Inflammatory mediators and the cardiovascular profile of young South Africans: the African-PREDICT study

Abstract

Motivation: Cardiovascular disease (CVD) remains a leading cause of death, accounting for approximately 17.9 million deaths annually, with 75% occurring in low-and middle-income countries. A number of studies have implicated inflammation in the development of CVD. However, the majority of studies have focused on only a few well-known inflammatory mediators, such as C-reactive protein (CRP). The potential role of numerous other mediators in CVD remains largely unexplored. While many questions remain, a pattern has emerged suggesting that lifestyle behaviours, such as dietary salt or fruit and vegetable intake, contribute to the release of inflammatory mediators. This may result in changes in cardiovascular structure and function, potentially leading to the development of CVD. Even in the early phases of CVD development, raised levels of known inflammatory markers have been linked with changes in cardiovascular function such as raised blood pressure (BP). It is therefore important to explore the relationship between a detailed range of inflammatory mediators and measures of BP, sodium and potassium intake at a young age. Aim: The central aim of this study was to present a detailed inflammatory mediator profile and describe how it relates to sodium and potassium excretion and the cardiovascular profile of young, healthy South African adults. Methods: This study used data from the African Prospective study on the Early Detection and Identification of Cardiovascular disease and Hypertension (African-PREDICT). Data was collected using standard procedures and included a demographic questionnaire, body composition, accelerometry data, cardiovascular measurements, as well as biochemical analyses of all relevant biomarkers, including the multiplex analysis of 22 inflammatory mediators. A sub-sample of the total baseline cohort was followed over 4.5 years. In Manuscript 1 we analysed data for participants who took part in the baseline phase of the study (n=1202). Participants using anti-inflammatory medication or with missing biochemical analyses data were excluded, resulting in a population size of n=1189. In Manuscript 2 participants with missing sodium and potassium data were additionally excluded, resulting in a baseline population size of n=991. In Manuscript 3, data from the first 407 participants included in both the baseline and the follow–up phase of the study was analysed. Participants with missing ambulatory blood pressure data were excluded, resulting in a population size of n=358. Statistical Analyses: Variables with non-Gaussian distributions were logarithmically transformed and interactions of sex as well as black and white ethnicity were investigated. Groups were compared using dependent and independent t-tests, Chi-square and McNemar tests. Factor analyses of the multiple inflammatory mediators were performed to identify clusters of inflammatory mediators using the factor function of SPSS. Pearson, partial and multivariable-adjusted regression analyses were used to determine associations. Results and Conclusions: In Manuscript 1, we determined how a detailed range of inflammatory mediators related to blood pressure. Due to interactions of ethnicity, we also compared inflammatory profiles between young black and white adults. For pro-inflammatory mediators, the black adults reflected higher C-reactive protein, interferon-inducible T-cell alpha chemoattractant, and macrophage inflammatory protein 3 alpha (all p≤0.008), but lower interferon-gamma, interleukin (IL)-1β, IL-8, IL-12, IL-17A, and tumour necrosis factor alpha (all p≤0.048) than the white adults. For anti-inflammatory mediators the black group reflected lower levels of IL-5, IL-10 and IL-13 (all p≤0.012)), resulting in generally higher pro-to-anti-inflammatory ratios in black than white adults (p≤0.001). In mediators with both pro- and anti-inflammatory functions, the black group reflected lower granulocyte-macrophage colony-stimulating factor and IL-6 (both p≤0.010). These patterns were confirmed when participants were stratified according to hypertensive status, sex and socio-economic status. Numerous measures of BP differed significantly between black and white populations. However, no relationship was found between inflammatory mediators and BP.