Qasim Atif, Mehta Nehal N, Tadesse Mahlet G, Wolfe Megan L, Rhodes Thomas, Girman Cynthia, Reilly Muredach P
Cardiovascular Institute and Institute for Translational Medicine and Therapeutics, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
J Am Coll Cardiol. 2008 Jul 15;52(3):231-6. doi: 10.1016/j.jacc.2008.04.016.
We evaluated the hypothesis that plasma levels of adiponectin and leptin are independently but oppositely associated with coronary artery calcification (CAC), a measure of subclinical atherosclerosis. In addition, we assessed which biomarkers of adiposity and insulin resistance are the strongest predictors of CAC beyond traditional risk factors, metabolic syndrome, and plasma C-reactive protein (CRP).
Adipokines are fat-secreted biomolecules with pleiotropic actions that converge in diabetes and cardiovascular disease.
We examined the association of plasma adipocytokines with CAC in 860 asymptomatic, nondiabetic participants in the SIRCA (Study of Inherited Risk of Coronary Atherosclerosis).
Plasma adiponectin and leptin levels had opposite and distinct associations with adiposity, insulin resistance, and inflammation. Plasma leptin was positively (top vs. bottom quartile) associated with higher CAC after adjustment for age, gender, traditional risk factors, and Framingham risk scores (tobit regression ratio 2.42 (95% confidence interval [CI]: 1.48 to 3.95; p = 0.002) and further adjustment for metabolic syndrome and CRP (tobit regression ratio: 2.31; 95% CI: 1.36 to 3.94; p = 0.002). In contrast, adiponectin levels were not associated with CAC. Comparative analyses suggested that levels of leptin, interleukin-6, and soluble tumor necrosis factor receptor-2, as well as the homeostasis model assessment of insulin resistance (HOMA-IR) index, predicted CAC scores, but only leptin and HOMA-IR provided value beyond risk factors, metabolic syndrome, and CRP.
In SIRCA, although both leptin and adiponectin levels were associated with metabolic and inflammatory markers, only leptin was a significant independent predictor of CAC. Of several metabolic markers, leptin and the HOMA-IR index had the most robust, independent associations with CAC.
我们评估了如下假设，即脂联素和瘦素的血浆水平与冠状动脉钙化（CAC）独立但呈相反关联，冠状动脉钙化是亚临床动脉粥样硬化的一项指标。此外，我们评估了除传统危险因素、代谢综合征和血浆C反应蛋白（CRP）之外，哪些肥胖和胰岛素抵抗生物标志物是CAC的最强预测因子。
脂肪因子是脂肪分泌的具有多效性作用的生物分子，这些作用在糖尿病和心血管疾病中相互关联。
我们在冠状动脉粥样硬化遗传风险研究（SIRCA）中的860名无症状、非糖尿病参与者中研究了血浆脂肪细胞因子与CAC的关联。
血浆脂联素和瘦素水平与肥胖、胰岛素抵抗和炎症呈相反且不同的关联。在校正年龄、性别、传统危险因素和弗雷明汉风险评分后（托比特回归比率2.42（95%置信区间[CI]：1.48至3.95；p = 0.002），血浆瘦素与较高的CAC呈正相关（最高四分位数与最低四分位数相比），进一步校正代谢综合征和CRP后（托比特回归比率：2.31；95%CI：1.36至3.94；p = 0.002）。相比之下，脂联素水平与CAC无关。比较分析表明，瘦素、白细胞介素-6、可溶性肿瘤坏死因子受体-2水平以及胰岛素抵抗稳态模型评估（HOMA-IR）指数可预测CAC评分，但只有瘦素和HOMA-IR在危险因素、代谢综合征和CRP之外具有预测价值。
在SIRCA中，尽管瘦素和脂联素水平均与代谢和炎症标志物相关，但只有瘦素是CAC的显著独立预测因子。在几种代谢标志物中，瘦素和HOMA-IR指数与CAC的关联最为稳健和独立。
