Beyond blood pressure: Arterial stiffness as a new biomarker of cardiovascular disease

doi:10.1016/j.jash.2007.09.002

Journal of the American Society of Hypertension

Volume 2, Issue 3, May–June 2008, Pages 140-151

https://doi.org/10.1016/j.jash.2007.09.002 Get rights and content

Abstract

Arterial stiffness of the large, elastic conduit arteries is considered a risk marker of vascular aging, as well as a new biomarker of cardiovascular (CV) disease. Arterial stiffness also plays an important role in the development of isolated systolic hypertension (ISH) in the middle-aged and elderly population. ISH is characterized by an increase in pulse pressure (PP) in association with a rise in systolic blood pressure (SBP) and a fall in diastolic blood pressure (DBP). Increased PP, however, is not always a good surrogate for arterial stiffening because of the frequent discrepancy between peripheral brachial and central aortic PP values due to varying pressure amplification. Therefore, noninvasive, easily performed methods for more direct measurement of arterial stiffness and wave reflection, such as aortic pulse wave velocity (PWV) and pulse wave analysis, have been developed for clinical use. The present review aims to provide an understanding of the pathophysiology of arterial stiffness and wave reflection, to review the various techniques for their measurement, and to explore their usefulness in predicting CV risk and therapeutic benefit in comparison with traditional brachial artery cuff blood pressure (BP) by sphygmomanometry.

Introduction

In recent years, hemodynamic profiling of blood pressure (BP) has become an important modality for assessing cardiovascular (CV) risk in a variety of clinical states.1, 2 Brachial artery cuff BP–a strong and independent predictor of morbidity and mortality in hypertension, coronary heart disease (CHD), heart failure, stroke, and kidney disease–remains the gold standard for clinical assessment of CV risk.3, 4 More recently, however, age-related stiffening of central elastic arteries and wave reflection, resulting in increased pulse pressure (PP) and the development of isolated systolic hypertension (ISH), play a crucial role in CV disease.5, 6 The subject of this article is the potential value of hemodynamic profiling of arterial stiffness and wave reflection in assessing CV risk. The main questions to be considered: how useful are measurements of arterial stiffness and wave reflection, in comparison with brachial artery cuff BP, as possible biomarkers for early detection of CV disease and assessment of antihypertensive therapy?

Section snippets

Pulsatile and Steady State Hemodynamics

The arterial pulse wave consists of a pulsatile component (PP) during systole and a steady component of mean arterial pressure (MAP) during diastole. PP, the difference between peak systolic blood pressure (SBP) and end diastolic blood pressure (DBP), represents the pressure increment over and above the existing DBP that results from ventricular contraction and ejection of arterial blood into the aorta.⁷ At any given ventricular ejection, cardiac output and heart rate, large artery stiffness,

The Function of Elastic-Containing Conduit Arteries

The arterial system has dual interrelated functions: 1) to provide a sufficient quantity of blood to various tissues of the body (the conduit function), and 2) to convert highly pulsatile flow into more continuous flow at the level of the small arteries (the cushioning, compliance, or capacitance function).8, 9 In a youthful arterial system, flow pulsastility is dampened primarily by elastin-containing central arteries — the thoracic aorta and its most proximal branches, which fulfill the bulk

How do Hemodynamic Mechanisms Impact Blood Pressure Components?

Both increased PVR and increased central arterial stiffness and early wave reflection elevate SBP. In contrast, DBP rises with increased PVR but falls with increased stiffness and early wave reflection; the relative contribution of each determines the ultimate DBP. Diastolic hypertension is arbitrarily defined as a DBP of equal or greater than 90 mm Hg. There are two subtypes of diastolic hypertension: 1) isolated diastolic hypertension (IDH; DBP ≥ 90 mm Hg and SBP < 140 mm Hg) and 2)

Pathological Consequences of Increased Vascular Stiffness

The relationship between BP and CHD risk as a function of age was examined in the Framingham Heart Study.¹⁰ From the age of 20 to 79 years there was a continuous, graded shift from DBP to SBP and eventually to PP as predictors of CHD risk (Figure 2). From age 60 onward, when considered with SBP, DBP was negatively related to CHD risk, so that PP emerged as the best predictor. In contrast with the elderly, all three BP indices in the Framingham Heart Study¹⁰ were equally predictive of CHD risk

Pitfalls in the Diagnostic Value of Pulse Pressure as a Surrogate for Arterial Stiffness

There are pitfalls in the use of peripheral brachial BP components, especially SBP and PP, in predicting CV risk. First, brachial artery BP is frequently inaccurately and imprecisely measured. SBP can be measured with more precision than DBP, despite the former having a broader range than the latter. The calculation of PP is even less precise and accurate because of the summation of measurement errors for SBP and DBP. Second, increased PP and the development of ISH are a late manifestation of

Peripheral Pressure Amplification

The central pressure waveform is produced by two major components, a forward traveling wave, generated by ventricular ejection, and a reflected wave arriving back from the periphery.7, 8 The smooth forward-going wave is influenced by intermittent ventricular ejection and by mechanical properties of the aorta and other large elastic arteries, which serve to buffer the pressure changes. In contrast, the reflected wave is influenced by the elastic properties of the entire arterial system,

Direct Measurements of Arterial Stiffness

Local methods for determining stiffness can be measured in superficial vessels, such as the carotid arteries, by ultrasound or in deep arteries, such as the aorta, by magnetic resonance imaging or echo tracking techniques.¹ Because these methods are costly, time-consuming, and require a high degree of technical expertise, they are not practical for wide clinical use.

Systemic arterial stiffness techniques, such as diastolic decay, based on an electrical circuit and a modified Windkessel model,

Correlation of Arterial Stiffness and Wave Reflections with Disease States

Measures of arterial stiffness are associated with CV risk factors and target organ damage in a variety of cross-sectional studies. Aortic PWV was associated with visceral adiposity, as measured by abdominal tomography and waist circumference, in the elderly health, Aging, and Body Composition (ABC) Study; these findings were independent of age, gender, and BP.²⁵ It has long been known that diabetes negates the CV protective effects of being a young woman; indeed, there is evidence that greater

Arterial Stiffness and Wave Activity as Predictors of Future Cardiovascular Events

During the past several years, there have been a number of longitudinal studies which show arterial stiffness to have independent predictive value for CV disease (Table). Longitudinal measurement of aortic PWV predicted CV mortality in end-stage renal disease (ESRD),⁴⁰ in essential hypertension,¹⁵ in the elderly,⁴¹ and in type 2 diabetes/glucose intolerance⁴²; aortic PWV predicted CHD events⁴³ and fatal stroke events⁴⁴ in essential hypertension; aortic PWV predicted CV mortality and events in

Therapeutic Studies

Numerous placebo-controlled trials, drug comparison trials, and large meta-analyses of drug treatment, including the Trialists Collaboration study,⁵⁷ have shown that BP reduction was the primary determinant of the benefit of antihypertensive drug treatment. However, an even larger meta-regression analysis⁵⁸ not only confirmed the importance of lowering BP in reducing CV events, but also showed a specific class effect benefit of about 10% for angiotensin-converting enzyme (ACE) inhibitors (ACEI)

Conclusions

Over the past several years, there has been an explosion of publications showing that arterial stiffness is an independent predictor of CV risk. Indeed, central BP, as a measure of arterial stiffness, is more influenced by wave reflection, more affected by BP altering drugs, and more predictive of CV risk than is brachial BP. Perhaps the most suitable population for future clinical assessment of arterial stiffness will be the young and early middle-aged individuals with marginal CV risk factors

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Review articleBeyond blood pressure: Arterial stiffness as a new biomarker of cardiovascular disease

Abstract

Introduction

Section snippets

Pulsatile and Steady State Hemodynamics

The Function of Elastic-Containing Conduit Arteries

How do Hemodynamic Mechanisms Impact Blood Pressure Components?

Pathological Consequences of Increased Vascular Stiffness

Pitfalls in the Diagnostic Value of Pulse Pressure as a Surrogate for Arterial Stiffness

Peripheral Pressure Amplification

Direct Measurements of Arterial Stiffness

Correlation of Arterial Stiffness and Wave Reflections with Disease States

Arterial Stiffness and Wave Activity as Predictors of Future Cardiovascular Events

Therapeutic Studies

Conclusions

J Am Coll Cardiol

J Am Coll Cardiol

Am J Hypertens

Am J Hypertens

Kidney Int

Am J Cardiol

Lancet

Am J Hypertens

J Am Coll Cardiol

European Network for Non-invasive Investigation of Large ArteriesExpert consensus document on arterial stiffness: methodological issues and clinical applications

Eur Heart J

Central blood pressure measurements and antihypertensive therapy

Hypertension

JAMA

2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)

Eur Heart J

Predominance of isolated systolic hypertension among middle-aged and elderly US hypertensives

Hypertension

Hemodynamic patterns of age-related changes in blood pressure: the Framingham Heart Study

Circulation

McDonald's blood flow in arteries: theoretical, experimental and clinical principles

Mechanisms, pathophysiology, and therapy of arterial stiffness

Arterioscler Thromb Vasc Biol

Does the relation of blood pressure to coronary heart disease risk change with aging?The Framingham Heart Study

Circulation

Effect of aging on the prognostic significance of ambulatory systolic, diastolic, and pulse pressure in essential hypertension

Circulation

Importance of arterial pulse pressure as a predictor of coronary heart disease risk in PROCAM

Eur Heart J

Ambulatory pulse pressure: a potent predictor of total cardiovascular risk in hypertension

Hypertension

Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients

Hypertension

Prospective evaluation of a method for estimating ascending aortic pressure from the radial artery pressure waveform

Hypertension

Clinical utility of aortic pulses and pressures calculated from applanated radial-artery pulses

Hypertension

Central pulse pressure and mortality in end-stage renal disease

Hypertension

Increased pulse wave velocity is not associated with elevated augmentation index in patients with diabetes

J Hypertens

Haemodynamic basis for the development of left ventricular failure in systolic hypertension and for its logical therapy

J Hypertens

Arterial wave reflections and survival in end-stage renal failure

Hypertension

Determinants of accelerated progression of arterial stiffness in normotensive subjects and in treated hypertensive subjects over a 6-year period

Circulation

Aortic stiffness is associated with visceral adiposity in older adults enrolled in the study of health, aging, and body composition

Hypertension

Sex differences in age-related stiffening of the aorta in subjects with type 2 diabetes

Hypertension

Review article
Beyond blood pressure: Arterial stiffness as a new biomarker of cardiovascular disease