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The discussion delves into the impact of blood lipids, particularly APOB, on cardiovascular risk. The conversation between Dr. Cromwell and Dave Feldman explores the complexities of blood lipid levels and their association with cardiovascular disease risk. Dr. Cromwell, a lipidologist, emphasizes the significance of APOB-containing lipoproteins in atherosclerosis development. Dave, a citizen scientist, shares his experience with elevated LDL cholesterol on a ketogenic diet, sparking a debate on whether high LDL levels pose a risk in the context of optimal metabolic health.
The conversation transitions to discussing the lipid energy model and atherosclerotic pathways. Dr. Cromwell and Dave elaborate on the mechanisms behind APOB-containing lipoproteins' role in atherosclerosis progression. They explore how macrophages, foam cells, and the transcytosis process contribute to plaque formation and inflammation within the artery walls. The dialogue sheds light on the intricate processes involved in lipid metabolism and atherosclerosis development.
Further, the discussion touches on immune responses and their influence on mortality outcomes. The participants examine the importance of immune system modulation on cardiovascular and all-cause mortality. Dr. Cromwell highlights how factors like metabolic vulnerability and inflammation play a critical role in determining mortality risks beyond just APOB-related considerations. The conversation delves into the complexities of mortality predictors and the multifaceted influences on overall health outcomes.
An exploration of the long-term effects of LDL reduction on all-cause mortality is presented. The dialogue scrutinizes the impact of lifelong, low APOB levels on mortality outcomes, especially when considering factors like metabolic health and inflammation. The participants deliberate on whether sustained LDL reduction leads to improved longevity and lower all-cause mortality rates. The conversation navigates through the intricacies of utilizing APOB data to predict mortality risks and the broader implications of lipid management on overall health and longevity.
Lean mass hypersponders, individuals with high LDL cholesterol due to metabolic adaptation to a low-carb diet, present a unique challenge in assessing cardiovascular risk. Studies suggest that these individuals may have a lower incidence of atherosclerosis even with high LDL levels. However, the long-term impact of persistently elevated LDL on plaque formation and cardiovascular events remains uncertain. Examining genetic markers like PCSK9 loss of function and metabolic vulnerability through non-invasive imaging may clarify the risk profile of lean mass hypersponders.
Metabolic health plays a crucial role in the relationship between lipid levels and cardiovascular risk. Even in cases where individuals exhibit high LDL cholesterol, addressing metabolic health through dietary adjustments can help lower LDL levels and potentially mitigate cardiovascular risk. Understanding the cumulative exposure of high LDL over time is essential in assessing the progression of atherosclerosis and the risk of cardiovascular events.
Managing cardiovascular risk in individuals with elevated LDL cholesterol involves a nuanced approach. While genetic factors like PCSK9 deficiency may offer insights into atherosclerosis risk, lifestyle modifications such as dietary changes and lipid-lowering medications may be necessary to reduce long-term cardiovascular risk. Incorporating non-invasive imaging techniques and genetic markers can provide valuable information on plaque progression and individualized risk assessment.
In cases where lifestyle interventions may not sufficiently lower LDL levels, statins could be considered to manage cardiovascular risk effectively. Considering the safety and efficacy of statins based on real-world data and patient outcomes is crucial in determining the appropriate treatment strategy for individuals with persistently high LDL cholesterol. Collaborating with statin safety task forces and lipid associations can guide clinicians in optimizing treatment plans for cardiovascular risk management.
Assessing the frequency of adverse effects associated with medications, such as statins, is crucial. Understanding the context of adverse signals in large exposure populations can help mitigate risks and make informed decisions about treatment.
The intensity and dosage of statins play a significant role in determining the occurrence of adverse events. Moderate intensity statins used at appropriate dosages show low incidents of side effects compared to high intensity statins, which may lead to more adverse signals.
Statin therapy guidelines emphasize selective use based on specific criteria such as atherosclerotic cardiovascular disease, high LDL cholesterol levels, and validated risk factors. Evaluating individual risk profiles and enhancing factors are important considerations before initiating statin therapy.
Balancing the risks and benefits of statin therapy is crucial, especially for individuals with concerns about adverse effects. Understanding the probability of side effects and the potential benefits of treatment helps in making informed decisions and personalized approaches to statin usage.
Some people follow a ketogenic diet seeking to lose weight, feel more energised, or gain control over their eating habits. Others may turn to this diet in an effort to treat conditions such as epilepsy, bipolar disorder, diabetes and inflammatory diseases. Regardless of their reasoning for adopting this eating pattern, a key question remains: is there ever an instance where having high LDL cholesterol levels on a ketogenic diet can be safe? In Episode #311, I’m joined by Dr William Cromwell, MD and Dave Feldman to explore this question.
In this discussion, Dr William Cromwell and Dave Feldman share their professional opinions on whether high cholesterol on a keto diet is a problem. We investigate where their opinions align and where they differ, where Dave’s hypotheses diverge from the norm, and what we do and don’t know with the available evidence. We also explore the significance of ApoB, lifespan and healthspan considerations, research Dave is currently conducting, and much more.
Specifically, we discuss:
Connect with Dr William Cromwell: Twitter/X, LinkedIn, and https://www.mylipid.com/. Discover more of his work with Precision Health Reports: Twitter/X, LinkedIn, Facebook, Instagram, and at https://precisionhealthreports.com/.
Connect with Dave Feldman: Twitter/X, YouTube, and Instagram, and discover more of his work at https://citizensciencefoundation.org/, https://ownyourlabs.com/, and https://cholesterolcode.com/.
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