title: Predictors of antihypertensive drug responses: initial data from a placebo-controlled, randomized, cross-over study with four antihypertensive drugs (The GENRES Study).
abstract: 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.
authors.affiliation: Department of Medicine, University of Helsinki, and Biomedicum Helsinki, Helsinki, Finland.
authors.forename: Timo P
authors.initials: TP
authors.lastname: Hiltunen
authors.forename: Timo
authors.initials: T
authors.lastname: Suonsyrjä
authors.forename: Tuula
authors.initials: T
authors.lastname: Hannila-Handelberg
authors.forename: Kristian J
authors.initials: KJ
authors.lastname: Paavonen
authors.forename: Helena E
authors.initials: HE
authors.lastname: Miettinen
authors.forename: Timo
authors.initials: T
authors.lastname: Strandberg
authors.forename: Ilkka
authors.initials: I
authors.lastname: Tikkanen
authors.forename: Reijo
authors.initials: R
authors.lastname: Tilvis
authors.forename: Pertti J
authors.initials: PJ
authors.lastname: Pentikäinen
authors.forename: Juha
authors.initials: J
authors.lastname: Virolainen
authors.forename: Kimmo
authors.initials: K
authors.lastname: Kontula
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D017311:Amlodipine / Q000627:therapeutic use; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017298:Bisoprolol / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004232:Diuretics / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005387:Finland; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015203:Reproducibility of Results; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004232:Diuretics; D006852:Hydrochlorothiazide; D017311:Amlodipine; D019808:Losartan; D017298:Bisoprolol