Power to identify a genetic predictor of antihypertensive drug response using different methods to measure blood pressur
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RESEARCH
Open Access
Power to identify a genetic predictor of antihypertensive drug response using different methods to measure blood pressure response Stephen T Turner1*, Gary L Schwartz1, Arlene B Chapman3, Amber L Beitelshees4, John G Gums5,6, Rhonda M Cooper-DeHoff5,7, Eric Boerwinkle8, Julie A Johnson5,7 and Kent R Bailey2
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. Keywords: hypertension, blood pressure monitoring, antihypertensive drug therapy, beta-blocker, thiazide diuretic, plasma renin activity
Background Although office blood pressure (BP) measurements remain the standard-of-care, averages of out-of-office measurements are more reproducible [1]. Out-of-office averages have also been reported to be more strongly correlated with subclinical target organ damage [2,3] and to better predict future cardiovascular disease * Correspondence: [email protected] 1 Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA Full list of author information is available at the end of the article
events [4-6] than office measurements. Not surprisingly, BP responses to antihypertensive drug therapy are more precisely and accurately determined by out-of-office than office measurements, which are influenced by white coat and placebo effects [7,8]. Consequently, greater use o
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