摘要
Objective:We investigated whether disturbance of calcium and phosphate metabolism is associated with the presence and severity of calcific aortic valve disease (CAVD) in patients with normal or mildly impaired renal function. Methods:We measured serum levels of calcium, phosphate, alkaline phosphatase (AKP), intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25-OHD), and biomarkers of bone turnover in 260 consecutive patients with normal or mildly impaired renal function and aortic valve sclerosis (AVSc) (n=164) or stenosis (AVS) (n=96) and in 164 age- and gender-matched controls. Logistic regression models were used to determine the association of mineral metabolism parameters with the presence and severity of CAVD. Results:Stepwise increases were observed in serum levels of calcium, phosphate, AKP, and iPTH from the control group to patients with AVS, and with reverse changes for 25-OHD levels (al P〈0.001). Similarly, osteocalcin, procol agen I N-terminal peptide, andβ-isomerized type I col agen C-telopeptide breakdown products were significantly increased stepwise from the control group to patients with AVS (al P〈0.001). In patients with AVS, serum levels of iPTH were positively, in contrast 25-OHD levels were negatively, related to trans-aortic peak flow velocity and mean pressure gradient. After adjusting for relevant confounding varia-bles, increased serum levels of calcium, phosphate, AKP, and iPTH and reduced serum levels of 25-OHD were in-dependently associated with the presence and severity of CAVD. Conclusions: This study suggests an association between mineral metabolism disturbance and the presence and severity of CAVD in patients with normal or mildly impaired renal function. Abnormal bone turnover may be a potential mechanism.
目的:探讨在肾功能正常或轻度受损(肾小球滤过率≥60 ml/(min·1.73 m2))人群中矿物质代谢紊乱与钙化性主动脉瓣疾病的发生和严重性是否相关。创新点:以具有代表性和临床价值的肾功能正常或轻度受损人群为研究对象,首次尝试通过骨转换生物标志物检测探讨钙化性主动脉瓣疾病的可能机制。方法:入选260例经超声心动图诊断钙化性主动脉瓣疾病患者(164例钙化性主动脉瓣硬化,96例钙化性主动脉瓣狭窄)和164例年龄及性别匹配对照组人群,检测矿物质代谢和骨转换生化标志物,应用多因素回归分析矿物质代谢与钙化性主动脉瓣疾病的发生和严重性的关系,并初步探讨可能机制。结果显示,从对照组到钙化性主动脉瓣硬化至狭窄患者,血钙、血磷、碱性磷酸酶和甲状旁腺素(i PTH)水平进行性升高,25羟-维生素D(25-OHD)水平进行性降低,各组间差异具有统计学显著性(P<0.001);同样,骨转换生化标志物骨钙素(BGP)、I型前胶原N端前肽(PINP)和β-胶原特殊序列(β-CTx)水平进行性升高,各组间差异具有统计学显著性(P<0.001)。在钙化性主动脉瓣狭窄患者中,i PTH水平与跨瓣峰值流速和平均跨瓣压差显著正相关,25-OHD则显著负相关。经校正相关因素后,多因素回归分析显示,血钙、血磷、碱性磷酸酶和i PTH水平升高及25-OHD水平下降和钙化性主动脉瓣疾病的发生和严重性密切相关。结论:矿物质代谢紊乱与钙化性主动脉瓣疾病的发生和严重性密切相关,异常骨转换可能是其发生机制。
基金
Project supported by the Science and Technology Commission of Shanghai Municipality(No.114119a8800),China