Presence of arachidonoyl-carnitine is associated with adverse cardiometabolic responses in hypertensive patients treated with atenolol

Liming Weng, Yan Gong, Jeffrey Culver, Stephen J. Gardell, Christopher Petucci, Alison M. Morse, Reginald F. Frye, Stephen T. Turner, Arlene Chapman, Eric Boerwinkle, John Gums, Amber L. Beitelshees, Peggy R. Borum, Julie A. Johnson, Timothy J. Garrett, Lauren M. McIntyre, Rhonda M. Cooper-DeHoff

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Introduction: Atenolol, a commonly prescribed β blocker for hypertension, is also associated with adverse cardiometabolic effects such as hyperglycemia and dyslipidemia. Knowledge of the mechanistic underpinnings of these adverse effects of atenolol is incomplete. Objective: We sought to identify biomarkers associated with risk for these untoward effects of atenolol. We measured baseline blood serum levels of acylcarnitines (ACs) that are involved in a host of different metabolic pathways, to establish associations with adverse cardiometabolic responses after atenolol treatment. Methods: Serum samples from Caucasian hypertensive patients (n = 224) who were treated with atenolol in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study were interrogated using a quantitative LC/MS assay for a large number of unique ACs in serum. For the 23 ACs that were detected in serum from ≥80 % of all patients, we conducted linear regression for changes in cardiometabolic factors with baseline AC levels, baseline cardiometabolic factors, age, sex, and BMI as covariates. For the 5 ACs that were detected in serum from 20 to 79 % of the patients, we similarly modeled changes in cardiometabolic factors, but with specifying the AC as present/absent in the regression. Results: Among the 28 ACs, the presence (vs. absence) of arachidonoyl-carnitine (C20:4) was significantly associated with increased glucose (p = 0.0002), and was nominally associated with decreased plasma HDL-C (p = 0.017) and with less blood pressure (BP) lowering (p = 0.006 for systolic BP, p = 0.002 for diastolic BP), after adjustment. Conclusion: Serum level of C20:4 is a promising biomarker to predict adverse cardiometabolic responses including glucose and poor antihypertensive response to atenolol.

Original languageEnglish (US)
Article number160
JournalMetabolomics
Volume12
Issue number10
DOIs
StatePublished - Oct 1 2016

Keywords

  • Acylcarnitine
  • Arachidonoyl-carnitine
  • Atenolol
  • C20:4
  • Cardiometabolic syndrome
  • Hypertension
  • Pharmacometabolomics

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Clinical Biochemistry

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    Weng, L., Gong, Y., Culver, J., Gardell, S. J., Petucci, C., Morse, A. M., Frye, R. F., Turner, S. T., Chapman, A., Boerwinkle, E., Gums, J., Beitelshees, A. L., Borum, P. R., Johnson, J. A., Garrett, T. J., McIntyre, L. M., & Cooper-DeHoff, R. M. (2016). Presence of arachidonoyl-carnitine is associated with adverse cardiometabolic responses in hypertensive patients treated with atenolol. Metabolomics, 12(10), [160]. https://doi.org/10.1007/s11306-016-1098-2