Systemic microvascular rarefaction is correlated with dysfunction of late endothelial progenitor cells in mild hypertension: a substudy of EXCAVATION-CHN1.

ABSTRACT

BACKGROUND: Hypertension often presents with microvascular rarefaction (MVR), which is closely associated with impaired angiogenesis. Early detection of MVR is essential for systemic assessment in patient with hypertension. We aimed to determine the systemic MVR through both optical coherence tomography angiography (OCTA) and intravital capillaroscopy, and to investigate their respective efficacies and related mechanisms associated with late endothelial progenitor cells (LEPCs) dysfunction. METHODS: Seventy-one hypertensive and sixty-nine age-match normotensive subjects were included in this study. All subjects received intravital capillaroscopy for skin capillary density (SCD) and OCTA for retinal capillary density (RCD) and non-perfused areas (R-NPA). Subsequently, correlation of LEPCs activities and microvascular rarefaction were examined. RESULTS: Compared with normotensive subjects, hypertensive patients had significantly lower RCD [(52.9 ± 2.9)% vs. (57.8 ± 1.6)%, P < 0.01] and higher R-NPA [(0.12 ± 0.07) mm2 vs. (0.053 ± 0.020) mm2, P < 0.01]. SCD correlated positively with RCD but negatively with R-NPA [(RCD OR = 0.40, 95% CI 0.25-0.67, P < 0.01); (R-NPA OR = 0.39, 95% CI - 0.0029 to 0.0011, P < 0.01)]. The discriminative powers of RCD performed best (AUC 0.79 versus SCD AUC 0.59, P < 0.001) followed by R-NPA (AUC 0.73 versus SCD AUC 0.59, P < 0.001) for systolic blood pressure. Similar pattern is also found for diastolic blood pressure (RCD AUC 0.80 versus SCD AUC 0.54, P < 0.001; R-NPA AUC 0.77 versus SCD AUC 0.54, P < 0.001). Furthermore, LEPCs tube formation was impaired in hypertensive patients (36.8 ± 2.3 vs. 28 ± 3.7, P < 0.01). After multivariate adjustments, positive correlation existed between RCD or R-NPA with LEPCs tube formation (RCD ß = 0.64, 95% CI 0.34-0.91, P < 0.01; R-NPA ß = - 24.67, 95% CI - 43.14 to - 4.63, P < 0.05) but not with SCD (ß = 0.082, 95% CI 0.01-0.18, P = 0.085). CONCLUSION: Compared to intravital capillaroscopy, OCTA is a more precise technique for early detection of hypertensive microvascular rarefaction, which is associated with the fall in LEPC-mediated angiogenesis. Both of OCTA and LEPCs function can help identify hypertension-related capillary abnormality. Trail Registration The trial is a substudy of EXCAVATION-CHN1, registered at clinicaltrials.gov as NCT02817204 (June 26, 2016).