Liming Weng1, Yan Gong1, Jeffrey Culver2, Stephen J Gardell2, Christopher Petucci2, Alison M Morse3, Reginald F Frye1, Stephen T Turner4, Arlene Chapman5, Eric Boerwinkle6, John Gums1, Amber L Beitelshees7, Peggy R Borum8, Julie A Johnson1, Timothy J Garrett9, Lauren M McIntyre9, Rhonda M Cooper-DeHoff1. 1. 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. 2. Metabolomics Core, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL, USA; Southeast Center for Integrated Metabolomics (SECIM), University of Florida, Gainesville, FL, USA. 3. Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL, USA. 4. Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA. 5. Renal Division, School of Medicine, Emory University, Atlanta, GA, USA. 6. Human Genetics and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, USA. 7. Department of Medicine and Program in Personalized and Genomic Medicine, University of Maryland, Baltimore, MD, USA. 8. Department of Food Science and Human Nutrition, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, USA. 9. 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.
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.
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 hypertensivepatients (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.
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