The Effects Of Differing Administration Time On The Circadian Ryhthm Of Very Old Hypertensive Patients

Objective: To adapt to the constantly changing external and internal environment, all biological organisms need to make reactions and regulations at any time. As one of the physiological parameters, blood pressure always changes instantly, and maintains fluctuating either in health people or hypertensive individuals. In most cases, the fluctuation of blood pressure has a rhythm with a period of approximately 24 hours, which called circadian rhythm or diurnal rhythm. According to characters of the fluctuation, blood pressure rhythms can be divided into four types: 1. Dipper, which defined as a 10-20% fall in nocturnal BP; 2. Extreme dipper, which with a nocturnal fall greater than 20%; 3. Non-dipper, with a nocturnal fall less than 10%; and 4. Reverse-dipper, as less than 0% at most fall in nocturnal BP. In recent years, many studies showed that abnormal circadian rhythm is linked to the progressive injury of target organs and the triggering of cardiac and cerebrovascular events,which is an independent risk factor for the occurrence and development of cardiovascular disease. During the past decades, 24-hour ambulatory blood pressure monitoring (ABPM) has been extensively applied,by which we can observe circadian rhythm of blood pressure more easily. Meanwhile, with the economic improvement, octogenarian accounts for a growing proportion of the population. Due to the special aspects of elderly hypertensive patients, the treatment is different from general hypertensive patients. How to control blood pressure and regulate abnormal circadian rhythm at the same time is the most significant problem in chronotherapy. At present, domestic and international studies has not obtained the consistent conclusion that the effect of changing the dosing time of long-acting antihypertensive drugs on circadian rhythm of blood pressure,and clinical studies on the hypertension patients≥80 years of age is still absent. In this study, we compared bedtime dosing of long-acting antihypertensive drugs with morning dosing in very old people by ABPM,and observed the changes of circadian rhythm, systolic pressure, diastolic pressure, mean arterial pressure, blood pressure variability and other related parameters, and then discussed its mechanism.Methods: In this study, we involved 52 hypertensive patients with age≥80 years, and their blood pressure were monitored by Japanese AND TM-2430 ambulatory blood pressure monitoring system. Among the participants, 27 cases were taking long-acting CCBs and 25 cases was taking ARBs. 30 males and 22 females were inclueded in this study with aged 80-90 years (84.80士3.32). We changed dosing time from 8:00 to 20:00. 24 hour ambulatory blood pressure was evaluated before and after the dosings schedule changed. All measurement data were represented by mean±standard deviation (±s). Measurement data between groups were compared by t-test, chi-square test was introduced to analyze the percentage, and P≤0.05 was defined as statistically different borderline.Results: 1 When morning medication, blood pressure parameters such as 24h MSBP, 24hMDBP, dMSBP, dMDBP, nMSBP were 135.21±11.86mmHg , 62.26±8.99mmHg , 133.05±10.42mmHg ,60.52±8.73mmHg , 136.32±10.92mmHg and 63.88±6.32mmHg respectively.When evening medication, blood pressure parameters such as 24h MSBP, 24hMDBP, dMSBP, dMDBP, nMSBP were 133.33±10.65mmHg, 63.42±9.50mmHg,132.91±11.05mmHg,60.78±8.69mmHg,135.62±10.58mmHg and 64.11±6.58mmHg respectively (P> 0.05).Although the dippers increased from 4 to 7 cases,proportion of dipper rhythm had not increased(χ2=0.91,P>0.05).2 The valsartan Sub-group analysis showed that when morning medication, blood pressure parameters such as 24h MSBP, 24hMDBP, dMSBP, dMDBP, nMSBP were 136.11±10.74mmHg,61.76±11.92mmHg,132.76±9.42mmHg,60.01±8.92mmHg,138.21±10.54mmHg and 62.74±6.45mmHg respectively。 When evening medication, blood pressure parameters such as 24h MSBP, 24hMDBP, dMSBP, dMDBP, nMSBP were 135.07±10.05mmHg, 62.80±8.32mmHg,131.68±10.25mmHg,60.95±8.88mmHg,136.62±9.83mmHg and 63.23±6.71mmHg respectively (P> 0.05).3 The nifedipine GITS Sub-group analysis showed that when morning medication, blood pressure parameters such as 24h MSBP, 24hMDBP, dMSBP, dMDBP, nMSBP were 134.11±10.63 , 63.59±9.03Hg ,135.15±11.07mmHg , 60.73±9.23mmHg , 133.35±9.73mmHg and 64.87±6.48mmHg respectively。When evening medication, blood pressure parameters such as 24h MSBP, 24hMDBP, dMSBP, dMDBP, nMSBP were 133.01±10.82mmHg,63.88±9.72mmHg,135.85±10.43mmHg,60.15±8.99mmHg, 132.62±10.01mmHg and 65.12±6.48mmHg respectively (P> 0.05).Although the dippers increased from 3 to 6 cases,proportion of dipper rhythm had not increased(χ2=0.53,P>0.05).Conclusion: 1 In the very elderly hypertensive patients , taking long-acting antihypertensive drugs at night have similar blood lowering effect compared with morning dosing schedule, but the circadian rhythm of blood pressure was not significantly changed.2 Compared with the morning dosing schedule, taking valsartan at evening had similar BP lowering effects, but the rhythm of blood pressure in the very old hypertensive patients with no significant changes, and can not increase the proportion of dipper rhythm.3 In elderly hypertensive patients, taking nifedipine GITS at evening have similar effects on blood pressure circadian rhythm.