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Published on: June 2, 2022
Vascular Calcification Progression Modulates the Risk Associated with Vascular Calcification Burden in Incident to
Antonio Bellasi1, Luca Di Lullo2, Domenico Russo3
1Department of Medicine, Division of Nephrology, Ente Ospedaliero Cantonale, 6900 Lugano, Switzerland.
Insights
Coronary artery calcification (CAC) progression predicts mortality in new hemodialysis patients. However, progression may reduce baseline CAC risk, and calcium-free binders may improve survival.
Area of Science:
- Nephrology
- Cardiology
- Radiology
Background:
- Chronic kidney disease (CKD) causes millions of deaths annually, primarily from cardiovascular (CV) diseases.
- Vascular calcification is a key non-traditional CV risk factor in CKD patients.
- Patients initiating hemodialysis (HD) face a high mortality risk, necessitating investigation of predictive factors.
Purpose of the Study:
- To investigate the association between coronary artery calcification (CAC) progression and all-cause mortality in patients new to hemodialysis.
- To explore the interplay between baseline CAC burden, CAC progression (CACP), and mortality risk.
- To assess the impact of calcium-free phosphate binders on the CACP-mortality relationship.
Main Methods:
- Post hoc analysis of the Independent study (NCT00710788).
- Computed tomography imaging for CAC quantification at baseline and 12 months in 414 incident HD patients.
- Survival analysis to evaluate associations of CAC burden, CACP, and mortality over a median 36-month follow-up.
Main Results:
- 106 deaths occurred during follow-up; older, diabetic patients with prior CV events had higher CAC burden.
- Both baseline CAC burden (HR: 1.29) and CACP (HR: 5.16) were independently associated with all-cause mortality.
- CACP mitigated the risk of baseline CAC burden (p=0.002); calcium-free phosphate binders attenuated the CACP-mortality link.
Conclusions:
- CAC burden and CACP are significant predictors of mortality in incident HD patients.
- CACP may paradoxically reduce the risk associated with baseline CAC, and its association with mortality is attenuated by calcium-free phosphate binders.
- Modulating CACP through interventions like specific medications or kidney transplantation may improve survival in this high-risk population.
Abstract:
Background: It is estimated that chronic kidney disease (CKD) accounts globally for 5 to 10 million deaths annually, mainly due to cardiovascular (CV) diseases. Traditional as well as non-traditional CV risk factors such as vascular calcification are believed to drive this disproportionate risk burden. We aimed to investigate the association of coronary artery calcification (CAC) progression with all-cause mortality in patients new to hemodialysis (HD). Methods: Post hoc analysis of the Independent study (NCT00710788). At study inception and after 12 months of follow-up, 414 patients underwent computed tomography imaging for quantification of CAC via the Agatston methods. The square root method was used to assess CAC progression (CACP), and survival analyses were used to test its association with mortality. Results: Over a median follow-up of 36 months, 106 patients died from all causes. Expired patients were older, more likely to be diabetic or to have experienced an atherosclerotic CV event, and exhibited a significantly greater CAC burden (p = 0.002). Survival analyses confirmed an independent association of CAC burden (hazard ratio: 1.29; 95% confidence interval: 1.17-1.44) and CACP (HR: 5.16; 2.61-10.21) with all-cause mortality. CACP mitigated the risk associated with CAC burden (p = 0.002), and adjustment for calcium-free phosphate binder attenuated the strength of the link between CACP and mortality. Conclusions: CAC burden and CACP predict mortality in incident to dialysis patients. However, CACP reduced the risk associated with baseline CAC, and calcium-free phosphate binders attenuated the association of CACP and outcomes, suggesting that CACP modulation may improve survival in this population. Future endeavors are needed to confirm whether drugs or kidney transplantation may attenuate CACP and improve survival in HD patients.
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