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

Stephen T Turner, Gary L Schwartz, Arlene B Chapman, Amber L Beitelshees, John G Gums, Rhonda M Cooper-Dehoff, Eric Boerwinkle, Julie A Johnson, Kent R Bailey, Stephen T Turner, Gary L Schwartz, Arlene B Chapman, Amber L Beitelshees, John G Gums, Rhonda M Cooper-Dehoff, Eric Boerwinkle, Julie A Johnson, Kent R Bailey

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.

Figures

Figure 1
Figure 1
Signal, noise, and total variances of the measured blood pressure responses to single-drug therapy with atenolol or hydrochlorothiazide and their weighted averages.
Figure 2
Figure 2
Signal-to-noise ratios of the measured blood pressure responses to single-drug therapy with atenolol or hydrochlorothiazide and their weighted averages.

References

    1. Parati G, Omboni S, Bilo G. Why Is Out-of-Office Blood Pressure Measurement Needed? Home Blood Pressure Measurements Will Increasingly Replace Ambulatory Blood Pressure Monitoring in the Diagnosis and Management of Hypertension. Hypertension. 2009;54:181–187. doi: 10.1161/HYPERTENSIONAHA.108.122853.
    1. Appel LJ, Stason WB. Ambulatory blood pressure monitoring and blood pressure self-measurement in the diagnosis and management of hypertension. Ann Intern Med. 1993;118:867–882.
    1. Mancia G, Parati G. Ambulatory blood pressure monitoring and organ damage. Hypertension. 2000;36:894–900.
    1. Bobrie G, Chatellier G, Genes N, Clerson P, Vaur L, Vaisse B, Menard J, Mallion JM. Cardiovascular prognosis of "masked hypertension" detected by blood pressure self-measurement in elderly treated hypertensive patients. JAMA. 2004;291:1342–1349. doi: 10.1001/jama.291.11.1342.
    1. Staessen JA, Den Hond E, Celis H, Fagard R, Keary L, Vandenhoven G, O'Brien ET. Antihypertensive treatment based on blood pressure measurement at home or in the physician's office: a randomized controlled trial. JAMA. 2004;291:955–964. doi: 10.1001/jama.291.8.955.
    1. Staessen JA, Thijs L, Fagard R, O'Brien ET, Clement D, de Leeuw PW, Mancia G, Nachev C, Palatini P, Parati G. et al.Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertension. Systolic Hypertension in Europe Trial Investigators [see comments] JAMA. 1999;282:539–546. doi: 10.1001/jama.282.6.539.
    1. Mancia G, Parati G. Office compared with ambulatory blood pressure in assessing response to antihypertensive treatment: a meta-analysis. J Hypertens. 2004;22:435–445.
    1. Ishikawa J, Carroll DJ, Kuruvilla S, Schwartz JE, Pickering TG. Changes in home versus clinic blood pressure with antihypertensive treatments: a meta-analysis. Hypertension. 2008;52:856–864. doi: 10.1161/HYPERTENSIONAHA.108.115600.
    1. Turner ST, Schwartz GL, Boerwinkle E. Personalized medicine for high blood pressure. Hypertension. 2007;50:1–5. doi: 10.1161/HYPERTENSIONAHA.107.087049.
    1. Preston RA, Materson BJ, Reda DJ, Williams DW, Hamburger RJ, Cushman WC, Anderson RJ. Age-race subgroup compared with renin profile as predictors of blood pressure response to antihypertensive therapy. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. JAMA. 1998;280:1168–1172. doi: 10.1001/jama.280.13.1168.
    1. Turner ST, Schwartz GL, Chapman AB, Beitelshees AL, Gums JG, Cooper-DeHoff RM, Boerwinkle E, Johnson JA, Bailey KR. Plasma renin activity predicts blood pressure responses to beta-blocker and thiazide diuretic as monotherapy and add-on therapy for hypertension. Am J Hypertens. 2010;23:1014–1022. doi: 10.1038/ajh.2010.98.
    1. Chapman AB, Schwartz GL, Boerwinkle E, Turner ST. Predictors of antihypertensive response to a standard dose of hydrochlorothiazide for essential hypertension. Kidney Int. 2002;61:1047–1055. doi: 10.1046/j.1523-1755.2002.00200.x.
    1. Canzanello VJ, Baranco-Pryor E, Rahbari-Oskoui F, Schwartz GL, Boerwinkle E, Turner ST, Chapman AB. Predictors of blood pressure response to the angiotensin receptor blocker candesartan in essential hypertension. Am J Hypertens. 2008;21:61–66. doi: 10.1038/ajh.2007.24.
    1. Finkielman JD, Schwartz GL, Chapman AB, Boerwinkle E, Turner ST. Reproducibility of blood pressure response to hydrochlorothiazide. J Clin Hypertens (Greenwich) 2002;4:408–412. doi: 10.1111/j.1524-6175.2002.00965.x.
    1. Finkielman JD, Schwartz GL, Chapman AB, Boerwinkle E, Turner ST. Lack of agreement between office and ambulatory blood pressure responses to hydrochlorothiazide. Am J Hypertens. 2005;18:398–402. doi: 10.1016/j.amjhyper.2004.10.021.
    1. Beitelshees AL, Gong Y, Bailey KR, Turner ST, Chapman AB, Schwartz GL, Gums JG, Boerwinkle E, Johnson JA. Comparison of office, ambulatory, and home blood pressure antihypertensive response to atenolol and hydrochlorthiazide. J Clin Hypertens (Greenwich) 2010;12:14–21. doi: 10.1111/j.1751-7176.2009.00185.x.
    1. Johnson JA, Boerwinkle E, Zineh I, Chapman AB, Bailey K, Cooper-DeHoff RM, Gums J, Curry RW, Gong Y, Beitelshees AL. et al.Pharmacogenomics of antihypertensive drugs: rationale and design of the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study. Am Heart J. 2009;157:442–449. doi: 10.1016/j.ahj.2008.11.018.
    1. Topouchian JA, El Assaad MA, Orobinskaia LV, El Feghali RN, Asmar RG. Validation of two devices for self-measurement of brachial blood pressure according to the International Protocol of the European Society of Hypertension: the SEINEX SE-9400 and the Microlife BP 3AC1-1. Blood Press Monit. 2005;10:325–331. doi: 10.1097/00126097-200512000-00008.
    1. O'Brien E, Mee F, Atkins N, O'Malley K. Accuracy of the SpaceLabs 90207 determined by the British Hypertension Society protocol. J Hypertens. 1991;9:573–574. doi: 10.1097/00004872-199106000-00016.
    1. Gill JS, Zezulka AV, Beevers DG, Davies P. Relation between initial blood pressure and its fall with treatment. Lancet. 1985;1:567–569.
    1. Snedecor GW, Cochran WG. Statistical methods. 7. Ames IA,: Iowa State Univ. Press; 1980.
    1. Risch N, Merikangas K. The future of genetic studies of complex human diseases. Science. 1996;273:1516–1517. doi: 10.1126/science.273.5281.1516.
    1. Cannella G, Paoletti E, Barocci S, Massarino F, Delfino R, Ravera G, Di Maio G, Nocera A, Patrone P, Rolla D. Angiotensin-converting enzyme gene polymorphism and reversibility of uremic left ventricular hypertrophy following long-term antihypertensive therapy. Kidney Int. 1998;54:618–626. doi: 10.1046/j.1523-1755.1998.00027.x.
    1. Levy D, Ehret GB, Rice K, Verwoert GC, Launer LJ, Dehghan A, Glazer NL, Morrison AC, Johnson AD, Aspelund T. et al.Genome-wide association study of blood pressure and hypertension. Nat Genet. 2009;41:677–687. doi: 10.1038/ng.384.
    1. Bell KJ, Hayen A, Macaskill P, Craig JC, Neal BC, Fox KM, Remme WJ, Asselbergs FW, van Gilst WH, Macmahon S. et al.Monitoring initial response to Angiotensin-converting enzyme inhibitor-based regimens: an individual patient data meta-analysis from randomized, placebo-controlled trials. Hypertension. 2010;56:533–539. doi: 10.1161/HYPERTENSIONAHA.110.152421.
    1. Macrae CA, Vasan RS. Next-generation genome-wide association studies: time to focus on phenotype? Circ Cardiovasc Genet. 2011;4:334–336. doi: 10.1161/CIRCGENETICS.111.960765.
    1. Mokwe E, Ohmit SE, Nasser SA, Shafi T, Saunders E, Crook E, Dudley A, Flack JM. Determinants of blood pressure response to quinapril in black and white hypertensive patients: the Quinapril Titration Interval Management Evaluation trial. Hypertension. 2004;43:1202–1207. doi: 10.1161/01.HYP.0000127924.67353.86.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren