MO741TUMOR NECROSIS FACTOR ALPHA AND MAGNESIUM ARE LINKED TO CARDIAC VALVE CALCIFICATION IN DIABETIC HEMODIALYSIS PATIENTS

Background and Aims The processes of cardiac valve calcification (CVC) in diabetic hemodialysis (HD) patients are not fully understood. In this context, it is reasonable to complex and comprehensively research the activity of chronic inflammation and magnesium (Mg) imbalance as cardiovascular risk factors in end-stage renal disease (ESRD). The main purpose of the current study was to determine the relationship of tumor necrosis factor alpha (TNF-α) and Mg levels with the presence and severity of CVC in diabetic patients with ESRD. Method We enrolled 136 patients undergoing HD (male/female, 78/58;age, 53.9±1.0 years; HD duration, 47.6±4.2 month) in this observational cross-sectional study. The study was performed in accordance with the provisions of the Declaration of Helsinki last revision. Depending on the presence of type 2 diabetes mellitus (T2DM) all subjects were divided into two groups: the 1st one – non-diabetic patients (n=88); the 2nd one – diabetic patients (n=48). Presence of CVC was detected by ultrasound. The mitral (MVC) and aortic (AVC) valve calcification degree were scored as follows: 1, no calcification; 2, valve thickening without calcification; 3, valve annulus or cusps calcification. Serum content of TNF-α as one of the key proinflammatory cytokine was determined by enzyme-linked immunosorbent assay. Serum Mg concentration was estimated by biochemical method. Data are expressed as means±SEM. Used nonparametric statistics methods: Mann-Whitney U-test, χ2-test, Spearman’s rank R correlations. Results In diabetic HD patients TNF-α content was higher (13.86±1.34 vs. 8.73±0.60 ng/L; Z=3.04, p=0.002) whereas Mg concentration (0.87±0.02 vs. 1.00±0.02 mmol/L; Z=4.91, p<0.001) – lower compared to non-diabetic ones, and in 2nd group indices of TNF-α and Mg were related (Rs=-0.68, p<0.001). CVC was detected in 66.6% of T2DM patients with predominance of calcification of both valves (35.4%) over isolated MVC (20.8%) and AVC (10.4%). Combined MVC and AVC in the 2nd group was observed 2.6 times more often (χ2=8.78, p=0.003) than in the 1st one. For the first time it was established that in diabetic patients with ESRD the presence of CVC closely associated with indices of TNF-α (Rs=0.51, p<0.001) and Mg (Rs=-0.57, p<0.001). The MVC as well as AVC degree were related with the content of TNF-α (Rs=0.49, p<0.001; Rs=0.52, p<0.001) and Mg concentration (Rs=-0.47, p<0.001; Rs=-0.50, p<0.001) respectively. Conclusion (1) T2DM in HD patients is characterized with an increase of serum TNF-α activity and simultaneous decreased of Mg content. (2) In diabetic patients with ESRD, both MVC and AVC are closely linked with the TNF-α accumulation and hypomagnesemia. (3) Chronic inflammation and Mg deficiency can be important factors of CVC progression and very high cardiovascular risk in diabetic HD patients.

MO907ASSOCIATION OF ADIPOSITY AND SARCOPENIA WITH CARDIAC VALVE CALCIFICATION IN PATIENTS ON MAINTENANCE HEMODIALYSIS. A CROSS-SECTIONAL STUDY

Background and Aims Cardiac valve calcification (CVC) is a common disorder in patients with end stage kidney disease (ESKD) and is a predictor of cardiovascular disease and all-cause mortality. Several risk factors are related to CVC in patients with ESKD which include higher age, dyslipidemia, hypertension and diabetes as well as inflammation, bone mineral disease and malnutrition. Moreover, visceral adiposity is associated with disturbed lipid metabolism and proinflammatory activity which could predispose for CVC. Furthermore, sarcopenia and dynapenia is a state common in patients with ESKD. Thus, the aim of this cross-sectional study is to investigate the relationship of adiposity, components of sarcopenia and malnutrition with cardiac valves calcification in patients on chronic hemodialysis. Method Adult patients that were on maintenance hemodialysis were eligible for entering the study. Recruitment took place from March 2019 to September 2020. Exclusion criteria included, patients with less than 6 months on hemodialysis, patients with cancer, inflammatory bowel disease, severe infection, cardiac valve disease prior to dialysis initiation, history of parathyroidectomy and intravenous albumin administration 3 months prior to nutritional assessment. Calcification of heart valves and systolic and diastolic function was assessed by using two-dimensional echocardiography. Nutritional assessment was made using the Geriatric Nutritional Risk Index. Conicity Index, Waist to Height Ratio, the Visceral Adiposity Index, the Lipid Accumulation Product, the Height to Waist Phenotype were also calculated. Waist, calf and mid arm circumference measurement was performed in the end of a midweek dialysis session. Muscle strength was based on a measurement of hand grip strength using a hydraulic hand dynamometer in the non-fistula hand prior to dialysis session. Dynapenia was considered for values < 16 kg in females and < 27kg in males. Serum biochemistry parameters such as total protein, albumin, calcium, phosphate, total cholesterol, triglycerides, HDL, LDL, CRP and iPTH were also measured. Results Overall, 130 patients were included in the study with a mean age of 66±12.47 years (68.5% males) and an average dialysis duration of 4.37±4.95 years. No cardiac valve calcification was found in 34.6%, while both aortic and mitral valve calcification was found in 41.5% of patients. Calcification only of the aortic (AVC) or mitral (MVC) valve was found in 14.6% and 9.2% respectively. Compared to non AVC group, AVC group had significantly higher age, higher prevalence of diastolic dysfunction, CRP values and CRP/albumin ratio and lower albumin to total proteins ratio. Patients with MVC showed significantly higher prevalence of diastolic dysfunction, higher levels of iPTH, CRP/albumin ratio and lower albumin to total proteins ratio. Adiposity, nutritional, anthropometric indices and sarcopenia parameters such as creatinine index, muscle power and physical performance status did not show any difference between all CVC groups. Increased age [OR (95%CI):1.06 (1.00-1.12) p=0.05], diastolic dysfunction [OR (95%CI): 3.07 (1.05-8.92); p=0.04], CRP/albumin ratio were associated with increased risk of AVC, whereas the CRP/albumin ratio appeared as the most powerful risk factor for mitral and for any CVC [OR (95%CI): 3.41 (1.40-8.28); p=0.007, OR (95%CI): 7.98 (2.62-24.98) p<0.001, respectively]. ROC analysis indicated that increased values of CRP/albumin ratio are strong positive predictors of AVC [AUC, 95%CI 0.66 (0.56-0.75) p=0.002], MVC [AUC, 95%CI 0.642 (0.545-0.74) p=0.005] and calcification of any valve [AUC, 95%CI 0.71 (0.615-0.806) p<0.001]. Conclusion Adiposity, nutritional, anthropometric indices and sarcopenia did not show to correlate with CVC in patients with ESKD on hemodialysis. Factors, such as diastolic dysfunction and notably increased CRP/albumin ratio were strong predictors of CVC.

Prognosis and risk factors of cardiac valve calcification in Chinese end-stage renal disease patients

Background Cardiac valve calcification (CVC) was an important risk factor for cardiovascular complication. But the prevalence, clinical features and risk factors for CVC in ESRD patients were not fully clear at present. In this study, we explored the possible risk factors and clinical characteristics of CVC happened in Chinese ESRD patients. Methods We conducted a retrospective case-control study on 433 cases of ESRD patients who received maintenance dialysis (MHD) for at least 3 months in the First Affiliated Hospital of Chongqing Medical University from October 2014 to December 2015. 93 patients were confirmed to happen cardiac valve calcification (CVC) by echocardiography, and 200 patients without CVC in the same period as control, matched with age and gender. The demographic data, clinical characteristics, and laboratory parameters of the two groups were analyzed. Results Of 433 cases of ESRD patients, the average annual incidence of CVC was 30.3%. The most common calcification was in aortic valve, followed by mitral valve. Dialysis age (P = 0.006, OR = 2.25), serum calcium (P = 0.046, OR = 2.04), diabetes (P = 0.037, OR = 1.81), and pulse pressure ( P < 0.001, OR = 3.22) were the risk factors of CVC, but serum albumin ( P = 0.047, OR = 0.54) was a protective factor for CVC. The ESRD patients with CVC were also more likely to suffer from arrhythmia, heart failure and coronary heart disease (CHD), and the all-cause mortality also increased significantly. Conclusions High prevalence of CVC happened in Chinese ESRD patients, which was a risk signal for severe atherosclerosis, more morbidity and mortality of cardiovascular events in ESRD patients. Dialysis age, serum calcium, diabetes, and pulse pressure were the independent risk factors of CVC in ESRD patients, while serum albumin was a protective factor.

P1030ENDOTHELIAL DYSFUNCTION AND CARDIAC VALVE CALCIFICATION IN PATIENTS WITH DIABETIC KIDNEY DISEASE UNDERGOING CHRONIC HEMODIALYSIS

Background and Aims The character of endothelial dysfunction (ED), especially of nitric oxide (NO) system, in patients with diabetic kidney disease (DKD) undergoing chronic hemodialysis (HD) was not asserted enough. In this condition not clearly established the relationship of structural and functional activity of endothelium with the presence and severity of cardiac valve calcification (CVC) as independent predictor of cardiovascular morbidity and mortality. The purpose of the current study was to determine the role of ED in mechanisms of mitral (MVC) and aortic (AVC) valve calcification in HD patients with DKD. Method We enrolled 136 patients undergoing HD (male/female, 78/58; age, 53.9±1.0 years; HD duration, 47.6±4.2 month) in this observational cross-sectional study. According to the study design, depending on the presence of type 2 diabetes mellitus with kidney injury patients were divided into two groups: the 1st one – without DKD (n=88); the 2nd one – with DKD (n=48). All subjects underwent echocardiographical examination for detection of CVC; the MVC and AVC degree were scored as follows: 1, no calcification; 2, valve thickening without calcification; 3, valve annulus or cusps calcification. Vasomotional function of endothelium was assessed using a test with reactive hyperemia (brachial artery flow-mediated dilatation (FMD)). Plasma content of nitrites (NO2), circulating endothelial cells (СECs) and serum concentration of C-reactive protein (CRP) were measured as markers of ED. Data are expressed as means±SEM. Used nonparametric statistics methods: Mann-Whitney U-test, χ2-test, Spearman’s rank R correlations. Results In group of HD patients with DKD indices of СECs (22.3±1.3 vs. 14.2±0.7 × 104/L, Z=4.98, p&lt;0.001), CRP (9.94±1.12 vs. 7.07±1.09 mg/L, Z=3.47, p&lt;0.001) were higher, and NO2 (4.16±0.41 vs. 9.01±1.37 umol/L, Z=3.15, p=0.002), FMD (2.27±0.66 vs. 5.13±0.52%, Z=3.26, p=0.001) – lower compared to the group without diabetes. CVC was detected in 66.6% of patients with DKD with predominance of calcification of both valves (35.4%) over isolated MVC (20.8%) and AVC (10.4 %). Combined valve calcification in the HD patients of the 2nd group was observed 2.6 times more often (χ2=8.78, p=0.003) than in the 1st one. For the first time it was established that in DKD the presence of CVC closely associated with indices of FMD (Rs=-0.59, p&lt;0.001), NO2– (Rs=-0.56, p&lt;0.001), СECs (Rs=0.63, p&lt;0.001) and СRP (Rs=0.54, p&lt;0.001). The MVC as well as AVC degree were related with the level of FMD (Rs=-0.47, p&lt;0.001; Rs=-0.43, p=0.003), content of NO2– (Rs=-0.40, p=0.005; Rs=-0.62, p&lt;0.001), СECs (Rs=0.47, p&lt;0.001; Rs=0.62, p&lt;0.001) and СRP (Rs=0.48, p&lt;0.001; Rs=0.41, p=0.004) concentrations respectively. Conclusion (1) HD patients with DKD are combined with damaged endothelium, disturbance of vasoreactivity and lack of NO. (2) Type 2 diabetes mellitus with kidney injury is characterized by the large-scale combined MVC and AVC, which in turn are closely associated with the ED markers. (3) Complex estimation of the character of CVC and endothelium activity in HD patients with DKD permits a better identification of their cardiovascular risk.

P1391PROGRESSION OF CALCIFICATION AND ITS RISK FACTORS IN CHINESE DIALYSIS PATIENTS

Background and Aims The China Dialysis Calcification Study (CDCS) aims to investigate prevalence and progression of vascular calcification (VC) as well as predictive values of VC in Chinese dialysis patients. This abstract reports VC progression and its risk factors during 4-year follow-up. Method The CDCS is a nationwide, multicenter observational study. 1497 dialysis patients from 24 centers in China were enrolled from 2014-2015 and continuously followed up for 4 years. Coronary artery calcification (CAC), abdominal aortic calcification (AAC) and cardiac valve calcification (CVC) were assessed at baseline and 4-year follow-up. CAC was assessed by Agatston score measured by electron beam computed tomography or multi-detector computed tomography. AAC was assessed by Kauppila score measured by plain lateral lumbar radiograph. CVC was measured by echocardiography. Progression was defined by comparing VC images at baseline with those at 4-year. When CAC/AAC scores at 4-year were greater than baseline, CAC/AAC were considered progressed; when there were more cardiac valves involved at 4-year than baseline, CVC was considered progressed. Logistic progression model was used to investigate the risk factors for calcification progression. Results 711 patients completed 4-year follow-up and 680 of them had calcification tests. Patients had the same type assessments (CAC, AAC or CVC) at both baseline and 4-year were included in analysis. At the 4-year follow-up, 89.4% (608/680) patients had at least one site vascular calcification (CAC, AAC or CVC), CAC affected the highest proportion of patients. Prevalence of CAC, AAC and CVC were 81.0% (517/638), 79.3% (310/391) and 45.6% (308/675), respectively. Progression of CAC was observed in 93.9% (368/392) patients with presence of baseline CAC, and 51.3% (123/240) patients without baseline CAC. CAC progression at 4-year follow-up was stratified by baseline CAC score (Figure1). Progression of AAC was observed in 96.5% (165/171) patients with presence of baseline AAC, and 63.8% (139/218) patients without baseline AAC. AAC progression at 4-year follow-up was stratified by baseline AAC score (Figure2). Progression of CVC from single to double cardiac valve calcification was observed in 33.3% (40/120) patients, and cardiac valve calcification occurred in 33.4% (162/485) patients without baseline CVC after 4-year follow-up. Multivariate logistic regression analysis results are showed in Figure3. Variables significantly increased the risk of calcification progression were baseline calcification score, abdominal obesity, hypertension, and calcium, phosphorous, iPTH during 4-year follow-up. Conclusion In the 4 years follow-up, progression of calcification is common among dialysis patient, and is associated with higher baseline severity, medical history and disease management.

Association between Serum Dickkopf-1 (DKK-1) Glycoprotein and Calcific Deposits on Cardiac Valves and Carotid Intimal-Medial Thickness in Hemodialysis Patients

Background: Cardiac valve calcification (CVC) is common in hemodialysis (HD) patients, and associated with cardiovascular and all-cause mortality. Once believed to be a passive process, it is now understood that the Wnt signaling pathway has a major role. The aim of the current study was to assess the relationship between circulating DKK-1, a negative regulator of the Wnt signaling pathway, and CVC, as well as carotid intimal-medial thickness (CIMT) in HD patients. Methods: We enrolled 74 consecutive adults on maintenance HD. Echocardiographic calcification of the mitral valve (MV) and aortic valve (AV) were detected according to Wilkins score (range 0–4), and the study of Tenenbaum et al. [Int J Cardiol. 2004 Mar;94(1):7–13] (range 0–4), respectively. CVC severity was calculated by a supposed score (range 0–8) that represents the sum of calcification grade of MV and AV. CVC severity was classified into absent (CVC score = 0), mild (CVC score = 1–2), moderate (CVC score = 3–4), and severe (CVC score ≥5). Demographic and biochemical data were collected in addition to serum DKK-1 levels and CIMT. Results: CVC was present in 67 patients (91.0%). There was a highly significant negative correlation between serum DKK-1 level and CVC score (r = –0.492; p ≤ 0.001), as well as CIMT (r = –0.611; p ≤ 0.001). Age and CIMT were independent determinants of CVC. Conclusions: CVC is almost present in all HD patients. DKK-1 seems to have a direct relation with CVC and CIMT in HD patients. Age is the strongest independent determinant of CVC.

Serum Alkaline Phosphatase Level Predicts Cardiac Valve Calcification in Maintenance Hemodialysis Patients

Purpose: Cardiac valve calcification (CVC) is frequently occurred in maintenance hemodialysis (MHD) patients and is associated with cardiovascular and all-cause mortality. This study aimed to evaluate the relationships between risk factors and extent of CVC and further provide the treatment target in MHD patients. Methods: One hundred and forty-five patients who received MHD ≥3 months were enrolled. CVC was assessed by an echocardiographic, semi-quantitative manner called global cardiac calcium scoring system (GCCS), and demographic, clinical, and laboratory parameters including mineral metabolism markers were collected. Results: The average age of the patients was 50 ± 12 years, and 54.5% were men. The mean GCCS was 1.8 ± 2.4; 57.2% of patients had GCCS ≥1. Age, dialysis vintage, serum alkaline phosphatase (ALP), and intact parathyroid hormone levels were positively correlated with CVC, whereas serum albumin levels were negatively related to CVC, based on univariate analysis. With multivariate linear regression analysis, serum ALP was the only bone-derived biomarker that showed significant correlation with CVC. Serum ALP ≥232 U/L was a robust predictor of CVC and was associated with the likelihood of GCCS ≥1 (OR 3.92, 95% CI 1.37–11.2, p = 0.011). The decision tree model was used to identify ALP ≥232 U/L and age ≥60 years as important determinative variables in the prediction of CVC in MHD patients. Conclusion: Serum ALP level is significantly associated with CVC in MHD patients. ALP is suggested to be a promising interventional target for cardiovascular calcification in MHD patients.