What is Lipoprotein(a) [Lp(a)] and how is it managed in patients, especially those with a family history of cardiovascular disease or additional risk factors such as hypertension, diabetes mellitus, or obesity?

Understanding Lipoprotein(a): A Patient Guide

What is Lipoprotein(a)?

Lipoprotein(a), or Lp(a), is a cholesterol-carrying particle in your blood that significantly increases your risk for heart attacks, strokes, and heart valve disease—and unlike regular cholesterol, it cannot be lowered through diet, exercise, or standard cholesterol medications. 1

• Lp(a) is composed of an LDL ("bad cholesterol") particle attached to a special protein called apolipoprotein(a) 1
• Your Lp(a) level is determined 70-90% by your genes, not your lifestyle, which is why it runs strongly in families 2
• Approximately 20-30% of people worldwide (more than one billion individuals) have elevated Lp(a) levels that increase cardiovascular risk 1

Why Does Lp(a) Matter?

Elevated Lp(a) causes heart disease through multiple dangerous mechanisms: it promotes cholesterol buildup in arteries, triggers inflammation, increases blood clotting, and causes calcium deposits in heart valves. 3, 1

• People with both elevated Lp(a) and elevated LDL cholesterol face a 10-fold or higher risk of heart attack compared to those with normal levels of both 3
• Even when your regular cholesterol is well-controlled with medications, elevated Lp(a) leaves you with significant remaining cardiovascular risk 4, 5
• Lp(a) increases your risk for heart attacks, strokes, peripheral arterial disease, heart failure, and calcific aortic valve stenosis 1

What Level is Considered Elevated?

The threshold where cardiovascular risk demonstrably increases is Lp(a) >30 mg/dL (or >75 nmol/L), which represents the 75th percentile in white populations. 2

• European guidelines define significant risk at Lp(a) >50 mg/dL (approximately 100-125 nmol/L) 2
• Risk increases progressively with higher Lp(a) levels, with particularly high risk at levels >100 mg/dL 2
• Different laboratories may report Lp(a) in different units (mg/dL or nmol/L), and a conversion factor of 1 mg/dL = 3.17 nmol/L can be used 2

Who Should Be Tested?

You should have your Lp(a) measured at least once in your lifetime if you have premature heart disease, a family history of early heart attacks or strokes, familial high cholesterol, or recurrent cardiovascular events despite optimal treatment. 2

• Measure Lp(a) if you have had a heart attack or stroke at a young age without obvious risk factors 3
• Measure Lp(a) if you have a family history of premature cardiovascular disease or elevated Lp(a) 2
• Measure Lp(a) if you have familial hypercholesterolemia (genetic high cholesterol) 3
• Measure Lp(a) if you have recurrent cardiovascular events despite being on optimal cholesterol-lowering therapy 2
• Children with elevated Lp(a) have a fourfold increased risk of acute ischemic stroke, and the risk of recurrent strokes increases more than tenfold when Lp(a) is above the 90th percentile 2

How is Elevated Lp(a) Managed?

Primary Strategy: Aggressive LDL Cholesterol Reduction

The cornerstone of managing elevated Lp(a) is achieving the lowest possible LDL cholesterol level—ideally below 70 mg/dL—using high-intensity statin medications, as this reduces cardiovascular events even though residual risk from Lp(a) remains. 2

• Evidence from multiple randomized trials demonstrates that when Lp(a) is elevated, cardiovascular event rates remain higher at any achieved LDL-C level, confirming unaddressed Lp(a)-mediated residual risk 2
• High-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily) should be initiated immediately 2
• Important caveat: Standard LDL cholesterol laboratory tests include cholesterol from Lp(a) particles, which means your true LDL cholesterol may actually be lower than reported 2

Medications That Lower Lp(a)

Niacin (vitamin B3) at doses up to 2000 mg/day is currently the most effective conventional medication for Lp(a) reduction, lowering levels by 30-35%. 3, 2

• Niacin can be considered in addition to statin therapy, especially for patients with very high Lp(a) levels (>60-100 mg/dL) 2
• Side effects of niacin include flushing, elevated blood sugar, and potential liver toxicity, requiring monitoring 2

PCSK9 inhibitors (evolocumab or alirocumab) provide dual benefit: they reduce LDL cholesterol by 50-60% AND lower Lp(a) by approximately 25-30%. 2

• PCSK9 inhibitors should be considered for high-risk patients with Lp(a) >100 mg/dL or those with additional risk factors 2
• These medications are given as injections every 2-4 weeks 2

Advanced Treatment: Lipoprotein Apheresis

For patients with very high Lp(a) (>60 mg/dL) who continue to have cardiovascular events despite optimal medical therapy, lipoprotein apheresis—a procedure similar to dialysis that filters Lp(a) from the blood—reduces Lp(a) by up to 80% and cardiovascular events by approximately 80%. 2

• Apheresis is typically performed every 1-2 weeks and requires specialized centers 2
• This treatment is reserved for refractory cases with recurrent events or disease progression despite maximally-tolerated medications 2

What Doesn't Work to Lower Lp(a)?

Diet, exercise, and weight loss do not significantly lower Lp(a) levels because 70-90% of variation is genetically determined. 2

• Standard statin medications may actually increase Lp(a) levels slightly, despite their cardiovascular benefits through LDL cholesterol reduction 2
• Ezetimibe (Zetia) does not lower Lp(a) 4
• Lifestyle modifications remain critically important for managing all other cardiovascular risk factors, even though they don't lower Lp(a) 2

Managing All Other Risk Factors

Because Lp(a) cannot be easily lowered, it is absolutely critical to aggressively control all other modifiable cardiovascular risk factors. 2

• Blood pressure should be controlled to <130/80 mmHg 2
• If you have diabetes, maintain HbA1c <7% (or individualized target) 2
• Achieve and maintain a healthy body weight 2
• Engage in at least 150 minutes of moderate-intensity aerobic exercise weekly 2
• Stop smoking completely 2
• Manage stress and depression, as these affect cardiovascular health 6

Family Screening

If you have elevated Lp(a), your first-degree relatives (parents, siblings, children) should be tested, as elevated Lp(a) is inherited in an autosomal dominant pattern with high penetrance. 2

• This means each of your children has a 50% chance of inheriting elevated Lp(a) if you have it 2
• Early identification allows for earlier intervention and risk factor management 2

Future Treatments

Promising new therapies called antisense oligonucleotides (pelacarsen) and small interfering RNA (olpasiran) are in clinical trials and can reduce Lp(a) by 80-90%, with results from large outcome trials expected in the coming years. 4, 5

• These medications work by blocking the liver's production of Lp(a) 4
• If proven effective and safe in ongoing trials, they may become available for patients with very high Lp(a) levels and high cardiovascular risk 4

Key Takeaways

• Lp(a) is a genetic, lifelong cardiovascular risk factor that affects 20-30% of the population 1
• Elevated Lp(a) (>30 mg/dL) significantly increases risk for heart attacks, strokes, and heart valve disease 2, 1
• The primary management strategy is aggressive LDL cholesterol reduction to <70 mg/dL using high-intensity statins 2
• Additional Lp(a)-lowering options include niacin (30-35% reduction) and PCSK9 inhibitors (25-30% reduction) 2
• Lipoprotein apheresis is reserved for severe cases with recurrent events despite optimal therapy 2
• Aggressive management of all other cardiovascular risk factors (blood pressure, diabetes, smoking, weight, exercise) is essential 2
• Family members should be screened, as Lp(a) elevation is strongly inherited 2