Lp(a): The Genetic Risk Factor You Can't Change
Lipoprotein(a) is an independent genetic risk factor for cardiovascular disease. Elevated Lp(a) increases risk of heart attack, stroke, and aortic stenosis regardless of LDL levels.
Reference: < 50 nmol/L (optimal), 50-75 nmol/L (borderline), 75-120 nmol/L (high), > 120 nmol/L (very high) nmol/L
Key Takeaway
Lp(a) is genetically determined and doesn't respond meaningfully to lifestyle or most medicationsNordestgaard BG, et al. 2010. If you have elevated Lp(a), you need to be extra aggressive about lowering other risk factors—especially LDL-C, since Lp(a) risk multiplies LDL riskVittinghoff E, et al. 2021.
What is Lp(a)?
Lipoprotein(a), pronounced "lipoprotein little-a," is an LDL-like particle with an additional protein called apolipoprotein(a) attachedTsimikas S, 2017. This extra protein makes Lp(a) especially dangerous—it promotes both plaque buildup (atherosclerosis) and blood clots (thrombosis).
Unlike other lipids, Lp(a) is 80-90% determined by geneticsNordestgaard BG, et al. 2010. Your Lp(a) level is essentially set at birth and remains stable throughout life. Diet, exercise, and most medications have minimal effect.
Why Lp(a) Matters
- Independent risk factor: Elevated Lp(a) increases risk regardless of LDL-CVittinghoff E, et al. 2021
- Dual threat: Promotes both atherosclerosis AND thrombosisTsimikas S, 2017
- Common: 1 in 5 people have elevated Lp(a) (＞50 nmol/L)
- Under-recognized: Not included in standard lipid panels
- Multiplier effect: High Lp(a) + high LDL = dramatically higher risk
- Optimal (＜ 30 nmol/L): Lowest genetic riskEAS, 2021
- Near Optimal (30-49 nmol/L): Low risk
- Borderline (50-75 nmol/L): Moderately increased risk
- High (75-120 nmol/L): 2-3x increased cardiovascular riskNordestgaard BG, et al. 2010
- Very High (> 120 nmol/L): 3-5x increased cardiovascular risk, equivalent to heterozygous familial hypercholesterolemia
The Multiplicative Effect
Lp(a) risk multiplies the risk from other factorsVittinghoff E, et al. 2021:
The Inheritance Pattern
Lp(a) follows an autosomal dominant pattern with incomplete penetrance. If one parent has elevated Lp(a), each child has a 50% chance of inheriting itEAS, 2021. Testing family members is recommended when elevated Lp(a) is discovered—this can identify risk early and enable preventive care.
Emerging Treatments
Currently, no FDA-approved medications specifically lower Lp(a), but several are in developmentArngrimsson R, et al. 2022:
- PCSK9 inhibitors: Lower Lp(a) by 20-30% (secondary effect)
- Niacin: Lowers Lp(a) by 20-30% but side effects limit use
- Antisense oligonucleotides: In trials, can lower Lp(a) by 80%+
- RNA interference therapies: In trials, similar dramatic reductions
For now, the best approach is aggressive management of other risk factorsAHA, 2022.
When to Test Lp(a)
- Everyone: Test once in lifetime (guidelines now recommend)CDC, 2023
- Family history: Of premature heart disease or high Lp(a)
- Personal history: Early heart attack, stroke, or calcific aortic stenosis
- Risk assessment: When deciding on statin therapy intensity
Related Testing
- LDL-C: Primary treatment target when Lp(a) is high
- ApoB: Total atherogenic particle count
- hs-CRP: Inflammation modifies Lp(a) risk
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