Doctoral Degrees (Medical Physiology)

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Browsing Doctoral Degrees (Medical Physiology) by Author "Everson, Frans Pieter"

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    HIV/AIDS and air pollution as emerging cardiovascular risk factors in Cape Town populations : is endothelial function a marker of effect
    (Stellenbosch : Stellenbosch University, 2020-03) Everson, Frans Pieter; Strijdom, Hans; De Boever, P.; Nawrot, T. S.; Goswami, N.; Stellenbosch University. Faculty of Medical Sciences. Dept of Biomedical Sciences: Medical Physiology.
    ENGLISH ABSTRACT: Background: HIV and antiretroviral therapy (ART) are associated with cardiovascular disease (CVD). Concomitantly,air pollution is a global health concern and associated with CVD. Although South Africa (SA) has the largest HIV population, ART roll-out programme and also one of the most carbon-intensive economies in world, the effects of these emerging cardiovascular risk factors remain under investigated. Aim: The current study aimed to investigate whether endothelial function (an early marker of cardiovascular risk/disease) is a marker of effect of HIV, ART and air pollution in a study cohort residing in the Cape Town region. Methods: Volunteering participants were recruited from health-care clinics in Worcester and Cape Town. A health questionnaire was completed (demographic, lifestyle, and socioeconomic information), anthropometric measurements taken (BMI and blood pressure) and fasting blood and urine samples collected from each participant for chemical pathology and biomarker analyses. Sub-study 1 followed a repeated measures design (baseline and 18-month follow-up visit) to investigate the effects of HIV (viral load) and ART (pre- vs. post-ART treatment and an 18-month ART treatment period) on markers of endothelial function. Sub-study 2 investigated the effects of personal air pollution exposure (NO2 and BTEX via passive diffusion samplers) in a repeated measures design (baseline and 6-month follow-up visit) on markers of endothelial function. Markers of endothelial function for both sub-studies included: tumor necrosis factor-alpha (TNF-α), high sensitivity C-reactive protein (hsCRP), intercellular adhesion molecule-1 (ICAM-1),vascular cellular adhesion molecule-1 (VCAM-1), e-selectin, p-selectin, vascular endothelial growth factor (VEGF), plasminogen activator inhibitor-1 (PAI-1), retinalmicrovascular calibres (including central retinal arteriolar/venular equivalent (CRAE; CRVE), CRAE/CRVE ratio (AVR)) and flow-mediated dilation (FMD). Results: Sub-study 1: Each interquartile range (IQR) increment increase in viral load (1300 copies mRNA/ml) was associated with CRVE (9.29 μm), AVR (-0.016) and %FMD (-2.13%). Compared to baseline, initiating ART was associated with VCAM-1 (-148 ng/ml), VEGF (40.6%), PAI-1 (14.12 ng/ml) and CRVE (-6.42 μm). An 18-month ART treatment period was associated with TNF-α (-1.22 pg/ml), ICAM-1 (-45%), e-selectin (-5.57 ng/ml) CRVE (–7.00 μm) and % FMD (-9.8%). Sub-study 2: Each IQR increment increase in NO2 (7.0 μg/m³) was associated with VEGF (-18.9%), CRVE (-2.93 μm) and baseline brachial artery diameter (-0.29 μm). Benzene (IQR: 3.3 μg/m³) was associated with p-selectin (-5.8 pg/ml), toluene (IQR: 30.0 μg/m³) was associated with PA1-1 (7.2 ng/ml). Ethyl-benzene (IQR: 3.8 μg/m³) was associated with VCAM-1 (-4.9%) and PA1-1 (9.1 ng/ml). m+p-Xylene and o-Xylene (IQR 3.8 μg/m³ respectively) were associated with VCAM-1 (-1.47% and -4.5%) and PA1 (3.08 ng/ml and 11.7 ng/ml). 3+4MHA (1380 ng/ml) was associated with %FMD (-0.40%). Discussion and Conclusion: The study showed that endothelial function is a marker of effect of HIV, ART and air pollutants (NO2 and BTEX) in the current study population, and that HIV and air pollution contribute to an increased cardiovascular risk profile while ART exhibited varying effects. This study underscores the relevance of these emerging cardiovascular risk factors in South Africa and the greater sub-Saharan Africa region. This study strongly supports the need for further investigation, also in study populations beyond the Western Cape.