Use of Lipoprotein(a) in Clinical Practice
- 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 2022;Aug 28:[Epub ahead of print].
The following are key points to remember about this National Lipid Association statement on the use of lipoprotein(a) [Lp(a)] in clinical practice:
- Lp(a) is a form of low-density lipoprotein (LDL) associated with apolipoprotein(a), a unique protein attached to the apolipoprotein B segment of LDL.
- Lp(a) concentrations in plasma are 80%-90% genetically determined. Because Lp(a) levels are relatively stable over a lifetime, repeat measurement of Lp(a) is generally unnecessary, provided the initial result was not obtained during an acute illness.
- Numerous studies provide strong evidence of a causal link between elevated Lp(a) and myocardial infarction, ischemic stroke, valvular aortic stenosis (VAS), coronary artery stenosis, carotid stenosis, femoral artery stenosis, heart failure, cardiovascular mortality, and all-cause mortality. The relationships are independent of LDL cholesterol (LDL-C) or other lipid concentrations.
- The pathophysiologic mechanism by which Lp(a) increases risk is unclear. Some in vitro and animal studies suggest that apolipoprotein(a) inhibits fibrinolysis, thus increasing thrombosis. Other evidence suggests that oxidized phospholipids acting on Lp(a) may promote endothelial dysfunction, lipid deposition, inflammation, and calcification.
- Measurement of Lp(a) has not been standardized and is subject to bias. When possible, clinicians should use assays that report results in nmol/L and which are calibrated against the World Health Organization/International Federation of Clinical Chemistry and Laboratory Medicine secondary reference material (Class I recommendation).
- In Caucasian patients, Lp(a) levels of 100 nmol/L or 50 mg/dL—which correspond to the 80th population percentile—may be considered a risk-enhancing factor favoring the initiation of statin therapy. Distribution of Lp(a) levels differs among ethnic groups. African-Americans have an approximately threefold higher median Lp(a) than Caucasian populations.
- After shared decision-making, Lp(a) testing is reasonable (Class IIa recommendation) to clarify risk assessment in patients:
- Whose first-degree relatives have premature atherosclerotic cardiovascular disease (ASCVD) (men <55 years; women <65 years).
- With primary severe hypercholesterolemia (LDL-C ≥190 mg/dL) or suspected familial hypercholesterolemia.
- With premature ASCVD, particularly in the absence of traditional risk factors.
- With multiple major ASCVD events or one major ASCVD event and multiple high-risk conditions, in order to identify those most likely to benefit from proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor therapy.
- Lp(a) testing may be reasonable (Class IIb recommendation) in patients with:
- Intermediate (7.5%-19.9%) or borderline (5%-7.4%) 10-year ASCVD risk to aid in the decision regarding initiation of statin therapy in those ages 40-75 years.
- Less-than-anticipated LDL-C reduction despite adherence to lipid therapy.
- Family history of elevated Lp(a).
- Calcific VAS.
- Recurrent or progressive ASCVD despite adequate control of other risk factors.
- There is currently no targeted treatment to lower Lp(a), which has demonstrated impact on ASCVD outcomes or VAS progression. Neither lifestyle therapy nor statin therapy impacts Lp(a) levels. PCSK9 inhibitors lower Lp(a), but the contribution of Lp(a) reduction to reduced ASCVD risk is undetermined. Lipoprotein apheresis lowers Lp(a) and is selectively used for patients with elevated Lp(a) and recurrent ASCVD events. Antisense oligonucleotides are undergoing investigation as a novel Lp(a) targeting treatment.
- Clinical benefit in patients with elevated Lp(a) has been demonstrated with statin therapy in primary and secondary prevention studies. Patients on statin therapy who have elevated Lp(a) are the most likely to receive benefit from more aggressive LDL-C lowering therapy, including ezetimibe or PCSK9 inhibitors. Lp(a) levels may be useful to reclassify ASCVD risk and aid in decisions regarding pharmacotherapy.
Clinical Topics: Cardiovascular Care Team, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Valvular Heart Disease, Vascular Medicine, Advanced Lipid Testing, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents, Primary Hyperlipidemia, Statins, Acute Heart Failure, Heart Failure and Cardiac Biomarkers
Keywords: Aortic Valve Stenosis, Apolipoproteins, Carotid Stenosis, Cholesterol, LDL, Constriction, Pathologic, Coronary Stenosis, Dyslipidemias, Fibrinolysis, Heart Failure, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, Hyperlipoproteinemia Type II, Inflammation, Life Style, Lipoproteins, Lipoprotein(a), Myocardial Infarction, Myocardial Ischemia, Patient Care Team, PCSK9 protein, human, Phospholipids, Proprotein Convertase 9, Risk Assessment, Risk Factors, Secondary Prevention, Stroke, Thrombosis, Vascular Diseases
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