Perticone Francesco, Perticone Maria, Maio Raffaele, Sciacqua Angela, Andreucci Michele, Tripepi Giovanni, Corrao Salvatore, Mallamaci Francesca, Sesti Giorgio, Zoccali Carmine
Department of Medical and Surgical Sciences, Campus Universitario di Germaneto, V.le Europa, 88100 Catanzaro, Italy.
Hypertension. 2015 Oct;66(4):874-80. doi: 10.1161/HYPERTENSIONAHA.115.06117.
Tissue nonspecific alkaline phosphatase, promoting arterial calcification in experimental models, is a powerful predictor of total and cardiovascular mortality in general population and in patients with renal or cardiovascular diseases. For this study, to evaluate a possible correlation between serum alkaline phosphatase levels and endothelial function, assessed by strain gauge plethysmography, we enrolled 500 naïve hypertensives divided into increasing tertiles of alkaline phosphatase. The maximal response to acetylcholine was inversely related to alkaline phosphatase (r=−0.55; P<0.001), and this association was independent (r=−0.61; P<0.001) of demographic and classical risk factors, body mass index, estimated glomerular filtration rate, serum phosphorus and calcium, C-reactive protein, and albuminuria. At multiple logistic regression analysis, the risk of endothelial dysfunction was ≈3-fold higher in patients in the third tertile than that of patients in the first tertile. We also tested the combined role of alkaline phosphatase and serum phosphorus on endothelial function. The steepness of the alkaline phosphatase/vasodilating response to acetylcholine relationship was substantially attenuated (P<0.001) in patients with serum phosphorus above the median value when compared with patients with serum phosphorus below the median (−5.0% versus −10.2% per alkaline phosphatase unit, respectively), and this interaction remained highly significant (P<0.001) after adjustment of all the previously mentioned risk factors. Our data support a strong and significant inverse relationship between alkaline phosphatase and endothelium-dependent vasodilation, which was attenuated by relatively higher serum phosphorus levels.
组织非特异性碱性磷酸酶在实验模型中可促进动脉钙化，是普通人群以及患有肾脏或心血管疾病患者全因死亡率和心血管死亡率的有力预测指标。在本研究中，为了评估血清碱性磷酸酶水平与通过应变片体积描记法评估的内皮功能之间可能存在的相关性，我们纳入了500例初发高血压患者，并将其按照碱性磷酸酶水平升高分为三个三分位数组。乙酰胆碱的最大反应与碱性磷酸酶呈负相关（r = -0.55；P < 0.001），并且这种关联独立于人口统计学和经典危险因素、体重指数、估计肾小球滤过率、血清磷和钙、C反应蛋白以及蛋白尿（r = -0.61；P < 0.001）。在多因素逻辑回归分析中，处于第三个三分位数组的患者发生内皮功能障碍的风险比处于第一个三分位数组的患者高约3倍。我们还测试了碱性磷酸酶和血清磷对内皮功能的联合作用。与血清磷低于中位数的患者相比，血清磷高于中位数的患者中碱性磷酸酶/乙酰胆碱血管舒张反应关系的斜率显著降低（P < 0.001）（分别为每单位碱性磷酸酶-5.0% 与 -10.2%），并且在调整所有上述危险因素后，这种相互作用仍然高度显著（P < 0.001）。我们的数据支持碱性磷酸酶与内皮依赖性血管舒张之间存在强烈且显著的负相关关系，而相对较高的血清磷水平会减弱这种关系。
