What Elevated Lipoprotein(a) Means
An elevated Lipoprotein(a) level indicates you have a genetically determined, causal, and independent risk factor for atherosclerotic cardiovascular disease (heart attacks, strokes, peripheral arterial disease) and aortic valve stenosis that persists even when your LDL cholesterol is well-controlled. 1, 2
Understanding the Biology and Risk
Lp(a) is fundamentally different from other cholesterol markers because 70-90% of your level is determined by genetics rather than lifestyle factors like diet or exercise. 1, 3
The particle consists of an LDL-like component attached to apolipoprotein(a), which resembles plasminogen but lacks fibrinolytic activity, creating both atherosclerotic and thrombotic risk. 2, 4
Lp(a) particles are approximately 7-fold more atherogenic than LDL particles on a per-particle basis, promoting atherosclerosis, inflammation, and blood clot formation through multiple mechanisms. 1
Risk Thresholds and What They Mean
The traditional threshold where cardiovascular risk demonstrably increases is >30 mg/dL (or >75 nmol/L), representing approximately the 75th percentile in white populations. 1, 5
European guidelines define significant risk at >50 mg/dL (approximately 100-125 nmol/L), affecting approximately 20% of the global population. 1, 2
Risk increases progressively with higher levels, with particularly high risk at >100 mg/dL. 1
Even when your LDL cholesterol is optimally controlled with statins, elevated Lp(a) confers residual cardiovascular risk that remains unaddressed by standard lipid-lowering therapy. 2, 5
Critical Clinical Implications
Standard "LDL-C" laboratory measurements include Lp(a)-cholesterol content (contributing approximately 30-45% of Lp(a) mass), meaning your true LDL-C may actually be lower than reported, but your total atherogenic particle burden is higher. 1, 5
Patients with both elevated Lp(a) and elevated LDL cholesterol face a 10-fold or higher risk of myocardial infarction compared to those with neither risk factor. 1
The risk is substantially greater in patients with existing coronary artery disease (risk ratio 2.37) compared to asymptomatic individuals (risk ratio 1.48). 1
Who Should Be Screened
You should have Lp(a) measured if you have any of the following: 1, 5
- Premature cardiovascular disease without evident risk factors
- Family history of premature CVD or elevated Lp(a)
- Familial hypercholesterolemia
- Recurrent cardiovascular events despite optimal lipid-lowering therapy
- ≥5% 10-year risk of fatal CVD according to risk algorithms
- Intermediate CVD risk by traditional risk scores (Framingham, PROCAM, ESC Heart Score)
Special Population Considerations
Children with elevated Lp(a) have a 4-fold increased risk of acute ischemic stroke, and the risk of recurrent stroke increases more than 10-fold when Lp(a) is >90th percentile. 1, 5
First-degree relatives should be screened because elevated Lp(a) is inherited in an autosomal dominant pattern with high penetrance. 1
Lp(a) levels are substantially increased in chronic kidney disease and end-stage renal disease, and serve as an independent predictor of coronary heart disease events and mortality in CKD patients. 1, 5
Management Approach
The primary management strategy is aggressive LDL cholesterol reduction to the lowest achievable level, with a target LDL-C <70 mg/dL, as this reduces cardiovascular events even in patients with elevated Lp(a), though residual risk remains. 1
Pharmacological Options for Direct Lp(a) Reduction:
Niacin (1-2 g/day) reduces Lp(a) by 30-35% and is currently the most effective conventional medication specifically for Lp(a) reduction, though you must monitor for flushing, hyperglycemia, and hepatotoxicity. 1, 4
PCSK9 inhibitors (evolocumab or alirocumab) reduce Lp(a) by approximately 25-30% while providing an additional 50-60% LDL-C reduction, and should be considered for high-risk patients with Lp(a) >100 mg/dL or additional risk factors. 1
Lipoprotein apheresis reduces Lp(a) by up to 80% and should be considered for patients with Lp(a) >60 mg/dL who develop cardiovascular events or disease progression despite optimal medical therapy, with German studies demonstrating approximately 80% reduction in cardiovascular events. 1
Critical Pitfall to Avoid:
- Statins and ezetimibe may actually increase Lp(a) mass and Lp(a)-C levels, despite their cardiovascular benefits through LDL-C reduction. 1, 5 This means you still need statins for LDL-C control, but they won't address your Lp(a) risk.
Monitoring Considerations
Serial monitoring of Lp(a) is generally not necessary as levels are genetically determined and remain stable throughout life, except during specific drug treatment trials or in patients with chronic kidney disease where levels may fluctuate. 1
Lp(a) should be measured once using an isoform-insensitive assay. 4