Who should have their Lipoprotein(a) (Lp(a)) levels measured?

Lipoprotein(a): Description and Measurement Indications

What is Lipoprotein(a)?

Lipoprotein(a) [Lp(a)] is a genetically-determined, highly atherogenic lipoprotein particle that functions as an independent and causal risk factor for atherosclerotic cardiovascular disease, aortic valve stenosis, and ischemic stroke. 1, 2, 3

• Lp(a) is a modified LDL particle containing apolipoprotein(a), with 70-90% of its variation determined by genetics rather than lifestyle factors 1, 4
• The particle is approximately 7-fold more atherogenic than standard LDL particles on a per-particle basis 4
• Lp(a) promotes cardiovascular disease through multiple mechanisms: cholesterol accumulation in arterial walls, pro-inflammatory effects mediated by oxidized phospholipids, and anti-fibrinolytic/pro-thrombotic properties 4, 3
• Levels remain relatively stable throughout a person's lifetime, making a single measurement sufficient for most patients 5, 6

Who Should Have Lp(a) Measured?

Primary High-Priority Indications

Measure Lp(a) in patients with premature cardiovascular disease or stroke, particularly when traditional risk factors fail to explain the vascular disease. 5, 1

• Patients with a personal history of premature atherosclerotic CVD (men <55 years, women <65 years) should have Lp(a) measured 1, 7
• All patients with familial hypercholesterolemia require Lp(a) measurement, as they face compounded cardiovascular risk and potential aortic valve calcification 5, 1, 2
• First-degree relatives of patients with premature CAD or Lp(a) levels >200 nmol/L should be screened, given the autosomal dominant inheritance pattern 1, 2, 7

Intermediate Risk and Risk Refinement

Patients at intermediate cardiovascular risk by standard calculators (Framingham, PROCAM, ESC Heart Score) should have Lp(a) measured, as levels >50 mg/dL warrant reclassification to higher risk category. 5, 1

• The European consensus threshold of 10-year risk of fatal CVD ≥3% warrants Lp(a) measurement 1, 4
• Borderline risk patients (<15% 10-year cardiovascular event risk) benefit from Lp(a) measurement for risk stratification 7

Recurrent or Progressive Disease

Measure Lp(a) in patients with recurrent or rapidly progressive vascular disease despite optimal lipid-lowering therapy. 5, 1, 2

• These patients represent a critical group where elevated Lp(a) may explain residual cardiovascular risk despite controlled LDL-cholesterol 1, 8

Additional Clinical Scenarios

• Patients with calcific aortic valve stenosis should have Lp(a) measured, as elevated levels are causally associated with valve disease 2, 7
• Patients with low HDL-cholesterol, genetic defects in hemostasis or homocysteine metabolism, diabetes mellitus, or autoimmune diseases warrant measurement 1
• Hemodialysis and chronic kidney disease patients should be screened, as Lp(a) levels are 2-3 fold elevated in these populations and independently predict cardiovascular events 5, 4

Risk Thresholds and Clinical Significance

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. 2, 4

• European guidelines use >50 mg/dL (approximately 100-125 nmol/L) as the threshold for significant risk requiring reclassification 1, 2, 4
• Risk increases progressively with higher levels, with particularly high risk at >100 mg/dL 4
• Patients with both elevated Lp(a) and elevated LDL-cholesterol face a 10-fold or higher risk of myocardial infarction compared to those with normal levels 1, 2

Critical Clinical Pitfalls

• Standard "LDL-C" laboratory measurements include Lp(a)-cholesterol content (approximately 30-45% of Lp(a) mass), meaning true LDL-C may be lower than reported 4
• Statins may actually increase Lp(a) mass and Lp(a)-C levels, though their overall cardiovascular benefit remains 4
• Lifestyle modifications (diet, exercise, weight loss) do not significantly lower Lp(a) levels due to its genetic determination 4
• Serial monitoring is generally unnecessary as levels remain stable throughout life, except during specific drug treatment trials or in chronic kidney disease 4