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Circulation. 2002;106:2673-2679
Published online before print October 28, 2002, doi: 10.1161/01.CIR.0000039106.89299.AB
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(Circulation. 2002;106:2673.)
© 2002 American Heart Association, Inc.


Clinical Investigation and Reports

Impairment in Cardiac Autonomic Regulation Preceding Arterial Hypertension in Humans

Insights From Spectral Analysis of Beat-by-Beat Cardiovascular Variability

Daniela Lucini, MD, PhD; Giuseppe Sandro Mela, MD; Alberto Malliani, MD; Massimo Pagani, MD

From Centro di Ricerca sulla Terapia Neurovegetativa (D.L., M.P.), Dipartimento Scienze Cliniche L. Sacco (D.L., A.M., M.P.), University of Milano, Milano, Italy, and DIMI (G.S.M.), University of Genova, Genova, Italy.

Correspondence to Massimo Pagani, MD, FACC, Medicina I, Ospedale L. Sacco, Università di Milano, Via GB Grassi, 74, 20157 Milano, Italy. E-mail mp{at}ctnv.unimi.it

Background— Subjects in the upper-normal range of arterial pressure have an excess cardiovascular risk, which suggests that other factors, such as impaired autonomic regulation, might be implicated. This study was designed to assess whether noninvasive markers of cardiac and vascular autonomic regulation might already be altered in subjects with high-normal arterial pressure levels.

Methods and Results— We performed an observational study on a population comprising 300 subjects of both sexes with arterial pressure ranging from 90/60 to 210/120 mm Hg, who were divided into 3 groups (each n=100) with average systolic pressures of 103, 133, and 163 mm Hg. Autonomic regulation was inferred from spectral analysis of RR interval and systolic arterial pressure variability, considering rest and stand-induced changes, to account for sympathetic excitatory components. Significant alterations in markers of sinoatrial regulation (increased low-frequency normalized units, reduced high-frequency normalized units, and {alpha}-index) were already apparent in subjects in the second tertile, ie, those with arterial pressure within normal limits. Markers of vascular regulation instead showed significant alterations in the third (hypertensive) tertile. In response to standing, changes in markers of sinoatrial modulations were gradually reduced, whereas those of vascular regulation were increased. A tight link between progression of arterial pressure and the continuum of changes in autonomic markers as shown by simple correlation analysis appeared strongly affected by age and was spread across many spectral analysis–derived variables. Hypertensive autonomic dysregulation was particularly apparent in the youngest group.

Conclusions— RR-variability parameters might prove useful to assess, with longitudinal studies, the mechanistic role of autonomic impairment in the increased risk of prehypertensive conditions.


Key Words: nervous system, sympathetic • hypertension • aging • prevention




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