The relationship between markers of oxidative stress, inflammation and arterial compliance in a bi-ethnic population : the SABPA study

Abstract

Motivation : Cardiovascular disease (CVD) has become the major cause of mortality among the black population in South Africa. This might be due to rapid increase in urbanization seen in the last decade. It was further indicated that black Africans are more frequently diagnosed with heart failure than any of the other ethnic groups. Unhealthy lifestyle behaviors, such as excessive alcohol consumption and tobacco use, are known to augment oxidative stress and inflammation, and as a result these two factors may lead to increased arterial stiffness, either directly by oxidative stress, or indirectly by activating inflammatory processes. Oxidative stress is an imbalance between oxidants and antioxidants. Oxidative damage is characterized by an increase in the levels of oxidation products of macromolecules, such as thiobarbituric acid reactive substances (TBARS) and protein carbonyls. TBARS are an end-product of lipid peroxidation and levels of TBARS were shown to independently predict cardiovascular events such as coronary heart disease. The antioxidant defense system, such as the enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase acts to combat oxidative stress. However, lower antioxidant enzyme activity such as GPx activity allows accumulation of peroxide molecules and is associated with increased risk of cardiovascular events. Increased arterial stiffness is independently associated with cardiovascular morbidity and mortality in various population groups. Arterial stiffness is characterized by structural and functional alterations of the intrinsic elastic properties of arteries, leading to decreased arterial compliance (Cwk) and increased total peripheral resistance (TPR). Differences between black and white Africans have been established by numerous investigators, finding that blacks are more prone to increased oxidative stress, inflammation (CRP, IL-6) and arterial stiffness; however, studies investigating the link between these factors in a population with high prevalence of CVD are scant. Aim : The aim of the study was to compare markers of oxidative stress (TBARS), antioxidant capacity (GPx), inflammation (CRP, IL-6), arterial compliance (Cwk) and vascular resistance (TPR) between black and white South Africans. A further aim was to determine whether oxidative stress, antioxidant capacity and inflammation are related to Cwk and TPR in this study population. Methodology This sub-study, which is embedded in the Sympathetic Activity and Ambulatory Blood Pressure in Africans (SABPA) study, included a total of 359 participants, 173 black and 186 white men and women between the age of 28 and 68. The participants of this study were from North-West Province of South Africa and data of the follow up phase of this study was used in this sub-study. The follow up phase was conducted between February and May 2011/2012. Methodology : This sub-study, which is embedded in the Sympathetic Activity and Ambulatory Blood Pressure in Africans (SABPA) study, included a total of 359 participants, 173 black and 186 white men and women between the age of 28 and 68. The participants of this study were from North-West Province of South Africa and data of the follow up phase of this study was used in this sub-study. The follow up phase was conducted between February and May 2011/2012. Standardized methods were used to capture all data and included anthropometric measurements, cardiovascular measurements namely, Windkessel compliance (Cwk), total peripheral resistance (TPR), mean arterial pressure (MAP), pulse pressure (PP), diastolic blood pressure (DBP) and systolic blood pressure (SBP). Biochemical analyses included the antioxidant markers, superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), total glutathione (tGSH) and the lipid peroxidation marker thiobarbituric acid reactive substances (TBARS), as well as inflammatory makers C-reactive protein (CRP) and interleukin-6 (IL-6). The groups were stratified by ethnicity in line with the aims but not by sex, since no interaction of sex existed for the associations between cardiovascular and oxidative stress markers. T-tests and Chi-square tests were used to compare means and proportions, respectively. Pearson and partial regression analyses were used to determine correlations between cardiovascular markers and markers of oxidative stress and inflammation. This was followed by multiple regression analyses to investigate whether independent associations exist between the cardiovascular and oxidative stress variables in both ethnic groups. P-values ≤0.05 were deemed significant. Results and conclusion : In this study black participants had worse cardiovascular (as indicated by higher SBP, DBP, TPR, MAP and lower Cwk all p≤0.013), inflammatory (as indicated by higher CRP and IL-6 levels p<0.001) and lipid profiles (as indicated by higher total cholesterol, low density cholesterol and, triglyceride levels p≤0.01) when compared to the white participants. Black participants also had higher levels of TBARS (p=0.018) despite their higher antioxidant enzyme activities GPx (p=0.005) and GR (p=0.019) compared to their white counterparts. Unadjusted regression analyses showed a negative relationship of Cwk with TBARS (r=- 0.25; p=0.002) and a positive relationship of TPR with TBARS (r=0.21; p=0.031) in black participants. In white participants a negative correlation existed between Cwk and GPx (r=- 0.16; p=0.025), whereas TPR correlated positively with GPx (r=0.17; p=0.026). After adjustments were made for age, sex and BMI, the above mentioned correlations remained and an association between MAP and TBARS (r=0.17; p=0.049) became significant in the blacks, while a positive correlation of DBP (r=0.17; p=0.028) and MAP (r=0.17; p=0.032) with GPx became significant in the white group. In multiple regression analyses, a positive independent association of both MAP (β=0.21; p=0.032) and TPR (β=0.18; p=0.018) with TBARS was found, as well as a negative independent association between Cwk and TBARS in the black group. These associations remained after excluding hypertensive participants. In the white group a positive association of both MAP (β=0.17; p=0.011) and TPR (β=0.13; p=0.047) with GPx and a negative association between Cwk and GPx (β=-0.10; p=0.019) were also indicated to be independent of various covariates. In conclusion, decreased arterial compliance and increased vascular resistance associated with increased oxidative damage independent of hypertensive status in black participants. These results suggest that oxidative stress plays a role in early vascular changes in a black population prone to the development of cardiovascular disease.