Cardiac Calcification Research Articles

Cardiac valves calcification and HDL-C in patients with aortic valve sclerosis

Background and Aims : Growing evidence has demonstrated the influence of many atherosclerotic risk factors on cardiac valve calcification (CVC), which is correlated with higher cardiovascular and all-cause mortality risk. The aim of this study was to investigate the effect of high-density lipoprotein cholesterol (HDL-C) on both mitral and aortic valve calcification (AVC) in individuals with AVC.Methods: Sixty-four patients with AVC, prior the intervention, were prospectively enrolled and underwent blood sampling for biochemical analysis and multi-slice computed tomography (MSCT) without contrast. Primary end points were the quantification of (1) mitral annulus calcification (MAC) and AVC, calculated by the median MAC and AVC scores (both were defined by Agatston units (AU) according to MSCT findings) and (2) the HDL-C level (defined by a direct enzymatic method). The study took place between 3 tertiary hospitals in Greece from October 2019 to November 2020.Results: The median age of all participants was 75.3 years (IR=7.4). The median HDL-C, MAC and AVC score was 46.9 mg/dl (IR 12.4) and 737.4 AU (IR=1218.5), respectively. According to the bivariate analysis results, a statistically significant correlation was found between HDL-C levels and the MAC and AVC score, with increased levels of HDL-C being related to decreased levels of CVC (r=-0.318, p=0.014).Conclusions: A significant inverse correlation between the HLD-C and CVC was confirmed in individuals with AVC. The above findings raise great interest for further research on pathophysiological mechanisms of valvular calcification and suggest that HDL-C may be an important treatment target to attenuate the development and progress of CVC. Background and Aims : Growing evidence has demonstrated the influence of many atherosclerotic risk factors on cardiac valve calcification (CVC), which is correlated with higher cardiovascular and all-cause mortality risk. The aim of this study was to investigate the effect of high-density lipoprotein cholesterol (HDL-C) on both mitral and aortic valve calcification (AVC) in individuals with AVC. Methods: Sixty-four patients with AVC, prior the intervention, were prospectively enrolled and underwent blood sampling for biochemical analysis and multi-slice computed tomography (MSCT) without contrast. Primary end points were the quantification of (1) mitral annulus calcification (MAC) and AVC, calculated by the median MAC and AVC scores (both were defined by Agatston units (AU) according to MSCT findings) and (2) the HDL-C level (defined by a direct enzymatic method). The study took place between 3 tertiary hospitals in Greece from October 2019 to November 2020. Results: The median age of all participants was 75.3 years (IR=7.4). The median HDL-C, MAC and AVC score was 46.9 mg/dl (IR 12.4) and 737.4 AU (IR=1218.5), respectively. According to the bivariate analysis results, a statistically significant correlation was found between HDL-C levels and the MAC and AVC score, with increased levels of HDL-C being related to decreased levels of CVC (r=-0.318, p=0.014). Conclusions: A significant inverse correlation between the HLD-C and CVC was confirmed in individuals with AVC. The above findings raise great interest for further research on pathophysiological mechanisms of valvular calcification and suggest that HDL-C may be an important treatment target to attenuate the development and progress of CVC.

Comparative analysis of fibroblast growth Factor-23 as a correlate of cardiovascular disease among individuals with chronic kidney disease, hypertensives, and healthy controls.

Chronic kidney disease (CKD) is a global growing public health epidemic with attending morbidity and huge financial cost. Cardiovascular disease (CVD), a major complication of CKD, contributes to its excessive mortality rate. The aetio-pathogenesis of the excess burden of CVD in CKD is a feature yet to be unravelled. Fibroblast growth factor-23 (FGF-23) has been implicated as a risk factor for CVD among patients with CKD. However, most of these studies were predominantly among the Caucasian population. This study aims to determine the correlation between FGF-23 and CVD among Nigerians with CKD. A cross-sectional comparative study composed of three groups: participants with CKD, hypertensives without CKD, and healthy individuals, represented as group 1, 2, and 3, respectively. Information obtained included demographic data and occurrence of risk factors for CVD. Cardiovascular risks were assessed by echocardiography and all the participants had kidney function tests done with plasma FGF-23. The study sample size consisted of 135 participants. The mean (SD) age for participants with CKD and controls were 50.2 (12.7), 54.3 (15.5), and 40.2 (14.1) years, respectively. The median [interquartile range (IQR)] of plasma FGF-23 for participants with CKD 210 (139-304) RU/ml, and controls 124 (86-170) RU/ml, and 71 (38 - 89) RU/ml P < 0.001. Most participants with CKD had left ventricular hypertrophy (LVH) (80.0%), compared to the controls; 28.9% and 6.7% P < 0.001. Similarly, majority of participants with CKD had elevated plasma FGF-23 with LVH (85.7%) compared to controls 55.6% and 11.5%, whereas for aortic valve calcification with elevated plasma FGF-23 among CKD and controls were 53.6% (P = 0.29), 37.0% (P = 0.03), and 19.2% (P = 0.06), respectively. Individuals with CKD had frequencies of elevated plasma FGF-23, LVH, and cardiac valve calcification, which are surrogates of cardiovascular events.

Biatrial and interatrial septal calcification in the setting of rheumatic heart disease and mitral and tricuspid valves replacement

BackgroundAlthough cardiac calcifications are described in the literature, calcification of atria is less frequently reported. There have been few case studies about atrial wall calcification in the literature, most of which were in middle-age females and were attributable to chronic heart diseases including rheumatic heart disease and valve replacement. In majority of the reported cases, interatrial septum has been spared. Only one case of bilateral atrial wall calcification has been reported prior to the current report, which has been in a patient with renal failure, calciphylaxis and long-term haemodialysis and calcium supplement intake.Case presentationThe patient was a 57-year-old female with history of rheumatic valvular heart disease and two prior valve replacement surgeries. She didn’t have any history of renal function impairment and haemodialysis or calcium supplements intake. Her laboratory data showed anaemia, increased cardiac biomarkers and active urinalysis. Performed echocardiography showed moderate right ventricular dilation with relatively poor contraction, normal left ventricular size and contraction, dilated right and left atria and good prosthetic valve function. On computed tomography (CT) scan, calcification of left atrial posterior and free walls, interatrial septum and right atrial free wall were noted. Evidence of hepatic congestion and cirrhosis was seen in abdominal CT scan and ultrasonography.ConclusionAtrial wall calcification is a rare finding but is important to report since it can complicate cardiac surgeries. It's also probable that this kind of dystrophic calcification could not be detected during routine echocardiography and CT scan should be performed in suspected cases.

Intracranial and heart valve calcifications in hemodialysis patients-Interrelationship and clinical impact.

Arterial calcification is an integral component of active atherosclerosis and is an independent risk factor for cardiovascular disease. Atherosclerosis is a systemic, life-threating disease that may occur at different sites and in various clinical presentations. Intracranial and valvular calcifications are common among dialysis patients and have been associated with poor cardiovascular outcomes. The aim of this study was to assess the clinical impact of valvular and intracranial arterial calcifications on mortality among chronic hemodialysis patients. A blinded neuroradiologist graded intracranial calcifications (ICC) of all hemodialysis patients who underwent brain computerized tomography (CT) from 2015 to 2017 in our institution. Valvular calcifications were assessed by echocardiography. Only hemodialysis patients with available echocardiography and brain CT were included. This study included 119 patients (mean age 70.6 ± 12.6 years, 57.1% men, and mean dialysis vintage 25.8 ± 42.6months). Among the cohort, 19 (16%) had no cardiac or brain calcifications and 65 (54.6%) had both valvular and intracranial calcifications. Considering the patients with no calcification as the reference group yielded adjusted odds ratios for all-cause mortality of 3.68 (95%CI 1.55-8.75) among patients with any brain calcifications, p=0.002. While valvular calcifications alone did not increase the 1-year mortality rate, ICC was the most important predictor of all-cause 1-year mortality in the study cohort. We found an independent association between ICC and the risk of death among hemodialysis patients. Assessing ICC may contribute to the risk stratification of hemodialysis patients. These calcifications are no less important than valvular calcifications.

Coronary artery- and aortic valve calcifications in patients with Philadelphia-negative myeloproliferative neoplasms

BackgroundPatients with the hematological cancers Philadelphia-negative Myeloproliferative Neoplasms (MPNs) have an increased risk of cardiovascular disease. However, whether MPNs have an increased burden of cardiac calcification has not been thoroughly investigated. Our aim is to investigate whether patients with MPNs have an increased burden of cardiac calcification that could help explain their increased risk of cardiovascular disease. Methods and resultsWe recruited 161 patients (mean age 65 years, 52% men) with an MPN diagnosis between 2016 and 2018. Coronary artery calcium score (CACS) and aortic valve calcification (AVC) were measured by cardiac computer tomography, and detailed information on cardiovascular risk factors was recorded. MPNs were matched on age and sex, with 805 controls from the Copenhagen General Population Study. A CACS>400 was present in 26% of MPNs and 19% of controls (p = 0.031). AVC was present in 58% of MPNs and 34% of controls (p < 0.0001). After adjustment for cardiovascular risk factors, the odds ratio (OR) of a CACS>400 was 1.9 (95% CI 1.2–3.1, p = 0.008) in MPNs compared to controls, and the OR of AVC was 4.4 (95% CI 2.9–6.9, p < 0.0001) in MPNs compared to controls. ConclusionPatients with MPNs have a significantly higher prevalence of a CACS >400 and AVC, compared to controls from the general population. The association between MPN and a CACS>400 or AVC remains significant after adjustment for cardiovascular risk factors. These novel data support the hypothesis that MPNs have an increased burden of cardiac calcifications, independent of other cardiovascular risk factors.

Evaluation of the relationship between cardiac calcification and cardiovascular disease using the echocardiographic calcium score in patients undergoing peritoneal dialysis: a cross-sectional study.

An echocardiographic calcium score (ECS) predicts cardiovascular disease (CVD) in the general population. Its utility in peritoneal dialysis (PD) patients is unknown. This cross-sectional study assessed 125 patients on PD. The ECS (range 0-8) was compared between subjects with CVD and those without. Among the subjects, 54 had CVD and 71 did not. Subjects with CVD were older (69 years vs. 56 years, P < 0.001) and had a higher prevalence of diabetes mellitus (DM) (81.5% vs. 45.1%, P < 0.001). They had lower diastolic blood pressure (72 mmHg vs. 81 mmHg, P < 0.001), lower phosphate (1.6 mmol/L vs. 1.9 mmol/L, P = 0.002), albumin (30 g/L vs. 32 g/L, P = 0.001), parathyroid hormone (34.4 pmol/L vs. 55.8 pmol/L, P = 0.002), total cholesterol (4.5 vs. 4.9, P = 0.047), LDL cholesterol (2.4 mmol/L vs. 2.8 mmol/L, P = 0.019) and HDL cholesterol (0.8 mmol/L vs. 1.1 mmol/L, P = 0.002). The ECS was found to be higher in subjects with CVD than in those without (2 vs. 1, P = 0.001). On multivariate analysis, only DM and age were independently associated with CVD. The ECS was significantly higher in PD patients with CVD than in those without, reflecting a higher vascular calcification burden in the former. It is a potentially useful tool to quantify vascular calcification in PD patients.

MO790: Arteriovenous Fistula Calcifications—Risk Factors and Impact on Arteriovenous Fistula Functionality

Abstract BACKGROUND AND AIMS Vascular calcifications have been recognized as frequent findings in patients with end-stage renal disease (ESRD) and have intricate mechanisms, including chronic kidney disease—mineral and bone disorders (CKD-MBD), inflammation and advanced atherosclerosis. The pathogenesis of arteriovenous fistula (AVF) calcifications is not fully understood, since it involves many other factors related to haemodialysis (HD) such as haemodynamic variables or vessel wall shear stress. The current study aims to assess the risk factors related to AVF calcifications and the impact on AVF functionality. METHOD The study included 174 chronic HD patients, mean age 58 ± 12 years, 35% female, median AVF duration 44 ± 52 months, with 35.9% radio-cephalic AVF, 12.1% brachio-basilic AVF, 52% brachio-cephalic AVF. The same nephrologist performed Doppler and B-mode AVF US scans in order to record AVF calcifications (defined as areas of hyperechogenicity with or without posterior shadowing within the arterial wall), as well as other complications (stenosis, partial thrombosis, aneurysms). In the same month of the AVF ultrasound assessment, cardiac echocardiography was performed in order to assess valvular calcifications. Laboratory parameters were analysed in the same month (Hb, calcium, phosphorus, serum bicarbonate, iPTH, albumin, ferritin, CRP). Dialysis efficiency (mean eKt/V in the month of ultrasound assessment) was recorded. The AVF survival was followed for 1 year after the initial evaluation, or up to the patient's death/transplantation. Statistical analysis was performed using MedCalc 14.8.1.0. RESULTS In our group, we found that the prevalence of AVF calcifications was 38% (66/174). Significantly more radiocephalic AVFs (47%) had calcifications than brachio-cephalic (38%) or brachio-basilic AVFs (15%), P = 0.04. The presence of calcifications was associated with longer AVF duration (P &amp;lt; .001), the presence of concomitant AVF stenosis (P = .04) and lower Hb levels (P = .02). The presence of AVF calcifications was not significantly associated with age, cardiac calcifications, or the presence of diabetes mellitus. Moreover, there was no statistically significant difference between the eKT/v values obtained in the group with AVF calcifications versus without AVF calcifications. We used the Cox proportional hazards model adjusted for standardized predicted values to determine whether patients with AVF calcifications had an increased risk of AVF failure. We found that after 1 year, 18,1% AVFs with calcifications had failed (12/66) while only 4.6% AVFs without calcifications had failed (5/108) [P = 0.02, hazard ratio (HR) 3.5, 95% confidence interval (95% CI) 1–11.3]. CONCLUSION The prevalence of AVF calcifications was 38% and affects radio-cephalic AVFs the most. AVF calcifications detected through ultrasound represent a risk factor for AVF failure, but the mechanism might be different from the pathways engaged in other vascular calcifications associated with CKD. We found no correlation with concomitant cardiac calcifications or CKD-MBD related biochemical changes. We found that AVF calcifications rather associate with HD-related factors (longer AVF duration and the presence of AVF stenosis). We suggest that periodic screening via ultrasound may be an easy method to diagnose AVF calcifications.

MO762: Effect of the Combined use of Magnesium Aspartate and L-Carnitine on the Progression of Heart Valve Disease and Endothelial Damage in Diabetic Haemodialysis Patients

Abstract BACKGROUND AND AIMS The problem of treatment and prevention of heart valve disease (HVD) as a predictor of cardiovascular events in type 2 diabetic patients undergoing haemodialysis (HD) is far from a satisfactory solution. In this context, it is reasonable to develop new therapeutic strategies based on advances of science of the important role of magnesium deficiency, chronic inflammation and endothelial damage in mechanisms of cardiac valve calcification (CVC) formation. Thus, the purpose of the present study was to evaluate the effect of the combined use of magnesium aspartate and L-carnitine on the progression of HVD and endothelial injury in the dynamics of complex 12-month treatment of diabetic HD patients. METHOD A total of 42 type 2 diabetic HD patients were included in this prospective cohort study (male, 26; age, 59.5 ± 0.7 years; HD duration, 31.2 ± 4.6 months; diabetes mellitus duration, 174.6 ± 7.8 months). Depending on the treatment program, patients were divided into two groups: the main group (n = 22) in addition to basic treatment (hypoglycemic, antihypertensive therapy, according to indications—correction of anemia, hyperparathyroidism, hyperphosphatemia) was treated by a combination of magnesium aspartate (0.5 g/day orally) and L-carnitine (1 g/day parenterally after each HD session (three times weekly); the comparison group (n = 20) was only on the standard therapy. Complex treatment lasted 12 months; administration of L-carnitine was performed continuously throughout the year, while magnesium aspartate—by three 2-month courses/year. The structure of mitral (MV) and aortic (AV) valves was detected by ultrasound and characterized as normal, thickening and calcification. Plasma content of circulating endothelial cells (CECs) was determined by phase contrast microscopy. Quantitative data are expressed as means ± SEM, qualitative ones—as %. Wilcoxon T-test was used for comparison of the dependent variables and the Mann–Whitney U-test was used for independent ones. RESULTS According to the data presented in Table 1, the incidence of new cases of both calcification of MV and AV in diabetic HD patients who received basic therapy was 10%/year, while the prevalence of CVC in subjects who included a combination of magnesium aspartate and L-carnitine in the standard treatment after 12 months of observation did not change. By the end of the follow-up, the CECs number in patients, who were on complex therapy, was 48.1% (20.6 ± 1.8 versus 9.9 ± 1.4 ×104/L; Z = 3.93, P &amp;lt;0.001) from baseline, a similar index in patients receiving basic treatment was 70.9% (24.7 ± 2.1 versus 17.5 ± 1.5 ×104/L, Z = 2.81; P = 0.005), and after 1 year the main group and the comparison group on the plasma content of desquamated endothelial cells (P &amp;lt;0.001) differed. CONCLUSION (1) The combined use of magnesium aspartate and L-carnitine, in addition to the basic 12-month treatment, prevents the progression of HVD and provides an effective reduction of damaged endothelium in type 2 diabetic HD patients. (2) Long-term modified treatment may reduce the cardiovascular risk in these subjects.

An optimized machine learning framework for predicting intradialytic hypotension using indexes of chronic kidney disease-mineral and bone disorders

Intradialytic hypotension (IDH) is the most common acute complication in hemodialysis (HD) sessions and is associated with increased morbidity and mortality in HD patients. To prevent the episode of IDH, it is critical to predict its occurrence. Chronic kidney disease-mineral and bone disorders (CKD-MBD) induce cardiac and vascular calcification, which impairs the compensatory mechanisms of blood pressure during HD. In this study, we proposed a feature selection framework called BSWEGWO_KELM to analyze 1940 records from 178 HD patients, which was based on an enhanced grey wolf optimization (GWO) algorithm and the kernel extreme learning machine (KELM). Then, global optimization experiments, together with feature selection experiments on public data sets and HD dataset, were performed to verify the effectiveness of the BSWEGWO_KELM method. The experimental results showed that the established BSWEGWO_KELM had the capability of screening out the key indicators such as dialysis vintage, mean arterial pressure (MAP), alkaline phosphatase (ALP), and intact parathyroid hormone (iPTH). Consequently, BSWEGWO_KELM can be applied as a practical and accurate method to predict IDH.

A Novel Idiopathic Atrial Calcification: Pathologic Manifestations and Potential Mechanism.

BackgroundCardiac calcification is a type of ectopic pathologic calcification of unknown etiology and mechanisms. Once diagnosed, the location, extent and morphology of the calcified lesions, as well as their functional significance in the heart, are usually the focus of case reports. Calcification is mostly distributed in myocardium, but rarely reported in atrium. In addition, because of limited sampling and complex pathological mechanisms, the etiology underlying the formation of these calcified lesions also remains unclear.MethodsTwo cardiac calcifications were found in a patient, died of trauma-induced subarachnoid hemorrhage after slightly drinking, during a standard autopsy. The location and morphological characteristics of the calcified lesions were determined by computed tomography (CT) and CT-based 3D reconstruction. The specific histopathological characteristics of the lesions were determined by multi-staining. The concentration of free calcium and inorganic pyrophosphate (PPi) in plasma reflected the change of calcium metabolism. The expression and membranal localization of the ATP Binding Cassette Subfamily C Member 6 (ABCC6) in hepatocytes were detected by immunofluorescence. The variants of the ABCC6 were detected by Sanger sequencing and potential pathogenic variants were further identified by in silico analysis.ResultsThe present study describes a patient with idiopathic calcification with two pear-shaped and irregularly hollow lesions symmetrically distributed in the patient's atrium. Massive accumulation of calcium salts was identified by multi-staining. For this patient, the plasma concentration of free calcium was higher than the control, indicating that calcium metabolism was disturbed. Furthermore, the plasma PPi of the patient was lower than the normal. By using immunofluorescence, the expression and membranal localization of ABCC6 was decreased and impaired in hepatocytes, respectively. Combined with Sanger sequencing and in silico analysis, 7 variants were identified.ConclusionsThis study described a novel patient with symmetrically distributed idiopathic atrial calcifications. Furthermore, all the results indicated that these pathologic calcifications may be secondary to reduced plasma PPi content due to ABCC6 dysfunction in hepatocytes. Moreover, these findings provided novel clues to the pathogenesis, clinical diagnosis and treatment of idiopathic atrial calcification in future.

Cardiac Calcifications: Phenotypes, Mechanisms, Clinical and Prognostic Implications.

Simple SummaryThe clinical relevance of vascular calcifications has increased in recent years, given the aging of the population and increased exposure to risk factors. Tissue calcification is often a point of no return that leaves no room for any medical therapy and limits the possibility of surgical and interventional treatments—a real insurmountable barrier. The diffusion of cardiac imaging methods has made the recognition of cardiac calcifications, at various levels and of variable extent, more and more frequent. The pathogenesis of calcifications is not unique but includes different mechanisms, depending on the specific site and disease, which, in turn, results in different phenotypes. Unfortunately, however, clinicians are not always aware of these different mechanisms and phenotypes. This concise, but in-depth, review explores the different molecular processes and their links with the specific clinical condition, and current therapeutic approaches to counteract calcifications.There is a growing interest in arterial and heart valve calcifications, as these contribute to cardiovascular outcome, and are leading predictors of cardiovascular and kidney diseases. Cardiovascular calcifications are often considered as one disease, but, in effect, they represent multifaced disorders, occurring in different milieus and biological phenotypes, following different pathways. Herein, we explore each different molecular process, its relative link with the specific clinical condition, and the current therapeutic approaches to counteract calcifications. Thus, first, we explore the peculiarities between vascular and valvular calcium deposition, as this occurs in different tissues, responds differently to shear stress, has specific etiology and time courses to calcification. Then, we differentiate the mechanisms and pathways leading to hyperphosphatemic calcification, typical of the media layer of the vessel and mainly related to chronic kidney diseases, to those of inflammation, typical of the intima vascular calcification, which predominantly occur in atherosclerotic vascular diseases. Finally, we examine calcifications secondary to rheumatic valve disease or other bacterial lesions and those occurring in autoimmune diseases. The underlying clinical conditions of each of the biological calcification phenotypes and the specific opportunities of therapeutic intervention are also considered and discussed.

Hyperphosphatemia is associated with cardiac valve calcification in chronic hypoparathyroidism.

To evaluate the association between metabolic abnormalities and cardiovascular risk factors in patients with chronic hypoparathyroidism (HPP). Patients 18years and older, glomerular filtration > 30mL/min/1.73 m2and no documented coronary artery disease were selected. Serum calcium, phosphorus, glucose, lipids, PTH, 25(OH)D and FGF23 were measured. Cardiovascular risk was estimated by the European Society of Cardiology (ESC) calculator. Transthoracic echocardiogram and carotid ultrasound were performed to detect carotid plaques (CP), carotid intima-media thickness (IMT), cardiac valve calcification (CVC), and left ventricular hypertrophy (LVH). Thirty-seven patients (94.6% female), aged 56.0 ± 13.5years and HPP duration 7.0 (4.0; 11.3) years, were included. Fifteen were classified as low cardiovascular risk, 9 as intermediate risk, 9 as high risk and none as very high risk. The prevalence of CP, CVC and LVH was 24.3%, 24.3% and 13.5%, respectively. IMT values were within normal ranges in all cohort.FGF23 were not associatedwithCP, IMT, CVC or LVH.After logistic regression, phosphorus was the only significant metabolic variable impacting CVC in univariate analysis (OR 2.795; 95% CI 1.132-6.905; p = 0.026), as well as in the multivariate analysis (OR 3.572; 95% CI 1.094-11.665; p = 0.035).Analysis by ROC curve showed serum phosphorus > 5.05mg/dL(AUC 0.748; CI 0.584-0.877; p = 0.05) as the best cutoff point associatedwith valve heart calcification (sensitivity 78%;negative predictive value91.3%). Hyperphosphatemia was associatedwith CVC in HPP patients.Further studies are needed to investigate whether the control of hyperphosphatemia may reduce cardiovascular risk in this population.

Prognosis and risk factors for cardiac valve calcification in Chinese end-stage kidney disease patients on combination therapy with hemodialysis and hemodiafiltration

Background Cardiac valve calcification (CVC) is an important risk factor for cardiovascular complications. However, limited data are available concerning the prevalence, clinical features and risk factors for CVC in end-stage kidney disease (ESKD) patients. In this study, we aimed to assess these parameters in Chinese ESKD patients receiving combination therapy with hemodialysis and hemodiafiltration. Methods We conducted a cross-sectional study on 293 ESKD patients undergoing combination therapy of hemodialysis and hemodiafiltration at the First Affiliated Hospital of Chongqing Medical University from October 2014 to December 2015. CVC was evaluated via echocardiography. Results ESKD patients with CVC had a higher prevalence of diabetes mellitus, aortic and/or coronary artery calcification, arrhythmia, heart failure and coronary heart disease; increased systolic, diastolic and pulse pressure; longer duration of hemodialysis and hypertension; reduced hemoglobin, albumin and high-density lipoprotein cholesterol levels; and increased serum calcium and calcium-phosphorus product levels compared with those without CVC. Logistic regression analysis showed that increased dialysis duration (p = 0.006, OR = 2.25), serum calcium levels (p = 0.046, OR = 2.04) and pulse pressure (p < 0.001, OR = 3.22), the presence of diabetes (p = 0.037, OR = 1.81) and decreased serum albumin levels (p = 0.047, OR = 0.54) were risk factors for CVC. The correlation analysis indicated a significantly increased CVCs prevalence with an increase prevalence of heart failure, aortic and coronary artery calcification. Conclusions CVC represents a common complication and a danger signal for cardiovascular events in ESKD patients undergoing combination therapy of hemodialysis and hemodiafiltration. The presence of diabetes, increased pulse pressure, long dialysis duration, hypoalbuminemia and high serum calcium levels were independent risk factors for CVC.

Osteomodulin attenuates smooth muscle cell osteogenic transition in vascular calcification.

RationaleVascular calcification is a prominent feature of late‐stage diabetes, renal and cardiovascular disease (CVD), and has been linked to adverse events. Recent studies in patients reported that plasma levels of osteomodulin (OMD), a proteoglycan involved in bone mineralisation, associate with diabetes and CVD. We hypothesised that OMD could be implicated in these diseases via vascular calcification as a common underlying factor and aimed to investigate its role in this context.Methods and resultsIn patients with chronic kidney disease, plasma OMD levels correlated with markers of inflammation and bone turnover, with the protein present in calcified arterial media. Plasma OMD also associated with cardiac calcification and the protein was detected in calcified valve leaflets by immunohistochemistry. In patients with carotid atherosclerosis, circulating OMD was increased in association with plaque calcification as assessed by computed tomography. Transcriptomic and proteomic data showed that OMD was upregulated in atherosclerotic compared to control arteries, particularly in calcified plaques, where OMD expression correlated positively with markers of smooth muscle cells (SMCs), osteoblasts and glycoproteins. Immunostaining confirmed that OMD was abundantly present in calcified plaques, localised to extracellular matrix and regions rich in α‐SMA+ cells. In vivo, OMD was enriched in SMCs around calcified nodules in aortic media of nephrectomised rats and in plaques from ApoE −/− mice on warfarin. In vitro experiments revealed that OMD mRNA was upregulated in SMCs stimulated with IFNγ, BMP2, TGFβ1, phosphate and β‐glycerophosphate, and by administration of recombinant human OMD protein (rhOMD). Mechanistically, addition of rhOMD repressed the calcification process of SMCs treated with phosphate by maintaining their contractile phenotype along with enriched matrix organisation, thereby attenuating SMC osteoblastic transformation. Mechanistically, the role of OMD is exerted likely through its link with SMAD3 and TGFB1 signalling, and interplay with BMP2 in vascular tissues.ConclusionWe report a consistent association of both circulating and tissue OMD levels with cardiovascular calcification, highlighting the potential of OMD as a clinical biomarker. OMD was localised in medial and intimal α‐SMA+ regions of calcified cardiovascular tissues, induced by pro‐inflammatory and pro‐osteogenic stimuli, while the presence of OMD in extracellular environment attenuated SMC calcification.

In Vivo Cardiac-specific Expression of Adenylyl Cyclase 4 Gene Protects against Klotho Deficiency-induced Heart Failure

Klotho is an aging-suppressor gene. Klotho gene deficiency causes heart failure in Klotho-hypomorphic mutant (KL (-/-)) mice. RNA-seq and western blot analysis showed that adenylyl cyclase type IV (AC4) mRNA and protein expression was largely decreased in cardiomyocytes of KL (-/-) mice. The objective of this study was to investigate whether in vivo cardiac-specific expression of AC4 gene protects against Klotho deficiency-induced heart failure. Interestingly, in vivo AAV-based cardiac-specific AC4 gene expression increased left ventricular fractional shortening, ejection fraction, stroke volume, and left ventricular end-diastolic volume in KL (-/-) mice, suggesting that cardiac-specific AC4 gene expression improves Klotho deficiency-induced heart dysfunction. Cardiac-specific AC4 gene expression also decreased Klotho deficiency-induced cardiac hypertrophy. Cardiac-specific AC4 gene expression alleviated Klotho deficiency-induced cardiac fibrosis and calcification. Furthermore, cardiac-specific AC4 gene expression attenuated mitochondrial dysfunction, superoxide accumulation and cardiomyocyte apoptotic cell death. Thus, downregulation of AC4 may contribute to Klotho deficiency-induced heart failure. Mechanistically, AAV2/9-αMHC-AC4 increased cardiomyocytic cAMP levels and thus regulated the PKA-PLN-SERCA2 signal pathway, which is critical in modulating calcium flux and mitochondrial function. In conclusion, cardiac-specific AC4 gene expression protects against Klotho deficiency-induced heart failure through increasing cardiomyocytic cAMP levels, which alleviates cAMP-dependent mitochondrial dysfunction, superoxide accumulation and apoptotic cell death. AC4 regulates superoxide levels via the cAMP-PKA pathway. AC4 could be a potential therapeutic target for heart failure associated with Klotho deficiency. Heart failure is the major cause of mortality in patients with chronic kidney disease (CKD). A decrease in Klotho levels is linked to CKD.

Cardiac valve calcification is associated with mortality in hemodialysis patients: a retrospective cohort study

BackgroundCardiac valve calcification (CVC) is common in end-stage renal disease (ESRD). We investigated the effect of CVC on all-cause and cardiovascular (CV) mortality in maintenance hemodialysis (MHD) patients.MethodsA retrospective cohort study was conducted on 434 hemodialysis patients who underwent echocardiography for qualitative assessment of valve calcification with complete follow-up data from January 1, 2014, to April 30, 2021. The baseline data between the CVC and non-CVC groups were compared. The Kaplan–Meier method was used to analyse all-cause and cardiovascular mortality. The association of CVC with all-cause and cardiovascular mortality was evaluated using multivariate Cox regression analysis.ResultsOverall, 27.2% of patients had mitral valve calcification (MVC), and 31.8% had aortic valve calcification (AVC) on echocardiography. Patients with CVC showed significantly higher all-cause (log-rank P < 0.001) and cardiovascular (log-rank P < 0.001) mortality rates than patients without CVC. In multivariate regression analyses, MVC (HR: 1.517, P = 0.010) and AVC (HR: 1.433, P = 0.028) were significant factors associated with all-cause mortality. MVC (HR: 2.340, P < 0.001) and AVC (HR: 2.410, P < 0.001) were also significant factors associated with cardiovascular mortality.ConclusionsMVC and AVC increased the risk of all-cause and cardiovascular mortality in MHD patients. Regular follow-up with echocardiography could be a useful method for risk stratification in MHD patients.

1,25-dihydroxyvitamin D deficiency is independently associated with cardiac valve calcification in patients with chronic kidney disease

Cardiac valve calcification is highly prevalent in patients with chronic kidney disease (CKD). Low vitamin D levels are associated with vascular calcification in CKD. However, the association between vitamin D levels and cardiac valve calcification is unknown. A total of 513 patients with pre-dialysis CKD were included in this cross-sectional study. Aortic valve calcification (AVC) and mitral valve calcification (MVC) were assessed using two-dimensional echocardiography. The associations between AVC and MVC and baseline variables were investigated using logistic regression analyses. In multivariable analysis, serum 1,25(OH)2D level was independently associated with AVC (odds ratio [OR], 0.87; P < 0.001) and MVC (OR, 0.92; P < 0.001). Additionally, age, diabetes, coronary heart disease, calcium × phosphate product, and intact parathyroid hormone levels were independently associated with AVC and MVC. Systolic blood pressure was independently associated with AVC. A receiver-operating characteristic (ROC) curve analysis showed that the best cutoff values of serum 1,25(OH)2D levels for predicting AVC and MVC were ≤ 12.5 and ≤ 11.9 pg/dl, respectively. Serum 1,25(OH)2D deficiency is independently associated with AVC and MVC in patients with CKD, suggesting that serum 1,25(OH)2D level may be a potential biomarker of AVC and MVC in these patients.

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.

Radiologist opinions regarding reporting incidental coronary and cardiac calcification on thoracic CT.

Objectives:Coronary and cardiac calcification are frequent incidental findings on non-gated thoracic computed tomography (CT). However, radiologist opinions and practices regarding the reporting of incidental calcification are poorly understood.Methods:UK radiologists were invited to complete this online survey, organised by the British Society of Cardiovascular Imaging (BSCI). Questions included anonymous information on subspecialty, level of training and reporting practices for incidental coronary artery, aortic valve, mitral and thoracic aorta calcification.Results:The survey was completed by 200 respondents: 10% trainees and 90% consultants. Calcification was not reported by 11% for the coronary arteries, 22% for the aortic valve, 35% for the mitral valve and 37% for the thoracic aorta. Those who did not subspecialise in cardiac imaging were less likely to report coronary artery calcification (p = 0.005), aortic valve calcification (p = 0.001) or mitral valve calcification (p = 0.008), but there was no difference in the reporting of thoracic aorta calcification. Those who did not subspecialise in cardiac imaging were also less likely to provide management recommendations for coronary artery calcification (p < 0.001) or recommend echocardiography for aortic valve calcification (p < 0.001), but there was no difference for mitral valve or thoracic aorta recommendations.Conclusion:Incidental coronary artery, valvular and aorta calcification are frequently not reported on thoracic CT and there are differences in reporting practices based on subspeciality.Advances in knowledge:On routine thoracic CT, 11% of radiologists do not report coronary artery calcification. Radiologist reporting practices vary depending on subspeciality but not level of training.

Correlation between Serum Magnesium Level and Cardiac Valve Calcification in Patients with Chronic Kidney Disease.

The aim of the study was to investigate the correlation between serum magnesium (Mg) level and cardiac valve calcification (CVC) in patients with chronic kidney disease (CKD). A total of 232 CKD patients hospitalized from August 2016 to December 2020 were divided into CVC and non-CVC groups. Their clinical data and laboratory examination results were compared, the risk factors for CVC in CKD patients were explored using logistic regression analysis, and Spearman's method was used to analyze the correlation between serum Mg level and CVC degree. According to the tertiles of mean serum Mg level, they were assigned into low serum Mg group (≤ 0.96 mmol/L), middle serum Mg group (0.97 - 1.07 mmol/L), and high serum Mg group (≥ 1.08 mmol/L). The relationship of serum Mg level with CVC risk in CKD patients was analyzed through the Cox regression model, and a prediction model was established using independent risk factors. Long CKD duration, low serum Mg level, high serum phosphorus (P) level, and high CKD stage were independent risk factors for CVC. Serum Mg level was significantly negatively correlated with the severity of CVC (r = -0.743, p < 0.05). The risk of CVC was significantly higher in low serum Mg group than that in high serum Mg group [hazard ratio (HR) = 2.852, 95% confidence interval (CI): 1.325 - 6.432, p = 0.005]. A CVC prediction model was established based on independent risk factors as follows: CVC predictive value = EXP [0.491 - 0.546 (CKD duration) - 0.454 (serum P level) + 2.145 (serum Mg level) - 0.812 (CKD stage)]/1 + EXP [0.491 - 0.546 (CKD duration) - 0.454 (serum P level) + 2.145 (serum Mg level) - 0.812 (CKD stage)]. The area under curve of the model was 0.750 (95% CI: 0.822 - 0.965), and that of the CVC prediction model for CKD patients in test set was 0.774 (95% CI: 0.761 - 0.975), showing no significant difference from that in training set (p > 0.05). Low serum Mg level serves as an independent risk factor for CVC in CKD patients, and may increase the risk of CVC. Therefore, the serum Mg level in CKD patients should be corrected timely in clinical practice.