Abstract P369: Hepatocyte Growth Factor is Positively Associated With Progression of Atherosclerosis: the Multi-Ethnic Study of Atherosclerosis

Introduction: Hepatocyte growth factor (HGF) is released in response to endothelial injury, and higher levels of circulating HGF are associated with atherosclerosis. However, the association of HGF with atherosclerosis progression is unknown. Hypothesis: Circulating HGF is positively associated with atherosclerosis progression, measured as progression of 1) carotid artery plaque and 2) coronary artery calcium (CAC). Methods: The Multi-Ethnic Study of Atherosclerosis is a large, population-based cohort study of adults aged 45-84 and free of clinical cardiovascular disease. Participants had HGF measured in serum at baseline (2000-02), and were followed for progression of carotid plaque and CAC through 2012. We defined CAC and carotid plaque progression as dichotomous variables (progression, no progression). Carotid plaque progression is an increase in the number of carotid plaques. We used the Hokanson method to define CAC progression as an increase of ≥ 2.5 mm 3 in the square root-transformed calcium volume score. Relative risk regression quantified the association between HGF and carotid plaque progression. Cox regression models using inverse-probability-of-attrition weights estimated the association of HGF with progression of CAC. All effect estimates are adjusted for potential confounding variables. Results: The cohort included 6714 Americans with HGF measurements: 2593 non-Hispanic white, 797 Chinese, 1848 black, and 1476 Hispanic Americans. In 3363 participants with measurements for both carotid plaque and HGF, each standard deviation (259 pg/ml) increase in HGF was associated with a 4% greater risk (95% CI: 1.01-1.07) of carotid plaque progression (n=1875), which did not differ by race/ethnicity (interaction p = 0.3). Out of 6714 participants with measurements for both CAC and HGF, 2994 had CAC progression during follow-up. The association of HGF with CAC progression differed by race/ethnicity (interaction p = 0.01). Each standard deviation increase of HGF was associated with a 10% greater risk of CAC progression in non-Hispanic white (95% CI: 1.05-1.16) and black Americans (95% CI: 1.03-1.17), while HGF was not associated with CAC progression in Chinese (p = 0.5) nor Hispanic (p = 0.7) American participants. Conclusions: Circulating HGF was associated with a modestly increased risk of atherosclerosis progression in this large and diverse population, with the strongest associations between HGF and CAC progression in non-Hispanic white and black Americans. Our results suggest that HGF may have utility as a marker of atherosclerosis progression in some populations.