When to Measure Lipoprotein(a)
Lipoprotein(a) should be measured at least once in patients with premature cardiovascular disease or stroke (especially when traditional risk factors don't fully explain the disease), those with a family history of premature CAD, patients with familial hypercholesterolemia, individuals at intermediate cardiovascular risk by standard calculators, and those with recurrent vascular events despite optimal medical therapy. 1, 2
Primary Indications for Lp(a) Testing
High-Priority Populations (Measure at Least Once)
Premature cardiovascular disease or stroke: Particularly when other risk factors fail to explain the presence of vascular disease 1
Family history of premature CAD: First-degree relatives with premature atherosclerotic CVD or those with Lp(a) levels >200 nmol/L 2, 3, 4
Personal history of myocardial infarction: Elevated Lp(a) is a significant independent risk factor requiring specific management strategies 2, 4
Familial hypercholesterolemia (FH): All patients with FH or other genetic dyslipidemia should have Lp(a) measured 1, 3
Calcific aortic valve stenosis: Lp(a) is causally associated with this condition 3, 4
Intermediate-Risk Populations
Intermediate cardiovascular risk by standard calculators: Patients falling into intermediate risk categories using Framingham, PROCAM, ESC Heart Score, or Australian/New Zealand risk calculators should have Lp(a) measured, as levels >50 mg/dL warrant reclassification into a higher risk category 1
Borderline 10-year cardiovascular risk: Those with <15% 10-year risk of cardiovascular events who need risk refinement 3
European consensus threshold: Patients with 10-year risk of fatal CVD ≥3% according to European guidelines 1
Additional Clinical Scenarios
Recurrent or rapidly progressive vascular disease: Especially in patients already on lipid-lowering medication—these patients should have Lp(a) measured repeatedly at regular intervals 1
Low HDL-cholesterol: Patients with persistently low HDL-C levels 1
Genetic defects in hemostasis or homocysteine metabolism: Including patients with blood clotting disorders or elevated homocysteine 1
Diabetes mellitus and autoimmune diseases: These conditions warrant Lp(a) assessment 1
Renal disease and hemodialysis patients: Particular attention should be paid to these populations, as Lp(a) levels are two- to three-fold elevated under these conditions 1
Frequency of Testing
Lp(a) levels remain stable throughout life due to their genetic determination, so most individuals need only one lifetime measurement unless elevated levels are identified. 5 However, patients on drug treatment for elevated Lp(a) or those with recurrent vascular disease should have repeat measurements at regular intervals to assess treatment efficacy 1, 2
Clinical Rationale
The recommendation for these specific populations is based on strong evidence that patients with both elevated Lp(a) and LDL cholesterol face a 10-fold or higher risk of myocardial infarction compared to those with normal levels 1, 2. The ACCF/AHA guidelines reviewed 36 prospective studies involving >125,000 participants and found continuous, independent associations of Lp(a) with increased risk for CHD and stroke 1.
Important Caveats
Assay standardization remains problematic: No commonly accepted reference standards exist, and comparisons between laboratories can be challenging 1
Threshold interpretation: Traditional thresholds are >30 mg/dL or >75 nmol/L (approximately 75th percentile in white populations), though the European Society of Cardiology suggests >50 mg/dL (~100-125 nmol/L) as clinically significant 2, 6
Testing is convenient: A single non-fasting blood draw is sufficient for most individuals 5
Management Implications
When elevated Lp(a) is identified, the most important next step is intensive treatment of traditional modifiable risk factors, especially LDL cholesterol, with lower LDL-C goals justified by the additional risk conferred by elevated Lp(a) 1, 2. This risk refinement directly impacts morbidity and mortality through more aggressive preventive strategies.