aDivision of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland
bRenal Electrolyte and Hypertension Division, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA
Correspondence to Matthew R. Weir, MD, Professor of Medicine, Head, Nephrology, 22 South Greene St, N3W143, University of Maryland Medical Center, Baltimore, MD 21201, USA. Tel: +1 410 328 5720; fax: +1 410 328 5685; e-mail: Mweir@medicine.umaryland.edu
Interest in the nature and velocity of pulse wave travel in the human circulation witnessed an innovative mix of technology and mathematics in the nineteenth and early twentieth centuries. A number of ingenious devices in the mid to late nineteenth century, in particular, were able to reveal graphically (often by a stylus-based indentation on a wax media) the complex nature of the pulse, typically obtained from the radial artery . In the mid-1920s, the first measurements of human pulse wave velocity appeared, with values remarkably similar to those recorded in the past 20 years as noninvasive technologies to measure velocity have become available . The usual unit in which pulse wave velocity is reported is in meters/second. Normal values for carotid-to-femoral pulse wave velocity in adults tend to rise 0.5–1 m/s with each decade . A healthy 45-year-old man or woman, for example, would be expected to have a carotid–femoral pulse wave velocity of 7 m/s. Pulse wave velocity values tend to be higher in diabetic patients, and tend to rise more quickly with age when hypertension is present. European investigators recommend using carotid–femoral values as these are more representative of the aortic values. Nonetheless, a large body of literature also exists on the role of brachial-to-ankle pulse wave velocity, a method commonly used in Asian cohorts . Because this method includes muscular as well as elastic arteries, the values are typically higher in patients than they would be if only the carotid–femoral beds were included . In addition, cuff-based oscillometric determination of pulse wave velocity is an emerging area .
In 2010, the first meta-analysis of the effects of pulse wave velocity on cardiovascular outcomes and death appeared . This analysis included 17 longitudinal studies, and almost 16 000 patients. Four of the cohorts studied were small end-stage renal disease populations; none of the cohorts were specifically chronic kidney disease (CKD) patients, not already on dialysis. The main message of the analysis was that carotid–femoral pulse wave velocity was an independent predictor of cardiovascular disease and death in a variety of populations. For death, in particular, each 1 m/s increase in carotid–femoral pulse wave velocity was associated with at least 15% increase in mortality (all-cause and cardiovascular mortality). An updated patient-level meta-analysis has recently appeared further supporting the independent predictive value of carotid–femoral pulse wave velocity .
The technology for measuring pulse wave velocity using oscillometric methodology has been successfully merged with 24-h blood pressure data collection in devices such as the Mobil-O-Graph . Importantly, validation of the pulse wave velocity data from this device has been confirmed in recent studies . In this issue of the Journal, Baumann et al. report the predictive value of pulse wave velocity determined from the oscillometric brachial method (Mobil-O-Graph) in patients with CKD stages 2–4. Using a value of 10 m/s as their median, they observed that death was substantially more common in those above, compared with those below, this value. The statistical significance of their findings remained robust when they factored age and diabetes into their analyses. The choice of 10 m/s is supported further by the recommendations of the European Society of Cardiology as a reasonable cut-off point for identifying those with clinically significant arterial stiffness.
What explains the relationship of arterial stiffness to death? Although it has not been the specific intent of studies, to date, to determine mechanisms of stiffness-related mortality, the accumulation of evidence points to several possibilities. First, stiffness generally does not develop in a vacuum. People with stiffer arteries tend to be older, hypertensive, diabetic, and perhaps have other exposures as well. The independence of stiffness as a predictor suggests that even within these populations just mentioned, there is a subset that appears well adapted (lower pulse wave velocity) and a group that has clearly higher stiffness and greater consequences. Secondly, it may be that more drug therapy is employed in those with greater stiffness, in which case the resistant blood pressure becomes a marker of the ineffectiveness of drugs to reduce blood pressure (which is a loading factor for pulse wave velocity). This exposes patients to electrolyte imbalances through more aggressive diuretic use and, in particular, hypokalemia. Alternatively, hyperkalemia is also a potential problem with the use of mineralocorticoid antagonists that are often employed in these patients. Third, greater stiffness contributes to greater left-ventricular afterload. This in turn could predispose the myocardium to thickening and the formation of fibrosis, and both of these processes carry risk of coronary heart disease and heart failure-related mortality. Finally, it may also be the case that greater degree of arterial stiffness, which has some hereditary aspects to it , identifies a group of people at endogenously higher risk for death by virtue of genes that travel with the stiffer phenotype.
To conclude, studies like those of Baumann et al. continue to support the value of arterial stiffness as a predictor of death and extend this finding to a nondialysis CKD population. That arterial stiffness did not predict CKD progression may be the consequence in their study of a modest sample size, and the disturbing recent recognition that patients with CKD frequently progress to worse kidney function, or surprisingly stabilize their kidney function in a nonlinear manner, defying conventional statistical attempts to model this outcome .
Conflicts of interest
There are no conflicts of interest.
1. O’Rourke MF. O’Rourke, Kelly, Avolio. History. The arterial pulse
. Philadelphia and London:Lea & Febiger; 1992. 3–14.
2. Bramwell JC, Hill A. Velocity of transmission of the pulse wave and elasticity of arteries. Lancet
3. Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors: establishing normal and reference, values. Eur Heart J
4. Safar ME, O’Rourke MF. The brachial-ankle pulse wave velocity. J Hypertens
5. Tanaka H, Munakata M, Kawano Y, Ohishi M, Shoji T, Sugawara J, et al. Comparison between carotid-femoral and brachial-ankle pulse wave velocity as measures of arterial stiffness. J Hypertens
6. Papaioannou TG, Argyris A, Protogerou AD, Vrachatis D, Nasothimiou EG, Sfikakis PP, et al. Noninvasive 24 h ambulatory monitoring of aortic wave reflection and arterial stiffness by a novel oscillometric device: the first feasibility and reproducibility study. Int J Cardiol
7. Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol
8. Ben-Shlomo Y, Spears M, Boustred C, May M, Anderson SG, Benjamin EJ, et al. Aortic pulse wave velocity improves cardiovascular event prediction: an individual participant meta-analysis of prospective observational data from 17,635 subjects. J Am Coll Cardiol
2013; S0735–1097(13) 0597–3 (Epub ahead of print).
9. Baumann M, Wassertheurer S, Suttmann Y, Burkhardt K, Heemann U. Aortic pulse wave velocity predicts mortality in chronic kidney disease stages 2–4. J Hypertens
10. Laurent S, Boutouyrie P, Lacolley P. Structural and genetic bases of arterial stiffness. Hypertension
11. Li L, Astor BC, Lewis J, Hu B, Appel LJ, Lipkowitz MS, et al. Longitudinal progression trajectory of GFR among patients with CKD. Am J Kidney Dis