Lipoprotein(a): What It Measures and Optimal Ranges
Lipoprotein(a) [Lp(a)] is a cardiovascular risk marker with optimal levels below 30 mg/dL (75 nmol/L), as elevated levels significantly increase risk for cardiovascular disease and aortic valve stenosis. 1
What is Lipoprotein(a)?
Lipoprotein(a) is a complex particle in the blood composed of:
- An LDL-like particle containing apolipoprotein B
- A unique glycoprotein called apolipoprotein(a) that is covalently linked to the LDL particle
- Contains approximately 30-45% cholesterol by mass 1
Lp(a) is primarily determined by genetics, with the LPA gene accounting for up to 90% of the concentration variability 2. Unlike other lipoproteins, Lp(a) levels:
- Show minimal response to lifestyle changes
- Are relatively stable throughout life after early childhood
- Are synthesized in the liver and cleared primarily through hepatic receptors 1
Reference Ranges and Risk Thresholds
Lp(a) levels show a highly skewed distribution in the population with:
- Normal/Optimal range: <30 mg/dL (<75 nmol/L) 1
- Moderately elevated: 30-50 mg/dL (75-125 nmol/L)
- Significantly elevated: >50 mg/dL (>125 nmol/L) 1
Risk thresholds based on population percentiles:
- 75th percentile: >47 mg/dL
- 90th percentile: >90 mg/dL
- 95th percentile: >116 mg/dL 3
Prevalence of Elevated Lp(a)
Elevated Lp(a) is surprisingly common:
- Levels >30 mg/dL are present in approximately 35% of the US population
- Levels >50 mg/dL are present in approximately 24% of the US population 3
- Even higher prevalence is seen in tertiary care settings (39.5% >30 mg/dL) 3
Clinical Significance and Risk Assessment
Elevated Lp(a) is causally linked to:
- Cardiovascular disease (myocardial infarction, stroke)
- Aortic valve stenosis
- Peripheral arterial disease
- Heart failure 2
Risk increases progressively with higher Lp(a) levels:
- Compared to individuals with Lp(a) <10 mg/dL, those with levels ≥100 mg/dL have a 2.14-fold increased risk of major adverse cardiovascular events in secondary prevention 4
- For every 50 mg/dL (105 nmol/L) reduction in Lp(a), there is an estimated 20% reduction in cardiovascular events 4
Important Considerations for Interpretation
- Lp(a) is included in standard LDL-C measurements, potentially masking true LDL-C levels 1
- Women tend to have slightly higher Lp(a) levels than men 5, 3
- Postmenopausal women may have approximately 8% higher levels than premenopausal women 5
- Lp(a) shows an inverse association with triglyceride levels, though this explains only about 0.5% of variation 5
- Statins and ezetimibe may actually increase Lp(a) levels, potentially limiting LDL-C reduction in those with elevated Lp(a) 1
When to Measure Lp(a)
According to guidelines, Lp(a) measurement should be considered in:
- Premature cardiovascular disease
- Familial hypercholesterolemia
- Family history of premature CVD or elevated Lp(a)
- Recurrent CVD despite optimal lipid-lowering therapy
- Patients with ≥5% 10-year risk of fatal CVD 1
Clinical Implications
For patients with elevated Lp(a):
- More aggressive management of other cardiovascular risk factors is warranted
- Lower LDL-C targets may be appropriate
- Specific Lp(a)-lowering therapies (antisense oligonucleotides) are in development and show promise for reducing levels by up to 90% 2
- Current therapies with modest Lp(a)-lowering effects include PCSK9 inhibitors (25-30% reduction) and lipoprotein apheresis (60-70% reduction) 2
Understanding Lp(a) levels is increasingly important in cardiovascular risk assessment, as approximately one billion people globally have elevated levels, making it one of the most common genetic risk factors for cardiovascular disease.