Lipoprotein(a) in clinical practice: New perspectives from basic and translational science

Abstract

Elevated plasma concentrations of lipoprotein(a) (Lp(a)) are a causal risk factor for coronary heart disease (CHD) and calcific aortic valve stenosis (CAVS). Genetic, epidemiological and in vitro data provide strong evidence for a pathogenic role for Lp(a) in the progression of atherothrombotic disease. Despite these advancements and a race to develop new Lp(a) lowering therapies, there are still many unanswered and emerging questions about the metabolism and pathophysiology of Lp(a). New studies have drawn attention to Lp(a) as a contributor to novel pathogenic processes, yet the mechanisms underlying the contribution of Lp(a) to CVD remain enigmatic. New therapeutics show promise in lowering plasma Lp(a) levels, although the complete mechanisms of Lp(a) lowering are not fully understood. Specific agents targeted to apolipoprotein(a) (apo(a)), namely antisense oligonucleotide therapy, demonstrate potential to decrease Lp(a) to levels below the 30–50 mg/dL (75–150 nmol/L) CVD risk threshold. This therapeutic approach should aid in assessing the benefit of lowering Lp(a) in a clinical setting.

Keywords:

• Lipoprotein(a)
• apolipoprotein(a)
• atherosclerosis
• fibrinolysis
• oxidized phospholipids
• inflammation
• lipoprotein metabolism
• cardiovascular disease
• therapy

Disclosure statement

MLK declares honoraria for membership on advisory boards and speakers’ bureaus for Ionis Pharmaceuticals, Sanofi, and Eli Lilly. MBB is a consultant from Ionis Pharmaceuticals. CAS declares no conflict of interest.

Additional information

Funding

MLK and MBB have received operating grants from the Canadian Institutes of Health Research (MOP-# 126076), the Heart and Stroke Foundation of Ontario (G-13–0003091), and a research contract from Ionis Pharmaceuticals. MLK has received a discovery grant from the Natural Sciences and Engineering Research Council (RGPIN/5006–2015), and research contracts from Regeneron Pharmaceuticals, Eli Lilly and Pfizer.