Mafune Aki, Iwamoto Takeo, Tsutsumi Yusuke, Nakashima Akio, Yamamoto Izumi, Yokoyama Keitaro, Yokoo Takashi, Urashima Mitsuyoshi
Division of Molecular Epidemiology, Jikei University School of Medicine, Tokyo, Japan.
Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Clin Exp Nephrol. 2016 Oct;20(5):731-739. doi: 10.1007/s10157-015-1207-y. Epub 2015 Dec 16.
Trimethylamine-N-oxide (TMAO) is a metabolite of phosphatidylcholine generated by gut microbiota and liver enzymes, and has recently been recognized as contributing to atherosclerosis. Elevated serum TMAO levels have been shown to increase the risk of cardiovascular disease (sudden death, myocardial infarction, or stroke) in patients undergoing elective coronary angiography. We aimed to clarify whether TMAO levels are associated with the number of infarcted coronary arteries as a measure of the severity of atherosclerosis, with adjustment using a priori-defined covariates such as kidney function.
By conducting a cross-sectional study of 227 patients who underwent cardiovascular surgery for coronary artery disease, valvular heart disease, or aortic disease, the association between serum TMAO levels as measured by HPLC-APCI-MS/MS and the number of infarcted coronary arteries was evaluated using ordered logistic regression models with adjustment of 10 covariates, including chronic kidney disease (CKD) stage. Unadjusted and adjusted odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were determined.
Significantly higher TMAO levels were observed in advanced-stage CKD (p ≤ 0.001). In fully adjusted models with the 10 covariates, a significantly increased number of infarcted coronary arteries was identified in the highest quartile and quintile of TMAO compared to the lowest quartile (OR 11.9; 95 % CI 3.88-36.7, p ≤ 0.001) and quintile (OR 14.1; 95 % CI 3.88-51.2; p ≤ 0.001), respectively, independent of dyslipidemia.
Higher serum TMAO levels may be associated with advanced CKD stages and with an increased number of infarcted coronary arteries in patients who undergo cardiovascular surgery.
氧化三甲胺(TMAO)是由肠道微生物群和肝脏酶产生的磷脂酰胆碱代谢产物,最近被认为与动脉粥样硬化有关。在接受选择性冠状动脉造影的患者中,血清TMAO水平升高已被证明会增加心血管疾病(猝死、心肌梗死或中风)的风险。我们旨在明确TMAO水平是否与梗死冠状动脉数量相关,以此作为动脉粥样硬化严重程度的指标,并使用诸如肾功能等预先定义的协变量进行校正。
通过对227例因冠状动脉疾病、心脏瓣膜病或主动脉疾病接受心血管手术的患者进行横断面研究,采用有序逻辑回归模型评估经高效液相色谱-大气压化学电离质谱/质谱法测定的血清TMAO水平与梗死冠状动脉数量之间的关联,并对包括慢性肾脏病(CKD)分期在内的10个协变量进行校正。确定未校正和校正后的比值比(OR)及95%置信区间(95%CI)。
在晚期CKD患者中观察到TMAO水平显著更高(p≤0.001)。在对10个协变量进行完全校正的模型中,与最低四分位数相比,TMAO最高四分位数(OR 11.9;95%CI 3.88-36.7,p≤0.001)和五分位数(OR 14.1;95%CI 3.88-51.2;p≤0.001)的梗死冠状动脉数量显著增加,且与血脂异常无关。
较高的血清TMAO水平可能与晚期CKD分期以及接受心血管手术患者梗死冠状动脉数量增加有关。