Deep Learning-Based Retinal Biomarker Captures Cardiovascular Risk in Hypertensive Abnormal Dippers Beyond Conventional Metrics

초록

Introduction: Among hypertensive subtypes, abnormal dippers — including non-dippers and risers — are characterized by blunted nocturnal blood pressure (BP) declines and are associated with poor prognosis. However, limited data exist on their relationship with deep learning-derived retinal biomarkers for cardiovascular risk. Hypothesis: We hypothesized that hypertensive individuals with abnormal dipping patterns would have a higher risk of cardiovascular disease (CVD) than normal dippers and that a retinal deep learning-based CVD risk score (Dr.Noon CVD score) would reflect higher cardiovascular burden from nocturnal hypertension compared to traditional risk markers. Goals: This study aimed to compare carotid intima-media thickness (CIMT), coronary artery calcification (CAC), and a deep learning-based retinal biomarker between normal and abnormal dippers. Methods: We analyzed 901 hypertensive patients from a 10-year prospective cohort at Severance Hospital, categorizing them as normal (>10% nocturnal drop, N = 463) or abnormal dippers (<10%, N = 438). Group comparisons of clinical variables were performed using chi-squared or nonparametric tests. CVD incidence was assessed by survival analysis. CIMT, CAC, and Dr.Noon CVD scores were compared using Wilcoxon rank-sum tests. Multivariate analyses adjusted for age, gender, and BMI. Results: Over 10 years, abnormal dippers had a higher cumulative incidence (p = 0.027) and adjusted hazard ratio of CVD events (HR 1.93, 95% CI 1.09-3.39). Age, gender, and BMI did not differ between groups (p > 0.05). Daytime BP was higher in normal dippers (135/82 vs. 132/80 mmHg; p < 0.006), while nighttime BP was higher in abnormal dippers (113/69 vs. 128/76 mmHg; p < 0.001). CIMT did not differ (p = 0.297), and CAC showed a borderline difference (p = 0.068). The Dr.Noon CVD score was higher in abnormal dippers (p = 0.006). In multivariate linear regression, abnormal dippers had a 2.08-point higher Dr.Noon CVD score compared to normal dippers (p < 0.001). Each one-year increase in age was associated with a 0.59-point increase (p < 0.001), suggesting abnormal dipping is comparable to around three years of aging regarding CVD risk. Conclusion: Abnormal nocturnal BP patterns are associated with elevated cardiovascular risk. Traditional risk markers did not fully capture this difference, whereas the deep learning-based retinal biomarker reflected the increased risk, likely due to its sensitivity to microvascular changes from nocturnal hypertension.