高血压的择时治疗.ppt

高血压的择时给药内容提纲:简简 介介 文献分析与评论文献分析与评论 结结 论论 123一、简 介血压昼夜节律 血压是血管内流动的血液对于单位面积血管壁的侧压力，在生理状态下，机体血压呈昼夜节律性波动。健康机体血压全天呈现双峰一谷、昼高夜低的杓型曲线：张振服,刘启德,杨蕾.血压昼夜节律特征及其分子调控机制J.现代生物医学进展,2011,11(6):1181-1183.一、简 介 但高血压患者、老年人、甚至部分健康人群中，其血压的昼夜节律特征可能有所变化。习惯上，根据夜间血压的下降情况分可将其分为4型：（1）杓型(dippers)：夜间血压较日间下降1020%；（2）非杓型(non-dippers)：夜间血压下降010%；（3）超杓型或深杓型(over-dippers或extreme-dippers)：夜间下降20%；（4）反杓型(reverse-dippers)：夜间血压水平高于日间者。大量临床资料研究表明，血压昼夜节律异常与高血压靶器官损害和心血管事件发生呈明显相关关系，是独立于血压水平的重要致病因素。目前高血压治疗重心：保护靶器官和降低心、保护靶器官和降低心、脑血管疾病的发生率和死脑血管疾病的发生率和死亡率。亡率。充分控制血压，包括增充分控制血压，包括增加药物剂量、改进降压药加药物剂量、改进降压药物以及联合运用具有协同物以及联合运用具有协同作用的药物等措施。作用的药物等措施。无论是单一药物治疗无论是单一药物治疗,还还是联合药物治疗是联合药物治疗,都存在一个都存在一个共同点共同点,即把降压药在早上一即把降压药在早上一次性服用次性服用(白天活动的开始或白天活动的开始或是在早饭时是在早饭时)。高血压患者中存在较高的非杓形血压高血压患者中存在较高的非杓形血压发病率发病率大多数降压药不能持续平稳作用大多数降压药不能持续平稳作用24h针对所有高血压患者都使用早上一次针对所有高血压患者都使用早上一次性给药的治疗策略是否恰当？性给药的治疗策略是否恰当？问问 题题一、简一、简 介介 近年来，国内外许多学者提出，全面的高血压治疗策略是在近年来，国内外许多学者提出，全面的高血压治疗策略是在控制血压的同时恢复高血压患者血压正常的近日节律，这就需要控制血压的同时恢复高血压患者血压正常的近日节律，这就需要调整降压药的给药时间。调整降压药的给药时间。蒲小波,杜一平.血压的近日节律与高血压的时间治疗学J.重庆医学,2009,38(21):2748-50.一、简一、简 介介二、文献分析与评论 Two earlier conducted morbidity trialsthe Syst-Eur and the Heart Outcomes Prevention Evaluation(HOPE)studies.nIn the Syst-Eur trial,participants were randomized to an evening schedule of either placebo or the dihydropyridine calcium channel blocker nitrendipine.nIn the HOPE study,participants in the active-treatment group ingested the angiotensin-converting enzyme inhibitor ramipril at bedtime,a critical piece of information withheld from the original publication.1、Staessen JA,Thijs L,Fagard R,and et al.The Systolic Hypertension in Europe Trial Investigators.Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertensionJ.JAMA,1999,282:539546.2、Yusuf S,Sleight P,Pogue J,and et al.The Heart Outcomes Prevention Evaluation Study Investigators.Effects of an angiotensin-converting-enzyme inhibitor,ramipril,on cardiovascular events in high-risk patientsJ.N.Engl.J.Med,2000,342:145153.二、文献分析与评论nBoth studies found that the evening drug administration schedule reduced the incidence of the non-dipping BP pattern among treated hypertensive patients.nFurthermore,the HOPE trial demonstrated that the treatment-conferred normalization of the 24-h BP dipping pattern was associated with a lower incidence of stroke and myocardial infarction relative to those displaying the abnormal non-dipper pattern.nHowever,the major shortcoming of both the Syst-Eur and HOPE trials is that each was devoid of a comparison treatment group randomized to morning therapy.Smolensky MH,Hermida RC,Ayala DE,and et al.Administration-time-dependent effects of blood pressure-lowering medications:basis for the chronotherapy of hypertensionJ.Blood Press Monit.,2010,15:173180.THE MAPEC STUDY:HYPERTENSION CHRONOTHERAPY AND CVD RISKnA total of 2156 hypertensive subjects were evaluated by 48-h ABPM at base-line and with identical assessment conducted annually,or more frequently(quarterly)if adjustment of treatment was required.nAt baseline,the two treatment-time groups were mostly comparable in terms of their clinic and mean ambulatory SBP and DBP and prevalence of non-dipping BP pattern.Francesco Portaluppi,Michael H.Smolensky.PERSPECTIVES ON THE CHRONOTHERAPY OF HYPERTENSION BASED ON THE RESULTS OF THE MAPEC STUDYJ.Chronobiology International,2010,27(8):16521667.Monitorizacin Ambulatoria para Prediccin de Eventos Cardiovasculares,i.e.,Ambulatory Blood Pressure Monitoring for Prediction of Cardiovascular Event(MAPEC).Results:nSubjects who ingested 1 of their medications at bedtime showed at their last available evaluation significantly lower mean sleeptime BP,higher sleep-time relative BP decline(an index of BP dipping calculated as(awake BP mean asleep BP mean)/awake BP mean 100),reduced prevalence of non-dipping(34%versus 62%;p .001),and higher prevalence of controlled ambulatory BP(62%versus 53%,p .001).Results:nAfter a median follow-up of 5.6 yrs,the group of subjects ingesting 1 BP-lowering medications at bedtime showed a significantly lower relative risk of total cardiovascular events than the group of subjects ingesting all medications upon awakening(0.39 0.290.51;.p .001).Conclusion:nResults from the prospective MAPEC study thus indicate that bedtime chronotherapy with 1 hypertension medications,compared to conventional upon-waking treatment with all medications,more effectively improves BP control,better decreases the prevalence of non-dipping and,most importantly,significantly reduces CVD morbidity and mortality.MECHANISMS UNDERLYING THE ADVANTAGE OF BEDTIME CHRONOTHERAPYnUnder usual circumstances,BP is normally lowest at night as is sodium excretion.However,in acute and chronic situations when sodium intake is excessive or its excretion hampered during the daytime,BP is adjusted by means of the pressure/natriuresis mechanism to the higher level needed to compensate overnight,thereby resulting in non-dipping 24h patterning(Bankir et al.,2008;Fujii et al.,1999;Uzu et al.,2001).nThe pressure-natriuresis mechanism and relationship is modulated during the daytime by the effects of upright posture and activity,such that it is mainly during the nighttime when sodium sensitivity(which is present in each person,but to a different extent)most strongly exerts its corrective effects,thus inducing the non-dipping BP patterning.Administration-time differences in the PK of BP medications.nHence,one might expect hypertensive medications to be cleared more slowly overnight,thereby potentially prolonging their duration of action when ingested at bedtime as compared to in the morning upon awakening(Hermida et al.,2007a).nAdministration-time differences in the PD of BP medications,in the absence of differences in PK,are also known(see Smolensky et al.,2010);they result from circadian rhythms in circulating drug-free fraction,rate-limiting steps of key biochemical and metabolic processes,receptor number and conformation,and/or second messenger and signaling pathways(Witte&Lemmer,2003).Implications：n(i)the concept of“normotensive non-dipper,”because the CVD risk of this BP phenotype is higher than that of a hypertensive dipper and as such the use of the term“normotensive”is misleading with the consequent risk of poor patient management;n(ii)the conceptual approach to treatment that entails achieving the homeostatic goal of constant or relatively invariable effect of BP-lowering throughout the 24-h dosing interval using once-a-day medications of high“smoothness index,”which appears questionable,even contraindicated,in the case of non-dipper patients;nand(iii)the reliance on current occasional cuff assessment of BP and related guideline thresholds/criteria to diagnose hypertension without regard for BP levels at other times of the day and night,particularly the sleep-time level and/or the extent of the nocturnal decline.三、结 论：杓形高血压杓形高血压非杓形高血压非杓形高血压杓形高血压患者应在每天早杓形高血压患者应在每天早上服用上服用1次可持续作用次可持续作用24h的的降压药。降压药。非杓形高血压患者非杓形高血压患者,将服药时间将服药时间改到晚上或睡觉时加服改到晚上或睡觉时加服1次或需次或需要时增加服药次数。要时增加服药次数。