Elevated Lipoprotein(a) (Lp[a]) is one of the leading inherited dyslipidemias associated with premature atherosclerotic cardiovascular disease (ASCVD) including coronary artery disease and ischemic stroke.^1,2 High plasma Lp(a) concentrations are also associated with aortic stenosis.³

In a recent poll, two questions were asked  pertaining to the indications of testing and clinical utility of Lp(a).

For the question, "In your clinical practice, in which of the following scenarios would you measure Lp(a) levels?", a majority (33%) of 120 respondents reported that they do not check Lp(a) levels while 26% measure Lp(a) if a patient has a personal or family history of premature ASCVD. Interestingly, approximately 24% measure Lp(a) at least once in each adult patient's lifetime regardless of known ASCVD or cardiovascular risk factors.

The 2018 American Heart Association (AHA)/American College of Cardiology (ACC) and the HEART UK guidelines do not recommend universal Lp(a) testing as yet.^4,1 The 2019 European Atherosclerosis Society and European Society of Cardiology (ESC) guidelines endorse the measurement of Lp(a) to be considered at least once in a lifetime to identify those with very high inherited Lp(a) levels >180 mg/dL (>430 nmol/L).⁵ The National Lipid Association (NLA) and HEART UK guidelines suggest that it may be reasonable to measure Lp(a) among those individuals with a personal history of or first-degree relatives with premature ASCVD and among those with severe hypercholesterolemia (LDL-C ≥190 mg/dL). The Canadian Cardiovascular Guidelines of 2016 recommend Lp(a) measurement in individuals with intermediate Framingham risk category (10–19%) or those with a family history of premature ASCVD.

In the second question, the respondents were asked about their management practice to treat elevated Lp(a) levels in patients with or without ASCVD. While 29.4% of respondents use statin therapy to treat patients with elevated Lp(a), approximately 24.3% do not use any medications.

Aggressive management of known ASCVD risk factors among patients with elevated Lp(a) with or without established ASCVD and/or aortic stenosis has shown outcomes benefit. Statins only marginally affect Lp(a) plasma levels with either no effect on or an increase of Lp(a) levels after statin treatment however, they decrease the overall risk of ASCVD events. In the Women's Health Initiative, carriers of rs3798220, a minor variant of Lp(a), had elevated Lp(a) levels and an increased ASCVD risk versus noncarriers.⁶ The carriers had increased benefit with use of aspirin therapy than noncarriers over 9.9 years of follow up. In secondary prevention patients, proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i), mipomersen and lipoprotein apheresis have all shown to significantly reduce plasma Lp(a) concentration. Recent phase II trial studies evaluating the use of AKCEA APO(a)-LRx, an antisense oligonucleotide targeting LPA mRNA (which encodes the main Lp(a) constituent, apolipoprotein[a]) conjugated with N-Acetylgalactosamine showed promising results for Lp(a) reduction.

References

1. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol. J Am Coll Cardiol 2019;73:3168-3209.
2. Authors/Task Force Members, ESC Committee for Practice Guidelines, ESC National Cardiac Societies. 2019 ESC/EAS guidelines for the management of dyslipidemias: lipid modification to reduce cardiovascular risk. Atherosclerosis 2019;290:140-205.
3. Wilson DP, Jacobson TA, Jones PH, et al. Use of lipoprotein(a) in clinical practice: a biomarker whose time has come. A scientific statement from the National Lipid Association. J Clin Lipidol 2019;13:374-92.
4. Cegla J, Neely RDG, France M, et al. HEART UK consensus statement on Lipoprotein(a): a call to action. Atherosclerosis 2019;291:62–70.
5. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS guidelines for the management of dyslipidemias: lipid modification to reduce cardiovascular risk. Atherosclerosis 2019;290:140-205.
6. Cook NR, Mora S, Ridker PM. Lipoprotein(a) and cardiovascular risk prediction among women. J Am Coll Cardiol 2018;72:287–296.

Clinical Topics: Dyslipidemia, Prevention, Valvular Heart Disease, Atherosclerotic Disease (CAD/PAD), Advanced Lipid Testing, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins

Keywords: Primary Prevention, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Acetylgalactosamine, Cholesterol, LDL, Cardiovascular Diseases, Lipoprotein(a), Coronary Artery Disease, Oligonucleotides, Antisense, Hypercholesterolemia, American Heart Association, Secondary Prevention, RNA, Messenger, Follow-Up Studies, Brain Ischemia, Risk Factors, Stroke, Atherosclerosis, Apolipoproteins A, Blood Component Removal, Aortic Valve Stenosis, Plasma, Proprotein Convertases, Subtilisins

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