Haissman Judith M, Knudsen Andreas, Hoel Hedda, Kjær Andreas, Kristoffersen Ulrik S, Berge Rolf K, Katzenstein Terese L, Svardal Asbjørn, Ueland Thor, Aukrust Pål, Lebech Anne-Mette, Nielsen Susanne D, Trøseid Marius
*Department of Infectious Diseases; †Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen; ‡Department of Infectious Diseases, Hvidovre University Hospital, Copenhagen, Denmark; §Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet; ‖Department of Clinical Science, University of Bergen; ¶Department of Heart Disease, Haukeland University Hospital; #Research Institute of Internal Medicine; **Institute of Clinical Medicine; ††K.G. Jebsen Inflammatory Research Center; and ‡‡Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway.
J Acquir Immune Defic Syndr. 2016 Feb 1;71(2):130-6. doi: 10.1097/QAI.0000000000000843.
HIV infection is associated with increased risk of coronary heart disease beyond that explained by traditional risk factors, and altered gut microbiota has been proposed as a potential trigger. Trimethylamine-N-oxide (TMAO) is a proatherogenic substance formed in the liver from trimethylamine, exclusively generated by gut microbiota from dietary phosphatidylcholine. We aimed to investigate whether TMAO is associated with subclinical and clinical coronary heart disease in HIV infection.
Two previously described cohorts were examined as follows: (1) cross-sectional cohort of HIV-infected persons and uninfected controls with known atherosclerotic plaque burden as assessed by myocardial perfusion scintigraphy, coronary artery calcium score, and intima-media thickness and (2) nested case-control study of HIV-infected persons with first-time myocardial infarction (MI) compared with HIV-infected persons without MI, assessed at 4 time points from before initiation of antiretroviral therapy (ART) to last sample before the case's MI (median: 51, range: 0-239 days).
There was no difference in plasma TMAO when comparing HIV-infected persons and uninfected controls. TMAO was elevated in HIV-infected persons with myocardial perfusion defects but was not associated with coronary artery calcium score, intima media thickness, or Framingham risk score. In the nested case control study, plasma TMAO was not associated with first-time MI. However, TMAO increased after ART introduction and was associated with the use of protease inhibitors in both cohorts.
TMAO was elevated in HIV-infected persons with myocardial perfusion defects, but was not associated with first-time MI. Our data question TMAO as a useful biomarker of cardiovascular risk in HIV infection, at least in ART-treated individuals.
HIV感染与冠心病风险增加相关，这一风险超出了传统危险因素所能解释的范围，肠道微生物群的改变被认为是一个潜在触发因素。氧化三甲胺（TMAO）是一种促动脉粥样硬化物质，由肝脏中的三甲胺形成，而三甲胺仅由肠道微生物群从膳食磷脂酰胆碱产生。我们旨在研究TMAO是否与HIV感染中的亚临床和临床冠心病相关。
对两个先前描述的队列进行如下检查：（1）通过心肌灌注闪烁显像、冠状动脉钙化评分和内膜中层厚度评估，对已知动脉粥样硬化斑块负担的HIV感染者和未感染对照进行横断面队列研究；（2）对首次发生心肌梗死（MI）的HIV感染者与未发生MI的HIV感染者进行巢式病例对照研究，在从开始抗逆转录病毒治疗（ART）前到病例发生MI前的最后一次样本采集的4个时间点进行评估（中位数：51天，范围：0 - 239天）。
比较HIV感染者和未感染对照时，血浆TMAO无差异。有心肌灌注缺陷的HIV感染者中TMAO升高，但与冠状动脉钙化评分、内膜中层厚度或弗雷明汉风险评分无关。在巢式病例对照研究中，血浆TMAO与首次MI无关。然而，ART引入后TMAO升高，且在两个队列中均与蛋白酶抑制剂的使用有关。
有心肌灌注缺陷的HIV感染者中TMAO升高，但与首次MI无关。我们的数据对TMAO作为HIV感染中心血管风险的有用生物标志物提出了质疑，至少在接受ART治疗的个体中如此。
