Barska Katarzyna, Kwiatkowska Wiesława, Knysz Brygida, Arczyńska Katarzyna, Karczewski Maciej, Witkiewicz Wojciech
Wrovasc-Integrated Cardiovascular Centre, Regional Specialist Hospital, Research and Development Center in Wroclaw, Wroclaw, Poland.
Department of Angiology, Regional Specialist Hospital, Research and Development Center in Wroclaw, Wroclaw, Poland.
PLoS One. 2017 Jul 27;12(7):e0181533. doi: 10.1371/journal.pone.0181533. eCollection 2017.
HIV infection is associated with an increased risk of cardiovascular disease in connection with atherosclerosis and thromboembolic complications. The pathogenesis of atherosclerosis is still unclear in this group of patients. Studies on pathogenesis of atherosclerosis in the general population emphasize the role of the extrinsic pathway of blood coagulation, particularly the tissue factor (TF) and tissue factor pathway inhibitor (TFPI). The effect of persistent activation of the immune system on enhanced expression of TF on the surface of monocytes in subjects infected with HIV is known to be correlated with the level of HIV RNA in blood serum.
The aim of this study was to evaluate the concentration of TF and its inhibitor TFPI in blood plasma, the impact of traditional and non-traditional cardiovascular risk factors on their concentration and the impact of both markers of haemostasis on the severity of subclinical atherosclerosis as assessed by the intima-media measurement of the carotid artery in HIV infected patients.
The study included 121 HIV-infected people with known clinical, immunological and virological status. The control group consisted of 42 healthy individuals, selected in terms of age and sex.
Higher concentrations of TF occurred in HIV-infected patients with a low current plasma HIV RNA level, nadir CD4+ T-cell count and longer duration of cumulative antiretroviral treatment. In multivariate analysis, it was the length of cumulative NRTI treatment that impacted on the concentration of TF. The determinants of cardiovascular disease (CVD) risk factors and inflammatory markers did not show any effect on the concentrations of TF. The TFPI level in HIV-infected patients was significantly higher than in the control group and was negatively correlated with the current level of HIV RNA and nadir CD4+ T-cell count, being higher in patients subjected to antiretroviral treatment. It was shown that the higher the cardiovascular risk and the higher the levels of total cholesterol, low-density lipoprotein cholesterol (LDL) and non-high-density lipoprotein cholesterol (non-HDL), the higher the concentrations of TFPI observed. The levels of TF and TFPI were positively correlated with carotid intima media thickness (cIMT); in the multivariate analysis, TF, non-HDL cholesterol and lifetime smoking (pack-years) independently affected the growth of cIMT. A similar effect on cIMT was demonstrated by TFPI.
HIV感染与动脉粥样硬化和血栓栓塞并发症相关的心血管疾病风险增加有关。在这组患者中，动脉粥样硬化的发病机制仍不清楚。对普通人群动脉粥样硬化发病机制的研究强调了凝血外源性途径的作用，特别是组织因子（TF）和组织因子途径抑制剂（TFPI）。已知HIV感染患者免疫系统的持续激活对单核细胞表面TF表达增强的影响与血清中HIV RNA水平相关。
本研究的目的是评估血浆中TF及其抑制剂TFPI的浓度，传统和非传统心血管危险因素对其浓度的影响，以及通过HIV感染患者颈动脉内膜中层测量评估的两种止血标志物对亚临床动脉粥样硬化严重程度的影响。
该研究纳入了121名已知临床、免疫和病毒学状况的HIV感染者。对照组由42名按年龄和性别选择的健康个体组成。
血浆HIV RNA水平低、CD4 + T细胞计数最低点低且累积抗逆转录病毒治疗持续时间长的HIV感染患者中TF浓度较高。在多变量分析中，影响TF浓度的是累积核苷类逆转录酶抑制剂（NRTI）治疗的时长。心血管疾病（CVD）危险因素和炎症标志物的决定因素对TF浓度没有任何影响。HIV感染患者的TFPI水平显著高于对照组，并且与当前HIV RNA水平和CD4 + T细胞计数最低点呈负相关，接受抗逆转录病毒治疗的患者中该水平更高。结果表明，心血管风险越高，总胆固醇、低密度脂蛋白胆固醇（LDL）和非高密度脂蛋白胆固醇（非HDL）水平越高，观察到的TFPI浓度就越高。TF和TFPI水平与颈动脉内膜中层厚度（cIMT）呈正相关；在多变量分析中，TF、非HDL胆固醇和终生吸烟（包年数）独立影响cIMT的增长。TFPI对cIMT也有类似影响。
