Does smoking impact on the association between oxidative stress and vascular function in young normotensives? the African-Predict study

MSc (Physiology), North-West University, Potchefstroom CampusCigarette smoking is one of the most important modifiable risk factors for the development of cardiovascular disease (CVD). Smoking not only plays a role in the onset of CVD, but it has a significant contribution to disease progression and fatal cardiovascular outcomes such as stroke. Globally, smoking kills 6 million people annually. In 2002, it was estimated that 15% of South Africans are smokers. Tobacco products contain a variety of toxic chemicals as well as reactive oxygen species (ROS) with the possibility of sustaining cardiovascular injury. Tobacco use increases the amount of oxidative stress by producing ROS and weakening the antioxidant defence system. Elevated levels of ROS react with membrane lipids, proteins, and nucleic acids, causing cellular dysfunction and death. Oxidative stress is one of the major contributors in the link between smoking and CVD. Oxidative stress has also been shown to increase pulse wave velocity (PWV). Higher levels of antioxidant enzymes such as glutathione peroxidase-3 (GPx-3) is associated with wider central retinal artery equivalent (CRAE). Cigarette smoke is associated with increased PWV and decreased compliance, suggesting an increase in arterial stiffness. Cigarette smoking also adversely impacts on the microvasculature, it has been linked to a wider central retinal vein equivalent (CRVE), and to a lesser extent larger or unchanged CRAE. The role of smoking on the association of oxidative stress with micro- and macrovasculature in smokers in a young South African population that does not yet present cardiovascular dysfunction is not well investigated. Methodology: We included 237 non-smokers (108 black and 129 white) and 145 smokers (78 black and 67 white) from Potchefstroom, South Africa aged between 20 and 30 years. All participants gave written informed consent prior to any measurements being performed. Anthropometric measurements (weight, height, waist circumference and body mass index) were measured. Carotid femoral PWV (cfPWV) was determined using a SphymoCor Xcel device, whereas CRAE and CRVE were determined by using retinal imaging with a Dynamic Vessel Analyser. Serum ROS was analyzed in order to describe oxidative stress and the Synergy H4 hybrid microplate reader was used. Serum cotinine levels were determined to differentiate smokers from non-smokers. Cotinine was analyzed using Chemiluminescence method of the Immulite. Two-way ANOVA and Chi-square tests were performed to compare means and proportions between groups. Person and partial correlation analyses were done and in partial correlations, adjustments were made for age, gender and body mass index (BMI). PWV was additionally adjusted for mean arterial pressure (MAP). Forward stepwise multiple regression analysis was performed to determine independent associations. Variables that were included in the multiple regression models were age, gender, BMI, systolic blood pressure (SBP), MAP, C-reactive protein (CRP), total cholesterol and ROS. PWV, CRAE, CRVE and AVR. Results: Regardless of smoking status, PWV, CRVE and ROS were similar between black and white groups, whereas CRAE and arterio-venous ratio (AVR) were higher in white than in black non-smokers. In single regression analysis, ROS correlated positively with the CRVE (r=0.29; p=0.014) and inversely with AVR (r=–0.37; p=0.002) in black smokers only. After partially correcting for age, gender and BMI only the association with AVR remained, and a positive correlation emerged between ROS and PWV in black smokers (r=0.24; p=0.042). In black smokers, we confirmed the independent associations of ROS with AVR (Adj. R2=0.19; β=–0.33; p=0.004), PWV (Adj. R2=0.35; β=–0.24; p=0.042), and an independent relationship of ROS and CRAE (Adj. R2=0.18; β=–0.25; p=0.034) emerged. Conclusions: Our results suggest that cigarette smoking modifies the relationship between ROS and vascular function and may contribute to a potential acceleration of increasing cardiovascular morbidities, especially among the black population.Master