Retinal microvascular calibre and blood pressure associated target organ damage : a bi-ethnic investigation within the SABPA study

Abstract

Background and aims Cardiovascular disease (CVD) is a global leading cause of mortality. Regardless of the various factors that may contribute to CVD development, hypertension (HT) is known to be a leading risk factor, which was recently reported to be the highest in South Africa. The prevalence of HT is known to be the highest in black populations, when compared to whites. However, limited data exists regarding biomarkers that may contribute to the development of HT in black populations. Since it is known that HT predisposes to distinctive structural and functional small vessel adaptations, the investigation of the micro-circulation has gained increased interest. Furthermore, the use of retinal imaging, using new and improved equipment such as the dynamic retinal vessel analyzer (DVA), a funduscope with applicable software, has increased. The retina allows non-invasive observation of the microcirculation. Analysis of the retinal microvasculature provides valuable information about the structure as well as the function of the vessels and can easily be obtained repeatedly over time. Data from population-based studies have shown that retinal vascular changes are related to risk of both clinical and subclinical CVD. The retina is distinctive in that it allows the direct sequelae of elevated BP to be visualised early, particularly changes in the retinal microvasculature. Changes in retinal vessel calibre have been linked to markers of target organ damage (TOD) such as left ventricular hypertrophy (LVH), vascular remodelling (increased carotid intima-madia thickness (cIMT), glomerular filtration rate (GFR), and nephropathy, as consequences of hypertension. However, findings regarding retinal vessel calibre and TOD remain limited and inconsistent. In addition, the associations between retinal blood vessel calibre, and its functional capacity, assessed upon light flicker provocation, and blood pressure associated TOD, have not yet been established. According to a review by Ikram et al. it has been suggested that the DVA should be used in retinal calibre analysis for better functional and dynamic aspects of the retinal microvasculature. Taking the high prevalence of HT in blacks into consideration, as well as their tendency to have a higher risk for developing TOD such as LVH and kidney disease, the relationship between retinal vessel calibre and markers of HT associated TOD warrants further investigation. Consequently, the aim of this study was to investigate the associations between blood pressure-related TOD with static and dynamic retinal calibre measurements in black and white participants. Our objectives were therefore to: a) determine whether measurements of BP-associated TOD (Cornell product, carotid intima media thickness (CIMT) and estimated glomerular filtration rate (eGFR) are associated with retinal vessel calibre and light flicker-induced retinal calibre changes (arteriolar dilation, constriction and venular dilation); and b) determine whether these relationships differ between a black and white population. Methodology - The present study was performed using data obtained from the follow-up phase of the SABPA (Sympathetic Activity and Ambulatory Blood Pressure in Africans) study which was conducted in February to May of 2011 and 2012. A total of 156 black (80 men and 76 women) and 179 white (86 men and 93 women) school teachers (aged 23–68 years) took part in this sub-study. Ambulatory blood pressure, cIMT, electrocardiogram (ECG) derived Cornell product, and the eGFR were determined as measures of TOD. Retinal images (for the determination of retinal vessel calibres) and vessel functional responses to a light-flicker were captured using the DVA. Anthropometric, biochemical analysis and lifestyle factors were measured using standard procedures. Results - A narrower central retinal artery equivalent (CRAE) and smaller arteriolar-to-venular ratio (AVR), and wider central retinal vein equivalent (CRVE) were independently associated with systolic blood pressure (SBP), whereas peak arteriolar dilation negatively associated with SBP only in black hypertensives (β=-0.12 ± 0.06; p=0.04). No independent associations were present between retinal vessel calibre and TOD measures. However, eGFR was positively associated with peak arteriolar dilation in the total group (β=0.29 ± 0.12; p=0.008), black men (β=0.29 ± 0.12; p=0.02), black women (β=0.29 ± 0.12; p=0.01), and black hypertensives (β=0.32 ± 0.12; p=0.007), and venular dilation in white hypertensives (β=0.24 ± 0.10; p=0.03). cIMTf associated negatively with peak arteriolar dilation in black hypertensives (β=-0.22 ± 0.10; p=0.03). Conclusion - In general, static retinal vessel calibre was associated with BP but not with TOD. However, the functional response of retinal arteriolar calibre to a light flicker stimulus was positively and independently associated with renal function (eGFR), as well as negatively associated with cIMTf, predominantly in blacks.