Cugini's syndrome in statu nascendi: Oratio contra morem prevalentem et pro chronobiologica ratione ad pressione sanguinis curandam

Germaine G Cornelissen-Guillaume, F. Halberg, L. Beaty, Y. Kumagai, E. Halberg, J. Halberg, J. Lee, O. Schwartzkopff, K. Otsuka

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


An increase in the circadian amplitude (A) of blood pressure (BP) had been reported to precede a rise in the circadian BP average (MESOR, M), as pre-hypertension in the stroke-prone Okamoto rat. In humans, children with a positive family history of high BP and/or related cardiovascular disease had, on average, a larger BP-A than children with a negative family history, and an elevated BP-A was associated with intermediate values of the left ventricular mass index (LVMI), whereas an elevation in BP-M was only observed for larger LVMI values. Against this background, with 24-hour ambulatory monitoring (ABPM) interpreted chronobiologically, Pietro Cugini (University 'La Sapienza' of Rome, Italy) has reported an elevation of both the circadian BP-M and BP-A as occurring with a minimal change (hypertensive) retinopathy. He determined by cosinor the extent of predictable BP change within a day as BP-2A, estimated by the least squares fit of a 24-hour cosine curve to the data. As compared to controls without retinopathy, he found a retinal end-organ involvement associated with average systolic (S) / diastolic (D) BP-Ms of 124/76 vs. 112/72 mmHg, with corresponding SBP/DBP-As of 12/10 vs. 8/7 mmHg. We refer to "Cugini's syndrome", suggesting the need for clarification, preferably in longitudinal studies, of any generalizable sequence in end-organ involvement, that may occur in the course of the development of some human Vascular Variability Disorders (VVDs) of unknown etiology, that include an elevation of the circadian BP-A and/or BP-M, concomitantly or separately in a sequence with the BP-A increase preceding that in BP-M, as in models of high BP in the rat or vice versa. Seven-day half-hourly or hourly around-the-clock monitoring of BP and HR variability interpreted chronobiologically, C-ABPM, as a minimum, is recommended for routine medical care to detect VVDs consisting of 1. MESOR-hypertension, MH; 2. Circadian Hyper-Amplitude-Tension, CHAT (BP overswing); 3. odd timing of the circadian rhythm of BP but not that of HR; 4. above-threshold pulse pressure; and/or 5. below-threshold HR variability. All conditions are best determined by 24-hour/7-day or, when abnormality is detected, longer C-ABPM. Eventually, all conditions will need to be assessed in the light of reference values from gender- and age-matched peers, as is now the case for the first three VVDs listed above. When C-ABPM is not practicable, a 7-day series of 3-hourly manual self-measurements during waking (and one measurement about mid-sleep) (C-MBPM) is recommended. When continuous monitoring becomes possible, as it is within the state of the science, detecting Cugini's syndrome will also become possible with the clarification as to whether any change in BP-M and/or BP-A occurs concomitantly or sequentially, with changes in BP-A anticipated to precede changes in BP-M.

Original languageEnglish (US)
Pages (from-to)e13-e24
JournalClinica Terapeutica
Issue numberSUPPL.2
StatePublished - 2010


  • Blood pressure
  • CHAT
  • Circadian
  • Ecphasia
  • Heart rate
  • MESOR-hypertension
  • Pulse pressure
  • Vascular Variability Syndrome (VVS)
  • Vascular variability disorder (VVD)


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