Heart rate and the rate-pressure product as determinants of cardiovascular risk in patients with hypertension*1

Inability to supply oxygen to the myocardium when demand is high appears to be related to several cardiovascular events, including transient myocardial ischemia, acute myocardial infarction, and sudden death. Myocardial oxygen consumption is correlated with the rate-pressure product (heart rate x systolic blood pressure) and this hemodynamic parameter has been shown to follow a circadian pattern similar to that observed with cardiovascular events. However, the clinical implications of this observation and the appropriate clinical interventions have not been studied. Therefore, the impact of the chronotherapeutic controlled-onset extended release delivery (COER-verapamil) on heart rate and the rate-pressure product was assessed and compared with that of nifedipine gastrointestinal therapeutic system (GITS), which is designed to provide a constant or homeostatic drug effect. A total of 557 hypertensive patients were enrolled in the 51-center, randomized, double-blind prospective study. Twenty-four-hour ambulatory blood pressure (BP) monitoring was performed at baseline, after 4 weeks of stable-dose therapy, and after 10 weeks of treatment; heart rate was assessed concomitantly. Heart rate, rate of rise (slope) of BP and heart rate, and the rate-pressure product were all reduced to a greater extent by COER-verapamil during the early morning hours compared with the nifedipine GITS treatment. Thus, COER-verapamil exerted a beneficial hemodynamic profile for the treatment of the increases in rate-pressure product typically observed in the early morning in patients with hypertension.