Use of Lipoprotein(a) in Clinical Practice

Publication Date: April 1, 2024
Last Updated: April 1, 2024

Recommendations

What's New In 2024

Epidemiological Data
  • The relationship between baseline Lp(a) level and ASCVD events is continuous and log-linear, with increased risk even at “lower-risk” levels.
  • Despite differences in Lp(a) levels among racial/ethnic groups, Lp(a)-attributable risk is similar, eliminating previous race-based definitions of elevated Lp(a).
  • Because accepted conversion factors to adjust for Lp(a)-C in LDL-C calculation have proven inaccurate, leading to under treatment of high-risk patients, such adjustments should not be used.

Treatment
  • Lipoprotein apheresis is the first therapy to receive a U.S. Food and Drug Administration indication for Lp(a) reduction, for use in high-risk patsients with FH, ASCVD, elevated Lp(a), and elevated LDL-C.
  • Emerging pharmacological agents that specifically target Lp(a) are in development and undergoing testing in clinical trials as potential future therapies.

Recommendations
  • Adults (aged ≥18 y): Measurement of Lp(a) in all adults is reasonable to refine risk assessment for ASCVD events (COR I, LOE B-NR).
  • When Lp(a) levels are used for ASCVD risk assessment, it is reasonable to use measurements ≥125 nmol/L (≥50 mg/dL) as levels suggesting high risk, levels <75 nmol/L (<30 mg/dL) as low risk, and levels between as intermediate risk (COR IIa, LOE B-NR).
  • The use of an adjustment factor to estimate Lp(a)-C for correction of calculated LDL-C is not recommended (COR III [no benefit], LOE C-EO).
  • Lipoprotein apheresis is an FDA-approved therapy for high-risk patients with FH and ASCVD (coronary or peripheral arteries) whose Lp(a) level remains ≥60 mg/dL (∼150 nmol/L) and LDL-C ≥ 100 mg/dL on maximally tolerated lipid-lowering therapy (COR IIa, LOE B-NR).

Laboratory measurement of lipoprotein(a)

For the measurement of Lp(a), it is recommended that an immunochemical assay that is calibrated against the WHO/IFCCLM secondary reference material should be used and reported in nmol/L.

(I, B-NR)
573

When using values of Lp(a) for clinical risk assessment and treatment decisions, the use of a factor to convert Lp(a) values from mg/dL to nmol/L is not recommended.

(III - No Benefit, C-EO)
573

The use of an adjustment factor to estimate Lp(a)-C for correction of calculated LDL-C is not recommended.

(III - No Benefit, C-EO)
573

Lipoprotein(a) testing in clinical practice

Adults (aged ≥18 y): Measurement of Lp(a) in all adults is reasonable to refine risk assessment for ASCVD events. (I, B-NR)
573
Youth (aged <18 y): Selective screening of Lp(a) is recommended in high-risk patients (e.g., clinically suspected or genetically confirmed FH, ischemic stroke of unknown cause, first-degree relatives with a history of premature ASCVD [age <55 years in men, <65 years in women], or first-degree relatives with elevated Lp(a)). (IIb, C-LD)
573
When Lp(a) levels are used for ASCVD risk assessment, it is reasonable to use measurements ≥125 nmol/L (≥50 mg/dL) as levels suggesting high risk, levels <75 nmol/L (<30 mg/dL) as low risk, and levels between as intermediate risk. (IIa, B-R)
573

III. Treatment

) In adults aged 40–75 y with a 10-y ASCVD risk of 7.5 %–19.9 %, the finding of an Lp(a) ≥125 nmol/L or ≥50 mg/dL is reasonable to be used as a risk-enhancing factor to favor initiation of a moderate- or high-intensity statin in those with on-treatment LDL-C ≥ 70 mg/dL (or non-HDL-C ≥ 100 mg/dL).

(IIa, B-NR)
573

In high-risk∗ or very-high-risk∗∗ patients with Lp(a) ≥125 nmol/L or ≥50 mg/dL, it is reasonable to consider more intensive LDL-C lowering to achieve greater ASCVD risk reduction.

(IIa, A)
573

In high-risk or very-high-risk patients taking a maximally tolerated statin, with Lp(a) ≥125 nmol/L or ≥50 mg/dL, the addition of ezetimibe is reasonable in those with on-treatment LDL-C ≥ 70 mg/dL (or non-HDL-C ≥ 100 mg/dL).

(IIa, B-R)
573

In high-risk or very-high-risk patients taking a maximally tolerated statin, with Lp(a) ≥125 nmol/L or ≥50 mg/dL, the addition of a PCSK9 inhibitor is reasonable in those with on-treatment LDL-C ≥ 70 mg/dL (or non-HDL-C ≥ 100 mg/dL).

(IIa, B-R)
573

Lipoprotein apheresis is reasonable for high-risk patients with FH and ASCVD (coronary or peripheral arteries) whose Lp(a) level remains ≥60 mg/dL (∼150 nmol/L) and LDL-C ≥ 100 mg/dL on maximally tolerated lipid-lowering therapy.

(IIa, B-NR)
573

Niacin or HRT with estrogen and progesterone, which lower Lp(a) concentration, is not recommended to reduce ASCVD risk.

(III - Harm, B-R)
573

Recommendation Grading

Overview

Title

Use of Lipoprotein(a) in Clinical Practice

Authoring Organization

National Lipid Association

Publication Month/Year

April 1, 2024

Last Updated Month/Year

April 30, 2024

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Document Objectives

Since the 2019 National Lipid Association (NLA) Scientific Statement on Use of Lipoprotein(a) in Clinical Practice was issued, accumulating epidemiological data have clarified the relationship between lipoprotein(a) [Lp(a)] level and cardiovascular disease risk and risk reduction. Therefore, the NLA developed this focused update to guide clinicians in applying this emerging evidence in clinical practice. We now have sufficient evidence to support the recommendation to measure Lp(a) levels at least once in every adult for risk stratification. Individuals with Lp(a) levels <75 nmol/L (30 mg/dL) are considered low risk, individuals with Lp(a) levels ≥125 nmol/L (50 mg/dL) are considered high risk, and individuals with Lp(a) levels between 75 and 125 nmol/L (30–50 mg/dL) are at intermediate risk. Cascade screening of first-degree relatives of patients with elevated Lp(a) can identify additional individuals at risk who require intervention. Patients with elevated Lp(a) should receive early, more-intensive risk factor management, including lifestyle modification and lipid-lowering drug therapy in high-risk individuals, primarily to reduce low-density lipoprotein cholesterol (LDL-C) levels. The U.S. Food and Drug Administration approved an indication for lipoprotein apheresis (which reduces both Lp(a) and LDL-C) in high-risk patients with familial hypercholesterolemia and documented coronary or peripheral artery disease whose Lp(a) level remains ≥60 mg/dL [∼150 nmol/L)] and LDL-C ≥ 100 mg/dL on maximally tolerated lipid-lowering therapy. Although Lp(a) is an established independent causal risk factor for cardiovascular disease, and despite the high prevalence of Lp(a) elevation (∼1 of 5 individuals), measurement rates are low, warranting improved screening strategies for cardiovascular disease prevention.

Target Patient Population

Patients with risk of atherosclerotic cardiovascular disease

Inclusion Criteria

Male, Female, Adolescent, Adult, Older adult

Health Care Settings

Ambulatory, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Assessment and screening, Management, Prevention

Diseases/Conditions (MeSH)

D050171 - Dyslipidemias, D020521 - Stroke, D009203 - Myocardial Infarction, D008074 - Lipoproteins, D011322 - Primary Prevention, D055502 - Secondary Prevention, D017270 - Lipoprotein(a)

Keywords

dyslipidemia, lipoprotein(a), lipoprotein

Source Citation

Marlys L. Koschinsky, Archna Bajaj, Michael B. Boffa, Dave L. Dixon, Keith C. Ferdinand, Samuel S. Gidding, Edward A. Gill, Terry A. Jacobson, Erin D. Michos, Maya S. Safarova, Daniel E. Soffer, Pam R. Taub, Michael J. Wilkinson, Don P. Wilson, Christie M. Ballantyne, A focused update to the 2019 NLA scientific statement on use of lipoprotein(a) in clinical practice, Journal of Clinical Lipidology, 2024, ISSN 1933-2874, https://doi.org/10.1016/j.jacl.2024.03.001

Supplemental Methodology Resources

Data Supplement, Evidence Tables