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

Abstract

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.

CYP2C9 genotype modifies activity of the renin–angiotensin–aldosterone system in hypertensive men

“…The design and first results of the GENRES Study have been described in detail [4,9]. Briefly, 313 moderately hypertensive [mean systolic/diastolic office blood pressures (OBPs) during placebo periods, 153/100 mmHg] Finnish men, aged 35-60 years, were screened.…”

“…OBP and 24-h ambulatory blood pressure (ABP) measurements were done at the end of each period. Baseline laboratory values were obtained at the end of the first placebo period [9]. Creatinine clearance was estimated using the modified Cockroft-Gault formula, (140 À age)  weight/[0.814  serum creatinine (mmol/l)], followed by adjustment for body surface area calculated using the Mosteller formula [SQRT (weight  height/3600)].…”

Common genetic variations of the renin–angiotensin–aldosterone system and response to acute angiotensin I-converting enzyme inhibition in essential hypertension

“…Although some widely used tests such as measurement of plasma renin activity (PRA) may provide some help [2,3], there is no commonly accepted biochemical technique to exactly predict individual responsiveness to a particular class of pharmacotherapy. With the advent of molecular genetic techniques during the past 25 years, much hope has been laid on pharmacogenomics as a novel approach to circumvent problems in individualized medical therapy of complex diseases (for review, see [4]).…”

STK39 variation predicts the ambulatory blood pressure response to losartan in hypertensive men

“…13 For the current study, post-hoc calculations were performed by using the G*Power 3 program 17 and the mean observed s.d. of DBP responses (4.25 mm Hg), 14 allele frequencies 0.50/0.50 (best-case scenario giving genotype group sizes 50-100-50) and an a-level of 0.0007. Assuming clinically meaningful DBP response levels of 2, 4 and 6 mm Hg for the genotype groups gives a power of 82%.…”

“…13 Plasma renin activity (PRA) and serum aldosterone levels were determined by radioimmunoassay (DiaSorin, Saluggia, Italy). 14 Replication study of circulating aldosterone and renin levels in referred hypertensive patients. The recruitment and characteristics of referred hypertensive patients have been described previously.…”