title: Cardiovascular risk and endothelial function in people living with HIV/AIDS: design of the multi-site, longitudinal EndoAfrica study in the Western Cape Province of South Africa.
abstract: There is growing evidence of an interaction between HIV-infection, anti-retroviral therapy (ART) and cardiovascular diseases (CVD). Epidemiological studies in Europe and North America have been observing a shift towards an increased incidence of coronary heart disease and acute myocardial infarctions in HIV-infected populations compared to the general population even after adjusting for traditional cardiovascular risk factors. Despite South Africa (and sub-Saharan Africa, SSA) being regarded as the epicentre of the global HIV epidemic, very little is known about the prevalence of cardiovascular risk factors and precursors of vascular disease in HIV-infected populations in this region. The knowledge gap is further widened by the paucity of data from prospective studies. We present the rationale, objectives and key methodological features of the EndoAfrica study, which aims to determine whether HIV-infection and ART are associated with altered cardiovascular risk and changes in vascular endothelial structure and function in adults living in the Western Cape Province of South Africa.
  
  
  
  In this longitudinal study, comprehensive cardiovascular assessments of HIV-negative and HIV-positive (with and without ART) study participants are performed by clinical and biochemical screening for traditional cardiovascular risk factors and biomarkers of CVD. Vascular and endothelial function is determined by brachial artery flow-mediated dilatation (FMD), carotid-intima-thickness (IMT) measurements and quantitative retinal blood vessel analyses, complemented by vascular endothelial biomarker assays. Finally, we aim to statistically determine whether HIV-infection and/or ART are associated with increased cardiovascular risk and vascular endothelial dysfunction, and determine whether there is progression/regression in these endpoints 18 months after the baseline assessments.
  
  
  
  The EndoAfrica study provides a unique opportunity to recruit a cohort of HIV-infected patients and HIV-negative controls who will be comprehensively and longitudinally assessed for cardiovascular risk and disease profile with vascular endothelial function as a potentially important intermediate cardiovascular phenotype. To our knowledge, it is the first time that such a systematic study has been established in the context of SSA and South Africa.
authors.affiliation: Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town, 8000, South Africa. jgstr@sun.ac.za.
authors.forename: Hans
authors.identifier: 0000-0003-3726-9153
authors.initials: H
authors.lastname: Strijdom
authors.affiliation: Environmental Risk and Health Unit, Flemish Institute for Technological Research (VITO), Boeretang 200, 2400, Mol, Belgium.|Centre for Environmental Studies, Hasselt University, Agoralaan, 3590, Diepenbeek, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: De Boever
authors.affiliation: Division of Molecular Biology and Human Genetics, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research and SAMRC Centre for Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town, 8000, South Africa.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Walzl
authors.affiliation: Cardio-Metabolic Research Group (CMRG), Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, 7600, South Africa.
authors.forename: M Faadiel
authors.initials: MF
authors.lastname: Essop
authors.affiliation: Centre for Environmental Studies, Hasselt University, Agoralaan, 3590, Diepenbeek, Belgium.|Department of Public Health and Primary Care, Leuven University, Kapucijnenvoer 35, 3000, Leuven, Belgium.
authors.forename: Tim S
authors.initials: TS
authors.lastname: Nawrot
authors.affiliation: Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town, 8000, South Africa.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Webster
authors.affiliation: Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town, 8000, South Africa.
authors.forename: Corli
authors.initials: C
authors.lastname: Westcott
authors.affiliation: Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town, 8000, South Africa.
authors.forename: Nyiko
authors.initials: N
authors.lastname: Mashele
authors.affiliation: Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town, 8000, South Africa.
authors.forename: Frans
authors.initials: F
authors.lastname: Everson
authors.affiliation: Division of Molecular Biology and Human Genetics, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research and SAMRC Centre for Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town, 8000, South Africa.
authors.forename: Stephanus T
authors.initials: ST
authors.lastname: Malherbe
authors.affiliation: Division of Molecular Biology and Human Genetics, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research and SAMRC Centre for Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town, 8000, South Africa.
authors.forename: Kim
authors.initials: K
authors.lastname: Stanley
authors.affiliation: Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Universitätsplatz 4, 8010, Graz, Austria.
authors.forename: Harald H
authors.initials: HH
authors.lastname: Kessler
authors.affiliation: Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Universitätsplatz 4, 8010, Graz, Austria.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Stelzl
authors.affiliation: Gravitational Physiology and Medicine Research Unit, Institute of Physiology, Medical University of Graz, Harrachgasse 21/V, 8010, Graz, Austria.
authors.forename: Nandu
authors.initials: N
authors.lastname: Goswami
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001916:Brachial Artery / Q000502:physiology / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology* / Q000821:virology*; D059168:Carotid Intima-Media Thickness; D004730:Endothelium, Vascular / Q000503:physiopathology / Q000821:virology; D016021:Epidemiologic Studies; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D008137:Longitudinal Studies; D011446:Prospective Studies; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology
chemical_list: D015415:Biomarkers
keywords: Antiretroviral therapy; Cardiovascular risk factors; HIV; South Africa; Vascular endothelial function