慢性肾脏病患者血浆同型半胱氨酸水平与左心室肥厚的相关性

Association of serum homocysteine with left ventricular hypertrophy in chronic kidney disease patients

目的探讨慢性肾脏病（CKD）患者血浆同型半胱氨酸（Hcy）水平与左心室肥厚的相关性。方法回顾性分析2010年4月-2013年10月间在复旦大学附属中山医院住院治疗的1302例非透析CKD患者的临床资料，根据左心室是否肥厚将CKD患者分为左心室肥厚组（325例）和非左心室肥厚组（977例）。采用循环酶法测定所有患者的血浆Hcy水平，经超声心动图检查测量左心室舒张末内径（LVDd）、左心室收缩末内径（LVDs）、左心室后壁厚度（LVPwT）、室间隔厚度（IVST）和射血分数（EF）。采用Spearman相关性分析不同血浆Hcy水平患者的左心室结构和功能。分别采用二分类Logistic回归和线性回归筛选与左心室肥厚和左心室质量分数（LVMI）相关的临床因素。结果左心室肥厚组的男性患者构成比、估算的肾小球滤过率（eGFR）、EF、血红蛋白、总胆固醇和血清钙水平均显著低于非左心室肥厚组（P值分P〈O．01、0．05），年龄、体重、高血压患者构成比、糖尿病患者构成比、LVMI、血清磷、全段甲状旁腺激素（iPTH）和血浆Hcy水平均显著高于非左心室肥厚组（P值均〈O．01）。Spearman相关性分析结果显示，血浆Hcy水平与LVMI呈正相关（p=0．384，P〈0．001），与EF呈负相关（p=0．113，P〈0．001）；进一步分析结果显示，随着血浆Hcy水平四分位数升高，离心性和向心性肥厚的患者呈增多趋势，LVMI呈升高趋势，EF呈下降趋势。单因素Logistic回归分析显示，年龄（β=0．266）、体重（β=0．174）、高血压史（β=0．318）、糖尿病史（β=0．092）、血红蛋白（β=-0．284）、eGFR（β=-0．335）、总胆固醇（β=-0．100）、血清钙（β=-0．057）、血磷（β=-0．226）、iPTH（β=0．264）、血浆Hcy水平（β=0．248）均与LVMI相关（P值均〈O．01），年龄（OR=1．039，95％CI为1．030～1．047）、性别（OR=0．696，95％CI为0．571～0．896）、体重（OR=1．030，95％CI为1．018～1．041）、高血压史（OR=5．077，95％CI为3．435～7．505）、糖尿病史（OR=1．035，95％CI为1．026～1．045）、血红蛋白（OR=0．976，95％CI为0．970-0．982）、eGFR（OR=0．973，95％CI为0．967～0．979）、总胆固醇（OR=0．883，95％CI为0．820～O．950）、血清钙（OR=0．365，95％CJ为0．172～0．773）、血磷（OR=5．089，95％CI为3．232～8．012）、iPTH（OR=1．005，95％CI为1．0041．007）、血浆Hcy水平（OR=1．055，95％CI为1．041～1．069）均与左心室肥厚相关（P值均〈O．01）。进一步的多因素回归分析显示，血浆Hcy水平是CKD患者LVMI增高和左心室肥厚的独立危险因素，CKD患者血浆Hcy水平每升高1μmol／L，LVMI升高0．110g／m。（95％CI为0．052-0．153，P〈0．001），左心室肥厚风险升高至1．024倍（95％CI为1．0081．041，P〈0．001）。结论高同型半胱氨酸血症是CKD患者左心室肥厚的独立危险因素。

Objective To analyze the relationship between plasma homocysteine （Hcy） level and left ventricular hypertrophy （LVH） in patients with chronic kidney disease （CKD）. Methods Clinical data of 1 302 pre-dialysis CKD patients admitted to Zhongshan Hospital from April 2010 to October 2013 were analyzed in this retrospective study. They were divided into LVH group （n = 325） and non-LVH group （n = 977）. Plasma Hcy was measured by circulating enzymatic method. Echocardiographic examination was performed to measure left ventricular end-diastolic dimension （LVDd）, left ventricular end systolic dimension （LVDs）, left ventricular posterior wall thickness （LVPWT）, interventricular septal thickness （IVST） and ejection fraction （EF）. Left ventricular structure and function was evaluated by Spearman correlation analysis. Binomial Logistic regression analysis and linear regression analysis were used to screen the clinical factors related to LVH and left ventricular mass index （LVMI）. Results The male ratio, estimateal glomerular filtration rate （eGFR）, EF, hemoglobin, total cholesterol and serum calcium in LVH group were significantly lower than those in non-LVH group （P〈 0.01 or 0.05）, while the age, weight, composition ratio of hypertension patients, composition ratio of diabetic patients, LVMI, serum phosphorus, immunoreative parathyroid hormone （iPTH） and Hcy in LVH group were significantly higher than those in non-LVH grouP （all P〈 0.01）. Spearman correlation analysis showed that Hcy was positively related to LVMI （p = 0. 384, P〈0. 001）, while negatively related to EF （p = -0. 113, P〈 0. 001）. With the increase of Hcy levels, the proportion of eccentric and concentric hypertrophy and the level of LVMI showed an increasing trend, while EF decreased gradually. In univariate Logistic regression analysis, age （β = 0. 266）, body weight （β = 0. 174）, hypertension （β = 0. 318）, diabetes mellitus （β = 0. 092）, hemoglobin （β = - 0. 284）, eGFR （β = - 0. 335）, total cholesterol （β= - 0. 100）, serum calcium （β = -0. 057）, serum phosphate （β = 0.226）, iPTH （β= 0. 264） and Hcy （β = 0. 248） were significantly associated with LVMI （all P〈 0.01）. Meanwhile, age （OR = 1. 039, 95% CI= 1. 030- 1. 047）, gender （OR = 0. 696, 95% CI= 0. 571 - 0.896）, body weight （OR = 1. 030, 95%CI= 1. 018 - 1. 041）, hypertension （OR = 5. 077, 95% CI= 3. 435- 7. 505）, diabetes mellitus （OR = 1. 035, 95 % CI： 1. 026 - 1. 045）, hemoglobin （ OR = 0. 976, 95 % CI = 0.970-0.982）, eGFR （OR=0.973, 95%C1= 0.967-0.979）, total cholesterol （OR=0.883, 95% CI： 0.820- 0. 950）, serum calcium （ OR = 0. 365, 95 % CI; 0. 172 - 0. 773）, serum phosphate （ OR = 5. 089, 95 % CI = 3. 232 - 8.012）, iPTH （OR= 1.005, 95% CI= 1.004-1.007） andHcy （0R=1.055, 95% CI 1.041-1.069） were significantly correlated with LVH （all P〈0.01）. Multivariate regression analyses revealed Hcy was independently associated with LVMI and LVH, LVMI was increased by 0.110 g/rn27 （95 % CI： 0.052-0. 153, P〈0. 001） and the incidence of LVH was increased by 102.4% （95% CI= 1. 008- 1. 041, P〈0. 001） when the concentration of serum Hcy increased by 1 μmol/L. Conclusion Hyperhomocysteinemia is an independent risk factor of LVH in pre-dialysis CKD patients. （Shanghai Med J, 2016, 39= 407-412）