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

Journal of Translational Medicine

Kent R Bailey²  Julie A Johnson⁷  Eric Boerwinkle⁵  Rhonda M Cooper-DeHoff⁷  John G Gums¹  Amber L Beitelshees³  Arlene B Chapman⁶  Gary L Schwartz⁴  Stephen T Turner⁴ 

[1] Department of Community Health and Family Medicine, University of Florida, Gainesville, FL, USA;Division of Biostatistics, Department of Health Sciences Research, Mayo Clinic, 200 First Street S.W, Rochester, MN, USA;Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA;Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA;Human Genetics and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, USA;Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA;Department of Medicine, University of Florida, Gainesville, FL, USA

关键词: plasma renin activity;    thiazide diuretic;    beta-blocker;    antihypertensive drug therapy;    blood pressure monitoring;    hypertension;   

Others  :  1206034
DOI  :  10.1186/1479-5876-10-47

 received in 2011-12-20, accepted in 2012-03-13,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Turner et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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