Review articleBeyond blood pressure: Arterial stiffness as a new biomarker of cardiovascular disease
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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Dr. Franklin is on the Speakers Bureau for Boehringer Ingelheim, Bristol-Myers Squibb, and Merck, and a Consultant for AtCor Medical, and Bristol-Myers Squibb.