Plasma osteoprotegerin, its correlates, and risk of heart failure: a prospective cohort study
Plasma osteoprotegerin, its correlates, and risk of heart failure: a prospective cohort study
复制标题
DOI：
10.1007/s10654-016-0172-4
复制
发表时间：
2017-02-01
影响因子：
13.6
通讯作者：
Weikert, Cornelia
中科院分区：
文献类型：
--
作者：
Di Giuseppe, Romina;Biemann, Ronald;Weikert, Cornelia
心力衰竭 (HF) 是一种涉及复杂血管、神经激素和免疫系统相互作用的致残性疾病。骨保护素 (OPG) 是一种骨调节细胞因子，被认为在骨骼、血管和免疫生物学中发挥着关键作用，在实验和临床心力衰竭中观察到其水平升高。在本研究中，我们旨在确定临床 OPG 的相关性，并研究作为心力衰竭血管和免疫激活标志物的升高的 OPG 是否可能与心力衰竭神经激素激活标志物 N 末端脑钠肽前体 (NT-proBNP) 相互作用，从而协同增加心力衰竭风险。我们使用了一项病例队列研究，该研究属于欧洲癌症和营养波茨坦前瞻性调查，包括 2647 名参与者，其中包括在平均随访 8.2 +/- 1.6 年期间发现的 252 例心力衰竭病例。在男性和女性中，观察到 OPG 与年龄、吸烟、流行的糖尿病、C 反应蛋白、性激素结合球蛋白以及仅男性流行的冠心病和尿酸之间存在显着的正相关。在女性中，OPG 还与高血压和胎球蛋白 A 呈正相关。经过多变量调整后，OPG 每增加一倍，男性心衰风险就会增加 3.01 倍（95% CI 1.49-6.06）。观察到 OPG 和 NT-proBNP 之间存在显着的相互作用。在男性中，与低水平的 OPG 和 NT-proBNP 组合相比，高水平的 OPG 和 NT-proBNP 与心力衰竭风险增加约五倍相关。在女性中，没有观察到关联。这些发现表明，在男性中，不同的免疫、神经激素和血管病理生理途径的激活可能会增加心力衰竭的风险。
Heart failure (HF) is a disabling condition involving complex vascular, neurohormonal and immune systems' interactions. Osteoprotegerin (OPG), a bone-regulatory cytokine, has been suggested to play a key role in skeletal, vascular, and immune biology, with elevated levels observed in both experimental and clinical HF. In the present study we aimed to identify clinical OPG correlates and investigated whether elevated OPG, as a marker of HF vascular and immune activation, may interact with N-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of HF neurohormonal activation, thus synergistically increasing HF risk. We used a case-cohort study, nested within the European Prospective Investigation into Cancer and Nutrition-Potsdam, comprising 2647 participants including 252 incident HF cases identified during a mean follow-up of 8.2 +/- 1.6 years. In both men and women significant positive associations were observed between OPG and age, smoking, prevalent diabetes, C-reactive protein, sex hormone-binding globulin, and additionally prevalent coronary heart disease and uric acid in men only. In women, OPG was furthermore positively related to hypertension and fetuin-A. After multivariable adjustment each doubling of OPG was associated with a 3.01-fold increased HF risk (95 % CI 1.49-6.06) in men. A significant interaction was observed between OPG and NT-proBNP. In men, a combination of high levels of both OPG and NT-proBNP, compared to a combination of low levels, was associated with an approximately fivefold increased HF risk. In women, no associations were observed. These findings suggest that, in men, the activation of different immune, neurohormonal, and vascular pathophysiological pathways may confer increased HF risk.