| dc.description.abstract | In especially black South Africans non-communicable diseases such as hypertension and cardiovascular disease (CVD) have become an increasing burden with increased morbidity and mortality. Currently South Africa is undergoing rapid urbanization which involves a nutrition transition that may be accompanied by micronutrient malnutrition. Selenium, an important micronutrient, is known to exert indirect antioxidant functions and thereby has beneficial effects in lowering inflammation and endothelial dysfunction through the selenoprotein, glutathione peroxidase (GPx). It was previously shown that a black South African black tend to have both lower selenium and GPx levels when compared to whites. Low selenium levels and expression of GPx may therefore increase oxidative stress, inflammation, endothelial dysfunction and consequently lead to the development of increased arterial stiffness, atherosclerosis and hypertension. To our best knowledge, studies investigating the associations of serum selenium and GPx activity, blood pressure, vascular resistance, arterial compliance, arterial stiffness, measures of the microvasculature as well as measures of large artery structure are limited in especially black populations. The central aim of this study was to determine whether serum selenium levels and GPx activity relate with estimates of cardiovascular structure and function in different black South African cohorts. Three different study populations were used in the thesis, including the SABPA study, the African-PREDICT study and the PURE study. All the data were collected according to standardised methods. The participants completed questionnaires and anthropometric, cardiovascular and biochemical measurements were performed. In the cross-sectional SABPA study, serum selenium, GPx activity, ambulatory blood pressure and arterial stiffness of 200 black and 209 white school teachers (aged 20-65 years) were measured. In the African-PREDICT study, which is also a cross-sectional study, 394 young healthy adults (20-30 years of age) were included. We determined serum selenium, GPx activity, microvascular measures (central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), arteriolar-to-venular ratio (AVR) and estimated glomerular filtration rate (eGFR)) and macrovascular measures (pulse wave velocity (PWV), 24h pulse pressure (PP) and augmentation index (AIx)). The PURE study was a longitudinal study, with 10-year follow-up data, which included measurements from baseline (N=987) and follow-up (N=718) of black adults from rural and urban areas in the North West province of South Africa. We measured serum selenium and blood pressure at baseline and carotid intima media thickness (IMT), cross-sectional wall area (CSWA), carotid-femoral pulse wave velocity (c-fPWV) and blood pressure at follow-up. In the first manuscript we found that serum selenium levels were significantly lower in black compared to white school teachers, independent of sex (p<0.001), with 10% of black men and 20% of black women being selenium deficient (<8 μg/100 ml). Inverse associations of 24h systolic blood pressure (SBP) (β=-0.19; p=0.039) and 24h diastolic blood pressure (DBP) (β=-0.21; p=0.029) with selenium were found only in white men. An inverse association between carotid-dorsalis pedis pulse wave velocity (c-dPWV) and GPx activity (β=−0.23; p=0.017) were also found in the same group. In this manuscript, we concluded that, lower serum selenium levels in black populations from the same geographical region as their white counterparts may have an impact on the loss of the vascular protective effects of selenium and selenoproteins such as GPx.
In the second manuscript, we found vascular protective associations between serum selenium and a microvascular measure (AVR (β=0.23; p=0.036)) in black women and with a macrovascular measure (24h PP (β=-0.15; p=0.048)) in white women. In turn, GPx activity also showed a protective association with a microvascular measure (eGFR) in white men (β=0.23; p=0.035), as well as with macrovascular measures (AIx, PP) in the black (β=-0.25; p=0.027) and white men (β=-0.22; p=0.035), and black women (β=-0.32; p=0.001). Therefore, our findings suggest a protective role for the micronutrient selenium and GPx on both the micro- and macro-vasculature in young, healthy bi-ethnic men and women. In the final manuscript we found that c-fPWV was negatively associated with baseline selenium (β=-0.09; p=0.016) after ten years in the normal selenium group. In the normal selenium group baseline (but not ten-year) blood pressure also associated negatively with baseline selenium (β=-0.09; p=0.007). Both IMT (β=0.12; p=0.001) and CSWA (β=0.10; p=0.003) associated positively with baseline selenium in the total group, normal and selenium deficient groups after ten years. In this manuscript we concluded that a long-term vascular protective association of selenium on arterial stiffness and blood pressure in black Africans with normal selenium levels were found, supporting the notion that selenium fulfils a vascular protective role. However, in contrast, we found a potentially detrimental association between selenium and carotid wall thickness, particularly evident in individuals within the highest quartile of serum selenium. In three different study populations we found consistently that selenium and GPx played a vascular protective role in these population groups from a healthy population between 20-30 years, before the onset of CVDs, a middle-aged population group (aged between 20-65 years) with >50% prevalence of hypertension and an older population group of >35 years where the onset of CVDs is evident over ten years (>50% prevalence of hypertension). In contrast, we found a possible detrimental association between selenium and carotid wall thickness, particularly evident in individuals within the highest quartile of serum selenium. However, our findings provide vascular protective associations of selenium and GPx. We suggest that it may be beneficial to ensure optimal selenium status to maintain its health effects and delay or avoid vascular deterioration and eventually CVD in later life. This may lead to preventative strategies to combat the high prevalence of CVDs in black South Africans | en_US |
