Available online 1 April 2024

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Lp(a) level should be measured at least once in all adults.

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Lp(a) levels represent a continuum of risk, not a risk threshold at a dichotomous cutpoint.

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Risk classification by Lp(a) level ranges from low (<75 nmol/L) to high (≥125 nmol/L).

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Lp(a) risk categories apply across races and ethnicities.

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High Lp(a) levels warrant early and more-intensive risk factor management.

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.

Section snippetsIntroduction (Preface)

The lipoprotein(a) [Lp(a)] field is rapidly evolving on many fronts, warranting this focused update to the 2019 National Lipid Association (NLA) Scientific Statement on Use of Lipoprotein(a) in Clinical Practice.1 Recent evidence has influenced our understanding of whom should have Lp(a) levels measured, how to interpret Lp(a) levels for use in risk assessment, and clinical management of patients with elevated Lp(a). The NLA now recommends: (1) measurement of Lp(a) levels at least once in every

Accumulating data from large, population-based studies indicate that elevated plasma Lp(a) is an important independent, causal risk factor for atherosclerotic cardiovascular disease and calcific aortic valve stenosis

The most notable of these studies are two analyses of the UK Biobank.2,3 Their enormous sample sizes (n = 460,506 and 413,734, respectively) allowed several key questions to be addressed with unprecedented statistical power.

First, a continuous, log-linear relationship between baseline Lp(a) and risk for atherosclerotic cardiovascular disease (ASCVD) events was observed, with a significant (albeit small) increase in risk at what would usually be considered “low-risk” levels of Lp(a)

The adult population

The risk for ASCVD events that is associated with Lp(a) is independent of LDL-C and is attributed to the atherogenic, proinflammatory, and prothrombotic properties of Lp(a).20 Lp(a) is associated with an increased risk of incident ASCVD even in the absence of a family history of heart disease.21 Systematic universal Lp(a) screening can improve health outcomes by increasing awareness of, and enabling precision in, ASCVD prevention strategies22 and individualization of therapy selection.23

How should Lp(a) be measured?

Lp(a) measurement is complicated by the unique structure of apolipoprotein(a) [apo(a)]. Apo(a) is characterized by a variable number of identically repeated kringle IV type 2 (KIV2) sequences (ranging from 3 to >40 copies) that correspond to differently sized isoforms of Lp(a).37 Therefore, antibodies that recognize epitopes in the KIV2 sequence tend to underestimate the concentrations of smaller Lp(a) isoform sizes (which tend to be associated with higher Lp(a) levels and higher ASCVD risk),

Risk assessment

The assessment of CVD risk offers the opportunity to implement tailored risk-reducing strategies, matching the intensity of pharmacological treatments to the absolute global risk of the patient. Several professional cardiology societies have identified high Lp(a) as a “risk-enhancing” or “risk-modifying” factor. The 2019 American College of Cardiology (ACC)/American Heart Association (AHA) Guideline on the Primary Prevention of CVD identified an elevated Lp(a) ≥125 nmol/L as a “risk-enhancing”

E. Summary

While specific Lp(a)-lowering therapies are not currently available, elevated Lp(a) is actionable now88(Table 2; Table 3). Lp(a) level should be measured at least once in all adults to identify individuals with high Lp(a) levels for implementation of early and intensive risk factor management. For CVD risk assessment, Lp(a) levels should be used to stratify patients as low risk (<75 nmol/L) or high risk (≥125 nmol/L), and individuals with Lp(a) levels in between should be considered as

Use of AI and AI-assisted Technologies Statement

AI has not been used in the writing process.

Ethical Statement

This work does not involve the use of human subjects or animals.

CRediT authorship contribution statement

Marlys L. Koschinsky: Conceptualization, Writing – original draft, Writing – review & editing. Archna Bajaj: Writing – review & editing. Michael B. Boffa: Writing – original draft, Writing – review & editing. Dave L. Dixon: Writing – review & editing. Keith C. Ferdinand: Writing – review & editing. Samuel S. Gidding: Writing – original draft, Writing – review & editing. Edward A. Gill: Writing – review & editing. Terry A. Jacobson: . Erin D. Michos: Writing – original draft, Writing – review &

Declaration of interest statement

Marlys L. Koschinsky received honoraria from Novartis and Eli Lilly as a consultant and a research contract from Abcentra as an independent research contractor; Archna Bajaj received research support from Amgen, Ionis, Novartis, NewAmsterdam Pharma, and Regeneron and consulting fees from Kaneka; Michael B. Boffa has no interests to declare; Dave L. Dixon received research funding from Boehringer Ingelheim as a PI; Keith C. Ferdinand received consulting fees from Amgen, Sanofi, Novartis, Eli

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