Objective To determine if hepatocyte growth factor (HGF), a promising biomarker of coronary heart disease (CHD) given its release into circulation in response to endothelial damage, is associated with subclinical and clinical CHD in a racial/ethnic diverse population.
Methods HGF was measured in 6738 participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Highest mean HGF values (pg/mL) were observed in Hispanic, followed by African, non-Hispanic white, then Chinese Americans.
Results In all races/ethnicities, HGF levels were associated with older age, higher systolic blood pressure (SBP) and body mass index, lower high-density lipoprotein, diabetes and current smoking. In fully adjusted models, each SD higher HGF was associated with an average increase in coronary artery calcium (CAC) of 55 Agatston units for non-Hispanic whites (p<0.001) and 51 Agatston units for African-Americans (p=0.007) but was not in the other race/ethnic groups (interaction p=0.02). There were 529 incident CHD events, and CHD risk was 41% higher in African (p<0.001), 17% in non-Hispanic white (p=0.026) and Chinese (p=0.36), and 6% in Hispanic Americans (p=0.56) per SD increase in HGF.
Conclusion In a large and diverse population-based cohort, we report that HGF is associated with subclinical and incident CHD. We demonstrate evidence of racial/ethnic heterogeneity within these associations, as the results are most compelling in African-Americans and non-Hispanic white Americans. We provide evidence that HGF is a biomarker of atherosclerotic disease that is independent of traditional risk factors.
- coronary disease
- risk factors
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Contributor Study design: SJB, CB, PAD, NBL, EJB, CLW. Data collection: SJB, NQH, MYT. Data analysis: PAD, NBL, MA. Outcome adjudication: MJB, JFP. Manuscript draft: All authors contributed, read and approved the final manuscript.
Funding This research was supported by the National Institutes of Health (NIH) contracts N01-HC-95159, N01-HC-95160,
N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-
95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169 from the NHLBI at NIH and by grants UL1-TR-000040 and UL1-TR-001079 from
National Center for Research Resources at NIH. Funding for adhesion protein levels was provided by the NHLBI by grant R01 HL98077. The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of
participating MESA investigators and institutions can be found at
Competing interests None declared.
Ethics approval MESA and its ancillary studies were approved by the Institutional Review Board at participating centers and all participants gave written informed consent.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement MESA Coordinating Center distributes only deidentified Datasets (with HIPAA defined identifiers removed) to Recipient Investigators with approved manuscripts proposals in
compliance with MESA and NHLBI/NIH data privacy and sharing standard practices and
policy. Additionally, access to MESA datasets require completion of a Data Distribution Agreement (MESA Data and Materials Distribution Agreement if the Investigator is not
at a MESA-affiliated institution) and review and approval of a detailed proposal by MESA Publications and Steering Committees for soundness in science, methodology and adherence to MESA policy. Manuscript pen drafts (and presentation abstracts) are also reviewed by these same committees.