Emiliana Ferramosca

Pulse Wave Velocity Is Inversely Related to Vertebral Bone Density in Hemodialysis Patients

Abnormalities of bone mineral metabolism in patients with stage-5 chronic kidney disease may contribute to the high incidence of cardiovascular disease. Noninvasive imaging methods may help predict the simultaneous presence of vasculopathy and bone disease. Accordingly, we measured pulse wave velocity and bone mineral density (BMD), and T-scores (number of SDs below the BMD of a younger reference group) of the spine by both dual energy x-ray absorptiometry and quantitative computed tomography (QCT) in 110 maintenance hemodialysis patients. Older age, white race, diabetes mellitus, lower diastolic blood pressure, and lower albumin levels were associated with lower QCT-assessed T-scores (each P<0.05). After age and multivariable adjustment, pulse wave velocity (PWV) increased as QCT BMD decreased (the prevalence of PWV ≥9 m/s was 32.4%, 61.8%, and 76.5% for participants in the highest to the lowest tertile of QCT-assessed BMD; P<0.001). In contrast, there was no relationship between spine dual energy x-ray absorptiometry-BMD and PWV. In unadjusted models, thoracic spine QCT-assessed T-scores correlated significantly, albeit weakly, with aorta calcification (r=0.22; P=0.01) but not with coronary calcification. The odds ratio of PWV ≥9 m/s for patients taking vitamin D3 or its analogs was 0.51 (95% CI: 0.19 to 1.39). In conclusion, low spine BMD is associated with increased PWV in stage-5 chronic kidney disease, supporting the notion of a close interaction of vascular and bone disease in this patient group. QCT and not dual energy x-ray absorptiometry should be used to assess spine BMD in dialysis patients.

All-cause Mortality in Hemodialysis Patients with Heart Valve Calcification

BACKGROUND AND OBJECTIVES Calcification of the mitral and aortic valves is common in dialysis patients (CKD-5D). However, the prognostic significance of valvular calcification (VC) in CKD is not well established. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS 144 adult CKD-5D patients underwent bidimensional echocardiography for qualitative assessment of VC and cardiac computed tomography (CT) for quantification of coronary artery calcium (CAC) and VC. The patients were followed for a median of 5.6 years for mortality from all causes. RESULTS Overall, 38.2% of patients had mitral VC and 44.4% had aortic VC on echocardiography. Patients with VC were older and less likely to be African American; all other characteristics were similar between groups. The mortality rate of patients with calcification of either valve was higher than for patients without VC. After adjustment for age, gender, race, diabetes mellitus, and history of atherosclerotic disease, only mitral VC remained independently associated with all-cause mortality (hazard ratio [HR], 1.73; 95% confidence interval [CI], 1.03 to 2.91). Patients with calcification of both valves had a two-fold increased risk of death during follow-up compared with patients without VC (HR, 2.16; 95% CI, 1.14 to 4.08). A combined CT score of VC and CAC was strongly associated with all-cause mortality during follow-up (HR for highest versus lowest tertile, 2.21; 95% CI, 1.08 to 4.54). CONCLUSIONS VC is associated with a significantly increased risk for all-cause mortality in CKD-5D patients. These findings support the use of echocardiography for risk stratification in CKD-5D as recently suggested in the Kidney Disease Improving Global Outcomes guidelines.

Cardiac valve calcification is a marker of vascular disease in prevalent hemodialysis patients

BACKGROUND Vascular and valvular calcifications are a common finding in chronic kidney disease (CKD) patients and are associated with increased morbidity and mortality. We investigated the hypothesis that calcification of the cardiac valves is a marker of coronary artery calcification (CAC) and thoracic aorta calcification (AoC) in hemodialysis (CKD-5) patients. METHODS This was a cross-sectional study of 145 maintenance CKD stage 5 (CKD-5) patients. All patients underwent electron beam tomography for quantification of CAC and AoC score via the Agatston score. The presence of calcification of the cardiac valves was assessed by standard bi-dimensional echocardiography. RESULTS Eighty-four of the study patients (58%) had echocardiographic evidence of valvular calcification. A significant and graded association between valvular calcification and CAC as well as AoC was detected. Patients with 1 or 2 calcified valves had a significantly greater likelihood of having a CAC score >1,000 (odds ratio [OR] = 5.94; 95% confidence interval [95% CI], 1.91-18.44; p=0.002; and OR=3.27; 95%CI, 1.36-7.88; p=0.007, respectively). Similarly, the presence of 1 or 2 calcified valves was associated with an eightfold and threefold increased probability of an AoC score greater than the third quartile, respectively. CONCLUSIONS This cross-sectional analysis shows that calcification of the cardiac valves is closely associated with vascular calcification, an established marker of risk in prevalent hemodialysis patients.

Arterial Stiffness in Chronic Kidney Disease: The Usefulness of a Marker of Vascular Damage

Increased arterial stiffness is a marker of vasculopathy in chronic kidney disease (CKD) patients, suggesting a significant cardiovascular damage. Detection of arterial stiffness provides physicians with useful prognostic information independent of traditional cardiovascular (CV) risk factors. In addition, this knowledge may help guide appropriate therapeutic choices and monitor the effectiveness of antihypertensive therapies. We review the relationship between arterial stiffness and CKD, as well as the prognostic implications of increased arterial stiffness and the potential therapeutic strategies to ameliorate arterial compliance and outcome in CKD.

The density of calcified plaques and the volume of calcium predict mortality in hemodialysis patients

BACKGROUND AND AIM In the general population lipid-rich plaques are prone to rupture and healing of the plaque involves calcification. Patients undergoing hemodialysis have a severe derangement of mineral metabolism and calcification of the arterial tree may have different implications. METHODS Between 2004 and 2005, 125 hemodialysis patients (60 men) underwent computed tomography imaging for quantification of coronary artery calcium via the Agatston and the Volume methods. Since the Agatston score is derived by multiplying the density by the volume of a calcified lesion, the Agatston/Volume ratio (AVR) is an indication of the density (i.e. calcium accumulation) within the plaque. RESULTS Patients were classified as high AVR (>1) or low (≤1) AVR. Survival analyses tested the association between AVR and all-cause mortality during a median follow-up of 5 years. The mean age was 57.2±13.5 years; 75% of the patients had AVR >1. The mortality rate of patients with AVR >1 was significantly higher than in patients with AVR ≤1 (Hazard Ratio(HR): 2.46; 95% Confidence Intervals(CI): 1.16-5.21, p ≤0.018). After adjustment for confounders, AVR >1 remained independently associated with all-cause mortality (HR: 2.24; 95% CI: 1.02-4.88, p ≤0.042). There was a significant interaction of plaque density and calcium volume on mortality. CONCLUSIONS Increased plaque density is an independent predictor of all-cause mortality in hemodialysis patients. These data suggest that increased calcium content in the coronary arteries of patients in dialysis is an index of high-risk rather than a marker of plaque stabilization.

Acetate-Free Biofiltration

Acetate-free biofiltration (AFB) is a hemodiafiltration technique that, technically as well as biologically speaking, has all the premises for being a perfectly biocompatible technique capable of satisfying even the demands of critical patients laden with comorbidities. Important clinical benefits to patients have been reported, such as a better correction of acid-base balance, an improved nutritional status and a better hemodynamic stability. In particular, as far as the cardiovascular instability is concerned, several studies have shown that the rationale behind a better hemodynamic stability is the overall absence of acetate usually present in the dialysis bath, which often leads to an impaired vascular tone and a reduced cardiac contractility. One of the powerful features of AFB is its adaptability to new devices and tools which can be easily and safely used. In AFB, potassium modulation in the dialysate is easily achieved. Thus, patients with elevated levels of predialysis potassium and a tendency to develop both intra- and interdialysis arrhythmias benefit most. Lastly, the possibility to associate AFB with devices like Hemocontrol (which allows for a feedback conditioning of blood volume) broadens its practical scope, not only for use with hypotension-prone patients, but also with hypertensive patients with massive increases in their interdialysis body weight. In this category of patients, avoiding the risk of dangerous hypovolemias allows for the achievement of dry body weight, thereby facilitating the control of arterial blood pressure and minimizing the clinical consequences of a chronic fluid overload.

Integration of clinical and imaging data to predict death in hemodialysis patients.

In a prior publication, we demonstrated that a model integrating clinical and simple imaging data predicted the presence and severity of coronary artery calcification in prevalent hemodialysis patients. Herein we report the ability of the same model to predict all‐cause death. We assessed all‐cause mortality in 141 consecutive maintenance hemodialysis patients from two dialysis centers followed for a median of 79 months from enrollment. Patients were risk stratified according to a simple cardiovascular calcification index (CCI) that included patients age, dialysis vintage, calcification of the cardiac valves, and abdominal aorta. The mean patients’ age was 55 ± 14 years. Abdominal aorta calcification was present in 57% of the patients, and 44% and 38% had aortic and mitral valve calcification, respectively. During follow‐up, 75 deaths (93 deaths per 1000 person‐years) were recorded. The CCI was linearly associated with risk of death, such that the unadjusted hazard risk (HR) increased by 12% for each point increase in CCI (P < 0.001). Further adjustments for age, sex, study center, diabetes mellitus, history of cardiovascular disease, hypertension, congestive heart failure, left ventricular hypertrophy, systolic, and diastolic blood pressure did not substantially change the strength of this association (HR 1.10; 95%CI: 1.00–1.21; P = 0.03). The CCI is a simple clinical model that can be used to risk stratify maintenance hemodialysis patients.

Ethiopathogenesis, Diagnosis and Prevention of Vascular Calcification in End Stage Renal Disease

Extensive atherosclerosis and heavy vascular and valvular calcifications are common complications of end stage renal disease (ESRD) and are very likely related to the high incidence of cardiovascular disease in these patients. The greatly increased incidence of cardiovascular disease is only partly explained by traditional risk factors for atherosclerosis. In ESRD, vascular calcification occurs both in the vascular intima layer and in the tunica media. Intimal calcification is disseminated and is characteristically associated with damaged and abnormally functioning endothelium, and macrophage and vascular smooth muscle cell (VSMC) infiltration typical of atherosclerosis. On the contrary, medial calcification occurs in patchy distribution and the most frequent cell types found in its vicinity are the VSMC and macrophage. The uremic state is associated with numerous metabolic abnormalities and endocrine disturbances primarily involving calcium and phosphorus metabolism. Furthermore, chronic kidney disease and dialysis are considered states of active and strong inflammatory response. These dysfunctions occur early in the course of renal failure and likely contribute to the development and progression of vascular calcification and atherosclerosis. For many years, vascular calcification was considered solely the result of a passive deposition of hydroxyapatite crystals in the arterial wall due to elevated calcium-phosphate ion product. However, a large body of evidence has now shown that this is a highly regulated process governed by factors that closely resemble calcium deposition in bone tissue. In fact, vascular calcification requires changes in the phenotype of VSMC and the expression of several proteins normally involved in bone metabolism. This review is centered on the etiopathogenesis of vascular calcification in ESRD, its detection with modern imaging modalities and the therapeutic approaches currently available to slow its progression.

Arterial Stiffness, Pulse Wave Analyses: What Can’t Blood Pressure Tell you in Chronic Kidney Disease

Increased arterial stiffness is emerging as a useful marker of cardiovascular damage. A growing body of evidence suggests that the stiffening of the conduit arteries is linearly associated with poor survival in the general population and high-risk population such as Chronic Kidney Disease (CKD) patients. Indeed, the loss of the elastic properties of conduit arteries induces an increase in the central pulse pressure and cardiac workload leading to left ventricular hypertrophy and reduced coronary and capillary perfusion. Notably, all these changes are independent of mean blood pressure and other established cardiovascular risk factors. Though, evidence is still inconclusive, some preliminary data suggest that arterial stiffness and central blood pressure evaluation can be of use for risk stratification and treatment individualization. We herein summarize the current evidence supporting the usefulness of arterial stiffness assessment for CKD patients’ management.

Coronary artery calcium screening: implications for clinical practice

Cardiovascular disease is the most common cause of death in the Western hemisphere, and in the majority of cases the event announcing the presence of atherosclerosis is either sudden death or a disabling myocardial infarction or stroke. Although traditional risk factors are present in most individuals suffering a cardiovascular event, the prognostic ability of risk factors to predict events in the short term is limited. The focus of research has therefore turned to the application of noninvasive modalities to image the atherosclerotic plaque in its preclinical stages. Measurements of coronary artery calcium serve as a quantitative reflection of the severity of coronary artery disease, and greater calcium burdens correlate with more advanced disease. Coronary artery calcium has been shown in several studies to add prognostic value to traditional risk factors in patients at intermediate risk, and in this group of patients it may be cost effective. There is, however, an inherent danger in raising the cost of care by increasing downstream unnecessary testing if such screening were to be applied to low-risk individuals. This article is a systematic review of the most relevant literature regarding the utilization of coronary artery calcium screening as a tool to refine risk assessment and to evaluate the efficacy of therapy for atherosclerosis.