Aortic-Brachial Stiffness Mismatch and Mortality in Dialysis Population

Abstract

C ardiovascular disease is the leading cause of mortality in patients with chronic kidney disease. 1,2 Aortic stiffness, which results in increased pulse pressure (PP), cardiac overload, and left ventricular hypertrophy, is an established predictor for cardiovascular morbidity and mortality in chronic kidney disease. [3][4][5] Physiologically, the aorta is much more elastic than peripheral muscular arteries providing a physiological stiffness gradient. This physiological gradient of stiffness generates reflecting sites, which dampens the transmission of forward travelling pressure into the microcirculation. In normal aging, aortic stiffness increases to a greater extent than peripheral muscular arteries, resulting in equalization or even reversal of stiffness gradient (aortic stiffness>muscular artery stiffness), referred to as stiffness mismatch. 6-9 Attenuation or reversal of physiological stiffness gradient has been proposed to cause vascular damage through enhanced transmission of forward travelling wave energy into the microcirculation. 9,10In a longitudinal study with repeated measures of aortic and brachial stiffness in hemodialysis patients, we observed an accelerated progression of aortic stiffness and a significant reduction in brachial stiffness. 11 The regression of brachial stiffness was associated to higher degree of aortic stiffness, therefore, leading to an enhanced aortic-brachial stiffness mismatch. In the context of this study, we hypothesized that aortic-brachial stiffness mismatch, as evaluated by the ratio of aortic and brachial pulse wave velocity (PWV) ratio, may prove to be a better prognostic predictor of mortality in dialysis population than aortic PWV. Therefore, the objectives of this study were to examine the nonadjusted and adjusted effect of the PWV ratio on overall mortality and to study its relative predictive value as compared with well-known central and peripheral hemodynamic parameters.Abstract-We hypothesized that increased aortic stiffness (central elastic artery) combined with a decrease in brachial stiffness (peripheral muscular artery) leads to the reversal of the physiological stiffness gradient (ie, mismatch), promoting end-organ damages through increased forward pressure wave transmission into the microcirculation. We, therefore, examined the effect of aortic-brachial stiffness mismatch on mortality in patients in need of dialysis. In a prospective observational study, aortic-brachial arterial stiffness mismatch (pulse wave velocity ratio) was assessed using carotid-femoral pulse wave velocity divided by carotid-radial pulse wave velocity in 310 adult patients on dialysis. After a median follow-up of 29 months, 146 (47%) deaths occurred. The hazard ratio (HR) for mortality related to PWV ratio in a Cox regression analysis was 1.43 (95% confidence interval [CI], 1.24-1.64; P<0.001 per 1 SD) and was still significant after adjustments for confounding factors, such as age, dialysis vintage, sex, cardiovascular disease, diabetes mellitus, smoking status, and weight (HR...

Aortic Aging in ESRD: Structural, Hemodynamic, and Mortality Implications

“…In contrast, brachial (or femoral) ( Table 1) stiffness remains almost stable throughout aging ( Figure 1B, Table 2) and cannot negate for the effect of premature aortic aging on pressure transmission. 2,28, 29 Fortier et al 30 proposed arterial stiffness gradient as an independent index of ESRD survival. In our study, the predictive value of the arterial stiffness gradient depends entirely on aortic PWV changes.…”

“…In our study, the predictive value of the arterial stiffness gradient depends entirely on aortic PWV changes. In the paper by Fortier et al, 30 the stiffness gradient was expressed as aortic PWV/brachial PWV and not in the usual way as (brachial PWV/aortic PWV) 0.5 . 2 The population in the work by Fortier et al 30 was older and included patients with diabetes, and the population was characterized principally by unusually low brachial PWV, which could account for the stiffness gradient as a better predictor.…”

“…In the paper by Fortier et al, 30 the stiffness gradient was expressed as aortic PWV/brachial PWV and not in the usual way as (brachial PWV/aortic PWV) 0.5 . 2 The population in the work by Fortier et al 30 was older and included patients with diabetes, and the population was characterized principally by unusually low brachial PWV, which could account for the stiffness gradient as a better predictor. However, the most important finding to consider in such studies is that, with aging, the aorta undergoes marked structural and geometric changes and becomes stiff and tortuous, with increased length, diameters, and wall thickness.…”

Pulse wave velocity differs between ulcerative colitis and chronic kidney disease

“…During aging, since the stiffness of the central elastic arteries increases to a greater extent than that of peripheral muscular arteries [2], the aortic/brachial stiffness gradient is first equalized (aortic stiffness = brachial artery stiffness), and then even reverted (aortic stiffness N brachial artery stiffness). This process, called aortic-brachial stiffness mismatch [3][4][5], has important hemodynamic and clinical consequences since it reduces the reflection waves, increasing the reflection site distance, causes vascular damage through the enhanced transmission of forward energy waves into the microcirculation [5], contributes to the pathogenesis of white matter lesions of the brain [6] and renal dysfunction [7,8] and, at least in patients with ESRD, is strongly and independently associated with increased mortality [9].inflammatory bowel disease (IBD) [10], we reported that aortic stiffness was increased [11] and that the aortic stiffening was reduced by antitumor necrosis factor (anti-TNF) therapy in young patients with IBD [12]. These findings were confirmed in several studies performed by independent groups, in meta-analyses performed by our group [13][14][15], and in a meta-analysis performed by an independent group that, methodologic issues aside [16], has also reported both increased intima-media thickness and reduced flow-mediated dilation in patients with IBD [17].…”

“…Both CKD and ulcerative colitis (UC) are characterized by an increase of aortic stiffness [1,9,[11][12][13][14][15]17]. However, since the causes and the mechanisms involved in the arterial stiffening seem to be different [10,20], also the arterial phenotype, the hemodynamic and the clinical consequences could be different in UC and CKD.…”