Clinical and Experimental Hypertension · Mar 3, 2026

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

By Küçüksevgili B, Dogru MT, Kandemir H et al.

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.

doi.org/10.1080/10641963.2026.2637683Open accessPubMed 41774498Biomarkers