The Journal for Nurse Practitioners
Volume 5, Issue 10 , Pages 745-751, November 2009

How Stiff Are Your Arteries? An Emerging Vital Sign for Determining Cardiovascular Disease Risk

  • Debra J. Barksdale

      Affiliations

    • Debra J. Barksdale, PhD, FNP-BC, ANP-BC, CNE, FAANP, is an associate professor at the University of North Carolina at Chapel Hill, a practicing primary care NP, and a NIH-funded researcher. Her program of research focuses on stress and cardiovascular disease, specifically hypertension.
    • ,
  • Jeongok G. Logan

      Affiliations

    • Jeongok Gang Logan, MSN, RN, is a nurse on a cardiothoracic step down unit and a PhD candidate at UNC-Chapel Hill. Her dissertation research is focused on stress, blood pressure, arterial stiffness, and heart rate variability in Korean Americans.

Article Outline

Abstract 

Arterial stiffness is an indicator of cardiovascular risk and disease. This paper discusses the pathophysiology and specific measures of arterial stiffness (augmentation index and pulse wave velocity) and methods for determining arterial stiffness, including applanation tonography, pulse pressure, Ambulatory Arterial Stiffness Index, impedance cardiography, ultrasound, and magnetic resonance imaging. As issues related to the utility of arterial stiffness in clinical practice (eg, standardization and validation) are resolved through research, primary care providers should recognize this emerging “vital sign” as an important cardiovascular assessment tool for their patients.

Keywords:  arterial stiffness , cardiovascular risk , hypertension , pulse wave analysis , pulse wave velocity

 

Arterial stiffness has been shown to be an independent predictor of cardiovascular events, including stroke and myocardial infarction, among others.1 In determining arterial stiffness, wave forms from the aorta are analyzed, providing information on the stiffness of large arteries, thereby offering a more sensitive measure of variation in the systolic-diastolic blood pressure cycle. Further, arterial stiffness may also provide a more sensitive predictor of cardiovascular and stroke risk in some populations, such as women and older adults.1, 2 For example, Noon et al2 found that women had stiffer arteries than men of similar ages, placing them at greater risk for cardiovascular disease.

Peripheral blood pressure (BP) is a basic and frequent vital sign used to indicate cardiovascular risk.3, 4 Currently, the gold standard for blood pressure (BP) measurement is to obtain diastolic (DBP) and systolic pressure (SBP) using a sphygmomanometer to measure peripheral brachial artery pressure. Conventional BP measurement only captures two BP points (the maximum pressure when the heart is contracting and the minimum pressure when the heart is at rest) and does not adequately record critical phases across the BP curve. In addition, conventional BP does not capture cardiac function and pressure at an important source—the aorta.5, 6 Through analysis of aortic wave forms, measures of arterial stiffness provide a more comprehensive and perhaps more accurate measure of cardiovascular function than typical peripheral BP measurements.

Recognition of the importance of arterial stiffness is not new; however, there was a loss of interest in its value during the early 20th century. It was assumed that the stiffening of arteries was part of the normal aging process and therefore lacked useful clinical relevance.7 Recently, there has been a resurgence of interest in arterial stiffness as an indicator of cardiovascular health, and multiple research studies have suggested that measures of arterial stiffness are better predictors of cardiovascular disease risk than traditional measures of BP.1, 8, 9

The purpose of this paper is to provide an overview of arterial stiffness as an emerging indicator of cardiovascular disease risk that can be useful in clinical practice. We will define arterial stiffness and discuss its physiological mechanisms and contributions to disease pathology. Further, we will discuss issues regarding the utility and measurement of arterial stiffness in primary care practice.

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What is Arterial Stiffness? 

Arterial stiffness or arteriosclerosis refers to hardening of arterial walls and is often confused with atherosclerosis. The arterial wall has 3 layers, the intima, the media, and the adventia. The intima is the innermost layer and contains endothelial cells. The media contains elastin, collagen, and smooth muscle cells.10 Arteriosclerosis is mainly caused by medial degeneration involving decreased elastin and increased collagen fibers.11 On the other hand, atherosclerosis is characterized by a thickening of the intima with buildup of plaques that contain lipid-laden macrophages and may result in decreased blood flow to the affected area.11 Because atherosclerosis results in hardening of arteries, atherosclerosis can be said to be a specific type of arteriosclerosis.

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The Effects of Stiff Arteries 

The stiffness of an artery is determined by the relationships of collagen and elastin in the vasculature, which determine its degree of distensability.1 A number of factors contribute to arterial stiffness, including: endothelial dysfunction, modified vascular wall proteins, genetics, inflammation, and chronically elevated blood pressure.1, 12

The elastic properties of large arteries play an essential role in cardiovascular hemodynamics through the buffering of the wave volume and the propagation of the pressure pulse.13 When blood is ejected into the aorta, a pressure wave is generated and transmitted throughout the body. When the walls of the arteries lose their elastic properties they become stiff, which causes the pulse waves to increase in both pressure and velocity. In other words, when arteries are stiff, the wave form reflects faster and later in systolic, resulting in an increase in SBP, left ventricular load, and pulse pressure. This increase in aortic SBP and load ultimately contributes to greater risk for cardiovascular disease.14 Increased BP can further reduce the large arteries' capacity to cushion the pressure when blood is ejected from the ventricle of the heart.13 Elastic arteries buffer the wave velocity, but when arteries are stiff, the faster wave reflections lead to increased load on the heart and altered coronary flow. Therefore, the aortic pressure wave form is an important determinant of cardiac function and coronary perfusion.15

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Circadian Variations in the Pressure Wave Form 

Cardiovascular mechanisms exhibit variations throughout the day. In fact, it has been well documented that most cardiovascular events, including sudden cardiac death, peak in the early morning between 6 and 11 a.m. Using aortic pulse wave patterns, Papaioannou and colleagues9 found significant variations in wave reflection intensity in a study of 7 healthy women and 6 healthy men (mean age: 40.7, SD 16.5 years) and the greatest increase was at 8 a.m. within one hour of awakening. They postulated that increased intensity of reflected waves in the morning along with the increase in BP and heart rate upon awakening may result in increased afterload in the left ventricle and increased demand for oxygen from the myocardium. These series of physiological variations may contribute to acute early morning cardiovascular vulnerability, especially when arteries are stiff. Although the sample size seems small to make such grand associations, this study was longitudinal, with 12 measures per subject (total of 156 measures) over a period of 12 hours. These researchers estimated that this sample size would give an efficient 80% power to detect change by 7% in the measure of arterial stiffness (a = 0.05 and B = 0.20 two-tailed test).9

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Deriving Measure of Arterial Stiffness 

Arterial stiffness is commonly defined by augmentation index and pulse wave velocity (PWV). Derived from the arterial pulse wave form, the augmentation index (AIx) is a measure of the rise in pressure within the arterial system. Specifically, augmentation index is the augmentation pressure (difference between maximal central aortic systolic pressure and pressure at the first peak of the pulse wave) divided by the aortic pulse pressure (the maximal difference between SBP and DBP) expressed as percentages16 (Figure 1). Higher AIx values indicate increased wave reflection from the periphery and/or early return of the reflected wave as a result of arterial stiffness. The AIx can be affected by multiple factors, including left ventricular ejection, PWV, timing of reflection, arterial tone, structure at peripheral reflecting sites, BP, and heart rate.17

  • View full-size image.
  • Figure 1. 

    Systolic pressure-aortic systolic pressure; diastolic pressure-aortic diastolic pressure;pulse pressure-difference between the systolic and diastolic pressures. Time: T0, start of the waveform; T1, time from start of wave form to the first peak (outgoing pressure wave); T2, time from start of wave form to the second peak (reflected pressure wave). Ejection duration: time from start of wave form to the closure of the aortic valve; augmentation pressure, difference between maximum pressure at T2 and pressure at the first peak at T1. Augmentation index is the augmentation pressure divided by the pulse pressure * 100 (Aix 5 (P/PP) * 100).(Laurent et al,1 Williams et al,15 Mackenzie et al.7)

PWV, a direct measure of arterial stiffness, determines the speed of movement of the blood through the arterial system.18 A higher PWV is associated with stiffer arteries and higher cardiovascular mortality and increased cardiac events.19 Stiffer arteries will have higher PWV; thus, a more compliant aorta will have a lower PWV. Carotid-femoral PWV is currently accepted as the gold standard for determining arterial stiffness because it is measured along the aortic and aorto-iliac pathway. The thoracic and abdominal aorta makes the largest contribution to the arterial buffering function (cushioning function).1, 20

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Measuring Arterial Stiffness in Primary Care 

Pulse Wave Analysis, AIx, and PWV 

Pulse wave analysis may facilitate early identification of cardiovascular risk and associated conditions including hypertension, diabetes, diastolic heart failure, renal disease, and hypercholesterolemia. Although there are multiple ways of measuring arterial stiffness, we are most experienced with using SphygmoCor (AtCor Medical, Sydney, Australia), which can be used in primary care (Figure 2). SphygmoCor pulse wave analysis uses applanation tonometry to measure pressure or tension in the artery. Applanation means to flatten and a tonometer is a device or probe for placing tension or pressure on the skin over the artery. When the artery is flattened but not occluded, a pressure wave form can be obtained using high-frequency ultrasound specifications. Pulse wave analysis can be performed from the radial artery on the dominant arm using applanation tonometry and a central wave is derived from each of the peripheral wave forms using software associated with the SphygmoCor system.

This technique requires operator training and works best with central arteries, which might not always be easily accessible, thereby necessitating the use of superficial arteries.7 This non-invasive procedure takes a 10-second snapshot of the arterial pressure wave from the radial artery and derives the ascending aortic pressure wave, thus providing cardiovascular measurements such as the AIx as well as central aortic BP (Figure 3). By using the SphygmoCor, providers are able to detect and measure arterial stiffness and other parameters associated with alterations in coronary artery perfusion pressure. Reference values for pulse wave analysis (using SphygmoCor) for white Europeans and black South Africans, based on age and gender, have been reported by Shiburi et al21 and Wojciechowska et al,22 respectively. Further, Koivistoinen et al23 have reported reference values for PWV based on 799 healthy Finnish adults between the age of 25 and 76 years. Some other devices described in the literature for determining PWV include the Complior System (Colson, Les Lilas, France), Arteriograph (TensioMed, Budapest, Hungary), and PulsePen (DiaTecne, Milan, Italy).1, 24, 25 Further research is needed on reference values across devices and for racial and ethnic groups.

Other Methods for Determining Arterial Stiffness 

There are multiple other methods for determining the degree of arterial stiffness, including: determination of pulse pressure, the Ambulatory Arterial Stiffness Index, impedance cardiography, and measures obtained by ultrasound and magnetic resonance imaging (MRI). Most of these might not be feasible for the primary care practice. Nevertheless, these options are briefly discussed so that the primary care provider can make informed decisions about referring or recommending further assessment of arterial stiffness in determining cardiovascular risk or the extent of actual cardiovascular disease.

Pulse pressure 

Pulse pressure is the difference between SBP and DBP and is affected by several factors, including cardiac output and the stiffness of the arteries. A pulse pressure of 40 mmHg is normal in a person with a normal blood pressure (120/80 mmHg: 120−80 = 40). Pulse pressure provides information about arterial stiffness in that when arteries are stiff, DBP may be low in reference to SBP; therefore, pulse pressure is increased. When the pulse pressure is increased, coronary artery perfusion is altered, thereby leading to increased risk of myocardial infarction.

No special equipment is needed other than a standard BP monitoring device. The measure of pulse pressure is only as reliable as the measures of BP used to calculate it. Further, these measures are less reliable in certain groups such as older adults because in the 5th or 6th decade of life, DBP ceases to increase and in many cases even drops.6, 7, 26 Pulse pressure therefore widens with age. In addition, pulse pressure alone may not be sufficient because a pulse pressure of 40 mmHg for a blood pressure of 140/100 would not be considered normal because the BP is not normal. Nevertheless, research indicates that pulse pressure is an important indicator of cardiovascular risk.7, 26, 27

Ambulatory Arterial Stiffness Index (AASI) 

The AASI as proposed by Li and colleagues (2006) is derived from 24-hour BP measurements. The AASI is based on a statistical calculation. A regression slope is determined for DBP and SBP based on a 24-hour blood pressure recording. AASI is one minus the regression slope. AASI would then be on a 0 to 1 scale, with stiffer arteries having a higher value. Some studies have shown that AASI is closely related to augmentation index and PWV.12 The utility of AASI as a predictor of cardiovascular risk and disease is currently being explored and debated.12, 28, 29 Additional validation of the AASI is recommended.

Impedance cardiography 

Impendence cardiography is a procedure for detecting cardiovascular and blood flow properties using sensors that detect electrical signals. Systemic vascular resistance (an indicator of arterial stiffness) is one of the many hemodynamic parameters that can be determined. With this procedure, a current is transmitted through the chest, which travels through the aorta. The impedance or resistance to the current is measured and used to calculate hemodynamic parameters, including: cardiac output, stroke volume, vascular resistance, acceleration index, systolic time ratio, left ventricular ejection time, pre-ejection period, and left cardiac work/index, among others.

Koivistoinen et al23 describe whole-body impedance cardiography as a non-invasive, easy to operate, and reliable method for evaluating arterial stiffness by PWV. They recommend it for screening patients who are at risk for, or early in, the cardiovascular or vascular disease. Aortic impedance is also a noninvasive procedure that has been used to determine arterial stiffness. Though complex and sophisticated, the technique is described as being consistent with simpler measures of arterial stiffness.30

Ultrasound and MRI 

Ultrasound can be used to determine arterial stiffness in terms of distensibility and compliance by measuring the changes in diameter during systole and diastole.1, 31 Ultrasound is noninvasive but expensive and is usually not readily available in the primary care office. There are other issues related to the use of ultrasound in determining arterial stiffness: it must be used on larger, easily accessible arteries; resolution limitations pose difficulties in detecting small changes in the diameter of vessels; and it requires an operator skilled in imaging vessels walls.7 Arterial distensibility and compliance can also be determined by MRI.12 Although non-invasive, MRI is expensive and is not frequently used to assess arterial stiffness in the general patient population.

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Clinical Application in Primary Care 

Pulse wave analysis is useful in clinical situations because it allows the provider to evaluate the impact of arterial stiffness on the heart, providing a useful indicator of patient risk and disease progression.24 Further, cardiovascular assessment and treatment decisions (especially pharmaceutical management) can be more skillfully tailored to meet individual patient needs.12 Other reported benefits of evaluating cardiovascular status by pulse wave analysis include improved assessment and management of diabetes, heart failure, and renal disease.1, 8, 12 Through pulse wave analysis, the effects of arterial stiffness, such as increased demand on the left ventricle and decreased perfusion pressure through the coronary arteries, can be evaluated. Therefore, pulse wave analysis can provide important information on an individual's risk for heart attack, heart failure, and stroke.

The good news is that arterial stiffness can be reduced. There are non-pharmacological and pharmacological mechanisms for reducing arterial stiffness and many of these are accepted interventions for lifestyle modifications. Exercise, low-salt diet, weight reduction, reducing alcohol intake, garlic, alpha-linoleic acid, fish oil, and hormone replacement therapy have all been associated with reductions in arterial stiffness through research.1 Pharmaceuticals, including drugs used for managing hypertension, congestive heart failure, dyslipidemia, and diabetes, have also been shown to improve arterial stiffness.1, 12, 15 Good clinical management of arterial stiffness includes both lifestyle modifications and pharmaceutical management.

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Implications and Conclusion 

Our purpose was to introduce the concept of arterial stiffness as an emerging and valid measure of cardiovascular risk and disease that can be assessed and monitored in primary care. Arterial stiffness is regarded as both a biomarker of, and a risk factor for, cardiovascular disease. That is, arterial stiffness can be considered a “vital sign” for determining cardiovascular function (like conventional blood pressure is), but if abnormal, it becomes a risk factor (like hypertension, which is both a cardiovascular disease and a risk factor for other cardiovascular diseases). Indeed, there are current issues related to the widespread measurement of arterial stiffness in clinical practice.

One issue is consistency and interpretation of measures across techniques and equipment. For example, Rajzer et al25 compared 3 different devices for measuring PWV. They found differences in measures based on the calculation of transit time. Therefore, some devices produced higher PWV than others. Because they were not able to determine which device was correct, these researchers advocate for the establishment of uniform principles for computing PWV.

Further, there is still debate over which method of arterial stiffness is most valuable, reliable, and useful for determining arterial stiffness in clinical situations.12 As we have indicated, there are a number of methods for determining arterial stiffness and, although PWV is currently the front runner in debate,31 more research is needed to confirm its utility as a useful marker of cardiovascular risk in primary care.12

Standards are being set and evaluated for measurement and interpretation of arterial stiffness indices. In 2006, Laurent and colleagues published a document entitled Expert Consensus Document on Arterial Stiffness: Methodological Issues and Clinical Application, which explicated 10 position statements related to measuring arterial stiffness. Other researchers such as Adiyaman et al,28 Koivistoinen et al,23 and Wojciechowska et al22 have begun to establish parameters for measures of arterial stiffness using various devices.

While widespread usage of arterial stiffness as an indicator of cardiovascular disease risk and severity has not occurred in primary care, it is a recognized indicator of cardiovascular status. Providers should be aware of this emerging “vital sign,” and its potential implications for use in managing patients with, or at risk for, cardiac and vascular conditions. Indices of arterial stiffness show promise of being more sensitive and specific indicators of cardiovascular status than traditional brachial blood pressure measurement.

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References 

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 In compliance with national ethical guidelines, the authors report no relationships with business or industry that would pose a conflict of interest.

PII: S1555-4155(09)00475-9

doi:10.1016/j.nurpra.2009.08.018

The Journal for Nurse Practitioners
Volume 5, Issue 10 , Pages 745-751, November 2009

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