Serum endothelin-1 and endothelin-2 levels in healthy controls and circadian hypertension phenotypes: A comparison of dipper and non-dipper patients

Objective The aim of this study was to evaluate serum endothelin-1 (ET-1) and endothelin-2 (ET-2) levels in patients with dipper and non-dipper hypertension compared to normotensive controls and to investigate the potential diagnostic value of these biomarkers in distinguishing circadian blood pressure phenotypes.Methods This prospective case–control study included 163 participants classified into three groups based on 24-hour ambulatory blood pressure monitoring (ABPM): normotensive controls (n = 60), dipper hypertensive (n = 61), and non-dipper hypertensive (n = 42) patients. Dipper status was defined as a 10% nocturnal reduction in both systolic and diastolic blood pressure. Individuals with diabetes, established cardiovascular disease, or secondary hypertension were excluded. Serum endothelin-1 (ET-1) ET-1 and endothelin-2 (ET-2) ET-2 levels were analyzed using double-antibody sandwich ELISA kits.Results ET-1 levels were significantly lower in dipper hypertensive patients (p < 0.001) compared to other groups. Conversely, ET-2 levels did not significantly differ between hypertensive phenotypes. ET-1 proved to be a strong diagnostic marker for distinguishing non-dipper hypertension (AUC = 0.830, sensitivity 83.3%, specificity 75.4%). While advanced age independently predicted the non-dipper pattern (OR = 1.101, p = 0.002), BMI and D-dimer were associated with the dipper phenotype.Conclusion This study identifies serum endothelin-1 is a strong, independent marker of the non-dipper hypertensive phenotype, which is associated with increased cardiovascular risk. The preservation of low endothelin-1 levels in dipper hypertension patients reflects intact endothelial and circadian regulation, whereas the absence of this response in non-dipper patients indicates impaired vascular adaptation. The inverse association of endothelin-2 with non-dipper status further suggests a protective buffering role that may be attenuated by increasing metabolic burden.