Lower-Limb Pulse Wave Velocity: Correlations and Clinical Value

COMMENTARY

Lower-limb pulse wave velocity: correlations and clinical value

Giuseppe Schillaci and Giacomo Pucci

Hypertension Research (2013) 36, 679–681; doi:10.1038/hr.2013.47; published online 9 May 2013

lthough the objective recording of between central and peripheral arteries. The central arteries such as the aorta; therefore, Aarterial pulse as a tool for estimating clinical significance of PWV in muscular lower-limb PWV is a less reliable marker of vascular stiffness was developed about 150 arterial segments, including the lower limbs, arterial aging than is carotid-femoral years ago, many years before the measure- has been less studied so far. PWV.12–15 The divergent effects of aging on ment of arterial pressure became possible,1 In the present issue of Hypertension the peripheral and central arteries might clinical and scientific interest in sphygmo- Research, Wohlfahrt et al.10 further report be related to the different structural graphy tapered off by the end of the on the stiffness of muscular arteries and its characteristics of these arteries. Peripheral nineteenth century and remained negligible correlates by examining the predictors of arteries such as the brachial, femoral and throughout most of the twentieth century. carotid-femoral and lower-limb PWV. tibial arteries are classified as muscular The reasons for this declining fortune were Compared with a previous study by the arteries and are composed mainly of clearly recognized in 1931 by Paul Dudley same group,11 this paper examines a larger smooth muscle cells with small amounts of White, who wrote in his classic cardiology and more heterogeneous population of 911 extracellular matrix. Central arteries such as textbook that ‘the difficult and bothersome individuals from the Czech post-MONICA the aorta and carotid and subclavian arteries technique and the obscurity concerning study, a cross-sectional survey at the general are examples of elastic arteries, which are interpretation in the minds of most population level. In both cases, PWV was composed of smooth muscle cells with larger physicians prevented a wide adoption of the evaluated by using an electrocardiogram- amounts of elastin, collagen and other method’.2 The situation has changed gated tonometric approach. Lower-limb extracellular matrix proteins forming substantially in the last few decades, when a PWV was found to be higher than carotid- multiple layers of elastic lamellae.16 Thus, renewed and growing interest into vascular femoral PWV especially at younger ages, and elastin depletion and collagen deposition stiffness has been mainly driven by the the PWV gradient between the aorta and with advancing age are more prominent in availability of devices able to measure lower-limb territories was progressively elastic arteries and explain the greater age- noninvasively pulse wave velocity (PWV), a reduced by aging. Moreover, whereas dependent stiffness increase in central direct measure of arterial stiffness. femoral-ankle PWV was higher in men, the arteries. PWV is a simple and direct way to assess effects of age on lower-limb PWV were The paper by Wohlfahrt et al.10 also the stiffness of a given arterial segment, weaker and significantly less pronounced in confirms that lower-limb PWV has no provided that the arterial path is included men than in women. The impact of strong relationship with major cardio- between two palpable pulses, and path length traditional cardiovascular risk factors on vascular risk factors. Diabetes mellitus has and transit time are both measurable. To PWV was also investigated. Whereas been associated with preferential stiffening of date, most of the published data on the diabetes, hypertension, dyslipidemia, waist the large elastic arteries, and an independent clinical and prognostic significance of arterial circumference and chronic kidney disease influence of diabetes has been reported on stiffness have been based on carotid-femoral had an independent relationship with carotid-femoral, but not on lower-limb PWV,3–6 which is basically a measure of the carotid-femoral PWV, high blood pressure PWV.17,18 More importantly, at variance stiffness of aorta, an elastic artery. Some was the only cardiovascular risk factor to be with the carotid-femoral PWV, the PWV of studies have also shown the adverse independently related to lower-limb PWV. muscular arterial segments has not been prognostic significance of brachial-ankle Finally, ankle systolic blood pressure was shown to predict adverse cardiovascular PWV,7–9 although this parameter is a more closely related to carotid-femoral prognosis or to correlate with the global combination of both elastic and muscular PWV than to femoral-ankle PWV, and the atherosclerotic burden.19,20 arterial segments and does not differentiate latter was lower in subjects with a low ankle- What are the clinical implications brachial blood pressure index (ABI) than in of an elevated lower-limb arterial PWV? A those with a normal ABI. reduced glomerular filtration rate has been G Schillaci and G Pucci are at Unit of Internal Medicine, It is generally accepted that stiffening of accompanied by a parallel increase in both Department of Medicine, University of Perugia, Terni University Hospital, Terni, Italy the peripheral arteries is less of an age- elastic (aortic) and muscular (upper limb) E-mail: [email protected] dependent process than stiffening of the arterial stiffness, probably as a result of Commentary 680

common inflammatory mechanisms, as well former includes intima-media thickening significant relationship between peripheral as the development of arterial calcifications and the formation of the atherosclerotic circulation and symptoms of arterial and sodium-related alterations in extracellu- plaque, whereas the latter is characterized insufficiency, and an indirect measure of lar matrix composition.21 However, the renal by the progressive degeneration and calcifica- local artery stiffness, namely b-index.29,31 resistive index, a widely accepted ultrasono- tion of the arterial media. A low ABI is the More recently, Hashimoto et al.33 have graphic marker of renal microvascular result of the presence of an atherosclerotic analyzed the relationship of lower-limb damage, was independently correlated with plaque with a consequent downstream blood blood flow evaluated by Doppler ultrasound aortic-, but not femoral-dorsalis pedis, PWV. pressure fall, whereas a high ABI is generally profile with carotid-femoral and lower-limb This finding suggests that aortic stiffness may assumed to reflect arterial incompressibility PWV, evaluated by applanation tonometry in cause renal microvascular damage possibly due to extended calcification that generates 138 hypertensive patients without peripheral through increased central pulse pressure, artifactually higher values of ankle blood arterial disease. They found that, which in turn may be transmitted toward pressure. Thus, the low values of lower-limb independently of distending blood pressure, and across glomeruli, and initiate glomeru- PWV observed by Wohlfahrt et al.10 in augmented pressure and other determinants, losclerosis and/or tubulointerstitial damage.22 individuals with peripheral artery disease increased carotid-femoral PWV was Similar to aortic PWV, lower-limb PWV may and a low ABI are likely to be ‘falsely’ low associated with a decreased reverse femoral be reduced by treatments for major cardio- values, attributable to the stenosis reducing flow, a decreased diastolic forward flow and a vascular risk factors, such as statins23–25 and blood flow and distending pressure disappearance of diastolic forward flow. By blood pressure-lowering drugs.26 downstream. The absence of an association contrast, lower-limb PWV was not related to Muscular-artery PWV also shows signifi- between high ABI and high lower-limb PWV any of the above findings but showed an cant gender-related differences. The physio- when brachial mean arterial pressure is independent inverse relationship with the logical determinants of femoral PWV were accounted for as a confounding factor acceleration time of forward systolic flow.33 evaluated by Vermeersch et al.27 in a large confirms the evidence that PWV in a given Therefore, for a given blood pressure, an healthy population by means of the arterial segment is a function of invasive increased femoral stiffness generates a reduc- Bramwell–Hill formula. They found that distending pressure, which in turn may not tion in the time to the peak of incident flow PWV in the femoral artery is higher in necessarily be mirrored by externally wave and an early transition from accelera- men, whereas characteristic impedance (Zc), measured pressure. tion to deceleration, whereas increased aortic a measure related directly to PWV and Another important aspect derived from stiffness leads to decreased accumulation of inversely to arterial cross-sectional area, is the combined evaluation of carotid-femoral reverse flow caused by a reduction in the higher in women. In both genders, aging was PWV and femoral-ankle PWV is the critical aortic ‘windkessel effect’, which translates accompanied by a decrease in local Zc, role of arterial stiffness as a determinant of into a decreased diastolic lower-limb blood despite unchanged values of PWV. These lower-limb perfusion. Increased stiffness of flow. It is noteworthy that modifications of findings indicate that both body size and the arteries of the lower limbs has indeed flow waveform profile, such as the decrease stroke volume may be important deter- been associated with impaired arterial blood in the flow pulsatility index, have been minants of arterial stiffness, and their effects flow,28 subclinical hypoxia of the foot29,30 proposed as a contributing factor in the on PWV are higher in the peripheral and ischemic symptoms of the lower development of arteriosclerosis.34 muscular arteries than that in the aorta. extremities.31 Physiologically, the resistance Overall, carotid-femoral and lower-limb These and other differences are important to flow in a given arterial segment is generally PWV may interfere with lower-limb perfu- to keep in mind when investigating PWV in composed of two elements: a constitutive sion through different pathways, and their different arterial territories. component, which is related to the combined evaluation might be of clinical In the study by Wohlfahrt et al.,10 a small vasoconstrictor tone of arterioles, and a utility. Direct measurement of the two para- proportion of the examined population (6%) phasic component, the above mentioned Zc, meters is quick, simple and reproducible. A was affected by peripheral arterial disease, which determines the relationship between thorough assessment of the factors that affect manifested as a low or high ABI. In both pulsatile pressure and pulsatile flow in the lower-limb PWV, including blood pressure cases, independently of age and brachial arterial segment.32 Although it is well values and an abnormal ABI, is necessary to blood pressure, carotid-femoral PWV was established that peripheral resistance is fully appreciate the physiological and prac- higher than in people with a normal ABI. inversely related to blood flow in the lower tical value of lower-limb PWV in different By contrast, lower-limb PWV was lower in limbs, less data are available on the research and clinical settings. subjects with a reduced ABI and was not relationship between arterial stiffness and significantly different in people with a blood flow. Suzuki et al.28 investigated the CONFLICT OF INTEREST normal ABI and those with a high ABI. relationship between lower-limb PWV and The authors declare no conflict of interest. Interestingly, for any given level of brachial popliteal flow in diabetic patients without blood pressure, carotid-femoral PWV was peripheral arterial disease. They found that independently related to high values of patients in the highest tertile of lower-limb ankle blood pressure, whereas this PWV had decreased total popliteal inflow 1 Moss SW. The sphygmograph in America: writing the pulse. Am J Cardiol 2006; 97: 580–587. relationship was not found for lower-limb volumes compared with subjects in the lower 2 White PD. Heart Disease. Macmillan, New York, 1931: PWV. Thus, lower-limb PWV had less power tertile, particularly for the lower late diastolic 192–205. 3 Blacher J, Guerin AP, Pannier B, Marchais SJ, Safar to predict lower-limb arterial disease than did component. However, their method for ME, London GM. Impact of aortic stiffness on survival carotid-femoral PWV. lower-limb PWV was indirectly derived in end-stage renal disease. Circulation 1999; 99: In contrast to the upper limbs, lower-limb from brachial-ankle transit time and was 2434–2439. 4 Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B, arteries are highly prone to developing both somewhat questionable as a real measure of Guize L, Ducimetiere P, Benetos A. Aortic stiffness is atherosclerosis and arteriosclerosis. The lower-limb PWV. Other authors found a an independent predictor of all cause and

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