Dysangco Andrew, Liu Ziyue, Stein James H, Dubé Michael P, Gupta Samir K
Division of Infectious Diseases, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
Department of Biostatistics, Indiana University School of Medicine and School of Public Health, Indianapolis, Indiana, United States of America.
PLoS One. 2017 Aug 17;12(8):e0183511. doi: 10.1371/journal.pone.0183511. eCollection 2017.
HIV-infected patients have an increased risk of cardiovascular disease (CVD). Impaired endothelial function is an early risk factor for CVD in the general population. It is presumed that HIV infection is associated with impaired endothelial function, but results have been inconsistent.
Our objectives were to determine the relationships between HIV infection, virologic suppression with antiretroviral therapy (ART), in vivo measures of conduit artery and microvascular endothelial function, and circulating biomarkers of pathways associated with CVD.
We performed a cross-sectional analysis of three prospectively enrolled groups from a single center: 28 were HIV-infected and virologically-suppressed on a regimen of FTC/TDF/EFV (HIV+ART+), 44 were HIV-infected but not on ART (HIV+ART-), and 39 were HIV-uninfected healthy volunteers (HIV-) matched to the HIV+ART- group for age, sex, smoking status, and height. None had diabetes, uncontrolled hypertension, known CVD, or other pro-inflammatory condition. Flow mediated dilation (FMD), nitroglycerin-mediated dilation (NTGMD), reactive hyperemia velocity time integral (RHVTI), and FMD/RHVTI of the brachial artery were measured, as well as circulating biomarkers of systemic inflammation, metabolism, oxidative stress, and endothelial activation.
No significant differences were found amongst the three groups in FMD (P = 0.46), NTGMD (P = 0.42), RHVTI (P = 0.17), and FMD/RHVTI (P = 0.22) in unadjusted comparisons. Adjusted ANOVA models which included brachial artery diameter, demographics, and conventional CVD risk factors did not appreciably change these findings. In pairwise comparisons, the HIV+ART- group had significantly higher soluble tumor necrosis factor receptor II, soluble CD163, β-2 microglobulin, interferon-γ- induced protein-10, tissue inhibitor of metalloproteinase-1, and vascular cell adhesion molecule-1 compared to the other two groups (all p<0.05). Correlates of endothelial function differed between study groups.
Although untreated HIV infection was associated with elevated levels of several biomarkers of inflammation and endothelial activation, we were unable to demonstrate differences in measures of conduit artery and microvascular endothelial function in this study population.
HIV感染患者患心血管疾病（CVD）的风险增加。内皮功能受损是普通人群中CVD的早期危险因素。据推测，HIV感染与内皮功能受损有关，但结果并不一致。
我们的目的是确定HIV感染、抗逆转录病毒疗法（ART）的病毒学抑制、 conduit动脉和微血管内皮功能的体内测量以及与CVD相关途径的循环生物标志物之间的关系。
我们对来自单一中心的三个前瞻性入组组进行了横断面分析：28例HIV感染患者接受FTC/TDF/EFV方案治疗且病毒学抑制（HIV+ART+），44例HIV感染但未接受ART治疗（HIV+ART-），39例未感染HIV的健康志愿者（HIV-），在年龄、性别、吸烟状况和身高方面与HIV+ART-组匹配。所有人均无糖尿病、未控制的高血压、已知的CVD或其他促炎病症。测量肱动脉的血流介导的扩张（FMD）、硝酸甘油介导的扩张（NTGMD）、反应性充血速度时间积分（RHVTI）和FMD/RHVTI，以及全身炎症、代谢、氧化应激和内皮激活的循环生物标志物。
在未调整的比较中，三组在FMD（P = 0.46）、NTGMD（P = 0.42）、RHVTI（P = 0.17）和FMD/RHVTI（P = 0.22）方面未发现显著差异。纳入肱动脉直径、人口统计学和传统CVD危险因素的调整后方差分析模型并未明显改变这些结果。在两两比较中，与其他两组相比，HIV+ART-组的可溶性肿瘤坏死因子受体II、可溶性CD163、β-2微球蛋白、干扰素-γ诱导蛋白-10、金属蛋白酶组织抑制剂-1和血管细胞粘附分子-1显著更高（所有p<0.05）。研究组之间内皮功能的相关因素有所不同。
虽然未经治疗的HIV感染与多种炎症和内皮激活生物标志物水平升高有关，但在本研究人群中，我们未能证明conduit动脉和微血管内皮功能测量存在差异。
