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Morena-Carrere M, Jaussent I, Chenine L, Dupuy AM, Bargnoux AS, Leray-Moragues H, Klouche K, Vernhet H, Canaud B, Cristol JP. Severe Coronary Artery Calcifications in Chronic Kidney Disease Patients, Coupled with Inflammation and Bone Mineral Disease Derangement, Promote Major Adverse Cardiovascular Events through Vascular Remodeling. Kidney Blood Press Res 2024; 50:33-45. [PMID: 39602894 PMCID: PMC11844697 DOI: 10.1159/000542418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Accepted: 10/28/2024] [Indexed: 11/29/2024] Open
Abstract
INTRODUCTION Cardiovascular (CV) diseases persist as the foremost cause of morbidity/mortality among chronic kidney disease (CKD) patients. This paper examines the values of coronary artery calcification (CAC) and biomarkers of CV on major adverse CV events (MACE)/CV death in a sample of 425 non-dialysis CKD patients. METHODS At inclusion, patients underwent chest multidetector computed tomography for CAC scoring and biomarkers of CV risk including CRP, mineral metabolism markers, fibroblast growth factor-23 (FGF-23), α-Klotho, osteoprotegerin, tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin, matrix gla protein (both dephosphorylated uncarboxylated [dp-ucMGP] and total uncarboxylated), and growth differentiation factor-15 (GDF-15) were measured. Patients were followed for a median of 3.61 years (25th-75th percentiles = 1.92-6.70). RESULTS Our results reported that CAC was a major independent factor of MACE/CV mortality showing a hazard ratio of 1.71 95% (confidence interval = 1.00-2.93) after adjustment for age, gender, diabetes, and history of CV events for patients with CAC >300. Interestingly, CAC effect was further enhanced in the presence of low levels of 25(OH) vitamin D3 or α-Klotho and high levels of intact parathyroid hormone (PTH), high-sensitive C reactive protein, FGF-23, osteoprotegerin, sclerostin, dp-ucMGP, or GDF-15. CONCLUSION CAC constitutes a significant CV risk, further exacerbated by inflammation, hyperparathyroidism, and regulation of bone molecules implicated in calcification progression. This finding aligns with the original concept of multiple hits. Consequently, addressing the detrimental environment that fosters plaque vulnerability, reducing chronic low-grade inflammation, and normalizing mineral metabolism markers (such as vitamin D and PTH) and bone-regulating molecules may emerge as a viable therapeutic strategy.
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Affiliation(s)
- Marion Morena-Carrere
- PhyMedExp, University of Montpellier, INSERM, CNRS, Department of Biochemistry and Hormonology, University Hospital Center of Montpellier, Montpellier, France
| | | | - Leila Chenine
- Department of Nephrology, University Hospital Center of Montpellier, Montpellier, France
| | - Anne-Marie Dupuy
- Department of Biochemistry and Hormonology, University Hospital Center of Montpellier, Montpellier, France
| | - Anne-Sophie Bargnoux
- PhyMedExp, University of Montpellier, INSERM, CNRS, Department of Biochemistry and Hormonology, University Hospital Center of Montpellier, Montpellier, France
| | | | - Kada Klouche
- PhyMedExp, University of Montpellier, INSERM, CNRS, Department of Intensive Care Medicine, University Hospital Center of Montpellier, Montpellier, France
| | - Hélène Vernhet
- Department of Radiology, University Hospital Center of Montpellier, Montpellier, France
| | - Bernard Canaud
- University of Montpellier, Nephrology, Montpellier, France
| | - Jean-Paul Cristol
- PhyMedExp, University of Montpellier, INSERM, CNRS, Department of Biochemistry and Hormonology, University Hospital Center of Montpellier, Montpellier, France
- Charles Mion Foundation, AIDER-Santé, Montpellier, France
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Fusaro M, Pereira L, Bover J. Current and Emerging Markers and Tools Used in the Diagnosis and Management of Chronic Kidney Disease-Mineral and Bone Disorder in Non-Dialysis Adult Patients. J Clin Med 2023; 12:6306. [PMID: 37834950 PMCID: PMC10573159 DOI: 10.3390/jcm12196306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 09/19/2023] [Accepted: 09/27/2023] [Indexed: 10/15/2023] Open
Abstract
Chronic kidney disease (CKD) is a significant public health concern associated with significant morbidity and has become one of the foremost global causes of death in recent years. A frequent comorbidity of CKD is secondary hyperparathyroidism (SHPT), exemplified by high serum parathyroid hormone (PTH) levels. The mineral metabolism disturbances resulting from CKD and progression to SHPT are currently considered part of the definition of chronic kidney disease-mineral and bone disorder (CKD-MBD). However, CKD-MBD does not only include abnormalities in laboratory-measured parameters; it is a complex condition characterized by dysregulation of bone turnover, mineralization, growth and strength, accompanied by vascular or another soft-tissue calcification. Together, this increases the risk of bone fractures, cardiovascular disease, and overall mortality in CKD-MBD patients. Monitoring serum markers is essential in diagnosing SHPT and CKD-MBD, and there are several recognized indicators for prognosis, optimal clinical management and treatment response in late-stage kidney disease patients receiving dialysis. However, far fewer markers have been established for patients with non-dialysis CKD. This review provides an overview of current and emerging markers and tools used in the diagnosis and management of CKD-MBD in non-dialysis adult patients.
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Affiliation(s)
- Maria Fusaro
- National Research Council (CNR)—Institute of Clinical Physiology (IFC), Via G. Moruzzi 1, 56124 Pisa, Italy
- Department of Medicine, University of Padova, Via Giustiniani, 2, 35128 Padova, Italy
| | - Luciano Pereira
- Institute of Investigation and Innovation in Health, University of Porto, 4200-135 Porto, Portugal
- INEB—National Institute of Biomedical Engineering, University of Porto, 4150-180 Porto, Portugal
- DaVita Kidney Care, 4200-448 Porto, Portugal
- Faculty of Medicine, University of Porto, 4200-250 Porto, Portugal
| | - Jordi Bover
- Nephrology Department, University Hospital Germans Trias i Pujol (HGiTP), 08916 Barcelona, Spain
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3
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Dai Z, Zhang X. Pathophysiology and Clinical Impacts of Chronic Kidney Disease on Coronary Artery Calcification. J Cardiovasc Dev Dis 2023; 10:jcdd10050207. [PMID: 37233174 DOI: 10.3390/jcdd10050207] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 05/05/2023] [Accepted: 05/06/2023] [Indexed: 05/27/2023] Open
Abstract
The global prevalence of chronic kidney disease (CKD) has increased in recent years. Adverse cardiovascular events have become the main cause of life-threatening events in patients with CKD, and vascular calcification is a risk factor for cardiovascular disease. Vascular calcification, especially coronary artery calcification, is more prevalent, severe, rapidly progressive, and harmful in patients with CKD. Some features and risk factors are unique to vascular calcification in patients with CKD; the formation of vascular calcification is not only influenced by the phenotypic transformation of vascular smooth muscle cells, but also by electrolyte and endocrine dysfunction, uremic toxin accumulation, and other novel factors. The study on the mechanism of vascular calcification in patients with renal insufficiency can provide a basis and new target for the prevention and treatment of this disease. This review aims to illustrate the impact of CKD on vascular calcification and to discuss the recent research data on the pathogenesis and factors involved in vascular calcification, mainly focusing on coronary artery calcification, in patients with CKD.
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Affiliation(s)
- Zhuoming Dai
- Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha 410011, China
| | - Xiangyu Zhang
- Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha 410011, China
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4
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Sun XJ, Liu NF. Diabetic mellitus, vascular calcification and hypoxia: A complex and neglected tripartite relationship. Cell Signal 2021; 91:110219. [PMID: 34921978 DOI: 10.1016/j.cellsig.2021.110219] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Revised: 12/11/2021] [Accepted: 12/11/2021] [Indexed: 11/15/2022]
Abstract
DM (diabetic mellitus) and its common vascular complications VC (vascular calcification), are increasingly harmful to human health. In recent years, the research on the relationship between DM and VC is also deepening. Hypoxia, as one of the pathogenic factors of many disease models, is also closely related to the occurrence of DM and VC. There are some studies on the role of hypoxia in the pathogenesis of DM and VC respectively, but no one has made an in-depth summary of the systematic connection between hypoxia, DM and VC. Therefore, what we want to review in this article are the relationship between DM, VC and hypoxia, respectively, as well as the role of hypoxia in the development of DM and VC, which has little concern but is a novel and potentially target that may provide some new ideas for the prevention and treatment of DM, VC, especially diabetic VC.
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Affiliation(s)
- Xue-Jiao Sun
- Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao, Nanjing 210009, PR China
| | - Nai-Feng Liu
- Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao, Nanjing 210009, PR China.
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Bonato FOB, Karohl C, Canziani MEF. Diagnosis of vascular calcification related to mineral and bone metabolism disorders in chronic kidney disease. J Bras Nefrol 2021; 43:628-631. [PMID: 34910796 PMCID: PMC8823916 DOI: 10.1590/2175-8239-jbn-2021-s104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Accepted: 06/24/2021] [Indexed: 11/22/2022] Open
Affiliation(s)
| | - Cristina Karohl
- Universidade Federal do Rio Grande do Sul, Porto Alegre, RS,
Brazil
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6
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Wu PY, Lee SY, Chang KV, Chao CT, Huang JW. Gender-Related Differences in Chronic Kidney Disease-Associated Vascular Calcification Risk and Potential Risk Mediators: A Scoping Review. Healthcare (Basel) 2021; 9:979. [PMID: 34442116 PMCID: PMC8394860 DOI: 10.3390/healthcare9080979] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 07/26/2021] [Accepted: 07/28/2021] [Indexed: 12/13/2022] Open
Abstract
Vascular calcification (VC) involves the deposition of calcium apatite in vascular intima or media. Individuals of advanced age, having diabetes mellitus or chronic kidney disease (CKD) are particularly at risk. The pathogenesis of CKD-associated VC evolves considerably. The core driver is the phenotypic change involving vascular wall constituent cells toward manifestations similar to that undergone by osteoblasts. Gender-related differences are observed regarding the expressions of osteogenesis-regulating effectors, and presumably the prevalence/risk of CKD-associated VC exhibits gender-related differences as well. Despite the wealth of data focusing on gender-related differences in the risk of atherosclerosis, few report whether gender modifies the risk of VC, especially CKD-associated cases. We systematically identified studies of CKD-associated VC or its regulators/modifiers reporting data about gender distributions, and extracted results from 167 articles. A significantly higher risk of CKD-associated VC was observed in males among the majority of original investigations. However, substantial heterogeneity exists, since multiple large-scale studies yielded neutral findings. Differences in gender-related VC risk may result from variations in VC assessment methods, the anatomical segments of interest, study sample size, and even the ethnic origins of participants. From a biological perspective, plausible mediators of gender-related VC differences include body composition discrepancies, alterations involving lipid profiles, inflammatory severity, diversities in matrix Gla protein (MGP), soluble Klotho, vitamin D, sclerostin, parathyroid hormone (PTH), fibroblast growth factor-23 (FGF-23), and osteoprotegerin levels. Based on our findings, it may be inappropriate to monotonously assume that male patients with CKD are at risk of VC compared to females, and we should consider more background in context before result interpretation.
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Affiliation(s)
- Patrick Yihong Wu
- School of Medicine, National Taiwan University College of Medicine, Taipei 100233, Taiwan;
| | - Szu-Ying Lee
- Nephrology Division, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County 640, Taiwan; (S.-Y.L.); (J.-W.H.)
| | - Ke-Vin Chang
- Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital BeiHu Branch, Taipei 10845, Taiwan;
| | - Chia-Ter Chao
- Graduate Institute of Toxicology, National Taiwan University College of Medicine, Taipei 100233, Taiwan
- Nephrology Division, Department of Internal Medicine, National Taiwan University College of Medicine, Taipei 100233, Taiwan
- Nephrology Division, Department of Internal Medicine, National Taiwan University Hospital BeiHu Branch, Taipei 10845, Taiwan
| | - Jenq-Wen Huang
- Nephrology Division, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County 640, Taiwan; (S.-Y.L.); (J.-W.H.)
- Nephrology Division, Department of Internal Medicine, National Taiwan University College of Medicine, Taipei 100233, Taiwan
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Evaluating the Independent Impact of Renal Function Decline on Coronary Artery Calcification in Patients Undergone Cardiac CT Scan. Nephrourol Mon 2021. [DOI: 10.5812/numonthly.113534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background: Cardiovascular events are the leading global cause of death. Calcification of coronary arteries is a common complication of renal failure and the leading cause of death in this population. However, its multifactorial mechanism is not fully understood. Objectives: The current study aimed to, firstly, investigate the association between renal dysfunction and the calcification of coronary arteries in patients with severe and milder stages of renal failure and, secondly, to determine the role of this variable by eliminating the effect of established confounding factors. Methods: Following a retrospective design, 261 patients with cardiovascular risk factors or atypical symptoms were investigated. Estimated GFR (glomerular filtration rate) was calculated using both Cockcroft-Gault and MDRD equations. An ECG-gated multidetector CT scan was performed to calculate CACS (coronary artery calcification score) using the Agatston method. The presence of significant CAC (coronary artery calcification) was defined as CACS > 100. Univariate and multivariate analyses were performed using binary logistic regression. Results: A total of 134 cases were diagnosed with CAC, and the mean CACS was 83.4 ± 18. According to univariate analysis, older age, male gender, systolic and diastolic blood pressure, and higher TG levels were correlated with the degree of CAC. HbA1C showed a weak correlation with CACS (P-value = 0.04). Renal insufficiency resulted in increased CAC, and lower eGFR (calculated with both Cockgraft-Gault and MDRD equations) was associated with higher calcification (P-value < 0.01). Our analysis shows that serum Ca, P, LDL, and HDL levels do not have a significant influence on calcification changes. After adjusting for confounding factors, male sex, age, triglyceride level, and eGFR were recognized as independent risk factors for CACS ≥ 100, a marker of coronary artery atherosclerosis. However, HbA1C and systolic and diastolic blood pressure were no longer considered as factors that contribute to the risk of CAC. Conclusions: We observed a gradual and independent association between lower eGFR and higher CAC scores.
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Dube P, DeRiso A, Patel M, Battepati D, Khatib-Shahidi B, Sharma H, Gupta R, Malhotra D, Dworkin L, Haller S, Kennedy D. Vascular Calcification in Chronic Kidney Disease: Diversity in the Vessel Wall. Biomedicines 2021; 9:biomedicines9040404. [PMID: 33917965 PMCID: PMC8068383 DOI: 10.3390/biomedicines9040404] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 04/01/2021] [Accepted: 04/05/2021] [Indexed: 12/14/2022] Open
Abstract
Vascular calcification (VC) is one of the major causes of cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). VC is a complex process expressing similarity to bone metabolism in onset and progression. VC in CKD is promoted by various factors not limited to hyperphosphatemia, Ca/Pi imbalance, uremic toxins, chronic inflammation, oxidative stress, and activation of multiple signaling pathways in different cell types, including vascular smooth muscle cells (VSMCs), macrophages, and endothelial cells. In the current review, we provide an in-depth analysis of the various kinds of VC, the clinical significance and available therapies, significant contributions from multiple cell types, and the associated cellular and molecular mechanisms for the VC process in the setting of CKD. Thus, we seek to highlight the key factors and cell types driving the pathology of VC in CKD in order to assist in the identification of preventative, diagnostic, and therapeutic strategies for patients burdened with this disease.
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9
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Laurain A, Rubera I, Duranton C, Rutsch F, Nitschke Y, Ray E, Vido S, Sicard A, Lefthériotis G, Favre G. Alkaline Phosphatases Account for Low Plasma Levels of Inorganic Pyrophosphate in Chronic Kidney Disease. Front Cell Dev Biol 2020; 8:586831. [PMID: 33425894 PMCID: PMC7793922 DOI: 10.3389/fcell.2020.586831] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Accepted: 11/16/2020] [Indexed: 01/19/2023] Open
Abstract
Introduction Patients on dialysis and kidney transplant recipients (KTR) present the syndrome of mineral and bone disorders (MBD), which share common traits with monogenic calcifying diseases related to disturbances of the purinergic system. Low plasma levels of inorganic pyrophosphate (PPi) and ectopic vascular calcifications belong to these two conditions. This suggests that the purinergic system may be altered in chronic kidney disease with MBD. Therefore, we perform a transversal pilot study in order to compare the determinants of PPi homeostasis and the plasma levels of PPi in patients on dialysis, in KTR and in healthy people. Patients and Methods We included 10 controls, 10 patients on maintenance dialysis, 10 early KTR 3 ± 1 months after transplantation and nine late KTR 24 ± 3 months after transplantation. We measured aortic calcifications, plasma and urine levels of PPi, the renal fractional excretion of PPi (FePPi), nucleoside triphosphate hydrolase (NPP) and ALP activities in plasma. Correlations and comparisons were assessed with non-parametric tests. Results Low PPi was found in patients on dialysis [1.11 (0.88–1.35), p = 0.004], in early KTR [0.91 (0.66–0.98), p = 0.0003] and in late KTR [1.16 (1.07–1.45), p = 0.02] compared to controls [1.66 (1.31–1.72) μmol/L]. Arterial calcifications were higher in patients on dialysis than in controls [9 (1–75) vs. 399 (25–526) calcium score/cm2, p < 0.05]. ALP activity was augmented in patients on dialysis [113 (74–160), p = 0.01] and in early KTR [120 (84–142), p = 0.002] compared to controls [64 (56–70) UI/L]. The activity of NPP and FePPi were not different between groups. ALP activity was negatively correlated with PPi (r = −0.49, p = 0.001). Discussion Patients on dialysis and KTR have low plasma levels of PPi, which are partly related to high ALP activity, but neither to low NPP activity, nor to increased renal excretion of PPi. Further work is necessary to explore comprehensively the purinergic system in chronic kidney disease.
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Affiliation(s)
- Audrey Laurain
- Faculty of Medicine, Côte d'Azur University, Nice, France.,UMR 7073, Laboratory of Physiology and Molecular Medicine (LP2M), Centre National de la Recherche Scientifique, Nice, France.,Nephrology Department, University Hospital, Nice, France
| | - Isabelle Rubera
- UMR 7073, Laboratory of Physiology and Molecular Medicine (LP2M), Centre National de la Recherche Scientifique, Nice, France
| | - Christophe Duranton
- UMR 7073, Laboratory of Physiology and Molecular Medicine (LP2M), Centre National de la Recherche Scientifique, Nice, France
| | - Frank Rutsch
- Department of General Pediatrics, Muenster University Children's Hospital, Muenster, Germany
| | - Yvonne Nitschke
- Department of General Pediatrics, Muenster University Children's Hospital, Muenster, Germany
| | - Elodie Ray
- Department of Vascular Medicine and Surgery, University Hospital, Nice, France
| | - Sandor Vido
- Nephrology Department, University Hospital, Nice, France
| | - Antoine Sicard
- Faculty of Medicine, Côte d'Azur University, Nice, France.,Nephrology Department, University Hospital, Nice, France
| | - Georges Lefthériotis
- Faculty of Medicine, Côte d'Azur University, Nice, France.,UMR 7073, Laboratory of Physiology and Molecular Medicine (LP2M), Centre National de la Recherche Scientifique, Nice, France.,Department of Vascular Medicine and Surgery, University Hospital, Nice, France
| | - Guillaume Favre
- Faculty of Medicine, Côte d'Azur University, Nice, France.,UMR 7073, Laboratory of Physiology and Molecular Medicine (LP2M), Centre National de la Recherche Scientifique, Nice, France.,Nephrology Department, University Hospital, Nice, France
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Li Z, Wu J, Zhang X, Ou C, Zhong X, Chen Y, Lu L, Liu H, Li Y, Liu X, Wu B, Wang Y, Yang P, Yan J, Chen M. CDC42 promotes vascular calcification in chronic kidney disease. J Pathol 2019; 249:461-471. [PMID: 31397884 DOI: 10.1002/path.5334] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 07/16/2019] [Accepted: 08/06/2019] [Indexed: 01/12/2023]
Abstract
Vascular calcification is prevalent in patients with chronic kidney disease (CKD) and a major risk factor of cardiovascular disease. Vascular calcification is now recognised as a biological process similar to bone formation involving osteogenic differentiation of vascular smooth muscle cells (VSMCs). Cell division cycle 42 (CDC42), a Rac1 family member GTPase, is essential for cartilage development during endochondral bone formation. However, whether CDC42 affects osteogenic differentiation of VSMCs and vascular calcification remains unknown. In the present study, we observed a significant increase in the expression of CDC42 both in rat VSMCs and in calcified arteries during vascular calcification. Alizarin red staining and calcium content assay revealed that adenovirus-mediated CDC42 overexpression led to an apparent VSMC calcification in the presence of calcifying medium, accompanied with up-regulation of bone-related molecules including RUNX2 and BMP2. By contrast, inhibition of CDC42 by ML141 significantly blocked calcification of VSMCs in vitro and aortic rings ex vivo. Moreover, ML141 markedly attenuated vascular calcification in rats with CKD. Furthermore, pharmacological inhibition of AKT signal was shown to block CDC42-induced VSMC calcification. These findings demonstrate for the first time that CDC42 contributes to vascular calcification through a mechanism involving AKT signalling; this uncovered a new function of CDC42 in regulating vascular calcification. This may provide a potential therapeutic target for the treatment of vascular calcification in the context of CKD. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Affiliation(s)
- Zehua Li
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China.,Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, PR China.,Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China
| | - Ji Wu
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China.,Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, PR China.,Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China
| | - Xiuli Zhang
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China.,Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, PR China.,Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China
| | - Caiwen Ou
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China.,Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, PR China.,Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China
| | - Xinglong Zhong
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China.,Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, PR China.,Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China
| | - Yanting Chen
- Department of Pathophysiology, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou, PR China
| | - Lihe Lu
- Department of Pathophysiology, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou, PR China
| | - Hailin Liu
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China.,Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, PR China.,Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China
| | - Yining Li
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China.,Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, PR China.,Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China
| | - Xiaoyu Liu
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China.,Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, PR China.,Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China
| | - Bo Wu
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China.,Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, PR China.,Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China
| | - Yuxi Wang
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China.,Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, PR China.,Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China
| | - Pingzhen Yang
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China.,Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, PR China.,Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China
| | - Jianyun Yan
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China.,Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, PR China.,Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China
| | - Minsheng Chen
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China.,Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, PR China.,Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China
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Wang XR, Zhang JJ, Xu XX, Wu YG. Prevalence of coronary artery calcification and its association with mortality, cardiovascular events in patients with chronic kidney disease: a systematic review and meta-analysis. Ren Fail 2019; 41:244-256. [PMID: 31014155 PMCID: PMC6493287 DOI: 10.1080/0886022x.2019.1595646] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
PURPOSE To date, the prevalence and prognostic role of coronary artery calcification (CAC) in patients with chronic kidney disease (CKD) have been investigated in several studies, but have yielded conflicting results. The aim of this meta-analysis is to derive a more precise estimation of CAC prevalence in CKD patients and its association with cardiovascular events and mortality. METHODS The relevant literature was identified and evaluated from inception until July 2018 through multiple search strategies on PubMed, Embase, and Web of Science. Cross-sectional or cohort (baseline data) studies reporting CAC prevalence were included. Data extracted from eligible studies were used to calculate effect estimates (ESs) and 95% confidence intervals (95%CI). We searched databases for observational studies that explored baseline CAC and subsequent cardiovascular or all-cause mortality risk in CKD patients. RESULTS The meta-analysis included 47 studies; 38 of these were included in the final analysis of CAC prevalence. The pooled prevalence of CAC in random effect model was 60% (95%CI 53-68%). CAC was positively associated with an increased risk of all-cause mortality (hazard ratio [HR] 3.44; 95%CI 2.40-4.94), cardiovascular mortality (HR 3.87; 95%CI 2.06-7.26), and cardiovascular events (HR 2.09; 95%CI 1.19-3.67), when comparing individuals in the top CAC score group to those in the bottom CAC score group. CONCLUSIONS The pooled prevalence of CAC is highly prevalent. CAC is independently associated with all-cause and cardiovascular mortality risk as well as cardiovascular events among CKD patients. In view of the high heterogeneity, larger clinical trials are still needed.
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Affiliation(s)
- Xue-Rong Wang
- a Department of Nephrology , The First Affiliated Hospital of Anhui Medical University , Hefei , China.,b Department of Nephrology , The Second Hospital of Anhui Medical University , Hefei , China
| | - Jing-Jing Zhang
- a Department of Nephrology , The First Affiliated Hospital of Anhui Medical University , Hefei , China.,b Department of Nephrology , The Second Hospital of Anhui Medical University , Hefei , China
| | - Xing-Xin Xu
- a Department of Nephrology , The First Affiliated Hospital of Anhui Medical University , Hefei , China
| | - Yong-Gui Wu
- a Department of Nephrology , The First Affiliated Hospital of Anhui Medical University , Hefei , China
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12
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Lee JH, Rizvi A, Hartaigh BÓ, Han D, Park MW, Roudsari HM, Stuijfzand WJ, Gransar H, Lu Y, Callister TQ, Berman DS, DeLago A, Hadamitzky M, Hausleiter J, Al-Mallah MH, Budoff MJ, Kaufmann PA, Raff GL, Chinnaiyan K, Cademartiri F, Maffei E, Villines TC, Kim YJ, Leipsic J, Feuchtner G, Pontone G, Andreini D, Marques H, de Araújo Gonçalves P, Rubinshtein R, Achenbach S, Shaw LJ, Chow BJW, Cury RC, Bax JJ, Chang HJ, Jones EC, Lin FY, Min JK, Peña JM. The Predictive Value of Coronary Artery Calcium Scoring for Major Adverse Cardiac Events According to Renal Function (from the Coronary Computed Tomography Angiography Evaluation for Clinical Outcomes: An International Multicenter [CONFIRM] Registry). Am J Cardiol 2019; 123:1435-1442. [PMID: 30850210 DOI: 10.1016/j.amjcard.2019.01.055] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Revised: 01/18/2019] [Accepted: 01/22/2019] [Indexed: 01/07/2023]
Abstract
The prognostic performance of coronary artery calcium score (CACS) for predicting adverse outcomes in patients with decreased renal function remains unclear. We aimed to examine whether CACS improves risk stratification by demonstrating incremental value beyond a traditional risk score according to renal function status. 9,563 individuals without known coronary artery disease were enrolled. Estimated glomerular filtration rate (eGFR, ml/min/1.73 m2) was ascertained using the modified Modification of Diet in Renal Disease formula, and was categorized as: ≥90, 60 to 89, and <60. CACS was categorized as 0, 1 to 100, 101 to 400, and >400. Multivariable Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (95% CI) for major adverse cardiac events (MACE), comprising all-cause mortality, myocardial infarction, and late revascularization (>90 days). Mean age was 55.8 ± 11.5 years (52.8% male). In total, 261 (2.7%) patients experienced MACE over a median follow-up of 24.5 months (interquartile range: 16.9 to 41.1). Incident MACE increased with higher CACS across each eGFR category, with the highest rate observed among patients with CACS >400 and eGFR <60 (95.1 per 1,000 person-years). A CACS >400 increased MACE risk with HR 4.46 (95% CI 1.68 to 11.85), 6.63 (95% CI 4.03 to 10.92), and 6.14 (95% CI 2.85 to 13.21) for eGFR ≥90, 60 to 89, and <60, respectively, as compared with CACS 0. Further, CACS improved discrimination and reclassification beyond Framingham 10-year risk score (FRS) (AUC: 0.70 vs 0.64; category free-NRI: 0.51, all p <0.001) for predicting MACE in patients with impaired renal function (eGFR < 90). In conclusion, CACS improved risk stratification and provided incremental value beyond FRS for predicting MACE, irrespective of eGFR status.
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Affiliation(s)
- Ji Hyun Lee
- Dalio Institute of Cardiovascular Imaging, Department of Radiology, New York-Presbyterian Hospital and Weill Cornell Medicine, New York, New York; Division of Cardiology, Department of Internal Medicine, Myongji Hospital, Hanyang University Medical Center, Goyang-si, South Korea; Division of Cardiology, Severance Cardiovascular Hospital and Severance Biomedical Science Institute, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea
| | - Asim Rizvi
- Dalio Institute of Cardiovascular Imaging, Department of Radiology, New York-Presbyterian Hospital and Weill Cornell Medicine, New York, New York; Department of Radiology, Mayo Clinic, Rochester, Minnesota
| | - Bríain Ó Hartaigh
- Dalio Institute of Cardiovascular Imaging, Department of Radiology, New York-Presbyterian Hospital and Weill Cornell Medicine, New York, New York
| | - Donghee Han
- Dalio Institute of Cardiovascular Imaging, Department of Radiology, New York-Presbyterian Hospital and Weill Cornell Medicine, New York, New York; Division of Cardiology, Severance Cardiovascular Hospital and Severance Biomedical Science Institute, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea
| | - Mahn Won Park
- Dalio Institute of Cardiovascular Imaging, Department of Radiology, New York-Presbyterian Hospital and Weill Cornell Medicine, New York, New York
| | - Hadi Mirhedayati Roudsari
- Dalio Institute of Cardiovascular Imaging, Department of Radiology, New York-Presbyterian Hospital and Weill Cornell Medicine, New York, New York
| | - Wijnand J Stuijfzand
- Dalio Institute of Cardiovascular Imaging, Department of Radiology, New York-Presbyterian Hospital and Weill Cornell Medicine, New York, New York
| | - Heidi Gransar
- Department of Imaging, Cedars Sinai Medical Center, Los Angeles, California
| | - Yao Lu
- Department of Healthcare Policy and Research, New York-Presbyterian Hospital and the Weill Cornell Medical College, New York, New York
| | | | - Daniel S Berman
- Department of Imaging and Medicine, Cedars Sinai Medical Center, Los Angeles, California
| | | | - Martin Hadamitzky
- Department of Radiology and Nuclear Medicine, German Heart Center, Munich, Germany
| | - Joerg Hausleiter
- Medizinische Klinik I der Ludwig-Maximilians-Universität München, Munich, Germany
| | - Mouaz H Al-Mallah
- Houston Methodist DeBakey Heart & Vascular Center, Houston Methodist Hospital, Houston, Texas
| | - Matthew J Budoff
- Department of Medicine, Los Angeles Biomedical Research Institute, Torrance, California
| | - Philipp A Kaufmann
- Department of Nuclear Medicine, University Hospital and University of Zurich, Zurich, Switzerland
| | - Gilbert L Raff
- Department of Cardiology, William Beaumont Hospital, Royal Oak, Michigan
| | - Kavitha Chinnaiyan
- Department of Cardiology, William Beaumont Hospital, Royal Oak, Michigan
| | - Filippo Cademartiri
- Cardiovascular Imaging Center, Department of Radiology, SDN IRCCS, Naples, Italy
| | - Erica Maffei
- Department of Radiology, Area Vasta 1/ASUR Marche, Urbino, Italy
| | - Todd C Villines
- Department of Cardiology, Walter Reed National Military Medical Center, Bethesda, Maryland
| | - Yong-Jin Kim
- Seoul National University Hospital, Seoul, South Korea
| | - Jonathon Leipsic
- Department of Medicine and Radiology, University of British Columbia, Vancouver, British Columbia, Canada
| | - Gudrun Feuchtner
- Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria
| | | | | | - Hugo Marques
- UNICA, Unit of Cardiovascular Imaging, Hospital da Luz, Lisboa, Portugal
| | | | - Ronen Rubinshtein
- Department of Cardiology at the Lady Davis Carmel Medical Center, The Ruth and Bruce Rappaport School of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Stephan Achenbach
- Department of Cardiology, Friedrich-Alexander-University Erlangen-Nuremburg, Erlangen, Germany
| | - Leslee J Shaw
- Dalio Institute of Cardiovascular Imaging, Department of Radiology, New York-Presbyterian Hospital and Weill Cornell Medicine, New York, New York
| | - Benjamin J W Chow
- Department of Medicine and Radiology, University of Ottawa, Ottawa, Ontario, Canada
| | - Ricardo C Cury
- Department of Radiology, Miami Cardiac and Vascular Institute, Miami, Florida, USA
| | - Jeroen J Bax
- Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Hyuk-Jae Chang
- Division of Cardiology, Severance Cardiovascular Hospital and Severance Biomedical Science Institute, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea
| | - Erica C Jones
- Dalio Institute of Cardiovascular Imaging, Department of Radiology, New York-Presbyterian Hospital and Weill Cornell Medicine, New York, New York
| | - Fay Y Lin
- Dalio Institute of Cardiovascular Imaging, Department of Radiology, New York-Presbyterian Hospital and Weill Cornell Medicine, New York, New York
| | - James K Min
- Dalio Institute of Cardiovascular Imaging, Department of Radiology, New York-Presbyterian Hospital and Weill Cornell Medicine, New York, New York
| | - Jessica M Peña
- Dalio Institute of Cardiovascular Imaging, Department of Radiology, New York-Presbyterian Hospital and Weill Cornell Medicine, New York, New York.
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13
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Fujii H, Kono K, Nishi S. Characteristics of coronary artery disease in chronic kidney disease. Clin Exp Nephrol 2019; 23:725-732. [PMID: 30830548 PMCID: PMC6511359 DOI: 10.1007/s10157-019-01718-5] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2018] [Accepted: 02/07/2019] [Indexed: 02/07/2023]
Abstract
Patients with chronic kidney disease (CKD) commonly experience cardiovascular disease (CVD), and a major cause of death in these patients is CVD. Therefore, the prevention of CVD progression is very crucial in patients with CKD. Recently, this relationship between CKD and CVD has increasingly been examined, and a concept termed “cardiorenal syndrome” has been advocated. Coronary artery disease (CAD) and myocardial injury are crucial factors that contribute to the occurrence of CVD. The initial step CAD is endothelial dysfunction that can be detected as a decrease in the coronary flow reserve (CFR). The previous studies have reported that decreased CFR is significantly correlated to coronary events and mortality. Furthermore, CFR reduces with a decline in the kidney function. Another important presentation of CAD is coronary artery calcification. Vascular calcification is a crucial pathophysiological state, particularly in patients with CKD, and it affects the stability of coronary atherosclerotic plaque. In CKD, not only the traditional risk factors but also CKD-related non-traditional risk factors play key roles in CVD progression. Therefore, the mechanisms responsible for CVD progression are very complex; however, their clarification is crucial to improve the prognosis in patients with CKD.
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Affiliation(s)
- Hideki Fujii
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.
| | - Keiji Kono
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Shinichi Nishi
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
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14
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Choi YJ, Park JB, Hwang IC, Lee SP, Kim HK, Kim YJ, Sohn DW. Proteinuria is an independent predictor of rapid progression of mild to moderate aortic stenosis in patients with preserved renal function. Int J Cardiovasc Imaging 2018; 35:481-489. [PMID: 30343402 DOI: 10.1007/s10554-018-1473-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Accepted: 10/12/2018] [Indexed: 11/28/2022]
Abstract
Although proteinuria is a well-known risk factor for cardiovascular disease, its relationship with the progression of aortic stenosis (AS) has not been established. Our aim was to investigate the relationship between proteinuria (detected by urine dipstick test) and AS progression (assessed by the annualized reduction rate of aortic valve area [AVA]). A total of 460 patients with mild to moderate AS (defined by a peak velocity of 2.0-4.0 m/s) without end-stage renal disease who underwent two echocardiograms at least 3 months apart were included. The progression of AS was significantly faster in patients with proteinuria than those without (108 patients vs. 352 patients; annualized reduction rate of AVA, - 7.7 ± 13.5% vs. - 4.5 ± 11.6%; p = 0.017). The relationship between the presence of proteinuria and the accelerated progression of AS was significant among patients with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 (- 11.0 ± 17.5% vs. - 4.2 ± 10.0%; p < 0.001), but not among those with eGFR 15-60 mL/min/1.73 m2 (- 5.8 ± 10.3 vs. - 5.3 ± 14.8%; p = 0.822). When stratified by the presence of diabetes, the association of proteinuria with AS progression was only significant in patients without diabetes (- 8.1 ± 12.0% vs. - 8.1 ± 15.7%; p = 0.018). Multivariable logistic regression analysis identified that the presence of proteinuria was an independent predictor of AS progression. The progression of AS was accelerated in patients with mild to moderate AS and proteinuria, particularly among those with preserved renal function and no diabetes.
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Affiliation(s)
- You-Jung Choi
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jun-Bean Park
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. .,Cardiovascular Center, Seoul National University Hospital, Seoul, Republic of Korea. .,Division of Cardiology, Department of Internal Medicine, Office of Medical Education, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.
| | - In-Chang Hwang
- Division of Cardiology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - Seung-Pyo Lee
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.,Cardiovascular Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Hyung-Kwan Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.,Cardiovascular Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Yong-Jin Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.,Cardiovascular Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Dae-Won Sohn
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.,Cardiovascular Center, Seoul National University Hospital, Seoul, Republic of Korea
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15
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Li B, Li Y, Zhang T, Song L, Lei C, Zhao Y, He B, Zhao Y, Yin B, Jin X, Li T. Preptin is a new predictor of coronary artery calcification. Clin Chim Acta 2018; 485:133-138. [PMID: 29958889 DOI: 10.1016/j.cca.2018.06.038] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2018] [Revised: 06/22/2018] [Accepted: 06/25/2018] [Indexed: 01/07/2023]
Abstract
BACKGROUND We aimed to assess whether an elevated preptin level is associated with coronary artery calcification (CAC). METHODS Two hundred and twenty participants with suspected cardiovascular disease were recruited. CAC was measured using 320-row-detector dynamic volume CT, and the patients were divided into 2 groups: the non-CAC group (with an Agatston score = 0) and the CAC group (with an Agatston score > 0). RESULTS The serum preptin level was significantly elevated in the CAC group compared with the non-CAC group. In logistic regression analysis, preptin, as well as age, gender, hypertension history and history of β-blocker use, were independent predictors of a positive CAC score. The highest preptin quintile of patients had a higher CAC level compared with other quintiles. Binary logistic regression analyses showed that the highest preptin quintile had a 2.9-time increased odds ratio of an elevated CAC level than the other 4 quintile patients. CONCLUSIONS This study demonstrated that serum preptin was associated with coronary artery calcification.
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Affiliation(s)
- Bo Li
- Department of Cardiology, Central Hospital of Zibo, NO, 54, Gong Qing Tuan Xi Road, Zibo 255036, PR China
| | - Yuhua Li
- Department of Imaging, Central Hospital of Zibo, NO, 54, Gong Qing Tuan Xi Road, Zibo 255036, PR China
| | - Tongtong Zhang
- Department of Clinical Laboratory, Central Hospital of Zibo, NO, 54, Gong Qing Tuan Xi Road, Zibo 255036, PR China
| | - Litao Song
- Department of Imaging, Central Hospital of Zibo, NO, 54, Gong Qing Tuan Xi Road, Zibo 255036, PR China
| | - Chengbin Lei
- Department of Clinical Laboratory, Central Hospital of Zibo, NO, 54, Gong Qing Tuan Xi Road, Zibo 255036, PR China
| | - Yan Zhao
- Department of Clinical Laboratory, Central Hospital of Zibo, NO, 54, Gong Qing Tuan Xi Road, Zibo 255036, PR China
| | - Bing He
- Department of Imaging, Central Hospital of Zibo, NO, 54, Gong Qing Tuan Xi Road, Zibo 255036, PR China
| | - Yunhe Zhao
- Department of Cardiology, Central Hospital of Zibo, NO, 54, Gong Qing Tuan Xi Road, Zibo 255036, PR China
| | - Bo Yin
- Department of Cardiology, Central Hospital of Zibo, NO, 54, Gong Qing Tuan Xi Road, Zibo 255036, PR China
| | - Xiaodong Jin
- Department of Geriatrics, Central Hospital of Zibo, NO, 54, Gong Qing Tuan Xi Road, Zibo 255036, PR China.
| | - Tao Li
- Center of Translational Medicine, Central Hospital of Zibo, NO, 54, Gong Qing Tuan Xi Road, Zibo 255036, PR China.
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16
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Jover E, Silvente A, Marin F, Martinez‐Gonzalez J, Orriols M, Martinez CM, Puche CM, Valdés M, Rodriguez C, Hernández‐Romero D. Inhibition of enzymes involved in collagen cross‐linking reduces vascular smooth muscle cell calcification. FASEB J 2018; 32:4459-4469. [DOI: 10.1096/fj.201700653r] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Eva Jover
- Hospital Clínico Universitario Virgen de la ArrixacaUniversidad de MurciaInstituto Murciano de Investigatión Biosanitaria (IMIB)‐ArrixacaMurciaSpain
- Bristol Medical School of Translational Health SciencesUniversity of BristolBristolUnited Kingdom
| | - Ana Silvente
- Hospital Clínico Universitario Virgen de la ArrixacaUniversidad de MurciaInstituto Murciano de Investigatión Biosanitaria (IMIB)‐ArrixacaMurciaSpain
| | - Francisco Marin
- Hospital Clínico Universitario Virgen de la ArrixacaUniversidad de MurciaInstituto Murciano de Investigatión Biosanitaria (IMIB)‐ArrixacaMurciaSpain
- Centro de Investigatión Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV)MadridSpain
| | - Jose Martinez‐Gonzalez
- Centro de Investigatión Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV)MadridSpain
- Instituto de Investigaciones Biomédicas de Barcelona‐Consejo Superior de Investigaciones Cientificas (IIBB‐CSIC)Institut d'Investigacions Biomèdiques (IIB)‐Sant PauBarcelonaSpain
| | - Mar Orriols
- Centro de Investigatión Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV)MadridSpain
| | | | - Carmen María Puche
- Hospital Clínico Universitario Virgen de la ArrixacaUniversidad de MurciaInstituto Murciano de Investigatión Biosanitaria (IMIB)‐ArrixacaMurciaSpain
| | - Mariano Valdés
- Hospital Clínico Universitario Virgen de la ArrixacaUniversidad de MurciaInstituto Murciano de Investigatión Biosanitaria (IMIB)‐ArrixacaMurciaSpain
- Centro de Investigatión Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV)MadridSpain
| | - Cristina Rodriguez
- Centro de Investigatión Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV)MadridSpain
- Institut de Recerca del Hospital de la Santa Creu i Sant Pau‐Programa Instituto Catalán de Ciencias Cardiovasculares (ICCC)IIB‐Sant PauBarcelonaSpain
| | - Diana Hernández‐Romero
- Hospital Clínico Universitario Virgen de la ArrixacaUniversidad de MurciaInstituto Murciano de Investigatión Biosanitaria (IMIB)‐ArrixacaMurciaSpain
- Centro de Investigatión Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV)MadridSpain
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17
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Fujii H, Kono K, Nakai K, Goto S, Nishii T, Kono A, Nishi S. Effects of Lanthanum Carbonate on Coronary Artery Calcification and Cardiac Abnormalities After Initiating Hemodialysis. Calcif Tissue Int 2018; 102:310-320. [PMID: 29058057 DOI: 10.1007/s00223-017-0347-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2017] [Accepted: 10/13/2017] [Indexed: 12/14/2022]
Abstract
It is known that calcium-containing phosphate binders are more closely associated with the progression of vascular calcification than non-calcium-containing phosphate binders. In this study, we investigated the effect of the non-calcium-containing phosphate binder, lanthanum carbonate on the progression of coronary artery calcification and cardiovascular abnormalities compared to that of calcium-containing phosphate binder in chronic kidney disease patients during the early period after initiating hemodialysis. This was a randomized open-label study in which patients were divided into the calcium carbonate or lanthanum carbonate group. We evaluated blood samples, coronary artery calcification using high-resolution computed tomography, and cardiac abnormalities using echocardiography prior to and after initiating hemodialysis. Cardiac dimension and systolic function were significantly improved in the lanthanum carbonate group compared to those in the calcium carbonate group. Although statistically significant differences were not observed in all the patients, only among patients with moderate coronary artery calcification, the changes in coronary artery calcification score at 18 months were significantly smaller in the lanthanum carbonate group than those in the calcium carbonate group. The percent change in coronary artery calcification at 18 months was significantly correlated with the serum fibroblast growth factor 23 levels at 18 months (r = 0.245, P < 0.05). This significant correlation was particularly strong in patients with moderate coronary artery calcification (r = 0.593, P < 0.001). Our study suggests that lanthanum carbonate ameliorates cardiac abnormalities, and may slow coronary artery calcification development in patients with moderate coronary artery calcification, during the early period following hemodialysis initiation.
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Affiliation(s)
- Hideki Fujii
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.
| | - Keiji Kono
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Kentaro Nakai
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Shunsuke Goto
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Tatsuya Nishii
- Division of Radiology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Atsushi Kono
- Division of Radiology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Shinichi Nishi
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
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18
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Gregg LP, Adams-Huet B, Li X, Colbert G, Jain N, de Lemos JA, Hedayati SS. Effect Modification of Chronic Kidney Disease on the Association of Circulating and Imaging Cardiac Biomarkers With Outcomes. J Am Heart Assoc 2017; 6:JAHA.116.005235. [PMID: 28679558 PMCID: PMC5586272 DOI: 10.1161/jaha.116.005235] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Background Cardiac troponin T and brain natriuretic peptide (BNP) are elevated in >50% of dialysis patients and are associated with poor outcomes. Few data investigated these associations in earlier chronic kidney disease (CKD). Methods and Results We studied whether CKD modified associations of elevated BNP, N‐terminal‐pro‐BNP, high‐sensitivity cardiac troponin T, coronary artery calcification, and left ventricular hypertrophy with all‐cause death and cardiovascular death/events in 3218 multiethnic individuals followed for 12.5 years, and whether biomarkers added prognostic information to traditional cardiovascular risk factors in CKD. Of the cohort, 279 (9%) had CKD. There were 296 deaths and 218 cardiovascular deaths/events. Of non‐CKD individuals, 7% died and 6% had cardiovascular death/event versus 32% and 30% of CKD participants, P<0.001 for both. The interaction between BNP and CKD on death was significant (P=0.01): the adjusted hazard ratio in CKD was 2.05, 95% CI (1.34, 3.14), but not significant in non‐CKD, 1.04 (0.76, 1.41). CKD modified the association of high‐sensitivity cardiac troponin T with cardiovascular death/event, adjusted hazard ratio 3.34 (1.56, 7.18) in CKD versus 1.65 (1.16, 2.35) in non‐CKD, interaction P=0.09. There was an interaction between N‐terminal‐pro‐BNP and CKD for death in those without prior cardiovascular disease. Addition of each biomarker to traditional risk factors improved risk prediction, except coronary artery calcification was not discriminatory for cardiovascular death/event in CKD. Conclusions Cardiac biomarkers, with the exception of coronary artery calcification, prognosticated outcomes in early‐stage CKD as well as, if not better than, in non‐CKD individuals, even after controlling for estimated glomerular filtration rate, and added to information obtained from traditional cardiovascular risk factors alone.
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Affiliation(s)
- L Parker Gregg
- Division of Nephrology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX
| | - Beverley Adams-Huet
- Division of Biostatistics, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX
| | - Xilong Li
- Division of Biostatistics, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX
| | - Gates Colbert
- Division of Nephrology, Department of Medicine, Baylor University Medical Center, Dallas, TX
| | - Nishank Jain
- Division of Nephrology, Department of Medicine, University of Arkansas, Little Rock, AR
| | - James A de Lemos
- Division of Cardiology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX
| | - S Susan Hedayati
- Division of Nephrology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX .,Division of Nephrology, Medical Service, Veterans Affairs North Texas Health Care System, Dallas, TX
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19
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Choi HY, Lee CJ, Lee JE, Yang HS, Kim HY, Park HC, Kim HC, Chang HJ, Park SH, Kim BS. Loss of nighttime blood pressure dipping as a risk factor for coronary artery calcification in nondialysis chronic kidney disease. Medicine (Baltimore) 2017; 96:e7380. [PMID: 28658167 PMCID: PMC5500089 DOI: 10.1097/md.0000000000007380] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Diurnal variations in blood pressure (BP) loss are closely associated with target organ damage and cardiovascular events. The quantity of coronary artery calcification (CAC) correlates with the atherosclerotic plaque burden, and an increased quantity indicates a substantially increased risk of cardiovascular events. This study investigated the nighttime diurnal variation in BP loss associated with CAC in patients with chronic kidney disease (CKD).Of the 1958 participants, we enrolled 722 participants with CKD without a history of acute coronary syndrome or symptomatic coronary artery disease. CAC was measured with computed tomography. BP was measured using 24-hour ambulatory BP monitoring. Central BP was measured using a SphygmoCor waveform analysis system.Participants with CAC had significantly higher 24-hour systolic, daytime systolic, and nighttime systolic ambulatory BP and central systolic BP. The percentage of participants with dipping loss was significantly higher among those with CAC. Multivariate logistic regression analysis indicated that dipping loss and dipping ratio were independently associated with CAC after adjusting for traditional and nontraditional cardiovascular risk factors and other BP parameters, including measurements of office-measured BP and central BP. The dipping status improved risk prediction for CAC after considering traditional risk factors and office-measured BP, using the net reclassification improvement and integrated discrimination improvement.Nighttime loss of diurnal variation in BP is an independent risk factor for CAC in CKD patients.
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Affiliation(s)
| | - Chan Joo Lee
- Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul
| | - Jung Eun Lee
- Department of Internal Medicine, Yong-In Severance Hospital, Yonsei University College of Medicine, Yong-In
| | | | | | | | - Hyeon Chang Kim
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Hyuk-Jae Chang
- Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul
| | - Sung-Ha Park
- Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul
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20
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Disthabanchong S, Boongird S. Role of different imaging modalities of vascular calcification in predicting outcomes in chronic kidney disease. World J Nephrol 2017; 6:100-110. [PMID: 28540199 PMCID: PMC5424431 DOI: 10.5527/wjn.v6.i3.100] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Revised: 03/27/2017] [Accepted: 04/19/2017] [Indexed: 02/06/2023] Open
Abstract
Vascular calcification (VC) is common among patients with chronic kidney disease (CKD). The severity of VC is associated with increased risk of cardiovascular events and mortality. Risk factors for VC include traditional cardiovascular risk factors as well as CKD-related risk factors such as increased calcium and phosphate load. VC is observed in arteries of all sizes from small arterioles to aorta, both in the intima and the media of arterial wall. Several imaging techniques have been utilized in the evaluation of the extent and the severity of VC. Plain radiographs are simple and readily available but with the limitation of decreased sensitivity and subjective and semi-quantitative quantification methods. Mammography, especially useful among women, offers a unique way to study breast arterial calcification, which is largely a medial-type calcification. Ultrasonography is suitable for calcification in superficial arteries. Analyses of wall thickness and lumen size are also possible. Computed tomography (CT) scan, the gold standard, is the most sensitive technique for evaluation of VC. CT scan of coronary artery calcification is not only useful for cardiovascular risk stratification but also offers an accurate and an objective analysis of the severity and progression.
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21
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Yokomichi H, Nagai A, Hirata M, Kiyohara Y, Muto K, Ninomiya T, Matsuda K, Kamatani Y, Tamakoshi A, Kubo M, Nakamura Y, Yamagata Z. Survival of macrovascular disease, chronic kidney disease, chronic respiratory disease, cancer and smoking in patients with type 2 diabetes: BioBank Japan cohort. J Epidemiol 2017; 27:S98-S106. [PMID: 28209242 PMCID: PMC5350597 DOI: 10.1016/j.je.2016.12.012] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2016] [Revised: 12/12/2016] [Accepted: 12/15/2016] [Indexed: 01/09/2023] Open
Abstract
Background The number of patients with diabetes is increasing worldwide. Macrovascular disease, chronic kidney disease, chronic respiratory disease, cancer and smoking frequently accompany type 2 diabetes. Few data are available related to mortality of Asians with diabetes associated with these serious comorbidities. The present study aimed to quantify the excess mortality risks of type 2 diabetic patients with comorbidities. Methods We analysed the available records of 30,834 Japanese patients with type 2 diabetes from the BioBank Japan Project between 2003 and 2007. Men and women were followed up for median 8.03 and 8.30 years, respectively. We applied Cox proportional hazard model and Kaplan–Meier estimates for survival curves to evaluate mortality in diabetic patients with or without macrovascular disease, chronic respiratory disease, chronic kidney disease, cancer and smoking. Results Adjusted hazard ratios (HRs) for mortality were 1.39 (95% CI, 1.09–1.78) for male sex, 2.01 (95% CI, 1.78–2.26) per 10-year increment of age. Adjusted HRs of primary interest were 1.77 (95% CI, 1.42–2.22), macrovascular disease; 1.58 (95% CI, 1.08–2.31), chronic respiratory disease; 2.03 (95% CI, 1.67–2.47), chronic kidney disease; 1.16 (95% CI, 0.86–1.56), cancer; and 1.74 (95% CI, 1.30–2.31), current smoking. Conclusions Diabetic patients with a past or current history of chronic kidney, macrovascular or respiratory diseases or smoking habit have exhibited the highest risk of mortality. Data were limited to those of survivors of comorbidities but we propose the need to improve comorbidities and terminate cigarette smoking for better prognosis in patients with diabetes.
Fatal diseases frequently accompany diabetes. Data for survival of Asian patients with diabetes with comorbidities are scarce. Comorbid chronic kidney disease was associated with the most fatalities. Current smoking was as fatal as 10 years of ageing in diabetic patients. Values of 1% HbA1c and 10 mmHg blood pressure confer 11% excess mortality risk.
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Affiliation(s)
- Hiroshi Yokomichi
- Department of Health Sciences, University of Yamanashi, Yamanashi, Japan.
| | - Akiko Nagai
- Department of Public Policy, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Makoto Hirata
- Laboratory of Genome Technology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Yutaka Kiyohara
- Hisayama Research Institute for Lifestyle Diseases, Fukuoka, Japan
| | - Kaori Muto
- Department of Public Policy, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Toshiharu Ninomiya
- Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Koichi Matsuda
- Laboratory of Molecular Medicine, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Yoichiro Kamatani
- Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Akiko Tamakoshi
- Department of Public Health, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Michiaki Kubo
- RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Yusuke Nakamura
- Laboratory of Molecular Medicine, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | | | - Zentaro Yamagata
- Department of Health Sciences, University of Yamanashi, Yamanashi, Japan
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22
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Dieter BP, McPherson SM, Afkarian M, de Boer IH, Mehrotra R, Short R, Barbosa-Leiker C, Alicic RZ, Meek RL, Tuttle KR. Serum amyloid a and risk of death and end-stage renal disease in diabetic kidney disease. J Diabetes Complications 2016; 30:1467-1472. [PMID: 27522272 PMCID: PMC5435122 DOI: 10.1016/j.jdiacomp.2016.07.018] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2016] [Revised: 07/20/2016] [Accepted: 07/20/2016] [Indexed: 01/09/2023]
Abstract
AIMS To determine if serum levels of serum amyloid A (SAA) predict death and end-stage renal disease in a cohort of people with diabetic kidney disease. METHODS In a longitudinal cohort study of 135 participants with type 2 diabetes and diabetic kidney disease, serum samples were assayed for SAA. Censored time-to-event analyses in Cox-proportional hazard models were utilized to assess SAA as a predictor of the primary outcome of death and end-stage renal disease. RESULTS Participants were 73% Mexican-American (99/135) and 55% men (75/135), with a mean±SD age of 57±7.5years. At baseline, participants had hemoglobin A1c of 8.6±2.3%, systolic blood pressure of 153±27mm Hg, body mass index of 31±9kg/m2, median urine-albumin-to-creatinine ratio of 1861mg/g (interquartile range 720-3912mg/g), and estimated glomerular filtration rate of 55.7±22.3ml/min/1.73m2. Over a median duration of follow-up of 3.5years, 44% (60/135) of participants experienced a primary outcome event. The hazards ratio for the primary outcome was 3.03 (95% CI 1.43-6.40, p=0.003) in the highest (>1.0 μg/ml) compared to the lowest (<0.55 μg/ml) SAA tertile in a model adjusted for urine-albumin-to-creatinine ratio, estimated glomerular filtration rate, age, sex, and race/ethnicity. Addition of SAA as a covariate improved the model C-statistic (Δ c=0.017). CONCLUSIONS In a longitudinal cohort study of participants with type 2 diabetes and DKD, higher levels of serum SAA predicted higher risk of death and ESRD. SAA is a promising targetable biomarker for DKD.
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Affiliation(s)
- Brad P Dieter
- Providence Medical Research Center, Providence Health Care.
| | - Sterling M McPherson
- Providence Medical Research Center, Providence Health Care; Washington State University
| | - Maryam Afkarian
- University of Washington; Nephrology Division, Kidney Research Institute
| | - Ian H de Boer
- Washington State University Elson S. Floyd College of Medicine; University of Washington; Nephrology Division, Kidney Research Institute
| | | | - Robert Short
- Washington State University Elson S. Floyd College of Medicine
| | | | - Radica Z Alicic
- Providence Medical Research Center, Providence Health Care; University of Washington
| | - Rick L Meek
- Providence Medical Research Center, Providence Health Care
| | - Katherine R Tuttle
- Providence Medical Research Center, Providence Health Care; University of Washington; Nephrology Division, Kidney Research Institute
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23
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Afkarian M, Zelnick LR, Ruzinski J, Kestenbaum B, Himmelfarb J, de Boer IH, Mehrotra R. Urine matrix metalloproteinase-7 and risk of kidney disease progression and mortality in type 2 diabetes. J Diabetes Complications 2015; 29:1024-31. [PMID: 26412030 PMCID: PMC5389898 DOI: 10.1016/j.jdiacomp.2015.08.024] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2015] [Revised: 08/25/2015] [Accepted: 08/30/2015] [Indexed: 02/06/2023]
Abstract
AIMS The renin-angiotensin-aldosterone system (RAAS), bone morphogenetic protein (BMP) and WNT pathways are dysregulated in diabetic kidney disease (DKD). Urine excretion of angiotensinogen, gremlin-1 and matrix metalloproteinase-7 (MMP-7), components of the RAAS, BMP and WNT pathways, respectively, is increased in DKD. We asked if this increase is associated with subsequent progression to end-stage renal disease (ESRD) or death. METHODS Using time-to-event analyses, we examined the association of baseline urine concentration of these proteins with progression to ESRD or death in a predominantly Mexican-American cohort with type 2 diabetes and proteinuric DKD (n=141). RESULTS Progression to ESRD occurred for 38 participants over a median follow-up of 3.0years; 39 participants died over a median follow-up of 3.6years. Urine MMP-7 and gremlin-1 were associated with increased risk of ESRD after adjustment for demographic and clinical covariates. Angiotensinogen showed a U-shaped relationship with ESRD, with the middle tertile associated with lowest risk of ESRD. After additional adjustment for glomerular filtration rate and albuminuria, all associations with ESRD lost significance. Only urine MMP-7 was associated with mortality, and this association remained robust in the fully adjusted model with a Hazard ratio of 3.59 (95% confidence interval 1.31 to 9.85) for highest vs. lowest tertile. Serum MMP-7 was not associated with mortality and did not attenuate the association of urine MMP-7 with mortality (HR 4.03 for highest vs. lowest urine MMP-7 tertile). CONCLUSIONS Among people with type 2 diabetes and proteinuric DKD, urine MMP-7 concentration was strongly associated with subsequent mortality.
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MESH Headings
- Aged
- Cohort Studies
- Diabetes Mellitus, Type 2/complications
- Diabetes Mellitus, Type 2/ethnology
- Diabetes Mellitus, Type 2/mortality
- Diabetes Mellitus, Type 2/urine
- Diabetic Nephropathies/complications
- Diabetic Nephropathies/epidemiology
- Diabetic Nephropathies/mortality
- Diabetic Nephropathies/physiopathology
- Disease Progression
- Female
- Follow-Up Studies
- Glomerular Filtration Rate
- Hospitals, Public
- Hospitals, Urban
- Humans
- Kidney/physiopathology
- Kidney Failure, Chronic/complications
- Kidney Failure, Chronic/epidemiology
- Kidney Failure, Chronic/mortality
- Kidney Failure, Chronic/physiopathology
- Los Angeles/epidemiology
- Male
- Matrix Metalloproteinase 7/urine
- Mexican Americans
- Middle Aged
- Prospective Studies
- Renal Insufficiency/complications
- Renal Insufficiency/epidemiology
- Renal Insufficiency/mortality
- Renal Insufficiency/physiopathology
- Risk
- Up-Regulation
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Affiliation(s)
- Maryam Afkarian
- Kidney Research Institute and Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA.
| | - Leila R Zelnick
- Kidney Research Institute and Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA; Department of Biostatistics, University of Washington
| | - John Ruzinski
- Kidney Research Institute and Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA
| | - Bryan Kestenbaum
- Kidney Research Institute and Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA
| | - Jonathan Himmelfarb
- Kidney Research Institute and Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA
| | - Ian H de Boer
- Kidney Research Institute and Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA
| | - Rajnish Mehrotra
- Kidney Research Institute and Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA
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24
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von Scholten BJ, Reinhard H, Hansen TW, Lindhardt M, Petersen CL, Wiinberg N, Hansen PR, Parving HH, Jacobsen PK, Rossing P. Additive prognostic value of plasma N-terminal pro-brain natriuretic peptide and coronary artery calcification for cardiovascular events and mortality in asymptomatic patients with type 2 diabetes. Cardiovasc Diabetol 2015; 14:59. [PMID: 25990319 PMCID: PMC4489401 DOI: 10.1186/s12933-015-0225-0] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Accepted: 05/06/2015] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND In patients with type 2 diabetes, cardiovascular disease (CVD) is the major cause of morbidity and mortality. We evaluated the combination of NT-proBNP and coronary artery calcium score (CAC) for prediction of combined fatal and non-fatal CVD and mortality in patients with type 2 diabetes and microalbuminuria (>30 mg/24-h), but without known coronary artery disease. Moreover, we assessed the predictive value of a predefined categorisation of patients into a high- and low-risk group at baseline. METHODS Prospective study including 200 patients. All received intensive multifactorial treatment. Patients with baseline NT-proBNP > 45.2 ng/L and/or CAC ≥ 400 were stratified as high-risk patients (n = 133). Occurrence of fatal- and nonfatal CVD (n = 40) and mortality (n = 26), was traced after 6.1 years (median). RESULTS High-risk patients had a higher risk of the composite CVD endpoint (adjusted hazard ratio [HR] 10.6 (95 % confidence interval [CI] 2.4-46.3); p = 0.002) and mortality (adjusted HR 5.3 (95 % CI 1.2-24.0); p = 0.032) compared to low-risk patients. In adjusted continuous analysis, both higher NT-proBNP and CAC were strong predictors of the composite CVD endpoint and mortality (p ≤ 0.0001). In fully adjusted models mutually including NT-proBNP and CAC, both risk factors remained associated with risk of CVD and mortality (p ≤ 0.022). There was no interaction between NT-proBNP and CAC for the examined endpoints (p ≥ 0.31). CONCLUSIONS In patients with type 2 diabetes and microalbuminuria but without known coronary artery disease, NT-proBNP and CAC were strongly associated with fatal and nonfatal CVD, as well as with mortality. Their additive prognostic capability holds promise for identification of patients at high risk.
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Affiliation(s)
| | - Henrik Reinhard
- Steno Diabetes Center, Niels Steensens Vej 1, Gentofte, 2820, Denmark.
| | | | - Morten Lindhardt
- Steno Diabetes Center, Niels Steensens Vej 1, Gentofte, 2820, Denmark.
| | - Claus Leth Petersen
- Center for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, University of Copenhagen, Compenhagen, Denmark.
| | | | | | - Hans-Henrik Parving
- Rigshospitalet, Copenhagen, Denmark. .,University of Copenhagen, Copenhagen, Denmark.
| | - Peter Karl Jacobsen
- The Heart Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
| | - Peter Rossing
- Steno Diabetes Center, Niels Steensens Vej 1, Gentofte, 2820, Denmark. .,University of Copenhagen, Copenhagen, Denmark. .,Aarhus University, Aarhus, Denmark.
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25
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Jover E, Marín F, Quintana M, Pérez-Andreu J, Hurtado JA, Rodríguez C, Martínez-González J, González-Conejero R, Valdés M, Hernández-Romero D. CALU polymorphism A29809G affects calumenin availability involving vascular calcification. J Mol Cell Cardiol 2015; 82:218-27. [PMID: 25823396 DOI: 10.1016/j.yjmcc.2015.03.015] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2015] [Revised: 03/09/2015] [Accepted: 03/24/2015] [Indexed: 01/07/2023]
Abstract
Calumenin inhibits gamma-carboxylation of matrix-Gla-protein preventing BMP2-dependent calcification. Our aim was to explore the clinical relevance and functionality of the CALU polymorphism rs1043550, and the relationship of calumenin time-dependent expression profile with the active calcification of human vascular smooth muscle cells (hVSMC). Coronary artery calcium score and lesion severity were assessed by cardiac computed tomography in 139 consecutive low-risk patients genotyped for rs1043550. Polymorphic (G) allele carriage was associated with lower calcium (OR: 6.19, p=0.042). Calcified arteries from CALU 'A' allele carriers undergoing cardiovascular surgery exhibited higher residual calcification, higher calumenin immunostaining and lower matrix-Gla-protein, contrary to 'G' allele carriers. In a luciferase reporter system in vascular cells, polymorphic 'G' allele reduced the mRNA stability by 30% (p < 0.05). Osteogenic high-phosphate media induced active differentiation of hVSMC onto functional osteoblast-like cells as demonstrated by extracellular matrix mineralization and osteoblast markers expression. Calumenin was early over-expressed at day 3 (p < 0.05), but decreased thereafter (mRNA and protein) with implications on gamma-carboxylation system. Calumenin was found released and co-localizing with extracellular matrix calcifications. The CALU polymorphism rs1043550 affects mRNA stability and tissue availability of calumenin thus supporting the protective clinical significance. Calumenin shows a time-dependent profile during induced calcification. These data demonstrate a novel association of vascular calcification with the VSMC phenotypic transition into osteoblast-like cells. Moreover, hyperphosphatemic stimuli render calumenin accumulation in the mineralized extracellular matrix.
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MESH Headings
- Alleles
- Calcium/metabolism
- Calcium-Binding Proteins/genetics
- Calcium-Binding Proteins/metabolism
- Cell Culture Techniques
- Cell Differentiation
- Cells, Cultured
- Coronary Vessels/metabolism
- Coronary Vessels/pathology
- Extracellular Matrix/metabolism
- Extracellular Matrix Proteins/metabolism
- Humans
- Muscle, Smooth, Vascular/metabolism
- Muscle, Smooth, Vascular/pathology
- Myocytes, Smooth Muscle/cytology
- Myocytes, Smooth Muscle/metabolism
- Osteoblasts/cytology
- Osteoblasts/metabolism
- Polymorphism, Single Nucleotide
- RNA Stability/genetics
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Vascular Calcification/genetics
- Vascular Calcification/metabolism
- Matrix Gla Protein
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Affiliation(s)
- Eva Jover
- Hospital Clínico Universitario Virgen de la Arrixaca, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain
| | - Francisco Marín
- Hospital Clínico Universitario Virgen de la Arrixaca, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain.
| | - Míriam Quintana
- Hospital Clínico Universitario Virgen de la Arrixaca, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain
| | - Joaquín Pérez-Andreu
- Hospital Clínico Universitario Virgen de la Arrixaca, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain
| | - José Antonio Hurtado
- Hospital Clínico Universitario Virgen de la Arrixaca, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain
| | - Cristina Rodríguez
- Centro de Investigación Cardiovascular, CSIC-ICCC, Instituto de Investigación Biomédica Sant Pau (IIB Sant Pau), Barcelona, Spain
| | - José Martínez-González
- Centro de Investigación Cardiovascular, CSIC-ICCC, Instituto de Investigación Biomédica Sant Pau (IIB Sant Pau), Barcelona, Spain
| | | | - Mariano Valdés
- Hospital Clínico Universitario Virgen de la Arrixaca, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain
| | - Diana Hernández-Romero
- Hospital Clínico Universitario Virgen de la Arrixaca, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain
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26
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Morena M, Jaussent I, Dupuy AM, Bargnoux AS, Kuster N, Chenine L, Leray-Moragues H, Klouche K, Vernhet H, Canaud B, Cristol JP. Osteoprotegerin and sclerostin in chronic kidney disease prior to dialysis: potential partners in vascular calcifications. Nephrol Dial Transplant 2015; 30:1345-56. [PMID: 25854266 DOI: 10.1093/ndt/gfv081] [Citation(s) in RCA: 93] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2014] [Accepted: 02/23/2015] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Osteoprotegerin (OPG), sclerostin and DKK1 constitute opposite bone turnover inhibitors, OPG inhibiting osteoclastogenesis while sclerostin and DKK1 exerting their inhibitory effects on osteoblastogenesis. Both proteins have been recognized as strong risk factors of vascular calcifications in non-dialysis chronic kidney disease (ND-CKD) patients. The aim of this study was to investigate the relationships between these inhibitors and coronary artery calcifications (CAC) in this population. METHODS A total of 241 ND-CKD patients [143 males; 69.0 (25.0-95.0) years; median estimated glomerular filtration rate using CKD-EPI 35.1 (6.7-120.1) mL/min/1.73 m(2)] were enrolled in this cross-sectional study. All underwent chest multidetector computed tomography for CAC scoring. OPG, sclerostin, DKK1 and mineral metabolism markers including PTH and bone alkaline phosphatase were measured. Logistic regression analyses were used to study the relationships between CAC and these markers. RESULTS Decline in renal function was associated with a significant increase in OPG and sclerostin while a slight but significant decrease in DKK1 was observed. The main crude associations with presence of CAC were a high level of OPG [OR = 2.55 95% confidence interval (95% CI) (1.35-4.82) for a level ranging from 6.26 to 9.15 pmol/L and OR = 5.74 95% CI (2.87-11.5) for a level ≥9.15 pmol/L; P < 0.0001] and a high level of sclerostin [OR = 2.64 95% CI (1.39-5.00) for a level ranging from 0.748 to 1.139 ng/mL and OR = 3.78 95% CI (1.96-7.31) for a level ≥1.139 ng/mL; P = 0.0002]. A logistic regression model clearly showed that the risk to present CAC was significantly increased when both OPG (≥6.26 pmol/L) and sclerostin (≥0.748 ng/mL) levels were high [crude model: OR = 11.47 95% CI (4.54-29.0); P < 0.0001; model adjusted for age, gender, diabetes, body mass index and smoking habits: OR = 5.69 95% CI (1.76-18.4); P = 0.02]. No association between DKK1 and presence of CAC was observed. CONCLUSIONS Our results strongly suggest that bone turnover inhibitors, OPG and sclerostin, are independently associated with CAC with potential additive effects in ND-CKD patients.
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Affiliation(s)
- Marion Morena
- Laboratoire de Biochimie, CHRU de Montpellier, Montpellier, France Institut de Recherche et de Formation en Dialyse, Montpellier, France U1046 INSERM, UMR9214 CNRS, Université de Montpellier, Montpellier, France
| | - Isabelle Jaussent
- U1061 INSERM, Montpellier, France Université de Montpellier, Montpellier, France
| | - Anne-Marie Dupuy
- Laboratoire de Biochimie, CHRU de Montpellier, Montpellier, France
| | - Anne-Sophie Bargnoux
- Laboratoire de Biochimie, CHRU de Montpellier, Montpellier, France U1046 INSERM, UMR9214 CNRS, Université de Montpellier, Montpellier, France
| | - Nils Kuster
- Laboratoire de Biochimie, CHRU de Montpellier, Montpellier, France U1046 INSERM, UMR9214 CNRS, Université de Montpellier, Montpellier, France
| | - Leila Chenine
- Service de Néphrologie, CHRU de Montpellier, Montpellier, France
| | | | - Kada Klouche
- U1046 INSERM, UMR9214 CNRS, Université de Montpellier, Montpellier, France Service de Réanimation Métabolique, CHRU de Montpellier, Montpellier, France
| | - Hélène Vernhet
- Service de Radiologie, CHRU de Montpellier, Montpellier, France
| | - Bernard Canaud
- Institut de Recherche et de Formation en Dialyse, Montpellier, France Université de Montpellier, Néphrologie, Montpellier, France Fresenius Medical Care, Bad Homburg, Germany
| | - Jean-Paul Cristol
- Laboratoire de Biochimie, CHRU de Montpellier, Montpellier, France Institut de Recherche et de Formation en Dialyse, Montpellier, France U1046 INSERM, UMR9214 CNRS, Université de Montpellier, Montpellier, France
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27
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Colbert G, Jain N, de Lemos JA, Hedayati SS. Utility of traditional circulating and imaging-based cardiac biomarkers in patients with predialysis CKD. Clin J Am Soc Nephrol 2015; 10:515-29. [PMID: 25403922 PMCID: PMC4348678 DOI: 10.2215/cjn.03600414] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Cardiac biomarkers, such as cardiac troponin T (cTnT), brain natriuretic peptide (BNP), and N-terminal-pro-BNP (NT-pro-BNP), are commonly used to diagnose acute coronary syndrome and congestive heart failure exacerbation in symptomatic patients. Levels of these biomarkers are frequently chronically elevated in asymptomatic patients with ESRD who are receiving maintenance dialysis. Other imaging biomarkers commonly encountered in nephrologists' clinical practice, such as coronary artery calcium measured by computed tomography, left ventricular hypertrophy, and carotid intima-media thickness, are also frequently abnormal in asymptomatic patients with ESRD. This article critically reviews the limited observational data on associations between cTnT, BNP, NT-pro-BNP, coronary artery calcium, left ventricular hypertrophy, and carotid intima-media thickness with cardiovascular events and death in non-dialysis-dependent patients with CKD. Although sufficient evidence suggests that these biomarkers may be used for prognostication, the diagnostic utility of cTnT, BNP, and NT-pro-BNP remain challenging in patients with CKD. Decreased renal clearance may affect the plasma levels of these biomarkers, and upper reference limits were originally derived in patients without CKD. Until better data are available, higher cutoffs, or a rise in level compared with previous values, have been proposed to help distinguish acute myocardial infarction from chronic elevations of cTnT in symptomatic patients with CKD. Additionally, it is not known whether these biomarkers are modifiable and amenable to interventions that could change hard clinical outcomes in patients with CKD not yet undergoing long-term dialysis.
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MESH Headings
- Biomarkers/blood
- Calcinosis/diagnostic imaging
- Carotid Intima-Media Thickness
- Coronary Artery Disease/complications
- Coronary Artery Disease/diagnostic imaging
- Humans
- Hypertrophy, Left Ventricular/blood
- Hypertrophy, Left Ventricular/complications
- Hypertrophy, Left Ventricular/diagnostic imaging
- Kidney Failure, Chronic/blood
- Kidney Failure, Chronic/complications
- Kidney Failure, Chronic/therapy
- Natriuretic Peptide, Brain/blood
- Peptide Fragments/blood
- Renal Dialysis
- Tomography, X-Ray Computed
- Troponin T/blood
- Ventricular Dysfunction, Left/blood
- Ventricular Dysfunction, Left/complications
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Affiliation(s)
| | | | - James A de Lemos
- Division of Cardiology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas; and
| | - S Susan Hedayati
- Division of Nephrology and Division of Nephrology, Medical Service, Veterans Affairs North Texas Health Care System, Dallas, Texas
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Bashir A, Moody WE, Edwards NC, Ferro CJ, Townend JN, Steeds RP. Coronary Artery Calcium Assessment in CKD: Utility in Cardiovascular Disease Risk Assessment and Treatment? Am J Kidney Dis 2015; 65:937-48. [PMID: 25754074 DOI: 10.1053/j.ajkd.2015.01.012] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2014] [Accepted: 01/07/2015] [Indexed: 02/08/2023]
Abstract
Coronary artery calcification (CAC) is a strong predictor of cardiovascular event rates in the general population, and scoring with multislice computed tomography commonly is used to improve risk stratification beyond clinical variables. CAC is accelerated in chronic kidney disease, but this occurs as a result of 2 distinct pathologic processes that result in medial (arteriosclerosis) and intimal (atherosclerosis) deposition. Although there are data that indicate that very high CAC scores may be associated with increased risk of death in hemodialysis, average CAC scores in most patients are elevated at a level at which discriminatory power may be reduced. There is a lack of data to guide management strategies in these patients based on CAC scores. There are even fewer data available for nondialysis patients, and it is uncertain whether CAC score confers an elevated risk of premature cardiovascular morbidity and mortality in such patients. In this article, we review the evidence regarding the utility of CAC score for noninvasive cardiovascular risk assessment in individuals with chronic kidney disease, using a clinical vignette that highlights some of the limitations in using CAC score and considerations in risk stratification.
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Affiliation(s)
- Ahmed Bashir
- Department of Cardiology, Nuffield House, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, United Kingdom
| | - William E Moody
- Department of Cardiology, Nuffield House, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, United Kingdom; Clinical Cardiovascular Science, School of Clinical & Experimental Medicine, University of Birmingham, Edgbaston, Birmingham, United Kingdom
| | - Nicola C Edwards
- Department of Cardiology, Nuffield House, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, United Kingdom; Clinical Cardiovascular Science, School of Clinical & Experimental Medicine, University of Birmingham, Edgbaston, Birmingham, United Kingdom
| | - Charles J Ferro
- Department of Renal Medicine, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, United Kingdom
| | - Jonathan N Townend
- Department of Cardiology, Nuffield House, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, United Kingdom
| | - Richard P Steeds
- Department of Cardiology, Nuffield House, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, United Kingdom.
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Prediction of mortality using a multi-bed vascular calcification score in the Diabetes Heart Study. Cardiovasc Diabetol 2014; 13:160. [PMID: 25496604 PMCID: PMC4266952 DOI: 10.1186/s12933-014-0160-5] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2014] [Accepted: 11/27/2014] [Indexed: 11/17/2022] Open
Abstract
Background Vascular calcified plaque, a measure of subclinical cardiovascular disease (CVD), is unlikely to be limited to a single vascular bed in patients with multiple risk factors. Consideration of vascular calcified plaque as a global phenomenon may allow for a more accurate assessment of the CVD burden. The aim of this study was to examine the utility of a combined vascular calcified plaque score in the prediction of mortality. Methods Vascular calcified plaque scores from the coronary, carotid, and abdominal aortic vascular beds and a derived multi-bed score were examined for associations with all-cause and CVD-mortality in 699 European-American type 2 diabetes (T2D) affected individuals from the Diabetes Heart Study. The ability of calcified plaque to improve prediction beyond Framingham risk factors was assessed. Results Over 8.4 ± 2.3 years (mean ± standard deviation) of follow-up, 156 (22.3%) participants were deceased, 74 (10.6%) from CVD causes. All calcified plaque scores were significantly associated with all-cause (HR: 1.4-1.8; p < 1x10−5) and CVD-mortality (HR: 1.5-1.9; p < 1×10−4) following adjustment for Framingham risk factors. Associations were strongest for coronary calcified plaque. Improvement in prediction of outcome beyond Framingham risk factors was greatest using coronary calcified plaque for all-cause mortality (AUC: 0.720 to 0.757, p = 0.004) and the multi-bed score for CVD mortality (AUC: 0.731 to 0.767, p = 0.008). Conclusions Although coronary calcified plaque and the multi-bed score were the strongest predictors of all-cause mortality and CVD-mortality respectively in this T2D-affected sample, carotid and abdominal aortic calcified plaque scores also significantly improved prediction of outcome beyond traditional risk factors and should not be discounted as risk stratification tools. Electronic supplementary material The online version of this article (doi:10.1186/s12933-014-0160-5) contains supplementary material, which is available to authorized users.
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30
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Barreto FC, de Oliveira RB, Benchitrit J, Louvet L, Rezg R, Poirot S, Jorgetti V, Drüeke TB, Riser BL, Massy ZA. Effects of pyrophosphate delivery in a peritoneal dialysis solution on bone tissue of apolipoprotein-E knockout mice with chronic kidney disease. J Bone Miner Metab 2014; 32:636-44. [PMID: 24442863 DOI: 10.1007/s00774-013-0541-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2013] [Accepted: 10/31/2013] [Indexed: 12/31/2022]
Abstract
Vascular calcification (VC) is a risk factor for cardiovascular mortality in the setting of chronic kidney disease (CKD). Pyrophosphate (PPi), an endogenous molecule that inhibits hydroxyapatite crystal formation, has been shown to prevent the development of VC in animal models of CKD. However, the possibility of harmful effects of exogenous administration of PPi on bone requires further investigation. To this end, we examined by histomorphometry the bone of CKD mice after intraperitoneal PPi administration. After CKD creation or sham surgery, 10-week-old female apolipoprotein-E knockout (apoE(-/-)) mice were randomized to one non-CKD group or 4 CKD groups (n = 10-35/group) treated with placebo or three distinct doses of PPi, and fed with standard diet. Eight weeks later, the animals were killed. Serum and femurs were sampled. Femurs were processed for bone histomorphometry. Placebo-treated CKD mice had significantly higher values of osteoid volume, osteoid surface and bone formation rate than sham-placebo mice with normal renal function. Slightly higher osteoid values were observed in CKD mice in response to very low PPi dose (OV/BV, O.Th and ObS/BS) and, for one parameter measured, to high PPi dose (O.Th), compared to placebo-treated CKD mice. Treatment with PPi did not modify any other structural parameters. Mineral apposition rates, and other parameters of bone formation and resorption were not significantly different among the treated animal groups or control CKD placebo group. In conclusion, PPi does not appear to be deleterious to bone tissue in apoE(-/-) mice with CKD, although a possible stimulatory PPi effect on osteoid formation may be worth further investigation.
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Affiliation(s)
- Fellype C Barreto
- INSERM Unit 1088, UFR de Médecine et Pharmacie, Picardie University Jules Verne (UPJV), 1, Rue des Louvels, bat A, 3ème, 80037, Amiens Cedex, France
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31
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Chang JF, Feng YF, Peng YS, Hsu SP, Pai MF, Chen HY, Wu HY, Yang JY. Combined alkaline phosphatase and phosphorus levels as a predictor of mortality in maintenance hemodialysis patients. Medicine (Baltimore) 2014; 93:e106. [PMID: 25319440 PMCID: PMC4616292 DOI: 10.1097/md.0000000000000106] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Hyperphosphatemia-induced vascular calcification and higher alkaline phosphatase (ALP) levels-related high-turnover bone diseases are linked to mortality among patients with chronic kidney disease (CKD). Nonetheless, no large epidemiological study in patients with CKD has been conducted to investigate the interaction and joint effect of hyperphosphatemia and higher ALP levels on mortality.We analyzed 11,912 maintenance hemodialysis patients from January 2005 to December 2010. Unadjusted and adjusted hazard ratios (aHRs) of death were calculated for different categories of serum phosphorus and ALP using the Cox regression model. The modification effect between serum phosphorus and ALP on mortality was determined using an interaction product term.Both hypophosphatemia (<3.0 mg/dL) and hyperphosphatemia (>7.0 mg/dL) were associated with incremental risks of death (aHR: 1.25 [95% confidence intervals (CIs): 1.09-1.44], and 1.15 [95% CI: 1.01-1.31], respectively) compared to the lowest hazard ratio (HR) group (5 mg/dL ≤ phosphorus<6 mg/dL). ALP levels were linearly associated with incremental risks for death (aHR: 1.58 [95% CI: 1.41-1.76] for the category of ALP>150 U/L). In the stratified analysis, patients with combined higher ALP (>150 U/L) and hyperphosphatemia (>7.0 mg/dL) had the greatest mortality risk (aHR: 2.25 [95% CI: 1.69-2.98] compared to the lowest HR group (ALP ≤ 60 U/L and 4 mg/dL ≤ phosphorus<5 mg/dL). Although the effect of hyperphosphatemia on mortality seemed stronger in higher ALP levels, the interaction was not statistically significant (P=0.22).The association between serum phosphorus levels and mortality was not limited to higher ALP levels. Regardless of serum ALP levels, we may control serum phosphorus levels merely toward the normal range. While considering the joint effect of ALP and hyperphosphatemia on mortality, the optimal phosphorus range should be stricter.
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Affiliation(s)
- Jia-Feng Chang
- Divison of Nephrology (J-FC, Y-SP, S-PH, M-FP, H-YC, H-YW, J-YY), Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City; Graduate Institute of Basic Medicine (J-FC), Fu Jen Catholic University; and Department of Nursing (Y-FF), Jiate Excelsior Co, Ltd, Taipei, Taiwan
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Cox AJ, Hsu FC, Freedman BI, Herrington DM, Criqui MH, Carr JJ, Bowden DW. Contributors to mortality in high-risk diabetic patients in the Diabetes Heart Study. Diabetes Care 2014; 37:2798-803. [PMID: 24989706 PMCID: PMC4392938 DOI: 10.2337/dc14-0081] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Not all individuals with type 2 diabetes and high coronary artery calcified plaque (CAC) experience the same risk for adverse outcomes. This study examined a subset of high-risk individuals based on CAC >1,000 mg (using a total mass score) and evaluated whether differences in a range of modifiable cardiovascular disease (CVD) risk factors provided further insights into risk for mortality. RESEARCH DESIGN AND METHODS We assessed contributors to all-cause mortality among 371 European American individuals with type 2 diabetes and CAC >1,000 from the Diabetes Heart Study (DHS) after 8.2 ± 3.0 years (mean ± SD) of follow-up. Differences in known CVD risk factors, including modifiable CVD risk factors, were compared between living (n = 218) and deceased (n = 153) participants. Cox proportional hazards regression models were used to quantify risk for all-cause mortality. RESULTS Deceased participants had a longer duration of type 2 diabetes (P = 0.02) and reduced use of cholesterol-lowering medications (P = 0.004). Adjusted analyses revealed that vascular calcified plaque scores were associated with increased risk for mortality (hazard ratio 1.31-1.63; 3.89 × 10(-5) < P < 0.03). Higher HbA1c, lipids, and C-reactive protein and reduced kidney function also were associated with a 1.1- to 1.5-fold increased risk for mortality (3.45 × 10(-6) < P < 0.03) after adjusting for confounding factors. CONCLUSIONS Even in this high-risk group, vascular calcification and known CVD risk factors provide useful information for ongoing assessment. The use of cholesterol-lowering medication seemed to be protective for mortality.
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Affiliation(s)
- Amanda J Cox
- Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC
| | - Fang-Chi Hsu
- Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC
| | - Barry I Freedman
- Department of Internal Medicine-Nephrology, Wake Forest School of Medicine, Winston-Salem, NC
| | - David M Herrington
- Department of Internal Medicine-Cardiology, Wake Forest School of Medicine, Winston-Salem, NC
| | - Michael H Criqui
- Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, CA
| | - J Jeffrey Carr
- Department of Radiologic Sciences, Wake Forest School of Medicine, Winston-Salem, NC
| | - Donald W Bowden
- Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC
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33
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Izumi Y, Hayashi M, Morimoto R, Cheng XW, Wu H, Ishii H, Yasuda Y, Yoshikawa D, Izawa H, Matsuo S, Oiso Y, Murohara T. Impact of circulating cathepsin K on the coronary calcification and the clinical outcome in chronic kidney disease patients. Heart Vessels 2014; 31:6-14. [DOI: 10.1007/s00380-014-0570-z] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2014] [Accepted: 08/15/2014] [Indexed: 12/26/2022]
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Rear R, Meier P, Bell RM. Implications of Kidney Disease in the Cardiac Patient. Interv Cardiol Clin 2014; 3:317-331. [PMID: 28582216 DOI: 10.1016/j.iccl.2014.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Traditional cardiovascular risk factors, particularly hypertension and diabetes, are common in the disease processes of both renal and cardiac pathology. Unfortunately the coexistence of renal impairment is not an innocent bystander in cardiovascular disease; it disorder not only increases the prevalence and severity of cardiovascular disease, but also negatively affects prognostic outcomes and the safety and efficacy of cardiac interventions. This article discusses the role and impact of kidney disease in the cardiac patient in 3 key common cardiovascular processes: coronary artery disease, arrhythmia, and heart failure.
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Affiliation(s)
- Roger Rear
- General and Interventional Cardiology Department, The Heart Hospital, University College Hospitals NHS Trust, 16-18 Westmoreland Street, London, W1G 8PH, UK; Clinical Research Department, The Hatter Cardiovascular Institute, University College London, 37 Chenies Mews, London, WC1E 6HX, UK
| | - Pascal Meier
- General and Interventional Cardiology Department, The Heart Hospital, University College Hospitals NHS Trust, 16-18 Westmoreland Street, London, W1G 8PH, UK
| | - Robert M Bell
- General and Interventional Cardiology Department, The Heart Hospital, University College Hospitals NHS Trust, 16-18 Westmoreland Street, London, W1G 8PH, UK; Clinical Research Department, The Hatter Cardiovascular Institute, University College London, 37 Chenies Mews, London, WC1E 6HX, UK.
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Stompór T. Coronary artery calcification in chronic kidney disease: An update. World J Cardiol 2014; 6:115-129. [PMID: 24772252 PMCID: PMC3999332 DOI: 10.4330/wjc.v6.i4.115] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2013] [Revised: 02/10/2014] [Accepted: 03/17/2014] [Indexed: 02/06/2023] Open
Abstract
Arterial calcification is a well-recognized complication of advanced atherosclerosis. Chronic kidney disease (CKD) is characterized by significantly more pronounced, disseminated and fast-progressing calcification of the vascular system, including the coronary arteries. New computed tomography-based imaging techniques allow for the noninvasive assessment and monitoring of calcification in different vascular sites. Coronary artery calcification (CAC) develops early in the course of CKD and is tightly associated with mineral and bone disorders, which include but are not limited to secondary hyperparathyroidism. In this review, recent data on the pathogenesis of CAC development and progression are discussed, with a special emphasis on fibroblast growth factor 23 and its co-receptor, klotho. The prevalence, progression and prognostic significance of CAC are reviewed separately for patients with end-stage renal disease treated with dialysis, kidney transplant recipients and patients with earlier stages of CKD. In the last section, therapeutic considerations are discussed, with special attention paid to the importance of treatment that addresses mineral and bone disorders of CKD.
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Vipattawat K, Kitiyakara C, Phakdeekitcharoen B, Kantachuvesiri S, Sumethkul V, Jirasiritham S, Stitchantrakul W, Disthabanchong S. Vascular calcification in long-term kidney transplantation. Nephrology (Carlton) 2014; 19:251-256. [PMID: 24447254 DOI: 10.1111/nep.12210] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/14/2014] [Indexed: 02/05/2023]
Abstract
AIM Vascular calcification (VC) is common among patients with chronic kidney disease (CKD) due to the strong prevalence of cardiovascular and CKD-related risk factors such as diabetes mellitus (DM), hypertension and phosphate retention. Kidney transplantation improves kidney function and abnormal mineral metabolism at the same time. It remains unclear whether kidney transplantation favourably impacts VC in the long-term. METHODS The present study examined VC in 132 kidney transplant (KT) recipients who had been transplanted for longer than one year. The severity of VC was compared to 129 CKD stages 5-5D patients on a kidney transplant (KT) waiting list. RESULTS The median KT vintage was 88 months. The prevalence of VC among KT and CKD patients were 54.5% and 62.8%, respectively, (P = 0.2). There were no differences in age, gender, body mass index (BMI), the prevalence of DM or CVD between the two groups. Among patients with calcification, a more severe degree was observed in KT recipients (P = 0.01). Aging, DM, CVD and dialysis vintage were associated with significant VC in both groups. The degree of VC in KT recipients was more pronounced than that in CKD patients among those who experienced prolonged dialysis vintage (>2 years) (P = 0.04). Among KT recipients, the severity of VC increased with the length of time after transplantation and became more substantial after 5 years. CONCLUSIONS Long-term KT recipients demonstrated a more severe degree of VC compared to matched CKD stages 5-5D patients. The severity of VC became more pronounced among those with longer transplant vintage and was in part influenced by past dialysis experience.
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Affiliation(s)
- Kotcharat Vipattawat
- Division of Nephrology, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
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No independent association of serum phosphorus with risk for death or progression to end-stage renal disease in a large screen for chronic kidney disease. Kidney Int 2013; 84:989-97. [PMID: 23615501 DOI: 10.1038/ki.2013.145] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2012] [Revised: 02/01/2013] [Accepted: 02/14/2013] [Indexed: 02/06/2023]
Abstract
Whether higher serum phosphorus levels are associated with a higher risk for death and/or progression of chronic kidney disease (CKD) is not well established, and whether the association is confounded by access and barriers to care is unknown. To answer these questions, data of 10,672 individuals identified to have CKD (estimated glomerular filtration rate <60 ml/min per 1.73 m(2)) from those participating in a community-based screening program were analyzed. Over a median follow-up of 2.3 years, there was no association between quartiles of serum phosphorus and all-cause mortality (adjusted hazards ratio for serum phosphorus over 3.3 to 3.7, over 3.7 to 4.1, and over 4.1 mg/dl, respectively: 1.22 (0.95-1.56), 1.00 (0.76-1.32), and 1.00 (0.75-1.33); reference, serum phosphorus of 3.3 mg/dl and below). Individuals in the highest quartile for serum phosphorus had a significantly higher risk for progression to end-stage renal disease (ESRD) (unadjusted hazards ratio, 6.72 (4.16-10.85)); however, the risk became nonsignificant on adjustment for potential confounders. There was no appreciable change in hazards ratio with inclusion of variables related to access and barriers to care. Additional analyses in subgroups based on 12 different variables yielded similar negative associations. Thus, in the largest cohort of individuals with early-stage CKD to date, we could not validate an independent association of serum phosphorus with risk for death or progression to ESRD.
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Fish RS, Klootwijk E, Tam FWK, Kleta R, Wheeler DC, Unwin RJ, Norman J. ATP and arterial calcification. Eur J Clin Invest 2013; 43:405-12. [PMID: 23398250 DOI: 10.1111/eci.12055] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2012] [Accepted: 01/12/2013] [Indexed: 12/21/2022]
Abstract
BACKGROUND Arterial calcification (AC) is a major health problem associated with extreme morbidity and a shortened survival. It is currently without any effective treatment. ATP and the purinergic system in general are now emerging as being important in the pathogenesis of AC and potentially provide a new focus for novel therapies. METHODS This review systematically analyses and discusses the current literature examining the relevance of the purinergic system to AC. Particular emphasis is given to the enzymes associated with ATP metabolism and their role in maintaining a balance between promotion and inhibition of arterial mineralization. Points of controversy are highlighted, and areas for future research are suggested. CONCLUSION The potential roles of ATP and the purinergic system in AC are beginning to be elucidated. While further work is necessary, current knowledge suggests that several components of the purinergic system could be targeted to develop new treatments for AC.
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Affiliation(s)
- Richard S Fish
- UCL Centre for Nephrology, UCL Medical School, London, UK.
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Sheppard RJ, Schiffrin EL. Inhibition of the renin-angiotensin system for lowering coronary artery disease risk. Curr Opin Pharmacol 2013; 13:274-9. [PMID: 23523606 DOI: 10.1016/j.coph.2013.03.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2013] [Revised: 03/01/2013] [Accepted: 03/01/2013] [Indexed: 01/15/2023]
Abstract
The renin-angiotensin system when activated exerts proliferative and pro-inflammatory actions and thereby contributes to progression of atherosclerosis, including that occurring in the coronary arteries. It thus contributes as well to coronary artery disease (CAD). Several clinical trials have examined effects of renin-angiotensin system inhibition for primary and secondary prevention of coronary heart disease. These include important trials such as HOPE, EUROPA and PEACE using angiotensin converting enzyme inhibitors, VALIANT, OPTIMAAL and TRANSCEND using angiotensin receptor blockers, and the ongoing TOPCAT study in patients with preserved ejection fraction heart failure, many of who also have coronary artery disease. Data are unavailable as yet of effects of either direct renin inhibitors or the new angiotensin receptor/neprilysin inhibitor agents. Today, inhibition of the renin-angiotensin system is standard-of-care therapy for lowering cardiovascular risk in secondary prevention in high cardiovascular risk subjects.
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Affiliation(s)
- Richard J Sheppard
- Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital and Lady Davis Institute for Medical Research, McGill University, Montreal, PQ, Canada
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40
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Change in ankle-brachial index over time and mortality in diabetics with proteinuria. Clin Nephrol 2012; 78:335-45. [PMID: 22784559 PMCID: PMC4407335 DOI: 10.5414/cn107463] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/18/2012] [Indexed: 11/18/2022] Open
Abstract
Peripheral arterial disease is common in diabetic chronic kidney disease (CKD) and is characterized either by abnormally low or high ankle-brachial index (ABI). Whether low or high ABI carries similar prognostic value is unknown. The association of baseline ABI with all-cause mortality over 40 ± 21 months (mean ± SD) was ascertained in 167 proteinuric diabetics (age 57 ± 7 years; median urine protein-creatinine, 2.5 mg/mg). Association of change in ABI with all-cause mortality was determined in 75 subjects with normal ABI (0.9 - 1.3) at baseline. Among 167 participants, 41% had an abnormal ABI: < 0.9, 18%; and > 1.3 or non-compressible arteries, 23%. Only individuals with low ABI had a significantly higher risk for all-cause mortality (hazards ratio (95% confidence interval), HR: 2.23 (1.07, 4.65)). In subjects with normal ABI at baseline with follow-up measurement (n = 75), vascular disease worsened in 39% over 23 ± 6 months: 17% had either a decrease in ABI by ≥ 0.1 or a final ABI < 0.9, and 21% had a final ABI > 1.3 or noncompressible arteries. Only individuals who had a decrease in ABI over time had a significantly higher risk for death (adjusted HR, 7.41 (1.63, 33.65)). Peripheral arterial disease is not uncommon and progresses rapidly in individuals with diabetes and proteinuria. Low or declining ABI is a strong predictor of all-cause mortality. Routine measurement of ABI is a simple bed-side procedure that may permit easy risk-stratification in diabetic CKD patients.
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Singh DK, Winocour P, Summerhayes B, Kaniyur S, Viljoen A, Sivakumar G, Farrington K. Prevalence and progression of peripheral vascular calcification in type 2 diabetes subjects with preserved kidney function. Diabetes Res Clin Pract 2012; 97:158-65. [PMID: 22386825 DOI: 10.1016/j.diabres.2012.01.038] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2011] [Revised: 01/03/2012] [Accepted: 01/05/2012] [Indexed: 11/30/2022]
Abstract
AIMS To determine predictors of prevalence and progression of peripheral vascular calcification (VC) in type 2 diabetes (DM) subjects with preserved kidney function. METHODS Fifty-eight subjects (age 63 ± 11.6 years) with type 2 DM and serum creatinine <125 μmol/l were studied. A CT scan of femoral, posterior tibial and dorsalis pedis arteries was carried out at baseline and at one year. Serum osteoprotegerin (OPG) and RANKL were measured along with routine biochemistry. RESULTS Seventy-eight percent of patients had baseline VC, 47% with femoral VC, 49% with VC at two sites - femoral and foot, and 4% foot VC alone. Age, ethnicity, peripheral neuropathy and eGFR were independent predictors of baseline VC. Baseline calcification was the most important predictor of VC progression and was present in all subjects with progression compared to 35% of non-progressors (p < 0.001). Exclusion of demographic factors from models revealed neuropathy and serum OPG levels as independent predictors of both; baseline VC and progression. CONCLUSIONS Subjects with type 2 DM and well-preserved renal function had a high prevalence of VC, which was rapidly progressive especially in those with baseline VC. Age, ethnicity, neuropathy, smoking and eGFR were predictors of baseline VC and progression.
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Affiliation(s)
- Dhruv K Singh
- Renal Unit, East and North Herts NHS Trust, SG1 4AB, UK.
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TOUSSAINT NIGELD, PEDAGOGOS EUGENIE, TAN SVENJEAN, BADVE SUNILV, HAWLEY CARMELM, PERKOVIC VLADO, ELDER GRAHAMEJ. Phosphate in early chronic kidney disease: Associations with clinical outcomes and a target to reduce cardiovascular risk. Nephrology (Carlton) 2012; 17:433-44. [DOI: 10.1111/j.1440-1797.2012.01618.x] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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Test characteristics of the ankle-brachial index and ankle-brachial difference for medial arterial calcification on X-ray in type 1 diabetes. J Vasc Surg 2012; 56:721-7. [PMID: 22560306 DOI: 10.1016/j.jvs.2012.02.042] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2011] [Revised: 02/17/2012] [Accepted: 02/18/2012] [Indexed: 01/12/2023]
Abstract
OBJECTIVE Medial arterial calcification (MAC) is common in diabetes, has a characteristic appearance on X-ray imaging, and has been linked with peripheral arterial stiffness and cardiovascular disease. However, few studies have measured X-ray MAC. It has been suggested that an ankle-brachial index (ABI) >1.30 or an ankle-brachial difference (ABD) >75 mm Hg may identify X-ray MAC, but test characteristics are unknown. We hypothesized that an ABI >1.30 and ABD >75 mm Hg would have high specificity but low sensitivity for MAC on X-ray imaging. METHODS This was a cross-sectional study of 185 community-living individuals with type 1 diabetes. The ABI and the ABD were assessed. The outcome was linear "tram-track" calcifications in the lower limbs characteristic of MAC. RESULTS Mean age was 32 ± 6 years, and mean diabetes duration was 23 ± 7 years. X-ray MAC was noted in 97 individuals (57%), 15 (8%) had ABI >1.30, and 14 (8%) had ABD >75 mm Hg. As assessed by the ABI, the area under the receiver operating characteristic curve for MAC was modest (0.65) and was slightly higher for the ABD (0.75). An ABI >1.30 had high specificity (99%) and positive predictive value (93%) but poor sensitivity (14%) and an overall accuracy of 55% for MAC. An ABD >50 mm Hg remained highly specific (98%) but had higher sensitivity (30%) and overall accuracy (62%). CONCLUSIONS Individuals with type 1 diabetes and an ABI >1.30 or ABD >50 mm Hg are very likely to have MAC on X-ray imaging, yet many with MAC will not have an ABI or ABD above these thresholds. Given the high specificity, evaluating high ABI or ABD may be useful to understand correlates of MAC but may underestimate MAC prevalence.
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Morena M, Jaussent I, Halkovich A, Dupuy AM, Bargnoux AS, Chenine L, Leray-Moragues H, Klouche K, Vernhet H, Canaud B, Cristol JP. Bone biomarkers help grading severity of coronary calcifications in non dialysis chronic kidney disease patients. PLoS One 2012; 7:e36175. [PMID: 22567137 PMCID: PMC3342257 DOI: 10.1371/journal.pone.0036175] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2012] [Accepted: 03/27/2012] [Indexed: 02/06/2023] Open
Abstract
Background Osteoprotegerin (OPG) and fibroblast growth factor-23 (FGF23) are recognized as strong risk factors of vascular calcifications in non dialysis chronic kidney disease (ND-CKD) patients. The aim of this study was to investigate the relationships between FGF23, OPG, and coronary artery calcifications (CAC) in this population and to attempt identification of the most powerful biomarker of CAC: FGF23? OPG? Methodology/Principal Findings 195 ND-CKD patients (112 males/83 females, 70.8 [27.4–94.6] years) were enrolled in this cross-sectional study. All underwent chest multidetector computed tomography for CAC scoring. Vascular risk markers including FGF23 and OPG were measured. Logistic regression analyses were used to study the potential relationships between CAC and these markers. The fully adjusted-univariate analysis clearly showed high OPG (≥10.71 pmol/L) as the only variable significantly associated with moderate CAC ([100–400[) (OR = 2.73 [1.03;7.26]; p = 0.04). Such association failed to persist for CAC scoring higher than 400. Indeed, severe CAC was only associated with high phosphate fractional excretion (FEPO4) (≥38.71%) (OR = 5.47 [1.76;17.0]; p = 0.003) and high FGF23 (≥173.30 RU/mL) (OR = 5.40 [1.91;15.3]; p = 0.002). In addition, the risk to present severe CAC when FGF23 level was high was not significantly different when OPG was normal or high. Conversely, the risk to present moderate CAC when OPG level was high was not significantly different when FGF23 was normal or high. Conclusions Our results strongly suggest that OPG is associated to moderate CAC while FGF23 rather represents a biomarker of severe CAC in ND-CKD patients.
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Affiliation(s)
- Marion Morena
- Laboratoire de Biochimie, CHRU de Montpellier, Montpellier, France
- Institut de Recherche et de Formation en Dialyse, Montpellier, France
- UMR 204, Nutripass, Université Montpellier I, Montpellier, France
| | | | - Aurore Halkovich
- Laboratoire de Biochimie, CHRU de Montpellier, Montpellier, France
| | - Anne-Marie Dupuy
- Laboratoire de Biochimie, CHRU de Montpellier, Montpellier, France
| | - Anne-Sophie Bargnoux
- Laboratoire de Biochimie, CHRU de Montpellier, Montpellier, France
- UMR 204, Nutripass, Université Montpellier I, Montpellier, France
| | - Leila Chenine
- Service de Néphrologie-Hémodialyse et Soins Intensifs, CHRU de Montpellier, Montpellier, France
| | - Hélène Leray-Moragues
- Service de Néphrologie-Hémodialyse et Soins Intensifs, CHRU de Montpellier, Montpellier, France
| | - Kada Klouche
- UMR 204, Nutripass, Université Montpellier I, Montpellier, France
- Service de Réanimation Métabolique, CHRU de Montpellier, Montpellier, France
| | - Hélène Vernhet
- Service de Radiologie, CHRU de Montpellier, Montpellier, France
| | - Bernard Canaud
- Institut de Recherche et de Formation en Dialyse, Montpellier, France
- UMR 204, Nutripass, Université Montpellier I, Montpellier, France
- Service de Néphrologie-Hémodialyse et Soins Intensifs, CHRU de Montpellier, Montpellier, France
| | - Jean-Paul Cristol
- Laboratoire de Biochimie, CHRU de Montpellier, Montpellier, France
- UMR 204, Nutripass, Université Montpellier I, Montpellier, France
- * E-mail:
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Disthabanchong S. Vascular calcification in chronic kidney disease: Pathogenesis and clinical implication. World J Nephrol 2012; 1:43-53. [PMID: 24175241 PMCID: PMC3782198 DOI: 10.5527/wjn.v1.i2.43] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2011] [Revised: 10/21/2011] [Accepted: 02/10/2012] [Indexed: 02/06/2023] Open
Abstract
Cardiovascular disease is the leading cause of death among patients with chronic kidney disease (CKD). Vascular calcification (VC) is one of the independent risk factors associated with cardiovascular disease and cardiovascular mortality in both the general population and CKD patients. Earlier evidence revealed substantially higher prevalence of VC in young adults on chronic hemodialysis compared to the general population in the same age range, indicating the influence of CKD-related risk factors on the development of VC. Pathogenesis of VC involves an active, highly organized cellular transformation of vascular smooth muscle cells to bone forming cells evidenced by the presence of bone matrix proteins in the calcified arterial wall. VC occurs in both the intima and the media of arterial wall with medial calcification being more prevalent in CKD. In addition to traditional cardiovascular risks, risk factors specific to CKD such as phosphate retention, excess of calcium, history of dialysis, active vitamin D therapy in high doses and deficiency of calcification inhibitors play important roles in promoting the development of VC. Non-contrast multi-slice computed tomography has often been used to detect coronary artery calcification. Simple plain radiographs of the lateral lumbar spine and pelvis can also detect VC in the abdominal aorta and femoral and iliac arteries. Currently, there is no specific therapy to reverse VC. Reduction of calcium load, lowering phosphate retention using non-calcium containing phosphate binders, and moderate doses of active vitamin D may attenuate progression. Parenteral sodium thiosulfate has also been shown to delay VC progression.
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Affiliation(s)
- Sinee Disthabanchong
- Sinee Disthabanchong, Division of Nephrology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
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Ricardo AC, Lash JP, Fischer MJ, Lora CM, Budoff M, Keane MG, Kusek JW, Martinez M, Nessel L, Stamos T, Ojo A, Rahman M, Soliman EZ, Yang W, Feldman HI, Go AS. Cardiovascular disease among hispanics and non-hispanics in the chronic renal insufficiency cohort (CRIC) study. Clin J Am Soc Nephrol 2012; 6:2121-31. [PMID: 21896829 DOI: 10.2215/cjn.11341210] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
BACKGROUND AND OBJECTIVES Hispanics are the largest minority group in the United States. The leading cause of death in patients with chronic kidney disease (CKD) is cardiovascular disease (CVD), yet little is known about its prevalence among Hispanics with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We conducted cross-sectional analyses of prevalent self-reported clinical and subclinical measures of CVD among 497 Hispanics, 1638 non-Hispanic Caucasians, and 1650 non-Hispanic African Americans, aged 21 to 74 years, with mild-to-moderate CKD at enrollment in the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic CRIC (HCRIC) studies. Measures of subclinical CVD included left ventricular hypertrophy (LVH), coronary artery calcification (CAC), and ankle-brachial index. RESULTS Self-reported coronary heart disease (CHD) was lower in Hispanics compared with non-Hispanic Caucasians (18% versus 23%, P = 0.02). Compared with non-Hispanic Caucasians, Hispanics had a lower prevalence of CAC >100 (41% versus 34%, P = 0.03) and CAC >400 (26% versus 19%, P = 0.02). However, after adjusting for sociodemographic factors, these differences were no longer significant. In adjusted analyses, Hispanics had a higher odds of LVH compared with non-Hispanic Caucasians (odds ratio 1.97, 95% confidence interval, 1.22 to 3.17, P = 0.005), and a higher odds of CAC >400 compared with non-Hispanic African Americans (odds ratio, 2.49, 95% confidence interval, 1.11 to 5.58, P = 0.03). Hispanic ethnicity was not independently associated with any other CVD measures. CONCLUSIONS Prevalent LVH was more common among Hispanics than non-Hispanic Caucasians, and elevated CAC score was more common among Hispanics than non-Hispanic African Americans. Understanding reasons for these racial/ethnic differences and their association with long-term clinical outcomes is needed.
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Affiliation(s)
- Ana C Ricardo
- Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
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Di Iorio B, Bellasi A, Russo D. Mortality in kidney disease patients treated with phosphate binders: a randomized study. Clin J Am Soc Nephrol 2012; 7:487-93. [PMID: 22241819 DOI: 10.2215/cjn.03820411] [Citation(s) in RCA: 164] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND OBJECTIVES Dietary phosphorous overload and excessive calcium intake from calcium-containing phosphate binders promote coronary artery calcification (CAC) that may contribute to high mortality of dialysis patients. CAC has been found in patients in early stages of nondialysis-dependent CKD. In this population, no study has evaluated the potential role of phosphorus binders on mortality. This study aimed to evaluate all-cause mortality as the primary end point in nondialysis-dependent CKD patients randomized to different phosphate binders; secondary end points were dialysis inception and the composite end point of all-cause mortality and dialysis inception. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This is a randomized, multicenter, nonblinded pilot study. Consecutive outpatients (n=212; stage 3-4 CKD) were randomized to either sevelamer (n=107) or calcium carbonate (n=105). Phosphorus concentration was maintained between 2.7 and 4.6 mg/dl for patients with stage 3-4 CKD and between 3.5 and 5.5 mg/dl for patients with stage 5 CKD. The CAC score was assessed by computed tomography at study entry and after 6, 12, 18, and 24 months. All-cause mortality, dialysis inception, and the composite end point were recorded for up to 36 months. RESULTS In patients randomized to sevelamer, all-cause mortality and the composite end point were lower; a nonsignificant trend was noted for dialysis inception. CONCLUSIONS Sevelamer provided benefits in all-cause mortality and in the composite end point of death or dialysis inception but not advantages in dialysis inception. Larger studies are needed to confirm these results.
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Affiliation(s)
- Biagio Di Iorio
- Department of Nephrology, Ospedale A. Landolfi di Solofra, Avellino, Italy.
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Tofik R, Torffvit O, Rippe B, Bakoush O. Urine IgM-excretion as a prognostic marker for progression of type 2 diabetic nephropathy. Diabetes Res Clin Pract 2012; 95:139-44. [PMID: 22078636 DOI: 10.1016/j.diabres.2011.10.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2011] [Revised: 09/08/2011] [Accepted: 10/06/2011] [Indexed: 10/15/2022]
Abstract
UNLABELLED Although the clinical manifestations of type 2 diabetic nephropathy and decline in kidney function are similar to those in type 1, the clinical course and the renal structural changes are more heterogeneous in type 2 diabetic patients. Previous studies have shown that an increased urine IgM excretion in patients with type 1 diabetic nephropathy was associated with poor outcome. In the present follow-up study we examine the prognostic value of baseline urine IgM excretion in patients with type 2 diabetes mellitus. METHODS A cohort of 106 (74 male and 32 female) patients with type 2 diabetes regularly attending our diabetes out-patient clinic at Skane University Hospital in Lund. They were recruited prospectively under the period between 1992 and 2004. Patients were followed-up until January 2009. The end point was cardiovascular (CV) death or end-stage renal disease (ESRD). The median follow-up time was 5 years (0.5-13 years). Participants were divided according to degree of albuminuria and IgM-uria. RESULTS During follow-up time, 28 (19 male and 9 female) patients died of CV events and 41 (26 male and 15 female) developed ESRD. The risk of CV mortality was 2.4 fold, and the risk of renal failure 4.9 fold higher in patients with increased urine IgM excretion compared to patients with low urine IgM excretion. Stratified analysis showed that an increased urine IgM excretion was an independent predictor of renal and cardiovascular death irrespective of the degree of albuminuria (HR=3.6, 95% CI: 2.1-6.0, P<0.001). In conclusion, type 2 diabetic nephropathy patients with high urine IgM excretion rates carry an increased risk of renal and cardiovascular death.
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Affiliation(s)
- Rafid Tofik
- Department of Nephrology, Lund University, Lund, Sweden.
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Joergensen C, Reinhard H, Schmedes A, Hansen PR, Wiinberg N, Petersen CL, Winther K, Parving HH, Jacobsen PK, Rossing P. Vitamin D levels and asymptomatic coronary artery disease in type 2 diabetic patients with elevated urinary albumin excretion rate. Diabetes Care 2012; 35:168-72. [PMID: 22040839 PMCID: PMC3241314 DOI: 10.2337/dc11-1372] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Coronary artery disease (CAD) is the major cause of morbidity and mortality in type 2 diabetic patients. Severe vitamin D deficiency has been shown to predict cardiovascular mortality in type 2 diabetic patients. RESEARCH DESIGN AND METHODS We investigated the association among severe vitamin D deficiency, coronary calcium score (CCS), and asymptomatic CAD in type 2 diabetic patients with elevated urinary albumin excretion rate (UAER) >30 mg/24 h. This was a cross-sectional study including 200 type 2 diabetic patients without a history of CAD. Severe vitamin D deficiency was defined as plasma 25-hydroxyvitamin D (p-25[OH]D3) <12.5 nmol/L. Patients with plasma N-terminal pro-brain natriuretic peptide >45.2 ng/L or CCS ≥400 were stratified as being high risk for CAD (n= 133). High-risk patients were examined by myocardial perfusion imaging (MPI; n = 109), computed tomography angiography (n = 20), or coronary angiography (CAG; n = 86). Patients' p-25(OH)D3 levels were determined by high-performance liquid chromatography/tandem mass spectrometry. RESULTS The median (range) vitamin D level was 36.9 (3.8-118.6) nmol/L. The prevalence of severe vitamin D deficiency was 9.5% (19/200). MPI or CAG demonstrated significant CAD in 70 patients (35%). The prevalence of CCS ≥400 was 34% (68/200). Severe vitamin D deficiency was associated with CCS ≥400 (odds ratio [OR] 4.3, 95% CI [1.5-12.1], P = 0.005). This association persisted after adjusting for risk factors (4.6, 1.5-13.9, P = 0.007). Furthermore, severe vitamin D deficiency was associated with asymptomatic CAD (adjusted OR 2.9, 1.02-7.66, P = 0.047). CONCLUSIONS In high-risk type 2 diabetic patients with elevated UAER, low levels of vitamin D are associated with asymptomatic CAD.
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Chang JH, Sung JY, Nam HE, Jeong H, Jo MY, Hwang YH, Jung JY, Lee HH, Chung W, Sung YM, Kim S. Role of coronary artery calcification score on the decrease in GFR among subjects with CT coronary angiography. Clin Exp Hypertens 2011; 34:24-30. [PMID: 22148962 DOI: 10.3109/10641963.2011.628725] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
OBJECTIVE Higher levels of coronary artery calcification score (CACS) are associated not only with an increased risk for cardiovascular death, but also with lower glomerular filtration rates (GFRs). However, its role in renal disease progression in patients has not been elucidated. MATERIALS AND METHODS We evaluated the change of estimated GFR in 279 nondialytic outpatients, who had undergone computed tomographic coronary angiography and follow-up over a period of 3 months. RESULTS The mean age of the participants was 57.7 ± 10.5 years, and the mean GFR was 88.2 ± 15.7 mL/min/1.73 m(2). Although there was no difference in baseline GFR between the CACS ≤ 200 AU group (n = 240) and the CACS > 200 AU group (n = 39), the latter group had a lower level of final GFR and higher annual reduction rate of GFR than the former group after an observation period of 13.1 ± 5.97 months. After adjusting for confounding variables, including age, gender, baseline GFR, albumin, and proteinuria, high levels of CACS showed an independent association with an annual reduction rate of GFR (r = -0.142, P = .048). CONCLUSIONS The results suggest that CACS was related to an annual decrease in GFR and may predict the faster decline in GFR in patients with symptoms requiring computed tomographic coronary angiography.
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Affiliation(s)
- Jae Hyun Chang
- Department of Internal Medicine, Gachon University of Medicine and Science, Incheon, Korea
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