Clinical and molecular approaches to individualize antihypertensive drug therapy

Figures & data

Table I. Stepwise multiple regression modelling of ambulatory blood pressure responses to four antihypertensive monotherapies. P values, direction of the effect, and semipartial R² values are shown.

	Amlodipine responses						Bisoprolol responses						Hydrochlorothiazide responses						Losartan responses
	Systolic			Diastolic			Systolic			Diastolic			Systolic			Diastolic			Systolic			Diastolic
	P	Eff.	PtR^2	P	Eff.	PtR^2	P	Eff.	PtR^2	P	Eff.	PtR^2	P	Eff.	PtR^2	P	Eff.	PtR^2	P	Eff.	PtR^2	P	Eff.	PtR2
Placebo BP level	6E-13	+	0.18	1E-11	+	0.17	0.002	+	0.05	1E-4	+	0.07	4E-5	+	0.07	1E-4	+	0.07	0.003	+	0.04	2E-4	+	0.06
Age	4E-4	+	0.04	6E-6	+	0.07	ns			ns			0.05	+	0.02	ns			0.09	+	0.01	ns	+
Waist-hip ratio	ns			ns			ns			ns			ns			ns			ns			0.04		0.02
Smoking	0.09	+	0.01	0.06	+	0.01	0.06	–	0.02	ns			ns			ns			ns			ns
Earlier diuretic use	ns			0.02	–	0.02	ns			ns			ns			ns			ns			ns
Renin	ns			ns			0.01	+	0.03	0.02	+	0.02	0.05	–	0.02	0.008	–	0.03	1E-4	+	0.06	1E-5	+	0.08
Aldo/renin	0.04	+	0.01	ns			ns			ns			ns			ns			ns			ns
S-Sodium	ns			ns			ns			ns			ns			ns			0.06	+	0.02	0.003	+	0.04
S-Potassium	ns			ns			ns			ns			0.04	–	0.02	ns			ns			0.05	+	0.01
S-Calcium	(0.14)	–		0.02	–	0.02	ns			ns			ns			ns			ns			ns
S-Creatinine	ns			ns			ns			ns			ns			ns			ns			(0.10)	+
S-Glucose	ns			ns			ns			ns			ns			ns			0.005	–	0.04	6E-4	–	0.05
S-Cholesterol	5E-5	–	0.05	0.003	–	0.03	0.02	–	0.02	(0.13)	–		ns			ns			ns			ns
S-Triglycerides	ns			ns			ns			ns			0.03	–	0.02	ns			ns			ns
dU-Sodium	2E-5	–	0.06	0.01	–	0.02	ns			ns			ns			0.08	–	0.01	ns			ns
dU-Albumin	ns			ns			ns			ns			0.04	–	0.02	0.06	–	0.02	ns			ns
R^2 of the model		0.39			0.35			0.09			0.09			0.19			0.12			0.13			0.22

P values > 0.10 in parentheses indicate conditional significancies for the next modelling step (not included in the final model). The following predictors were included in the analyses but were not significant predictors of any of the BP responses: earlier antihypertensive medication use, body mass index, S-Aldosterone, S-Insulin, and S-Urate. Abbreviations: + /– = better/poorer BP response with increasing explanatory variable value; Aldo/renin = S-aldosterone to plasma renin activity ratio; BP = blood pressure; dU = daily urinary excretion; Eff. = effect; ns = P > 0.10; PtR² = drop in R² if the variable was removed from the model; Renin = plasma renin activity; S = fasting serum.

Figure 1. Ambulatory 24-h systolic (A) and diastolic (B) blood pressure responses to losartan in the lowest and the highest quartiles of plasma renin activity (PRA) and serum sodium. Means and SDs are shown. Statistical significance between the extreme quartiles was calculated with Student's t test. SBP = systolic blood pressure; DBP = diastolic blood pressure; PRA = plasma renin activity.

Figure 2. Ambulatory 24-h systolic (A) and diastolic (B) blood pressure responses to amlodipine in the lowest and the highest quartiles of serum cholesterol and calcium. For abbreviations and statistics, see legend to Figure 1.