Serum Alkaline Phosphatase and Risk of Incident Cardiovascular Disease: Interrelationship with High Sensitivity C-Reactive Protein
Serum Alkaline Phosphatase and Risk of Incident Cardiovascular Disease: Interrelationship with High Sensitivity C-Reactive Protein
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DOI：
10.1371/journal.pone.0132822
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发表时间：
2015-07-13
期刊：
影响因子：
3.7
通讯作者：
Dullaart, Robin P. F.
中科院分区：
文献类型：
--
作者：
Kunutsor, Setor K.;Bakker, Stephan J. L.;Dullaart, Robin P. F.
研究背景碱性磷酸酶（ALP）与心血管疾病（CVD）的发病风险相关，但这种相关性的一些重要方面，如形态和独立于已确定的危险因素等，还没有被详细描述。我们评估了碱性磷酸酶与心血管疾病风险的关联，并确定其效用为CVD的风险prediction.MethodsAlkaline磷酸酶活性进行了测量基线在PREVEND前瞻性队列，涉及6,974名参与者年龄在28-75岁，没有预先存在的CVD。风险比（95%的置信区间[ CI]）和风险歧视和重新分类的措施进行了assessed.ResultsDuring一个中位数为10.5年的随访，737名参与者发展CVD。血清ALP与几种CVD危险标志物相关，其中年龄（r = 0.30; P < 0.001）、γ-谷氨酰转移酶（r = 0.26; P < 0.001）和C-反应蛋白（CRP）（r = 0.25; P < 0.001）相关性最强。碱性磷酸酶与心血管疾病风险之间存在非线性的“J”型关系。在校正常规危险因素的分析中，ALP值最高五分位数与最低五分位数1-4的比较中，CVD的风险比（95%CI）为1.34（1.14 - 1.56; P< 0.001），在额外校正潜在混杂因素后仍为1.33（1.13 - 1.55; P< 0.001）。然而，在调整CRP 1.24后，这种相关性有所减弱（1.05至1.45; P= 0.009）。除了ALP的信息，CVD风险预测模型包含已建立的风险因素没有改善C-指数或净classification.ConclusionsAvailable证据表明ALP活性和CVD风险之间的非线性关联，这是部分依赖于CRP。考虑到传统的
BackgroundAlkaline phosphatase (ALP) has been suggested to be associated with cardiovascular disease (CVD) risk, however, important aspects of the association, such as shape and independence from established risk factors, have yet to be characterized in detail. We assessed the association of ALP with CVD risk and determined its utility for CVD risk prediction.MethodsAlkaline phosphatase activity was measured at baseline in the PREVEND prospective cohort involving 6,974 participants aged 28-75 years without pre-existing CVD. Hazard ratios (95% confidence intervals [ CI]) and measures of risk discrimination and reclassification were assessed.ResultsDuring a median follow-up of 10.5 years, 737 participants developed CVD. Serum ALP was correlated with several risk markers for CVD, with strongest correlations for age (r = 0.30; P < 0.001), gamma-glutamyltransferase (r = 0.26; P < 0.001), and C-reactive protein (CRP) (r = 0.25; P < 0.001). There was a non-linear "J-shaped" relationship between ALP and CVD risk. In analyses adjusted for conventional risk factors, the hazard ratio (95% CI) for CVD in a comparison of the top quintile versus bottom quintiles 1-4 of ALP values was 1.34 (1.14 to 1.56; P< 0.001), which persisted after additional adjustment for potential confounders 1.33 (1.13 to 1.55; P< 0.001). However, the association was somewhat attenuated after adjustment for CRP 1.24 (1.05 to 1.45; P= 0.009). Addition of information on ALP to a CVD risk prediction model containing established risk factors did not improve the C-index or net reclassification.ConclusionsAvailable evidence suggests a non-linear association between ALP activity and CVD risk, which is partly dependent on CRP. Taking account of conventional