title: Presence of arachidonoyl-carnitine is associated with adverse cardiometabolic responses in hypertensive patients treated with atenolol.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Serum level of C20:4 is a promising biomarker to predict adverse cardiometabolic responses including glucose and poor antihypertensive response to atenolol.
authors.affiliation: Department of Pharmacotherapy and Translational Research and Division of Cardiovascular Medicine, Colleges of Pharmacy and Medicine, Center for Pharmacogenomics, University of Florida, P.O. Box 100486, Gainesville, FL 32610-0486, USA.
authors.forename: Liming
authors.initials: L
authors.lastname: Weng
authors.affiliation: Department of Pharmacotherapy and Translational Research and Division of Cardiovascular Medicine, Colleges of Pharmacy and Medicine, Center for Pharmacogenomics, University of Florida, P.O. Box 100486, Gainesville, FL 32610-0486, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Metabolomics Core, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL, USA; Southeast Center for Integrated Metabolomics (SECIM), University of Florida, Gainesville, FL, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Culver
authors.affiliation: Metabolomics Core, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL, USA; Southeast Center for Integrated Metabolomics (SECIM), University of Florida, Gainesville, FL, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Gardell
authors.affiliation: Metabolomics Core, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL, USA; Southeast Center for Integrated Metabolomics (SECIM), University of Florida, Gainesville, FL, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Petucci
authors.affiliation: Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Morse
authors.affiliation: Department of Pharmacotherapy and Translational Research and Division of Cardiovascular Medicine, Colleges of Pharmacy and Medicine, Center for Pharmacogenomics, University of Florida, P.O. Box 100486, Gainesville, FL 32610-0486, USA.
authors.forename: Reginald F
authors.initials: RF
authors.lastname: Frye
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Turner
authors.affiliation: Renal Division, School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Arlene
authors.initials: A
authors.lastname: Chapman
authors.affiliation: Human Genetics and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.affiliation: Department of Pharmacotherapy and Translational Research and Division of Cardiovascular Medicine, Colleges of Pharmacy and Medicine, Center for Pharmacogenomics, University of Florida, P.O. Box 100486, Gainesville, FL 32610-0486, USA.
authors.forename: John
authors.initials: J
authors.lastname: Gums
authors.affiliation: Department of Medicine and Program in Personalized and Genomic Medicine, University of Maryland, Baltimore, MD, USA.
authors.forename: Amber L
authors.initials: AL
authors.lastname: Beitelshees
authors.affiliation: Department of Food Science and Human Nutrition, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, USA.
authors.forename: Peggy R
authors.initials: PR
authors.lastname: Borum
authors.affiliation: Department of Pharmacotherapy and Translational Research and Division of Cardiovascular Medicine, Colleges of Pharmacy and Medicine, Center for Pharmacogenomics, University of Florida, P.O. Box 100486, Gainesville, FL 32610-0486, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Johnson
authors.affiliation: Southeast Center for Integrated Metabolomics (SECIM), University of Florida, Gainesville, FL, USA; Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Garrett
authors.affiliation: Southeast Center for Integrated Metabolomics (SECIM), University of Florida, Gainesville, FL, USA; Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: McIntyre
authors.affiliation: Department of Pharmacotherapy and Translational Research and Division of Cardiovascular Medicine, Colleges of Pharmacy and Medicine, Center for Pharmacogenomics, University of Florida, P.O. Box 100486, Gainesville, FL 32610-0486, USA.
authors.forename: Rhonda M
authors.initials: RM
authors.lastname: Cooper-DeHoff
keywords: Acylcarnitine; Arachidonoyl-carnitine; Atenolol; C20:4; Cardiometabolic syndrome; Hypertension; Pharmacometabolomics