Laboratory tests as predictors of the antihypertensive effects of amlodipine, bisoprolol, hydrochlorothiazide and losartan in men: results from the randomized, double-blind, crossover GENRES Study.
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.
Suonsyrjä
Timo
T
Department of Medicine, University of Helsinki, and Biomedicum Helsinki, Helsinki, Finland.
Hannila-Handelberg
Tuula
T
Paavonen
Kristian J
KJ
Miettinen
Helena E
HE
Donner
Kati
K
Strandberg
Timo
T
Tikkanen
Ilkka
I
Tilvis
Reijo
R
Pentikäinen
Pertti J
PJ
Kontula
Kimmo
K
Hiltunen
Timo P
TP
D000328:Adult; D017311:Amlodipine / Q000494:pharmacology / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017298:Bisoprolol / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000097:blood*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005544:Forecasting; D006801:Humans; D006852:Hydrochlorothiazide / Q000494:pharmacology / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy*; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012083:Renin / Q000097:blood*; D012964:Sodium / Q000652:urine*; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D017311:Amlodipine; D012964:Sodium; D012083:Renin; D019808:Losartan; D002118:Calcium; D017298:Bisoprolol