Hepatocyte growth factor demonstrates racial heterogeneity as a biomarker for coronary heart disease

Abstract

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. 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 and BMI, lower HDL, diabetes, and current smoking. In fully adjusted models, each standard deviation (SD) higher HGF was associated with an average increase in coronary artery calcium of 55 Agatston units for non-Hispanic white (p<0.001) and 51 for African (p=0.007) Americans, 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 (p=0.56) Americans 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 and non-Hispanic white Americans. We provide evidence that HGF is a biomarker of atherosclerotic disease that is independent of traditional risk factors.

Increased hepatocyte growth factor levels over 2 years are associated with coronary heart disease: the Multi-Ethnic Study of Atherosclerosis (MESA)

“…3,4 In the Multi-Ethnic Study of Atherosclerosis (MESA), higher levels of HGF are associated with a greater burden of subclinical atherosclerosis and an increased risk of coronary heart disease. 5 These results provide preliminary evidence of the potential of HGF as a clinical biomarker of CHD. However, the clinical significance of changes in HGF levels over time is unknown.…”

“…This extends our prior observation that higher levels of HGF measured at baseline are associated with risk of cardiovascular disease. 5 In contrast, change in HGF was not associated with change in subclinical atherosclerosis as measured by coronary artery calcium, albeit power was limited.…”

“…For example, previous work in MESA showed that HGF was positively associated with race/ ethnicity, increasing age, higher body mass index (BMI) and systolic blood pressure, lower HDL levels, hypertensive and diabetic status, and current smokers. 5 Furthermore, HGF levels were associated with CAC in non-Hispanic white and African Americans. Similarly, HGF was associated with CHD risk but the results were most compelling in the African Americans and non-Hispanic whites.…”

The incremental prognostic value of sIL-2R and HGF in acute ischemic stroke

“…The other underlying mechanisms might include promoting the migration of immune cells and secretion of pro-inflammatory chemokines [21] and accelerating the progression of atherosclerotic lesions [22], thus increasing the risk of unfavorable prognosis. Clinically, HGF is a biomarker of atherosclerotic disease [23] and positively associated with the incidence of stroke [24,25]. Zhu et al reported that HGF was associated with mortality but not disability at 3 months after ischemic stroke onset [18].…”

The incremental prognostic value of sIL-2R and HGF in acute ischemic stroke

“…In recent years, serum HGF has emerged as a novel biomarker for cardiovascular and cerebrovascular diseases. Bielinski et al [19] reported that HGF is a biomarker of atherosclerotic disease and is associated with subclinical and incident coronary heart disease. Moreover, Susen et al [20] found that high serum HGF is an independent predictor of a composite of death and myocardial infarction.…”