Cardiovascular biomarkers in vertically HIV-infected children without metabolic abnormalities
Introduction
HIV infection is associated with vascular dysfunction and adverse cardiovascular outcomes, likely driven by up-regulation of inflammatory pathways, accumulation of classical cardiovascular risk factors and ART-related metabolic disturbances [1]. The scope of cardiovascular disease may become even greater in years to come in the special population of vertically HIV-infected subjects, with lifelong exposure to inflammation and metabolic abnormalities. Indeed, previous studies suggest that vertically HIV-infected adolescents already exhibit subclinical atherosclerosis [2], [3], [4].
Although extensively analyzed, the pathophysiology of atherosclerosis within HIV infection remains to be entirely elucidated. HIV-infection is characterized by increased concentrations of proinflammatory cytokines, such as C-reactive protein (CRP) and interleukin (IL)-6, even under viral suppression [5]. Importantly, some of these markers strongly predict cardiovascular disease and mortality [6], [7]. Soluble CD14 (sCD14), a marker of monocyte activation used as an indirect measure of microbial translocation, has been associated to disease progression and mortality, although its relation to endothelial dysfunction remains controversial [8], [9]. Most of the evidence in this field comes from studies performed in adults, and data supporting increased levels of proinflammatory cytokines during childhood are controversial [2], [3], [4], [10], [11].
Unraveling the proatherogenic pathways up-regulated in vertically HIV-infected individuals remains critical in order to design strategies for cardiovascular disease prevention in this particular population. In this scenario, we assessed relations between intima-media thickness (IMT) and proinflammatory cytokines [IL-6, CRP, myeloperoxidase (MPO)], tissue plasminogen activator (tPA), adhesion molecules [Soluble vascular cell adhesion molecule-1 (sVCAM-1), and pSelectine] and sCD14, in a cohort of ART-treated HIV-infected children and adolescents and healthy controls.
Section snippets
Study design and eligibility criteria
We performed a sub-study within an ongoing longitudinal, observational study evaluating cardiovascular risk in HIV-infected children and healthy controls [12]. Participants with available plasma samples were included in this analysis. Exclusion criteria included acute or opportunistic infections, family history of premature CVD, chronic conditions and use of medications other than ART.
The study was reviewed and approved by the Ethics Committee and Clinical Research of the participating
Study population and between group comparison of clinical characteristics
A total of 64 HIV-infected children and adolescents and 30 healthy controls were included, with a mean age of 14.1 ± 5.0 years. Main characteristics of both cohorts are summarized in Table 1.
HIV-infected and uninfected subjects showed similar age, gender, BMI, blood pressure and frequency of hypertension. Of note, there were no significant differences between groups regarding levels of total cholesterol, HDLc or LDLc, and only triglycerides were mildly elevated. Although median IMT was slightly
Discussion
In this study we evaluated carotid atherosclerosis and an extensive panel of biomarkers involved in inflammatory, endothelial, and hemostatic pathways in a cohort of vertically ART-treated HIV-infected subjects and healthy controls. No differences in lipids, BMI, visceral obesity or IMT were found between groups. In this scenario of lack of relevant ART mediated metabolic disorders and good disease control we found similar levels of most biomarkers between both groups, with the exception of
Authors contributions to the work
T. Sainz, study design, data analysis, writing. L. Díaz, laboratory analysis and interpretation. ML. Navarro, recruitment, data collection and analysis Hospital Gregorio Marañón. P. Rojo, recruitment, data collection and analysis Hospital 12 de Octubre. D. Blázquez, recruitment, data collection and analysis Hospital 12 de Octubre. J. Ramos, recruitment, data collection and analysis Hospital de Getafe. M. Alvarez; data collection and analysis S. Serrano-Villar, study design, statistical
Funding
This work was partially supported by a Small Grant Award from the European Society of Pediatric Infectious Diseases (ESPID) and the Fondo para la Investigación Sanitaria (FIS grant: PI12/01483) of the Spanish Ministry of Science and Innovation. Philips Healthcare kindly provided portable ultrasound equipment for the purpose of the study. T.S. and S.S-V are funded by grants from the Spanish Ministry of Science and Innovation (Ayudas para Contratos de Formación en Investigación Río Hortega). L.D.
Acknowledgments
The authors would like to particularly acknowledge all the children and adolescents as well as their families for their participation in this study. The authors would like to thank all the professionals involved, and particularly the ones integrating the Pediatric branch of the National AIDS Research Network of Spain (CORISPE). We acknowledge the Paediatric HIV-BioBank integrated in the Spanish AIDS Research Network and collaborating Centers, supported by the Instituto de Salud Carlos III,
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