AJH 1997;10:1175–1189 REVIEW Vascular Compliance and Cardiovascular Disease A Risk Factor or a Marker? Downloaded from https://academic.oup.com/ajh/article/10/10/1175/156506 by guest on 28 September 2021 Stephen P. Glasser, Donna K. Arnett, Gary E. McVeigh, Stanley M. Finkelstein, Alan J. Bank, Dennis J. Morgan, and Jay N. Cohn athophysiologic changes in the blood vessels aorta of the aortic trunk in Chinese has a larger diam- are associated with a wide variety of cardio- eter and thinner media than that in Australians and vascular events, but our ability to assess vas- population differences such as these may be geneti- cular structure and function are limited. Al- cally determined.2 Studies have suggested that the Pthough arteriography provides some information angiotensin II type 1 receptor (AT1) gene is involved in regarding intimal pathology, it provides little informa- the development of aortic stiffness.3 A conceptual ex- tion about the structure of the arterial wall or its ample where abnormalities in vascular compliance physiology. A reduction in arterial compliance has might be both a risk factor and a marker is hyperten- long been regarded as a potentially useful indicator of sion. Hypertension may alter arterial wall tone and 1 the presence of arterial disease. Changes in the arte- structure increasing blood pressure, which results in a rial wall leading to reductions in arterial compliance decrease in compliance (ie, the decrease in compliance may precede the onset of clinically apparent disease, is a marker for hypertension). Alternatively, when and may identify individuals at risk before disease sclerotic changes occur in vessels arising from diseases onset (symptoms due to disease are, in general, late that may or may not increase blood pressure, de- manifestations of alterations in organ function). The creased compliance becomes a risk factor for the de- ability to predict alterations in vascular structure and velopment of hypertension. In the following discus- function before the onset of clinical diseases such as sions, it should be kept in mind that there is both atherosclerosis, hypertension, and diabetes mellitus morphologic (structural) and functional heterogeneity has potential advantages. Whether reduced vascular in the different vascular beds. Also, there is no ac- compliance precedes the development of cardiovascu- cepted ‘‘gold standard’’ methodology for estimating lar disease (ie, is a risk factor) or is the consequence of vascular compliance, so comparison of results ob- established cardiovascular disease (ie, a marker) is a tained with differing methodologies is difficult if not matter of debate. To qualify as a risk factor the pres- impossible. ence of a condition must increase the probability of disease compared to those without the condition (im- DEFINITION OF COMPLIANCE, plying stronger causality). DISTENSIBILITY, ELASTICITY, Recent studies have suggested that the ascending AND STIFFNESS There exist a number of terms characterizing vascular wall dynamics, so that some studies report results in Received January 27, 1997. Accepted June 10, 1997. terms of stiffness or elastic modulus (Ep), whereas From the Department of Internal Medicine, Division of Cardiol- others report compliance or distensibility. See the Ap- ogy (SPG, AJB, DJM, JNC), and the Division of General Medicine (GEM), the Department of Laboratory Medicine and Pathology, pendix for a further definition of those terms. In this Division of Health Computer Sciences (SMF), School of Medicine, article, cross-sectional area is used as the reference and the Division of Epidemiology, School of Public Health (DKA), vascular dimension. Vessel diameter or volume can University of Minnesota, Minneapolis, Minnesota. Address correspondence and reprint requests to Stephen P. also be used, although it should be cautioned that Glasser, 3500 E. Fletcher Ave., Suite 218, Tampa, FL 33613. during growth and aging, vessel diameter and volume © 1997 by the American Journal of Hypertension, Ltd. 0895-7061/97/$17.00 Published by Elsevier Science, Inc. PII S0895-7061(97)00311-7 1176 GLASSER ET AL AJH–OCTOBER 1997–VOL. 10, NO. 10, PART 1 are not necessarily concordant. Compliance will be ties of the arterial tree, they have limitations. For in- defined as the change in area for a given change in stance, many of these models assume that the arterial pressure, whereas distensibility is the fractional wall is uniform in terms of compliance, and thereby change in area for a given change in pressure (by assume that the arterial tree is nontapering and non- using the percent change in area rather than absolute branching. The models that do attempt to take these change, blood vessels of different size can be more aspects into account are usually too complex for clin- readily compared). Elastic modulus is a term that ical use. Vascular tone has traditionally been assessed describes the stiffness of the blood vessel wall. Unlike by determining systemic vascular resistance (SVR), compliance, it is independent of size or geometry; and which is a calculation based on steady state flow that is defined as the change in wall stress for a given does not exist in the pulsatile arterial system. As a change in strain (see the discussion of wall stress and relatively crude measure of arterial homeostasis, SVR strain below). Since the relationship between stress is determined by the arterioles and not the large con- Downloaded from https://academic.oup.com/ajh/article/10/10/1175/156506 by guest on 28 September 2021 and strain in blood vessels is nonlinear, the term in- duit vessels, and, therefore is not influenced by large cremental elastic modulus is used and is defined as the vessel compliance. slope of a tangent to the stress-strain curve. The non- Characteristics of Blood Pressure Somewhat sim- linear relationship between pressure and area or stress plistically, blood pressure can be characterized by con- and strain requires that a single value of compliance, sidering two variables: mean arterial pressure and distensibility, or elastic modulus cannot be reported pulse pressure. Mean arterial pressure is dependent for a blood vessel. Rather, these values must be spec- on cardiac output and peripheral vascular resistance, ified at a given pressure. To more fully understand and represents the steady state component of blood compliance, a brief discussion of the Windkessel con- pressure. Pulse pressure is more complex and is influ- cept follows. enced by arterial stiffness, which is a term used to Windkessel Concept The arterial system represents describe a vessel’s ability to undergo deformation, a network of vessels designed to convert intermittent stroke volume, and left ventricular ejection rate (since flow from the heart to a continuous and steady flow as much as 66% of the stroke volume remains in the across the capillaries (the Windkessel effect). The level aorta and large arteries at the end of systole, the of vascular tone, wave reflection, compliance, and in- compliance of this ‘‘compartment’’ is a major determi- ertance are important contributors to this process. The nant of pulsatile flow). Pulsatile pressure is influenced Windkessel concept can be portrayed in mechanical or by the summation of forward (ie, the pressure wave electrical terms. Stephen Hale likened the arterial sys- established when the stroke volume is ejected into the tem to a contemporary fire engine device that con- aorta) and reflected (the wave generated when the verted intermittent spurts of water from a pump to forward propagated wave meets a change in imped- smooth flow by the use of a cushioning device that ance pressure waves) (ie, resistance/compliance mis- was an inverted air filled dome (called a Windkessel).1 match). These forward and reflecting waves primarily The fire engine consisted of a pump (the electronic depend on the system’s compliance. For a more com- plete discussion of this area the reader is referred to equivalent being a voltage source that generates cur- 4 rent, ie, flow). The Windkessel served as the compli- McDonald. ance component (the electronic equivalent being a Wall Stress and Strain If one accepts the postulate capacitor), the fire hose represented the conduit func- that the consequences of vascular damage are related tion of the arterial system, the wall of the hose pro- not only to the level of mean arterial pressure but to viding the recoil effect (contributing to inertance), and pulsatile pressure as well, then an understanding of the nozzle introduced resistance (electronically por- the different kinds of wall stress that the arterial vas- trayed by a resistor). A number of models have been culature deals with is important. Stress is the intensity created in order to approximate the properties of the of force over a unit of area, and may be expansile arterial tree; in many engineering problems, complex (consisting of distending pressures that are both cir- systems are often reduced to more elementary electri- cumferential and longitudinal, this is called tensile cal models. The simplest electrical model of the Wind- stress), compressive, longitudinal, and shear (stress kessel consists of a resistor and capacitor connected in that is tangential to the axis of flow). Shear stress also parallel to a voltage source, representing the left ven- has longitudinal dynamics, but reflects the fact that tricle. Although this basic Windkessel and more com- fluids such as blood move in layers, with flow in the plex models are useful, they fail to represent the phe- middle of the stream moving more rapidly than at the nomenon of wave transmission and reflection within vessel-blood interface. Shear stress may be an impor- the arterial tree, so that other models have also been tant determinant in stimulating the release of endo- used to account for that phenomenon. Although all thelium-derived relaxing factor and prostaglandins these models are useful in representing many proper- that affect smooth muscle tone.5 Strain (the ratio of AJH–OCTOBER 1997–VOL.