Power to identify a genetic predictor of antihypertensive drug response using different methods to measure blood pressure response

• Type of Material: Article
• Authors: Stephen T. Turner, Mayo Clinic; Gary L. Schwartz, Mayo Clinic; Arlene Chapman, Emory University; Amber L. Beitelshees, University of Maryland; John G. Gums, University of Florida; Rhonda M. Cooper-DeHoff, University of Florida; Eric Boerwinkle, University of Texas Health Science Center; Julie A. Johnson, University of Florida; Kent R. Bailey, Mayo Clinic
• Language: English
• Date: 2012-03-13
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2012 Turner et al; licensee BioMed Central Ltd.
• License: Creative Commons Attribution 2.0 Generic
• Final Published Version (URL): http://dx.doi.org/10.1186/1479-5876-10-47
• Title of Journal or Parent Work: Journal of Translational Medicine
• ISSN: 1479-5876
• Volume: 10
• Issue: 1
• Start Page: 47
• End Page: 47
• Grant/Funding Information: Funding was from NIH Pharmacogenetics Research Network grant U01-GM074492; K23 grants HL091120 (A. L. Beitelshees) and HL086558 (R. M. Cooper-DeHoff); CTSA grants UL1-RR092890 (University of Florida), UL1-RR025008 (Emory University), and UL1-RR024150 (Mayo Clinic); and funds from the Mayo Foundation.
• Keywords: Life Sciences & Biomedicine; OFFICE; GENOME-WIDE ASSOCIATION; Science & Technology; MANAGEMENT; blood pressure monitoring; THERAPY; plasma renin activity; hypertension; HYDROCHLOROTHIAZIDE; SELF-MEASUREMENT; antihypertensive drug therapy; Medicine, Research & Experimental; beta-blocker; thiazide diuretic; HOME; PROTOCOL; MEDICINE, RESEARCH & EXPERIMENTAL; ESSENTIAL-HYPERTENSION; METAANALYSIS; Research & Experimental Medicine
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Biostatistics

Abstract

Background: To determine whether office, home, ambulatory daytime and nighttime blood pressure (BP) responses to antihypertensive drug therapy measure the same signal and which method provides greatest power to identify genetic predictors of BP response.Methods: We analyzed office, home, ambulatory daytime and nighttime BP responses in hypertensive adults randomized to atenolol (N = 242) or hydrochlorothiazide (N = 257) in the Pharmacogenomic Evaluation of Antihypertensive Responses Study. Since different measured BP responses may have different predictors, we tested the "same signal" model by using linear regression methods to determine whether known predictors of BP response depend on the method of BP measurement. We estimated signal-to-noise ratios and compared power to identify a genetic polymorphism predicting BP response measured by each method separately and by weighted averages of multiple methods.Results: After adjustment for pretreatment BP level, known predictors of BP response including plasma renin activity, race, and sex were independent of the method of BP measurement. Signal-to-noise ratios were more than 2-fold greater for home and ambulatory daytime BP responses than for office and ambulatory nighttime BP responses and up to 11-fold greater for weighted averages of all four methods. Power to identify a genetic polymorphism predicting BP response was directly related to the signal-to-noise ratio and, therefore, greatest with the weighted averages.Conclusion: Since different methods of measuring BP response to antihypertensive drug therapy measure the same signal, weighted averages of the BP responses measured by multiple methods minimize measurement error and optimize power to identify genetic predictors of BP response.