Effects on Heart Rate Variability of Isosorbide-5-Mononitrate and Metoprolol in Patients with Recent Onset of Angina pectoris

Abstract

Background: β-Blockers reduce sympathetic tone, increase vagal tone and improve prognosis in ischaemic heart disease. Nitroglycerin, being a vasodilator, may theoretically have an opposite effect and worsen the prognosis. The purpose of the present study was to analyse heart rate variability (HRV), which reflects autonomic tone, in angina patients on isosorbide-5-mononitrate (IS-5-MN) and/or metoprolol. Methods and Results: Thirty-two patients (32–81 years old), with recently developed angina (median duration: 3 months), showing no other disease and on no drugs, were Holter-monitored 24–48 h at baseline and after 4–5 days on IS-5-MN (mean daily dose: 33 mg), on metoprolol (mean daily dose: 184 mg) and on the combined treatment. Recordings were analysed on the Marquette Series 8000 Holter scanner. Both IS-5-MN and metoprolol significantly reduced myocardial ischaemia (ST integral) and ventricular tachycardias. Metoprolol induced significant changes in the following parameters (baseline versus metoprolol): high-frequency peak 9 ± 4 versus 11 ± 4 ms (p < 0.001), low-to-high frequency ratio 2.5 ± 0.6 versus 1.9 ± 0.6 (p < 0.0001), root mean square of RR interval difference 23 ± 7 versus 31 ± 9 ms (p < 0.0001), RR intervals differing more than 50 ms from the preceding one 4.8 ± 3.9 versus 10.0 ± 7.0% (p < 0.0001), mean of all 5-min standard deviations 50 ± 12 versus 56 ± 11 ms (p < 0.001) and mean RR interval 819 ± 90 versus 1,019 ± 120 ms (p < 0.00001). The combined treatment caused approximately the same HRV changes as metoprolol alone. IS-5-MN had no significant effect on any HRV parameter, neither alone nor in combination with metoprolol. Conclusion: A clinically effective dose of metoprolol had potentially positive effects on HRV with increase in vagal and decrease in sympathetic tone while IS-5-MN had no effect on HRV, neither positive nor negative, neither alone nor in combination with metoprolol.