What is Lipoprotein(a) (Lp(a))?

From the Guidelines

Lipoprotein(a) (Lp(a)) is a specialized type of LDL cholesterol particle that contains an additional protein called apolipoprotein(a) and is an independent risk factor for cardiovascular disease, with high levels primarily determined by genetics 1.

Definition and Risk Factors

Lp(a) is a constituent of apolipoprotein(a) [Apo(a)] bound to apolipoprotein B-100, and its levels are mainly determined by genetic traits. The European Society of Cardiology (ESC) guidelines recommend measuring Lp(a) in patients at high risk of cardiovascular disease (CVD) and targeting levels below 50 mg/dL 1.

• Lp(a) particles have pro-atherogenic and pro-thrombotic properties, and several observational studies suggest a causal association between Lp(a) levels and CVD events, including emergent outcomes in the elderly, such as heart failure and calcific aortic valve stenosis 1.
• High levels of Lp(a) in the blood represent an independent risk factor for cardiovascular disease, including heart attacks and strokes.

Management and Treatment

• Unlike regular LDL cholesterol, Lp(a) levels don't respond well to traditional cholesterol-lowering medications like statins.
• Currently, there are no FDA-approved medications specifically targeting Lp(a), though PCSK9 inhibitors (evolocumab, alirocumab) and niacin may modestly reduce levels.
• For patients with elevated Lp(a), the focus remains on aggressively managing other cardiovascular risk factors through statins, blood pressure control, diabetes management, smoking cessation, and lifestyle modifications.

Future Directions

• New therapies specifically targeting Lp(a), including antisense oligonucleotides, are currently in clinical trials and show promise for future management of this important cardiovascular risk factor.
• The European consensus statement published in 2010 recommends measuring Lp(a) in patients with a 10-year risk of fatal CVD 3% and more, and particular attention should be paid to haemodialysis patients and patients with renal disease since under these conditions Lp(a) is two- to three-fold elevated 1.

From the Research

Definition and Structure of Lipoprotein(a) (Lp(a))

• Lipoprotein(a), or Lp(a), is structurally similar to low-density lipoprotein (LDL) but differs in that it contains glycoprotein apolipoprotein(a) [apo(a)] 2.
• Lp(a) is a low-density lipoprotein (LDL) cholesterol-like particle bound to apolipoprotein(a) 3.

Risk Factors and Associations

• Elevated Lp(a) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis 2, 3.
• Lp(a) levels are genetically determined, and it is estimated that 20%-25% of the global population has an Lp(a) level ≥50 mg/dL (or ≥125 nmol/L) 2, 3.
• Elevated Lp(a) levels are associated with a residual cardiovascular risk despite traditional risk factor optimization, including LDL cholesterol reduction 3.
• Lp(a) is a causal genetic risk factor for cardiovascular disease 4.

Screening and Management

• Candidates for Lp(a) screening include patients with a personal or family history of premature cardiovascular disease, familial hypercholesterolemia, recurrent cardiovascular events, or inadequate LDL cholesterol (LDL-C) responses to statins 4.
• Reducing LDL-C to the lowest attainable value with a high-potency statin should be the primary focus of lipid-modifying therapies 4.
• If the Lp(a) level is 30 mg/dL or higher in a patient who has the aforementioned characteristics plus residual LDL-C elevations (≥70-100 mg/dL) despite maximum-potency statins or combination statin therapy, the clinician may consider adding niacin (up to 2 g/d) 4.
• Lp(a) testing provides the opportunity to reclassify ASCVD risk and drive intensive cardiovascular risk factor management in individuals with elevated Lp(a) 5.

Treatment and Therapies

• Diet and lifestyle interventions have little to no effect on Lp(a) levels 2.
• Lipoprotein apheresis is the only approved treatment for elevated Lp(a) but is time-intensive for the patient and only modestly effective 2.
• Pharmacological approaches to reduce Lp(a) levels and its associated risks are of significant interest; however, currently available lipid-lowering therapies have limited effectiveness in reducing Lp(a) levels 2.
• Emerging nucleic acid-based therapies, such as the antisense oligonucleotide pelacarsen and the small interfering RNA olpasiran, are generating interest because of their potent Lp(a)-lowering effects 3.