Noncalcified Coronary Plaque Burden Mediates the Association of Hepatic Steatosis With Major Adverse Cardiovascular Events: Insights from the PROMISE Trial
Author Block: J. M. Brendel1, T. Mayrhofer1, N. Kerkovits1, S. Ersözlü1, M. Kolossvary2, M. T. Lu1, M. Ferencik3, P. Douglas4, B. Foldyna1; 1Boston, MA/US, 2Budapest/HU, 3Portland/US, 4Durham/US
Purpose: To investigate whether HS is related to plaque volume, plaque burden, and MACE, and whether coronary plaque composition mediates the relationship between HS and MACE.
Methods or Background: Hepatic steatosis (HS) has been linked to major adverse cardiovascular events (MACE) independently of other cardiovascular risk factors and the extent of coronary artery disease. However, the association between HS, advanced plaque measures, and MACE remains unclear.
A central core laboratory analyzed PROMISE participants randomized to the CT arm. HS was assessed on non-contrast CT using standard hepatic and splenic attenuation methods. Coronary CT angiography was used to quantify total, calcified, noncalcified, and low-attenuation plaque volume and burden (% vessel volume). Multivariable regression and mediation analyses assessed relationships between HS, plaque components, and MACE (death, myocardial infarction, unstable angina hospitalization; median follow-up 25 months, IQR: 18–33).
Results or Findings: Among 3,637 patients (60.6±8.2 years, 51.4% female), 25.5% had HS and were slightly younger, more often male, had more cardiovascular risk factors, and a higher MACE rate (4.1% vs. 2.5%), all p<0.05. After adjustment for clinical risk factors, HS was associated exclusively with greater noncalcified plaque burden (NCPB, β 1.25%; 95%CI 0.02–2.49; p=0.047). HS conferred increased MACE risk independent of atherosclerotic cardiovascular disease risk score, obesity, obstructive stenosis, and NCPB (aHR 1.69; 95%CI, 1.12–2.54; p=0.012). NCPB accounted for 11% of the association between HS and MACE.
Conclusion: HS is linked to greater NCPB and to MACE, independent of clinical risk factors and advanced CT plaque measures. HS should be considered when stratifying cardiovascular risk and may inform medical therapy.
Limitations: Median follow-up of just over 2 years limits the ability to assess long-term outcomes.
Funding for this study: This study was supported by NIH/NHLBI grants #1R01HL098236, #1R01HL098237, #1R01HL098305, #1R01HL170877-01, #1R01HL146145-01A1. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: All participants provided written informed consent, and the trial was approved by local or central institutional review boards (ClinicalTrials.gov NCT01174550)