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Abstract: PO1775

Tryptophan Metabolites Associate with Subclinical and Incident Cardiovascular Disease in CKD

Session Information

Category: Hypertension and CVD

  • 1401 Hypertension and CVD: Epidemiology, Risk Factors, and Prevention

Authors

  • Benitez, Trista Marie, University of Michigan, Ann Arbor, Michigan, United States
  • Vanderwoude, Elizabeth, University of Michigan, Ann Arbor, Michigan, United States
  • Han, Yun, University of Michigan, Ann Arbor, Michigan, United States
  • Byun, Jaeman, University of Michigan, Ann Arbor, Michigan, United States
  • Cheofor, Vetalise Konje, University of Michigan, Ann Arbor, Michigan, United States
  • Gillespie, Brenda W., University of Michigan, Ann Arbor, Michigan, United States
  • Saran, Rajiv, University of Michigan, Ann Arbor, Michigan, United States
  • Mathew, Anna Vachaparampil, University of Michigan, Ann Arbor, Michigan, United States
Background

Inflammation and oxidative stress contribute to the increased cardiovascular disease (CVD) burden in CKD patients. Altered tryptophan catabolism via the kynurenine pathway associates with CVD, but the ability of these specific metabolites to act as biomarkers of CVD risk in CKD warrants further research.

Methods

We measured tryptophan metabolites using targeted mass spectrometry in moderate to severe CKD patients (n=325; median follow-up 3 years). Vascular calcification at the coronary artery and aorta was measured using a 4-slice LightSpeed QXi and reported as Agatston scores. Incident CVD events included myocardial infarction, coronary revascularization procedures, stroke, transient ischemic attack, new-onset heart failure, sudden cardiac death, and peripheral vascular disease requiring revascularization or amputation. Multiple linear regression and Cox proportional hazard analyses assessed the relationship of tryptophan metabolites to subclinical markers of CVD and CVD events.

Results

We found that lower baseline tryptophan levels predicted increased aortic calcification in a fully adjusted model controlling for demographics, CVD history, traditional risk factors, renal function, CRP, and serum albumin (p=0.006). Higher baseline levels of anthranilic acid and hydroxyanthranilic acid predicted increased coronary calcification and higher total Agatston score, respectively, in the fully adjusted model (p=0.03 and p=0.03). One unit decrease in serum tryptophan at baseline is associated with 70% decrease in time to incident CVD event when adjusting for demographics, CVD history, risk factors, and renal function (HR: 0.31, p = 0.04). Increased anthranilic acid and quinolinic acid independently reduced time to incident CVD event (HR: 1.88, p=0.02; HR: 1.56, p=0.02 respectively), but were not significant in the fully adjusted model.

Conclusion

Lower tryptophan levels are associated with increased aortic calcification and decreased time to incident CVD events. Higher levels of anthranilic acid, hydroxyanthranilic acid, and quinolinic acid are associated with subclinical CVD. Together, these data demonstrate that catabolism of tryptophan via the kynurenine pathway is associated with subclinical CVD and predicts cardiovascular events in CKD.

Funding

  • Other NIH Support