CIRCULATING CERAMIDE AS A POTENTIAL BIOMARKER FOR ISOLATED NOCTURNAL HYPERTENSION

Abstract

Objective: Isolated nocturnal hypertension (INH) is a subtype of hypertension characterized as an elevated blood pressure (BP) at nighttime only. To identify potential new biomarkers related with INH, we compared serum metabolite profiles between INH and normotensive controls. Design and method: Twenty-four-hour ambulatory BP monitoring was performed with Mobil-O-graph (IEM, Germany) monitors in untreated outpatients. INH was defined as a nocturnal BP greater or equal to 120/70 mmHg and daytime BP less than 135/85 mmHg at both two visits within a month. Age-sex matched normotensives (NT) were included as controls. We applied untargeted liquid chromatography tandem mass spectrometry (LC-MS) to detect serum metabolites. Multiple algorithms were first run in a training set (40 INH and 40 NT) and then in a test set (22 INH and 19 NT) to select and verify potential biomarkers. We computed student's P-values corrected by multiple comparison and VIP (Variable Importance in the Projection) score. Based on the results of untargeted LC-MS, we quantified 8 circulating sphingolipids, including sphingomyelin (SM) (d18:1/16:0), SM (d18:1/18:0), SM (d18:1/24:1), ceramide (Cer) (d18:1/16:0), Cer (d18:1/18:0), Cer (d18:1/24:1), sphingosine and sphingosine-1-phosphate in the test set by a targeted LC-MS method. Results: Orthogonal partial least squares-discriminant analysis (OPLS-DA) demonstrated a clear separation of metabolite profiles of INH patients from NT controls (R2 = 0.747, Q2 = 0.672). Cer (d18:1/16:0) had significant association with INH (odds ratio (OR) = 0.290 per SD, 95% confidence interval (CI), 0.125–0.715, P trend = 0.0027). The ceramide score, calculated as a sum of concentrations of the three ceramides, was associated with a lower risk of INH across extreme quartiles (OR = 0.592, 95% CI, 0.400–0.875, P trend = 0.0085). Moreover, Cer (18:1/16:0) significantly improved the diagnostic prediction of INH (P = 0.04). Conclusions: Our study illustrated a novel association between plasma ceramide concentration and INH. More research on ceramides in hypertensive pathobiology might be warranted.