What is the lipoprotein(a) (Lp(a)) blood test?

What is the Lipoprotein(a) Blood Test?

Lipoprotein(a) [Lp(a)] is a blood test that measures a genetically determined, cholesterol-containing lipoprotein particle that serves as an independent, causal risk factor for atherosclerotic cardiovascular disease and calcific aortic valve stenosis. 1, 2

Structure and Composition

Lp(a) is a unique lipoprotein particle consisting of an LDL-like core with apolipoprotein B-100 covalently linked via a disulfide bridge to apolipoprotein(a), a carbohydrate-rich glycoprotein that distinguishes it from all other lipoproteins. 3, 4

• The lipid core of Lp(a) is virtually indistinguishable from LDL, containing approximately 30-45% cholesterol by mass 1, 2
• Apolipoprotein(a) is built from repetitive kringle domains highly homologous to plasminogen, creating substantial size heterogeneity with more than 30 different isoforms 3
• Each Lp(a) particle contains one molecule of apolipoprotein B-100, similar to LDL 4

Genetic Determination and Stability

Approximately 70-90% of Lp(a) concentration variability is determined by the LPA gene, making it one of the most genetically determined lipid parameters. 5, 3, 6

• Lp(a) levels are established by age 5 and remain stable throughout life, requiring only a single lifetime measurement in most circumstances 2, 3
• Plasma concentrations range from <0.1 mg/dL to >300 mg/dL, showing several-hundred-fold interindividual variability 6
• Unlike other lipoproteins, Lp(a) levels are minimally impacted by lifestyle modifications or most lipid-lowering drugs 4, 6

Measurement and Reporting

Lp(a) is measured by immunoassay and can be expressed either as mass concentration (mg/dL) or molar concentration (nmol/L), though standardization remains challenging due to size heterogeneity of apolipoprotein(a). 5, 1

• A conversion factor of 3.17 can be used (1 mg/dL = 3.17 nmol/L), though this is an approximation 5
• Each laboratory may use its own reference values due to lack of a common reference material 5
• The cholesterol content of Lp(a) is included in standard "LDL-C" laboratory measurements, potentially overestimating true LDL-C in patients with elevated Lp(a) 1, 2

Clinical Significance and Risk Thresholds

Elevated Lp(a) is defined as >30 mg/dL (approximately 75 nmol/L), representing the 75th percentile in white populations where cardiovascular risk demonstrably increases, though European guidelines use >50 mg/dL as the high-risk threshold. 1, 2, 3

• Approximately 20% of the Caucasian population and even higher frequencies in African-American and Asian-Indian populations have levels >50 mg/dL 6, 7
• Elevated Lp(a) confers more than two-fold increased risk for coronary artery disease, myocardial infarction, ischemic stroke, peripheral arterial disease, heart failure, and calcific aortic valve stenosis 2, 6, 8
• Individuals with both elevated Lp(a) (>30 mg/dL) and elevated LDL cholesterol face a 10-fold or higher risk of myocardial infarction compared to those with normal levels of both 2

Who Should Be Tested

The European Society of Cardiology recommends measuring Lp(a) at least once in patients with premature cardiovascular disease or stroke, family history of premature CAD or elevated Lp(a), familial hypercholesterolemia, intermediate cardiovascular risk by standard calculators, and recurrent vascular events despite optimal therapy. 5, 2

• Patients with ≥5% 10-year risk of fatal CVD according to European guidelines warrant measurement 5, 2
• First-degree relatives of patients with elevated Lp(a) should be screened, as it is inherited in an autosomal dominant pattern 2, 3
• Hemodialysis and chronic kidney disease patients should be assessed, as Lp(a) levels are 2-3 fold elevated in these populations 5, 2

Critical Pitfalls to Avoid

Do not assume that achieving LDL-C targets eliminates cardiovascular risk in patients with elevated Lp(a), as multiple randomized trials demonstrate higher event rates at any achieved LDL-C level when Lp(a) is elevated. 3

• Serial monitoring of Lp(a) is generally unnecessary except when evaluating response to specific Lp(a)-lowering therapies, as levels remain genetically stable 5, 3
• Standard lipid-lowering drugs (statins, ezetimibe) may actually increase Lp(a) mass levels by 5-10% despite their overall cardiovascular benefit 3