Uric acid is an independent predictor of cardiac allograft vasculopathy after heart transplantation

Rabea Asleh, Megha Prasad, Alexandros Briasoulis, Valentina Nardi, Rosalyn Adigun, Brooks S. Edwards, Naveen L. Pereira, Richard C. Daly, Amir Lerman, Sudhir S. Kushwaha

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Background: Cardiac allograft vasculopathy (CAV) is a major complication after heart transplantation (HT). Uric acid (UA) may play a role in CAV due to its role in stimulating T-cell–mediated immunity. Sirolimus is associated with CAV attenuation through a number of mechanisms, including immune-mediated effects. We aimed to determine whether UA is an independent predictor of CAV and whether conversion to sirolimus as primary immunosuppression modulates UA levels. Methods: We retrospectively analyzed a cohort of 224 patients who underwent HT between 2004 and 2015 and had serial coronary intravascular ultrasound (IVUS) studies. Serum UA levels were measured at baseline and last follow-up IVUS in all participants. CAV progression was assessed by measuring the change in plaque volume (ΔPV) and plaque index (ratio of plaque volume to vessel volume [ΔPI]) between last follow-up and baseline IVUS after correction for time of follow-up. Results: Patients with high (≥7 mg/dl) compared with low (<7 mg/dl) UA had increased median ΔPV (0.33 [interquartile range 0.08 to 0.93] vs 0.07 [–0.17 to 0.38] mm3/mm/year; p < 0.001) and ΔPI (2.0% [0.31% to 3.9%] vs 0.33% [–1.2% to 2.0%]; p < 0.001). Elevated UA levels were associated with a significantly increased risk of developing significant CAV progression (ΔPV >0.50 mm3/mm) (hazard ratio 2.2, 95% confidence interval 1.1 to 4.6; p = 0.037). Sirolimus resulted in decreased UA levels (5.8 ± 1.4 vs 5.2 ± 1.5; p = 0.002) and patients converted to sirolimus and had low UA levels had the least CAV progression (p < 0.001). After adjustment for potential confounders, change in UA level was also an independent predictor of CAV progression. Conclusions: UA is an independent predictor of CAV after HT. Sirolimus is associated with decreased UA levels and may explain one of the mechanisms by which sirolimus attenuates CAV progression.

Original languageEnglish (US)
Pages (from-to)1083-1092
Number of pages10
JournalJournal of Heart and Lung Transplantation
Volume37
Issue number9
DOIs
StatePublished - Sep 2018

Keywords

  • cardiac allograft vasculopathy
  • coronary intravascular ultrasound
  • heart transplantation
  • immunosuppression
  • uric acid

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

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