Administration Time-dependent Effect Of Aspirin On Blood Pressure Variability And Morning Blood Pressure Surge Of Coronary Heart Disease Patients Without A History Of Hypertension

Objective: The incidence of coronary heart disease and cerebrovasculardisease has been, with the development of society, increasing significantly anddramatically than ever before. Nowadays, they have become the leading causeof death. Aspirin (ASA), also known as acetylsalicylic acid, is part of a groupof medication called nonsteroidal anti-inflammatory drugs(NSAIDs). ASA isoften used as an antipyretic to reduce fever, as an analgesic to relieve minoraches and pains, and as an anti-inflammatory and antirheumatic medicationthrough inhibition of arachidonic acid metabolism and prostaglandin synthesisby inhibition of cyclo-oxygenase. Ever since synthesized in1897, it hasplayed an decisive role in the prevention and treatment of rheumatic disease,rheumatoid arthritis, coronary heart disease and cerebrovascular disease.With further research, more novel pharmacological actions of ASAwere being disclosed. Trials abroad have showed that aspirin administered atbedtime but not on awakening could lower BP. Among healthy people,24hblood pressure fluctuates from day and night, and such fluctuation is known ascircadian rhythms. Blood pressure variability (BPV) refers to the degree offluctuation of blood pressure in a certain period of time. The morning bloodpressure surge (MBPS) refers to blood pressure increases steeply in themorning when people awake. BPV has been associated with target organdamage and MBPS correlates with cerebral and cardiac events. Themechanism of antihypertensive effect of ASA administered at bedtime is stillnot clear. Researchers postulated that this decrease could be attributed to thereduction in the nocturnal peak of plasma renin activity, and enhancement inthe NO release of vascular endothelium. But these presumptions remain under debate. China has a large population and limited medical resources, to exploreand disclose more effect of aspirin will result in great social and economicefficiencies, since it is of low cost, high safety and cost performance.Methods: A total of19patients who were in hospital during October2011to March2012and diagnosed as coronary heart disease without a historyof hypertension were included. The exclusion criteria were diagnosed essentialhypertension, secondary hypertension, severe liver or renal insufficiency(ALT were2.5times upper limit of normal or GFR＜30ml·min~-11.73m~-2), ofclotting disorders, with a history of peptic ulcer or cerebral hemorrhage,abnormal platelet count (PLT>300×10~9/L or <100×10~9/L)and those whocan not adhere to follow-up or with poor compliance. Among the participants,aged57.53±9.28,10were diagnosed as unstable angina(UA) and9as acutemyocardial infarction(AMI) and84.21%were man. During the study period,7UA and5AMI patients received coronary angiography.The study has a two-period crossover design, all the subjects wererandomly assigned to two arms (group A or group B). Two periods, lastingtwo weeks respectively, were designed for each subject to go through.Subjects in group A were assigned to the first2-week taking ASA100mg/d onawakening, then to the second2-week taking ASA100mg/d at bedtime.Subjects in group B were assigned to the first2-week taking ASA100mg/d atbedtime first and then to the second2-week taking ASA100mg/d onawakening. All subjects underwent24h ambulatory blood pressure monitoringat admission and after each intervention period.24-hour ambulatory blood pressure monitoring (ABPM, SpaceLabsMedical90207) was employed in this study. Blood pressure is automaticallymeasured every15minutes in the daytime (6:00~22:00) and every30minutes in the nighttime (22:00~6:00). There is no restriction on dailyactivities and subjects were instructed to keep the measured arm steady whenthe machine is about to take a reading. The blood pressure information istransferred from the monitor to the computer for organization andinterpretation. Parameters include the mean BP (24hSBP, dSBP, nSBP, mSBP, 24hDBP, dDBP, nDBP, mDBP) and the mean BPV (24hSDSBP, dSDSBP,nSDSBP,24hSDDBP, dSDDBP, nSDDBP).Statistical analysis: all of the statistical analysis were performed usingSPSS version16.0(SPSS Inc). Variables are presented as mean±SD. Generallinear model t test is used to deal accurately with the repeated measurementsand cross-over design that obtained from each subject, the null hypothesis wasrejected when2-tailed P＜0.05.Results:①The mean value of BP: the blood pressure of daytime ishigher than that of24-hour, and the latter one is higher than that of nighttime.②The variability of SBP and DBP: the BPV of24-hour is higher than that ofdaytime, and the latter one is higher than that of nighttime. The systolic bloodpressure variability is higher than that of diastolic when assessed as thestandard deviation, on the contrary, lower when assessed as the coefficient ofvariation.③The change of blood pressure levels and BPV in baseline andafter two intervention periods was of no significance in group A, which is inconsistent with group B.Conclusions: The effect of time-dependent administration of low-doseaspirin on blood pressure variability and morning blood pressure surge ofcoronary heart disease patients without a history of hypertension is notsignificant. The administration time-dependent effect of aspirin is not seen inthis study.