Department of Nephrology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Arterioscler Thromb Vasc Biol. 2012 Sep;32(9):2327-35. doi: 10.1161/ATVBAHA.112.248609. Epub 2012 Jun 7.
Adipocyte fatty acid-binding protein (A-FABP) abundantly expressed in mature adipocytes and activated macrophages has dramatic effects on atherosclerosis in mice. Whether this pathophysiological role of A-FABP may also apply to atherosclerotic disease in humans is still unknown. This study investigated associations among serum A-FABP levels, cardiovascular risk factors, and long-term secondary cardiovascular disease (CVD) outcome in patients with coronary heart disease.
Serum A-FABP levels were measured in 1069 patients with prevalent coronary heart disease and a 10-year prospective follow-up was conducted (median, 119.5 [interquartile range, 74.1-120.6] months). During this period 204 patients (incidence, 24.0/1000 patient-years) experienced a secondary cardiovascular disease event (defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal cerebrovascular stroke). At baseline, circulating A-FABP was positively associated with a cluster of metabolic and inflammatory risk factors and independently predicted the presence of the metabolic syndrome (odds ratio per unit increase of natural log-transformed A-FABP, 2.95; 95% CI, 2.22-3.92, P<0.001). On long-term follow-up, subjects with high baseline A-FABP showed an increased risk for secondary cardiovascular disease events (hazard ratio per unit increase, 1.52; 95% CI, 1.18-1.95; P=0.001), which was attenuated after multivariable adjustment (hazard ratio 1.30; 95% CI, 0.98-1.73). In contrast, A-FABP remained significantly associated with cardiovascular death even after multivariable adjustment (hazard ratio, 1.75; 95% CI, 1.17-2.62, P=0.007).
Circulating A-FABP levels are associated with long-term prognosis in patients with coronary heart disease and may represent an important pathophysiological mediator of atherosclerosis, which may point to a new target of treatment options.
脂肪细胞脂肪酸结合蛋白(A-FABP)在成熟脂肪细胞和活化的巨噬细胞中大量表达,对小鼠动脉粥样硬化有显著影响。A-FABP 的这种病理生理作用是否也适用于人类的动脉粥样硬化疾病尚不清楚。本研究探讨了冠心病患者血清 A-FABP 水平与心血管危险因素及长期二级心血管疾病(CVD)结局之间的关系。
在 1069 例现患冠心病患者中测量了血清 A-FABP 水平,并进行了 10 年的前瞻性随访(中位数为 119.5[四分位距,74.1-120.6]个月)。在此期间,204 例患者(发生率为 24.0/1000 患者年)发生了二级心血管疾病事件(定义为心血管死亡、非致死性心肌梗死或非致死性脑卒中等)。在基线时,循环 A-FABP 与一组代谢和炎症危险因素呈正相关,并独立预测代谢综合征的存在(每单位自然对数转换的 A-FABP 增加的优势比,2.95;95%置信区间,2.22-3.92,P<0.001)。在长期随访中,基线 A-FABP 较高的患者发生二级心血管疾病事件的风险增加(每单位增加的风险比,1.52;95%置信区间,1.18-1.95;P=0.001),但在多变量调整后风险降低(风险比 1.30;95%置信区间,0.98-1.73)。相反,即使在多变量调整后,A-FABP 仍与心血管死亡显著相关(风险比,1.75;95%置信区间,1.17-2.62,P=0.007)。
循环 A-FABP 水平与冠心病患者的长期预后相关,可能是动脉粥样硬化的一个重要病理生理介质,这可能为治疗选择提供一个新的靶点。