肌肉量降低对维持性血液透析患者冠状动脉钙化进展的影响

Effect of muscle mass reduction on the progression of coronary artery calcification in maintenance hemodialysis patients

目的评估维持性血液透析(maintenance hemodialysis,MHD)患者冠状动脉(冠脉)钙化程度和进展速度,探讨MHD患者冠脉钙化进展的危险因素。方法研究对象来自2013年1月1日至2017年12月31日在复旦大学附属华山医院接受MHD治疗的患者。该研究分为横断面研究及前瞻性队列研究2个部分。采用多层螺旋CT法检测冠脉钙化程度并计算冠脉钙化积分(coronary artery calcium score,CACS)。横断面研究纳入62例MHD患者,根据基线CACS将患者分为低钙化组(CACS<100)和高钙化组(CACS≥100),比较两组患者营养及骨矿物质代谢指标的差异。采用多元线性回归模型分析CACS与肌肉量及实验室指标的相关性。因6例患者失访,前瞻性队列研究入选56例定期随访的MHD患者,根据每年CACS增长速度将患者分为缓慢进展组(ΔCACS<100组)和快速进展组(ΔCACS≥100组)。采用Logistic回归分析法分析冠脉钙化进展的危险因素。采用Hosmer-Lemeshow拟合优度检验和受试者工作特征曲线评估多因素Logistic回归模型效能。结果横断面研究中,62例患者年龄为(62.34±10.82)岁,中位透析龄为78(39,139)个月。33例男性患者中,与低钙化组(n=7)比较,高钙化组(n=26)年龄较大(t=-2.281,P=0.030),血三酰甘油较高(Z=-1.985,P=0.047),两组肌肉量的差异无统计学意义;29例女性患者中,与低钙化组(n=14)比较,高钙化组(n=15)肌肉量/身高^(2)(t=-2.600,P=0.015)和血钙(t=-2.641,P=0.014)均较高,血红蛋白较低(t=2.531,P=0.018),两组肌肉量的差异无统计学意义。多元线性回归分析结果显示,超敏C反应蛋白(β=0.425,P=0.022)与男性患者基线CACS独立相关,肌肉量/细胞外液量(β=-0.580,P=0.001)与女性患者基线CACS独立相关。前瞻性队列研究中,56例患者年龄为(59.82±11.14)岁,中位透析龄为82(40,146)个月。缓慢进展组(n=22)和快速进展组(n=34)间全因死亡率差异无统计学意义,但快速进展组发生心血管事件的比例显著高于缓慢进展组(P=0.017)。相比缓慢进展组,快速进展组男性比例较高(χ^(2)=4.791,P=0.029),年龄较大(Z=-2.131,P=0.038),基线肌肉量/细胞外液量(Z=2.482,P=0.016)和高密度脂蛋白胆固醇(t=2.133,P=0.042)较低,肌肉量减少速度即(Δ肌肉量·身高^(-2)·年^(-1))较快(Z=-2.282,P=0.023)。多因素Logistic回归分析结果显示,肌肉量减少速度(OR=0.089,95%CI 0.010~0.792,P=0.030)和基线CACS(OR=1.003,95%CI 1.000~1.005,P=0.021)是MHD患者冠脉钙化进展的独立相关因素。结论基线CACS较高和肌肉量下降速度较快是MHD患者冠脉钙化进展的独立危险因素。

Objective To evaluate the extent and progression of coronary artery calcification in maintenance hemodialysis(MHD)patients,and to explore the risk factors of rapid progression of coronary artery calcification in MHD patients.Methods The patients who underwent MHD in the Huashan Hospital affiliated to Fudan University from January 1,2013 to December 31,2017 were enrolled.This study included cross-sectional study and prospective cohort study.Multi-slice spiral computed tomography was used to measure coronary artery calcification,and coronary artery calcium score(CACS)was calculated.In the cross-sectional study,62 MHD patients were enrolled.According to baseline CACS,the patients were divided into low calcification group(CACS<100)and high calcification group(CACS≥100).The nutritional and bone mineral metabolism indexes were compared between the two groups.Multiple linear regression analysis was used to analyze the correlation between CACS and muscle mass and laboratory indicators.Since 6 patients were lost to follow-up,56 MHD patients who were followed-up regularly were enrolled in the prospective cohort study.According to the progression of CACS,the patients were divided into slow progression group(ΔCACS/year<100)and rapid progression group(ΔCACS/year≥100).Logistic regression equation was used to analyze the risk factors of coronary calcification progression.Hosmer-Lemeshow goodness of fit test and receiver operating characteristic curve were used to evaluate the performance of multivariate logistic regression model.Results In the cross-sectional study,the age of 62 patients was(62.34±10.82)years old,and the median dialysis age was 78(39,139)months.Among the 33 male patients,compared with the low calcification group(n=7),the high calcification group(n=26)had older age(t=-2.281,P=0.030)and higher blood triglyceride(Z=-1.985,P=0.047),and there was no statistically significant difference in muscle mass between the two groups;among the 29 female patients,the muscle mass/height^(2)(t=-2.600,P=0.015)and serum calcium(t=-2.641,P=0.014)in the high calcification group(n=15)were both higher than those in the low calcification group(n=14),and the hemoglobin level was lower(t=2.531,P=0.018),and the difference in muscle mass between the two groups was not statistically significant.High sensitivity C-reactive protein(β=0.425,P=0.022)was independently correlated with CACS in male patients,and muscle mass/extracellular water(β=-0.580,P=0.001)was independently correlated with CACS in female patients.In the prospective cohort study,the age of 56 patients was(59.82±11.14)years old,and the median dialysis age was 82(40,146)months.There was no significant difference in all-cause mortality between slow progression group(n=22)and rapid progression group(n=34),but the proportion of cardiovascular events in rapid progression group was significantly higher than that in slow progression group(P=0.017).Compared with the slow progression group,the rapid progression group had higher proportion of males(χ^(2)=4.791,P=0.029),older age(Z=-2.131,P=0.038),lower baseline muscle mass/extracellular water(Z=2.482,P=0.016)and high-density lipoprotein cholesterol(t=2.133,P=0.042),and faster rate of muscle mass loss(Δmuscle mass·height^(-2)·year^(-1))(Z=-2.282,P=0.023).Multivariate logistic regression analysis results showed that muscle mass loss(OR=0.089,95%CI 0.010-0.792,P=0.030)and baseline CACS(OR=1.003,95%CI 1.000-1.005,P=0.021)were influencing factors for progression of coronary artery calcification in MHD patients.Conclusion Increasing baseline CACS and rapid reduction in muscle mass are risk factors for the progression of coronary artery calcification in MHD patients.