Vascular Compliance and Cardiovascular Disease A Risk Factor or a Marker?

Pathophysiologic changes in the blood vessels are associated with a wide variety of cardiovascular events, but our ability to assess vascular structure and function are limited. Although arteriography provides some information regarding intimal pathology, it provides little information about the structure of the arterial wall or its physiology. A reduction in arterial compliance has long been regarded as a potentially useful indicator of the presence of arterial disease.1 Changes in the arterial wall leading to reductions in arterial compliance may precede the onset of clinically apparent disease, and may identify individuals at risk before disease onset (symptoms due to disease are, in general, late manifestations of alterations in organ function). The ability to predict alterations in vascular structure and function before the onset of clinical diseases such as atherosclerosis, hypertension, and diabetes mellitus has potential advantages. Whether reduced vascular compliance precedes the development of cardiovascular disease (ie, is a risk factor) or is the consequence of established cardiovascular disease (ie, a marker) is a matter of debate. To qualify as a risk factor the presence of a condition must increase the probability of disease compared to those without the condition (implying stronger causality). Recent studies have suggested that the ascending aorta of the aortic trunk in Chinese has a larger diameter and thinner media than that in Australians and population differences such as these may be genetically determined.2 Studies have suggested that the angiotensin II type 1 receptor (AT1) gene is involved in the development of aortic stiffness.3 A conceptual example where abnormalities in vascular compliance might be both a risk factor and a marker is hypertension. Hypertension may alter arterial wall tone and structure increasing blood pressure, which results in a decrease in compliance (ie, the decrease in compliance is a marker for hypertension). Alternatively, when sclerotic changes occur in vessels arising from diseases that may or may not increase blood pressure, decreased compliance becomes a risk factor for the development of hypertension. In the following discussions, it should be kept in mind that there is both morphologic (structural) and functional heterogeneity in the different vascular beds. Also, there is no accepted “gold standard” methodology for estimating vascular compliance, so comparison of results obtained with differing methodologies is difficult if not impossible. There exist a number of terms characterizing vascular wall dynamics, so that some studies report results in terms of stiffness or elastic modulus (Ep), whereas others report compliance or distensibility. See the Appendix for a further definition of those terms. In this article, cross-sectional area is used as the reference vascular dimension. Vessel diameter or volume can also be used, although it should be cautioned that during growth and aging, vessel diameter and volume are not necessarily concordant. Compliance will be defined as the change in area for a given change in pressure, whereas distensibility is the fractional change in area for a given change in pressure (by using the percent change in area rather than absolute change, blood vessels of different size can be more readily compared). Elastic modulus is a term that describes the stiffness of the blood vessel wall. Unlike compliance, it is independent of size or geometry; and is defined as the change in wall stress for a given change in strain (see the discussion of wall stress and strain below). Since the relationship between stress and strain in blood vessels is nonlinear, the term incremental elastic modulus is used and is defined as the slope of a tangent to the stress-strain curve. The nonlinear relationship between pressure and area or stress and strain requires that a single value of compliance, distensibility, or elastic modulus cannot be reported for a blood vessel. Rather, these values must be specified at a given pressure. To more fully understand compliance, a brief discussion of the Windkessel concept follows. The arterial system represents a network of vessels designed to convert intermittent flow from the heart to a continuous and steady flow across the capillaries (the Windkessel effect). The level of vascular tone, wave reflection, compliance, and inertance are important contributors to this process. The Windkessel concept can be portrayed in mechanical or electrical terms. Stephen Hale likened the arterial system to a contemporary fire engine device that converted intermittent spurts of water from a pump to smooth flow by the use of a cushioning device that was an inverted air filled dome (called a Windkessel).1 The fire engine consisted of a pump (the electronic equivalent being a voltage source that generates current, ie, flow). The Windkessel served as the compliance component (the electronic equivalent being a capacitor), the fire hose represented the conduit function of the arterial system, the wall of the hose providing the recoil effect (contributing to inertance), and the nozzle introduced resistance (electronically portrayed by a resistor). A number of models have been created in order to approximate the properties of the arterial tree; in many engineering problems, complex systems are often reduced to more elementary electrical models. The simplest electrical model of the Windkessel consists of a resistor and capacitor connected in parallel to a voltage source, representing the left ventricle. Although this basic Windkessel and more complex models are useful, they fail to represent the phenomenon of wave transmission and reflection within the arterial tree, so that other models have also been used to account for that phenomenon. Although all these models are useful in representing many properties of the arterial tree, they have limitations. For instance, many of these models assume that the arterial wall is uniform in terms of compliance, and thereby assume that the arterial tree is nontapering and nonbranching. The models that do attempt to take these aspects into account are usually too complex for clinical use. Vascular tone has traditionally been assessed by determining systemic vascular resistance (SVR), which is a calculation based on steady state flow that does not exist in the pulsatile arterial system. As a relatively crude measure of arterial homeostasis, SVR is determined by the arterioles and not the large conduit vessels, and, therefore is not influenced by large vessel compliance. Somewhat simplistically, blood pressure can be characterized by considering two variables: mean arterial pressure and pressure. arterial pressure is on and vascular and represents the steady state component of blood pressure. pressure is more complex and is influenced by arterial which is a term used to a ability to and left as as of the volume in the aorta and large at the of the compliance of this is a of pulsatile flow). pressure is influenced by the of (ie, the pressure wave established when the volume is into the and (the wave when the wave a change in pressure (ie, and on the compliance. 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A term resistance to Elastic in stress for a given change in is often used as a measure of vessel to wall of of change in area to the The to flow by the arterial system. The vessel and used by some to to or large vessel compliance or or vessel compliance as from the electrical Windkessel