，以探索这些链接。

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) (7343 CHD; 6499 stroke), UK Biobank (1825; 1474), 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 sub-types 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. In 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 7787 and 22 802 CHD cases and between 6499 and 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 reveal notable differences in associations by SFA sub-types and call for further studies, especially RCTs, to explore these links.