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Apolipoprotein A-1
(Major HDL Apolipoprotein – Anti-atherogenic Lipid Marker)
Synonyms
- ApoA-1
- Apolipoprotein A1
- HDL-ApoA-1
- Major HDL apoprotein
- Apo AI
Units of Measurement
mmol/L, µmol/L, g/L, mg/dL, mg/100mL, mg%, mg/mL
Description
Apolipoprotein A-1 (ApoA-1) is the main structural protein of high-density lipoprotein (HDL) and plays a crucial role in reverse cholesterol transport - the process by which HDL removes cholesterol from peripheral tissues and delivers it to the liver.
ApoA-1 levels directly reflect:
- HDL functionality (more accurate than HDL-C alone)
- Cardiovascular risk
- Lipid metabolism disorders
Low ApoA-1 is one of the strongest biochemical markers of atherosclerotic cardiovascular disease (ASCVD).
Physiological Role
1. Reverse Cholesterol Transport
ApoA-1:
- Activates LCAT (lecithin–cholesterol acyltransferase)
- Promotes cholesterol efflux via ABCA1 receptors
- Forms nascent HDL particles
- Delivers cholesterol to liver for excretion
2. Anti-Inflammatory & Antioxidant Effects
- Inhibits LDL oxidation
- Reduces vascular inflammation
- Protects endothelium
3. Anti-thrombotic Properties
- Modulates platelet function
- Improves endothelial nitric oxide activity
Clinical Significance
Low ApoA-1 (Most Important)
Strongly associated with:
- High cardiovascular risk
- Coronary artery disease (CAD)
- Metabolic syndrome
- Type 2 diabetes
- Familial hypoalphalipoproteinemia
- Tangier disease (ApoA-1 deficiency)
Low ApoA-1 → dysfunctional HDL → increased atherosclerosis.
High ApoA-1
Considered protective:
- Lower ASCVD risk
- Good HDL function
- May occur with exercise, estrogen therapy, moderate alcohol intake
Reference Intervals
Adult Reference Ranges
| Population | ApoA-1 (g/L) | mg/dL | Interpretation |
| Men | 1.05 – 1.60 | 105 – 160 | Normal |
| Women | 1.20 – 1.90 | 120 – 190 | Normal (higher physiologically) |
Cardiovascular Risk Thresholds
- Low ApoA-1:
- Men: < 1.05 g/L (<105 mg/dL)
- Women: < 1.20 g/L (<120 mg/dL)
- Men: < 1.05 g/L (<105 mg/dL)
- High (protective): > 1.60 g/L in men; > 1.90 g/L in women
Children
- 1.0 – 1.8 g/L depending on age
Unit Meanings
| Unit | Meaning |
| mmol/L | millimole per liter |
| µmol/L | micromole per liter |
| g/L | grams per liter |
| mg/dL | milligrams per deciliter |
| mg/100mL | equivalent to mg% |
| mg% | mg per 100 mL |
| mg/mL | milligrams per milliliter |
Diagnostic Uses
1. Cardiovascular Risk Assessment
ApoA-1 is an independent predictor of:
- Myocardial infarction
- Stroke
- Atherosclerosis progression
More reliable than HDL-C, especially when HDL is dysfunctional.
2. ApoB/ApoA-1 Ratio (Very Important)
ApoB/ApoA-1 ratio=atherogenicity index\text{ApoB/ApoA-1 ratio} = \text{atherogenicity index}ApoB/ApoA-1 ratio=atherogenicity index
Interpretation:
- < 0.6: low risk
- 0.6 – 0.8: moderate risk
- > 0.8: high risk (very strong marker)
3. Metabolic Syndrome
Low ApoA-1 integral in metabolic dyslipidemia.
4. Severe Genetic Disorders
- Tangier disease: ApoA-1 extremely low
- Familial ApoA-1 deficiency: premature CVD
5. Therapy Monitoring
Tracks response to:
- Statins
- Niacin
- CETP inhibitors (experimental)
- Lifestyle changes
Analytical Notes
- Measured using immunonephelometry or immunoturbidimetry.
- Fasting sample preferred but not mandatory.
- Levels affected by:
- Smoking (↓)
- Estrogen therapy (↑)
- Inflammation (↓ during acute phase)
- Smoking (↓)
Clinical Pearls
- ApoA-1 is a better indicator of HDL functionality than HDL cholesterol.
- Low ApoA-1 is the strongest lipoprotein predictor of premature myocardial infarction.
- High ApoA-1 is cardioprotective even when HDL-C is normal.
- The ApoB/ApoA-1 ratio outperforms LDL-C in predicting CVD in some populations.
- ApoA-1 is stable and does not vary significantly day-to-day.
Interesting Fact
ApoA-1 is the major component of HDL’s “good cholesterol”, but unlike HDL-C, it reflects quality, not just quantity - making it superior in assessing cardiovascular protection.
References
- Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Lipoproteins & Apolipoproteins.
- IFCC Working Group - Apolipoprotein Standardization.
- AHA/ACC Guidelines - Cholesterol & Risk Assessment.
- Mayo Clinic Laboratories - ApoA-1 Test Catalog.
- ARUP Consult - Lipid Disorders & Apolipoproteins.
- NIH / MedlinePlus - ApoA-1 Overview.
- Clinical Lipidology Texts - HDL Function & Atheroprotection.