Hepatocyte growth factor is associated with greater risk of extracoronary calcification: results from the multiethnic study of atherosclerosis

Abstract

Background: Hepatocyte growth factor (HGF) is a biomarker with potential for use in the diagnosis, treatment and prognostication of cardiovascular disease (CVD). Elevated HGF is associated with calcification in the coronary arteries. However, knowledge is limited on the role HGF may play in extracoronary calcification (ECC). This study examined whether HGF is associated with ECC in the aortic valve (AVC), mitral annulus (MAC), ascending thoracic aorta and descending thoracic aortic (DTAC).

Methods: At baseline, adults aged 45-84 years, free of CVD, in the Multi-Ethnic Study of Atherosclerosis had HGF and ECC measured by ELISA and cardiac CT scan, respectively. ECC measurements were repeated after an average of 2.4 years of follow-up. Prevalent ECC was defined as Agatston score >0 at baseline. Incident ECC was defined as Agatston score >0 at follow-up among participants with Agatston score=0 at baseline. We used Poisson and linear mixed-effects regression models to estimate the association between HGF and ECC, adjusted for sociodemographic and CVD risk factors.

Results: Of 6648 participants, 53% were women. Mean (SD) age was 62 (10) years. Median (IQR) of HGF was 905 (757-1087) pg/mL. After adjustment for CVD risk factors, the highest HGF levels (tertile 3) were associated with greater prevalence and extent of AVC, MAC and DTAC at baseline compared with the lowest tertile (tertile 1). Additionally, the risk of incident AVC and MAC increased by 62% and 45%, respectively, in demographic-adjusted models. However, the associations were not statistically significant in fully adjusted models. The highest HGF levels were also associated with 10% and 13% increase in MAC and DTAC progression, respectively, even after adjustment for CVD risk factors.

Conclusion: Higher HGF levels were significantly associated with a greater risk of calcification at some extracoronary sites, suggesting an alternate biological pathway that could be targeted to reduce CVD risk.

Keywords: Atherosclerosis; Biomarkers; Cardiac Imaging Techniques; Epidemiology; Heart Valve Diseases.

Figure 1

Flowchart of study participants. ATAC, ascending thoracic aorta; AVC, aortic valve; DTAC, descending thoracic aortic; ECC, extracoronary calcification; HGF, hepatocyte growth factor; MAC, mitral annulus; MESA, Multi-Ethnic Study of Atherosclerosis.

Figure 2

Distribution of prevalent ECC by HGF tertiles. Green: first tertile of HGF; orange: second tertile of HGF; red: third tertile of HGF. ATAC, ascending thoracic aorta; AVC, aortic valve; DTAC, descending thoracic aortic; ECC, extracoronary calcification; HGF, hepatocyte growth factor; MAC, mitral annulus.

Figure 3

Distribution of incident ECC by HGF tertiles. Green: first tertile of HGF; orange: second tertile of HGF; red: third tertile of HGF. ATAC, ascending thoracic aorta; AVC, aortic valve; DTAC, descending thoracic aortic; ECC, extracoronary calcification; HGF, hepatocyte growth factor; MAC, mitral annulus.