Betatrophin Predicts Cardiovascular Events Independently from the Presence of Type 2 Diabetes and Coronary Artery Disease

Betatrophin, also known as ANGPTL8 or lipasin is a nutritionally-regulated protein secreted by the liver and adipose tissue. It is associated with type 2 diabetes mellitus (T2DM) and lipid metabolism. Whether betatrophin is associated with the risk for cardiovascular events is unknown and is addressed in the present study. We measured betatrophin in 553 patients undergoing coronary angiography for the evaluation of established or suspected stable coronary artery disease (CAD) and prospectively recorded cardiovascular events in these patients during a follow-up period of up to 8 years. During follow-up, 301 cardiovascular events occurred. The incidence of cardiovascular events was significantly higher in patients with T2DM (n=161) than in those who did not have diabetes (47.2% vs. 34.4%; p=0.005). Betatrophin was significantly and inversely associated with cardiovascular events both univariately (HR 0.64 [95% CI 0.47-0.87], p=0.004) and after full adjustment including T2DM and baseline CAD (HR 0.55 [95% CI 0.40-0.76], p<0.001). The inclusion of betatrophin to a basic prediction model for the cardiovascular event risk significantly increased model performance (NRI=0.188, p<0.01).

In conclusion, this study for the first time shows that betatrophin predicts cardiovascular events independently from conventional risk factors including the presence of T2DM.