Study Shows An Increase in the Levels of Hepatocyte Growth Factors Associated with a Higher Risk of Cardiovascular Disease

Fahad Alkhalfan, M.D.
By Fahad Alkhalfan, M.D. on

A study led by Paul Decker showed that changes in the levels of hepatocyte growth factor (HGF) were an independent predictor of the incidence of coronary heart disease. The findings of this research letter published in the American Heart Journal could help understand the role of HGF in coronary heart disease.

Hepatocyte growth factor (HGF), a potential biomarker of coronary heart disease (CHD), is released into the circulation in response to endothelial damage. Higher levels of HGF are associated with adverse cardiovascular risk factors and higher rates of myocardial infarction and coronary atherosclerosis. However, whether a change in HGF correlates with a change in the risk of cardiovascular disease is not known. The Multi-Ethnic Study of Atherosclerosis (MESA) previously demonstrated that higher levels of HGF were associated with a greater burden of subclinical atherosclerosis and an increased risk of coronary heart disease. The investigators aimed to use the data collected from MESA to determine if the change in HGF over time was associated with a change in the progression of atherosclerosis and incidence of CHD.

Conventional risk factors for atherosclerotic diseases have been identified over the last 6 decades and have been incorporated into clinical risk scores. Ethnic-specific expression and regulation patterns of circulating biomarkers associated with CHD may contribute to differences in disease rates and provide insight into pathological mechanisms of atherosclerosis. In a large and diverse population-based cohort, we report that change in HGF is an independent predictor of incident CHD.” – Paul Dekcer, M.S.

Serum HGF was measured at baseline and two years later in 2,379 patients. Additionally, traditional risk factors of cardiovascular disease such as hypertension and diabetes were assessed. The change in coronary artery calcium (CAC) score was used as a measure of subclinical atherosclerosis. The investigators assessed whether a change in HGF influenced a change in CAC score.

At the end of two years, there were 183 coronary heart disease events (including myocardial infarction, cardiac arrest, definite angina, and cardiovascular death). The authors found that there was no association between change in HGF score and a change in coronary artery calcium score by 2 years. However, there was an association between change in HGF score and the occurrence of a CHD related event. The risk of an event was 40% higher for every 1 standard deviation increase in HGF (p = 0.001). Even after adjusting for confounders, the association remained significant (OR 1.35, p = 0.005). While this was mainly observed in Hispanic patients and non-Hispanic white patients, there was no statistical evidence to suggest that there was a difference between the races.

Given its angiogenic properties, HGF is believed to be involved in atherosclerotic disease and therefore, the occurrence of a cardiovascular event. The findings of this study extend the previous observations that demonstrated that a high HGF is associated with an increased risk of cardiovascular events. The study does have its limitations. The event rate was relatively low in all race groups, which could have made looking for effect modification difficult. When discussing the results of the study, Paul Decker wrote, “Conventional risk factors for atherosclerotic diseases have been identified over the last 6 decades and have been incorporated into clinical risk scores. Ethnic-specific expression and regulation patterns of circulating biomarkers associated with CHD may contribute to differences in disease rates and provide insight into pathological mechanisms of atherosclerosis. In a large and diverse population-based cohort, we report that change in HGF is an independent predictor of incident CHD.”

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