Large arterial stiffness and associated cardiovascular risk factors in black South Africans

[摘要] Motivation:Sub-Saharan African countries face a double burden of disease due to a high prevalence of infectious diseases such as Human Immunodeficiency Virus infection (HIV) and tuberculosis, as well as non-communicable diseases such as cardiovascular disease. The high prevalence of cardiovascular disease in South Africa, especially in the black population, places significant strain on the overburdened public health system. Literature indicates that large artery stiffness is an early predictor of cardiovascular disease and mortality in various populations. Increased large artery stiffness places significant strain on the heart by increasing the afterload and by decreasing coronary blood flow during diastole. Furthermore, large artery stiffness is a risk factor for organ damage as it increases the transmission of pulsatile systolic pressure into the microcirculation of organs such as the brain and kidney.Numerous reports indicate that blood pressure and age are the strongest predictors of large artery stiffness. However, other factors, including cardiometabolic risk factors and health behaviours, may also affect large artery stiffness. Obesity, lipids, inflammation, endothelial activation, renal function, liver function, oxidative stress and health behaviours such as alcohol use, tobacco use and physical inactivity have all been associated with large artery stiffness in previous reports.The scantiness of longitudinal data concerning large artery stiffness measured with the gold standard method (carotid-femoral pulse wave velocity) has thus far inhibited an investigation into factors affecting large artery stiffness in black populations. The identification of such factors in black South Africans may enable policy makers to plan and implement prevention strategies that will successfully reduce the prevalence of morbidity and mortality due to cardiovascular disease in South Africa. Aim: The central aim of this study was to investigate large artery stiffness (as measured by carotid-femoral PWV) and its associations with non-modifiable and modifiable risk factors in the understudied black South African population. Therefore, a young and older black population were included in this thesis and large artery stiffness and associated risk factors were investigated cross-sectionally in both populations, as well as longitudinally in the older population.Methodology: This sub-study included data from both the African Prospective study on the Early Detection and Identification of Cardiovascular Disease and HyperTension (African-PREDICT) and the South African leg of the international Prospective Urban and Rural Epidemiology (PURE) study, conducted in the North West Province (PURE-SA-NWP). For the purposes of this thesis, all HIV-infected participants were excluded from both study populations. The PURE-SA-NWP study is a longitudinal study with a baseline (conducted in the year 2005) and two follow-up data collections (conducted in 2010 and again in 2015). For manuscript two, baseline and 10-year follow-up data were used, and for manuscript three, five-year follow up data (representing baseline data for this manuscript) and 10-year follow-up data were used.For both studies, data was collected according to standardised methods. Participants completed general and health questionnaires, in which socio-economic factors, alcohol, tobacco and medication use were reported. Anthropometric and cardiovascular measurements were performed. Carotid-femoral pulse wave velocity was measured with the Sphygmocor XCEL device according to the most recent recommendations. Biological sampling took place, which enabled the biochemical analyses of relevant metabolic, inflammatory, endothelial activation, oxidative stress, renal function and liver function markers. As part of the statistical analyses, variables without a normal distribution were logarithmically transformed. I compared variable means and proportions with independent t-test and Chi-square tests, dependent t-tests and Wilcoxon tests, analyses of variance and analyses of covariance when adjustments were needed. Relationships between variables were established with Pearson's correlation coefficients and partial correlation coefficients (when adjustments were needed). Independent associations with and predictors of large artery stiffness were determined with multi-variate linear regression analyses. In all instances, a p-value of <0.05 were regarded as significant.Results and conclusions of each manuscript: The central aim of this thesis was achieved by the results of three manuscripts. In the first manuscript, large artery stiffness was compared in young black and white adults and the associations of health behaviours with arterial stiffness were determined. Mean arterial pressure (MAP) was higher in the black participants (p<0.001), but carotid-femoral pulse wave velocity (cfPWV) was similar in young black and white adults (6.37 ± 0.73 vs. 6.36 ± 0.73 m/s; p=0.89) after adjustment for MAP. Higher levels of gamma-glutamyltransferase (GGT) (p<0.001), cotinine, reactive oxygen species, interleukin-6 and monocyte-chemoattractant protein-1 (all p<0.02) were found in the black group. GGT associated independently and positively with cfPWV in both black and white adults after multiple-adjustment in multiple regression analyses (β=0.15; p�?.049 in both groups). No association was found with smoking or physical activity, but cfPWV inversely associated with body mass index in the whites. These results indicated that, already at a young age, black populations may be more vulnerable to early vascular ageing and subsequent CVD development, due to higher GGT levels and an elevated cardiovascular risk profile.Manuscript 2 investigated whether traditional cardiovascular risk factors and health behaviours predicted large artery stiffness in a black South African population 10 years later. At follow-up, 25.3 % of the population (age 65 ± 9.57 years) had a cfPWV greater than 10 m/s. In multivariate-adjusted regression analyses, the strongest predictors of cfPWV were MAP, age and heart rate (all p<0.024). Urban locality (adjusted R2=0.31, β=0.12, p=0.001), self-reported alcohol use (β=0.11, p=0.018) and plasma glucose (β=0.08 p=0.023) associated positively with follow-up cfPWV. Body mass index (BMI) associated negatively with cfPWV (β=-0.15, p=0.001), but no associations with sex, smoking, inflammatory markers, lipids or antihypertensive medication were found. When self-reported alcohol use was replaced with GGT, the latter also associated independently with cfPWV (β=0.09, p=0.028). These results suggest that a health profile associated with excessive alcohol use, such as residing in an urban location, elevated plasma glucose levels and a low BMI may predispose black South Africans to stiffer arteries. This observation encourages the development of public health strategies that target excessive alcohol use in South Africa.In the final manuscript, biomarkers known to modulate arterial function in other populations (metabolic, inflammatory, endothelial activation and oxidative stress) were investigated with regard to large artery stiffness in young and older black South Africans who self-reported no alcohol-use. Cross-sectional data from young (aged 24.7 ± 3.24 years) black adults and five-year follow-up data from older (aged 61.6 ± 9.77 years) black adults were included. Of the variety of biomarkers investigated in multivariable-adjusted regression analyses, only plasma glucose (adjusted R2=0.24, β=0.21, p<0.001) and glycated haemoglobin (adjusted R2=0.22, β=0.17, p=0.002) independently predicted cfPWV five years later in the older black adults. In the younger group, no associations were found. These results highlight the possible role of dysglycaemia in the development of CVD in Africa. Furthermore, it prompts public health education about the importance of managing sugar intake and body weight throughout the life course.General conclusion: This study shows for the first time that health behaviour, especially alcohol use, is predictive of large artery stiffness over 10 years in black South Africans. Young black adults already seem to be at a higher risk for cardiovascular disease due to a health profile which exhibits higher inflammation, oxidative stress, tobacco use and an independent positive association between arterial stiffness and GGT. In an older black population not consuming alcohol, arterial health is compromised by dysglycaemia. These results emphasise the importance of maintaining a healthy lifestyle throughout the life-course, in order to avoid early vascular ageing

[发布机构] North-West University