2138. Elevations of Short Chain Dicarboxylacylcarnitine (SCDA) Levels Precede Major Cardiovascular Events in HIV-Infected Persons
Session: Poster Abstract Session: HIV Cardiovascular Disease, Lipids, and Diabetes
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • IDSA Poster 2016 Okeke Metabolomics_Final.pdf (153.0 kB)
  • Background: HIV-infected persons are at increased risk for major cardiovascular disease (CVD) events compared to uninfected persons. The excess risk of CVD events in HIV-infected persons cannot be explained by traditional risk factors alone. Biomarkers to assist in CVD risk stratification in HIV-infected persons are lacking. Short chain dicarboxylacylcarnitines (SCDA), a mitochondrial metabolite shown to predict CVD events in uninfected persons, have never been studied in persons with HIV.

    Methods: We conducted a targeted metabolomics analysis of plasma samples from 24 pairs of virally suppressed HIV-infected persons from the Duke HIV CVD Cohort, in a case-control format. Cases were defined as HIV-infected persons with documentation of acute myocardial infarction or diagnosis of severe coronary artery disease (CAD) by cardiac catheterization. HIV-infected cases without a history of CAD were matched 1:1 by age, race, sex, mean SBP and CD4 count. Only samples that preceded CAD diagnosis were included. Tandem flow injection mass spectrometry was used to quantify levels of a validated targeted metabolite panel (N=63). To reduce data complexity, we consolidated metabolites with collinear measures into interpretable factors using principal component analysis (PCA). Comparison of factor levels between cases and controls was done by student’s T-test.

    Results:

    48 HIV-infected persons were included in the analysis. Patient characteristics were: mean age 52.4 ± 8.1; 50% Black, 79% male; mean systolic BP 138mm Hg; mean BMI: 26.5kg/m2 for cases and 26.8 kg/m2 for controls; mean most recent CD4 573 cells/mm3 for cases, 476 cells/mm3 for controls. Based on metabolite levels, 14 factors were derived. The SCDA-derived factor (Ci4-DC/C4-DC, C5-DC, C6-DC, C10-OH/C8-DC, C12-OH/C10-DC, C6:1-DC/C8:1-OH, C8:1-DC acylcarnitines] was one of only two factors that revealed markedly higher plasma levels in cases than controls (p = 0.06).

    Conclusion: HIV-infected persons with known major CAD events have significantly higher circulating levels of SCDA prior to their event than HIV-infected persons without known CAD. Although larger studies are ongoing for validation, SCDA may be an important biomarker in optimizing CVD risk stratification for HIV-infected persons.

    Nwora Lance Okeke, MD1, Susanna Naggie, MD, MHS2, Damian Craig, Ph.D3, Michael Muehlbauer, Ph.D4, Olga Ilkayeva, Ph.D4 and Svati Shah, MD4,5, (1)Medicine -Infectious Diseases, Duke University Medical Center, Durham, NC, (2)Infectious Diseases Research, Duke Clinical Research Institute, Durham, NC, (3)Duke Molecular physiology Institute, Durham, NC, (4)Duke Molecular Physiology Institute, Durham, NC, (5)Medicine-Cardiology, Duke University Medical Center, Durham, NC

    Disclosures:

    N. L. Okeke, None

    S. Naggie, None

    D. Craig, None

    M. Muehlbauer, None

    O. Ilkayeva, None

    S. Shah, None

    Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.