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Objective: Individual blood pressure responses to antihypertensive therapy are difficult to predict. To improve optimization of antihypertensive therapy, we analyzed correlations of relevant laboratory tests with blood pressure responses to four antihypertensive monotherapies., Methods: In the GENRES study, 208 Finnish men aged 35-60 years with moderate hypertension used amlodipine 5 mg, bisoprolol 5 mg, hydrochlorothiazide 25 mg and losartan 50 mg daily, each for 4 weeks as a monotherapy in a double-blind, randomized, placebo-controlled crossover study; that is, each subject received each type of monotherapy in a random order. The treatment periods were preceded and separated by 4-week placebo periods. Ambulatory 24-h and office blood pressure measurements were carried out after all study periods. Data from several biochemical tests were correlated to antihypertensive drug responses., Results: Serum total calcium concentration was negatively correlated with blood pressure responses to amlodipine (P values 0.001-0.002). Plasma renin activity was positively correlated with blood pressure responses to losartan (P values 0.001-0.005) and bisoprolol (P values 0.03-0.17), and negatively with blood pressure responses to hydrochlorothiazide (P values 0.01-0.07). Daily urinary excretion of sodium was negatively correlated with ambulatory blood pressure responses to amlodipine (P values 0.001-0.01)., Conclusions: In this carefully controlled study, marked individual variations in antihypertensive drug responsiveness were found to correlate to several baseline laboratory parameters. The negative correlation between serum calcium levels and amlodipine responses is intriguing and suggests an underlying mechanistic association. Collectively, our data imply that laboratory tests may have some value in prediction of the efficacy of various antihypertensive drug therapies, although great patient-to-patient variation remains an obstacle for exact predictive classification.

Background: Only a minority of hypertensive individuals is adequately controlled for their hypertension, partially because reliable predictors for efficient antihypertensive drug therapy are lacking., Methods: In a prospective, randomized, double-blind, cross-over, placebo-controlled study (The GENRES Study), 208 moderately hypertensive Finnish men (aged 35 to 60 years) were treated for 4 weeks with antihypertensive drugs from four different classes: amlodipine (5 mg), bisoprolol (5 mg), hydrochlorothiazide (25 mg), or losartan (50 mg) daily. Each individual received each of the four monotherapies in a randomized order. Four-week placebo periods were included before and between drug treatment periods. Antihypertensive responses were assessed with 24-h ambulatory and office measurements and analyzed according to age, body mass index, triceps skin fold thickness, waist-to-hip ratio, duration of hypertension, number of previous antihypertensive drugs, number of affected parents, and blood pressure (BP) levels, and profiles during placebo periods., Results: The median BP responses in 24-h ambulatory recordings (systolic/diastolic) were 11/8 mm Hg for bisoprolol, 9/6 mm Hg for losartan, 7/5 mm Hg for amlodipine, and 5/2 mm Hg for hydrochlorothiazide. The highest pairwise within-subject correlations in BP responses were seen for the combinations of bisoprolol-losartan and amlodipine-hydrochlorothiazide. The BP responses to bisoprolol and losartan did not vary according to the variables. Amlodipine and hydrochlorothiazide responses were positively correlated with age, placebo BP level, and lower night-time dipping on placebo., Conclusions: Baseline clinical and BP parameters may be used to predict the efficacy of antihypertensive therapies. The GENRES Study material should provide an excellent platform for future pharmacogenetic analyses of antihypertensive drug responsiveness.