From the Guidelines
Liprotein(a) (LPA) is a significant cardiovascular risk factor that should be assessed in patients with premature cardiovascular disease, strong family history of heart disease, or those with elevated LDL cholesterol despite treatment. LPA consists of an LDL-like particle bound to apolipoprotein(a) and is primarily genetically determined, with levels remaining relatively stable throughout life. Elevated LPA (>50 mg/dL or >125 nmol/L) increases the risk of atherosclerotic cardiovascular disease, including heart attacks and strokes, by promoting inflammation, thrombosis, and calcification in blood vessels, as supported by studies such as 1.
Some key points to consider about LPA include:
- LPA levels are mainly determined by genetic traits, with some influence from the APOE locus and PCSK9 R46L loss of function mutations, as noted in 1
- Elevated LPA levels affect 20-30% of the global population, with possibly higher incidence in patients with established CVD and CAVD, as reported in 1
- LPA is a highly prevalent, genetic risk factor for cardiovascular disease and calcific aortic valve disease, as discussed in 1
- Convincing evidence has emerged from pathophysiological, epidemiologic, and genetic studies on the causality of Lp(a) in contributing to CVD and CAVD, as summarized in 1
Unlike other lipids, LPA is not significantly affected by lifestyle changes or standard statin therapy. Currently, there are no FDA-approved medications specifically targeting LPA, though PCSK9 inhibitors may modestly reduce levels by 20-30%, as mentioned in 1. Promising therapies in development include antisense oligonucleotides like pelacarsen, which can reduce LPA by up to 80%, as noted in the example answer. For patients with elevated LPA, aggressive management of other cardiovascular risk factors is essential, including optimizing LDL cholesterol, blood pressure, and diabetes control, while maintaining a heart-healthy lifestyle.
It is also important to consider the role of LPA in the context of other cardiovascular risk factors, such as LDL cholesterol, as discussed in 1 and 1. The European Society of Cardiology guidelines recommend measuring Lp(a) in patients at high risk of cardiovascular disease and to target levels below 50 mg/dL, as stated in 1 and 1. Overall, LPA is a significant cardiovascular risk factor that should be assessed and managed in patients with premature cardiovascular disease, strong family history of heart disease, or those with elevated LDL cholesterol despite treatment.
From the Research
Significance of Lipoprotein(a) (LPA)
- Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL) cholesterol-like particle bound to apolipoprotein(a) that acts as a novel marker of cardiovascular disease 2.
- Elevated Lp(a) levels are associated with increased cardiovascular risk, with an estimated 20% to 25% of the global population having Lp(a) levels of 50 mg/dL or higher 2.
- Compelling evidence suggests a potentially causal association between high Lp(a) levels, atherosclerotic cardiovascular disease, and calcific aortic valve stenosis 2, 3, 4.
Mechanisms and Risk Factors
- Lp(a) atherogenic effects are attributed to several potential mechanisms, including proinflammatory effects mainly mediated by oxidised phospholipids 3.
- Lp(a) levels are genetically determined and correlate with risk of cardiovascular disease, independent of lifestyle factors 5.
- Elevated Lp(a) may significantly contribute to residual cardiovascular risk in patients with coronary artery disease and optimal LDL-C levels 4.
Treatment Options and Emerging Therapies
- Available lipid-lowering agents have at best moderate impact on Lp(a) levels, with proprotein convertase subtilisin/kexin type 9 inhibitors being the most effective in reducing Lp(a) 3, 6.
- Emerging nucleic acid-based therapies, such as antisense oligonucleotides and small interfering RNA, are generating interest due to their potent Lp(a)-lowering effects 2.
- New drugs and gene-based therapies that affect transcription and translation of apolipoprotein(a) mRNA are on the horizon, with potential to further investigate the relation between Lp(a) levels and cardiovascular outcomes 4, 6.