Is Lipoprotein(a) Considered Investigational?
No, lipoprotein(a) measurement is not investigational—it is an established, genetically-determined cardiovascular risk factor with clear guideline recommendations for measurement in specific high-risk populations, though specific Lp(a)-lowering therapies remain under investigation. 1, 2
Current Status of Lp(a) as a Clinical Biomarker
Lp(a) is recognized as an independent and causal risk factor for atherosclerotic cardiovascular disease by major cardiovascular societies, supported by extensive Mendelian randomization studies and epidemiological data 1, 3
The European Atherosclerosis Society has issued a IIa recommendation with level of evidence C for measuring Lp(a) in specific patient populations, indicating this is an accepted clinical practice rather than investigational 1
The Canadian Cardiovascular Society and National Lipid Association have similarly endorsed Lp(a) measurement in their guidelines, further establishing its clinical utility 1
Lp(a) has been studied since its discovery in 1963, with mounting evidence over decades establishing its role in cardiovascular disease 1
Established Clinical Indications for Lp(a) Measurement
The following are guideline-supported indications where Lp(a) measurement is recommended, not investigational:
Patients with premature cardiovascular disease without evident risk factors 2, 4
Individuals with familial hypercholesterolemia, as Lp(a) elevation increases their already high cardiovascular risk 2, 4
Patients with family history of premature CVD or elevated Lp(a) 2, 4
Patients with recurrent cardiovascular events despite optimal lipid-lowering therapy, where Lp(a) may explain residual risk 1, 2
Patients with ≥5% 10-year risk of fatal CVD according to risk algorithms like SCORE 1, 4
What Remains Investigational
While Lp(a) measurement itself is established, certain aspects remain under investigation:
Specific Lp(a)-lowering therapies are investigational, including antisense oligonucleotides and small interfering RNA therapies that can reduce Lp(a) by up to 90% 1, 3
The Lp(a)HORIZON trial is ongoing to determine whether selective Lp(a) lowering with antisense oligonucleotides reduces major cardiovascular events 3
Testing of the "Lp(a) hypothesis"—that lowering Lp(a) reduces cardiovascular events—remains the subject of active clinical trials, though observational data from lipoprotein apheresis studies suggest benefit 1
Current Management Approach (Non-Investigational)
Aggressive LDL-cholesterol reduction is the primary management strategy for patients with elevated Lp(a), with lower LDL-C goals recommended for these high-risk patients 2, 5
Lipoprotein apheresis is an established (though resource-intensive) therapy that reduces Lp(a) by up to 80% and has been associated with approximately 80% reduction in cardiovascular events 2, 5
PCSK9 inhibitors reduce Lp(a) by approximately 25-30% while primarily targeting LDL-C, and are approved therapies (not investigational) 2, 5
Niacin reduces Lp(a) by 30-35% and is currently recommended as the most effective conventional medication for Lp(a) reduction 2, 5
Key Clinical Thresholds (Established, Not Investigational)
Traditional threshold for elevated Lp(a) is >30 mg/dL (approximately 75 nmol/L), representing the 75th percentile in white populations where cardiovascular risk begins to increase 2, 4, 5
European guidelines use >50 mg/dL (approximately 100-125 nmol/L) to define significant risk, though this higher threshold should not prevent treatment consideration at lower levels 1, 2
Risk increases progressively with higher Lp(a) levels, with particularly high risk at >100 mg/dL 1, 4
Common Clinical Pitfalls
Failing to measure Lp(a) in appropriate high-risk patients represents underutilization of an established biomarker, not avoidance of an investigational test 4
Lp(a)-C content is included in standard "LDL-C" laboratory measurements, which can affect interpretation of lipid profiles and achievement of LDL-C targets—this is an established clinical consideration, not investigational 1, 2, 4
Statins and ezetimibe may actually increase Lp(a) mass and Lp(a)-C levels, an established phenomenon that clinicians should recognize when managing these patients 1, 2, 4