Cardiology Department, Clinical Medical Center Zvezdara, Belgrade, Serbia.
Endocrine. 2010 Feb;37(1):148-56. doi: 10.1007/s12020-009-9282-z. Epub 2009 Nov 20.
The main cytokines regulating bone remodeling are the receptor activator of nuclear factor-κB ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG). Recent data have linked RANKL and OPG to cardiovascular disease as well. NT-pro-BNP and adiponectin are well-established biomarkers of heart failure reflecting neuroendocrine activation in this multi-complex disorder. The objective of this article was to investigate whether RANKL is associated with neuroendocrine activation in 75 elderly males with mild to moderate congestive heart failure (CHF) and left ventricular ejection fraction <40%. The control group consisted of 20 healthy male volunteers with matching age and body mass index (BMI). Serum RANKL (sRANKL), OPG, NT-pro-BNP, adiponectin, leptin, clinical, and echocardiography parameters were evaluated. In comparison to the control group, the CHF patients showed significantly increased sRANKL levels [126.8 (122.6) vs. 47.8 (44.4) pg/ml, P < 0.0001]. There was a significant relative risk of systolic CHF in elderly males associated with increased sRANKL above the calculated cut-off of 83 pg/ml [OR = 10.286 (95%CI 3.079-34.356), P < 0.0001; RR = 3.600 (95%CI = 1.482-8.747)]. In the CHF patients, the log-transformed values of sRANKL levels correlated positively with the log-transformed values of the serum NT-pro-BNP and adiponectin levels (P = 0.004, r = 0.326 and P = 0.037, r = 0. 241, respectively), while inversely correlated with the BMI and creatinine clearance (P = 0.015, r = -0.281 and P = 0.042, r = -0.236, respectively). In multivariate regression model, sRANKL was a significant determinant of NT-pro-BNP independent of age, BMI and creatinine clearance (P = 0.002, R (2) = 0.546). In conclusion, our study suggests that in elderly males with systolic heart failure sRANKL was significantly associated with parameters of neuroendocrine activation such as NT-pro-BNP and adiponectin. Further studies are needed to elucidate the potential role of sRANKL in the complex pathogenesis of heart failure.
调节骨重塑的主要细胞因子是核因子-κB 配体受体激活剂（RANKL）及其诱饵受体骨保护素（OPG）。最近的数据也将 RANKL 和 OPG 与心血管疾病联系起来。NT-pro-BNP 和脂联素是心力衰竭的既定生物标志物，反映了这种多因素疾病中的神经内分泌激活。本文的目的是研究在 75 名年龄在 65 岁以上、射血分数<40%的轻中度充血性心力衰竭（CHF）男性中，RANKL 是否与神经内分泌激活有关。对照组由 20 名年龄和体重指数（BMI）相匹配的健康男性志愿者组成。评估血清 RANKL（sRANKL）、OPG、NT-pro-BNP、脂联素、瘦素、临床和超声心动图参数。与对照组相比，CHF 患者的 sRANKL 水平明显升高[126.8（122.6）比 47.8（44.4）pg/ml，P<0.0001]。在年龄较大的男性中，与计算出的 83pg/ml 以上的 sRANKL 截断值相比，与收缩性 CHF 相关的 sRANKL 升高的相对风险显著增加[OR=10.286（95%CI 3.079-34.356），P<0.0001；RR=3.600（95%CI=1.482-8.747）]。在 CHF 患者中，sRANKL 水平的对数与血清 NT-pro-BNP 和脂联素水平的对数呈正相关（P=0.004，r=0.326 和 P=0.037，r=0.241），而与 BMI 和肌酐清除率呈负相关（P=0.015，r=-0.281 和 P=0.042，r=-0.236）。在多元回归模型中，sRANKL 是 NT-pro-BNP 的一个重要决定因素，独立于年龄、BMI 和肌酐清除率（P=0.002，R（2）=0.546）。总之，我们的研究表明，在患有收缩性心力衰竭的老年男性中，sRANKL 与神经内分泌激活的参数（如 NT-pro-BNP 和脂联素）显著相关。需要进一步的研究来阐明 sRANKL 在心力衰竭复杂发病机制中的潜在作用。
