Effects of diltiazem retard on ambulatory blood pressure and heart rate variability in patients with essential hypertension

BACKGROUND: Dihydropyridine calcium antagonists increase heart rate due to reflex activation of the sympathetic nervous system, although these effects are less obvious for long-acting agents. OBJECTIVE: To study the effects of diltiazem retard, a long-acting nondihydropyridine calcium antagonist, on 24h blood pressure, heart rate and autonomic nerve activity in patients with essential hypertension. DESIGN: Randomized crossover design. METHODS: Thirteen patients [five men and eight women, aged 64+/-2 years (mean+/-SEM)] were administered placebo or diltiazem retard (100-200mg once daily) for 4 weeks each. Ambulatory monitoring of blood pressure and heart rate, and electrocardiography were carried out at the end of each period using a multibiomedical recorder (TM-2425). Autonomic nerve activity was evaluated by power spectral analysis of variability of heart rate using the high-frequency component as an index of parasympathetic nerve activity and the ratio of the low-frequency component and the high-frequency component as an index of sympathovagal balance. RESULTS: Treatment with diltiazem retard significantly decreased 24h average blood pressure and heart rate by 11.6+/-3.6/5.7+/-1.8mmHg and 5.0+/-1.1 beats/min, respectively. The changes in daytime and night-time values were comparable. Diltiazem retard also significantly decreased daytime and 24h low:high-frequency-component ratio (2.0+/-0.2 versus 1.7+/-0.2 and 1. 8+/-0.2 versus 1.6+/-0.2, respectively). CONCLUSIONS: These results indicate that diltiazem retard is effective as a once-daily antihypertensive agent and has favorable effects on heart rate and the autonomic nervous system.