Epicardial Fat Volume Is Associated with Endothelial Dysfunction, but not with Coronary Calcification: From the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Abstract Background The increase in epicardial fat volume (EFV) is related to coronary artery disease (CAD), independent of visceral or subcutaneous fat. The mechanism underlying this association is unclear. Coronary artery calcium (CAC) score and endothelial dysfunction are related to coronary events, but whether EFV is related to these markers needs further clarification. Objectives To evaluate the association between automatically measured EFV, cardiovascular risk factors, CAC, and endothelial function. Methods In 470 participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) with measures of EFV, CAC score and endothelial function, we performed multivariable models to evaluate the relation between cardiovascular risk factors and EFV (response variable), and between EFV (explanatory variable) and endothelial function variables or CAC score. Two-sided p <0.05 was considered statistically significant. Results Mean age was 55 ± 8 years, 52.3% of patients were men. Mean EFV was 111mL (IQ 86-144), and the prevalence of CAC score=0 was 55%. In the multivariable analyses, increased EFV was related to female sex, older age, waist circumference, and triglycerides (p<0.001 for all). Higher EFV was associated with worse endothelial function: as compared with the first quartile, the odds ratio for basal pulse amplitude were (q2=1.22, 95%CI 1.07-1.40; q3=1.50, 95%CI 1.30-1.74; q4=1.50, 95%CI 1.28-1.79) and for peripheral arterial tonometry ratio were (q2=0.87, 95%CI 0.81-0.95; q3=0.86, 95%CI 0.79-0.94; q4=0.80, 95%CI 0.73-0.89), but not with CAC score>0. Conclusion Higher EFV was associated with impaired endothelial function, but not with CAC. The results suggest that EFV is related to the development of CAD through a pathway different from the CAC pathway, possibly through aggravation of endothelial dysfunction and microvascular disease.

研究背景：心外膜脂肪体积（epicardial fat volume, EFV）升高与冠状动脉疾病（coronary artery disease, CAD）相关，且该关联独立于内脏或皮下脂肪。目前二者关联的潜在机制尚未阐明。冠状动脉钙化（coronary artery calcium, CAC）评分与内皮功能障碍均与冠状动脉事件存在关联，但EFV是否与这些标志物存在关联仍需进一步验证。
研究目的：评估自动测量的心外膜脂肪体积、心血管危险因素、冠状动脉钙化评分与内皮功能之间的关联。
研究方法：本研究纳入巴西成人健康纵向研究（Brazilian Longitudinal Study of Adult Health, ELSA-Brasil）中470名完成心外膜脂肪体积、冠状动脉钙化评分及内皮功能检测的参与者，通过多变量模型分别分析：1）心血管危险因素与心外膜脂肪体积（因变量）的关联；2）心外膜脂肪体积（自变量）与内皮功能指标或冠状动脉钙化评分的关联。本研究采用双侧检验，以p<0.05为具有统计学意义的判定标准。
研究结果：本研究参与者的平均年龄为55±8岁，其中男性占比52.3%。平均心外膜脂肪体积为111mL，四分位距为86~144mL；冠状动脉钙化评分为0的参与者占比为55%。多变量分析结果显示，心外膜脂肪体积升高与女性性别、年龄增长、腰围增大及甘油三酯水平升高显著相关（所有指标p<0.001）。心外膜脂肪体积升高与内皮功能恶化呈显著相关：与第一四分位数组相比，基础脉搏振幅的比值比依次为（q2=1.22，95%置信区间1.07~1.40；q3=1.50，95%置信区间1.30~1.74；q4=1.50，95%置信区间1.28~1.79），外周动脉张力比值的比值比依次为（q2=0.87，95%置信区间0.81~0.95；q3=0.86，95%置信区间0.79~0.94；q4=0.80，95%置信区间0.73~0.89）；但心外膜脂肪体积升高与冠状动脉钙化评分>0无显著关联。
研究结论：心外膜脂肪体积升高与内皮功能受损相关，但与冠状动脉钙化评分无显著关联。本研究结果提示，心外膜脂肪体积通过不同于冠状动脉钙化的通路参与冠状动脉疾病的发生发展，其潜在机制可能为加重内皮功能障碍与微血管病变。