Plasma renin activity predicts blood pressure responses to beta-blocker and thiazide diuretic as monotherapy and add-on therapy for hypertension

Abstract

Background: Age and race categories or renin profiling have been recommended to predict blood pressure responses to monotherapy with a beta-blocker or thiazide diuretic. Whether these or other characteristics predict blood pressure responses when the drugs are administered as add-on therapy is uncertain.

Methods: We evaluated predictors of blood pressure response in 363 men and women < or =65 years of age with primary hypertension (152 blacks, 211 whites), 86 of whom (24%) were untreated and 277 of whom (76%) were withdrawn from previous antihypertensive drugs before randomization to either atenolol followed by addition of hydrochlorothiazide (N = 180) or hydrochlorothiazide followed by addition of atenolol (N = 183). Responses were determined by home blood pressure averages before and after each drug administration. Race, age, plasma renin activity, and other characteristics including pretreatment blood pressure levels were incorporated into linear regression models to quantify their contributions to prediction of blood pressure responses.

Results: Plasma renin activity and pretreatment blood pressure level consistently contributed to prediction of systolic and diastolic responses to each drug administered as mono- and as add-on therapy. Higher plasma renin activity was consistently associated with greater blood pressure responses to atenolol and lesser responses to hydrochlorothiazide. The predictive effects of plasma renin activity were statistically independent of race, age, and other characteristics.

Conclusions: Plasma renin activity and pretreatment blood pressure level predict blood pressure responses to atenolol and hydrochlorothiazide administered as mono- and as add-on therapy in men and women < or =65 years of age.

Figure 1

Frequency distribution histograms of systolic blood pressure responses to atenolol and hydrochlorothiazide administered as monotherapy and as add-on therapy (to the other drug), adjusted for differences in pretreatment blood pressure levels. Mean ± standard deviation of adjusted blood pressure response is given above each histogram. Negative x-axis values indicate decline in blood pressure in response to drug treatment. Y-axis values are numbers of participants (counts).

Figure 2

Frequency distribution histograms of diastolic blood pressure responses to atenolol and hydrochlorothiazide administered as monotherapy and as add-on therapy (to the other drug), adjusted for differences in pretreatment blood pressure levels. Mean ± standard deviation of adjusted blood pressure response is given above each histogram. Negative x-axis values indicate decline in blood pressure in response to drug treatment. Y-axis values are numbers of participants (counts).

Figure 3

Predicted blood pressure responses as a function of plasma renin activity. The plotted points are at the observed 10th, 25th, 50th, 75th, and 90th percentiles of plasma renin activity distributions prior to mono- and add-on therapy. Participants were randomized to receive atenolol monotherapy followed by hydrochlorothiazide add-on therapy (N = 180) or hydrochlorothiazide monotherapy followed by atenolol add-on therapy (N = 183). The predicted blood pressure responses at each renin percentile are from a single linear regression model in which all other predictors (race, sex, age, log hypertension duration, current smoker, ethanol intake, height, waist circumference, and baseline blood pressure) were held constant at their respective mean values. DBP, diastolic blood pressure; SBP, systolic blood pressure.