Untreated Secondary Hypertension Is Associated With Distinct Retinal Microvascular Remodeling Assessed by Adaptive Optics Imaging

Objective: Secondary hypertension is characterized by chronic exposure to hormonal excess that may induce microvascular injury beyond blood pressure elevation alone. Adaptive optics retinal imaging enables direct in vivo quantification of retinal arteriolar structure with near-histological resolution. We hypothesized that untreated secondary hypertension is associated with a distinct microvascular remodeling phenotype compared with essential hypertension. Design and method: We prospectively enrolled patients with secondary hypertension due to primary aldosteronism, Cushing syndrome, or pheochromocytoma/paraganglioma, and patients with essential hypertension undergoing adaptive optics retinal imaging. Primary outcomes were retinal wall-to-lumen ratio and wall cross-sectional area. Propensity scores were derived using multivariable logistic regression including demographic and clinical covariates. Patients with secondary hypertension were matched 1:3 to essential hypertension controls without replacement using a caliper of 0.2 standard deviations of the logit of the propensity score, with exact matching on sex. Outcomes were analyzed using generalized estimating equations with robust standard errors to account for clustering within matched sets. A prespecified subgroup analysis evaluated patients examined prior to surgical treatment. Results: The unmatched cohort included 60 patients with secondary hypertension and 957 with essential hypertension. Fifty-seven patients with secondary hypertension were matched to 162 controls. In the matched cohort (n = 219), mean age was 55.8 ± 12.4 years and mean systolic blood pressure was 133 ± 17 mmHg. In the cohort of patients who received surgical treatment, secondary hypertension was independently associated with baseline lower wall-to-lumen ratio (β = -0.049, 95% confidence interval -0.071 to -0.026; p < 0.001) and higher wall cross-sectional area (β = +432.5, 95% confidence interval +382.1 to +482.9; p < 0.001). However, no association secondary hypertension with wall-to-lumen ratio or wall cross-sectional area was seen in the overall matched cohort. Conclusions: These findings suggest a specific hypertrophic remodeling pattern related to hormonal excess that may partially regress after causal treatment in the subgroup of patients with secondary hypertension assigned to surgery.