Coronary Artery Calcification in Hemodialysis and Peritoneal Dialysis

Background: Vascular calcification is seen in most patients on dialysis and is strongly associated with cardiovascular mortality. Vascular calcification is promoted by phosphate, which generally reaches higher levels in hemodialysis than in peritoneal dialysis. However, whether vascular calcification develops less in peritoneal dialysis than in hemodialysis is currently unknown. Therefore, we compared coronary artery calcification (CAC), its progression, and calcification biomarkers between patients on hemodialysis and peritoneal dialysis. Methods: We measured CAC in 134 patients who had been treated exclusively with hemodialysis (n = 94) or peritoneal dialysis (n = 40) and were transplantation candidates. In 57 of them (34 on hemodialysis and 23 on peritoneal dialysis), we also measured CAC progression annually up to 3 years and the inactive species of desphospho-uncarboxylated matrix Gla protein (dp-ucMGP), fetuin-A, osteoprotegerin. We compared CAC cross-sectionally with Tobit regression. CAC progression was compared in 2 ways: with linear mixed models as the difference in square root transformed volume score per year (ΔCAC SQRV) and with Tobit mixed models. We adjusted for potential confounders. Results: In the cross-sectional cohort, CAC volume scores were 92 mm3 in hemodialysis and 492 mm3 in peritoneal dialysis (adjusted difference 436 mm3; 95% CI –47 to 919; p = 0.08). In the longitudinal cohort, peritoneal dialysis was associated with significantly more CAC progression defined as ΔCAC SQRV (adjusted difference 1.20; 95% CI 0.09 to 2.31; p = 0.03), but not with Tobit mixed models (adjusted difference in CAC score increase per year 106 mm3; 95% CI –140 to 352; p = 0.40). Peritoneal dialysis was associated with higher osteoprotegerin (adjusted p = 0.02) but not with dp-ucMGP or fetuin-A. Conclusions: Peritoneal dialysis is not associated with less CAC or CAC progression than hemodialysis, and perhaps with even more progression. This indicates that vascular calcification does not develop less in peritoneal dialysis than in hemodialysis.

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Uncarboxylated matrix Gla protein (ucMGP) is associated with coronary artery calcification in haemodialysis patients

Thrombosis and Haemostasis ◽

10.1160/th08-04-0241 ◽

2009 ◽

Vol 101 (02) ◽

pp. 359-366 ◽

Cited By ~ 63

Author(s):

Cees Vermeer ◽

Melanie Stenger ◽

Georg Mühlenbruch ◽

Andreas Mahnken ◽

Ulrich Gladziwa ◽

...

Keyword(s):

Coronary Artery ◽

Vascular Calcification ◽

Coronary Artery Calcification ◽

High Sensitivity ◽

Matrix Gla Protein ◽

Reactive Protein ◽

Dialysis Vintage ◽

The Mean ◽

Hs Crp ◽

Apparently Healthy

SummaryMatrix γ-carboxyglutamate (Gla) protein (MGP) is a potent local inhibitor of cardiovascular calcification and accumulates at areas of calcification in its uncarboxylated form (ucMGP). We previously found significantly lower circulating ucMGP levels in patients with a high vascular calcification burden. Here we report on the potential of circulating ucMGP to serve as a biomarker for vascular calcification in haemodialysis (HD) patients. Circulating ucMGP levels were measured with an ELISA-based assay in 40 HD patients who underwent multi-slice computed tomography (MSCT) scanning to quantify the extent of coronary artery calcification (CAC). The mean ucMGP level in HD patients (193 ± 65 nM) was significantly lower as compared to apparently healthy subjects of the same age (441 ± 97 nM; p < 0.001) and patients with rheumatoid arthritis (RA) without CAC (560 ± 140 nM; p < 0.001). Additionally, ucMGP levels correlated inversely with CAC scores (r = –0.41; p = 0.009), and this correlation persisted after adjustment for age, dialysis vintage and high-sensitivity C-reactive protein (hs-CRP). Since circulating ucMGP levels are significantly and inversely correlated with the extent of CAC in HD patients, ucMGP may become a tool for identifying HD patients with a high probability of cardiovascular calcification.

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Fetuin-A in patients undergoing peritoneal dialysis with coronary artery calcification

Annales UMCS Pharmacia ◽

10.2478/v10080-008-0068-z ◽

2008 ◽

Vol 21 (1) ◽

pp. 361-364

Author(s):

Beata Wojtysiak-Duma ◽

Dariusz Duma ◽

Agata Burska ◽

Krzysztof Janicki ◽

Katarzyna Zakaszewska ◽

...

Keyword(s):

Peritoneal Dialysis ◽

Coronary Artery ◽

Coronary Artery Calcification ◽

Fetuin A

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Predicting Coronary Artery Calcification by Using the Difference in Bone Mineral Densities of the Spine and Hip: A Retrospective Cross-Sectional Study in Korea

Aging Medicine and Healthcare ◽

10.33879/amh.2019.124-1902.006 ◽

2019 ◽

Vol 10 (4) ◽

pp. 133-138

Author(s):

Ji Hyun Moon ◽

◽

Yun Hwan Oh ◽

Hyeon Ju Kim ◽

Mi Hee Kong ◽

...

Keyword(s):

Coronary Artery ◽

Bone Mineral ◽

Coronary Artery Calcification ◽

Cross Sectional Study ◽

Sectional Study ◽

Cross Sectional ◽

The Difference

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Relationship Between Fetuin-A, Inflammation, Coronary Artery Calcification in Hemodialysis and Peritoneal Dialysis Patients

Turkish Nephrology Dialysis Transplantation ◽

10.5262/tndt.2012.1002.02 ◽

2012 ◽

Vol 21 (02) ◽

pp. 111-117 ◽

Cited By ~ 1

Author(s):

Kultigin Turkmen ◽

Hatice Kayikcioglu ◽

Orhan Ozbek ◽

Abduzhappar Gaipov ◽

Fatma Humeyra Yerlikaya ◽

...

Keyword(s):

Peritoneal Dialysis ◽

Coronary Artery ◽

Coronary Artery Calcification ◽

Dialysis Patients ◽

Fetuin A

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Matrix Gla protein is associated with coronary artery calcification as assessed by electron-beam computed tomography

Thrombosis and Haemostasis ◽

10.1160/th03-08-0572 ◽

2004 ◽

Vol 91 (04) ◽

pp. 790-794 ◽

Cited By ~ 88

Author(s):

Yuji Ikari ◽

Cees Vermeer ◽

Paul Dissel ◽

Kotaro Hasegawa ◽

Atsushi Shioi ◽

...

Keyword(s):

Computed Tomography ◽

Electron Beam ◽

Coronary Artery ◽

Vascular Calcification ◽

Coronary Artery Calcification ◽

Matrix Gla Protein ◽

Arterial Calcification ◽

Enzyme Linked Immunosorbent Assay ◽

Electron Beam Computed Tomography ◽

Increased Risk

SummaryMatrix Gla protein (MGP) is an extracellular matrix protein with wide tissue distribution. It has been demonstrated that the expression of MGP is detected not only in the normal blood vessels but also calcified atherosclerotic plaques, and that MGP deficient mice develop extensive arterial calcification. MGP is thought to be a regulator of vascular calcification. A recent clinical study demonstrates the association between polymorphisms of the MGP gene and increased risk of myocardial infarction. However, there are no reports of the relationship between serum MGP levels and coronary artery calcification (CAC). We evaluated the severity of CAC using electron-beam computed tomography (EBCT), and measured serum MGP levels by enzyme-linked immunosorbent assay in 115 subjects with suspected coronary artery disease. CAC scores were correlated with traditional risk factors, such as age, gender, hypertension, diabetes, hyperlipidemia and smoking. The serum MGP levels were lower in patients with CAC than in those without CAC (p<0.001). As the severity of CAC increased, there was a significant decrease in serum MGP levels. Serum MGP levels (U/L) were 116.7 ± 20.3, 104.9 ± 19.2, 95.2 ± 15.2 and 82.2 ± 19.7, (medians 115.5, 105.0, 94.8, and 81.9) for the subjects with normal (CAC score=0), mild (CAC score=1 to 99), moderate (CAC score=100 to 400), and severe (CAC score >400) coronary calcification, respectively. We found that serum MGP levels are inversely correlated with the severity of CAC. These data suggest a possible role for MGP in the development of vascular calcification.

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MO563HIGH DIALYSATE MAGNESIUM AND CORONARY ARTERY CALCIFICATION IN MAINTENANCE HEMODIALYSIS PATIENTS*

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab086.001 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Praopilad Srisuwarn ◽

Arkom Nongnuch ◽

Sethanant Sethakarun ◽

Sutipong Jongjirasiri ◽

Chanika Sritara ◽

...

Keyword(s):

Coronary Artery ◽

Vascular Calcification ◽

Coronary Artery Calcification ◽

Serum Magnesium ◽

Laboratory Data ◽

Magnesium Concentration ◽

Maintenance Hemodialysis ◽

Agatston Score ◽

The Difference ◽

Severe Calcification

Abstract Background and Aims Cardiovascular calcification is highly prevalent among patients with end-stage renal disease (ESRD). Low normal serum magnesium has been linked to a more severe degree of vascular calcification and a decrease in patient survival. An inhibitory effect of extracellular magnesium on osteogenic transformation of vascular smooth muscle cells and the upregulation of anti-calcification protein have been confirmed in vitro. Increased dialysate magnesium concentration has also been shown to lower calcification propensity of the serum of maintenance hemodialysis (HD) patients. Method This study is an investigator initiated, single-blinded, parallel-group, matched case-control clinical trial that investigated the effect of high dialysate magnesium concentration for 24 weeks on the progression of coronary artery calcification (CAC) in maintenance HD patients. The changes in laboratory data and bone mineral density (BMD) were also examined. Seventy-six ESRD patients underwent CAC screening by multi-slice computed tomography and BMD measurement by dual-x-ray absorptiometry. Only patients with Agatston score>300 were included. They were matched according to the initial CAC score that fell within 20% of one another. Twenty patients were assigned to high dialysate magnesium concentration of 1.75 mEq/L and the matched controls were kept on standard dialysate magnesium concentration of 0.7 mEq/L. CAC and BMD measurements were repeated after 24 weeks. Laboratory data were obtained prior to dialysis at study entry, 8-week intervals during the study and 2 weeks after the study ended. Results There were no significant differences in age, sex, BMI, underlying diseases, dialysis vintage, medications, baseline CAC scores and BMD. The median baseline CAC Agatston score (Volume score) were 1923 (720) and 1672 (785) in the standard and high dialysate groups, respectively. At the end of the study, a significant increase in the CAC score was observed in both groups. Because majority of the included patients had severe calcification burden at baseline, patients were categorized into 2 subgroups using the median baseline CAC Agatston (1600) and Volume scores (700) as cut-offs. Among patients with CAC Agatston score <=1600, CAC score increased significantly in the standard dialysate magnesium group (P<0.01) but was stable in the high dialysate magnesium group (P=0.33). Among patients with CAC Agatston score >1600, the severity of CAC worsened in both groups. The progression of CAC was analyzed by the difference between the follow-up and the baseline square root transformed Agatston and Volume scores. In subgroup of patients with less severe calcification, more patients in the standard dialysate magnesium group progressed compared to the high dialysate magnesium group (P=0.03). In subgroup of patients with more severe calcification, the number of progressors were comparable among the 2 groups. Serum and ionized magnesium levels increased substantially during the study and returned to baseline after the return to standard dialysate magnesium concentration. The highest predialysis serum magnesium was 3.8 mg/dL. Most patients who received high dialysate magnesium reported the disappearance of symptoms of muscle cramps (P=0.01) and requested the high dialysate magnesium be continued after the end of the study. There were no significant changes in serum calcium, phosphate or PTH levels. The decline in BMD was observed in both groups but the difference did not reach statistical significance. Conclusion High dialysate magnesium was well tolerated and could ameliorate the progression of CAC in maintenance HD patients with mild to moderate vascular calcification.

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Arterial Stiffness as a Risk Factor for Subclinical Coronary Artery Calcification in Predialysis Chronic Kidney Disease: From the KNOW-CKD Study

Kidney & Blood Pressure Research ◽

10.1159/000499648 ◽

2019 ◽

Vol 44 (3) ◽

pp. 426-434 ◽

Cited By ~ 3

Author(s):

Young Youl Hyun ◽

Hyang Kim ◽

Kook-Hwan Oh ◽

Curie Ahn ◽

Sue K. Park ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Coronary Artery ◽

Kidney Disease ◽

Arterial Stiffness ◽

Coronary Artery Calcification ◽

Cardiac Computed Tomography ◽

Cross Sectional Study ◽

Tobit Regression ◽

Cross Sectional ◽

Multivariate Logistic Model

Background/Aims: Both arterial stiffness and coronary artery calcification (CAC) are important predictors of cardiovascular disease in the general population and in chronic kidney disease (CKD) patients. Recent studies on arterial stiffness and CAC in subjects with preserved renal function have verified the association between the two. However, the relationship is not well evaluated in CKD patients. Methods: This cross-sectional study analyzed 1,385 predialysis CKD patients from the KNOW-CKD cohort. Participants were divided into four groups according to brachial-ankle pulse wave velocity (baPWV) quartile. Coronary artery calcium scores (CACS) were assessed using cardiac computed tomography and CAC was defined as a CACS >100. Results: CAC prevalence was higher in the higher baPWV groups (6.4, 9.8, 23.7, and 43.8% for the 1st to 4th quartiles of baPWV, respectively, p < 0.001). In Tobit regression analyses that were fully adjusted for traditional and renal cardiovascular risk factors, the CACS ratio comparing the highest and lowest baPWV quartiles was 3.03 (95% CI, 1.59–6.87). Similarly, the OR for CAC in the highest baPWV quartile compared to the lowest quartile was 1.98 (95% CI, 1.09–3.60) in a fully adjusted multivariate logistic model. Results were consistent across analyses with different cutoffs for CAC or with different clinically relevant subgroups. Conclusion: Increased arterial stiffness measured by high baPWV was associated with CAC in a predialysis CKD cohort. Longitudinal studies are needed to determine the effect of arterial stiffness on the development or progression of CAC in CKD.

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Role of Matrix Gla Protein in the Complex Network of Coronary Artery Disease: A Comprehensive Review

Life ◽

10.3390/life11080737 ◽

2021 ◽

Vol 11 (8) ◽

pp. 737

Author(s):

Marko Kumric ◽

Josip A. Borovac ◽

Tina Ticinovic Kurir ◽

Dinko Martinovic ◽

Ivan Frka Separovic ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Complex Network ◽

Vascular Calcification ◽

Vitamin K ◽

Clinical Decision Making ◽

Large Body ◽

Matrix Gla Protein ◽

Artery Disease

Coronary artery disease (CAD) is widely recognized as one of the most important clinical entities. In recent years, a large body of accumulated data suggest that coronary artery calcification, a process highly prevalent in patients with CAD, occurs via well-organized biologic processes, rather than passively, as previously regarded. Matrix Gla protein (MGP), a vitamin K-dependent protein, emerged as an important inhibitor of both intimal and medial vascular calcification. The functionality of MGP hinges on two post-translational modifications: phosphorylation and carboxylation. Depending on the above-noted modifications, various species of MGP may exist in circulation, each with their respective level of functionality. Emerging data suggest that dysfunctional species of MGP, markedly, dephosphorylated-uncarboxylated MGP, might find its application as biomarkers of microvascular health, and assist in clinical decision making with regard to initiation of vitamin K supplementation. Hence, in this review we summarized the current knowledge with respect to the role of MGP in the complex network of vascular calcification with concurrent inferences to CAD. In addition, we discussed the effects of warfarin use on MGP functionality, with concomitant implications to coronary plaque stability.

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Sport specific incidence and progression of coronary artery calcification among amateur athletes: a follow-up of the Measuring Athletes Risk of Cardiovascular events (MARC) study

European Heart Journal ◽

10.1093/ehjci/ehaa946.3118 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

V Aengevaeren ◽

A Mosterd ◽

T.L Braber ◽

H.M Nathoe ◽

T.M.H Eijsvogels ◽

...

Keyword(s):

Coronary Artery ◽

Coronary Artery Calcification ◽

Cardiovascular Events ◽

Coronary Atherosclerosis ◽

Sport Performance ◽

Funding Source ◽

Cross Sectional ◽

Amateur Athletes ◽

Entire Cohort

Abstract Background Emerging evidence indicates increased coronary atherosclerosis in amateur athletes. However, previous studies were limited by its cross-sectional design and limited sample size, preventing the exploration of sport specific associations with coronary atherosclerosis. Purpose We aimed to compare the incidence and progression of coronary artery calcification (CAC) between runners, cyclists and other types of athletes using a prospective cohort study with repetitive measurements. Methods Asymptomatic middle-aged men, who previously underwent a sports medical evaluation without abnormalities, were recruited in the Measuring Athlete's Risk of Cardiovascular events (MARC) study (n=318) and were asked to participate in this follow-up study. CT imaging was performed to assess CAC scores. Data was collected between 2012–2014 (i.e. baseline) and 2019–2020 (i.e. follow-up). We categorized participants as runners, cyclists or “other” sports (e.g. water polo, tennis, hockey, etc.) based on their dominant sport performance at baseline. Results We included 260 men in this interim analysis, with an average follow-up time of 6.3±0.5 years. Age (61.4±6.4 years), systolic blood pressure (143±20 mmHg), BMI (25.2±2.8 kg/m2), LDL-cholesterol (3.2±0.9 mmol/L), smoking (0.3 [0–8] pack years) and family history of coronary heart disease (28%) did not differ between runners (n=64), cyclists (n=75) and other athletes (n=121, all p>0.05). CAC was present in 137 (53%) men at baseline, which increased to 181 (70%) at follow-up. CAC scores increased from 1 [0–33] to 33 [0–129]. Cyclists had a lower CAC prevalence and CAC scores compared to individuals performing other sports at follow-up (Figure 1). Of those without CAC at baseline (n=123, 47%), cyclists less often developed CAC during follow-up compared with runners (adjusted OR=0.36 [0.17–0.79], p=0.01). In the entire cohort, CAC progression (ln delta CAC+1) was less prominent in cyclists than runners (adjusted B=−0.75 [−1.39 to −0.11], p=0.02), whereas progression of CAC in participants performing other sports did not differ from the runners. In participants with CAC at baseline, cyclists also had less CAC progression than runners (B=−0.49 [−0.95 to −0.02], p=0.04). Conclusion Cyclists have a lower incidence and less progression of CAC during 6 years of follow-up compared with runners and individuals performing other sports. Figure 1. Sport specific CAC prevalence and scores Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Hartstichting

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