Ankle-brachial index and bone turnover in patients on dialysis.

An association between atherosclerosis and osteoporosis has been reported in several studies. This association could result from local intraosseous atherosclerosis and ischemia, which is shown by limb osteoporosis in patients with peripheral artery disease (PAD), but also could result from bidirectional communication between the skeleton and blood vessels. Systemic bone disorders and PAD are frequent in ESRD. Here, we investigated the possible interaction of these disorders. For 65 prevalent nondiabetic patients on hemodialysis, we measured ankle-brachial pressure index (ABix) and evaluated mineral and bone disorders with bone histomorphometry. In prevalent patients on hemodialysis, PAD (ABix<0.9 or >1.4/incompressible) was associated with low bone turnover and pronounced osteoblast resistance to parathyroid hormone (PTH), which is indicated by decreased double-labeled surface and osteoblast surface (P<0.001). Higher osteoblast resistance to PTH in patients with PAD was characterized by weaker correlation coefficients (slopes) between serum PTH and double-labeled surface (P=0.02) or osteoblast surface (P=0.03). The correlations between osteoclast number or eroded surface and serum mineral parameters, including PTH, did not differ for subjects with normal ABix and PAD. Common vascular risk factors (dyslipidemia, smoking, and sex) were similar for normal, low, and incompressible ABix. Patients with PAD were older and had high C-reactive protein levels and longer hemodialysis vintage. These results indicate that, in prevalent nondiabetic patients with ESRD, PAD associates with low bone turnover and pronounced osteoblast resistance to PTH.

Vascular calcifications, arterial aging and arterial remodeling in ESRD.

BACKGROUND: Accelerated arterial aging and inadequate outward arterial remodeling are observed in end-stage renal disease (ESRD) patients. Whether these changes could be closely associated with arterial calcifications has never been investigated. METHODS: 155 ESRD patients and 105 age-, sex-, and blood pressure-matched control subjects were included. Common carotid artery (CCA) pressure, diameter, intima-media thickness, elastic modulus, and presence of calcified plaques were measured ultrasonographically. Carotid artery stiffness was determined from simultaneously recorded CCA diameter and stroke changes in diameter and CCA pressure waveforms, obtained by applanation tonometry. RESULTS: Compared with control subjects, ESRD patients had increased CCA systolic and pulse pressures (p < 0.001), larger CCA diameter (p < 0.001) and CCA intima-media thickness (p < 0.01) and similar CCA relative wall thickness. In ESRD patients the arterial remodeling was associated with increased CCA elastic modulus/stiffness (p < 0.001). In ESRD patients the association between CCA elastic modulus and age was characterized by a steeper slope (p = 0.03), but after separation of uremic patients according to the presence of calcifications, the accelerated aging was observed only in calcified subjects. Despite higher CCA systolic and pulse pressures, the CCA relative wall thickness was similar to controls indicating an inadequate pressure-associated remodeling. Moreover, the positive systolic pressure/relative thickness correlation observed in control subjects was lost with paradoxical negative correlation in calcified ESRD patients (p = 0.03). CONCLUSION: These results indicate that, in ESRD patients, accelerated arterial aging and inadequate arterial hypertrophy are closely associated with the calcifications of arterial walls. Inadequate hypertrophy is responsible for high circumferential stress applied on the vessels.

Assessment and significance of arterial stiffness in patients with chronic kidney disease.

PURPOSE OF REVIEW: To review the most recent publications concerning the pathophysiology and clinical impact of arterial stiffening in patients with chronic kidney disease and those with end-stage renal disease. RECENT FINDINGS: The results of recent studies confirmed that arterial stiffening is independently associated with decreased glomerular filtration rate and increased decline in parallel kidney function, and is predictive of kidney disease progression and the patient's cardiovascular outcome. Arterial stiffening is of multifactorial origin, including arterial calcifications, systemic inflammation, malnutrition, vitamin deficiencies, endothelial dysfunction, and bone activity. SUMMARY: Arterial stiffness and intensity of wave reflections are considered the principal determinants of systolic blood and pulse pressures, and their measurements are increasingly used to assess cardiovascular risk. Aortic stiffness has independent predictive value for all-cause and cardiovascular mortality in general populations and in patients with end-stage renal disease. Arterial stiffening in patients with chronic kidney disease and those with end-stage renal disease is of multifactorial origin with extensive arterial calcifications representing a major covariate. Carotid-femoral pulse wave velocity is a direct measure of aortic stiffness and is the 'gold standard' for its evaluation in clinical and epidemiological studies.

Arterial structure and function in end-stage renal disease.

Cardiovascular disease is a major cause of morbidity and mortality in patients with end-stage renal disease (ESRD). Macrovascular disease develops rapidly in ESRD patients and is responsible for the high incidence of left ventricular hypertrophy, ischemic heart disease, cerebrovascular accidents, and peripheral artery diseases. Occlusive lesions due to atheromatous plaques frequently cause these complications; however, atherosclerosis represents only one form of structural response to metabolic and hemodynamic alterations interfering with the "natural" process of aging. The spectrum of arterial alterations in ESRD is broader, including large artery remodeling, changes in viscoelastic properties, and stiffening of arterial walls. Nonatheromatous remodeling principally changes the dampening function of arteries, characterized by stiffening of arterial walls and with deleterious effects on the left ventricle and coronary perfusion. The origin of arterial stiffening in ESRD patients is multifactorial, with extensive arterial calcifications as an important covariate.

Association of bone activity, calcium load, aortic stiffness, and calcifications in ESRD.

An inverse relationship between arterial calcifications and bone activity has been documented in patients with ESRD. Calcium overload is associated with arterial calcification, which is associated with arterial stiffening. Whether bone activity interacts with calcium load, aortic stiffness, or arterial calcification is unknown. This study assessed the impact of bone activity on the relationships between the dosage of calcium-containing phosphate binders and aortic stiffness (measured by pulse wave velocity) or abdominal aorta calcification score. Aortic stiffness and calcification were both positively associated with calcium load and negatively associated with bone activity. A significant interaction was found between dosage of calcium-containing phosphate binders and bone activity such that calcium load had a significantly greater influence on aortic calcifications and stiffening in the presence of adynamic bone disease. Independent of any other factor, including dosage of calcium-containing phosphate binders, adynamic bone was associated with greater aortic stiffening, suggesting cross-talk between the bone and arterial walls.

Mineral metabolism and arterial functions in end-stage renal disease: potential role of 25-hydroxyvitamin D deficiency.

In ESRD, arterial function is abnormal, characterized by decreased capacitive function (arterial stiffening) and reduced conduit function, shown by diminished flow-mediated dilation (FMD). The pathophysiology of these abnormalities is not clear, and this cross-sectional study analyzed possible relationships among arterial alterations and cardiovascular risk factors, including mineral metabolism parameters, such as serum parathormone, and vitamin D "nutritional" and "hormonal" status by measuring serum 25-hydroxyvitamin D [25(OH)D(3)] and 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] levels. Aortic stiffness (pulse wave velocity), brachial artery (BA) distensibility (echotracking; n = 42), BA FMD (hand-warming; n = 37), and arterial calcification scores (echography and plain x-rays) were measured in 52 stable and uncomplicated patients who were on hemodialysis. 25(OH)D(3) and 1,25(OH)(2)D(3) serum levels were low and weakly correlated (r = 0.365, P < 0.05). After adjustment for BP and age, multivariate analyses indicated that 25(OH)D(3) and 1,25(OH)(2)D(3) were negatively correlated with aortic pulse wave velocity (P < 0.001) and positively correlated with BA distensibility (P < 0.01) and FMD (P < 0.001). Arterial calcification scores were not independently associated with 25(OH)D(3) and 1,25(OH)(2)D(3) serum concentrations. These results suggest that nutritional vitamin D deficiency and low 1,25(OH)(2)D(3) could be associated with arteriosclerosis and endothelial dysfunction in patients who have ESRD and are on hemodialysis.

Cardiovascular disease in the dialysis population: prognostic significance of arterial disorders.

PURPOSE OF REVIEW: Cardiovascular disease is a major factor in the high mortality of patients with end-stage renal disease, and this population is particularly appropriate to analyse the impact of cardiovascular risk markers on outcome. RECENT FINDINGS: Cardiovascular risk markers in end-stage renal disease include age, left ventricular mass, carotid intima-media thickness, blood pressure and aortic stiffness (pulse wave velocity). Aortic pulse wave velocity has been shown to be an independent predictor of cardiovascular mortality in patients with end-stage renal disease and the general population. Aortic pulse wave velocity has the highest sensitivity and specificity as a predictor of cardiovascular death in end-stage renal disease patients. Pulse wave velocity is an integrated index of vascular function and structure, and is a major determinant of systolic hypertension, thereby increasing left ventricular afterload, left ventricular hypertrophy and left ventricular oxygen consumption. Decreased diastolic blood pressure, another consequence of arterial stiffening, is associated with decreased coronary perfusion contributing to ischaemic heart disease and evolution of adaptive into maladaptive left ventricular hypertrophy. SUMMARY: Aortic stiffness measurements could serve as an important tool in identifying end-stage renal disease patients at higher risk of cardiovascular disease. The ability to identify these patients would lead to better risk stratification and earlier and more cost-effective preventive therapy.

Arteriosclerosis, vascular calcifications and cardiovascular disease in uremia.

PURPOSE OF REVIEW: Arterial calcification in chronic kidney disease (CKD) is associated with increased cardiovascular risk. The mechanisms responsible for arterial calcification include alterations of mineral metabolism and expression of mineral-regulating proteins. RECENT FINDINGS: Arterial calcification is similar to bone formation, involving differentiation of vascular smooth muscle cells (VSMCs) into phenotypically distinct osteoblast-like cells. Elevated phosphate and/or calcium trigger a concentration-dependent increase of calcium precipitates in VSMC in vitro. The calcification is initiated by VSMC release of membrane-bound matrix vesicles and formation of apoptotic bodies. The presence of serum prevents these changes, indicating the presence of calcification inhibitors. Arterial calcification occurs in two sites: the tunica intima and tunica media. Intimal calcification is a marker of atherosclerotic disease and is associated with arterial stenotic lesions. Medial calcification influences outcome by promoting arterial stiffening whose principal consequences are left-ventricular hypertrophy and altered coronary perfusion. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in CKD patients. Age, duration of dialysis, smoking and diabetes are risk factors for the development of arterial calcification in end-stage renal disease. Oversuppression of parathyroid hormone and low bone turnover potentiate the development of arterial calcification. SUMMARY: Arterial disease in CKD patients is characterized by extensive calcification. Evidence has accumulated pointing to the active and regulated nature of the calcification process. Elevated phosphate and calcium may stimulate sodium-dependent phosphate cotransport involving osteoblast-like changes in cellular gene expression. Arterial calcification is responsible for stiffening of the arteries with increased left-ventricular afterload and abnormal coronary perfusion as the principal clinical consequences.

Stiffness of capacitive and conduit arteries: prognostic significance for end-stage renal disease patients.

The aorta is the principal capacitive element of the arterial tree and its increased stiffness, determined by measurement of aortic pulse wave velocity (PWV), is a strong independent predictor of cardiovascular mortality in the general population and end-stage renal disease (ESRD) patients. Whether stiffness of ESRD patients' peripheral arteries has the same prognostic value has never been investigated. A cohort of 305 ESRD patients was followed for 70+/-49 months (mean+/-SD). Ninety-six deaths of cardiovascular origin occurred. At entry into the study, together with standard clinical and biochemical analyses, patients' aortic, brachial artery, and femorotibial PWV were determined. Based on Kaplan-Meier survival curve analyses and Cox proportional hazards analyses, adjusted for age, pulse pressure, and clinical data, aortic PWV was a significant and independent predictor of outcome. Neither brachial artery nor femotibial artery stiffness was able to predict cardiovascular outcome. Receiver operating characteristic curve analysis of aortic PWV indicated the cutoff value of 10.75 m/s, with 84% sensitivity, 73% specificity, 87% negative predictive value, and 72% positive predictive value. These results provide evidence that, in ESRD, increased stiffness of capacitive arteries, like the aorta, is an independent strong predictor of cardiovascular mortality, whereas stiffness of peripheral conduit arteries had no prognostic value.

Arterial calcifications and bone histomorphometry in end-stage renal disease.

Arterial calcification (AC) is a common complication of end-stage renal disease (ESRD). The mechanisms responsible are complex, including disturbances of mineral metabolism and active expression of various mineral-regulating proteins. An inverse relationship between AC and bone density has been documented in uremic patients. In the study presented here, which included 58 patients with ESRD on hemodialysis (HD), bone-histomorphometry characteristics were compared with the AC scores (0 to 4) determined according to the number of arterial sites with calcifications. Patients with AC scores of 0 (no calcifications), or 1 or 2 (mild calcifications) had similar serum parathyroid hormone levels and bone histomorphometry, with larger osteoclast resorption, higher osteoclast numbers, and larger osteoblastic and double tertracycline-labeled surfaces. In contrast, patients with high AC scores (3 and 4) were characterized by lower serum parathyroid hormone, low osteoclast numbers and osteoblastic surfaces, smaller or absent double tetracycline-labeled surfaces, and high percentages of aluminum-stained surfaces. According to multivariate analysis, AC score was positively associated with age (P < 0.0001), daily dose of calcium-containing phosphate binders (P = 0.009), and bone aluminum-stained surfaces (P = 0.037), and an inverse correlation was observed with osteoblastic surfaces (P = 0.001). A high AC score is associated with bone histomorphometry suggestive of low bone activity and adynamic bone disease. These findings suggest that therapeutic interventions associated with excessive lowering of parathyroid activity (parathyroidectomy, excessive calcium or aluminum load) favor lower bone turnover and adynamic bone disease, which could influence the development and progression of AC.

Arterial stiffness and function in end-stage renal disease.

Cardiovascular disease is a major cause of mortality in patients with end-stage renal disease, with damage to arteries as a major contributing factor. Arterial stiffness is a factor associated with high systolic and pulse pressure in these patients and is a strong independent factor associated with morbidity and mortality. Arterial stiffness is one of the principal factors opposing left ventricular ejection. The appropriate term to define the arterial factor(s) opposing left ventricular ejection is aortic input impedance. Aortic input impedance depends on TPR, arterial distensibility, and wave reflections. Distensibility defines the capacitive properties of arterial stiffness, whose role it is to dampen pressure and flow oscillations and to transform pulsatile flow and pressure in arteries into a steady flow and pressure in peripheral tissues. Stiffness is the reciprocal value of distensibility. These parameters are blood pressure dependent; arteries become stiffer at high pressure. While distensibility provides information about the elasticity of the artery as a hollow structure, the elastic incremental modulus characterizes the properties of the arterial wall biomaterials independent of vessel geometry. Alternatively, arterial distensibility can be evaluated by measuring pulse wave velocity, which increases with the stiffening of arteries. Arterial stiffening increases left ventricular afterload and alters the coronary perfusion. With increased pulse wave velocity, the wave reflections affects the aorta during systole, which increases systolic pressures and myocardial oxygen consumption and decreases diastolic blood pressure and coronary flow. The arterial stiffness is altered primarily in association with increased collagen content and alterations of extracellular matrix and calcification of the arterial wall. The arterial stiffening estimated by changes in aortic pulse wave velocity and intensity of wave reflections are independent predictors of survival in end-stage renal disease and in the general population. Improvement of arterial stiffening could be obtained by antihypertensive treatments as observed with calcium-channel blockers and angiotensin-converting enzyme inhibitors. Angiotensin-converting enzymes inhibitors increase AC and reduce wave reflections. It has been shown that reversibility of aortic stiffening and use of angiotensin-converting enzyme inhibitors had a favorable independent effect on survival in hypertensive patients with advanced renal disease.

Forearm reactive hyperemia and mortality in end-stage renal disease.

BACKGROUND: Reports on the general population indicated that decreased endothelial-mediated vasodilation has a prognostic impact on cardiovascular (CV) morbidity and mortality. Flow-dependent vasodilation of conduit arteries and ischemia-induced forearm reactive hyperemia are impaired in end-stage renal disease (ESRD). Whether deterioration of vasodilator function in ESRD patients has a prognostic impact has not been documented. The aim of this study was to determine whether the impaired forearm postischemic vasodilation is an independent predictor of mortality in ESRD patients, independently from CV end-organ damages, which are usually associated with decreased vasodilatory response. METHODS: Common carotid artery intima-media thickness (CCA-IMT), aortic stiffness (pulse wave velocity-PWV), and LV mass (LVM) were determined for 78 stable ESRD patients on hemodialysis. Forearm postischemic vasodilation [flow debt repayment (FDR)] was measured by venous plethysmography. All-cause mortality served as the outcome variable over a median follow-up of 60 +/- 27 months. RESULTS: Twenty-four deaths occurred (16 of CV origin). According to Cox regression adjusted for age, CCA-IMT, LVM, and PWV, all-cause mortality was independently associated with decreased FDR (RR 0.69 for every 10% increase; 95% CI 0.56-0.85; P= 0.0006) and increased aortic PWV (RR 1.16 for 1 m/s increase; 95% CI 1.04-1.29; P= 0.0091). CONCLUSION: Our data indicate that lower postischemic forearm reactive hyperemia is associated with all-cause mortality of ESRD patients, independently of the presence of end-organ damage such as LVH or arteriosclerosis.

Arterial stiffness: pathophysiology and clinical impact.

The ill effects of hypertension are usually attributed to a reduction in the caliber or the number of arterioles, resulting in an increase in total peripheral resistance (TPR). This definition does not take into account the fact that BP is a cyclic phenomenon with systolic and diastolic BP being the limits of these oscillations. The appropriate term to define the arterial factor(s) opposing LV ejection is aortic input impedance which depends on TPR, arterial distensibility (D), and wave reflections (WR). D defines the capacitive properties of arterial stiffness, whose role is to dampen pressure and flow oscillations and to transform pulsatile flow and pressure in arteries into a steady flow and pressure in peripheral tissues. Stiffness is the reciprocal value of D. These parameters are BP dependent, and arteries become stiffer at high pressure. In to D which provides information about the <> of artery as a hollow structure, the elastic incremental modulus (Einc) characterizes the properties of the arterial wall biomaterials, independently of vessel geometry. As an alternative, arterial D can be evaluated by measuring the pulse wave velocity (PWV) which increases with the stiffening of arteries. Arterial stiffening increases left ventricular (LV) afterload and alters the coronary perfusion. With increased PWV, the WR impacts on the aorta during systole, increasing systolic pressures and myocardial oxygen consumption, and decreasing diastolic BP and coronary flow. The arterial stiffness is altered primarily in association with increased collagen content and alterations of extracellular matrix (arteriosclerosis) as classically observed during aging or in arterial hypertension. The arterial stiffening estimated by changes in aortic PWV and intensity of WR are independent predictors of survival in end stage renal disease (ESRD) and general population. Improvement of arterial stiffening could be obtained by antihypertensive treatmen as observed with the calcium-channel blocker and ACE inhibitors. ACE inhibitors increased AC and reduced WR, and it has been shown that reversibility of aortic stiffening and use of ACE inhbitors had favorable independent effect on survival in hypertensive patients with advanced renal disease.

Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality.

BACKGROUND: Cross-sectional and follow-up studies on end-stage renal disease patients showed that arterial calcifications are associated with cardiovascular (CV) morbidity and are an independent predictor of all-cause and CV mortality. However, these studies did not examine the impact on prognosis according to the type of calcification, i.e. intimal vs medial. Arterial media calcification (AMC), a non-occlusive condition, affects haemodynamics differently from arterial intima calcification (AIC), which occurs in atherosclerotic plaques. The aim of this study was to investigate the prognostic value of AMC in relationship to all-cause or CV mortality for stable haemodialysis (HD) patients. METHODS: We included 202 such patients in the present study. At baseline, soft-tissue native radiograms of the pelvis and the thigh were analysed for the presence and type (AMC vs AIC) of arterial calcifications. All patients underwent B-mode ultrasonography of the common carotid artery to determine the presence of atherosclerotic calcified plaques, measurement of aortic pulse wave velocity and echocardiography. RESULTS: AIC was usually observed in older patients with a clinical history of atherosclerosis before starting HD treatment and typical risk factors associated with atherosclerotic disease. AMC was observed in young and middle-aged patients without conventional atherosclerotic risk factors. AMC was closely associated with the duration of HD and calcium-phosphate disorders, including the oral dose of elemental calcium prescribed as phosphate binder (CaCO(3)). Compared to patients with AIC, patients with AMC had a longer survival, but in turn their survival was significantly shorter than that of patients without calcifications. CONCLUSIONS: AMC is a strong prognostic marker of all-cause and CV mortality in HD patients, independently of classical atherogenic factors. The principal effect of AMC on arterial function is increased arterial stiffness.

Inflammation, arteriosclerosis, and cardiovascular therapy in hemodialysis patients.

BACKGROUND: Aortic stiffness and left ventricular hypertrophy (LVH) are predictors of mortality in hemodialysis (HD) patients. Attenuation of arterial stiffness and regression of LVH had a favorable effect on survival in these patients, but this favorable effect was observed in less than 50% of patients, the rest being resistant to therapeutical interventions. The aim of this study was to analyze the factors associated with this resistance to treatment. METHODS: 138 patients on HD were studied during a follow-up survey. From entry until the end of follow up, the changes of aortic pulse wave velocity (PWV) and of LV mass were measured in response to treatment with antihypertensive drugs and erythropoietin, together with measurements of blood chemistry, including high-sensitive C-reactive protein (CRP). Patients with decreased aortic PWV were considered to be responders (N = 68), the others to be nonresponders (N = 70). RESULTS: Nonresponders were older (P < 0.05) and had persistently higher systolic blood pressure (BP) and pulse pressure. Responders were treated more frequently with an ACE inhibitor (P < 0.001), and had lower serum CRP (P < 0.01). The baseline PWV, as well as the changes of PWV and LV mass during the follow-up were significantly and independently correlated with serum CRP level (P < 0.001). According to logistic regression after adjustment for age, gender, diabetes, history of CVD, and the nonspecific cardiovascular risk factors, the improvement of aortic stiffness and LV hypertrophy was positively associated with prescription of ACE inhibitor (P < 0.0001), and negatively with the serum CRP level (P < 0.01). CONCLUSION: These results indicate that in HD patients, the presence of low-grade inflammation decreases the efficiency of cardiovascular therapeutic interventions and participates in the persistence of cardiovascular hemodynamic overload.

Aortic pulse wave velocity index and mortality in end-stage renal disease.

BACKGROUND: Aortic pulse wave velocity (PWV) is a strong independent predictor of overall and cardiovascular mortality in patients with end-stage renal disease (ESRD). Nevertheless, because age, blood pressure, heart rate, and gender are strong determinants of both arterial stiffness and mortality, the individual relevance of PWV measurements remains controversial. METHODS: A cohort of 242 patients with ESRD undergoing hemodialysis was studied for a mean (+/- SD) duration of 78 +/- 46 months. At entry, together with standard clinical and biochemical analyses, PWV was measured using Doppler ultrasonography. On the basis of a nomogram established on 469 nonuremic subjects, a theoretical value of PWV was determined in ESRD patients according to their age, blood pressure, gender, and heart period. The PWV index (measured PWV - theoretical PWV) was then calculated for each individual ESRD patient. RESULTS: Based on Cox analysis, the PWV index, but neither pulse pressure nor cardiac mass, was a strong and independent predictor of both cardiovascular and overall mortality, together with age and time on dialysis before inclusion. Patients with positive (versus negative) PWV index had a twofold adjusted risk of mortality during the follow-up. Per each 1 meter/second PWV index increment, we observed a 34% (crude) and a 14% (adjusted) increase in both cardiovascular and overall mortality (P < 0.02 for all). CONCLUSION: In ESRD patients, the calculation of a PWV index provides information about cardiovascular and overall mortality risk with high predictive power, showing that PWV measurements provide discriminatory prognostic power over and above conventional cardiovascular risk factors.

Impairment of arterial function in chronic renal disease: prognostic impact and therapeutic approach.

Epidemiological and clinical studies have shown that damage to large arteries contributes to the high cardiovascular mortality in patients with end-stage renal disease (ESRD). Atherosclerosis is the most frequent cause of arterial damage. Occlusive lesions from atherosclerotic plaques (calcification) decrease the conduit function of arteries and reduce the elasticity of capacitance arteries (stiffening), affecting their dampening function. Arterial calcification and aortic stiffness are independent predictors of cardiovascular risk in the general population, and independent predictors of all-cause and cardiovascular mortality in ESRD patients. Successful treatment to reduce blood pressure (BP) and reverse aortic stiffness has a significant, BP-independent effect on survival in ESRD patients. However, response to such treatment may be limited in patients with microinflammation and raised levels of C-reactive protein.

Prognostic significance of arterial stiffness measurements in end-stage renal disease patients.

PURPOSE OF REVIEW: As epidemiological and clinical studies have shown that damage of large arteries is a major contributory factor to the high cardiovascular morbidity of patients with end-stage renal disease, such a population is particularly appropriate for analysis the impact of arterial stiffness on cardiovascular risk assessment and reduction strategies. RECENT FINDINGS: Aortic pulse wave velocity, a marker of aortic stiffness, has been shown to be a strong independent predictor of cardiovascular and all-cause mortality in patients with end-stage renal disease on hemodialysis. Local arterial stiffness assessment, namely carotid distensibility was also shown to predict cardiovascular risk, both in end-stage renal disease patients and in renal transplant recipients. Furthermore, it was shown in a therapeutic trial that the lack of aortic pulse wave velocity attenuation, despite significant drug-induced reduction in mean blood pressure, was a significant predictor of cardiovascular death in subjects with end-stage renal disease. These results support the hypothesis that measurement of aortic pulse wave velocity could help, not only in risk assessment strategies, but also in risk reduction strategies by monitoring arterial stiffness under different pharmacological regimens. The drug-related reduction of aortic pulse wave velocity could then give prognostic information, in addition to blood pressure reduction. SUMMARY: Aortic stiffness measurements could serve as an important tool in identifying end-stage renal disease patients at higher risk of cardiovascular disease. The ability to identify these patients would lead to better risk stratification and earlier and more cost-effective preventive therapy.

Iron therapy, advanced oxidation protein products, and carotid artery intima-media thickness in end-stage renal disease.

BACKGROUND: Increased common carotid artery intima-media thickness (CCA-IMT) is a marker of early atherosclerosis. Low-grade inflammation is associated with the pathogenesis of atherosclerosis. Low-grade inflammation and increased CCA-IMT are observed in end-stage renal disease (ESRD). Oxidative stress is involved in uremia-related inflammation. Advanced oxidation protein products (AOPP) are markers of oxidant-mediated protein damage in ESRD. Intravenous iron given to patients on hemodialysis (HD) might induce oxidative stress. We investigated the relationships between AOPP, iron therapy, and CCA-IMT in stable HD patients. METHODS AND RESULTS: Plasma AOPP and blood chemistry, including iron status, were analyzed in a cohort of 79 ESRD patients on HD. Measurements of CCA-IMT and CCA diameter, as assessed by B-mode ultrasonography, were obtained in 60 patients. AOPP levels were elevated in ESRD patients, and in univariate (r=0.42, P<0.0001) and multivariate analyses (r=0.38, P<0.001), they correlated with serum ferritin and with the intravenous iron dose received during the 12 months preceding the study (ferritin, P<0001; AOPP, P<0.01). Univariate and multivariate analyses identified the AOPP concentration as being significantly associated with CCA-IMT (P=0.0197) and CCA wall-to-lumen ratio (r=0.560, P<0.0001). Independently of AOPP concentration, cumulative iron dose was positively related to CCA-IMT (P=0.015) in patients <60 years. CONCLUSION: In ESRD patients, CCA-IMT and CCA wall-to-lumen ratio were associated with plasma AOPP, serum ferritin, and the annual intravenous iron dose administered. These findings support the concept of a role of oxidative stress in the early atherosclerosis of ESRD patients, which may be increased by the usually recommended doses of intravenous iron.