Systemic Inflammation Is Associated With Coronary Artery Calcification and All-Cause Mortality in Chronic Kidney Disease

Hwang, Ingyu; Park, Hyo Eun; Kim, Hack‐Lyoung; Kim, Hyue Mee; Park, Jun Bean; Yoon, Yeonyee E.; Lee, Seung–Pyo; Kim, Yong Jin

doi:10.1253/circj.cj-15-1224

Cited by 24 publications

(16 citation statements)

References 37 publications

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“…CKD patients suffer from complications including hyperphosphatemia, anemia, hypertension, hyperglycemia and so on. It is now widely accepted that hyperphosphatemia and hyperglycemia can accelerate VC (4,26), and other complications including hypercalcemia and systemic inflammation, which are also reported to be associated with VC in CKD patients (28,29). Hyperphosphatemia is very common in CKD patients no matter the cause of renal function loss.…”

Section: Discussionmentioning

confidence: 99%

Spironolactone dose‑dependently alleviates the calcification of aortic rings cultured in hyperphosphatemic medium with or without hyperglycemia by suppressing phenotypic transition of VSMCs through downregulation of Pit‑1

et al. 2019

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Vascular calcification (VC) is highly prevalent in chronic kidney disease (CKD), especially in patients with end stage renal disease and is strongly associated with cardiovascular morbidity and mortality. Clinical observations have demonstrated that hyperphosphatemia and hyperglycemia can accelerate VC. Spironolactone (SPL) has been proven to improve cardiovascular outcomes in clinical trials and its protective effect on VC has been reported recently; however, the underlying mechanisms are not completely understood and require further investigation. Furthermore, the current CKD rat models that are used to research VC do not match well with the clinical characteristics of CKD patients. Aortic rings were obtained from male Sprague-Dawley rats, then cultured in different media with varying phosphorus and glucose concentrations to investigate the effects and the possible mechanisms, as well as the effective serum concentrations of SPL, on VC and type III sodium-dependent phosphate cotransporter-1 (Pit-1) expression. SPL dose-dependently alleviated VC by suppressing the phenotypic transition of vascular smooth muscle cell (VSMCs) through downregulation of Pit-1 in a high phosphorus medium and even in a high phosphorus combined with high glucose medium. The combined effects of hyperglycemia and hyperphosphatemia on the calcification of aortic rings ex vivo were demonstrated. In conclusion to the best of our knowledge, this article is the first report on the effective serum concentrations of SPL capable of protecting VSMCs from calcification and provides the first experimental evidence for the combined effects of hyperglycemia and hyperphosphatemia on VC of aortic rings. Additionally, the Pit-1 protein level may be a novel index for evaluating the magnitude of VC in CKD patients.

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Section: Discussionmentioning

confidence: 99%

Spironolactone dose‑dependently alleviates the calcification of aortic rings cultured in hyperphosphatemic medium with or without hyperglycemia by suppressing phenotypic transition of VSMCs through downregulation of Pit‑1

et al. 2019

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“…The level of inflammation studied most extensively with hsCRP is well documented to be associated with an increased risk of cardiovascular disease . A previous report by Hwang et al showed that higher levels of hsCRP in patients screened for CAC was associated with acceleration of CAC and increase in mortality . Despite the interest in using hsCRP levels to select patients for therapy such as statins, there is controversy on the benefit and value of guiding treatment based on the hsCRP level .…”

Section: Discussionmentioning

confidence: 99%

“…Coronary artery disease remains the leading cause of mortality in the Western world . Coronary artery calcification (CAC) and systemic inflammation are both associated with an increased risk for cardiovascular events; however, the effect on the patients after percutaneous coronary intervention (PCI) remains to be elucidated …”

Section: Introductionmentioning

confidence: 99%

Combined and independent impact of coronary artery calcification and inflammation on risk for adverse cardiovascular events after percutaneous coronary intervention: Results from a large single‐center registry

Aoi

Baber

Kovacic

et al. 2020

Cathet Cardio Intervent

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Purpose Our study investigated the impact of coronary artery calcification (CAC) and systemic inflammation on risks for major adverse cardiovascular events (MACE) following percutaneous coronary intervention (PCI). Background CAC and systemic inflammation are known to be associated with an increased risk of cardiovascular events. Methods A total of 17,711 consecutive patients who underwent PCI in our hospital between January 1, 2009 and December 31, 2015 were categorized according to the degree of CAC (moderate/severe vs. none/mild) and high‐sensitivity C‐reactive protein (hsCRP) level (≥2 vs. <2 mg/L). MACE was defined as death, myocardial infarction (MI), or target vessel revascularization (TVR) occurring over 1 year. Results Within the four groups, patients with both moderate/severe CAC and elevated hsCRP (n = 1,814 [10.2%]) were older with more comorbid risk factors compared to those with moderate/severe CAC alone (n = 1,687 [9.5%]), elevated hsCRP alone (n = 7,597 [42.9%]) or neither abnormality (n = 6,613 [37.3%]). The analogous 1‐year MACE rates were 21.2, 14.9, 11.5, and 7.8%, respectively (p‐trend < .001). Results were unchanged after multivariable adjustment, suggesting synergistic adverse effects in patients with both CAC and elevated hsCRP. Conclusions The presence of both moderate/severe CAC and systemic inflammation confers a synergistic effect on risk for MACE following PCI, indicating the need for novel or more intense therapeutic interventions to mitigate risk in such patients.

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“…There is a high prevalence of rapid VC progression in patients with CKD 7 – 10 ) , which is prognostically related to the increased morbidity and mortality of CVD 11 – 15 ) . In this study, we discerned the relationship between CAC or AAC progression and renal functional/morphological changes and revealed the following results: CACS at baseline and DM were independent predictors for CAC progression.…”

Section: Discussionmentioning

confidence: 99%

“…Even in pre-dialysis patients with CKD, the high prevalence and rapid progression of VC is well recognized 7 – 10 ) . In addition, the presence and progression of VC is closely related to the increased morbidity and mortality of CVD 11 – 15 ) .…”

Section: Introductionmentioning

confidence: 99%

Impact of Renal Functional/Morphological Dynamics on the Calcification of Coronary and Abdominal Arteries in Patients with Chronic Kidney Disease

Ichii

Morimoto

Okumura

et al. 2017

JAT

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Aim: Fast-progressing vascular calcification (VC) is accompanied by renal atrophy and functional deterioration along with atherosclerosis in patients with chronic kidney disease (CKD). However, the relationship between VC progression and renal functional and/or morphological changes remains unclear.Methods: We included 70 asymptomatic patients with CKD without hemodialysis in our study. To identify temporal variations, the coronary artery calcification score (CACS), abdominal aortic calcification index (ACI), and renal parenchymal volume index (RPVI) were determined via spiral computed tomography scans taken during the study. We investigated significant factors related to annualized variations of CACS (ΔCACS/y) and ACI (ΔACI/y).Results: During the follow-up period (4.6 years), median values of CACS [in Agatston units (AU)] and ACI increased from 40.2 to 113.3 AU (p = 0.053) and from 13.2 to 21.7% (p = 0.036), respectively. Multivariate analysis revealed that CACS at baseline (p < 0.001) and diabetes mellitus (DM) status (p = 0.037) for ΔCACS/y and ACI at baseline (p = 0.017) and hypertension (HT) status (p = 0.046) for ΔACI/y were significant independent predictors. Furthermore, annualized RPVI variation was significantly related to both ΔCACS/y and ΔACI/y (R = −0.565, p < 0.001, and R = −0.289, p = 0.015, respectively). On the other hand, independent contributions of the estimated glomerular filtration rate (eGFR) and annualized eGFR variation to VC progression were not confirmed.Conclusion: The degree of VC at baseline, DM, HT, and changes in renal volume, but not eGFR, had a strong impact on VC progression in patients with CKD.

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Systemic Inflammation Is Associated With Coronary Artery Calcification and All-Cause Mortality in Chronic Kidney Disease

Cited by 24 publications

References 37 publications

Spironolactone dose‑dependently alleviates the calcification of aortic rings cultured in hyperphosphatemic medium with or without hyperglycemia by suppressing phenotypic transition of VSMCs through downregulation of Pit‑1

Spironolactone dose‑dependently alleviates the calcification of aortic rings cultured in hyperphosphatemic medium with or without hyperglycemia by suppressing phenotypic transition of VSMCs through downregulation of Pit‑1

Combined and independent impact of coronary artery calcification and inflammation on risk for adverse cardiovascular events after percutaneous coronary intervention: Results from a large single‐center registry

Impact of Renal Functional/Morphological Dynamics on the Calcification of Coronary and Abdominal Arteries in Patients with Chronic Kidney Disease

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