Lipoproteins and Lipoprotein(a): A GP’s Practical Guide Published: August 2025
Lipoproteins and Lipoprotein(a): A GP’s Practical Guide
Published: August 2025
Source: American Heart Association (AHA) – Clinicians’ Guide to Frequently Asked Questions About Lipoprotein(a) Testing
With added background on apolipoproteins and cholesterol transport for clarity
1. Why do fats need proteins in the blood?
• Fats (lipids) do not dissolve in water, and blood is water-based.
• To move through the bloodstream, fats attach to apolipoproteins, forming lipoproteins — particles that safely transport cholesterol and triglycerides to where the body needs them.
2. Main types of lipoproteins (from least to most dense):
1. Chylomicrons – Rich in triglycerides; deliver dietary fat from intestines.
2. VLDL (Very Low-Density Lipoprotein) – Carries triglycerides made in the liver to tissues.
3. IDL (Intermediate-Density Lipoprotein) – Transitional form from VLDL to LDL.
4. LDL (Low-Density Lipoprotein) – Delivers cholesterol to tissues; major cause of plaque build-up (“bad cholesterol”).
• Main protein: ApoB-100 — one per particle, making ApoB a direct count of harmful particles.
5. HDL (High-Density Lipoprotein) – Removes cholesterol from tissues to the liver (“good cholesterol”).
• Main protein: ApoA-I — generally protective.
6. Lp(a) (Lipoprotein(a)) is a genetically determined, modified form of LDL — People with elevated Lp(a) have both regular LDL and a genetically modified LDL particle that carries an extra Apo(a) protein, adding extra cardiovascular risk.
Lp(a) contains the standard ApoB-100 found in LDL, but also carries an extra protein called Apo(a). This added component makes it behave differently from regular LDL, increasing its tendency to stick to artery walls and promote atherosclerosis.
So most people’s main problem is high LDL, but for the 1 in 5 with genetically high Lp(a), it can add significant risk on top of LDL.
3. ApoA vs Apo(a) — Avoid the name trap of these proteins
• ApoA-I → Found in HDL, promotes cholesterol clearance, usually heart-protective.
• Apo(a) → Found only in Lp(a), harmful, increases clot and plaque risk.
• They sound similar but are completely different proteins with opposite health effects.
4. What is Lp(a) and why it matters
• Structure: LDL + ApoB-100 + extra Apo(a) protein.
• Genetics: Levels are fixed by the LPA gene — not affected by diet or exercise.
• Risks: Raises likelihood of coronary artery disease, stroke, and aortic valve stenosis.
• Prevalence: Elevated in about 15–20% of the general population; more common in African and South Asian ancestry.
5. When to test for Lp(a)
• Not a universal screening — test at least once in life if:
• Premature heart disease (men <55, women <65)
• Strong family history of early ASCVD
• Familial hypercholesterolemia (FH)
• Recurrent events despite good LDL control
• Unexplained high LDL or suspected FH
• Remember: LDL and ApoB are the primary targets in prevention; Lp(a) is a secondary risk-enhancing factor but critical in those with genetic elevation.
6. How to explain Lp(a) to patients
“Think of Lp(a) as LDL with a dangerous upgrade — it has an extra protein that makes it stick more tightly to artery walls. You can’t change it with lifestyle, but knowing your level helps us protect you better.”
7. Managing high Lp(a)
• No approved drugs yet to directly lower Lp(a).
• Reduce total cardiovascular risk by:
• Aggressive LDL lowering (statins, ezetimibe, PCSK9 inhibitors)
• Heart-healthy lifestyle (diet, activity, weight, no smoking)
• Screening first-degree relatives (cascade screening)
• Risk threshold: >50 mg/dL or >125 nmol/L.
8. Cascade screening
• Test parents, siblings, and children of affected patients.
• Benefits: early detection, timely prevention, family awareness.
9. Coverage and codes
• Many insurers cover one-time testing with appropriate documentation.
• Examples:
• ICD-10: Z83.430 (family history of elevated Lp(a)), E78.01 (familial hypercholesterolemia)
• CPT: 83695 (lab billing)
10. New treatments on the horizon
• Lipoprotein apheresis is used in extreme cases.
• Clinical trials are underway for Lp(a)-lowering drugs — results expected in coming years.
Key GP take-home points
1. Fats need apolipoproteins to travel — HDL (ApoA-I) is protective, LDL (ApoB) is harmful.
2. Lp(a) = LDL + extra Apo(a) protein — genetically determined, sticky, high-risk.
Lp(a) is elevated in a minority of people. This is why the AHA and other guidelines classify Lp(a) as an additional (“secondary”) risk-enhancing factor — it’s not the first target for management, but knowing if it’s elevated is crucial in high-risk or unexplained cases.
3. Primary aim: Control LDL/ApoB in everyone.
4. Secondary aim: Check Lp(a) once in high-risk patients — about 1 in 5 will have it elevated.
5. Use cascade screening to protect families.
6. Focus on total risk reduction while awaiting Lp(a)-specific therapies.
🔗 Educational Resource: www.heart.org/lpadiscovery
https://www.lipid.org/lpaguide