Lipoprotein(a) in atherosclerotic cardiovascular disease, type 2 diabetes, and liver disease

Lipoprotein(a) is a unique, atherogenic glycoprotein that was reported in humans more than six decades ago and is an independent risk factor for atherosclerotic cardiovascular disease, including myocardial infarction and stroke. The purpose of this article is to review lipoprotein(a) biology, associations with disease, treatment, and potential value of screening in pediatrics. Lipoprotein(a) has a lipid-rich core which contain triglycerides and cholesterol esters surrounded by a phospholipid shell containing an apolipoprotein B 100 covalently bound to apolipoprotein(a). Lipoprotein(a) levels increase from birth to age two years and remain stable afterward. Lipoprotein(a) has a six-fold greater association with coronary heart disease than low-density lipoprotein. Type 2 diabetes may be associated with obesity, metabolic dysfunction, and vascular endothelial inflammation, but low lipoprotein(a) levels. In children, there is no association between lipoprotein(a) levels and obesity. Metabolic dysfunction-associated steatotic liver disease may be associated with obesity, metabolic syndrome, diabetes, hypertension, metabolic dysfunction-associated steatohepatitis, hepatic fibrosis, and hepatocellular carcinoma. Patients with metabolic dysfunction-associated steatotic liver disease and low lipoprotein(a) levels may be more likely to develop hepatic fibrosis. Lipoprotein(a) levels may be decreased with some proprotein convertase subtilisin/kexin type 9 inhibitors, small interfering RNAs, and antisense oligonucleotides and lipoprotein apheresis, but not statin drugs. Universal pediatric lipoprotein(a) screening is being considered because it may predict atherosclerotic cardiovascular disease in adulthood. Graphical abstract illustrating the associations observed between high lipoprotein(a) (Lp[a]) levels and atherosclerotic cardiovascular disease (ASCVD). Low Lp(a) levels are associated with type 2 diabetes and hepatic fibrosis. As Lp(a) levels reach stability by age 2 years, it may be beneficial to implement universal pediatric Lp(a) screening. People of African and African American ancestry are at increased risk for having Lp(a) levels >50 mg/dL (Koschinsky et al., 2024; Nissen et al., 2022), and people with increased levels are asymptomatic until they have an ASCVD event. • Lipoprotein(a) level is an independent risk factor for atherosclerotic cardiovascular disease. • Lipoprotein(a) reaches adult levels in children by age two years. • Lipoprotein(a) levels have direct and inverse associations with metabolic diseases. • Treatments are being developed to lower elevated lipoprotein(a) levels. • Lipoprotein(a) screening identifies patients at risk for cardiovascular disease.