Impact of coronary artery calcification in hemodialysis patients: Risk factors and associations with prognosis

The risk factors of coronary artery calcification (CAC) and the impact of CAC on cardiovascular events, cardiovascular deaths, and all‐cause deaths in hemodialysis (HD) patients have not been fully elucidated. We examined the CAC score (CACS) in 74 HD patients using electron‐beam computed tomography. Fifty‐six patients underwent a second electron‐beam computed tomography after a 15‐month interval to evaluate CAC progression. We evaluated (1) the risk factors for CAC and its progression and (2) the impact of CAC on the prognosis. In the cross‐sectional study, HD vintage and high‐sensitive C‐reactive protein (hsCRP) were the independent risk factors for CAC. In the prospective cohort study, delta CACS (progression of CAC) was significantly correlated with hsCRP, fibrinogen, and serum calcium level in the univariate analysis. Stepwise multiple regression analysis revealed that only hsCRP was the independent risk factor for CAC progression in HD patients. Kaplan‐Meier survival analysis revealed that cardiovascular events (P<0.0001), cardiovascular deaths (P=0.039), and all‐cause deaths (P=0.026) were significantly associated with CACS. In conclusion, CAC had significantly progressed in HD patients during the 15‐month observation period. Microinflammation was the only independent risk factor for CAC progression in HD patients. The advanced CAC was a significant prognostic factor in HD patients, i.e., which was strongly associated with future cardiovascular events, cardiovascular deaths, and all‐cause deaths.     

Monocyte/lymphocyte ratio as a better predictor of cardiovascular and all‐cause mortality in hemodialysis patients: A prospective cohort study

Introduction: Patients with chronic kidney disease, especially those with end‐stage renal disease, have an increased risk of death. Previous studies have suggested neutrophil/lymphocyte ratio (NLR) was related to worse outcome in patients undergoing hemodialysis (HD). However, monocyte/lymphocyte ratio (MLR) has not been evaluated in HD patients. In this study, we prospectively studied the predictive value of MLR for all‐cause and cardiovascular mortality in HD patients and compared it with NLR. Methods: Patients who had been on a HD treatment for at least 6 months were enrolled. MLR was calculated by dividing the monocyte count by the lymphocyte count. Survival outcomes were estimated using the Kaplan‐Meier method and compared by the log‐rank test. Univariate and multivariate analyses were performed to evaluate the prognostic impact of MLR and other clinical factors on all‐cause and cardiovascular mortality. Results: Mortality rates for the lowest, middle, and highest MLR tertile group were 3.65, 7.02, and 11.15, respectively per 100 patient‐years. The Kaplan‐Meier analysis revealed that survival rates were significantly different among three MLR groups (P < 0.001). In multivariate Cox regression analyses, MLR was independently associated with all‐cause mortality (HR 4.842; 95% CI, 2.091–11.214; P < 0.001) and cardiovascular mortality (HR 6.985, 95% CI 1.943–25.115, P = 0.003) as continuous variables. NLR was not an independent predictor of all‐cause nor cardiovascular mortality after adjusted with MLR. Conclusions: The main finding of the study suggest that higher MLR was a strong and independent predictor of all‐cause and cardiovascular mortality and overwhelmed NLR among HD patients.     

Left ventricular mass index and aortic arch calcification score are independent mortality predictors of maintenance hemodialysis patients

To analyze predictive factors for all‐cause mortality, cardiovascular (CV) mortality, nonfatal CV events (CVE) in maintenance hemodialysis (MHD) patients, and to compare the effects of standard hemodialysis (HD) and online hemodiafiltration (HDF) on these factors and outcomes. A total of 333 MHD patients were prospectively followed up for 50 ± 15 months and all‐cause death, CV death and CVE were registered. At the baseline, demographic, clinical, and laboratory data of the whole population were recorded. Then, patients were stratified into two groups according to the dialysis modalities, HD (n = 268) and HDF (n = 65). At the end of 6th month, clinical and laboratory data were recorded again. The predictive factors at baseline for all‐cause mortality, CV mortality, and CVE were analyzed by Cox regression. The effects of HD and HDF on these factors at the 6th month and long‐term outcomes were compared by t‐test and Kaplan–Meier method, respectively. Age, gender, left ventricular mass index (LVMI), aortic arch calcification score (AoACS), hemoglobin (Hb) <10 g/dL, and ferritin >500 ng/mL maintained independent associations with all‐cause mortality. C‐reactive protein (CRP), LVMI, AoACS, and Hb <10 g/dL were associated with CV mortality. Prior cardiovascular disease (CVD), AoACS and LVMI were independent predictors of nonfatal CVE. Higher body mass index (BMI), body weight, total serum cholesterol, Hb concentration, and lower CRP level, LVMI, and AoACS were found in patients on HDF at the end of the 6th month. Improved outcomes with longer survival time for all‐cause mortality, CV mortality, and CVE were found in HDF group. Age, gender, LVMI, AoACS, Hb, and ferritin were predictors of all‐cause mortality in MHD patients. CRP, LVMI, AoACS, and Hb were associated with CV mortality. Prior CVD, AoACS, and LVMI were independent predictors of nonfatal CVE. HDF could improve BMI, body weight, total serum cholesterol, Hb, CRP, LVMI, AoACS, and long‐term outcomes, including all‐cause mortality, CV mortality, and CVE.     

Inflammation as a cause of malnutrition, atherosclerotic cardiovascular disease, and poor outcome in hemodialysis patients

Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in end‐stage renal disease (ESRD) patients treated by hemodialysis (HD). Although traditional risk factors are common in dialysis patients, they may not alone be sufficient to account for the unacceptable high prevalence of CVD in this patient group. Recent evidence demonstrates that chronic inflammation, a nontraditional risk factor that is commonly observed in HD patients, may cause malnutrition and progressive atherosclerotic CVD by several pathogenetic mechanisms. The cause(s) of inflammation in HD patients is multifactorial and includes both dialysis‐related (such as graft and fistula infections, bioincompatibility, impure dialysate, and back‐filtration) and dialysis‐unrelated factors. Although inflammation may reflect underlying CVD, an acute‐phase reaction may also be a direct cause of vascular injury. Available data suggest that proinflammatory cytokines play a central role in the genesis of both malnutrition and CVD in ESRD. Thus, it could be speculated that suppression of the vicious cycle of malnutrition, inflammation, and atherosclerosis (MIA syndrome) would improve survival in dialysis patients. As there is not yet any recognized, or even proposed, targeted treatment for ESRD patients with chronic inflammation; it would be of considerable interest to study the long‐term effect of various anti‐inflammatory treatment strategies on nutritional and cardiovascular status as well as outcome in these patients.     

Impact of arterial microcalcification of the vascular access on cardiovascular mortality in hemodialysis patients

Gross vascular calcification seen on imaging studies is common in hemodialysis (HD) patients, and is a significant predictor for cardiovascular mortality in HD patients. We have reported that arterial microcalcification (AMiC) of the vascular access is associated with increased aortic stiffness. This study investigated the impact of vascular access AMiC on cardiovascular mortality in HD patients. The study included 149 HD patients (mean age: 59.1 ± 13.9 years, 86 men and 63 women, 65.8% diabetic) who underwent vascular access surgery. Radial or brachial artery specimens were obtained intraoperatively, and pathologic examination was performed using von Kossa stain to identify AMiC. We compared all‐cause and cardiovascular mortality between patients with and without AMiC. The mean follow‐up was 37.8 ± 34.5 months, and AMiC was present in 38.8% (n = 57) of patients. The presence of diabetes (odds ratio: 16.49, 95% confidence interval: 1.81–150.36, P = 0.013) was the only independent risk factor for vascular access AMiC. During the observational period, there were 27 cardiovascular deaths. Kaplan–Meier analysis showed an increased cardiovascular mortality risk (log rank = 4.83, P = 0.028) in AMiC patients, and Cox regression analysis confirmed that AMiC was an independent predictor for cardiovascular mortality (hazard ratio: 2.35, 95% confidence interval: 1.09–5.09, P = 0.030). In conclusion, vascular access AMiC is a strong risk factor for cardiovascular mortality in HD patients.     

Cardiovascular disease on hemodialysis: Predictors of atherosclerosis and survival

Cardiovascular disease (CVD) is the leading cause of mortality in hemodialysis (HD) patients. This could not be explained by the known traditional CVD risk factors. In this study, we attempted to elucidate the factors influencing atherosclerosis, as measured by carotid artery intima-media thickness (IMT), in HD patients and their impact on cardiovascular mortality. A cohort of 50 patients started on HD was selected for this study. At baseline, IMT and the presence of atheromatous plaques were assessed. Plasma homocysteine (Hcy), malondialdehyde, total antioxidant capacity, von Willebrand factor, vitamins C, E, B₆, B₁₂, folate, and C-reactive protein (CRP) were also measured. Patients were followed up for 2 years to determine the impact of IMT and associated markers on mortality using survival analysis as well as Cox proportional hazard. At baseline, 40% of the patients had IMT>0.8 mm. They were older, had higher CRP (P<0.001), and lower serum albumin (P=0.03). Intima-media thickness >0.8 mm was associated with high calcium (risk ratio [RR]: 6.06; confidence interval [CI]: 0.75–12.25) and CRP (RR: 10.94 [CI: 2.56–46.74]). Fifteen patients (30%) died during the 2-year follow-up; the main cause of death was CVD (42%). The relative risk mortality was high with increased IMT (RR: 120.04 [CI: 4.18–3445.9]), Index of Coexistent Disease for CVD (RR: 4.04 [CI: 1.92–8.5]), and plasma Hcy (RR: 1.08 [CI: 1.02–1.13]). Markers of inflammation and increased serum calcium were significant predictors of increased carotid artery IMT. High IMT, Index of Coexistent Disease, and Hcy were associated with a high RR of all-cause mortality among a cohort of HD patients.     

Hemodialysis‐induced regional left ventricular systolic dysfunction

Introduction Hemodialysis (HD) patients are under observably elevated cardiovascular mortality. Cardiac dysfunction is closely related to death caused by cardiovascular diseases (CVD). In the general population, repetitive myocardial ischemia induced left ventricular (LV) dysfunction may progress to irreversible loss of contraction step by step, and finally lead to cardiac death. In HD patients, to remove water and solute accumulated from 48 or 72 hours of interdialysis period in a 4‐hour HD session will induce myocardial ischemia. In this study, we evaluated the prevalence and potential risk factors associated with HD‐induced LV systolic dysfunction and provide some evidences for clinical strategies. Methods We recruited 31 standard HD patients for this study from Fudan University Zhongshan hospital. Echocardiography was performed predialysis, at peak stress during HD (15 minutes prior to the end of dialysis), and 30 minutes after HD. Auto functional imaging (AFI) was used to assess the incidence and persistence of HD‐induced regional wall motion abnormalities (RWMAs). Blood samples were drawn to measure biochemical variables. Findings Among totally 527 segments of 31 patients, 93.54% (29/31) patients and 51.40% (276/527) segments were diagnosed as RWMAs. Higher cTnT (0.060 ± 0.030 vs. 0.048 ± 0.015 ng/mL, P = 0.023), phosphate (2.07 ± 0.50 vs. 1.49 ± 0.96 mmol/L, P = 0.001), UFR (11.00 ± 3.89 vs. 8.30 ± 2.66 mL/Kg/h, P = 0.039) and lower albumin (37.83 ± 4.48 vs. 38.38 ± 2.53 g/L, P = 0.050) were found in patients with severe RWMAs (RWMAs in more than 50% segments). After univariate and multivariate analysis, interdialytic weight gain (IDWG) was found as independent risk factor of severe RWMAs (OR = 1.047, 95%CI 1.155–4.732, P = 0.038). Discussion LV systolic dysfunction induced by HD is prevalent in conventional HD patients and should be paid attention to. Patients would benefit from better weight control during interdialytic period to reduce ultrafiltration rate.     

Plasma myeloperoxidase,NT‐proBNP,and troponin‐I in patients on CAPD compared with those on regular hemodialysis

Myeloperoxidase (MPO) is a hemoprotein that is released during inflammation and may lead to irreversible protein and lipid modification, increasing levels of oxidized low density lipoprotein, and promoting athrogenesis. Recently, it has been considered as a risk factor for cardiovascular diseases. Similarly, the measurement of carotid intima‐media thickness gives an indication about the degree of atherosclerosis and prediction of clinical cardiovascular events. Elevated white blood cells counts may indicate a state of acute inflammation and follow its progression. Dialysis patients are at a high risk of developing cardiovascular disease compared with healthy subjects. The role of N‐terminal pro‐brain natriuretic peptide and increased cardiac troponin in identification and prognostication of cardiovascular diseases in end‐stage renal disease patients has been investigated. The current study aimed to evaluate plasma MPO and its possible relationship with carotid intima‐media thickness, troponin I, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), and insulin resistance as measured by homeostatic model assessment (HOMA index) in a cohort of Saudi patients who are undergoing hemodialysis (HD) vs. continuous ambulatory peritoneal dialysis for end‐stage renal disease. Plasma MPO was significantly higher in patients on continuous ambulatory peritoneal dialysis (CAPD) than in those on HD and in normal subjects (P<0.001). Conversely, NT‐proBNP plasma levels were significantly higher in patients on HD (both predialysis and postdialysis) than in those on CAPD (P<0.01) and than normal subjects. Similarly, plasma troponin‐I levels were significantly higher in patients on HD compared with those of CAPD and than normal subjects (P<0.001). Plasma troponin‐I and NT‐proBNP levels were positively correlated in the 3 groups namely those on CAPD, Pre‐HD, and post‐HD (r: 0.464 and P=0.047; r: 0.330 and P=0.013; and r: 0.452 and P=0.024), respectively. There was no correlation between the MPO level and carotid intima‐media thickness (P>0.05). However, plasma MPO level correlated positively with the white blood cell count in patients on CAPD and in those on HD (P<0.05). Our findings suggest an increased oxidative stress in CAPD patients compared with HD patients, while the reported difference in plasma NT‐proBNP and troponin‐I may be related to the rapid decline of residual renal function in HD and type of membrane used in the HD dialysis procedure itself.     

Adiponectin and atherosclerosis risk factors in African hemodialysis patients: a population at low risk for atherosclerotic cardiovascular disease

Atherosclerotic cardiovascular disease (CVD) is the major cause of morbidity and mortality in hemodialysis (HD) patients. Adiponectin (ADPN), a recently discovered collagen-like protein, is secreted exclusively by adipocytes. It has anti-atherogenic properties and reduced serum ADPN levels have been shown to be predictive of cardiovascular events. In this study, we determined the atherosclerotic risk and the significance of ADPN levels in our HD patients and also examined its relationship to other traditional CVD risk factors. A cross-sectional study of 84 patients on maintenance HD (58 Blacks and 26 non-Blacks) and 63 healthy controls matched for age, sex and race (35 Blacks and 28 non-Blacks) was undertaken. Serum ADPN levels and other risk factors, including blood pressure, serum lipid, and C-reactive protein, were studied in HD patients and were compared with the controls. Carotid artery intima-media thickness and plaque occurrence was measured by B-mode ultrasonography while echocardiography was done according to American Society of Echocardiography guidelines. Serum ADPN levels were higher in the HD group compared with the control subjects (22.19 ± 0.98 mg/mL vs. 9.93 ± 0.68 mg/mL; P < 0.001). Higher ADPN levels in HD patients were associated with lower triglyceride levels. ADPN correlated positively (r = 0.49, P < 0.0001) with left ventricular mass index (LVMI) in the total study population. ADPN levels were raised in HD patients and correlated with LVMI, possibly because of the confounding effect of low glomerular filtration rate. ADPN levels were inversely related to risk factors for atherosclerosis and may provide possible targets for therapeutic interventions.     

Younger black patients have a higher risk of infection mortality that is mostly non‐dialysis related: A national study of cause‐specific mortality among U.S. maintenance dialysis patients

Introduction: While it has been well documented that in the U.S., black and Hispanic dialysis patients have overall lower risks of death than white dialysis patients, little is known whether their lower risks are observed in cause‐specific deaths. Additionally, recent research reported that younger black patients have a higher risk of death, but the source is unclear. Therefore, this study examined cause‐specific deaths among US dialysis patients by race/ethnicity and age. Methods: This national study included 1,255,640 incident dialysis patients between 1995 and 2010 in the United States Renal Data System. Five cause‐specific mortality rates, including cardiovascular (CVD), infection, malignancy, other known causes (miscellaneous), and unknown, were compared across blacks, Hispanics, and whites overall and stratified by age groups. Findings: After multiple adjustments, Hispanic patients had the lowest risk of mortality for every major cause in almost all ages. Compared with whites, blacks had a lower risk of death from CVD, malignancy and miscellaneous causes in most age groups, but not from infection. In fact, blacks had a higher risk of infection death than whites in ages 18–30 years (HR [95% CI] 1.94 [1.69–2.23]; P < 0.001), 31–40 years (HR 1.51 [1.40–1.63]; P < 0.001) and 41–50 years (HR 1.07 [1.02–1.12]; P = 0.009), which were partially attributed to their higher prevalence of AIDS nephropathy. For each race/ethnicity, more than two‐thirds of infection deaths were due to non‐dialysis related infections. Discussion: Hispanics had the lowest risk for each major cause of death. Blacks were less likely to die than whites from most causes, except infection. The previously reported higher overall mortality rate for younger blacks is attributed to their two‐fold higher infection mortality, which is mostly non‐dialysis related, suggesting a new direction to improve their overall health status. Research is greatly needed to determine social and biological factors that account for the survival gap in dialysis among different racial/ethnic groups.     

Prognostic significance of 25‐hydroxivitamin D entirely explained by a higher comorbidity burden: Experience from a South‐Eastern European Dialysis Cohort

Vitamin D deficiency is still a common problem particularly in the elderly and in individuals with various degrees of renal impairment. The present study aimed to evaluate the association between plasma concentrations of 25(OH)D and death in a large cohort of prevalent patients on hemodialysis (HD) from south‐east Romania, a typical Balkan region. This is an observational prospective study that included a total of 570 patients on maintenance HD. Study patients were classified into three groups by baseline 25(OH)D levels: (1) sufficient 25(OH)D—i.e., >30 ng/mL; (2) insufficient 25(OH)D—i.e., between 10 and 29 ng/mL; and (3) deficient 25(OH)D—i.e., <10 ng/mL. During the follow‐up period of 14 months, 68 patients (11.9%) died, the Kaplan–Meier analysis showing significant differences in all‐cause mortality for chronic kidney disease patients in different 25(OH)D groups (P = 0.002). Unadjusted Cox regression analysis also showed significant differences in survival. The multivariate Cox regression model showed no significant differences in survival according to vitamin D levels. Hazard ratio for death in the “<10 ng/mL” group was 1.619 (P = 0.190) and in the “10–30 ng/mL” group was 0.837 (P = 0.609). In our dialysis population with a high comorbidity burden, low 25(OH)D concentration was not associated with mortality in the adjusted Cox model, suggesting that vitamin D deficiency could represent only a non‐specific marker for a poor health status, with less impact on mortality.     

Pre‐ and Post Hemodialysis Procalcitonin Levels and Their Relationships with Immunoregulatory,Proinflammatory Cytokines in Chronic Hemodialysis Patients

Arteriosclerosis is characterized by stiffening of arteries. The incremental elastic modulus (Einc) measurement is a good marker of arterial wall stiffness. Arteriosclerosis is characterized by stiffening of arteries. Metabolic, inflammatory, and hemodynamic alterations cause structural changes and vascular complications in end‐stage renal disease. The aim of the present study was to evaluate the factors that may affect the development of arteriosclerosis by measurement of Einc in hemodialysis (HD) patients. Thirty‐two patients (16 men and 16 women) on chronic HD with a mean age of 42.2 ± 19.3 (range, 15–80) were included in the study. The carotid Einc was measured to determine arteriosclerosis by high‐resolution echo‐tracking system. Einc measurement was calculated from transcutaneous measurements of carotid arterial internal diameter and wall thickness and carotid pulse pressure. Common carotid compliance (CCC) and distensibility (CCD) were determined from changes in carotid artery diameter during systole and simultaneously measured carotid pulse pressure. Serum levels of calcium (Ca), phosphorus (P), parathormone (PTH), ferritin, C‐reactive protein (CRP), predialysis systolic blood pressure (SBP), predialysis diastolic blood pressure (DBP), pulse pressure (PP), age, HD duration, CCC, and CCD were correlated with Einc in all patients. A significant positive correlation was found between Einc and age (r = 0.40, p < 0.02), SBP (r = 0.39, p < 0.02), PP (r = 0.40, p < 0.02), Ca (r = 0.43, p < 0.01), CRP (r = 0.38, p < 0.02). As expected, Einc was correlated inversely with CCD (r = ?0.77, p < 0.0001). The correlation between Einc and HD duration, DBP, ferritin, P, PTH, and CCC was not significant. In conclusion, the stiffening of carotid artery in HD patients is related not only to hemodynamic changes (increased SBP and PP) but also to metabolic (increased Ca) and inflammatory (increased CRP) responses. Carotid Einc is an accepted independent risk factor for cardiovascular mortality. Because of the positive correlation between Einc and serum Ca, vitamin D and Ca‐containing P binder should be used carefully in HD patients.     

Inverse association between docosahexaenoic acid and mortality in patients on hemodialysis during over 10 years

We have previously conducted a cohort study to investigate n‐3 polyunsaturated fatty acids (PUFAs) in red blood cells (RBCs) and risk of all‐cause mortality in hemodialysis (HD) patients over 5 years and found that n‐3 PUFAs, especially docosahexaenoic acid (DHA), might be an independent predictor of all‐cause mortality. In the present study, we extended the study for another 5 years to determine whether DHA levels in RBCs still predict the mortality of HD patients during a 10‐year study period. The study cohort consisted of 176 patients (64.1 ± 12.0 [mean ± standard deviation] years of age, 96 men and 80 women) under HD treatment. The fatty acid composition of patients' RBCs was analyzed by gas chromatography. During the study period of 10 years, 97 deaths occurred. After adjustment for 10 confounding factors, the hazard ratio of all‐cause mortality of the HD patients in the highest DHA tertile (>8.1%) was 0.52 (95% confidence interval 0.30–0.91) compared with those in the lowest DHA tertile (<7.2%). However, other n‐3 PUFAs such as eicosapentaenoic acid and docosapentaenoic acid (n‐3) did not reveal any significant correlations. The level of DHA in RBCs could be an independent predictor of all‐cause mortality in HD patients even during a long period of follow‐up.     

Pulmonary hypertension in patients on chronic hemodialysis and with heart failure

Pulmonary hypertension (PH) is linked to chronic kidney disease. However, few studies have examined the prevalence, risk factors, or outcomes of PH in patients with chronic hemodialysis and concomitant heart failure. This retrospective cohort study enrolled 160 patients with a history of acute decompensated heart failure after maintenance hemodialysis therapy. All patients were prospectively observed until December 2013 or death. PH was defined as pulmonary artery systolic pressure >35 mmHg, as determined through echocardiography. Fifty‐one (32%) patients had PH, more of whom were female (70% vs. 52%, P = 0.04). The patients with PH had a lower body mass index (21.8 vs. 23.0, P = 0.03), higher cardiothoracic ratio (55% vs. 52%, P = 0.006), larger left atrium (38.5 vs. 35.7 mm, P = 0.01), and an increased proportion of mitral regurgitation (MR) (73% vs. 38%, P < 0.001) compared with the patients who did not have PH. In the multivariate regression analysis, MR was associated most strongly with PH (odds ratio 3.75, 95% confidence interval [CI]: 1.67–8.43, P = 0.001). In the multivariate Cox proportional hazard models, PH was related independently to all‐cause mortality (hazard ratio [HR], 3.11; 95% CI, 1.53–6.31; P = 0.002) and combined cardiovascular events (HR, 2.71; 95% CI, 1.66–4.44; P < 0.001) after the model was adjusted for conventional cardiovascular risk factors. PH is related to MR and independently associated with increased all‐cause mortality and cardiovascular events in patients with chronic hemodialysis and heart failure.     

Comparison of serum albumin,C‐reactive protein and carotid atherosclerosis as predictors of 10‐year mortality in hemodialysis patients

Serum albumin, C‐reactive protein (CRP), and the intima‐medial thickness of the common carotid artery (CA‐IMT) are associated with clinical outcomes in hemodialysis (HD) patients. However, it remains unclear which parameters are more reliable as predictors of long‐term mortality. We measured serum albumin, CRP, and CA‐IMT in 206 HD patients younger than 80 years old, and followed them for the next 10 years. One hundred sixty‐eight patients (age: 57 ± 11 years, time on HD: 11 ± 7 years) were enrolled in the analyses. We divided all patients into three tertiles according to their albumin levels, and conducted multivariate analyses to examine the impact on 10‐year mortality. Seventy‐three (43.5%) patients had expired during the follow‐up. Serum albumin was significantly lower in the expired patients than in the surviving patients (3.8 ± 0.3 vs. 4.0 ± 0.3, P<0.01), while CRP (4.7 ± 5.0 vs. 2.8 ± 3.5 g/L, P=0.01) and CA‐IMT (0.70 ± 0.15 vs. 0.59 ± 0.11 mm, P<0.01) were significantly higher in the expired group. The multivariate analysis revealed that there was a significantly higher risk for total mortality in HD patients with serum albumin <3.8 g/dL (odds ratio 5.04 [95% CI: 1.30–19.60], P=0.02) when compared with those with albumin >4.1 g/dL. In contrast, CRP and CA‐IMT did not associate with total death. It follows from these findings that serum albumin is more superior as a mortality predictor compared with CRP and CA‐IMT in HD patients.     

Association between novel indices of malnutrition-inflammation complex syndrome and cardiovascular disease in hemodialysis patients

Background: Inflammation and malnutrition are recognized as important risk factors for cardiovascular disease (CVD) in hemodialysis (HD) patients. Owing to substantial short‐term variability of serum C‐reactive protein (CRP), more reliable markers of malnutrition–inflammation complex syndrome should be sought with stronger associations with the risk of CVD in HD patients. We therefore explored the clinical relevance of a composite inflammatory index (prognostic inflammatory and nutritional index [PINI]) and of muscle protein mass indicators, derived from creatinine kinetics. Methods: This cross‐sectional study included 177 HD patients (89 women and 88 men; median age, 67.73 years). CVD and risk factors were assessed using medical charts, clinical examination, and biochemical measurements performed at inclusion. Lean body mass (LBM) was derived from creatinine kinetic modeling, whereas PINI was calculated as the ratio (CRP ×α1‐acid‐glycoprotein)/(albumin × transthyretin). Patients were divided according to the presence or absence of established CVD. Results: The traditional risk factors diabetes (odds ratio [OR], 5.83; p = 0.0045) and smoking (OR, 3.50; p < 0.02) were associated with an increase in prevalent CVD. Low transthyretin (OR, 3.79; p < 0.02) and high levels of CRP (OR, 2.70; p < 0.05), PINI (OR, 3.44; p < 0.02), observed LBM (OR, 3.01; p < 0.05), and the ratio of observed/expected LBM (OR, 4.24; p < 0.01) were associated with CVD after adjustment for age, sex, dialysis center, and dialysis vintage. After additional adjustment for diabetes and smoking, only PINI (OR, 2.85; p = 0.0446) and observed/expected LBM (OR, 2.96; p = 0.0361) were still significant. Conclusion: PINI and LBM are associated with increased relative risk for having CVD and could be used routinely to examine the degree of severity of malnutrition inflammation complex syndrome.     

Epicardial fat thickness is associated with impaired coronary flow reserve in hemodialysis patients

Cardiovascular disease (CVD) is the main cause of mortality in hemodialysis (HD) patients. Epicardial fat tissue (EFT) is a new risk factor in CVD. The aim of this study was to evaluate the association between EFT and coronary artery flow reserve (CFR), which is an early indicator of endothelial dysfunction in coronary vessels of HD patients. We performed a cross‐sectional study including 71 chronic HD patients and 65 age‐ and sex‐matched healthy controls. Epicardial fat tissue was significantly higher in HD patients when compared to healthy controls (6.53 ± 1.01 mm vs. 5.79 ± 1.06 mm, respectively, P < 0.001). On transthoracic Doppler echocardiography, CFR values were significantly lower in HD patients when compared to healthy controls (1.73 ± 0.11 vs. 2.32 ± 0.28, P < 0.001). Correlation analysis showed CFR values to be inversely correlated with EFT (r = ?0.287, P < 0.05). Multiple linear regression analysis was used to define independent determinants of EFT in HD patients. Artery flow reserve, age, body mass index and total cholesterol levels were independently correlated with EFT thickness. This study demonstrated that EFT was significantly higher among HD patients compared to healthy controls. In addition, this study was the first to demonstrate an inverse correlation between EFT and CFR in this patient population.     

P-selectin, E-selectin, and CD40L over time in chronic hemodialysis patients

The aim of this study was to measure P-selectin, E-selectin, and CD-4L levels over time in chronic hemodialysis (HD) patients. Thirty stable patients with end-stage renal failure undergoing chronic HD were included in the study. Blood samples were obtained before HD for measurement of P-selectin, E-selectin, and CD-40L. Measurements were performed at month 0 (T0), 3 (T2), 8 (T3), and 13 (T4). The levels of P-selectin, E-selectin, and CD40L were also analyzed according to the occurrence of cardiovascular disease (CVD) and to CVD-related mortality. The levels of CD40L and P-selectin changed significantly over time, decreasing at month 3 and 6 and returning at the T0 levels at month 13. Conversely, E-selectin levels did not. The levels of CD40L, P-selectin and E-selectin over time did not differ significantly between patients with age ≤ 65 or > 65 years, between patients with or without CVD, or between patients who died or who survived during the follow-up. In end-stage renal failure patients undergoing chronic HD, CD40L and P-selectin, but not E-selectin, showed a transient decrease over time, and the serum levels of these molecules were not associated with CVD or with CVD-related mortality.     

Positive association between plasma levels of oxidized low‐density lipoprotein and myeloperoxidase after hemodialysis in patients with diabetic end‐stage renal disease

End‐stage renal disease (ESRD) patients undergoing hemodialysis (HD) have a high prevalence of cardiovascular events. Low‐density lipoprotein (LDL) in dialysis patients has been shown to be susceptible to in vitro peroxidation; therefore, oxidized‐LDL (ox‐LDL) could be generated in these patients. Moreover, myeloperoxidase (MPO) released from activated neutrophils may play a role in the induction of LDL oxidation. The purpose of this study was to investigate the relationship between plasma ox‐LDL levels, plasma MPO levels, and serum high‐sensitivity C‐reactive protein (hs‐CRP) levels during initial HD in patients with diabetic ESRD. Patients (n = 28) had serial venous blood samples drawn before and after HD at the initial, second, and third sessions. Plasma ox‐LDL levels were measured using a specific monoclonal antibody (DLH3), and plasma MPO levels were measured using an enzyme‐linked immunosorbent assay kit. Plasma ox‐LDL levels and MPO levels after a single HD session increased significantly (ox‐LDL, P < 0.005; MPO, P < 0.0001) compared with levels before that HD session. However, the increase was transient since the levels returned to pre‐HD session levels. Additionally, plasma MPO levels showed a positive correlation with plasma ox‐LDL levels during HD (R = 0.62, P = 0.0029). No significant change was observed in serum hs‐CRP levels before and after each HD session. This study demonstrates that plasma MPO levels are directly associated with plasma ox‐LDL levels in diabetic ESRD patients during initial HD. These findings suggest a pivotal role for MPO and ox‐LDL in the progression and acceleration of atherosclerosis in patients undergoing HD.