Podcast Summary
Understanding LP Little A: A Distinct Lipoprotein Associated with Cardiovascular Disease: LP Little A is a unique lipoprotein linked to an elevated risk of cardiovascular disease. Recent research explores its structure, function, and potential treatments, including apheresis.
LP Little A, or Lipoprotein(a), is a topic of great interest to many listeners based on a recent poll conducted by the Peter Attia Drive podcast. LP Little A is a type of lipoprotein, which is a type of particle that transports cholesterol and other lipids in the blood. Bob Kaplan interviewed Peter Attia about LP Little A, discussing what it is, why it's important, and potential treatment options. LP Little A is distinct from other lipoproteins, such as LDL and HDL, and is associated with an increased risk of cardiovascular disease. The discussion delved into the structure and function of LP Little A, as well as the latest research on its role in health and disease. The podcast also covered potential treatments, including apheresis, which is a procedure that removes LP Little A from the blood. Overall, the interview provided valuable insights into this complex topic and addressed common questions from listeners. If you're interested in learning more about LP Little A, be sure to check out the show notes for additional resources and references.
Understanding Cholesterol and Lipoproteins: Cholesterol is essential for the body but requires lipoproteins for transportation. HDL is beneficial, while LDL, the primary atherosclerosis culprit, is misunderstood due to its name.
Cholesterol is an essential molecule for the body, and it cannot move freely in the bloodstream due to its hydrophobic nature. To transport cholesterol, it needs to be packaged in lipoproteins, the two most common being high-density lipoprotein (HDL) and low-density lipoprotein (LDL). While HDL is beneficial and not atherogenic, LDL, which is denser and has a longer residence time in the bloodstream, is considered the primary culprit in atherosclerosis. When interpreting cholesterol blood tests, it's essential to understand that the numbers represent the cholesterol concentration within the particles. Total cholesterol is the sum of cholesterol in all particles, while LDL cholesterol specifically refers to the cholesterol contained within LDL particles. The number of LDL particles, or LDL-P, is a more accurate predictor of atherosclerotic risk. Cholesterol is crucial for cellular membranes and the production of hormones. Despite its importance, it's often misunderstood and labeled as "bad." In reality, LDL, which carries cholesterol, is a necessary component for the body. The misconception arises because people don't realize that LDL stands for low-density lipoprotein, and its name refers to its density in a specific assay. Understanding the role of cholesterol, lipoproteins, and their respective densities is crucial for appreciating their significance in maintaining overall health.
LP(a)'s role in atherosclerosis: LP(a)'s presence, characterized by apolipoprotein(a), contributes to heart disease even in individuals with normal cholesterol levels.
While the size of LDL particles may not significantly impact their entry into the subintimal space between endothelial cells, retention and oxidation leading to inflammation are the primary causes of atherosclerosis. LP(a), a lesser-known lipoprotein, has recently gained attention due to its potential role in heart disease. Perilously high levels of LP(a) have been linked to heart attacks, even in individuals with seemingly healthy cholesterol levels. LP(a) is characterized by an additional protein called apolipoprotein(a) attached to its outer surface via a strong disulfide bond. The prevalence of elevated LP(a) levels is significant, affecting a substantial portion of the population, and its impact on heart health is an area of ongoing research. Understanding the role of LP(a) and its relationship to atherosclerosis could lead to new prevention and treatment strategies for cardiovascular diseases.
ApoA and plasminogen share similar cringle domains: The mass of ApoLittle A is determined by the number of repeating segments in its cringle domain 2, and the presence of ApoA bound to ApoLittle A on LDL particles may be more important than the mass of the LDL particles.
The protein Apo A, found in the lipoprotein ApoLittle A, shares structural similarities with the protein plasminogen due to their common cringle domains, specifically Kringle 4 and 5. The variation in the number of repeating segments in the cringle domain 2 of ApoA determines the mass of ApoLittle A. The resemblance between ApoA and plasminogen, particularly in the cringle domains, is significant, and the number of LDL particles carrying the ApoA covalently bound to ApoLittle A may be more crucial than the mass of the LDL particles themselves. Each LDL particle contains one ApoB, while an ApoA is associated with an ApoLittle A, not every LDL having an ApoA. The number of ApoLittle A particles bound to LDL particles through the Apob bond varies among individuals, and further research could explore the relationship between ApoA and ApoE variants and their impact on the presence and quantity of ApoLittle A.
Measuring LP little A: Mass vs. Particle Number: LP little A mass measures the total particle content, including apolipoprotein and other components, while LP little A particle number provides a more accurate count of individual particles. Both tests have limitations and should be used together for comprehensive risk assessment.
While measuring LP (lipoprotein) little A mass is common, it's not the most informative test. LP little A is a type of lipoprotein with apolipoprotein A attached to it. The difference between LP little a mass, LP little a cholesterol, and LP little a particle content lies in how they are measured. LP little A mass is the most ubiquitous test but it measures the total mass of the entire particle, including apolipoprotein A, apolipoprotein B, phospholipids, cholesterol, and triglycerides. However, two people with the same LP little A mass can have different numbers of particles due to varying lengths of the cringle domains, which determine the proportion of apolipoprotein A in the particle. Therefore, a low LP little A mass does not necessarily mean a high particle number, and vice versa. LP little A particle number, which is the counting of particles, is a more accurate measure but is less commonly used. It's important to note that both tests have limitations and should be considered in conjunction with other factors when evaluating cardiovascular risk.
Measuring LP(a) cholesterol vs LP(a) particle number: LP(a) particle number is the preferred method for evaluating LP(a) levels and cardiovascular risk, as the test for LP(a) cholesterol is not as accurate or widely used, and LP(a) particle size and molecular weight vary, making it difficult to compare between individuals.
While measuring LP(a) cholesterol can provide some information about cardiovascular risk, it is not as straightforward or reliable as measuring LDL particle number. LP(a) particles carry cholesterol, similar to LDL particles, but the test for LP(a) cholesterol is not as accurate or widely used as the test for LDL particle number. The molecular weight of LP(a) particles is not consistent due to the variability of its components, making it difficult to calculate and compare between individuals. The best available test for assessing LP(a) levels is the LP(a) particle number. A high LP(a) particle number indicates a higher risk for cardiovascular disease. Additionally, there is a proxy for LP(a) particle number, which is measuring the amount of oxidized phospholipids normalized for APO-B, providing almost a one-to-one mapping. APO-A, a component of LP(a) particles, has a high concentration of lysine, making it an effective scavenger of oxidized moieties, while APO-B does not. Therefore, measuring LP(a) particle number is the preferred method for evaluating LP(a) levels and cardiovascular risk.
LP(a) particles and cardiovascular disease: LP(a) particles, with unique cringle domains and oxidized phospholipid tails, are linked to cardiovascular disease. Elevated levels may indicate a genetic component, but their exact role is not yet clear.
LP(a) particles, which can be visualized through imaging techniques, have unique properties that may contribute to cardiovascular disease. These particles have cringle domains and tails that can be filled with oxidized phospholipids, which can be measured as a proxy for disease severity. Some individuals may have elevated LP(a) levels despite seemingly normal risk factors, suggesting a genetic component. The function of LP(a) is not yet fully understood, but it may have provided evolutionary benefits related to blood clotting. Further research is needed to understand the specific mechanisms by which LP(a) contributes to cardiovascular disease and how it differs between individuals.
Childbirth trauma could benefit from LP-little A particles, but may also increase aortic stenosis risk: Childbirth trauma may produce LP-little A particles that act as antioxidants, but their accumulation in the subendothelial space can lead to aortic stenosis, a condition causing heart failure. Regular screening for aortic stenosis is essential for those with elevated LP-little A levels.
Having experienced trauma during childbirth, such as bleeding requiring blood clotting products, could potentially provide a benefit due to the production of LP-little A particles. These particles can act as antioxidants, scavenging harmful substances in the body and transporting them to the liver for clearance. However, in today's higher inflammatory environment, these particles may accumulate in the subendothelial space and contribute to atherosclerosis, aortic stenosis, and enhanced venous thrombosis. Aortic stenosis, a condition where the aortic valve becomes calcified and narrowed, is a significant concern as it can lead to heart failure. Elevated LP-little A levels have been linked to about two-thirds of aortic stenosis cases. Regular screening for aortic stenosis is crucial for individuals with elevated LP-little A levels, regardless of age.
Monitoring and managing LP little a particles: Elevated LP little a levels increase risks for atherosclerosis and thromboembolic events, particularly for aortic stenosis and venous thromboembolism. Strategies like DVT prophylaxis, deep vein thrombosis prevention, and specific measures for long flights may help reduce risks.
LP (lipoprotein) little a particles, which can indicate an increased risk for atherosclerosis and thromboembolic events, require close monitoring and management. Although the exact cause-and-effect relationship is not yet definitively proven, the evidence suggests that these particles may enter the subintimal space more easily, be retained, and trigger inflammation and a pro-thrombotic response. While there is ongoing research, it is essential to consider the elevated risks associated with LP little a, particularly for aortic stenosis (hazard ratios ranging from 2 to 4.5) and venous thromboembolism (approximately 3x the risk). Although aspirin was once thought to be a simple solution, it may not be effective for everyone. Instead, strategies like DVT prophylaxis, deep vein thrombosis prevention, and specific measures for long flights may be recommended for those with elevated LP little a levels. Ultimately, ongoing research and clinical trials will provide more definitive answers about the role of LP little a in atherosclerosis and thromboembolic events.
Atherosclerosis: The Most Concerning Cardiovascular Risk with LP(a): Atherosclerosis, affecting over a third of the population, carries a significant 1.6 hazard ratio for cardiovascular conditions, making it the most concerning risk associated with LP(a). Apheresis, a treatment for LP(a), requires frequent sessions due to its short half-life.
While hazard ratios for various cardiovascular conditions, such as aortic stenosis, venous thromboembolism, and atherosclerosis, can be significant, the most concerning risk lies in atherosclerosis due to its high prevalence. Atherosclerosis carries a 1.6 hazard ratio, and even a 60% increase in risk on something that affects a third of the population is a major concern. The discussion also touched upon the prevalence and determination of elevated LP(a), which is based on mass levels, with normal levels defined as less than 30 milligrams per deciliter in the US and less than 50 milligrams per deciliter in Europe. Apheresis, a treatment that separates plasma, can be used to remove LP(a), but the frequency required for this treatment is significant due to the short half-life of these particles. Overall, it's crucial for healthcare professionals, particularly those in primary care, to understand the implications of LP(a) and atherosclerosis to effectively help patients manage their cardiovascular risks.
Treatment Options for High Lipoprotein(a): Niacin and apheresis have been used for LP(a) reduction, but their frequent use and side effects make them less desirable. PCSK9 inhibitors, a newer treatment, directly block PCSK9 to increase LDL receptors and reduce LP(a) levels.
While apheresis is a potential treatment for patients with high levels of lipoprotein(a) (LP(a)), it's an invasive and frequent process. Niacin, a historical treatment for lowering LP(a), is a contentious topic in the lipidology community due to its inconsistent benefits and potential side effects. Niacin works by lowering LDL, raising HDL, and decreasing LP(a) levels, but its effectiveness in saving lives is debated. Statins, commonly used cholesterol-lowering drugs, do not effectively lower LP(a) levels. More recently, PCSK9 inhibitors have emerged as a promising treatment option for LP(a) reduction. Statins work by inhibiting the HMG-CoA reductase enzyme, leading to increased LDL receptors on the liver surface for clearance of LDL particles. However, statins also produce more PCSK9, which degrades LDL receptors, resulting in a net enhanced clearance of LDL particles but no effect on LP(a) levels. PCSK9 inhibitors directly block PCSK9, leading to increased LDL receptor activity and subsequent LP(a) reduction. With the availability of PCSK9 inhibitors, apheresis and niacin may become less frequently used treatments for LP(a) management.
Managing Lipoprotein(a) Levels: A Complex Issue: Despite ongoing research, managing Lipoprotein(a) or LP(a) levels remains complex due to its clearance by various receptors, the debated effects of statins, and the need for additional treatments based on individual risk factors.
When it comes to managing lipid levels, particularly the controversial Lipoprotein(a) or LP(a), the current understanding is far from clear-cut. LP(a) is known to be cleared by various receptors, including LDL and VLDL receptors, but it's the last in line. Tom Dayspring explained that increasing LDL receptor expression or inhibiting PCSK9 could potentially help clear LP(a), as shown in a recent paper. However, PCSK9 inhibitors are not FDA-approved for this purpose. Moreover, the effects of statins on LP(a) levels are still a subject of debate. Some studies suggest that LP(a) levels may even increase on statins due to a decrease in APOB, making it seem like the denominator is being lowered. However, statins are primarily prescribed to lower LDL levels, not LP(a), and patients with elevated LP(a) may require additional treatments, such as statins, to reach optimal LDL targets. The exact approach depends on various factors, including family history, insulin resistance, and other risk factors. In summary, managing LP(a) levels remains a complex issue, and ongoing research is needed to better understand its role in cardiovascular disease and effective treatment strategies.
Hormone replacement therapy reduces LP(a) levels: Hormone replacement therapy, specifically estrogen, can lower LP(a) levels by up to 50%. However, the clinical role for hormone replacement therapy in cardiovascular disease risk reduction is uncertain.
While statins are effective in reducing LDL cholesterol levels, they may not significantly impact LP(a) levels. LP(a) is a subtype of LDL cholesterol that is linked to increased cardiovascular risk. However, hormone replacement therapy, specifically estrogen, has been shown to lower LP(a) levels by up to 50 percent. This effect may be mitigated by concomitant progesterone therapy. However, the clinical role for hormone replacement therapy in cardiovascular disease risk reduction is uncertain and not recommended. A new class of drugs called antisense oligonucleotides (ASOs) is currently being studied as they directly target and disrupt the synthesis of apo(a), the protein component of LP(a), offering a potential solution for lowering LP(a) levels. These drugs have completed phase one and phase two trials and are slowly enrolling in phase three trials. While these findings suggest that LP(a) may be an important risk factor for cardiovascular disease, the true risk and the best approach to mitigate it are still not definitively known.
Lipoprotein markers: Some influenced by lifestyle, others not: LP(a) production is mainly determined by the body, while triglycerides and LDL particles can be influenced by diet. Diet affects cholesterol synthesis and absorption, but the relationship between diet and LDL-P is less clear.
While some lipoprotein markers like triglycerides can be significantly influenced by lifestyle interventions such as diet, others like LP(a) seem less responsive. The production of LP(a) is mainly determined by how much the body makes, while clearance plays a secondary role. In contrast, triglycerides and LDL particles can be substantially affected by diet, which in turn influences cholesterol synthesis and absorption. Although the relationship between diet and LDL-P is less clear, some people may experience increased cholesterol synthesis when consuming high amounts of saturated fat. The impact of this on overall health is still a topic of debate.
Saturated fat vs monounsaturated fats on keto diet: Observing lipid profile changes on keto? Adjust saturated fat intake, increase monounsaturated fats for better processing and heart health.
While some people may experience changes in their lipid profiles when on a ketogenic diet, reducing saturated fat intake and increasing monounsaturated fats can help resolve the issue. The speaker's observation from numerous cases suggests that individuals may be consuming more saturated fat than they can process, leading to increased cholesterol synthesis and LDL cholesterol levels. However, it's essential to note that not all individuals react the same way to dietary changes, and some may have underlying inflammatory issues that contribute to their lipid profiles. The speaker emphasizes the importance of considering individual cases and monitoring markers like oxidized LDL and CRP to better understand the underlying causes. Ultimately, the goal is to identify the specific dietary components contributing to adverse effects and make adjustments accordingly to maintain heart health while adhering to a ketogenic diet.
LP little A's role in inflammation and cardiovascular disease: LP little A is linked to inflammation and cardiovascular disease, with very low levels potentially doubling the risk. Oxidized LDL and LP little A are related but distinct markers, and elevated levels of both, along with other markers, indicate local inflammation.
LP little A, or lipoprotein-associated phospholipase A2, plays a significant role in inflammation and cardiovascular disease. Oxidized LDL, or oxidized low-density lipoprotein, and LP little A are related but distinct markers. Elevated levels of LP little A, oxidized phospholipids, and other markers like fibrinogen, C-reactive protein, and homocysteine can indicate local inflammation. The hazard ratios from a 2007 study suggest that very low levels of LP little A may double the risk of cardiovascular disease. As we delve deeper into this topic, we uncover more complexities and unknowns, highlighting the importance of continuous learning. Despite the vast amount of information available, our current understanding is still in its infancy. The more we learn, the more we realize how much we don't know, a phenomenon known as the Dunning-Kruger effect. It's crucial for healthcare professionals to stay informed about the latest research and developments in this field to provide the best possible care for their patients.
Check your LP-PLA2 level for potential atherosclerotic disease risk: Patients should demand their healthcare providers check LP-PLA2 levels, especially with a family history. Physicians should learn more about LP-PLA2's significance in diagnosing and preventing cardiovascular diseases. An ICD-10 code exists for elevated LP-PLA2.
As a patient, it's essential to demand that your healthcare provider checks your LP-PLA2 (lipoprotein-associated phospholipase A2) level, especially if you have a family history of atherosclerotic disease. This is a non-negotiable requirement. For physicians, this discussion should encourage you to learn more about LP-PLA2 and its potential significance in diagnosing and preventing cardiovascular diseases. An ICD-10 code for elevated LP-PLA2 has recently been issued, indicating that this is not a niche issue. For those not directly involved, this podcast might not be relevant. More information, including links and resources, can be found on Peter Atia, MD's website. To stay updated on his research and insights, sign up for his weekly email newsletter. Connect with him on social media, particularly Twitter, to ask questions and engage in discussions. This podcast is for informational purposes only and does not constitute medical advice. Always consult your healthcare professional for medical concerns. Peter Atia discloses his conflicts of interest on his website.
