Evidence suggests ApoC-III reduction confers reduced CV risk

NEW ORLEANS — Genetic and other evidence indicate that elevated apolipoprotein C-III is a risk factor for CAD, and lowering it may reduce risk for CV events, according to a keynote lecture at the National Lipid Association Scientific Sessions.

In 47 years of study of ApoC-III, a triglyceride-rich lipoprotein, researchers now have a better understanding of its importance, Anne Tybjaerg-Hansen, MD, DMSc, professor of clinical biochemistry and translational molecular cardiology at Copenhagen University Hospital and the Faculty of Health and Medical Sciences, University of Copenhagen, Denmark, said during a presentation.

Anne Tybjaerg-Hansen

“ApoC-III is not the new guy on the block, it is the middle-aged guy on the block,” she said. “Unlike the rest of us, ApoC-III is becoming more interesting in middle age.”

Genetic studies have determined that loss-of-function mutations of the APOC3 gene are associated with reduced risk for ischemic vascular disease. One study estimated the risk reduction at more than 40%, Tybjaerg-Hansen said.

In addition, a population-based study in Denmark determined that increased triglycerides were associated with increased risk for MI and mortality, and randomized controlled trials have consistently shown a reduction in CV events associated with a reduction in triglycerides, she said. High triglycerides mark the presence of remnant particles which contain apoC-III, and remnants can cause atherosclerosis and CV events due to their cholesterol content. Further, Mendelian randomization studies suggest that the relationship between remnant cholesterol, defined as total cholesterol minus HDL- and LDL cholesterol, and ischemic heart disease is causal, according to Tybjaerg-Hansen.

Recent published studies comparing the effect of increased remnant cholesterol levels with increased LDL cholesterol levels on CV risk and mortality suggest that while both remnant cholesterol and LDL cholesterol associate with increased CV risk, only remnant cholesterol associates with increased mortality, she said.

This body of evidence suggests that an agent to inhibit APOC3 could be successful at reducing ischemic heart disease events, Tybjaerg-Hansen said.

“With triglyceride-rich remnant lipoproteins, the remnant cholesterol in these particles is causally associated with increased risk for ischemic heart disease,” she said. “Loss-of-function mutations of APOC3 are associated with large reductions in remnant cholesterol levels out to about 43% overall, and they are also associated with large reductions, about 40%, in risk for ischemic vascular disease. The new [agents targeting] APOC3 show very promising results at reducing ApoC-III levels and triglyceride levels, but we still need endpoint data.” – by Erik Swain

Reference:

Tybjaerg-Hansen A. Keynote Lecture – ApoC-III: Risk Factor, Pathophysiology and Target. Presented at: National Lipid Association Scientific Sessions; May 19-22, 2016; New Orleans.
Disclosure: Tybjaerg-Hansen reports no relevant financial disclosures.