Should I Test My Lp(a)
Last updated on April 24, 2025
For Informational Purposes Only
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Overview
Lipoprotein(a), or Lp(a), is a unique blood particle combining an LDL cholesterol core with a specialized protein called apolipoprotein(a). Unlike other lipoproteins, Lp(a) levels are predominantly determined by genetics rather than lifestyle factors, making them resistant to dietary changes and most conventional treatments. Recognized as an independent risk factor for cardiovascular disease, Lp(a) contributes to heart health problems through dual mechanisms: promoting atherosclerotic plaque formation and interfering with the body’s natural blood clot breakdown processes. This article explores Lp(a)’s structure, function, relationship to heart disease, testing options, and emerging treatment approaches to help readers understand this important but often overlooked cardiovascular risk factor.
What is Lp(a)?
Lipoprotein(a), or Lp(a), is a unique particle in the blood that combines a low-density lipoprotein (LDL) with a specialized protein called apolipoprotein(a). It has a distinctive structure where an LDL cholesterol particle is wrapped with this extra protein that gives it unique properties beyond regular cholesterol.
Lp(a) levels are primarily determined by genetics rather than lifestyle factors, with levels remaining relatively stable throughout a person’s life. Unlike other cholesterol markers, Lp(a) concentrations are largely resistant to dietary changes and most conventional cholesterol-lowering medications.
Multiple studies have established Lp(a) as an independent and causal risk factor for atherosclerotic cardiovascular disease, particularly heart attacks and strokes. It contributes to disease through two main mechanisms: promoting plaque formation in arteries similar to LDL cholesterol and uniquely interfering with the body’s natural blood clot breakdown process.
Elevated Lp(a) – generally considered to be above 50 mg/dL or 125 nmol/L – is common, with up to 1 billion people globally estimated to have levels that increase their cardiovascular risk. Research has shown that high Lp(a) increases risk even in people with otherwise normal cholesterol levels.
From an evolutionary perspective, Lp(a) likely played a beneficial role in wound healing and tissue repair by helping with blood clotting and delivering cholesterol for cell membrane repair. However, in modern times with longer lifespans, these same properties contribute to cardiovascular disease.
What’s the relationship between Lp(a) and other lipoproteins?
Lp(a) has a unique structure that combines elements of traditional lipoproteins with distinct properties. It consists of an LDL-like particle covalently bound to a specific glycoprotein called apolipoprotein(a), which gives it properties that are different from regular LDL. This structure means Lp(a) shares the lipid transport capabilities of LDL but has additional biological functions.
While LDL primarily transports cholesterol to tissues, Lp(a) carries both cholesterol and oxidized phospholipids that promote vascular inflammation and atherosclerosis. This dual role makes Lp(a) more atherogenic than comparable levels of LDL cholesterol alone. The apolipoprotein(a) component also resembles plasminogen structurally but interferes with fibrinolysis rather than promoting it.
Unlike other lipoproteins whose levels can be significantly modified by diet and lifestyle, Lp(a) concentrations are predominantly genetically determined by variations in the LPA gene. This genetic control means Lp(a) levels remain relatively stable throughout life and are minimally influenced by the interventions that effectively reduce other lipoprotein fractions.
Recent research has identified additional interactions between Lp(a) and other proteins, including autotaxin, which binds preferentially to Lp(a) compared to LDL. This binding enhances the production of lysophosphatidic acid, a pro-inflammatory and pro-calcific mediator. Such unique interactions further distinguish Lp(a) from other lipoproteins and contribute to its role in cardiovascular disease and calcific aortic valve stenosis.
From a measurement perspective, Lp(a) is often evaluated alongside other lipoprotein parameters, but its concentration should be considered separately when assessing cardiovascular risk. While other lipoproteins are typically measured by their cholesterol content, Lp(a) is best quantified by particle number (nmol/L) due to the variable cholesterol content of Lp(a) particles resulting from differences in apolipoprotein(a) size.
Is Lp(a) a type of cholesterol?
No, Lp(a) is not a type of cholesterol. While Lp(a) contains cholesterol as part of its structure (since it includes an LDL particle), it’s more accurate to describe it as a specialized lipoprotein complex. It’s essentially an LDL-like particle that is covalently bound to a specific glycoprotein called apolipoprotein(a), which gives Lp(a) unique properties beyond regular cholesterol.
This structural distinction is important because Lp(a) behaves differently in the body compared to other cholesterol-carrying lipoproteins. Its distinct molecular composition and biological activities make it an independent risk factor for cardiovascular disease that operates through mechanisms beyond those of regular cholesterol.
How does Lp(a) contribute to heart disease?
Lp(a) contributes to heart disease through two primary mechanisms. First, like LDL cholesterol, it can penetrate arterial walls and accumulate beneath the endothelium, promoting the development of atherosclerotic plaques. However, unlike regular LDL, Lp(a) carries oxidized phospholipids that enhance this inflammatory process.
The second mechanism involves Lp(a)’s unique structure. The apolipoprotein(a) component of Lp(a) shares structural similarities with plasminogen but interferes with normal fibrinolysis (the body’s natural clot-dissolving process). This promotes thrombosis and creates a dual threat—both plaque formation and increased blood clotting tendency.
Genetic studies have established Lp(a) as a causal risk factor for coronary heart disease, not merely an association. Variants in the LPA gene that result in elevated Lp(a) levels have been consistently linked to increased cardiovascular risk, independent of other risk factors.
Research shows that elevated Lp(a) increases cardiovascular risk even in individuals with low LDL cholesterol, highlighting its independent contribution to heart disease. The risk appears to be continuous with increasing Lp(a) concentrations, without a clear threshold below which it becomes irrelevant.
Lp(a) plays a particularly damaging role through oxidized phospholipids that it carries. These oxidized lipids trigger endothelial inflammation, promote monocyte activation and recruitment to vessel walls, and enhance foam cell formation—all critical processes in atherosclerosis development.
Beyond coronary arteries, Lp(a) contributes to multiple atherosclerotic diseases. Mendelian randomization studies have shown that genetically lower Lp(a) levels are associated with reduced risk of coronary heart disease, peripheral vascular disease, stroke, and heart failure, confirming its broad impact on cardiovascular health.
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Is Lp(a) bad?
Lp(a) isn’t inherently “bad” from an evolutionary perspective—it likely served important biological functions during human evolution, including wound healing, tissue repair, and infection defense through its ability to promote clotting and deliver cholesterol for cell membrane repair.
However, in modern contexts with longer lifespans, elevated Lp(a) levels—generally considered to be above 50 mg/dL or 125 nmol/L—are consistently associated with increased cardiovascular risk. The relationship appears dose-dependent, with higher levels corresponding to greater risk of atherosclerotic cardiovascular disease and aortic valve stenosis.
The risk of elevated Lp(a) is particularly notable when it occurs concurrently with other risk factors, such as elevated LDL cholesterol. In the Framingham Heart Study, individuals with both high Lp(a) and high LDL-C had a 43% increased risk of cardiovascular disease compared to those with high LDL-C alone.
Interestingly, very low Lp(a) levels may have their own drawbacks. Some research indicates that extremely low Lp(a) concentrations might be associated with an increased risk of type 2 diabetes, though this risk is generally considered minor compared to the cardiovascular benefits of lower Lp(a).
From a clinical perspective, Lp(a) is now recognized as an independent, genetic, and causal factor for cardiovascular disease, with substantial evidence supporting its pathogenic role. Current guidelines increasingly recommend measuring Lp(a) at least once in adulthood to identify individuals who may benefit from more aggressive management of other risk factors.
Why does the body produce Lp(a)?
The exact evolutionary purpose of Lp(a) isn’t fully understood, but research suggests it likely played beneficial roles in wound healing and tissue repair by promoting blood clotting and delivering cholesterol for cell membrane repair. This would have provided survival advantages to our ancestors when facing injuries and infections.
Lp(a) contains apolipoprotein(a), which has structural similarities to plasminogen but functions differently, potentially providing balance to the clotting system by inhibiting excessive fibrinolysis. This property would have been particularly valuable in an era before modern medicine when uncontrolled bleeding posed a significant survival threat.
The binding of oxidized phospholipids to Lp(a) suggests it may serve as a scavenger for pro-inflammatory molecules, potentially acting as part of the innate immune response to clear damaged cell membranes and pathogen-associated molecular patterns from circulation. These protective mechanisms would have been advantageous despite their contribution to atherosclerosis in modern times with longer lifespans.
Scientists have also proposed that Lp(a) may have evolved as a compensatory response to promote tissue healing following vascular injury. Its ability to transport lipids to damaged tissues could facilitate repair processes, while its pro-inflammatory and pro-thrombotic properties would help contain infections—functions that were more beneficial in shorter-lived populations with different environmental pressures than today.
Recent research has discovered that Lp(a) interacts with other proteins like autotaxin, suggesting additional biological roles beyond what we currently understand. These complex interactions indicate that Lp(a) likely serves multiple physiological functions that were evolutionarily advantageous, even as they contribute to cardiovascular disease in contemporary settings.
What medications lower Lp(a)?
Currently, there are no FDA-approved medications specifically designed to lower Lp(a) levels. Traditional cholesterol-lowering drugs like statins have minimal to no effect on Lp(a) concentrations and may actually increase Lp(a) in some patients, making them ineffective for this specific target.
PCSK9 inhibitors such as alirocumab and evolocumab have demonstrated modest Lp(a)-lowering effects, reducing levels by approximately 20-30%. In a post-hoc analysis of the ODYSSEY OUTCOMES trial, alirocumab’s Lp(a)-lowering effect contributed to cardiovascular benefit independently of its LDL-cholesterol reduction. However, these medications are not specifically approved for Lp(a) reduction.
The most promising emerging therapies are RNA-targeted treatments, particularly antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs). Olpasiran, an siRNA therapeutic targeting LPA mRNA, has demonstrated impressive Lp(a) reductions of 71-97% in early clinical trials. These targeted approaches address Lp(a) production directly at the genetic level.
Another advanced RNA therapeutic is pelacarsen (formerly AKCEA-APO(a)-LRx), an antisense oligonucleotide that has shown Lp(a) reductions of up to 80% in Phase 2 trials of patients with established cardiovascular disease. This hepatocyte-directed therapy directly suppresses apo(a) synthesis and has demonstrated a favorable safety profile.
Other emerging approaches include more potent Lp(a)-lowering medications like SLN360 and LY3819469, additional RNA-based therapies in earlier stages of development. Early results suggest these treatments may achieve Lp(a) reductions of up to 98%, representing a potentially transformative advance for patients with elevated Lp(a). These medications are currently undergoing clinical trials to confirm both their efficacy and safety.
Can statins raise Lp(a)?
Yes, statins can raise Lp(a) levels, an effect that has been documented across different types of statins (a class effect), though the magnitude varies significantly between individuals. This paradoxical increase occurs despite statins’ effectiveness in lowering LDL cholesterol and is often under-discussed in clinical practice since Lp(a) isn’t routinely measured.
Research suggests that statins may increase Lp(a) levels through enhanced hepatic production of apolipoprotein(a), as demonstrated by higher LPA mRNA levels in cell cultures exposed to statins. This effect creates a concerning situation where a medication that reduces overall cardiovascular risk through LDL-C reduction might simultaneously increase Lp(a)-associated risk in certain patients.
This statin-induced Lp(a) elevation appears to have particular clinical significance in patients who already have elevated baseline Lp(a) levels. For these individuals, the increase in Lp(a) may partially offset the cardiovascular benefits gained from LDL-C reduction, creating a mixed risk profile that requires careful consideration.
The Lp(a)-raising effect represents a notable difference between statins and newer lipid-lowering therapies like PCSK9 inhibitors, which generally reduce both LDL and Lp(a) levels. This differential effect may be particularly relevant for patients with genetic predisposition to high Lp(a), where statin-induced increases could potentially exacerbate their already elevated cardiovascular risk.
For patients with known elevated Lp(a) or significant cardiovascular risk factors, the latest clinical guidelines recommend monitoring Lp(a) levels before and after starting statin therapy to fully understand their complete cardiovascular risk profile and potentially guide decisions about supplementary therapeutic approaches.
If statins make my ApoB go down but my Lp(a) go up, how does my risk profile change?
A decrease in ApoB with an increase in Lp(a) creates a mixed risk picture that requires careful evaluation. The reduced ApoB generally lowers overall cardiovascular risk since ApoB-containing particles (especially LDL) are primary drivers of atherosclerosis. However, the increase in Lp(a) adds risk through both plaque formation and blood clotting mechanisms, potentially offsetting some of the benefit.
The net effect on your cardiovascular risk would depend on the magnitude of these opposing changes. If ApoB decreases substantially while Lp(a) increases only moderately, you would likely still experience a net reduction in risk. This is because statins’ LDL-lowering effects have been consistently shown to reduce cardiovascular events, even when Lp(a) increases.
Research indicates that even with elevated Lp(a), patients with well-controlled LDL-C levels experience better outcomes than those with both high LDL-C and high Lp(a). However, the benefits may not be as pronounced as in patients without elevated Lp(a), particularly in cases where Lp(a) increases are substantial.
For patients experiencing this mixed lipid response, newer treatment approaches may be worth considering. PCSK9 inhibitors have demonstrated the ability to lower both LDL-C and Lp(a), potentially providing a more comprehensive risk reduction than statins alone in patients with elevated Lp(a).
Current clinical guidelines suggest that even with statin therapy, patients with elevated Lp(a) remain at residual cardiovascular risk and may benefit from more aggressive management of other modifiable risk factors. This includes optimizing blood pressure, achieving ideal glycemic control, implementing lifestyle modifications, and potentially adding non-statin therapies when appropriate.
How do I ask for an Lp(a) test?
You can ask your healthcare provider to add Lp(a) to your next blood work by directly requesting the test with a simple statement like “I’d like to know my Lp(a) level given my interest in cardiovascular health” or “Could we check my Lp(a) level as part of my lipid panel?” Be aware that some insurance companies may not cover this test routinely, so you might want to inquire about potential costs.
The test is particularly relevant if you have a family history of early heart disease, especially heart attacks or strokes occurring before age 55 in men or before age 65 in women among your close relatives. Other indications include personal history of premature cardiovascular events, high cholesterol, or cardiovascular events despite normal cholesterol levels.
Current clinical guidelines from organizations like the National Lipid Association recommend measuring Lp(a) at least once in all adults to identify those with elevated levels who may benefit from more aggressive risk factor management. When discussing with your doctor, you can reference these guidelines as support for your request.
Since Lp(a) levels are genetically determined and remain relatively stable throughout life, you typically only need to test it once unless you’re monitoring changes due to medication or participating in clinical trials of Lp(a)-lowering therapies. This one-time testing makes it a cost-effective addition to your cardiovascular risk assessment.
If your doctor is unfamiliar with Lp(a) testing or hesitant to order it, you might consider seeking a consultation with a preventive cardiologist or lipid specialist who would be more familiar with advanced cardiovascular risk markers. Alternatively, direct-to-consumer testing is available through some commercial laboratories if you’re willing to pay out-of-pocket.
What other tests should I consider getting when I get an Lp(a) test?
A comprehensive cardiovascular risk assessment alongside Lp(a) typically includes a complete lipid panel (total cholesterol, LDL, HDL, triglycerides), along with ApoB measurement which counts all atherogenic particles. These tests provide a more complete picture of your lipid-related risk than any single marker alone.
Measuring inflammatory markers such as high-sensitivity C-reactive protein (hsCRP) can complement your Lp(a) assessment. This is particularly important because Lp(a) promotes vascular inflammation via oxidized phospholipids, and the combination of elevated Lp(a) and inflammation may indicate higher cardiovascular risk.
When assessing both Lp(a) and family history—two independent risk factors—additional tests for traditional risk factors like fasting glucose or HbA1c (for diabetes risk), blood pressure measurement, and assessment of smoking status and body mass index are essential. The combination of these factors with Lp(a) provides a more complete picture of your overall cardiovascular risk.
For patients with elevated Lp(a), especially those with family history of premature cardiovascular disease, imaging tests like coronary artery calcium scoring or CT angiography may be appropriate to assess for subclinical atherosclerosis. These can help determine whether the elevated Lp(a) has already contributed to arterial plaque formation.
The latest clinical guidelines recommend comprehensive risk assessment for patients with elevated Lp(a), including evaluation for additional genetic risk factors in specific cases, particularly for patients with extremely high Lp(a) levels or strong family history of premature cardiovascular disease.
What’s it like to get an Lp(a) test?
Getting an Lp(a) test is just like any routine blood test – a healthcare professional draws blood from a vein in your arm using a needle, which takes just a few minutes. You might feel a brief pinch when the needle goes in, and there could be slight bruising afterward.
Most people don’t need to fast before an Lp(a) test since the level is genetically determined and doesn’t fluctuate significantly with food intake, unlike other lipid tests. However, your doctor might request fasting if they’re doing other blood tests at the same time.
Where are Lp(a) tests available, and how much do they cost?
Lp(a) tests are available through most major medical laboratories in the United States, including Quest Diagnostics which offers the test for $45.00 plus a $6.00 physician service fee. This test measures blood levels of lipoprotein(a) to help assess cardiovascular risk, particularly in individuals with a personal or family history of premature cardiovascular disease.
Another major provider, Labcorp, offers the Lp(a) test through their OnDemand service for $49, which can be purchased directly without a prescription. Both Quest and Labcorp accept payment through Health Savings Accounts (HSA) and Flexible Spending Accounts (FSA), though standard insurance typically doesn’t cover these direct-to-consumer tests.
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Conclusion
Understanding Lp(a) represents an important frontier in cardiovascular risk assessment and personalized medicine. While elevated Lp(a) levels present a significant risk factor for heart disease and related conditions, awareness of your status through testing—widely available at major laboratories for approximately $45-50—provides valuable information for proactive health management. Though current treatment options remain limited, with conventional statins potentially increasing rather than decreasing Lp(a) levels, promising RNA-targeted therapies under development may soon offer effective interventions for those with elevated levels. Until then, comprehensive risk factor management and regular consultation with healthcare providers represent the best approaches for individuals with high Lp(a). As medical understanding evolves, Lp(a) testing and management will likely become increasingly central to cardiovascular preventive care.