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Abstract: PO2154

Identification of Novel Biomarkers and Pathways for Coronary Artery Calcification in Non-Diabetic Patients on Hemodialysis Using Metabolomic Profiling

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Chen, Wei, Montefiore Medical Center, Bronx, New York, United States
  • Fitzpatrick, Jessica, Hospital for Sick Children, Toronto, Ontario, Canada
  • Sozio, Stephen M., Johns Hopkins University, Baltimore, Maryland, United States
  • Jaar, Bernard G., Johns Hopkins University, Baltimore, Maryland, United States
  • Estrella, Michelle M., San Francisco VA Medical Center, San Francisco, California, United States
  • Riascos-Bernal, Dario F., Yeshiva University Albert Einstein College of Medicine, Bronx, New York, United States
  • Wu, Tong tong, University of Rochester Medical Center, Rochester, New York, United States
  • Qiu, Yunping, Yeshiva University Albert Einstein College of Medicine, Bronx, New York, United States
  • Kurland, Irwin J., Yeshiva University Albert Einstein College of Medicine, Bronx, New York, United States
  • Dubin, Ruth F., University of California San Francisco, San Francisco, California, United States
  • Chen, Yabing, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Parekh, Rulan S., Hospital for Sick Children, Toronto, Ontario, Canada
  • Bushinsky, David A., University of Rochester Medical Center, Rochester, New York, United States
  • Sibinga, Nicholas, Yeshiva University Albert Einstein College of Medicine, Bronx, New York, United States

Group or Team Name

  • PACE
Background

A better understanding of pathophysiology involving coronary artery calcification (CAC) in hemodialysis (HD) patients will help to develop new therapies. We sought to identify the differences in metabolomics profiles between HD patients with and without CAC.

Methods

This is a case-control study nested within a cohort of 568 incident HD patients from the Predictors of Arrhythmic and Cardiovascular Risk in ESRD (PACE) study. Cases were non-diabetics with a CAC score >100 (n=51), and controls were non-diabetics with a CAC score of 0 (n=48). We measured 452 serum metabolites in each participant using liquid chromatography–mass spectrometry. Metabolites and pathway scores were compared using Mann–Whitney U tests, partial least squares-discriminant analyses, and pathway enrichment analyses. Multiple logistic regression was used to examine the associations of key metabolites and pathways with CAC.

Results

Cases had a median CAC score of 466 (IQR 246-981). Compared to controls, cases were older (64±13 vs. 42±12 years) and were less likely to be African American (51% vs. 94%). We identified three metabolites in bile acid synthesis (chenodeoxycholic, deoxycholic, and glycolithocholic acids) and one metabolic pathway (arginine/proline metabolism) that were associated with CAC. After adjusting for demographics, higher levels of chenodeoxycholic, deoxycholic, and glycolithocholic acids were associated with higher odds of having CAC. Comparing the third with the first tertile of each bile acid, the adjusted OR (95% CI) was 6.34 (1.12-36.06), 6.73 (1.20-37.82), and 8.53 (1.50-48.49), respectively. Using the first principal component (PC1) score, arginine/proline metabolism was associated with CAC after adjusting for demographics [OR: 1.83 (95% CI: 1.06-3.15) per 1 unit higher in PC1 score], and the association remained significant after additional adjustments for statin use.

Conclusion

Among HD patients without diabetes mellitus, chenodeoxycholic, deoxycholic, and glycolithocholic acids may be potential biomarkers for CAC, and arginine/proline metabolism may emerge as a new pathway in the pathogenesis of CAC and could be a potential treatment target.

Funding

  • NIDDK Support