From the Guidelines
An elevated lipoprotein(a) (Lp(a)) is a significant and independent risk factor for cardiovascular disease, including atherosclerosis, heart attacks, and strokes, affecting 20-30% of the global population. Lp(a) levels are primarily determined by the LPA gene locus and remain relatively stable throughout life 1. Unlike other lipid parameters, Lp(a) doesn't respond well to traditional lipid-lowering therapies such as statins. Currently, there are no FDA-approved medications specifically targeting Lp(a), though PCSK9 inhibitors may modestly reduce levels by 20-30% 1.
Key Points to Consider
- Lp(a) is a highly prevalent genetic risk factor for cardiovascular disease and calcific aortic valve disease (CAVD) 1
- Elevated Lp(a) levels are generally accepted as >30–50 mg/dL or >75–125 nmol/L 1
- Lp(a) has unique atherogenic properties, including promoting inflammation, thrombosis, and oxidative stress in blood vessels
- For patients with elevated Lp(a), the focus should be on aggressive management of other cardiovascular risk factors, including optimizing LDL cholesterol, blood pressure control, diabetes management, smoking cessation, and lifestyle modifications
Management and Screening
- Screening for Lp(a) is particularly important in patients with premature cardiovascular disease, family history of early heart disease, or when cardiovascular events occur despite well-controlled traditional risk factors
- Aggressive management of cardiovascular risk factors is crucial in patients with elevated Lp(a) to reduce the risk of cardiovascular disease and CAVD 1
From the Research
Significance of Elevated LPA
- Elevated Lipoprotein(a) (Lp(a)) is a causal genetic risk factor for cardiovascular disease, with a continuous association between Lp(a) concentrations and cardiovascular risk 2, 3, 4.
- Lp(a) levels of 50 mg/dL or higher are associated with increased cardiovascular risk, affecting approximately 20% of the global population 2, 5, 4.
- Elevated Lp(a) contributes to residual cardiovascular risk in patients receiving standard-of-care LDL-lowering therapy 2, 5.
Association with Cardiovascular Disease
- Epidemiologic and genetic studies suggest a potentially causal association between elevated Lp(a) levels, atherosclerotic cardiovascular disease, and calcific aortic valve stenosis 2, 5, 4.
- Lp(a) is also associated with non-atherosclerotic endpoints such as venous thromboembolism 5.
- Carriers of genetic variants associated with high Lp(a) concentrations have a markedly increased risk for cardiovascular events 4.
Management and Treatment
- Current treatment guidelines recommend measurement of Lp(a) to identify patients with very high levels, particularly those with a family history of premature cardiovascular disease or elevated Lp(a) 5, 3, 6.
- Lipoprotein apheresis and proprotein convertase subtilisin/kexin type 9 inhibitors can lower Lp(a) levels, but their effectiveness in reducing cardiovascular risk is still being investigated 5, 3, 4.
- Emerging nucleic acid-based therapies, such as antisense oligonucleotides and small interfering RNA, have shown potent Lp(a)-lowering effects and are being evaluated for their potential to reduce cardiovascular risk 2, 5, 4, 6.