The Silent Risk: Why Lipoprotein(a) Could Be the Next Big Thing in Heart Health
- Saneka Chakravarty, MD, FACC
- Jun 14
- 4 min read
Updated: Jul 25
When it comes to cholesterol, you’ve probably heard about HDL (the “good” cholesterol), LDL (the “bad” one), and triglycerides. But there’s another lipoprotein that doesn’t get much attention — and it should. It’s called Lipoprotein(a)or Lp(a), and researchers believe it could be one of the most important, overlooked risk factors for heart disease and stroke.
So what exactly is Lp(a), and why should you — or your doctor — care?
What is Lipoprotein(a)?
Lipoprotein(a), pronounced "lipoprotein little a," is a particle in your blood made of LDL-like cholesterol and a unique protein called apolipoprotein(a) (or apo(a)). This odd pairing gives Lp(a) some nasty traits: not only does it promote plaque buildup in arteries (atherosclerosis), but it also interferes with your body’s ability to dissolve clots.
In other words, Lp(a) is like LDL on steroids — with both atherogenic (plaque-forming) and pro-thrombotic (clot-forming) powers.
Why It Matters: The Hidden Risk
Lp(a) is not influenced by diet or lifestyle — it’s genetically determined. That means you can have a stellar diet, exercise daily, and still carry high levels of Lp(a), putting you at risk for:
Early heart disease
Heart attacks and strokes (even with normal cholesterol)
Aortic valve stenosis (narrowing of the aortic valve)
In fact, a 2022 study in JAMA Cardiology found that people with very high Lp(a) levels had a 57% higher risk of cardiovascular events, independent of other risk factors.
Who Should Be Tested for Lp(a)?
Despite its importance, Lp(a) testing is not yet routine. Here's who should strongly consider getting tested:
Anyone with a personal or family history of early cardiovascular disease (before age 55 in men, 65 in women)
People with high LDL-C that doesn’t respond well to statins
Patients with aortic valve disease without a known cause
Anyone with a family history of high Lp(a)
A simple blood test can measure Lp(a) levels. Values are typically measured in nmol/L or mg/dL, and high-risk thresholds are generally considered:
Above 125 nmol/L
Or above 50 mg/dL
Lp(a): Disease Marker vs. Causal Factor?
The longstanding debate centers on whether Lp(a) is merely a biomarker of disease or a direct causal factor.
Arguments for Lp(a) as a Disease Marker:
• It is elevated in individuals with CVD but does not always correlate with disease severity.
• Some individuals with extremely high Lp(a) levels do not develop CVD, suggesting other modifying factors.
Arguments for Lp(a) as a Causal Factor:
• Mendelian Randomization Studies: Genetic studies show that Lp(a) levels are causally linked to CVD (Clarke et al., 2009).
• Oxidized Phospholipid Load: Lp(a) carries pro-inflammatory oxidized phospholipids that promote atherosclerosis.
• Aortic Valve Calcification Studies: High Lp(a) directly correlates with aortic stenosis progression.
Most evidence supports that Lp(a) is not just a biomarker but a direct contributor to disease.
Are There Treatments for High Lp(a)?
Currently, there are no approved drugs that specifically target Lp(a). However, the scientific world is racing to change that.
What We Can Do Now:
Niacin can reduce Lp(a) by 20–30%, but its use is limited due to side effects and unclear cardiovascular benefit. ( benefits may not outweigh risks).
PCSK9 inhibitors (like evolocumab and alirocumab) lower Lp(a) modestly (~20–30%) and are used for high-risk patients.
Lipoprotein apheresis, a dialysis-like process, is an option in severe cases but is costly and time-intensive.
Some studies showed that lowering LDL(bad cholesterol) to less than 50 mg/dl may make lipoprotein A levels less of a concern. So make sure you keep your bad cholesterol low.
An Anti inflammatory diet.
( A proper diet and statins still reduce cardiovascular risk in those with high lipoprotein(a) levels, even though they do not significantly lower Lp(a) itself. Diet and statins are effective at lowering LDL cholesterol (LDL-C), which is a major modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD). Statins may modestly increase Lp(a) concentrations, but this effect is small and does not outweigh their substantial benefit in reducing LDL-C and overall ASCVD risk.)
What’s Coming Soon:
The real excitement is in antisense oligonucleotides (ASOs) and RNA interference (RNAi) therapies.
Pelacarsen (an ASO) has shown reductions of up to 80% in Lp(a) levels in clinical trials.
Olpasiran (an RNAi drug) also demonstrated up to 98% reduction in a Phase 2 trial (NEJM, 2022).
These therapies are still in late-phase trials, but they’re showing enormous promise — potentially transforming how we treat Lp(a)-related cardiovascular risk.
Frequently Asked Questions
Q1: How often should I test Lp(a)?
A: Just once — unless new cardiovascular symptoms develop. Since levels are genetically set, they stay stable over a lifetime.
Q2: Can lifestyle changes help?
A: Unfortunately, no. Lp(a) levels are largely unaffected by diet, exercise, or statins. But healthy habits are still crucial to manage your overall heart risk.
Q3: Is Lp(a) included in standard cholesterol panels?
A: No. You need to specifically ask your doctor for an Lp(a) test.
Q4: My Lp(a) is high but my LDL is normal. Should I worry?
A: Yes. Even with normal LDL-C, high Lp(a) can independently raise your heart disease risk. It’s like having a hidden time bomb — awareness is the first step.
References
1. Lipoprotein(a): A Genetically Determined, Causal, and Prevalent Risk Factor for Atherosclerotic Cardiovascular Disease: A Scientific Statement From the American Heart Association. Reyes-Soffer G, Ginsberg HN, Berglund L, et al. Arteriosclerosis, Thrombosis, and Vascular Biology. 2022;42(1):e48-e60. doi:10.1161/ATV.0000000000000147.
2. Role of Lipoprotein(a) in Atherosclerotic Cardiovascular Disease: A Review of Current and Emerging Therapies. Alhomoud IS, Talasaz A, Mehta A, et al. Pharmacotherapy. 2023;43(10):1051-1063. doi:10.1002/phar.2851.
3. Lipoprotein(a) and its Significance in Cardiovascular Disease: A Review. Duarte Lau F, Giugliano RP. JAMA Cardiology. 2022;7(7):760-769. doi:10.1001/jamacardio.2022.0987.
4. Lipoprotein(a) as a Risk Factor for Cardiovascular Diseases: Pathophysiology and Treatment Perspectives. Vinci P, Di Girolamo FG, Panizon E, et al. International Journal of Environmental Research and Public Health. 2023;20(18):6721. doi:10.3390/ijerph20186721.
5. Existing and Emerging Strategies to Lower Lipoprotein(A). Schwartz GG, Ballantyne CM. Atherosclerosis. 2022;349:110-122. doi:10.1016/j.atherosclerosis.2022.04.020.
.
Final Thoughts
Lipoprotein(a) is one of the most important — and underdiagnosed — risk factors in cardiovascular medicine today. It’s invisible to standard cholesterol tests and immune to lifestyle changes, but that doesn’t mean it’s untreatable.
Ask your doctor. Know your numbers. Stay ahead of the curve.
Because when it comes to your heart, what you don’t know can hurt you.
Comments