Lipoprotein (a)

Lipoprotein(a), written as Lp(a) and pronounced “L-P-little-a,” is a unique lipoprotein particle that combines an LDL-like core with an additional protein called apolipoprotein(a). This distinctive structure makes Lp(a) doubly dangerous: it promotes atherosclerosis like LDL AND interferes with blood clot breakdown, increasing thrombosis risk. It’s essentially LDL’s more dangerous cousin.

Why does this matter? Lp(a) levels are primarily determined by genetics — about 90% inherited. Unlike LDL cholesterol, your Lp(a) level is set at birth and remains relatively constant throughout life. Standard cholesterol tests don’t measure Lp(a), so many people with elevated levels don’t know they carry this hidden risk factor. Approximately 20% of the population has elevated Lp(a), making it one of the most common genetic cardiovascular risk factors.

The good news: while we can’t yet dramatically lower Lp(a), knowing your level allows for more aggressive management of other risk factors. New therapies specifically targeting Lp(a) are in advanced development and may soon transform treatment.

Order Your Advanced Lipid Panel

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Key Benefits of Testing

Lp(a) testing uncovers a major genetic risk factor that standard lipid panels miss. Elevated Lp(a) can explain “unexplained” heart attacks in people with otherwise normal cholesterol — providing answers and guiding more aggressive prevention.

Because Lp(a) is genetically determined and stable, you typically only need to test once in your lifetime. That single test provides permanent risk information for you and potentially identifies risk in your family members who share your genetics.

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What Does This Test Measure?

Lp(a) testing measures the concentration of lipoprotein(a) particles in blood. The result can be reported in different units (mass or molar), so consistency in units is important when comparing results.

The Lp(a) Structure

Lp(a) is a complex particle with two key components:

LDL-like core: Contains apolipoprotein B (ApoB), cholesterol, and phospholipids — similar to an LDL particle.

Apolipoprotein(a) [apo(a)]: A unique protein attached to the ApoB. This protein resembles plasminogen, a clot-dissolving enzyme, but doesn’t function like it — so it interferes with clot breakdown.

This dual structure creates double danger:

• Atherogenic (plaque-forming) like LDL
• Pro-thrombotic (clot-promoting) due to apo(a)

Genetic Determination

Lp(a) levels are approximately 90% genetically determined by the LPA gene. Key points:

• Levels set by birth and stable throughout life
• Diet and exercise have minimal effect
• Most medications don’t significantly lower Lp(a)
• Wide variation between individuals (from nearly zero to very high)
• Ethnic variation exists (higher average in African ancestry)

Apo(a) Size Variation

The apo(a) protein varies in size between individuals due to different numbers of repeated sequences called “kringles.” Smaller apo(a) is associated with higher Lp(a) levels and potentially greater risk.

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Why This Test Matters

Independent Cardiovascular Risk Factor

Elevated Lp(a) increases risk of:

• Coronary artery disease and heart attacks
• Ischemic stroke
• Aortic valve stenosis (calcification)
• Peripheral artery disease

This risk is independent of LDL cholesterol and other traditional risk factors.

Explains “Unexplained” Events

When someone has a heart attack despite “normal” cholesterol, elevated Lp(a) is often the hidden culprit. Testing provides answers for patients and families seeking to understand premature cardiovascular disease.

Identifies Family Risk

Because Lp(a) is inherited, elevated levels in one family member suggest testing others. This allows early identification and prevention in relatives.

Guides Treatment Intensity

High Lp(a) justifies more aggressive management of modifiable risk factors. Since we can’t easily lower Lp(a) yet, we compensate by optimizing everything else — more aggressive LDL lowering, tighter blood pressure control, and lifestyle optimization.

Included in Standard LDL Measurement

An important technical point: standard LDL cholesterol tests include the cholesterol in Lp(a) particles. So someone with high Lp(a) may have “high LDL” that’s partly Lp(a)-cholesterol. Knowing Lp(a) helps interpret LDL results more accurately.

Aortic Valve Disease Risk

Lp(a) is uniquely associated with calcific aortic valve stenosis — it’s not just about coronary arteries. This expands who might benefit from knowing their Lp(a) level.

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What Can Affect Your Lp(a)?

Primary Determinant: Genetics

About 90% of Lp(a) variation is genetically determined. Your level is largely fixed at birth.

Factors That May INCREASE Lp(a)

Conditions:

• Kidney disease — can raise Lp(a)
• Nephrotic syndrome
• Menopause — levels may rise after menopause
• Hypothyroidism — mild elevation
• Acute illness or inflammation — transient increase

Medications:

• Some hormone therapies may affect levels

Factors That May DECREASE Lp(a) (Limited Options)

Current options with modest effects:

• Niacin — can reduce Lp(a) by 20-30%, but side effects limit use
• PCSK9 inhibitors — reduce Lp(a) by approximately 20-30%
• Estrogen therapy — may lower Lp(a) in postmenopausal women
• Lipoprotein apheresis — physically removes Lp(a) (for severe cases)

Minimal to no effect:

• Statins — don’t lower Lp(a) (may slightly increase)
• Diet and exercise — minimal effect on Lp(a)
• Most other lipid medications

Emerging therapies (in development):

• Antisense oligonucleotides targeting Lp(a) production
• Small interfering RNA (siRNA) therapies
• These may reduce Lp(a) by 80-90% or more in trials

Testing Considerations

Fasting not required: Lp(a) levels are stable regardless of meals.

Units matter: Results may be reported in mg/dL or nmol/L. These don’t convert simply due to apo(a) size variation. Use consistent units for comparison.

One-time testing usually sufficient: Since Lp(a) is genetically determined and stable, repeat testing is usually unnecessary unless initial results were during acute illness.

Ethnicity: Average levels differ by ancestry. People of African descent tend to have higher average Lp(a).

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When Should You Get Tested?

European Guidelines Recommend Testing Everyone At Least Once

The European Atherosclerosis Society recommends that all adults be tested for Lp(a) at least once in their lifetime to identify those with elevated levels.

Strong Indications for Testing

• Family history of premature cardiovascular disease (men <55, women <65)
• Personal history of premature cardiovascular disease
• Family history of elevated Lp(a)
• Familial hypercholesterolemia
• Recurrent cardiovascular events despite treatment
• Calcific aortic valve disease
• Cardiovascular risk assessment in intermediate-risk patients

Consider Testing

• Anyone wanting comprehensive cardiovascular risk assessment
• People with elevated LDL that doesn’t fully respond to statins
• Those with stroke or peripheral artery disease
• Family members of someone with high Lp(a)

Order Your Test

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Understanding Your Results

Lp(a) interpretation focuses on risk stratification:

Lp(a) Levels and Risk

Desirable Lp(a): Low levels are associated with minimal Lp(a)-related cardiovascular risk. Most people with low Lp(a) can focus on standard risk factors.

Moderately elevated Lp(a): Indicates increased cardiovascular risk. Warrants attention to other modifiable risk factors.

High Lp(a): Significantly elevated cardiovascular risk — comparable to having familial hypercholesterolemia. Aggressive management of all other risk factors is important.

Very high Lp(a): Substantially increased risk. Consider referral to lipid specialist. May be candidate for emerging therapies or apheresis in severe cases.

Population Distribution

Lp(a) distribution is highly skewed:

• Most people have relatively low levels
• About 20% have elevated levels
• A smaller percentage have very high levels carrying substantial risk

Units and Thresholds

Results may be reported in mg/dL or nmol/L. The threshold for elevated Lp(a) depends on the units used. Because apo(a) size varies, simple mathematical conversion between units is not accurate — look at the reference ranges provided with your results.

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What to Do About Elevated Results

Currently Available Strategies

Aggressively manage other risk factors:

• Lower LDL aggressively: Since Lp(a) is hard to change, compensate by getting LDL as low as possible. Consider more intensive statin therapy, adding ezetimibe or PCSK9 inhibitors.
• Optimize blood pressure: Tighter control reduces overall risk.
• Manage diabetes meticulously: If diabetic, optimal glucose control is essential.
• Don’t smoke: Smoking compounds Lp(a) risk significantly.
• Maintain healthy weight and exercise: Even though they don’t lower Lp(a), they reduce overall risk.
• Aspirin: May be considered in high-risk individuals (discuss with provider).

Niacin:

• Can lower Lp(a) by 20-30%
• Limited use due to side effects (flushing, glucose elevation)
• Not proven to reduce cardiovascular events specifically from Lp(a) lowering

PCSK9 inhibitors:

• Lower Lp(a) by approximately 20-30% in addition to LDL lowering
• May have greater benefit in those with elevated Lp(a)

Lipoprotein apheresis:

• Physical removal of Lp(a) from blood
• Reserved for very high Lp(a) with progressive cardiovascular disease
• Requires regular sessions (every 1-2 weeks)

Emerging Therapies (Watch This Space!)

Specific Lp(a)-lowering drugs are in advanced clinical trials:

• Can reduce Lp(a) by 80-90% or more
• If effective and safe, will transform Lp(a) management
• Results from large cardiovascular outcomes trials expected soon

Screen Family Members

Because Lp(a) is inherited, elevated levels in one family member warrant testing others. Early identification allows proactive prevention.

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Related Health Conditions

Coronary Artery Disease

Major Risk Factor: Elevated Lp(a) significantly increases coronary disease risk independent of LDL. It’s a common finding in premature heart attacks with otherwise “normal” cholesterol.

Aortic Valve Stenosis

Unique Association: Lp(a) is causally linked to calcific aortic valve disease — one of the few risk factors specifically associated with valve calcification.

Ischemic Stroke

Stroke Risk Factor: Elevated Lp(a) increases stroke risk through both atherosclerosis and its pro-thrombotic properties.

Familial Hypercholesterolemia

Compounding Risk: People with FH who also have elevated Lp(a) face particularly high risk. Lp(a) testing is recommended in all FH patients.

Peripheral Artery Disease

Leg Artery Risk: Elevated Lp(a) increases risk of atherosclerosis in leg arteries, contributing to claudication and limb ischemia.

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Why Testing Matters

Lp(a) is a silent, genetic time bomb for cardiovascular disease that standard cholesterol tests miss. A single test reveals this inherited risk factor, providing information for life. Knowing your Lp(a) empowers more aggressive prevention if elevated and provides reassurance if normal. As new Lp(a)-lowering therapies emerge, knowing your level becomes even more valuable.

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Related Biomarkers Often Tested Together

LDL Cholesterol — Standard LDL includes Lp(a)-cholesterol. Knowing both helps interpret results.

Apolipoprotein B (ApoB) — Lp(a) particles contain ApoB. Together they provide complete atherogenic particle assessment.

Total Cholesterol and HDL Cholesterol — Complete lipid picture for comprehensive risk assessment.

hs-CRP — Inflammation marker. Combined with Lp(a) for broader cardiovascular risk assessment.

Homocysteine — Another independent cardiovascular risk factor.

Note: Information provided in this article is for educational purposes and doesn’t replace personalized medical advice.