高血压伴肺动脉高压中二甲基精氨酸二甲氨基水解酶-1和精氨酸代谢失调的研究

Metabolism disorder of DDAH1 and ADMA in patients with hypertension accompanied by pulmonary arterial hypertension

目的探究血浆二甲基精氨酸二甲氨基水解酶-1(DDAH1)和非对称二甲基精氨酸(ADMA)在高血压伴肺动脉高压患者体内的水平变化及临床价值。方法回顾性分析2016年3月～2017年9月于湖北恩施土家族苗族自治州中心医院心血管内科收治的高血压伴肺动脉高压患者72例、单纯肺动脉高压患者43例,同期选取前来心内科就诊的单纯高血压患者80例,健康体检者78例。采用酶联免疫吸附法(ELISA)检测每组对象血浆ADMA和DDAH1水平。采用one-way ANOVA分析DDAH1和ADMA在各组中水平,采用受试者工作特征曲线(ROC)分析ADMA和DDAH1在诊断高血压伴肺动脉高压时的灵敏度和特异性,采用Logistic回归分析计算血浆ADMA和DDAH1水平预测高血压伴肺动脉高压的风险比(OR)及其95%置信区间(95%CI)。结果高血压伴肺动脉高压组和单纯高血压组ADMA水平显著高于单纯肺动脉高压组和健康组,且高血压伴肺动脉高压组ADMA水平显著高于单纯高血压组(P<0.05);高血压伴肺动脉高压组DDAH1活性显著低于单纯高血压组、单纯肺动脉高压组和健康组(P<0.05),而单纯高血压组、单纯肺动脉高压组与健康组间DDAH1活性差异无统计学意义(P>0.05)。经Logistic回归分析,在校正了年龄、性别、体质指数(BMI)、糖尿病、吸烟及血脂水平后,血浆高ADMA水平(OR=2.32,95%CI:1.76～3.14,P<0.001)和低DDAH1活性(OR=0.61,95%CI:0.13～0.87,P<0.001)仍与高血压伴肺动脉高压的发生相关。经ROC曲线分析,联合血浆ADMA与DDAH1区分高血压伴肺动脉高压组和非高血压伴肺动脉高压组(单纯高血压组、单纯肺动脉高压组及健康组)的AUC为0.924(95%CI:0.868～0.979,P<0.001),灵敏度85.5%,特异度98.6%。结论血浆ADMA与DDAH1水平可能是高血压伴肺动脉高压早期诊断的潜在标志物。

Objective To study the changes and clinical value of plasma dimethylarginine dimethylaminohydrola-1(DDAH1)and asymmetric dimethylargini(ADMA)in patients with hypertension accompanied by pulmonary arterial hypertension(PAH).Methods The patients with hypertension accompanied by PAH(n=72,hypertension+PAH group),patients with only PAH(n=43,PAH group),patients with only hypertension(n=80,hypertension group)and healthy controls(n=78,healthy group)were chosen from Department of Cardiovascular Medicine of Central Hospital of Enshi Tujia and Miao Autonomous Prefecture in Hubei Province from Mar.2016to Sept.2017.The levels of plasma ADMA and DDAH1were detected by using enzyme-linked immunosorbent assay(ELISA)in all groups.The levels of plasma ADMA and DDAH1were analyzed by using one-way ANOVA in all groups,and sensitivity and specificity of ADMA and DDAH1in diagnosis of hypertension accompanied by PAH were analyzed by using receiver operating characteristic curve(ROC).The odds ratio(OR)and95%confidence interval(95%CI)were calculated by using Logistic regression analysis in predicting risk of hypertension accompanied by PAH based on levels of plasma ADMA and DDAH1.Results The level of ADMA was significantly higher in hypertension+PAH group and hypertension group than that in PAH group and healthy group,and significantly higher in hypertension+PAH group than that in hypertension group(P<0.05).The activity of DDAH1was significantly lower in hypertension+PAH group than that in hypertension group,PAH group and healthy group(P<0.05).The difference in activity of DDAH1had no statistical significance among hypertension group,PAH group and healthy group(P>0.05).The results of Logistic regression analysis showed that,after correcting age,sex,BMI,diabetes,smoking and blood fat level,the higher level of ADMA(OR=2.32,95%CI:1.76~3.14,P<0.001)and lower activity of DDAH1(OR=0.61,95%CI:0.13~0.87,P<0.001)were still correlated to the occurrence of hypertension accompanied by PAH.The results of ROC analysis showed that AUC of combined ADMA and DDAH1was0.924(95%CI:0.868~0.979,P<0.001),sensitivity was85.5%and specificity was98.6%in differentiating hypertension+PAH group and non-hypertension+PAH group(hypertension group,PAH group and healthy group).Conclusion The levels of plasma ADMA and DDAH1may by latent biomarkers for early diagnosis of hypertension accompanied by PAH.