Heritability of The Retinal Microcirculation in Flemish Families

BACKGROUND Few population studies have described the heritability and intrafamilial concordance of the retinal microvessels, or the genetic or environmental correlations of the phenotypes of these vessels. METHODS We randomly selected 413 participants from 70 families (mean age, 51.5 years; 50.1% women) from a Flemish population. We postprocessed retinal images using IVAN software to generate the central retinal arteriole equivalent (CRAE), central retinal venule equivalent (CRVE), and arteriole-to-venule-ratio (AVR) from these images. We used SAGE version 6.2 and SAS version 9.2 to compute multivariate-adjusted estimates of heritability and intrafamilial correlations of the CRAE, CRVE, and AVR of the retinal microvessels in the images. RESULTS Sex, age, mean arterial pressure, and smoking explained up to 12.7% of the variance of the phenotypes of the retinal microvessels of the study participants. With adjustments applied for these covariates, the heritability estimates of CRAE, CRVE, and AVR were 0.213 (P = 0.044), 0.339 (P = 0.010), and 0.272 (P = 0.004), respectively. The parent-offspring correlations for CRAE, CRVE, and AVR were 0.118 (NS), 0.225 (P < 0.01), and 0.215 (P < 0.05), respectively. The corresponding values were 0.222 (P < 0.05), 0.213 (P < 0.05), and 0.390 (P < 0.001) for sib-sib correlations, respectively. The genetic and environmental correlations between CRAE and CRVE were 0.360 and 0.545 (P < 0.001 for both). CONCLUSION Our study showed moderate heritability for CRAE, CRVE, and AVR, and a significant genetic correlation of CRAE with CRVE in the Flemish population of our study. These findings suggest that genetic factors influence the diameter of the retinal microvessels, and that CRAE and CRVE share some genetic determinant

Conventional and Ambulatory Blood Pressure as Predictors of Retinal Arteriolar Narrowing

At variance with the long established paradigm that retinal arteriolar narrowing trails hypertension, several longitudinal studies, all based on conventional blood pressure (CBP) measurement, proposed that retinal arteriolar narrowing indicates heightened microvascular resistance and precedes hypertension. In 783 randomly recruited Flemish (mean age, 38.2 years; 51.3% women), we investigated to what extent CBP and daytime (10 am to 8 pm) ambulatory blood pressure (ABP) measured at baseline (1989-2008) predicted the central retinal arteriolar equivalent (CRAE) in retinal photographs obtained at follow-up (2008-2015). Systolic/diastolic hypertension thresholds were 140/90 mm Hg for CBP and 135/85 mm Hg for ABP. In multivariable-adjusted models including both baseline CBP and ABP, CRAE after 10.3 years (median) of follow-up was unrelated to CBP (P≥0.14), whereas ABP predicted CRAE narrowing (P≤0.011). Per 1-SD increment in systolic/diastolic blood pressure, the association sizes were -0.95 μm (95% confidence interval, -2.20 to 0.30)/-0.75 μm (-1.93 to 0.42) for CBP and -1.76 μm (-2.95 to -0.58)/-1.48 μm (-2.61 to -0.34) for ABP. Patients with ambulatory hypertension at baseline (17.0%) had smaller CRAE (146.5 versus 152.6 μm; P&lt;0.001) at follow-up. CRAE was not different (P≥0.31) between true normotension (normal CBP and ABP; prevalence, 77.6%) and white-coat hypertension (elevated CBP and normal ABP, 5.4%) and between masked hypertension (normal CBP and elevated ABP, 10.2%) and hypertension (elevated CBP and ABP, 6.8%). In conclusion, the paradigm that retinal arteriolar narrowing precedes hypertension can be explained by the limitations of CBP measurement, including nonidentification of masked and white-coat hypertension.</p