Plenary speakers in the spotlight: Robert Hegele, Henry Ginsberg

Professor Henry Ginsberg

ARE LIPOPROTEIN REMNANTS A REASONABLE TARGET FOR THERAPY?

Henry N. Ginsberg is the Irving Professor of Medicine at Columbia University College of Physicians and Surgeons, Associate Dean for Clinical and Translational Research, and Director of the Irving Institute for Clinical and Translational Research at Columbia University Medical Center in New York, New York, USA. His research interests focus on the regulation of plasma cholesterol and triglyceride blood levels, particularly the metabolism of apolipoprotein B–containing lipoproteins.

Lipoprotein remnants are formed from the lipolysis of triglycerides in triglyceride-rich lipoproteins (TGRL). Levels of TGRL remnants reflect the balance between lipolysis and remnant uptake. In people with atherogenic dyslipidaemia, elevated triglycerides are generated by an increase in fatty acid flux to the liver. This may be due to enhanced free fatty acid release from excess visceral adipose tissue or increased remnant lipoprotein delivery of triglycerides to the liver as a result of excess caloric consumption, leading to increased hepatic lipogenesis, and in turn increased assembly and secretion of very low-density lipoproteins.

Mechanistic and genetic studies show that TGRL remnant levels are associated with increased atherogenicity compared with their precursors due to elevated cholesterol content and extended plasma residence time. Mechanistic and genetic studies also support a link between remnants and increased atherosclerosis. This has led some to suggest that lipoprotein remnants may be a preferable therapeutic target, given that the association between triglycerides and cardiovascular risk is more contentious.

To establish TGRL remnants as a therapeutic target, there is clearly a need for randomised prospective trials of lipid-lowering treatment showing reductions in clinical events predicted by reductions in TGRL remnant levels independent of other risk factors.

Key references

1. Chapman MJ, Ginsberg HN, Amarenco P et al. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J 2011;32:1345-61.

2. Miller M, Stone NJ, Ballantyne C et al. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation 2011;123:2292-333.

3. ACCORD Study Group, Ginsberg HN, Elam MB, Lovato LC et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 2010;362:1563-74.