Cardiac Valvular Calcification Research Articles

Platelet activating factor acetylhydrolase is associated with cardiac valvular calcification in dialysis patients

Abstract Objectives The cardiovascular mortality risk is greatly increased in patients with chronic kidney disease (CKD), especially in dialysis patients, due to atherosclerosis. Platelet activating factor acetylhydrolase (PAF-AH) is an enzyme that hydrolyzes platelet activating factor (PAF). Valvular calcifications and PAF-AH are associated with atherosclerosis. However, little is known about the status of PAF-AH activity and valvular calcification in dialysis patients. Therefore, the aim of this study was to investigate the status of these parameters in CKD patients. Methods This study included 92 chronic renal failure (CRF) (dialysis group), and 86 CKD patients (non-dialysis group). Echocardiography was performed to assess valvular calcification. Results There was no significant difference between the dialysis and CKD groups in terms of PAF-AH activities. However, when comparisons were stratified according to the presence of valve calcification, higher PAF-AH activity and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were evident in patients with calcification compared to those without. Additionally, the CRF group also exhibited elevated PAF-AH and NT-proBNP levels. While elevated NT-proBNP persisted in the CKD group, in contrast, changes in PAF-AH were not significant. Conclusions The results of this study suggest that high PAF-AH and NT-proBNP levels are associated with valvular calcification in dialysis patients. Both biomarkers may be used as a risk factor for calcification. Furthermore, inhibition of PAF-AH activity may be a treatment target to reduce calcification.

Association of Cardiac Valve Calcification and 1-year Mortality after Lower-extremity Amputation in Diabetic Patients: A Retrospective Study.

Cardiac valve calcification predisposes patients to a higher risk of adverse cardiovascular events. This study aimed to investigate the association between cardiac valve calcification and 1-year mortality in diabetic patients after lower-extremity amputation. This was a retrospective study conducted on the clinical data of diabetic patients who underwent lower-extremity amputation admitted to the Sun Yat-sen Memorial Hospital, Guangzhou, Guangdong, China for diabetic foot ulcers needed lower extremity amputation surgery between July 2017 and March 2021. Detailed preoperative medical assessments were performed and recorded. Cardiac valve calcification was assessed using echocardiography at baseline. Oneyear follow-up assessments were conducted and included clinical visits, hospital record assessments, and telephone reviews to obtain the survival status of patients. Ninety-three diabetic patients participated in the study. The 1-year follow-up mortality rate after amputation was 24.7%. Compared to the survival group, the prevalence of cardiac valve calcification and the Revised Cardiac Risk Index (RCRI) were higher in the mortality group. In the Cox regression analysis, cardiac valvular calcification (HR=3.427, 95% CI=1.125- 10.443, p =0.030) was found to be an independent predictor of all-cause mortality after amputation. In addition, the patients with both aortic valve calcification and mitral annular calcification had a higher all-cause mortality rate (50%). Receiver operator characteristic curve analysis showed a stronger predictive ability when using a combination of calcified valve number and RCRI (AUC=0.786 95%, CI=0.676-0.896, p =0.000). In diabetic patients after lower-extremity amputation, cardiac valve calcification was associated with all-cause mortality during 1-year follow-up. Combination of calcified valve number and RCRI score showed a stronger predictive value for mortality.

Clinical Implication of Consistently Strict Phosphate Control for Coronary and Valvular Calcification in Incident Patients Undergoing Hemodialysis.

Serum phosphate control is crucial for the progression of vascular and valvular calcifications. Strict phosphate control is recently suggested; however, there is a lack of convincing evidence. Therefore, we explored the effects of strict phosphate control on vascular and valvular calcifications in incident patients undergoing hemodialysis. A total of 64 patients undergoing hemodialysis from our previous randomized controlled trial were included in this study. Coronary artery calcification score (CACS) and cardiac valvular calcification score (CVCS) were evaluated using computed tomography and ultrasound cardiography at baseline and 18 months after the initiation of hemodialysis. The absolute changes in CACS (ΔCACS) and CVCS (ΔCVCS) and the percent change in CACS (%ΔCACS) and CVCS (%ΔCVCS) were calculated. Serum phosphate level was measured at 6, 12, and 18 months after the initiation of hemodialysis. Moreover, phosphate control status was evaluated using the area under the curve (AUC) by the amount of time spent with a serum phosphate level of ≥ 4.5 mg/dL and the extent to which this threshold exceeded over the observation period. ΔCACS, %ΔCACS, ΔCVCS, and %ΔCVCS were significantly lower in the low AUC group than in the high AUC group. ΔCACS and %ΔCACS were also significantly lower. ΔCVCS and %ΔCVCS tended to be lower in patients whose serum phosphate level never exceeded 4.5 mg/dL than in those whose serum phosphate level continuously exceeded 4.5 mg/dL. AUC significantly correlated with ΔCACS and ΔCVCS. Consistently strict phosphate control may slow the progression of coronary and valvular calcifications in incident patients undergoing hemodialysis.

Soluble urokinase plasminogen activator receptor is associated with cardiovascular calcification in peritoneal dialysis patients.

Cardiovascular disease (CVD) is an important cause of morbidity and mortality in peritoneal dialysis (PD) patients. Cardiovascular calcification (CVC) is highly prevalent in PD patients and could predict their cardiovascular mortality. Soluble urokinase plasminogen activator receptor (suPAR) is closely associated with coronary artery calcification in hemodialysis patients and is an important predictor of CVD. However, the role of suPAR in PD patients is poorly understood. We investigated the relationship between serum suPAR and CVC in PD patients. Abdominal aortic calcification (AAC) was assessed by lateral lumbar radiography, coronary artery calcification (CAC) by multi-slice computed tomography, and cardiac valvular calcification (ValvC) by echocardiography. CVC was defined as confirmed presence of calcification in one site (AAC, CAC, or ValvC). Patients were divided into CVC group and non-CVC group. Demographic characteristics, biochemical variables, comorbidities, PD regimen, serum suPAR, and medication were compared between the two groups. Logistic regression was conducted to determine association between serum suPAR and presence of CVC. The receiver-operator curve (ROC) was plotted to calculate the area under the curve (AUC) for suPAR to identify CVC and ValvC. Of 226 PD patients, 111 (49.1%) had AAC, 155 (68.6%) had CAC, and 26 (11.5%) had ValvC. There were significant differences in age, BMI, diabetes, white blood cell, phosphorus, hs-CRP, suPAR, time on dialysis, total volume of dialysate, ultrafiltration, volume of urine, and Kt/V between CVC and non-CVC group. Serum suPAR was associated with CVC by multivariate logistic regression analysis in PD patients, especially in elderly patients. The levels of serum suPAR were closely related to the degree of AAC, CAC, and ValvC in PD patients. The incidence of CVC was higher in patients with higher levels of suPAR. The ROC curve showed that serum suPAR had a predictive value for CVC (AUC = 0.651), especially for ValvC (AUC = 0.828). Cardiovascular calcification is prevalent in PD patients. High levels of serum suPAR are associated with cardiovascular calcification in PD patients, especially in elderly patients.

Predictive role of cardiac valvular calcification in all-cause mortality of Chinese initial haemodialysis patients: a follow-up study of 4 years

BackgroundCardiac valvular calcification (CVC) is prevalent in haemodialysis (HD) patients. Its association with mortality in Chinese incident haemodialysis (IHD) patients remains unknown.MethodsA total of 224 IHD patients who had just begun HD therapy at Zhongshan Hospital, Fudan University, were enrolled and divided into two groups according to the detection of cardiac valvular calcification (CVC) by echocardiography. The patients were followed for a median of 4 years for all-cause mortality and cardiovascular mortality.ResultsDuring follow-up, 56 (25.0%) patients died, including 29 (51.8%) of cardiovascular disease. The adjusted HR related to all-cause mortality was 2.14 (95% CI, 1.05–4.39) for patients with cardiac valvular calcification. However, CVC was not an independent risk factor for cardiovascular mortality in patients who had just begun HD therapy.ConclusionCVC at baseline is an independent risk factor for all-cause mortality in HD patients and makes an independent contribution to the prediction of all-cause mortality. These findings support the use of echocardiography at the beginning of HD.

Inactive Matrix Gla Protein in Relation to Renal and Cardiac Functions and Cardiac Valvular Calcification Among Type 2 Diabetes Patients.

Matrix Gla protein (MGP) is a robust innate suppressor of the detrimental process of vascular calcification in the human body. The interrelationship between circulating MGP levels and renal and cardiac dysfunction, besides echocardiographic calcification score (ECS) was investigated in a sample of type 2 diabetes (T2D) patients. The study included 130 subjects. They were 95 patients with T2D and 35 age- and sex-matched healthy controls. Patients were further subdivided into 52 T2D patients without DKD (eGFR ⩾ 60 ml/minute/1.73 m²) and 43 T2D persons with DKD (eGFR > 60 ml/minute/1.73 m²). Serum MGP levels, determined by ELISA, renal function tests, lipid profile, and echocardiography were studied in all participants. Significantly elevated circulating inactive MGP level was noted in individuals having T2D compared to controls. It correlated negatively with eGFR and left ventricular (LV) diastolic and systolic functions and positively with indices of LV hypertrophy. ECS was significantly increased in both T2D groups compared to controls and in DKD group compared to the diabetic group without DKD. A significant positive correlation was observed between inactive MGP and ECS. Serum inactive MGP may contribute to the development of DKD and to the associated process of cardiac valvular calcification. It may be a beneficial diagnostic marker for early prediction of cardiac calcification and preclinical LV systolic and diastolic dysfunction in T2D patients, especially in those complicated with DKD.

Comparison of CT acquired cardiac valvular calcification scores in hemodialysis and peritoneal dialysis patients undergoing open heart surgery

Study objectiveData is scarce regarding which dialysis modality portends more severe cardiac valvular calcification (CVC). Our aim was to compare the degree of CVC in hemodialysis (HD) and peritoneal dialysis (PD) patient cohorts prior to open heart surgery (OHS) using a CT calcium score. Design, setting, and participantsDialysis patients who underwent OHS at our institution from 2009 to 2019 and who had pre-surgical cardiac CT were included in our study. We obtained duration of dialysis modality prior to their surgical date. There were two study cohorts to evaluate outcomes of interest: mitral and aortic calcification. CVC was assessed using the Agatston score. Logistic regression was performed to test for the association of PD and HD cumulative dialysis duration with presence of CVC. ResultsA total of 214 and 166 patients met inclusion for the mitral and aortic strata, respectively. Age, female sex, and BMI were associated with higher odds of presence of mitral calcification. Age and BMI were associated with higher odds of presence of aortic calcification, while female sex was associated with lower odds in the aortic strata. Cumulative years on PD and cumulative years on HD were not significantly associated with presence of CVC in either cohort. ConclusionPresence of mitral and aortic calcification for patients undergoing OHS was not significantly associated with cumulative length of PD or HD after adjusting for age, gender, and BMI suggesting that there may be more factors at play in the progression of CVC in end stage renal disease patients than what was previously established.

Abdominal aortic calcification as prognostic marker in continuous ambulatory peritoneal dialysis.

Patients with chronic kidney disease (CKD) on dialysis are at high risk of cardiovascular complications and mortality. We investigated the prognostic role of presence and severity of abdominal aortic calcification (AAC) detected by a simple lateral lumbar X-ray as a risk marker in CAPD. A prospective study was undertaken in 45 patients on CAPD (continuous ambulatory peritoneal dialysis). Lateral lumbar films of consented patients were checked for the presence of AAC at the level of L1-L4 lumbar vertebrae. The severity of aortic calcification was graded as per Antero-Posterior Severity Score (APSS). These APSS grades were correlated with the patient's demographic, biochemical, and echocardiographic findings. The patients were followed up prospectively for one year. 45 patients formed the study group. Mean standard deviation (SD) age and body mass index (BMI) were 57.2 (11.9) years and 25.8 (4.7) kg/m2, respectively. Males constituted 62% of the cohort. Average duration of dialysis was 34.3 months. Diabetic kidney disease was seen in 75%. The prevalence of AAC was 47%. AAC was positively correlated with age of patient (r=0.378; p=0.01). No correlation with BMI, diabetes, hypertension, dialysis vintage, serum calcium, phosphorus, and PTH was seen; whereas a trend towards negative correlation with alkaline phosphatase was seen. Mitral valve calcification had a significant association with APSS severity. Patients with severe APSS (≥4) had poor survival, with an average survival of 37 months (Log-rank test p=0.026). ROC analysis showed that APSS 3 predicted 1-year mortality with a specificity of 89% and sensitivity of 62% (AUC=0.73) (p=0.007). Abdominal aortic calcification was present in 47% of our CAPD patients. A simple lateral pelvic skiagram can be utilized as a cost-effective tool in prediction of All-cause mortality and cardiac valvular calcification.

Sex-specific correlates of valvular and arterial calcification burden in patients with moderate aortic stenosis

IntroductionThere are significant sex differences in the prevalence and severity of cardiac calcifying processes. Women harbour more severe mitral annular calcification (MAC), while men exhibit worse aortic valve (AVC) and...

Comparison of CT acquired valvular calcification scores in hemodialysis vs peritoneal dialysis patients undergoing open heart surgery

Abstract Background Several factors have been identified as independent risk factors for cardiac valvular calcification (CVC), including but not limited to age, inflammatory conditions, loss of calcification inhibitors, and dysregulated bone mineral metabolism. However, data is scarce regarding which dialysis modality portends more severe CVC. Purpose Our aim was to compare the degree of valvular calcification in hemodialysis (HD) and peritoneal dialysis (PD) patients prior to open heart surgery (OHS) using a computed CT calcium score. Methods Dialysis patients who underwent OHS at our institution from 2009–2019 who had a pre-surgical cardiac CT were grouped according to duration of dialysis modality prior to their surgical date. There were two study cohorts to evaluate outcomes of interest: mitral and aortic calcification. We included the first surgical record per patient for patients undergoing isolated CABG, or CABG+valve surgery (repair or replacement), or valve-only surgery (repair or replacement). To evaluate mitral calcification, we excluded any patients undergoing any mitral valve surgery (repair or replacement). We also excluded patients with a history of mitral valve repair/replacement. To evaluate aortic calcification, we excluded any patients undergoing any aortic valve surgery (repair or replacement). We also excluded patients with a history of aortic valve repair/replacement. Mitral annular and aortic valvular calcification were assessed using the Agatston score. Logistic regression was performed to test for the association of PD and HD cumulative dialysis duration with presence of valvular calcification. Results A total of 296 patients met inclusion criteria for at least one of the strata in our study. Of those, 214 met inclusion for the mitral strata, and 166 met criteria for the aortic strata (Table 1). In the logistic regression model for the mitral strata, age and female sex were associated with higher odds of presence of mitral calcification (Figure 1). Cumulative years on PD and cumulative years on HD were not significantly associated with presence of mitral calcification. In the logistic regression model for the aortic strata, age was associated with higher odds of presence of aortic calcification, while female sex was associated with lower odds (Figure 1). Cumulative years on PD and cumulative years on HD were not significantly associated with presence of aortic calcification. Conclusion Presence of mitral and aortic calcification for patients undergoing OHS was not significantly associated with cumulative length of PD or HD after adjusting for age and gender, suggesting that there may be more factors at play in the progression of valvular calcification in end stage renal disease patients than what was previously thought. Funding Acknowledgement Type of funding sources: None.

Prevalence and Correlates of Cardiovascular Calcification and Its Prognostic Effects Among Patients With Chronic Kidney Disease: Results From the C-STRIDE Study.

Background and Aims: The purpose of this study was to identify the characteristics and risk factors for cardiovascular calcification, and its relationship to prognosis, in patients with chronic kidney disease (CKD) stages 1–4.Methods: Cardiovascular calcification was evaluated at baseline by lateral abdominal radiography to detect abdominal aortic calcifications (AAC), and by echocardiogram to detect cardiac valvular calcifications (CVC), respectively. Demographic and laboratory data were collected and analyzed. Univariate and multivariable logistic regression model was used to explore the factors associated with the indicators of cardiovascular calcification, while Cox proportional hazards regression was used to examine the association between AAC/CVC and incidence of cardiovascular events and all-cause mortality.Results: A subgroup of 2,235 patients with measurement of AAC in the C-STRIDE study and a subgroup of 2,756 patients with CVC were included in the analysis. AAC was present in 206 patients (9.22%) and CVC was present in 163 patients (5.91%). Age, gender, history of cardiovascular diseases, smoking, hypertension, diabetes, levels of hemoglobin, low-density lipoprotein cholesterol, and uric acid were associated with prevalence of AAC, while only age, history of cardiovascular diseases, levels of serum albumin and low-density lipoprotein cholesterol were associated with prevalence of CVC (all p < 0.05).Survival analyses showed that cardiovascular events and all-cause mortality were significantly greater in patients with AACor with CVC (all p-values for log-rank tests <0.05). After adjustment for age, sex and estimated glomerular filtration rate (eGFR), AAC was associated with increased risk of all-cause mortality (hazard ratio = 1.67[95% confidence interval: 0.99, 2.79]), while CVC associated with that of cardiovascular events only among patients with comparatively normal eGFR (≥45 ml/min/1.73m2) (hazard ratio = 1.99 [0.98, 4.03]).Conclusion: Demographic and traditional cardiovascular risk factors were associated with cardiovascular calcification, especially AAC. AAC may be associated with risk of death for patients CKD of any severity, while CVC as a possible risk factor for cardiovascular disease only among those with mild to moderate CKD. Assessments of vascular calcification are need to be advanced to patients in the early and middle stages of chronic kidney disease and to initiate appropriate preventive measures earlier.

Cardiac valve calcification prevalence and association with neutrophil-to-lymphocyte ratio in newly diagnosed patients with non-dialysis chronic kidney disease stage 3-5.

Cardiac valvular calcification (CVC) is the main cause of cardiovascular disease and all-cause death in patients with chronic kidney disease (CKD). However, the relationship between Neutrophil lymphocyte ratio (NLR) and CVC in patients with CKD is not clear. In this study, we aimed to investigate the prevalence of CVC in newly diagnosed patients with non-dialysis CKD stage 3-5 and evaluate the correlation between NLR and CVC. A total of 483 newly diagnosed patients with non-dialysis CKD stage 3-5 were included. According to the presence of CVC, these patients were retrospectively divided into two groups: CVC group and non-CVC group. CVC was found in 80 patients (16.56 %), 53 (10.97 %) of whom had only aortic valve calcification (AVC), 18 (3.73 %) had mitral valve calcification (MVC), and 9 (1.86 %) had both AVC and MVC. The level of NLR in the CVC group was significantly higher than that in the non-CVC group (p=0.002). Multivariate logistic regression analysis showed that NLR was an independent risk factor for CVC (95% CI 1.017~1.225, p=0.020). ROC curve analysis showed that the area under the curve of NLR for predicting CVC was 0.610 (95% CI 0.543-0.676, p=0.002). The best cut-off point of NLR was 3.340, with a sensitivity of 49.4 % and a specificity of 70.0 %. CVC is not uncommon in newly diagnosed patients with non-dialysis CKD stage 3-5, and NLR is an independent risk factor for CVC (Tab. 4, Fig. 1, Ref. 34).

A novel deep intronic variant strongly associates with Alkaptonuria

Alkaptonuria is a rare autosomal recessive inherited disorder of tyrosine metabolism, which causes ochronosis, arthropathy, cardiac valvular calcification, and urolithiasis. The epidemiology of alkaptonuria in East Asia is not clear. In this study, patients diagnosed with alkaptonuria from January 2010 to June 2020 were reviewed. Their clinical and molecular features were further compared with those of patients from other countries. Three patients were found to have alkaptonuria. Mutation analyses of the homogentisate 1,2-dioxygenase gene (HGD) showed four novel variants c.16-2063 A > C, p.(Thr196Ile), p.(Gly344AspfsTer25), and p.(Gly362Arg) in six mutated alleles (83.3%). RNA sequencing revealed that c.16-2063 A > C activates a cryptic exon, causing protein truncation p.(Tyr5_Ile6insValTer17). A literature search identified another 6 patients with alkaptonuria in East Asia; including our cases, 13 of the 18 mutated alleles have not been reported elsewhere in the world. Alkaptonuria is rare in Taiwan and East Asia, with HGD variants being mostly novel and private.

Relation Between Matrix Gla Protein and Cardiac Vavular Calcifications in Haemodialysis Patients

Abstract Background Heart valve calcification was first described a century ago. Its pathologic features were first described by Dewitsky in 1910. Valvular heart disease is common in end-stage renal disease patients. The incidence of valvular heart disease is 5 times greater in dialysis patients than in the general population MGP plays a key role in the inhibition of tissue calcification, which was demonstrated in MGP-deficient mice Objective To detect the prevalence of cardiac valvular calcifications among end stage renal disease patients on prevalent haemodialysis and its relation to Matirx Gla protein. Patients and Methods Enrolled patients were recruited from Ain shams hospitals, divided into two groups according to the presence/absence of valvular calcifications on echocardiographic examination as follows: Group A: included patients with valvular calcifications. Group B: included patients without valvular calcifications. Results In current study, 19 (23.8%) patients showed mitral calcification, 30 (37.5%) showed aortic calcification and 44 (55.0%) had calcification in general as 5 patients had both mitral and aortic calcifications. In current study, the patient who had calcification were significantly older, heavier in weight and BMI and were had HD for longer than those who didn’t have calcification. Patient who had calcification had lower levels of both platelets and urea than those who didn’t have calcification. In current study, the mean ucMGP was 549.5 ± 160.1 and the patient who had calcification had higher levels of ucMGP than those who did not have calcification. There was a significant positive correlation between age, weight, BMI, duration of HD and ucMGP. And there was a significant negative correlation between platelet count, serum albumin and ucMGP. Conclusion In current study, MGP was able to significantly differentiate between patients with and without calcification at a cutoff point (&amp;gt;564 pg/mlv) with sensitivity 86.36%, specificity 97.22. Our study confirmed that older age, hypertension, diabetes mellitus low platelet, higher ucMGP and blood urea are the most predictive parameters of valvular calcifications in hemodialysis patients. Other markers were not associated with valvular calcifications. ucMGP serum levels can significantly differentiate between HD cases with valvular calcifications and those not and those who had findings in CXR.

Hyperphosphatemia and Cardiovascular Disease.

Hyperphosphatemia or even serum phosphate levels within the “normal laboratory range” are highly associated with increased cardiovascular disease risk and mortality in the general population and patients suffering from chronic kidney disease (CKD). As the kidney function declines, serum phosphate levels rise and subsequently induce the development of hypertension, vascular calcification, cardiac valvular calcification, atherosclerosis, left ventricular hypertrophy and myocardial fibrosis by distinct mechanisms. Therefore, phosphate is considered as a promising therapeutic target to improve the cardiovascular outcome in CKD patients. The current therapeutic strategies are based on dietary and pharmacological reduction of serum phosphate levels to prevent hyperphosphatemia in CKD patients. Large randomized clinical trials with hard endpoints are urgently needed to establish a causal relationship between phosphate excess and cardiovascular disease (CVD) and to determine if lowering serum phosphate constitutes an effective intervention for the prevention and treatment of CVD.

Prediction of All-Cause Mortality Using an Echocardiography-Based Risk Score in Hemodialysis Patients

Aim: To derive an echocardiography-based prognostic score for a 3-year risk of mortality in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD). Methods: 173 ESRD patients hospitalized in the second affiliated hospital of Soochow University from January 1, 2010, to July 31, 2016, were enrolled and followed up for 3 years. All subjects began to receive HD from recruitment. Baseline clinical and echocardiographic parameters were collected and screened for risk factors using univariate and multivariate analysis. The prognostic value of echocardiographic indexes was determined by concordance indexes and reclassification assay. Restricted cubic spline models (RCS) and forest plots were employed to visualize the association between risk factors and all-cause mortality. A multivariate nomogram including the identified factors was developed to estimate the prognosis. Results: After multivariate adjustment for advanced age, hypertension, diabetes, and decreased hemoglobin (Hb), echocardiographic indexes including left atrial diameter index (LADI), cardiac valvular calcification, and moderate to severe cardiac valve regurgitation were independently associated with the risk of 3-year mortality in HD patients. RCS showed that age, Hb, and LADI were positively associated with the risk of mortality. Adding multiple echocardiographic indexes to a basic model containing age, hypertension, diabetes, and Hb increased the concordance index and improved reclassification. A multivariate Cox model-derived nomogram showed the association between each factor and mortality by the end of follow-up. Conclusions: Echocardiographic indexes showed independent predictive power for mortality in ESRD patients and may constitute a promising prognostic tool in this population.

P1430BETA C-TERMINAL TELOPEPTIDE OF TYPE I COLLAGEN: CORRELATIONS WITH MINERAL METABOLISM PARAMETERS AND CARDIAC VALVULAR CALCIFICATIONS IN A COHORT OF HEAMODIALYSIS PATIENTS

Abstract Background and Aims Beta-carboxyterminal telopeptide of type I collagen (beta-CTx) is considered a marker of bone resorption in patients affected by osteoporosis. Nevertheless, its role in mineral bone disorder (MBD) of CKD patients is not clear. The aim of this study was to explore in a group of haemodialysis patients (HDp): 1) The levels of beta-CTx; 2) The correlation between beta-CTx levels and other mineral metabolism (MM) parameters; 3) The association between beta-CTx and CKD-MBD specific therapy 4) The relation between beta-CTx and cardiac valvular calcifications (VC). Method We studied a group of 21 HDp (F/M 9/12, age 68[54-78] years) randomly selected from the HDp actually followed-up in our Department. Dialysis vintage was 52[23-80] months. All HDp were on a three-weekly hemodialysis schedule, with a prescribed dialysate calcium of 1.5 mmol/l. Before the first dialysis session of the week, after the long interdialytic interval, the levels of beta-CTx, total and ionized calcium (tCa and iCa), Phosphorus (P), Magnesium (Mg), intact PTH (iPTH), total and bone isoform of alkaline phosphatase (tALP and bALP), 25-hydroxyvitamin D (25OHVD), 1,25-dihydroxyvitamin D (1,25OH2VD), and other general biochemical parameters were measured (Figure 1). At the same time, data concerning MM therapies were recorded. In all the studied patients, the presence of VC was searched in the the most recent echocardiographic study. Results Beta-CTx levels showed a significant positive correlation with tALP (r 0.92, p &amp;lt;0.0001), bALP (r 0.89, p &amp;lt;0.0001) and iPTH (r 0.87, p&amp;lt;0.0001) and a negative correlation with tCa (r – 0.43, p=0.05) and iCa (r – 0.52, p=0.01). No significant correlation was found with the other MM and general biochemical parameters and with the general features of the studied cohort. 18 patients (85.7%) were taking P binders (72.2% Ca-based and 27.8% Ca-free). In 20 patients (95.2%) vitamin D therapy, either in the natural, active or both natural and active form (35%, 15% and 50%, respectively) was prescribed. 6 patients (28.6%) were in therapy with Cinacalcet. No difference was found in beta-CTx levels according to the presence and the type of each of the above mentioned therapies. Conclusion Taking into account the limitations of this preliminary small size observational study, our data showed that beta-CTx levels are high in HDp. Beta-CTx correlates with iPTH, tALP and bALP. The negative correlation with tCa and iCa probably might be influenced by the negative correlation between iPTH and serum Calcium. Beta-CTx levels are not associated with CKD-MBD specific therapy or with cardiac valvular calcifications. Further prospective and randomized studies, including a higher number of HDp and possibly bone histology are needed to elucidate the possible role of beta-CTx as a marker of bone disease in HDp.

The influence of cardiac valvular calcification on all-cause and cardiovascular mortality in maintenance hemodialysis patients.

To investigate the effect of cardiac valve calcification (CVC) on all-cause and cardiovascular mortality in maintenance hemodialysis (MHD) patients. A retrospective cohort study was conducted in 183 long-term hemodialysis patients with complete follow-up data from January 1, 2012, to December 30, 2015. The baseline data between CVC and non-CVC groups were compared. Kaplan-Meier method was used to analyze all-cause and cardiovascular mortality. The effect of CVC on prognosis was analyzed using the Cox proportional hazardregressionmodel and subgroup analysis. Among 183 patients under hemodialysis, 104 (56.8%) were males, with an average age of 56.1 ± 17.0years and 68 (37.2%) were complicated with valvular calcification. The median follow-up period was 30.8months. All-cause and cardiovascular mortality were 50% vs. 14.8% and 25% vs. 7.0% in the CVC and non-CVC groups, respectively (P < 0.05). Kaplan-Meier indicated that differences in all-cause and cardiovascular mortality were statistically significant between the two groups (P < 0.001). Cox regression analysis showed that CVC significantly increased all-cause (hazards ratio [HR] 2.161 [1.083-4.315]) and cardiovascular mortality (3.435 [1.222-9.651]) after adjusting for multiple factors. Meanwhile, CVC also increases the incidence of new-onset cardiovascular events. Subgroup analysis revealed that all-cause and cardiovascular mortality were significantly higher in patients with aortic valve calcification (AVC) than in patients with mitral valve calcification (MVC). Multivariate calibration showed that AVC increased the risk of cardiovascular death (HR 5.486 [1.802-16.702]) (P < 0.05), whereas MVC did not. By further comparing the echocardiographic data of the two groups, the incidence of LVH and pulmonary hypertension in the AVC group was significantly higher than that in the MVC group. Valve calcification increases the risk of all-cause and cardiovascular mortality in MHD patients, also new-onset cardiovascular events, and aortic valve calcification contributes more to the risk of cardiovascular mortality.

SUN-225 Significant association between posterior mitral annular calcification and the mortality in maintenance hemodialysis patients

It is widely recognized that maintenance dialysis patients have many cardiovascular complications causing morbidity and mortality. The mortality rate due to cardiovascular disease (CVD) in maintenance dialysis patients is 10-30 times higher than that in the general population, making it a leading cause of death. Thus, risk stratification for CVD mortality is clinically important for improving survival in such individuals. Vascular calcification (VC) is common in maintenance hemodialysis patients and results in increased cardiovascular disease and both overall and cardiovascular mortality. Cardiac valve calcification, also frequently seen in hemodialysis patients, has been regarded as a marker of atherosclerosis, and its existence could not only affect therapeutic outcomes after coronary intervention, but is also predict factor of CVD morbidity. Furthermore, in maintenance hemodialysis patient cardiac valvular calcification is also correlated with mortality. However, no detailed investigation has been done on which part of the heart valve calcification is associated with mortality. The purpose of this study was to investigate the prevalence of calcification according to the location of heart valve leaflets and mitral annulus, and to clarify the association between them and the mortality in maintenance hemodialysis patients. This was a retrospective cohort study of a clinical database containing the medical records of 130 patients on maintenance HD who received hemodialysis during the period between February 2016 and January 2017 in a single center. Totally, 120 patients were involved in this study. Of whom, 72 (65.0%) patients were male, the mean age was 71.1 ± 11.1 years, and the median hemodialysis duration was 129.2 ± 96.4 months. Cardiac valve calcification was seen in 50 (41.7%) patients: 29 (24.2%) had aortic valve calcification and 41 (34.2%) had mitral annulus calcification (MAC) (Anterior MAC, 8 [6.6%], and posterior MAC, 41 [34.2%]) (Figure 1). A total of 22 (18.3%) patients died, including 11 (9.2%) as a result of cardiovascular death. Patients without pMAC had a higher all-cause survival rate compared with those with pMAC (88.6% versus 68.3%, log-rank P Figure2A). Patients without pMAC had a higher cardiovascular survival rate compared with those with pMAC (94.6% versus 79.4%, log-rank P=0.01, Figure2B). Multivariate cox proportional hazards analysis revealed that posterior MAC was independently positively correlated with all-cause death and cardiovascular death (HR for all-cause death, 5.924; P<0.01, HR for all-cause death and cardiovascular death, 17.746; P=0.01). The presence of posterior MAC, which is cheap and easy to detect with echocardiography, can predict all causes of death and cardiovascular death. This findings may further help risk stratification of maintenance hemodialysis patients in any dialysis center, including small dialysis center with limited medical resources, such as developing countries.

Non-alcoholic fatty liver disease and cardiovascular diseases: features of the comorbid course

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. NAFLD is a continuum of histological lesions of the liver from steatosis, non-alcoholic steatohepatitis (NASH), NASH with fibrosis, cirrhosis to hepatocellular carcinoma. The pathophysiology encompasses a dysfunction in fatty tissue (sub-cutaneous and visceral) associated with insulin-resistance and metabolic inflammation.Patients with NAFLD are at a higher risk of developing cardiovascular disease. NAFLD adversely affects not only the coronary arteries (promoting accelerated coronary atherosclerosis) but also all other anatomical structures of the heart, conferring an increased risk of cardiomyopathy (mainly left ventricular diastolic dysfunction and hypertrophy, leading to the development of congestive heart failure), cardiac valvular calcification (mainly aorticvalve sclerosis), cardiac arrhythmias (mainly atrial fibrillation) and some cardiac conduction defects. Studies have shown that the association between NAFLD and atherosclerotic cardiovascular diseases is independent of shared risk factors.