Test Summary
Lipoprotein(a)
Clinical use
- Refine risk assessment of atherosclerotic cardiovascular disease (ASCVD)
- Guide decisions on lipid-lowering therapy
Clinical background
Lipoprotein(a) (Lp[a]) is composed of a low-density lipoprotein (LDL) particle and an apolipoprotein B100 molecule linked by a disulfide bond to apolipoprotein(a) (apo[a]). An elevated Lp(a) level contributes to the pathogenesis of ASCVD1 and is an independent risk factor for myocardial infarction,1 ischemic stroke,2 atherosclerotic stenosis, aortic valve stenosis, cardiovascular mortality, and all-cause mortality.3 Thus, measurement of Lp(a) can help refine risk assessment of ASCVD.3
The association between the risk of ASCVD and elevated Lp(a) levels is linear above the median (20 nmol/L), with higher Lp(a) levels indicating increased risk.4 A high Lp(a) level (≥125 nmol/L) is considered a risk-enhancing factor and can be used to aid in personalizing ASCVD risk assessment.5 Elevated Lp(a) level is also an independent ASCVD risk factor for patients receiving statin treatment.6 Because Lp(a) levels are largely genetically determined, measuring Lp(a) levels once in a lifetime in the absence of acute illness may be sufficient for risk assessment and clinical decision-making.3
Recommendations on the Lp(a) cutpoint to identify high-risk individuals vary. The National Lipid Association recommends a universal cutpoint of ≥100 nmol/L3 whereas the American Heart Association (AHA) and American College of Cardiology (ACC) recommend a cutpoint of ≥125 nmol/L.5 Although a lower Lp(a) cutpoint was proposed to better predict ASCVD in Black populations,7 current evidence does not support the use of specific cutpoints for different racial or ethnic groups.3
Patients with familial hypercholesterolemia (FH) and high Lp(a) levels (approximately ≥100 nmol/L) are at greater ASCVD risk than those with lower Lp(a) levels.8 The European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) recommend measuring Lp(a) at least once in each adult to detect inherited high Lp(a) levels (>430 nmol/L), which are associated with very high lifetime risk of ASCVD.9 Selectively screening of Lp(a) in youth with confirmed or suspected FH may be considered.3
Diet, exercise, and the lipid-lowering statins appear ineffective in reducing Lp(a) levels in contrast to their effects on LDL-C. Patients with very high ASCVD risk, insufficient LDL-C lowering, and an elevated Lp(a) level ≥100 nmol/L may benefit from the addition of a PCSK9 inhibitor.3 Otherwise, medications that can reduce Lp(a) levels, such as a PCSK9 inhibitor, niacin, or lomitapide, are not recommended for ASCVD risk reduction owing to their lack of proven benefits and potential harms. For example, niacin therapy in addition to statin therapy in patients with ASCVD is associated with increased incidence of diabetes, bleeding, myopathy, and infection.3
Individuals suitable for testing
- Adults (men <55 and women <65 years of age) with premature ASCVD or who have first-degree relatives with premature ASCVD
- Adults with primary severe hypercholesterolemia (LDL-C ≥190 mg/dL) or suspected FH
- Adults at very high risk of ASCVD in order to predict the benefit of PCSK9 inhibitor therapy
Method
- Immunoturbidimetric
- Analytical specificity
- No crossreactivity with apolipoprotein B ≤200 mg/dL
- Not affected by the number of kringle IV repeats
- Calibrated with Lp(a) preparations standardized to the World Health Organization/International Federation of Clinical Chemistry reference material
- Result reported in nmol/L (nmol/L are the preferred units for measuring Lp[a] levels, which should not be directly converted from mg/dL owing to the different molecular weights of the Lp[a] isoforms3)
- Analytical measurement range: 10-200 nmol/L (reportable range: 10-600 nmol/L)
Interpretive information
The reference range cutpoint (75 nmol/L) approximates the Lp(a) 75th percentile in the Framingham Heart Study.10 In White individuals, Lp(a) levels below this cutpoint indicate Lp(a) is not a major contributor to ASCVD risk; low-risk cutpoints have not been established for other races nor ethnicities. Given the linear relationship between increasing Lp(a) levels and ASCVD risk,6 levels ≥75 nmol/L but <125 nmol/L5 may indicate intermediate (moderate) ASCVD risk. A high Lp(a) level may be used to prompt initiation or adjustment of LDL-C–lowering treatment in specific patient groups (Table).3
Table. Treatment Considerations for Specific Patient Groups With Lp(a) ≥100 nmol/L
Patient group3 |
Treatment considerations |
Adults aged 40-75 years with intermediate ASCVD riska and an LDL-C level ≥70 mg/dL or non-HDL-C level ≥100 mg/dL |
Initiation of a moderate- or |
Patients with highb or very highc ASCVD risk |
More intensive LDL-C lowering |
Patients with highb or very highc ASCVD risk who are on a maximally tolerated statin |
Addition of ezetimibe |
Patients with very high ASCVD riskc and an LDL-C level ≥70 mg/dL (or non-HDL-C level ≥100 mg/dL) who are on ezetimibe and a maximally tolerated statin |
Addition of a PCSK9 inhibitor |
| Non-HDL-C, Non-high-density lipoprotein cholesterol. | |
| a | 10-year risk of 7.5% to 19.9%.3 |
| b | Patients with clinical ASCVD: myocardial infarction, acute coronary syndrome, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, or peripheral artery disease (including aortic aneurysm).3 |
| c | Patients with a history of multiple major ASCVD events or 1 major ASCVD event and multiple high-risk conditions.3 |
Lp(a) levels may be increased in patients with acute phase reactions, such as infection, surgery, and tumor.11
Lp(a) testing is offered with (Quest and CHL test code 91729) or without (Quest test code 34604) enhanced reporting, which includes color-coding to display progressive risk.
References
- Kamstrup PR, Tybjaerg-Hansen A, Steffensen R, et al. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA. 2009;301(22):2331-2339. doi:10.1001/jama.2009.801
- Langsted A, Nordestgaard BG, Kamstrup PR. Elevated lipoprotein(a) and risk of ischemic stroke. J Am Coll Cardiol. 2019;74(1):54-66. doi:10.1016/j.jacc.2019.03.524
- 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;16(5):e77-e95. doi:10.1016/j.jacl.2022.08.007
- Patel AP, Wang M, Pirruccello JP, et al. Lp(a) (lipoprotein[a]) concentrations and incident atherosclerotic cardiovascular disease: new insights from a large national biobank. Arterioscler Thromb Vasc Biol. 2021;41(1):465-474. doi:10.1161/atvbaha.120.315291
- 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: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. Circulation. 2019;139(25):e1082-e1143. doi:10.1161/cir.0000000000000625
- Willeit P, Ridker PM, Nestel PJ, et al. Baseline and on-statin treatment lipoprotein(a) levels for prediction of cardiovascular events: individual patient-data meta-analysis of statin outcome trials. Lancet. 2018;392(10155):1311-1320. doi:10.1016/s0140-6736(18)31652-0
- Guan W, Cao J, Steffen BT, et al. Race is a key variable in assigning lipoprotein(a) cutoff values for coronary heart disease risk assessment: the Multi-Ethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol. 2015;35(4):996-1001. doi:10.1161/atvbaha.114.304785
- Alonso R, Andres E, Mata N, et al. Lipoprotein(a) levels in familial hypercholesterolemia: an important predictor of cardiovascular disease independent of the type of LDL receptor mutation. J Am Coll Cardiol. 2014;63(19):1982-1989. doi:10.1016/j.jacc.2014.01.063
- Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111-188. doi:10.1093/eurheartj/ehz455
- Marcovina SM, Koschinsky ML, Albers JJ, et al. Report of the National Heart, Lung, and Blood Institute workshop on lipoprotein(a) and cardiovascular disease: recent advances and future directions. Clin Chem. 2003;49(11):1785-1796. doi:10.1373/clinchem.2003.023689
- Min WK, Lee JO, Huh JW. Relation between lipoprotein(a) concentrations in patients with acute-phase response and risk analysis for coronary heart disease. Clin Chem. 1997;43(10):1891-1895.
Content reviewed 06/2023
34604 - Lipoprotein (a)
Elevated concentrations of Lp(a) are associated with increased risk of coronary artery disease.
91729 - Cardio IQ® Lipoprotein (a)
Reference ranges are provided as general guidance only. To interpret test results use the reference range in the laboratory report.
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