FACTORS DETERMINING THE BLOOD-PRESSURE RESPONSE TO ENALAPRIL AND NIFEDIPINE IN HYPERTENSION ASSOCIATED WITH NIDDM

OBJECTIVE-To examine the factors that determine the blood pressure res ponse to enalapril and nifedipine monotherapy in the treatment of hype rtension associated with non-insulin-dependent diabetes mellitus (NIDD M). RESEARCH DESIGN AND METHODS-After a 6-week placebo baseline period , 102 hypertensive NIDDM patients were randomly assigned, double-blind ly, to treatment with nifedipine retard (slow release) (n = 52) or ena lapril (n = 50). The daily dosage of enalapril was increased, if requi red, from 10 to 20 to 40 mg and that of nifedipine from 40 to 60 to 80 mg at 4-week intervals during the 12-week titration period. Blood pre ssure, 24-h urinary albumin excretion (UAE), biochemical data, and ser um angiotensin-converting enzyme (ACE) activity were measured at weeks -6, -4, 0, 4, 8, and 12. At week 0, venous blood was also sampled for baseline plasma atrial natriuretic peptide, renin, aldosterone, and s erum insulin concentrations. RESULTS-At week 12, the mean daily dose o f enalapril was 35 +/- 11.4 mg, and 27 (57%) patients were receiving t he maximum daily dose of 40 mg. In the nifedipine group, the mean dail y drug dose was 50 +/- 12.9 mg, and 4 (8%) were receiving the maximum daily dose of 80 mg. Despite a dose-dependent fall in the serum ACE ac tivity in the enalapril group, the mean arterial pressure (MAP) was re duced by only 8 mmHg throughout the 12-week titration period compared to a decline of 15, 18, and 19 mmHg at weeks 0, 4, and 12, respectivel y, in the nifedipine group (P = 0.01 between groups). In the enalapril group, changes in MAP between weeks 0 and 12 correlated significantly with baseline plasma glucose (r = 0.45, P = 0.001) and aldosterone co ncentrations (r = -0.32, P = 0.02) and UAE (r = 0.3, P = 0.04). There was no statistically significant correlation between the changes in MA P and baseline plasma renin concentration. On multivariate analysis, t he baseline renal function, glycemic control, and plasma aldosterone a nd serum insulin concentrations were all independently related to the changes in blood pressure in the enalapril-treated patients. No such s tatistical associations were observed in the nifedipine group. CONCLUS IONS-In hypertensive NIDDM patients, the activity of the renin-angiote nsin-aldosterone system, the level of serum insulin, glycemic control, renal function, and proteinuria may be important determinants of the blood pressure response to ACE inhibition. Good glycemic control may o ptimize the antihypertensive efficacy of concomitant ACE inhibitor the rapy.