Vascular endothelial dysfunction: The putative interface of emerging cardiovascular risk factors affecting populations living with and without HIV in Sub-Saharan Africa. (R-5414)

Vascular endothelial dysfunction (EDy) is an early precursor of cardiovascular disease. Early detection of this event can provide an opportunity for clinical interventions aimed at reversing EDy. Very few studies have investigated the association between HIV-infection and antiretroviral treatment (ART), and EDy in Sub-Saharan African (SSA) populations. Various studies have been reporting unprecedented increases in traditional cardiovascular risk factors (hypertension/diabetes mellitus/obesity/dyslipidaemia/smoking) in SSA populations, which could affect endothelial function. Furthermore, no data is available on the putative cardiovascular effects of environmental factors, particularly air pollution in SSA populations. Therefore, this study aims to investigate EDy as a putative common pathophysiological consequence of two societal/health challenges in SSA, namely emerging cardiovascular risk factors (HIV-infection, ART, and increased prevalence of traditional cardiovascular risk factors), and air pollution exposure. This study will be conducted on populations in three SSA countries (South Africa, Kenya and Côte d'Ivoire). The main study groups will be determined by the HIV and ART status of participants: (i) Group 1: Patients with HIV-1 infection, not yet on 1st line ART; (ii) Group 2: Patients with HIV-1 infection on ART, and (iii) Group 3: Participants without HIV infection (controls). Baseline investigations will include measurement of endothelial function using flow mediated dilatation, screening for hypertension, diabetes, obesity, dyslipidaemia and smoking and measurement of air pollution exposure. Serum will be stored as nested case-control design for subsequent analysis of EDy and vascular inflammation biomarkers. Baseline investigations will be repeated at 12 and 24 months, and provision will be made for additional air pollution measurements to allow for temporal changes. Epidemiological studies will be underpinned by animal and in vitro investigations in which the direct vascular and endothelial effects and mechanisms of 1st line ART regimes will be explored by investigating vascular function (rat aortic ring relaxation studies), endothelial cell function (cultured rat aortic endothelial cells), and signalling pathways involved with endothelial function/dysfunction (proteomics and Western blot analysis). Overall, human studies will be completed within 30 months, and animal studies within 24 months. This study will provide novel data regarding the overall prevalence of EDy, and effects of HIV infection and ART on vascular endothelial function in SSA populations. Furthermore, valuable information will be gained on the prevalence of traditional cardiovascular risk factors in the study populations, and will reveal whether a relationship exists between air pollution exposure and EDy in SSA. In summary, this study will be the first of its kind to investigate the proposed questions, and compare the results obtained in populations of three, regionally distinct SSA countries. In view of the clinical advantages of the detection of EDy, our study could help identify people who are at risk of developing future adverse cardiovascular events. The study findings could be used to compile educational and awareness material for health care workers and patients at health care sites on cardiovascular risk factors associated with HIV-infection and/or ART, as well as possible cardiovascular risk posed by exposure to air pollution.

Keywords:Cardiovascular risk factors, HIV

Disciplines:General biology, Plant biology

Project type:Collaboration project