Background Several studies have reported that the circulating concentration of hepatocyte growth factor (HGF) was increased in individuals with clinically overt atherosclerotic disease, including coronary heart disease and peripheral arterial disease. However, whether changes in the circulating concentration of HGF are associated with early atherosclerotic changes in apparently healthy individuals remains to be determined. Objective To investigate the relationship between the plasma concentration of HGF and carotid arterial remodeling. Methods Plasma concentrations of HGF were measured in 201 community-dwelling healthy residents free from any medications and signs and history of cardiovascular disease. Carotid intima-media thickness (IMT) and carotid internal diameter were determined by ultrasonography with a 7.5 MHz probe. The study participants were divided into four groups according to the presence or absence of carotid atherosclerosis (presence of plaque, IMT greater than or equal to 0.85 mm) and carotid arterial dilatation (diameter greater than or equal to 7.0 mm). Results Carotid arterial remodeling, atherosclerosis or dilatation, or combinations thereof, was associated with significantly greater concentrations of plasma HGF. Among risk factors, plasma HGF was significantly associated with advanced age (greater than or equal to 65 years), current smoking and diabetes mellitus, whereas sex, obesity, hypertension and hypercholesterolemia did not affect plasma concentrations of HGF. Multiple regression analysis showed that plasma HGF was independently associated with carotid arterial remodeling (atherosclerosis, dilatation, or both) in addition to age and systolic blood pressure. Conclusions These results indicate that the plasma concentration of HGF increases in relation to carotid arterial remodeling, independently of known risk factors for atherosclerosis. These findings further support a possible role of HGF in atherosclerosis. (C) 2001 Lippincott Williams & Wilkins.