Chronobiological Analysis by Ambulatory Blood Pressure Monitoring of the Hyperbaric and Hypobaric Indexes for Evaluation of the Antihypertensive Effect of Long-Acting Nifedipine

Background It has been suggested that chronobiology can provide new insights into the evaluation and treatment of cardiovascular disease. In the present study the hyperbaric index (hyperBI) and hypobaric index (hypoBI) were compared with the mean blood pressure (BP) over 24h to evaluate the antihypertensive effect of long-acting nifedipine on essential hypertension. Methods and Results Fourteen patients were treated with nifedipine CR (20-40mg/day) for 6 months. Ambulatory BP monitoring was performed before and after treatment. The hyperBI (mmHg・h/day) was calculated as the integrated BP area above the conventional upper limit (140/90mmHg for the daytime and 120/80mmHg at night), and the hypoBI was calculated as the integrated BP area below the conventional lower limit (110/60mmHg for the daytime and 100/50mmHg at night). At baseline, both the systolic and diastolic 24-h hyperBI values closely correlated with the 24-h mean BP (r=0.994 and 0.935, p<0.0001). Treatment with nifedipine significantly lowered both the 24-h mean systolic and diastolic BP (143±14/89±12 to 124±16/80±8mmHg, p<0.001/p=0.001), as well as the casual BP (167±11/101±8 to 140±13/86±10mmHg, p<0.001/p<0.01). Reduction of both the systolic and diastolic hyperBI values was statistically significant over the 24-h period (274±266 to 90±155, p=0.009; 145±187 to 41±63, p=0.024), as well as during the daytime (200±181 to 66±116, p=0.014; 105±120 to 24±38, p=0.017) and at night (systolic, 74±106 to 24±52, p=0.021). The 24-h mean BP was normalized, but a small excess BP load persisted despite treatment. There was no significant increase of systolic hypoBI during the 24-h period (1±2 to 25±30, p=0.065), the daytime (0±0 to 14±38, p=0.20), or at night (1±3 to 11±19, p=0,052). Similar findings were obtained for diastolic hypoBI. Conclusions Nifedipine CR improved the 24-h hyperBI and mean BP without causing excessive hypotension. These 2 parameters have a close relationship when assessment is done by 24-h BP monitoring. The hyperBI and hypoBI may assist in providing adequate antihypertensive therapy for individual patients by detecting an excessive BP load or hypotension, respectively.