三甲胺氧化物与冠心病合并2型糖尿病患者冠状动脉病变情况的相关性分析

Plasm trimethylamine-N-oxide level and association with lesion severity in coronary heart disease patients with type 2 diabetes mellitus

目的探讨三甲胺氧化物(TMAO)水平与冠心病合并2型糖尿病患者冠状动脉病变程度的相关性。方法该研究为横断面研究。连续收集2016年11月至2018年1月因疑诊冠心病于北京医院心内科导管室行冠状动脉造影的住院患者,根据是否合并糖尿病分为冠心病合并2型糖尿病组(CHD-DM组)和冠心病不合并糖尿病组(CHD-nDM组)。收集入选患者的一般临床资料。通过液相色谱串联质谱(LC-MS/MS)法检测患者血清TMAO水平。记录入选患者的冠状动脉病变支数并进行Gensini评分。采用Spearman相关分析评估TMAO与冠状动脉病变支数及Gensini评分的相关性。采用多因素logistic回归模型分析TMAO与高Gensini评分的相关性。结果研究共入组患者590例,其中CHD-DM组238例,CHD-nDM组352例。与CHD-nDM组比较,CHD-DM组患者年龄较大、体重指数较高、收缩压较高,具有高血压病史及他汀类药物应用史的患者比例较高(P均<0.05)。CHD-DM组多支病变(2支及以上)患者比例高于CHD-nDM组(P<0.001)。CHD-DM组患者Gensini评分高于CHD-nDM组(P<0.05)。与CHD-nDM组比较,CHD-DM组患者空腹血糖及糖化血红蛋白水平均较高(P均<0.001),低密度脂蛋白胆固醇水平较低(P<0.05),尿素水平较高(P<0.05),血红蛋白水平较低(P<0.05)。CHD-DM组患者血清代谢物TMAO水平为272.0(136.2,456.0)μg/L高于CHD-nDM组的171.1(99.3,289.6)μg/L(P<0.001)。Spearman相关分析结果显示,TMAO水平与冠心病患者冠状动脉病变支数及Gensini评分呈正相关(r值分别为0.178、0.189,P均<0.001),与年龄、血糖水平呈正相关(r值分别为0.260、0.111,P分别<0.001和0.01)。在校正了年龄和性别后,TMAO水平仍与冠心病患者冠状动脉病变支数及Gensini评分呈正相关(r值分别为0.101、0.230,P分别为0.02和<0.001),与血糖水平呈正相关(r=0.131,P<0.01)。校正了年龄、性别、体重指数、高血压史、血脂异常史、吸烟史、他汀类药物应用史以及低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、总胆固醇、甘油三酯、空腹血糖水平后,多因素logistic回归分析结果显示,TMAO水平仍与冠心病合并2型糖尿病患者Gensini评分呈正相关(OR=2.25,95%CI 1.16-4.38,P=0.017),但与冠心病不合并2型糖尿病患者Gensini评分无显著相关性(OR=1.29,95%CI 0.72-2.31,P=0.386)。结论冠心病合并2型糖尿病患者血TMAO水平明显升高,且其与此类患者冠状动脉病变程度独立相关。

Objective To investigate the association between trimethylamine-N-oxide(TMAO)and the degree of coronary atherosclerosis in coronary heart diseases(CHD)patients with type 2 diabetes mellitus.Methods Consecutive patients,who underwent coronary angiography due to suspected CHD in Beijing Hospital from November 2016 to January 2018,were screened in this cross-sectional study.According to blood glucose level,previous medical history and coronary angiography results,they were divided into CHD without type2 diabetes mellitus(CHD-nDM)group and CHD with type2 diabetes mellitus(CHD-DM)group.Plasma TMAO levels in each group were measured by LC-MS/MS.Spearman correlation analysis was used to evaluate the correlation between TMAO and the number of diseased vessels and Gensini scores.Multivariate logistic regression was used to analyze the correlation between TMAO and high Gensini scores.Results A total of 590 patients were enrolled in the study,including 238 patients in CHD-DM group and 352 patients in CHD-nDM group.Patients were older,body mass index,blood pressure level,prevalence of history of hypertension and statins use were higher in CHD-DM group than in CHD-nDM group(all P<0.05).The proportion of patients with multivessel disease(2 or more vessels)was also higher in CHD-DM group than in CHD-nDM group(P<0.001).Gensini score was higher in CHD-DM group than in CHD-nDM group(P<0.05).Fasting blood glucose,glycosylated hemoglobin and urea were significantly higher,while low-density lipoprotein cholesterol and hemoglobin were significantly lower in CHD-DM group than in CHD-nDM group(all P<0.05).The levels of TMAO was significantly higher in CHD-DM group than in CHD-nDM group(P<0.001).Spearman correlation analysis showed that TMAO was positively correlated with the number of diseased vessels,Gensini score,age and blood glucose level(r=0.178,0.189,0.260,0.111,respectively,all P<0.01).Multivariate logistic regression analysis showed that,TMAO level was still positively correlated with high Gensini score in CHD-DM group(OR=2.25,95%CI 1.16-4.38,P=0.017),but not in CHD-nDM group(OR=1.29,95%CI 0.72-2.31,P=0.386)after adjusting for age,sex,body mass index,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,total cholesterol,triglyceride,history of hypertension,hyperlipidemia,smoking and statin use.Conclusions In CHD patients with tupe 2 diabetes mellitus,the plasma TMAO level is significantly increased and is independent and positively correlated with the degree of coronary artery disease.