Myeloperoxidase and the vasculature in young adults: the African-PREDICT study
Background and motivation: Myeloperoxidase (MPO) is an enzyme with both pro-inflammatory and pro-oxidative functions. Previous studies in the United States have found MPO levels to be higher in African American than in white groups, but studies examining MPO levels in South Africa are scant. Recent findings indicated that increased circulating levels of MPO are linked to hypertension and stroke, especially in older populations. Early microvascular changes may aid in the prediction of cardiovascular disease (CVD). The retina is a unique site to investigate microvascular changes with non-invasive techniques, such as the Retinal Vessel Analyzer. Retinal vessel calibres can be determined from retinal fundus images to determine the central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE). In South African populations, CRVE was found to be wider and CRAE narrower in black adults when compared with white adults. Arterial narrowing is commonly associated with hypertension, whereas venular widening is associated with incident stroke. Retinal arterial narrowing is a difficult measure to estimate precisely and therefore a summary measure, the ratio of CRAE and CRVE, the arterio-to-venous ratio (AVR) was proposed. Arterio-to-venous ratio can be used as an index of the severity of arteriolar narrowing. Whether there are potential associations between MPO levels and the microvasculature among young black and white individuals with no apparent CVD still needs to be investigated. The African Prospective study on the Early Detection and Identification of Cardiovascular Disease and Hypertension (African-PREDICT) allows us to investigate the association between the microvasculature and MPO in young participants. Aim: To determine whether measures of the retinal microvasculature associate with MPO in young, bi-ethnic South African adults. Methods: We included the first 577 participants of the African-PREDICT study, aged 20-30 years, with complete retinal vessel calibre data at baseline, namely black (n=284) and white (n=285) men and women. Participants who presented with missing data for MPO (n=5) and those using anti-inflammatory medication (n=3) were excluded from this study. The final group consisted of 569 participants. Data on anthropometric measures including body height, weight, and waist circumference were collected, and body mass index was calculated. Clinic blood pressure was measured on the left arm in duplicate while participants remained in a rested seated position. The Retinal Vessel Analyzer was used to capture retinal images. The images were analysed to calculate CRAE and CRVE. Biochemical analyses included MPO, the lipid profile (triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol), gamma-glutamyltransferase (GGT), cotinine, high sensitivity C-reactive protein (CRP), white blood cell count, creatinine and serum peroxides, as an indicator of reactive oxygen species (ROS). Statistical analyses included independent T-tests and Chi-square tests to compare means and proportions. Single, partial and multiple regression analyses were performed to investigate the associations between the retinal vessel calibres and MPO while adjusting for age, waist circumference, systolic blood pressure, total energy expenditure (TEE), white blood cell count, GGT, HDL-C, cotinine and glucose. Results: Groups were divided based on interactions found for sex on the associations between CRVE and MPO (p=0.027) and between AVR and MPO (p=0.027), along with evidence in the literature reporting on different MPO levels and retinal microvascular calibres; found in black and white groups. No significant differences were found between black and white men (p=0.71) or women (p=0.95) when comparing MPO levels between the groups. When comparing black and white groups, CRAE and AVR (all p<0.05) were lower in the black men and women, and black women had a wider CRVE than white women (p=0.018). Only in white men a consistent positive association was found between CRVE and MPO (adj. R2=0.25; β=0.19; p=0.032) in unadjusted, partially adjusted and fully adjusted models. In black women, a positive association was found between CRAE (adj. R2=0.29; β=0.17; p=0.026) and AVR (adj. R2=0.052; β=0.18; p=0.041) with MPO in unadjusted, partially adjusted and fully adjusted models. Conclusion: In conclusion, our results suggest the involvement of MPO in retinal microvascular changes as early as in young adulthood. This finding seems to be dependent on ethnicity and sex.
- Health Sciences