Published online before print August 28, 2006, doi: 10.1161/01.HYP.0000239236.12524.d3
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(Hypertension. 2006;48:541.)
© 2006 American Heart Association, Inc.
Editorial Commentaries |
At the Beginning of Stiffening
Endothelial Dysfunction Meets "Pulsology"
From the Hospital S. Maria della Misericordia (P.V., F.A.), Clinical Research Unit–Preventive Cardiology, Perugia, Italy; and the Department of Internal Medicine (S.T.), University of Pisa, Pisa, Italy.
Correspondence to Paolo Verdecchia, Hospital S. Maria della Misericordia, University of Perugia, Clinical Research Unit–Preventive Cardiology, Piazzale G. Menghini, 1, 06100 Perugia, Italy. E-mail verdec{at}tin.it
Brachial cuff blood pressure (BP) continues to guide almost every decision related to the clinical management of the hypertensive patient. However, the BP within the central aorta (ie, aortic pressure) is receiving growing attention for 2 main reasons. First, brachial BP does not necessarily predict aortic pressure, and subjects with equal values of brachial cuff pressure may differ markedly in their aortic pressure.1 Second, aortic pressure may be superior to brachial BP for the prediction of several vascular complications, including the degree of carotid atherosclerosis,2 the extent of coronary artery disease,3 the likelihood of reocclusion after angioplasty,4 and, more important, the risk of major cardiovascular events.1,5
Aortic BP may be estimated noninvasively from analysis of peripheral radial artery waveforms with applanation tonometry. Although the reliability of derived aortic BP is crucially dependent on the validity of the transfer function used to generate the central aortic waveforms, the correspondence between estimated central aortic and intra-arterial systolic BP and pulse pressure (PP) seems to be quite close.6 In addition to central PP, pulse wave velocity (PWV) is another good marker of arterial wall stiffness and predictor of cardiovascular events in different clinical settings.7
Initial data suggest that endothelial dysfunction may play a role in the pathogenesis of arterial stiffening. An impaired endothelial function detected at the peripheral8 and coronary9 level has been associated with a wide peripheral PP. Through a decreased production of NO, endothelial dysfunction may increase arterial stiffness by promoting atherosclerosis or even inducing contraction of the surrounding vascular muscle cells.10
So far, a precise assessment of the relation between endothelial dysfunction and arterial stiffening had been almost precluded by the lack of direct measures of arterial stiffening (ie, PWV and aortic pressure) and the potential confounding effect of concomitant risk factors for atherosclerosis. Such a gap has been bridged by the study by McEniery et al11 published in this issue of Hypertension. The authors examined a large cohort of healthy volunteers who were free of cardiovascular disease, risk factors, and medication. In addition to peripheral and central PP, augmentation index (AIx), and PWV, the authors assessed brachial artery flow-mediated dilatation (FMD) as a measure of conduit artery endothelial function. They also assessed global endothelial function through the change in AIx in response to albuterol (which provides an endothelium-dependent dilatation) and nitroglycerin (which provides an endothelium-independent vasodilation).12 Global endothelial function showed a significant inverse association with aortic PWV and AIx and a closer association with central PP as compared with brachial PP. After adjustment for potential confounders including age and glucose, endothelial function maintained an independent association with aortic PWV and AIx. Worthy of interest, the association between global endothelial function and central PP was much higher as compared with the association observed with FMD. Taken together, these observations suggest that central PP is a better determinant of preclinical organ damage and that a method assessing global endothelial function can better predict cardiovascular risk as compared with a method, such as FMD, exploring a selected vascular district.
A limitation of this study was the inclusion of a percentage of smokers so that the study population cannot be defined as free of "risk factors." Although cigarette smoking did not show an independent association with the indices of aortic stiffness, it might have exerted some influence on endothelial function. Thus, the effect of endothelial dysfunction on arterial stiffness was not entirely free from the potentially confounding influence of risk factors. In addition, because global endothelial function was assessed by the same method used to measure arterial stiffness and central PP, the possibility exists that at least part of the relationship might be related to a possible common denominator. In this case, the relationship between FMD and central PP represents the real endothelial component of stiffness.
In the context of its limitations, this study has the merit to show for the first time that even in apparently healthy subjects with normal brachial BP, a depressed function of vascular endothelium may be associated with increased central PP and arterial stiffening. This might be the hidden first step of a vicious circle consisting of repeated cycles of distensions of the arterial wall, fragmentation, and depletion of elastin and final deposition of collagen with progressive worsening of arterial stiffness.13 Furthermore, the rise in systolic BP in the ascending aorta could lead to a rise in the left ventricular (LV) end-systolic stress, a major determinant of LV hypertrophy. The old finding that increased LV mass predicts the occurrence of hypertension in healthy normotensive subjects14 is compatible with a hidden rise in central BP antedating the overt development of hypertension detectable at the brachial artery level. The potential implications of these findings are summarized in the Figure. Thus, the marriage between endotheliology and pulsology celebrated in the present cross-sectional study by McEniery et al11 should stimulate longitudinal research to address the value of serial changes in endothelial function and arterial stiffness in apparently healthy subjects for prediction of hypertension and related organ damage.
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Acknowledgments |
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Disclosures
None.
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Footnotes |
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The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.
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References |
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Hypertension 2006 48: 602-608.
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