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Objectives: This study was designed to evaluate the long-term effects of combination therapy with an angiotensin-converting enzyme inhibitor and a beta-adrenergic blocking agent on the relation between the decrease in arterial pressure at rest and during exercise and the decrease in left ventricular mass., Background: A variety of antihypertensive drugs including angiotensin-converting enzyme inhibitors and beta-blockers have been shown to reduce ventricular hypertrophy, although little is known about combination therapy and the time course of such a reduction., Methods: Twenty-one patients with previously untreated essential hypertension were treated with a low dose combination of 50 mg of atenolol and 10 mg of enalapril once daily for 39 months. Cardiovascular findings were assessed by two-dimensionally guided M-mode echocardiography in the pretreatment phase and after 6 and 39 months of combination therapy., Results: Combination therapy reduced arterial pressure at rest from 161/108 to 130/86 mm Hg (p less than 0.001) and exercise arterial pressure at 100 W from 192/112 to 167/95 mm Hg (p less than 0.001). After 6 months of treatment, significant decreases in interventricular septal thickness (9%, p less than 0.001), posterior wall thickness (9%, p less than 0.001) and left ventricular mass index (16%, p less than 0.001) were demonstrated on the echocardiogram. After 39 months of therapy, reductions in these values were 28% (p less than 0.001), 29% (p less than 0.001) and 40% (p less than 0.001), respectively., Conclusions: Long-term treatment with combination therapy of atenolol and enalapril produced significant reductions in arterial pressure at rest and during exercise accompanied by a marked reduction of left ventricular mass. However, whereas arterial pressure decreased immediately and remained unchanged, left ventricular mass decreased more gradually and continued to decrease throughout the treatment period of greater than 3 years. Despite this marked reduction in left ventricular mass, left ventricular pump function was well preserved during rest and exercise.

The long-term effects of antihypertensive therapy on echocardiographically proven left ventricular hypertrophy (LVH) were investigated in 117 previously untreated hypertensive patients (mean age of 46 +/- 9 years; 15 women, 102 men). Twenty-two patients (group 1) received daily 100 mg of gallopamil, 25 (group 2) received 200 mg of metoprolol, 35 (group 3) received both 50 mg of atenolol and 20 mg of nifedipine (follow-up of 5 years), 14 (group 4) received 200 mg of acebutolol and 20 mg of nifedipine, and 21 (group 5) daily received 50 mg of atenolol and 10 mg of enalapril (follow-up of 4 years). For the entire population, there was a significant (p less than 0.001) decrease in left ventricular mass index (LVMI) of 24.5% after 1 year, which increased further to 44.1% after 5 years of treatment. In addition, fractional fiber shortening increased by 16% (p less than 0.001). In 82% of the patients, almost complete regression of LVH was achieved. However, the time course of regression of LVMI differed significantly between the five treatment groups, despite similar blood pressure reduction under resting conditions.

Patients with left ventricular hypertrophy (LVH) often exhibit manifestations of myocardial ischemia. In 17 hypertensive patients (group 1, mean age of 56 +/- 4 years, 10 females, 7 males) with ST-segment depression during the exercise electrocardiogram (ECG) and effort angina and normal coronary arteriograms, the left ventricular function at rest and during exercise was studied by heart catheterization. The results were compared with 17 hypertensive patients (group 2, mean age of 56 +/- 6 years, 6 females, 11 males) with coronary artery disease (CAD). The normal pulmonary wedge pressure at rest (group 1, 8.9 +/- 3 mm Hg; group 2, 8.9 +/- 3 mm Hg) was pathologically increased (p less than 0.001) in both groups (group 1, 27.1 +/- 5 mm Hg; group 2, 28.8 +/- 7 mm Hg) even at a work load of 50 W with a further increase at 75 W to 31 +/- 4 and 29.7 +/- 4 mm Hg, respectively. Cardiac output was normal. There was no significant correlation between ST-segment depression, pulmonary wedge pressure, LVH, and Holter ECG. Hypertensive patients without CAD may reveal a disturbed pump function due to ischemia even at low work loads, which does not differ significantly from patients with CAD. This may provoke subendocardial fibrosis and thereby contribute to the development of heart failure.

The effect of long-term therapy of hypertension with antihypertensive drugs was investigated in 117 previously untreated patients (15 women, 102 men; mean age 46.4 +/- 9 years) with echocardiographically proven left-ventricular hypertrophy. 22 patients (group 1) received 100 mg/d Gallopamil, 25 (group 2) received 200 mg/d Metoprolol, 35 daily received both 50 mg Atenolol and 20 mg Nifedipine (group 3), 14 received daily 200 mg Acebutolol plus 20 mg Nifedipine (group 4), and 21 (group 5) 50 mg Atenolol plus 10 mg Enalapril daily. The treatment period lasted a mean of 38 (36.2-42.3) months. Left-ventricular muscle mass index (LVMI) as well as septal and posterior-wall thickness decreased significantly after 12.8 and 38.5 months (P less than 0.001). After a mean of 38.5 months LVMI had decreased by 36.7% in group 1, 35.1% in group 2, 42.3% in group 3, 45% in group 4 and 39.6% in group 5. LVMI was within normal range (less than or equal to 95 g/m2) in 81 of the 117 patients (69.2%) at the end of the treatment period. There was, however, no significant increase of the end-diastolic dimension of the left ventricle, but a significant increase of "fractional shortening" as a measure of myocardial contractility.

Fourteen patients with previously untreated essential hypertension and left ventricular hypertrophy were treated with a fixed-dose combination of acebutolol 200 mg and nifedipine 20 mg once daily for a followup of 25.6 +/- 1.8 months. Echocardiography showed a significant decrease after a mean period of 6.6 months in interventricular septal thickness (14.8%, p less than 0.001), posterior wall thickness (14.8%, p less than 0.001), and left ventricular mass index (21.3%). After 25.6 months, the reductions were 29% (p less than 0.001), 28.1% (p less than 0.001), and 38.7% (p less than 0.001), respectively. Left wall thickness was significantly reduced, but left ventricular end-systolic and end-diastolic dimensions and fractional shortening remained unchanged. Treatment reduced resting blood pressure from 161/102 mmHg to 132/87 mmHg (p less than 0.001) and reduced exercise blood pressure at 100 W from 208/113 mmHg to 170/94 mmHg (p less than 0.001). Thus, nifedipine in combination with acebutolol produces significant blood-pressure reduction accompanied by regression of left ventricular hypertrophy without noticeable changes in left ventricular function.

In a previous study (1) we could show a significantly more pronounced reversal of LVH with metoprolol than with gallopamil, whereas the combined therapy with atenolol and nifedipine was even more effective. We now report in 121 previously untreated hypertensive patients the longterm effect of the beta-blocker metoprolol (200 mg/die); 25 patients, mean age 43.6 yrs., follow-up 32.1 +/- 3.5 months, group A); the calcium antagonist gallopamil, 26 patients, mean age 49.7 yrs., follow-up 36.2 +/- 2.6 months, group B); the combined therapy with 50 mg atenolol and 20 mg nifedipine, 35 patients, mean age 44.5 yrs., follow-up 31.7 +/- 1.1 months, group C); 200 mg acebutolol and 20 mg nifedipine, mean age 52.1 yrs., follow-up 31.8 +/- 1.8 months, group D); 50 mg atenolol and 10 mg enalapril, mean age 43.3 yrs., follow-up 31.9 +/- 1.3 months, group E). Similar results were obtained for intraventricular septal and posterior wall thickness. Left ventricular enddiastolic dimensions remained unchanged but fractional shortenings were significantly (p less than 0.05-p less than 0.01) increased after 32 months of treatment.

In 26 previously untreated patients with essential hypertension (mean age 49.7 +/- 11 years), the effect of long-term treatment with the calcium antagonist gallopamil (n = 13, 100 mg; n = 13, 150 mg daily) on blood pressure and left ventricular hypertrophy (LVH) was studied. After the treatment of 22.3 +/- 2.5 months, the blood pressure of 157 +/- 19/103 +/- 84 mm Hg at rest prior to therapy was significantly (p less than 0.001) reduced to 130 +/- 12/82 +/- 7.3 mm Hg. Blood pressure reduction was accompanied by a significant (p less than 0.001) decrease in left ventricular mass index from 170 +/- 49.8/m2 to 150 +/- 44 (11.9%) and 116 +/- 26 (31.9%) after 8.2 and 22.3 months, respectively. Interventricular septum (14.2 to 13.2 and 11.8 mm; 16.9%) and posterior wall thickness (11.5 to 10.4 and 9.4 mm; 18.3%) were also significantly (p less than 0.001) reduced, whereas left ventricular dimensions and fractional shortening were unchanged. We conclude that LVH from hypertension can be lessened by calcium antagonists without deterioration of left ventricular function.

We studied a total of 88 previously untreated hypertensives in order to determine the long-term effect of antihypertensive therapy on echocardiographically confirmed left ventricular hypertrophy. The drugs tested were the beta-blocker metoprolol (200 mg/day; 26 patients; mean age 43.9 years; follow-up 32 months), the calcium antagonist gallopamil (100-150 mg/day; 26 patients; mean age 49.7 years; follow-up 23 months) and a combination of 50 mg atenolol and 20 mg nifedipine (36 patients; mean age 44.2 years; follow-up 18 months). Despite similar reductions in resting blood pressure, each of the three therapeutical regimens had a different effect on the left ventricular mass index after 1 year of treatment: gallopamil reduced the index by 13.2% (170 +/- 49 to 148 +/- 41 g/m2, P less than 0.001), metoprolol by 21.9% (150 +/- 27 to 117 +/- 27 g/m2, P less than 0.001) and atenolol + nifedipine by 30.8% (148 +/- 33 to 103 +/- 21 g/m2, P less than 0.001). Similar results were obtained for interventricular septal (9.9, 15.4 and 20.7%, respectively) and posterior wall thicknesses (10.4, 16.7 and 24.1%, respectively). During the follow-up there was a further significant reduction in ventricular hypertrophy under all three treatments, but no significant changes in ventricular end-diastolic and end-systolic dimensions or in fractional shortening.

25 patients (24 males, 1 female; mean age 43.7 years), with previously untreated essential hypertension and echocardiographically proven left-ventricular hypertrophy, received metoprolol 200 mg daily over a period of 12.7 months, five of them additionally hydrochlorothiazide 25 mg. After four weeks, resting recumbent blood pressure had decreased from 157 +/- 18 systolic and 106 +/- 9 diastolic to 128 +/- 11 and 85 +/- 9, respectively; after 12.7 months to 123 +/- 12 and 83 +/- 8 mm Hg (P less than 0.001). On 100 W exercise the blood pressure fell from initially 206 +/- 13 and 117 +/- 9 168 +/- 12 and 97 +/- 9, after 12.7 months to 170 +/- 14 and 98 +/- 9 mm Hg. Left-ventricular mass fell from 147.0 +/- 26 g/m2 by 14% after 6.1 months, by 22.5% after 12.7 months (P less than 0.001). While the left-ventricular diameter in enddiastole and endsystole remained unchanged, septal thickness decreased from 15.5 +/- 2.1 to 14.2 +/- 2.2 mm after 6.1 months and 13.1 +/- 1.9 mm after 12.7 months (reduction of 15.5%). The corresponding values for the left-ventricular posterior wall were 11.9 +/- 1.6 before and 10.8 +/- 1.8 after 6.1 months and 10.1 +/- 1.4 mm after 12.7 months (reduction of 16%). Thus long-term administration of metoprolol resulted in a significant reduction in myocardial hypertrophy without impairment of ventricular function.

36 patients with previously untreated essential hypertension and left ventricular hypertrophy were treated with a fixed dose combination of atenolol 50 mg and sustained release nifedipine 20 mg once daily for a mean period of 12.1 months. Echocardiography showed a significant decrease after a mean period of 7.9 months in interventricular septal thickness (13.6%, p less than 0.01), posterior wall thickness (12.6%, p less than 0.001) and left ventricular mass index (18.3%). After 12.1 months the reductions were 20.7% (p less than 0.001), 22.5% (p less than 0.001) and 30.8% (p less than 0.001), respectively. Posterior wall thickness was significantly reduced, but left ventricular end-systolic and end-diastolic dimensions and fractional shortening remained unchanged. Treatment significantly reduced resting blood pressure from 153/105 mm Hg to 122/79 mm Hg (p less than 0.001), and exercise blood pressure at 100W from 189/109 to 157/93 mm Hg (p less than 0.001). Thus, nifedipine in combination with atenolol produces significant blood pressure reduction accompanied by regression of left ventricular hypertrophy without noticeable changes in left ventricular function.