Extended consensus on need and means to detect vascular variability disorders (VVDs) and vascular variability syndromes (VVSs)

Franz Halberg, Germaine G Cornelissen-Guillaume, Kuniaki Otsuka, Jarmila Siegelova, Bohumil Fišer, Jiří Dušek, Pavel Homolka, Salvador Sánchez de la Peña, R. B. Singh

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


Given that conventional health care practice is concerned mainly with high blood pressure (BP), and given the fact that other variability disorders -- circadian overswing, excessive pulse pressure, odd circadian BP timing and deficient heart rate (HR) variability (in their own right or in combination with MESOR-hypertension) -- are not diagnosed but contribute to cardiovascular disease risk, we wanted to find out 1. how many patients escape current diagnosis (and treatment), and 2. what are the risks such patients incur. A first available database consists of 297 patients (121 normotensives and 176 treated hypertensives). Each condition was considered separately, except that in the case of an excessive pulse pressure, all had also a high BP. In each case, the number of patients who have one, two, three or all four conditions (vascular variability disorders, VVDs) was counted. Their risk was assessed as the percentage incidence of morbid events (cerebral ischemic event, coronary artery disease, nephropathy, retinopathy) that occurred during the 6 years following the BP monitoring (used to diagnose the VVDs). Subjects had no history of morbidity at the time of monitoring. MESOR-Hypertension (MH). Of 176 patients, only 103 had uncomplicated MESOR-hypertension, 55 had one other complicating VVD, 15 had 2 (additional) VVDs and 3 had all 4 VVDs. This means that 41.5% of the hypertensives were only partly diagnosed. The undetected risk of these patients is greatly increased, from about 10% for uncomplicated MH to 100% for the 3 patients with all 4 VVDs. Excessive Pulse Pressure (EPP). Since all these patients also happened to have MH, it is not surprising that the increase in risk as a function of the number of VVDs present is similar to that found for patients with MH alone. Circadian Hyper-Amplitude-Tension (CHAT) and Deficient HR Variability (DHRV). These two conditions in their own right, without any complication by other VVDs, are found in 7 (CHAT) and 5 (DHRV) patients, representing 2.4% and 1.7% of the total population. These numbers are small in this study, yet if the percentages reflect what happens in the general population, this may actually represent MANY people who completely escape medical attention in the current system. Again, it is seen that when these conditions coexist with other VVDs, the incidence of morbid events is proportionately increased. There is actually a small exception to this general trend in the case of CHAT: the risk of CHAT alone is actually slightly higher than the risk of CHAT with one additional VVD (usually it is MH, and the two conditions may alternate, notably under treatment). This result is in keeping with the earlier result that CHAT is associated with a larger relative risk than MH in this population. In a second database, a population of 1,177 untreated, presumably normotensive subjects, MH was diagnosed in a total of 289 subjects, representing 24.6%. Among these subjects, 137 (47.4% of those diagnosed with MH) have at least one additional VVD that is not part of the current screening but increases the vascular disease risk beyond that associated with MH alone. VVDs other than MH occur in the absence of MH in very few patients with EPP and in more patients with CHAT and in yet more with BP ecphasia (an odd timing of the circadian rhythms in BP but not in that of HR) and in 87 patients with DHRV, that is for a total of 182 subjects, representing 15.5% of the study population. In view of the foregoing, the current guidelines for diagnosing abnormal, notably high BP in a substantial segment of the population have to be revised, according to a consensus meeting held at St. Anna Hospital, Masaryk University, Brno, Czech Republic, on October 6, 2008 (in the setting where instrumentation for beat-to-beat measurements of BP was developed) (1-3). Specifications are needed for the minimal number of measurements, for how long and how often they should be taken, including their temporal placement. Methods are also needed for the assessment of dynamics, in keeping with a document originally prepared for this meeting by Dr. Germaine Cornélissen, Professor of Integrative Biology and Physiology at the University of Minnesota, revised in Brno by those undersigned. The terms "normotension" and "hypertension" can be replaced by the terms "MESOR-normotension" (MN) and "MESOR-hypertension" (MH), respectively, whenever the conditions for a chronobiologically-interpreted 24-hour/7-day BP and HR monitoring (C-ABPM) are met. The term MH indicates only one of several VVDs that can combine to form sets of 2, 3, and n-component vascular variability syndromes (VVSs). For current health care practice, the foregoing diagnoses do not include changes in day-night ratios (DNRs). DNRs and their alterations are routinely computed for research. Thus far for predicting outcomes, DNRs were all inferior to the parametric and nonparametric assessment of VVDs, including some that carry a risk higher than MH itself. In diagnosing MESOR-pre-hypertension, correctly identified with a chronobiologic approach, the DNR misled: the DNR was normal in patients with minimal change retinopathy, and abnormal in the normal controls without any retinal involvement. Pre-diabetes was diagnosed chronobiologically, while the DNR failed to detect it. Any chronobiologically-assessed consequences of MESORhypotension (MO) have yet to be assessed in terms of outcomes and remain beyond the scope of this consensus. VVDs and VVSs derived from C-ABPM gauge an increased vascular disease risk, including conditions unnoticed in current practice, some of which may be treated. When the conditions for C-ABPM 24/7 are met, the term "Diagnosing hypertension" can be replaced by the wider scope of the terms "Diagnosis of VVDs and of VVSs".

Original languageEnglish (US)
Pages (from-to)279-305
Number of pages27
JournalWorld Heart Journal
Issue number4
StatePublished - 2011


  • Blood pressure ecphasia
  • Chat
  • Deficient heart rate variability
  • Excessive pulse pressure
  • MESOR-hypertension
  • MESOR-normotension
  • Outcome


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