Central blood pressure: getting to the heart of the matter

For over a century, blood pressure (BP) measurement at the brachial artery level has been the most widespread method used in daily clinical practice to describe the haemodynamic characteristics of the circulatory system due to its wide availability, satisfactory reproducibility and established prognostic value. SBP and DBP values determined at a given site of the arterial tree, however, may not be representative of the BP values at other sites [1]. It is well known that the periodically oscillating pulse wave generated in the arterial tree by left ventricular contraction undergoes a progressive distortion with distance. Generally, mean and diastolic pressures vary little from the aorta to the brachial artery due to the absence of significant resistance at the level of the large conduit arteries, whereas peripheral SBP and pulse pressure (PP) are greater than their corresponding aortic values. The reason for this phenomenon, known as amplification, is two-fold. First, peripheral arteries are usually stiffer than the aorta, thus the forward pressure wave created by ventricular contraction generates a higher PP in peripheral than in central arteries. Second, the arterial pressure waveform is a composite of the forward pressure wave and of a reflected wave, which is formed in the periphery − mainly at branch points or sites of impedance mismatch − and sums with the forward wave, thus generating the final pattern of the pressure pulse wave. As reflection sites are closer to peripheral sites than to central arteries, reflected waves generally merge with forward waves earlier in peripheral than in central arteries. The earlier arrival of the reflected wave superimposes to the forward wave, and further augments the SBP more in the periphery than in the aorta. This phenomenon, known as ‘augmentation’, can be quantified through the augmentation index, defined as the difference between the second and first systolic peaks expressed as a percentage of the PP. The net result of these two phenomena is that the amplitude of the pressure wave is higher in peripheral than in central arteries. Notably, the difference between central and peripheral pressure cannot be predicted on the basis of peripheral BP values alone, but depends on several factors. Amplification is higher in young patients and decreases with the patient's age. It, on the contrary, augments with increasing aortic stiffness, peripheral resistance, magnitude of wave reflection, as well as elevated heart rate values [2]. For instance, isolated systolic hypertension of the young [3] and elderly [4] are characterized by completely different central haemodynamic profiles, despite showing similar peripheral BP values. Central (aortic) pressure may theoretically be a better estimate of the true haemodynamic load imposed on the left ventricle and on coronary and brain circulation as compared with brachial pressure due to its being closer to the brain and the heart, but there is a need for more clinical data confirming the clinical value of central pressure. In the current issue of the Journal of Hypertension, Roman et al. [5] show that central BP might be superior to peripheral BP as a correlate of adverse cardiac remodelling. In a cross-sectional analysis [6] of a large cohort of 2585 Native Americans who were examined in the setting of the population-based Strong Heart Study, central BP was evaluated on the basis of radial–artery pressure waveform and a generalized transfer function, and left ventricular mass and geometry were determined by echocardiography. Left ventricular mass was adjusted according to its allometric relation with height (height2.7) in order to better take into account the effect of obesity [7], and left ventricular geometry was expressed as the ratio between posterior wall thickness and left ventricular radius (relative wall thickness). The two main findings of the study are that SBP is a stronger correlate of left ventricular mass and geometry than PP, and that central SBP and PP values are more tightly related to left ventricular mass and geometry than their corresponding brachial values. Systolic blood pressure versus pulse pressure The results of the study by Roman et al. [5] reinforce the view that SBP rather than PP is the BP component best related to left ventricular remodelling. In a large study carried out in 2545 untreated hypertensive individuals, all of whom had 24-h ambulatory BP monitoring, Verdecchia et al. [8] found that left ventricular mass was positively associated with all BP components (systolic, mean, diastolic and pulse), and all associations were closer with ambulatory BP as compared with office BP. However, in that study [8], 24-h SBP was the strongest independent BP determinant of left ventricular mass, and the association between PP and left ventricular mass was entirely explained by SBP. Similar results had been reported in population-based studies carried out in China [9], the Unites States [10] as well as in Italy, in the Pressioni Arteriose Monitorate E Loro Associazioni study [11]. The ascendancy of SBP over PP as independent determinant of left ventricular mass is plausible under several pathophysiological aspects. The increase in left ventricular mass in essential hypertension is thought to be primarily related to the increase in end-systolic stress [12], which includes SBP in its estimate. In this respect, the reported direct association between increased left ventricular mass and augmented late systolic component of the pressure waveform, resulting from an earlier peripheral reflection wave [13,14], is likely to be mediated by an augmented end-systolic stress. Left ventricular mass, an independent and continuous predictor of cardiovascular events [15], is generally considered as a sort of biological assay, which reflects and integrates over time the overall long-term cumulative effect of several haemodynamic and nonhaemodynamic risk factors for cardiovascular disease [16]. In contrast, PP as a measure of pulsatile vascular load is a more direct indicator of conduit vessel stiffness potentially associated with pathological processes of arterial wall, and indeed was found to be a stronger correlate of carotid atherosclerotic plaque burden and intima–media thickness than SBP [17–19]. Taken together, this [5] and the previous studies lead to the conclusion that SBP is the most robust parameter influencing left ventricular remodelling, whereas PP as a measure of cyclic stress is the strongest correlate of vascular hypertrophy and atherosclerotic burden. Central versus peripheral pressure The recent escalation in the scientific interest for central pressure as a physiologic parameter derives from new important developments in the field, including the availability of noninvasive devices, which are able to accurately estimate aortic pressure, the better understanding of waveforms and of their modifications in physiologic and pathologic conditions, and the publication of several clinical studies documenting its superiority over peripheral pressure as a predictor of cardiovascular damage and complications in the last few years. To date, at least eight longitudinal, event-based studies [19–26] have compared the prognostic ability of central and brachial BP in different clinical and population settings. With few exceptions [21], the above-mentioned studies [19,20,22–26] show that central BP, mainly PP, is a stronger predictor of cardiovascular outcomes than the corresponding brachial value. The current study provides unequivocal evidence in a large, population-based sample that central (aortic) BP is superior to peripheral BP in relating to left ventricular mass and concentric geometry. Results were obtained with the SphygmoCor device (AtCorMedical, West Ryde, New South Wales, Australia), the most widely used and most extensively validated device for the noninvasive measurement of central pressure. Given the independent prognostic significance of left ventricular mass [15], these data suggest central pressure as a potentially superior marker of cardiovascular risk than brachial BP. Study limitations Although of elevated scientific and technical quality, the study by Roman et al. [5] is not exempted from some limitations. First, the effect of age on the different impact of central and peripheral pressures on cardiac remodelling was not completely ruled out by the authors. It is well known that central SBP and PP increase with age more than the corresponding brachial values, as witnessed by the age-related decrease in PP amplification. Not unexpectedly, in the paper by Roman et al. [5], correction for age substantially reduced the relation between central SBP and left ventricular relative wall thickness (standardized regression coefficients decreased from 0.272 unadjusted to 0.127 adjusted, P < 0.001). The authors do not clarify whether, after adjustment for age, the regression coefficient of left ventricular relative wall thickness on central SBP was significantly different from that with brachial SBP. Second, the results were obtained in a population of Native Americans with a high prevalence of diabetes (20%) and obesity (average BMI 31.6 kg/m2) and cannot be extrapolated to other populations, although similar findings have been reported in a recent Chinese study [26]. Third, calibration of the radial–artery waveform was obtained with brachial SBP and DBP determined immediately before the procedure by sphygmomanometry, assuming that these values approximate radial SBP and DBP. This can introduce a systematic error in peripheral BP measurement, however, due to the fact that SBP and PP increase ongoing from the brachial to the radial artery (brachial–radial amplification). Calibration with brachial mean and diastolic pressure, which is also allowed with the SphygmoCor system (AtCorMedical), could minimize this bias. Other recently marketed devices such as the Arteriograph (TensioMed Ltd., Budapest, Hungary) and the Mobil-O-Graph (I.E.M. GmbH, Stolberg, Germany), which derive central pressure from brachial pressure waveform, may overcome the problem of brachial-to-radial amplification. Fourth, the SphygmoCor system (AtCorMedical) relies on a generalized transfer function, which has been developed to derive the aortic pressure waveform from the radial artery waveform [6]. A transfer function encodes the alterations introduced by a system (the arterial tree) on the original signal (the radial waveform), which generates the output (the aortic waveform), and assumes that the properties of the upper limb arteries are virtually identical between individuals. Most of the validation studies to date have been carried out in men undergoing diagnostic cardiac catheterization, and the accuracy of the transfer function in women [27], in individuals without coronary disease [28] and after exercise [29] has been questioned. In summary, evidence is accumulating that brachial pressure is not an accurate estimate of the central (aortic) BP load, and that central BP may be a stronger determinant of cardiovascular damage and complications in various clinical settings. Despite the great theoretical and clinical progress in the last few years, however, a number of research priorities remain before establishing central pressure as a new cardiovascular risk factor. Large-scale studies are required to determine normal values of central BP, and to assess whether reduction of central BP independently reduces cardiovascular risk over and above the effects on peripheral BP. In parallel, technical advancements are urgently needed to provide new accurate, reproducible, operator-independent, timesaving and easy-to-use devices for measuring central BP.