Relationship of bone mineral density with valvular and annular calcification in community-dwelling older people: The Cardiovascular Health Study.
Massera Daniele,Xu Shuo,Bartz Traci M,Bortnick Anna E,Ix Joachim H,Chonchol Michel,Owens David S,Barasch Eddy,Gardin Julius M,Gottdiener John S,Robbins John R,Siscovick David S,Kizer Jorge R
Archives of osteoporosis
Associations between bone mineral density and aortic valvular, aortic annular, and mitral annular calcification were investigated in a cross-sectional analysis of a population-based cohort of 1497 older adults. Although there was no association between continuous bone mineral density and outcomes, a significant association between osteoporosis and aortic valvular calcification in men was found. INTRODUCTION:The process of cardiac calcification bears a resemblance to skeletal bone metabolism and its regulation. Experimental studies suggest that bone mineral density (BMD) and valvular calcification may be reciprocally related, but epidemiologic data are sparse. METHODS:We tested the hypothesis that BMD of the total hip and femoral neck measured by dual-energy X-ray absorptiometry (DXA) is inversely associated with prevalence of three echocardiographic measures of cardiac calcification in a cross-sectional analysis of 1497 older adults from the Cardiovascular Health Study. The adjusted association of BMD with aortic valve calcification (AVC), aortic annular calcification (AAC), and mitral annular calcification (MAC) was assessed with relative risk (RR) regression. RESULTS:Mean (SD) age was 76.2 (4.8) years; 58% were women. Cardiac calcification was highly prevalent in women and men: AVC, 59.5 and 71.0%; AAC 45.1 and 46.7%; MAC 42.8 and 39.5%, respectively. After limited and full adjustment for potential confounders, no statistically significant associations were detected between continuous BMD at either site and the three measures of calcification. Assessment of WHO BMD categories revealed a significant association between osteoporosis at the total hip and AVC in men (adjusted RR compared with normal BMD = 1.24 (1.01-1.53)). In graded sensitivity analyses, there were apparent inverse associations between femoral neck BMD and AVC with stenosis in men, and femoral neck BMD and moderate/severe MAC in women, but these were not significant. CONCLUSION:These findings support further investigation of the sex-specific relationships between low BMD and cardiac calcification, and whether processes linking the two could be targeted for therapeutic ends.
10.1007/s11657-017-0347-y
Compensatory elevated serum intermedin levels are associated with increased vascular calcification in hemodialysis patients.
International urology and nephrology
INTRODUCTION:Vascular calcification (VC), which is a pathological process of abnormal calcium and phosphorus deposition in blood vessels, valves, heart and other tissues, is highly prevalent and predicts mortality in dialysis patients. Its mechanisms are complex and unclear. We presume that intermedin (IMD), a kind of small molecule active peptide, may play roles in VC in hemodialysis (HD) patients. This study aims to evaluate serum IMD levels and establish their relation to VC and other parameters in HD patients. METHODS:A total of 116 patients on maintenance HD treatment and 52 age- and sex-matched healthy controls were enrolled in this study. Serum IMD levels were measured by radioimmunoassay (RIA). VC was evaluated by abdominal aortic calcification scores. RESULTS:Serum IMD levels were significantly lower in HD patients than in controls [24.89 (13.55, 50.24) pg/ml vs. 137.79 (93.21, 201.64) pg/ml, P < 0.0001]. In addition, IMD was negatively correlated with the serum phosphate level (P = 0.036) in HD patients. However, compared with the group whose IMD levels were above the median, patients with IMD levels less than the median had a lower incidence of VC (P = 0.031). Multivariate logistic regression analyses revealed that serum IMD levels more than 24.89 pg/ml (P = 0.014, OR = 0.285), higher serum iPTH levels (P < 0.0001, OR = 1.093) and older age (P = 0.009, OR = 1.003) were significant independent determinant factors for VC in HD patients. CONCLUSION:The serum IMD levels were significantly lower in HD patients than that in healthy group. In addition to higher PTH levels and older age, compensatory elevated IMD levels may be an independently determinant factor for VC in HD patients. This was the first study about IMD and VC in dialysis patients.
10.1007/s11255-022-03240-2
Treatment to reduce vascular calcification in hemodialysis patients using vitamin K (Trevasc-HDK): A study protocol for a randomized controlled trial.
Haroon Sabrina-Wong-Peixin,Tai Bee-Choo,Ling Lieng-Hsi,Teo Lynette,Davenport Andrew,Schurgers Leon,Teo Boon-Wee,Khatri Priyanka,Ong Ching-Ching,Low Sanmay,Yeo Xi-Er,Tan Jia-Neng,Subramanian Srinivas,Chua Horng-Ruey,Tan Swee-Yaw,Wong Weng-Kin,Lau Titus-Wai-Leong
Medicine
INTRODUCTION:End stage renal failure patients on hemodialysis have significant vascular calcification This is postulated to be related to sub-clinical vitamin K deficiency, which is prevalent in hemodialysis patients. Vitamin K deficiency result in the failure of the matrix GLA protein (MGP) to undergo carboxylation. MGP is a natural local inhibitor of vascular calcification and the lack of functional carboxylated MGP may contribute to increase vascular calcification. Vitamin K supplement should therefore correct this anomaly and decrease the rate or severity of vascular calcification in this population of patients on long-term maintenance hemodialysis. Our study seeks to evaluate the prevalence and the progression of vascular calcification in a cohort of maintenance hemodialysis patients. It will also evaluate the efficacy of vitamin K supplementation in reducing the progression of vascular calcification in this group of patients. METHODS:This will be a single-center randomized, prospective and open-label interventional clinical trial of end stage renal failure patients on hemodialysis. We aim to recruit 200 patients. Eligible patients will be randomized to either the standard care arm or active treatment arm. Active treatment arm patients will receive standard care plus supplementation with oral vitamin K2 isoform 360 mcg 3 times weekly for a total duration of 18 months. Primary outcome measured will be absolute difference in coronary artery calcification score at 18-month between control and intervention arms. Secondary outcomes will be to compare absolute difference in aortic valve calcification, percentage of patients with regression of coronary artery calcification of at least 10%, absolute difference in aortic and systemic arterial stiffness, mortality from any cause and major adverse cardiovascular over the same period. DISCUSSION:Evidence of successful regression or retardation of vascular calcification will support the conduct of larger and longer-term trials aimed at reducing cardiovascular disease mortality and major adverse cardiovascular events in this high-risk population using a safe and inexpensive strategy TRIAL REGISTRATION:: ClinicalTrials.gov NCT02870829. Registered on 17 August 2016 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02870829National University Hospital's Institutional Review Board (2015/01000).
10.1097/MD.0000000000021906
Serum Thyrotropin Elevation and Coronary Artery Calcification in Hemodialysis Patients.
Cardiorenal medicine
INTRODUCTION:Hypothyroidism is highly prevalent in end-stage kidney disease patients, and emerging data show that lower circulating thyroid hormone levels lead to downregulation of vascular calcification inhibitors and coronary artery calcification (CAC) in this population. To date, no studies have examined the association of serum thyrotropin (TSH), the most sensitive and specific single biochemical metric of thyroid function, with CAC risk in hemodialysis patients. METHODS:In secondary analyses of patients from the Anti-Inflammatory and Anti-Oxidative Nutrition in Hypoalbuminemic Dialysis Patients trial, we examined serum TSH levels and CAC risk assessed by cardiac computed tomography scans collected within a 90-day period. We evaluated the relationship between serum TSH with CAC Volume (VS) and Agatston score (AS) (defined as >100 mm3 and >100 Houndsfield Units, respectively) using multivariable logistic regression. RESULTS:Among 104 patients who met eligibility criteria, higher TSH levels in the highest tertile were associated with moderately elevated CAC VS and AS in case-mix-adjusted analyses (ref: lowest tertile): adjusted ORs (95% CIs) 4.26 (1.18, 15.40) and 5.53 (1.44, 21.30), respectively. TSH levels >3.0 mIU/L (ref: ≤3.0 mIU/L) were also associated with moderately elevated CAC VS and AS. In secondary analyses, point estimates of incrementally lower direct free thyroxine levels trended toward elevated CAC VS and AS, although associations did not achieve statistical significance. CONCLUSIONS:In hemodialysis patients, higher serum TSH was associated with elevated CAC VS and AS. Further studies are needed to determine if thyroid hormone supplementation can attenuate CAC burden in this population.
10.1159/000525037
The impact of cholecalciferol on markers of vascular calcification in hemodialysis patients: A randomized placebo controlled study.
Alshahawey Mona,El Borolossy Radwa,El Wakeel Lamia,Elsaid Tamer,Sabri Nagwa Ali
Nutrition, metabolism, and cardiovascular diseases : NMCD
BACKGROUND AND AIM:Vascular calcification is an independent risk factor for cardiovascular diseases and all-cause mortality in end stage renal disease, and particularly in hemodialysis patients. Vitamin D deficiency has been shown to be associated with vascular calcification among this category of patients. Cholecalciferol or vitamin D3; the native inactivated 25-hydroxy vitamin D [25(OH)D], has been proposed to have a good impact on vascular calcification and vitamin D deficiency. However, clinical data is still limited. METHODS AND RESULTS:A prospective, randomized, placebo-controlled study was carried out to evaluate the effect of oral cholecalciferol on vascular calcification and 25(OH)D levels in hemodialysis patients. A total of sixty eligible hemodialysis patients were randomly assigned to either a treatment group (Oral 200.000IU Cholecalciferol per month) or a placebo group, for 3 months. Serum 25-hydroxy vitamin D (25(OH)D), fetuin-A, fibroblast growth factor (FGF-23), osteoprotegerin (OPG), calcium, phosphorus, their product (CaXP) and intact parathyroid hormone (iPTH) levels, were all assessed at baseline and at the end of the study. ClinicalTrials.gov registration number: NCT03602430. Cholecalciferol significantly increased serum levels of 25(OH)D and fetuin-A in the treatment group (p-value < 0.001), while no significant difference was observed in the placebo group. Cholecalciferol administration showed no effect on either FGF-23 or OPG. None of the treatment group patients experienced any adverse effects. CONCLUSION:Cholecalciferol was shown to be an effective, tolerable, inexpensive pharmacotherapeutic option to overcome vitamin D deficiency, with a possible modulating effect on fetuin-A, among hemodialysis patients. CLINICALTRIALS. GOV REGISTRATION NUMBER:NCT03602430.
10.1016/j.numecd.2020.09.014
Randomized Controlled Clinical Trial of the Effect of Treatment with Vitamin K2 on Vascular Calcification in Hemodialysis Patients (Trevasc-HDK).
Kidney international reports
Introduction:Vitamin K deficiency among patients on hemodialysis (HD) affects the function of matrix GLA protein (MGP), a potent vitamin K-dependent inhibitor of vascular calcification (VC). Methods:We conducted a single-center randomized controlled trial (RCT) on maintenance HD patients to examine if vitamin K2 supplementation can reduce progression of coronary artery calcification (CAC) over an 18-month study period. Patients were randomized to vitamin K2 group receiving menaquinone-7360 μg 3 times/wk or control group. The primary outcome was CAC scores at the end of the study period. The secondary outcomes were aortic valve calcification (AVC), carotid-femoral pulse wave velocity (cfPWV), aortic augmentation index (AIx), dephosphorylated undercarboxylated MGP (dp-ucMGP) levels, major adverse cardiac events (MACE), and vascular access events. Results:Of the 178 patients randomized, follow-up was completed for 138 patients. The CAC scores between the 2 groups were not statistically different at the end of 18 months (relative mean difference [RMD] 0.85, 95% CI 0.55-1.31). The secondary outcomes did not differ significantly in AVC (RMD 0.82, 95% CI 0.34-1.98), cfPWV (absolute mean difference [AMD] 0.55, 95% CI -0.50 to 1.60), and AIx (AMD 0.13, 95% CI -3.55 to 3.80). Supplementation with vitamin K2 did reduce dp-ucMGP levels (AMD -86, 95% CI -854 to -117). The composite outcome of MACE and mortality was not statistically different between the 2 groups (Hazard ratio = 0.98, 95% CI 0.50-1.94). Conclusion:Our study did not demonstrate a beneficial effect of vitamin K2 in reducing progression of VC in this population at the studied dose and duration.
10.1016/j.ekir.2023.06.011
[Association between sarcopenia and abdominal aortic calcification in maintenance hemodialysis patients].
Zhonghua yi xue za zhi
To investigate the relationship between sarcopenia and abdominal aortic calcification (AAC) in maintenance hemodialysis (MHD) patients. A cross-sectional study was conducted. MHD patients who underwent regular dialysis between January 2021 and January 2022 at hemodialysis center in Jiangdu People's Hospital Affiliated to Yangzhou University were enrolled. The incidence of sarcopenia in these patients was examined by measuring handgrip strength, gait speed and appendicular skeletal muscle mass index (ASMI) using bioelectrical impedance analysis. AAC score was measured by a lateral lumbar spinal radiograph. The general information of the patients was collected and the blood biochemical indexes were detected. These patients were divided into non-calcification group (=104) and calcification group (=127) according to the score of AAC. Multivariate logistic regression was used to analyze the related factors of AAC. A total of 231 MHD patients (134 males and 97 females) were enrolled in the study, with the mean age of (57.1±11.4) years. Among 231 hemodialysis patients, the incidence of sarcopenia and AAC were 46.3% (107 cases) and 55.0% (127 cases), respectively. The age [(60.2±11.1) vs (53.4±12.2) years, <0.001] and dialysis vintage [86 (46, 135) vs 57 (27, 109) months, =0.005] in calcification group were longer than these in the non-calcification group. The level of 25(OH)D [17.7 (13.5, 24.3) vs 20.5 (15.1, 28.1) μg/L, =0.008] and gait speed [(0.88±0.23) vs (1.01±0.20) m/s, =0.024], handgrip strength [(17.9±9.1) vs (20.7±9.9) kg, =0.013], ASMI [(6.65±2.24) vs (7.83±2.46) kg/m, <0.001] were lower. While, AAC score [12 (9, 19) vs 0 (0, 3), <0.001] and the incidence of sarcopenia [58.3% (74/127) vs 31.7% (33/104), <0.001] were higher in the calcification group than these in the non-calcification group. Multivariate logistic regression analysis indicated that sarcopenia (=1.928, 95%: 1.302-2.855, =0.001), decrease of 25(OH)D level (=0.969, 95%: 0.940-1.000, =0.047), age (=1.043, 95%: 1.015-1.072, =0.002), and dialysis vintage (=1.009, 95%: 1.004-1.015, =0.001) were related factors of AAC. Sarcopenia is associated with AAC in MHD patients. In clinical practice, attention should be paid to sarcopenia in MHD patients.
10.3760/cma.j.cn112137-20230615-01019
Effects of sodium thiosulfate on serum calcification factors in patients undergoing maintenance hemodialysis.
Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy
OBJECTIVE:To investigate the effect of sodium thiosulfate (STS) on serum calcification factors in patients undergoing maintenance hemodialysis. METHODS:Forty-four Patients were randomly divided into control group (n = 22) and observation group (n = 22) by envelope method (block 4 randomization). The control group received routine treatment while observation group was treated with STS on the basis of routine treatment. The biochemical indicators, including BUN, UA, SCr, Ca , P , calcium-phosphorus product, PTH, hs-CRP, TG, TC, HDL, LDL, and serum calcification factor MGP, FA, FGF-23, and OPG levels were compared before and after treatment. RESULTS:Control group had no statistically significant difference in the levels of vascular calcification factors MGP, FA, FGF-23, and OPG before and after treatment (p > 0.05). Whereas observation group had higher levels of MGP and FA, and lower levels of FGF-23 and OPG after treatment than before treatment (p < 0.05). The levels of MGP and FA in observation group were higher than those in control group, and FGF-23 and OPG were lower than those in control group (p < 0.05). CONCLUSION:It is speculated that sodium thiosulfate can alleviate the progression of vascular calcification by changing the levels of calcification factors.
10.1111/1744-9987.14029
Effect of lanthanum carbonate and calcium carbonate on the progression of coronary artery calcification among hemodialysis patients with vascular calcification risk: a randomized controlled trial.
Clinical and experimental nephrology
BACKGROUND:Coronary artery calcification (CAC) is predictive of cardiovascular events. We assessed whether a non-calcium-based phosphate binder, lanthanum carbonate (LC), could delay CAC progression compared with a calcium-based phosphate binder, calcium carbonate (CC), in hemodialysis patients. METHODS:This was a subsidiary of the LANDMARK study, which is a multicenter, open-label, randomized control study comparing LC and CC for cardiovascular events among Japanese hemodialysis patients with hyperphosphatemia who were at risk of vascular calcification. Participants were randomly assigned (1:1) to receive LC or CC. The changes in the total Agatston score of CAC 2 years from baseline were the primary outcome. Secondary outcomes included the changes in the total Agatston score at 1 year from baseline and the changes in serum phosphate, corrected calcium, and intact parathyroid hormone concentrations. RESULTS:Of 239 patients, 123 comprised the full analysis set. The median daily drug dose (mg) was 750 [interquartile range (IQR), 750‒1500] in the LC group and 3000 (IQR, 3000‒3000) in the CC group; it remained constant throughout the study period. There was no significant difference in the change in total Agatston score from baseline to 2 years between the LC and CC groups [368 (95% confidence interval, 57-680) in the LC group vs. 611 (105-1118) in the CC group; difference, 243 (- 352-838)]. CONCLUSIONS:LC-based treatment for hyperphosphatemia did not delay CAC for 2 years compared with CC-based treatment in hemodialysis patients with at least one risk factor for vascular calcification.
10.1007/s10157-022-02270-5
Intravenous sodium thiosulphate for vascular calcification of hemodialysis patients-a systematic review and meta-analysis.
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
BACKGROUND:Vascular calcification (VC) is a common comorbidity among patients with chronic kidney disease (CKD), indicating major cardiovascular events. This study aimed to evaluate the effects and safety of intravenous sodium thiosulphate (STS) for VC in CKD patients. METHODS:Electronic databases were searched for clinical trials that provided data comparing outcomes among patients treated with and without STS. The PRISMA guidelines were followed. Efficacy was assessed using calcification scores and arterial stiffness. Safety was examined by analyzing adverse symptoms, electrolytes and bone mineral density (BMD). Random-effects models were performed. Meta-regression and sensitivity analysis were done. The risk of bias was assessed using the Cochrane tools. RESULTS:Among the 5601 publications, 6 studies involving 305 participants (mean age: 56 years, male: 56.6%) with all participants on maintenance hemodialysis met eligibility criteria. For efficacy, the progression in Agatston scores in the coronary arteries [107 patients, mean difference (MD): -241.27, 95% confidence interval (95% CI): -421.50 to -61.03] and iliac arteries (55 patients, MD: -382.00, 95% CI: -751.07 to -12.93) was lower in the STS treated group compared with controls. The increase in pulse wave velocity was lower in the STS group (104 patients, MD: -1.29 m/s, 95% CI: -2.24 to -0.34 m/s). No association was found between the change in calcification scores and STS regimen. For safety, gastrointestinal symptoms (e.g. nausea) and increased anion gap acidosis were noted. No reduction in BMD by STS was observed. CONCLUSIONS:Intravenous STS may attenuate the progression of VC and arterial stiffness in hemodialysis patients. Large and well-designed randomized controlled trials are warranted.
10.1093/ndt/gfac171
Cardiovascular calcification in hemodialysis patients: A Qatar-based prevalence and risk factors study.
Qatar medical journal
BACKGROUND:Patients with end-stage kidney disease on hemodialysis (HD) have an increased risk of death due to the high prevalence of cardiovascular disease. Vascular calcification (VC) is predictive of cardiovascular disease and mortality. We conducted a study to evaluate the prevalence and risk factors for VC in dialysis patients in Qatar. METHODS:This is a retrospective nationwide study including all chronic ambulatory dialysis patients in Qatar from 2020 to 2022. We used our national electronic medical record to track demographics, clinical characteristics, comorbidities, laboratory values, and diagnostic data for each patient. Calcifications were assessed by echocardiography (routinely done for all our dialysis population per national protocol), computed tomography, X-ray, and ultrasound. The study protocol was approved by the local medical research ethics committee (MRC-01-20-377). RESULTS:842 HD patients were included in this study. Vascular calcifications (VC) were prevalent in 52.6% of patients. The main site of VC was Mitral valve calcifications in 55.5% of patients. Patients with VC were significantly older and had more prevalence of diabetes mellitus ( = 0.001 and = 0.006, respectively). There was no statistically significant difference between patients with calcifications and patients without calcifications regarding serum calcium, phosphorus, and PTH level. In multivariate analysis, age and diabetes significantly increased the risk factor for calcification (95% CI 1.033-1.065, < 0.0001, and 95% CI 1.128-2.272, < 0001, respectively). Moreover, higher vitamin D levels and higher doses of IV Alfacalcidol were significant risk factors for calcifications (95% CI 1.005-1.030, < 0.007, and 95% CI 1.092-1.270, < 0.0001, respectively). CONCLUSION:Our study found that vascular calcification was widespread among our dialysis population in Qatar. Implementing the practice of echocardiography in dialysis patients was extremely helpful and the most productive in detecting vascular calcification. Diabetes mellitus almost doubles the risk for vascular calcifications in dialysis patients. These results are beneficial in identifying risk factors for vascular calcification, which can help stratify dialysis patients' risk of cardiovascular disease and optimize prevention efforts.
10.5339/qmj.2024.18
Serum magnesium level and cardiac valve calcification in hemodialysis patients.
BMC cardiovascular disorders
INTRODUCTION:Cardiac valve calcification is closely related to cardiovascular disease. The aim of this study was to investigate the magnesium level and cardiac valve calcification in hemodialysis patients. METHODS:A cross-sectional study was conducted in 105 maintenance hemodialysis patients with complete follow-up data from June 2020 to May 2021 in Beijing Tsinghua Changgung Hospital, Tsinghua University. Baseline data, including sex, age, primary disease, liver and kidney function, electrolytes and parathyroid hormone, were recorded. According to their echocardiograms, patients were divided into a cardiac valve calcification group and a noncardiac valve calcification group, and the correlations between valve calcification and clinical data were analyzed. RESULTS:Of 105 patients under hemodialysis, 60 (56.6%) were male, with an average age of 62.1 ± 13.5 years and a mean dialysis duration of 58.8 ± 45.4 months. The majority of primary renal diseases were diabetic nephropathy (55, 51.9%). Approximately 64.8% of the 105 maintenance hemodialysis patients had cardiac valve calcification, and 35.2% were in the noncardiac valve calcification group. The independent t test and the chi-square test analysis showed that the cardiac valve calcification group had older age, higher smoking rate, diabetes mellitus, lower extremity arterial occlusion, coronary heart disease, and coronary artery calcification ratio but lower parathyroid hormone, serum calcium, serum magnesium, albumin, prealbumin, and high-density lipoprotein cholesterol levels (P < 0.05). Logistic regression analysis showed that age, diabetes mellitus, coronary artery calcification, lower serum magnesium, lower serum calcium, and lower parathyroid hormone levels were associated with valve calcification. CONCLUSION:The presence of cardiac valve calcification was associated with age, calcium, phosphorus and lower magnesium level. These factors we should pay more attention in clinical practice.
10.1186/s12872-023-03662-5