Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China.
NHC Key Laboratory of Assisted Circulation (Sun Yat-Sen University), Guangzhou, 510080, People's Republic of China.
BMC Med. 2023 Mar 29;21(1):117. doi: 10.1186/s12916-023-02836-4.
Epicardial adipose tissue (EAT) has been suggested to exert deleterious effects on myocardium and cardiovascular disease (CVD) consequence. We evaluated the associations of EAT thickness with adverse outcomes and its potential mediators in the community.
Participants without heart failure (HF) who had undergone cardiac magnetic resonance (CMR) to measure EAT thickness over the right ventricular free wall from the Framingham Heart Study were included. The correlation of EAT thickness with 85 circulating biomarkers and cardiometric parameters was assessed in linear regression models. The occurrence of HF, atrial fibrillation, coronary heart disease (CHD), and other adverse events was tracked since CMR was implemented. Their associations with EAT thickness and the mediators were evaluated using Cox regression and causal mediation analysis.
Of 1554 participants, 53.0% were females. Mean age, body mass index, and EAT thickness were 63.3 years, 28.1 kg/m, and 9.8 mm, respectively. After fully adjusting, EAT thickness positively correlated with CRP, LEP, GDF15, MMP8, MMP9, ORM1, ANGPTL3, and SERPINE1 and negatively correlated with N-terminal pro-B-type natriuretic peptide (NT-proBNP), IGFBP1, IGFBP2, AGER, CNTN1, and MCAM. Increasing EAT thickness was associated with smaller left ventricular end-diastolic dimension, thicker left ventricular wall thickness, and worse global longitudinal strain (GLS). During a median follow-up of 12.7 years, 101 incident HF occurred. Per 1-standard deviation increment of EAT thickness was associated with a higher risk of HF (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.19-1.72, P < 0.001) and the composite outcome consisting of myocardial infarction, ischemic stroke, HF, and death from CVD (adjusted HR [95% CI], 1.23 [1.07-1.40], P = 0.003). Mediation effect in the association between thicker EAT and higher risk of HF was observed with NT-proBNP (HR [95% CI], 0.95 [0.92-0.98], P = 0.011) and GLS (HR [95% CI], 1.04 [1.01-1.07], P = 0.032).
EAT thickness was correlated with inflammation and fibrosis-related circulating biomarkers, cardiac concentric change, myocardial strain impairment, incident HF risk, and overall CVD risk. NT-proBNP and GLS might partially mediate the effect of thickened EAT on the risk of HF. EAT could refine the assessment of CVD risk and become a new therapeutic target of cardiometabolic diseases.
URL: https://clinicaltrials.gov . Identifier: NCT00005121.
心外膜脂肪组织 (EAT) 已被认为对心肌和心血管疾病 (CVD) 后果有不良影响。我们评估了 EAT 厚度与不良结局的相关性及其在社区中的潜在介导因素。
纳入接受过心脏磁共振 (CMR) 检查以测量弗拉明汉心脏研究中右心室游离壁 EAT 厚度的无心力衰竭 (HF) 参与者。使用线性回归模型评估 EAT 厚度与 85 种循环生物标志物和心脏参数的相关性。自 CMR 实施以来，跟踪 HF、心房颤动、冠心病 (CHD) 和其他不良事件的发生情况。使用 Cox 回归和因果中介分析评估其与 EAT 厚度和中介物的关系。
在 1554 名参与者中，53.0%为女性。平均年龄、体重指数和 EAT 厚度分别为 63.3 岁、28.1 kg/m2 和 9.8 mm。完全调整后，EAT 厚度与 CRP、LEP、GDF15、MMP8、MMP9、ORM1、ANGPTL3 和 SERPINE1 呈正相关，与 N 末端 B 型利钠肽前体 (NT-proBNP)、IGFBP1、IGFBP2、AGER、 CNTN1 和 MCAM 呈负相关。EAT 厚度的增加与左心室舒张末期内径减小、左心室壁厚度增厚和整体纵向应变 (GLS) 恶化有关。在中位随访 12.7 年期间，发生了 101 例 HF 事件。EAT 厚度每增加 1 个标准差，HF 风险增加（调整后的危险比 [HR] 1.43，95%置信区间 [CI] 1.19-1.72，P<0.001）和包含心肌梗死、缺血性中风、HF 和 CVD 死亡的复合结局（调整后的 HR [95%CI]，1.23 [1.07-1.40]，P=0.003）。在 EAT 厚度与 HF 风险增加之间的关联中观察到中介效应，其与 NT-proBNP（HR [95%CI]，0.95 [0.92-0.98]，P=0.011）和 GLS（HR [95%CI]，1.04 [1.01-1.07]，P=0.032）有关。
EAT 厚度与炎症和纤维化相关的循环生物标志物、心脏向心性变化、心肌应变受损、HF 发病风险和整体 CVD 风险相关。NT-proBNP 和 GLS 可能部分介导了增厚的 EAT 对 HF 风险的影响。EAT 可以改进 CVD 风险评估，并成为治疗代谢性心血管疾病的新靶点。
网址：https://clinicaltrials.gov 。标识符：NCT00005121。
