Research Group Cardiovascular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert-Allee, 114-116, 14558, Nuthetal, Germany.
Institute of Epidemiology, Christian-Albrechts University Kiel, University Hospital Schleswig-Holstein (UK-SH), Campus Kiel, Niemannsweg 11, 24105, Kiel, Germany.
Eur J Epidemiol. 2017 Feb;32(2):113-123. doi: 10.1007/s10654-016-0172-4. Epub 2016 Jun 15.
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.
心力衰竭（HF）是一种涉及复杂的血管、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，它在骨骼、血管和免疫生物学中发挥着关键作用，在实验和临床 HF 中观察到其水平升高。本研究旨在确定临床 OPG 相关因素，并研究升高的 OPG 是否作为 HF 血管和免疫激活的标志物，与 N 端脑钠肽前体（NT-proBNP）相互作用，NT-proBNP 是 HF 神经激素激活的标志物，从而协同增加 HF 风险。我们使用了病例-队列研究，该研究嵌套在欧洲癌症前瞻性调查-波茨坦中，包括 2647 名参与者，其中 252 名参与者在平均 8.2±1.6 年的随访期间被诊断为 HF。在男性和女性中，OPG 与年龄、吸烟、现患糖尿病、C 反应蛋白、性激素结合球蛋白呈显著正相关，仅在男性中，OPG 与现患冠心病和尿酸呈正相关。在女性中，OPG 还与高血压和胎球蛋白 A 呈正相关。在多变量调整后，OPG 每增加一倍，HF 风险增加 3.01 倍（95%CI 1.49-6.06），男性有统计学意义。OPG 和 NT-proBNP 之间观察到显著的交互作用。在男性中，与低水平的 OPG 和 NT-proBNP 相比，高水平的 OPG 和 NT-proBNP 组合与 HF 风险增加约五倍相关。在女性中，未观察到相关性。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 HF 风险。
