Cornélissen Germaine, Halberg Franz, Bakken Earl, Singh Ram B, Otsuka Kuniaki, Tomlinson Brian, Delcourt Alain, Toussaint Guy, Bathina Srilakshmi, Schwartzkopff Othild, Wang Zhengrong, Tarquini Roberto, Perfetto Federico, Pantaleoni Giancarlo, Jozsa Rita, Delmore Patrick A, Nolley Ellis
Halberg Chronobiology Center, University of Minnesota, Minneapolis, MN, USA.
Biomed Pharmacother. 2004 Oct;58 Suppl 1:S69-86. doi: 10.1016/s0753-3322(04)80012-x.
Longitudinal records of blood pressure (BP) and heart rate (HR) around the clock for days, weeks, months, years, and even decades obtained by manual self-measurements (during waking) and/or automatically by ambulatory monitoring reveal, in addition to well-known large within-day variation, also considerable day-to-day variability in most people, whether normotensive or hypertensive. As a first step, the circadian rhythm is considered along with gender differences and changes as a function of age to derive time-specified reference values (chronodesms), while reference values accumulate to also account for the circaseptan variation. Chronodesms serve for the interpretation of single measurements and of circadian and other rhythm parameters. Refined diagnoses can thus be obtained, namely MESOR-hypertension when the chronome-adjusted mean value (MESOR) of BP is above the upper limit of acceptability, excessive pulse pressure (EPP) when the difference in MESOR between the systolic (S) and diastolic (D) BP is too large, CHAT (circadian hyper-amplitude tension) when the circadian BP amplitude is excessive, DHRV (decreased heart rate variability) when the standard deviation (SD) of HR is below the acceptable range, and/or ecphasia when the overall high values recurring each day occur at an odd time (a condition also contributing to the risk associated with 'non-dipping'). A non-parametric approach consisting of a computer comparison of the subject's profile with the time-varying limits of acceptability further serves as a guide to optimize the efficacy of any needed treatment by timing its administration (chronotherapy) and selecting a treatment schedule best suited to normalize abnormal patterns in BP and/or HR. The merit of the proposed chronobiological approach to BP screening, diagnosis and therapy (chronotheranostics) is assessed in the light of outcome studies. Elevated risk associated with abnormal patterns of BP and/or HR variability, even when most if not all measurements lie within the range of acceptable values, becomes amenable to treatment as a critical step toward prevention (prehabilitation) to reduce the need for rehabilitation (the latter often after costly surgical intervention).
通过手动自我测量(清醒时)和/或动态监测自动获取的长达数天、数周、数月、数年甚至数十年的全天血压(BP)和心率(HR)纵向记录显示,除了众所周知的日内较大波动外,大多数人(无论血压正常与否)的日间变异性也相当大。第一步,考虑昼夜节律以及性别差异和随年龄变化的情况,以得出特定时间的参考值(时间节点),同时积累参考值以考虑七天周期的变化。时间节点用于解释单次测量以及昼夜节律和其他节律参数。由此可以获得更精确的诊断,即当血压的时间生物学调整平均值(MESOR)高于可接受上限时为MESOR高血压,当收缩压(S)和舒张压(D)血压的MESOR差值过大时为脉压过大(EPP),当昼夜血压振幅过大时为昼夜高振幅张力(CHAT),当心率标准差(SD)低于可接受范围时为心率变异性降低(DHRV),和/或当每天反复出现的总体高值出现在异常时间时为言语错乱(这一情况也会增加“非勺型”相关风险)。一种非参数方法,即通过计算机将受试者的情况与随时间变化的可接受范围进行比较,进一步作为通过确定给药时间(时间治疗)和选择最适合使血压和/或心率异常模式正常化的治疗方案来优化任何所需治疗效果的指南。根据结果研究评估了所提出的血压筛查、诊断和治疗的时间生物学方法(时间治疗诊断学)的优点。与血压和/或心率变异性异常模式相关的风险升高,即使大多数(如果不是全部)测量值在可接受范围内,也可作为预防(预康复)的关键步骤进行治疗,以减少康复需求(后者通常在昂贵的手术干预之后)。