“The 4/4 was really viewed as, 'Boy, you're guaranteed to have an MI before 60.' And I think the evidence today suggests that once you normalize and correct for LDL particle number or ApoB, it stops mattering.”
Main Takeaways:
- Historically, ApoE 4/4 genotype was linked to a high risk of myocardial infarction by age 60.
- Current evidence suggests managing LDL particle number or ApoB can mitigate this risk.
Notes: Discussion on changing perspectives on ApoE 4/4 genotype
Tone: Reassuring
Relevance: 5/5
“Think of the litany of drugs we have for controlling hypertension and think about the litany of drugs we have to bring down ApoB.”
Main Takeaways:
- There are numerous medications available to manage hypertension and lower ApoB levels.
- Pharmacological interventions play a crucial role in controlling risk factors for cardiac disease.
- Continued pharmaceutical development is vital for disease management.
Notes: Discussion on the role of medications in disease prevention
Tone: Informative
Relevance: 4/5
“cholesterol is contained within the low density lipoproteins a better way to predict risk is to add up the concentration of all the apob particles so that number apob measured in milligrams per deciliter is the concentration of the entire burden of particles that are capable of undergoing the initiation and progression of atherosclerosis.”
Main Takeaways:
- ApoB measurement may provide a more accurate risk assessment for atherosclerosis than traditional LDL cholesterol levels.
- ApoB represents the total burden of atherogenic particles in the blood.
Notes: Discussion on cholesterol and cardiovascular risk.
Tone: Informative
Relevance: 5/5
“it can have to do with triglyceride burden so this is where insulin resistance really factors in to how apoB can go up”
Main Takeaways:
- Triglyceride levels are linked to insulin resistance.
- Insulin resistance can increase apoB levels, impacting metabolic health.
Notes: Discussing the impact of insulin resistance on lipid metabolism.
Tone: Analytical
Relevance: 4/5
“eliminate smoking and so similarly it makes no sense that we would look at a causal driver of asbd in the case of apob and kind of take an approach of well being at the 20th percentile or the 30th percentile the 40th percentile is acceptable none of those things really make sense you have something that is causing the disease you should eliminate it as soon as possible because it is an area under the curve problem.”
Main Takeaways:
- Smoking is a significant risk factor for diseases and should be eliminated.
- ApoB is identified as a causal driver of atherosclerotic cardiovascular disease (ASBD).
- The speaker advocates for the elimination of disease-causing factors rather than managing them at acceptable levels.
Notes: Discussion on disease prevention strategies
Tone: Cautious
Relevance: 5/5
“one of the biggest drivers of it in addition to things like high blood pressure and smoking and insulin resistance is apop so to be able to take that off the table sooner rather than later is going to has has C certain has the potential to take um atherosclerosis off its pedestal at the top of the uh list of killing.”
Main Takeaways:
- High blood pressure, smoking, and insulin resistance are major drivers of atherosclerosis.
- ApoB is also a significant factor in the development of atherosclerosis.
- Addressing these factors early can potentially reduce the impact of atherosclerosis.
Notes: Discussion on factors contributing to atherosclerosis
Tone: Cautious
Relevance: 5/5
“if you had an apob level below about 30 mg per deciliter, it wouldn't be possible to develop atherosclerosis.”
Main Takeaways:
- Low levels of apob are associated with a reduced risk of atherosclerosis.
- Peter Libby, an authority on the topic, supports this view.
Notes: Discussion on optimal apob levels for preventing atherosclerosis
Tone: Informative
Relevance: 5/5
“there are really four big things that are driving risk causally: apob, insulin resistance, hypertension, and smoking.”
Main Takeaways:
- Four major risk factors for cardiovascular diseases are identified.
- Managing these factors can significantly reduce disease risk.
Notes: Summarizing major health risks
Tone: Cautious
Relevance: 5/5
“if you swap that out with mono unsaturated fat or even polyunsaturated fat, their apob levels in our experience about half of the people who have this hyper response to saturated fat, if you isocalorically shift them to high monounsaturated fat, you fix the problem.”
Main Takeaways:
- Replacing saturated fats with mono- or polyunsaturated fats can improve lipid profiles in some individuals.
- This dietary change can reduce apoB levels in those sensitive to saturated fats.
- Not all individuals respond the same way to dietary fat changes.
Notes: Dietary advice for managing lipid levels
Tone: Advisory
Relevance: 5/5
“it turns out apob and ldlc are highly genetic which is what has allowed us to do the mandelian randomization studies that act as one of the you know there are basically three cornerstones of data that make it unambiguously clear of the relationship between LDL or apob and ascvd.”
Main Takeaways:
- APOB and LDLC levels are significantly influenced by genetics.
- Mandelian randomization studies have helped clarify the relationship between LDL, APOB, and cardiovascular disease.
- Genetic factors are a cornerstone in understanding lipid-related health risks.
Notes: Discussion on the genetic aspects of lipid levels
Tone: Informative
Relevance: 5/5
“the final drug so we can just wrap this up because I'm sure the listeners are tired of hearing about this stuff uh is a is a drug called bidic acid that is a prodrug so it's a very elegant drug uh it's taken as a pill uh but it's ineffective until it's metabolized by the liver and in the liver it then inhibits um cholesterol synthesis what makes this drug special is unlike statins this drug only works in the liver so statins work throughout the body they do most of their work in the liver but technically every cell is impacted by a Statin only hepatocytes are impacted by bondic acid and it lowers apob same way lowers cholesterol synthesis liver says I need more cholesterol puts more LDL receptors up pulls more LDL in LDL and cholesterol go down but no side effects no type to diabetes risk nothing nothing it's just it's only acting in the liver.”
Main Takeaways:
- Bempedoic acid (bidic acid) is a prodrug that only becomes active in the liver, where it inhibits cholesterol synthesis.
- It is unique in that it only affects hepatocytes, unlike statins which impact every cell.
- This drug lowers cholesterol effectively with no reported side effects or diabetes risk.
Notes: Discussion on the unique properties of bempedoic acid compared to other drugs.
Tone: Enthusiastic
Relevance: 5/5
“treating people in their 30s now making sure a person never ever walks around with an apob over 30 or 40 milligrams per deciliter making sure a person doesn't even spend one year with mild hypertension making sure a person is always metabolically healthy”
Main Takeaways:
- Advocates for early intervention in disease prevention, specifically in cardiovascular health.
- Highlights the importance of maintaining low levels of apolipoprotein B and controlling hypertension from a young age.
- Stresses the need for maintaining metabolic health throughout life.
Notes: Discussion on ultra-primary prevention strategies for cardiovascular diseases.
Tone: Proactive
Relevance: 5/5
“AAPOB is far better than LDL because APOB tells us about metabolic disease”
Main Takeaways:
- APOB is considered a more reliable marker for metabolic disease compared to LDL.
- Understanding metabolic disease markers is crucial for effective disease management.
Notes: Quoting an expert's opinion on metabolic disease markers
Tone: Neutral
Relevance: 5/5
“understand the labs that can give you a hint about your metabolic health so things like the you know apob fasting insulin fasting glucose triglycerides htl cholesterol hscrp an inflammatory marker uric acid vitamin D um I think I said fasting insulin um if you can look at these things every few months and actually be certain that you are like really in the optimal range for a lot of these things and you feel incredible you're probably eating the right diet”
Main Takeaways:
- Regular monitoring of specific biomarkers can indicate optimal metabolic health.
- Markers include apolipoprotein B, fasting insulin, fasting glucose, triglycerides, HDL cholesterol, high-sensitivity C-reactive protein, uric acid, and vitamin D.
- Maintaining these markers in optimal ranges can suggest that one's diet is appropriate.
Notes: Discussion on the importance of lab tests for assessing diet effectiveness.
Tone: Informative
Relevance: 5/5
“if you have damage to the endothelium yes apob is involved but this is necessary but not sufficient so if you have a component that's in involved and you have a system where there is constant damage to the endothelium like diabetes metabolic dysfunction is it possible that apob looks like more apob is bad but it's not actually beginning the process right”
Main Takeaways:
- Damage to the endothelium is necessary for atherosclerosis to start.
- ApoB is involved in the process but not sufficient on its own to cause the disease.
- Metabolic dysfunction, like diabetes, can exacerbate endothelial damage.
Notes: Debating the role of ApoB in cardiovascular disease
Tone: Analytical
Relevance: 4/5
“the American Heart Association the American colle of card College of Cardiology will recommend canola oil to you because it lowers your apob and they will tell you to limit saturated fat because it raises your apob when we also know that there are so many populations of Free Living humans with huge amounts of saturated fat in their diet and high cholesterol that don't have any incidence of atherosclerosis in their diets”
Main Takeaways:
- American Heart Association and American College of Cardiology recommend canola oil to lower ApoB.
- They advise limiting saturated fat as it raises ApoB.
- Populations consuming high saturated fat without processed foods show no increased atherosclerosis.
Notes: Discussion on dietary recommendations by health organizations
Tone: Critical
Relevance: 5/5
“as poly saturated fatty acids in seed oils lower your LDL lower your apob they're also increasing oxidized LDL and LP little a which are much stronger risk factors for cardiovascular disease but why is that never addressed”
Main Takeaways:
- Polyunsaturated fatty acids in seed oils can lower LDL and ApoB.
- They increase oxidized LDL and Lp(a), which are stronger cardiovascular risk factors.
- The negative effects of these increases are often not addressed in health discussions.
Notes: Critique of the overlooked risks of seed oils in diet
Tone: Concerned
Relevance: 4/5
“cardiovascular disease is the number one killer in the world today. And you can decrease your rate of cardiovascular disease by lowering APO.”
Main Takeaways:
- Cardiovascular disease is the leading cause of death globally.
- Lowering apolipoprotein B (APOB) levels is suggested to reduce the risk of cardiovascular disease.
Tone: Informative
Relevance: 5/5
“getting your apob checked is also important”
Main Takeaways:
- ApoB is a significant marker for cardiovascular risk, encompassing various lipoproteins including LDL.
- Monitoring ApoB can provide a broader understanding of cardiovascular health.
Notes: Discussion on the importance of various biomarkers in assessing cardiovascular health.
Tone: Advisory
Relevance: 4/5
“let's talk about blood tests what what do you think are um the three to five things that basically everybody if they can should know about what circulating in their blood I'm I'm imagining LDL HDL this kind of thing I guess apob is a big uh favorite of our our friend Peter AA um fasting blood glucose continuous blood glucose postmeal Etc just kind of evaluating how exercise food Etc impacts blood glucose”
Main Takeaways:
- Blood tests can provide crucial insights into metabolic health.
- Key metrics to monitor include LDL, HDL, and various forms of blood glucose measurements.
- These tests help evaluate how lifestyle factors like diet and exercise affect metabolic parameters.
Notes: Discussion on the importance of blood tests for monitoring health.
Tone: Informative
Relevance: 5/5
“there are so many other tests that I talked about in my book and that you've talked about on your podcast apob uric acid fasting insulin hom IR hscrp liver function tests ggt all these other tests that are great that can really tell us more about mitochondrial dysfunction oxidative stress chronic inflammation but the ones I'm mentioning are the ones that you will not have to fight with your doctor about like the the the everything I just mentioned like the doctor should order on an annual physical and it's really about us learning to act like read the Tea Leaves of what they're saying and not look at them in this algorithmic way but like how together if they're creeping up or if many of them are a little bit high like we need to focus all of our energy on improving mitochondrial capacity basically and and bring those numbers down which we can do very very quickly once you start getting the mitochondria moving through more of those substrates a lot of them will just naturally come down.”
Main Takeaways:
- Various blood tests can indicate mitochondrial dysfunction, oxidative stress, and inflammation.
- Regular monitoring of these biomarkers can help in managing and improving mitochondrial health.
- Improving mitochondrial function can naturally improve these biomarkers.
Notes: Discussion on the importance of various blood tests for monitoring metabolic health.
Tone: Encouraging
Relevance: 5/5
“could somebody have relatively High um LDL maybe even higher than um sort of highend of chart or even um above high-end apob but there's some sort of demand metabolic demand or or there they're weight training a lot or they're running marathons and so they need a lot of LDL”
Main Takeaways:
- High levels of LDL (low-density lipoprotein) might be influenced by increased metabolic demands such as intense physical activity.
- The speaker questions whether conditions like weight training or marathon running could necessitate higher LDL levels.
- This statement explores the functional role of LDL in relation to metabolic health.
Notes: Questioning the role of LDL in active individuals
Tone: Inquisitive
Relevance: 4/5
“if your objective is to not die from heart disease and only to die with it then you want apob as low as possible”
Main Takeaways:
- Lowering ApoB levels can significantly reduce the risk of dying from heart disease.
- Managing ApoB levels is crucial for those with a family history of cardiovascular diseases.
Notes: Discussing strategies for managing heart disease risk.
Tone: Advisory
Relevance: 5/5
“I know my apob numbers and it I might be that guy who's up in the you know above a hundred so I'm going to get this treated uh that's a promise to myself.”
Main Takeaways:
- The speaker is aware of their ApoB levels, which are above 100.
- ApoB is a marker for cardiovascular risk.
- The speaker intends to seek treatment based on these levels.
Notes: The speaker is discussing personal health monitoring.
Tone: Concerned
Relevance: 5/5
“we covered um the three major risk factors which were um blood pressure um keeping that in check don't smoke um and apob and we've now talked about the things to adjust apob levels.”
Main Takeaways:
- Identifies three major risk factors for disease: blood pressure, smoking, and ApoB levels.
- Emphasizes the importance of managing these factors for disease prevention.
Notes: Discussion on disease prevention strategies.
Tone: Informative
Relevance: 5/5
“ApoB is the thing that drives atherosclerosis.”
Main Takeaways:
- ApoB (Apolipoprotein B) is identified as a primary causative agent in the development of atherosclerosis.
- Managing ApoB levels is crucial for cardiovascular disease prevention.
Notes: Discussion on cardiovascular health and longevity
Tone: Cautious
Relevance: 5/5
“So it's this really young ApoB level of kind of 20 to 30 milligrams per deciliter, that makes it impossible to get atherosclerosis.”
Main Takeaways:
- Low ApoB levels (20-30 mg/dL) from a young age can prevent the development of atherosclerosis.
- Maintaining ApoB levels similar to those in youth may be key to preventing cardiovascular diseases.
Notes: Explaining the importance of maintaining low ApoB levels from a young age
Tone: Informative
Relevance: 5/5
“Medicine 2.0, which is what we're generally practicing today, when it comes to ASCVD says, look, we will treat you, we will lower that LDL cholesterol, they still don't talk about ApoB, but that's a very American thing.”
Main Takeaways:
- Medicine 2.0 focuses on lowering LDL cholesterol as a treatment for ASCVD.
- ApoB is not commonly discussed in American guidelines but is included in European and Canadian guidelines.
Notes: Discussion on differences in medical practices
Tone: Neutral
Relevance: 4/5
“the three things that have to happen for atherosclerotic disease are as follows the first is a molecule called A lipoprotein which Carri cholesterol through the body and specifically A lipoprotein that has an apob protein on it because there are lipoproteins that don't have apobs on them and we don't have to worry about those.”
Main Takeaways:
- ASCVD involves a specific type of lipoprotein with an apob protein.
- Not all lipoproteins contribute to ASCVD, only those with apob proteins.
- Understanding the role of apob in ASCVD can aid in targeted prevention strategies.
Notes: Speaker detailing the biochemical factors in ASCVD.
Tone: Technical
Relevance: 5/5
“the data on this is uh as unambiguous as any data are in medicine from clinical trials epidemiologic trials and mandelian randomization in other words you have the only three layers of evidence you can ever look to experimental data Mr and clinical EPI and they all say the same thing there is a log linear reduction in ascvd as apob goes down.”
Main Takeaways:
- Reduction in apob levels correlates with a decrease in ASCVD risk.
- Evidence from clinical trials, epidemiological studies, and Mendelian randomization supports this correlation.
- This relationship is one of the clearer findings in medical research regarding disease prevention.
Notes: Speaker summarizing evidence on apob's role in ASCVD.
Tone: Confident
Relevance: 5/5
“atherosclerosis is really driven by lipoproteins first and foremost so this apo anything that carries this apob protein on it so that's an ldl an lp little a vldl that's the that's the synchronon that is they that is the necessary but not sufficient element to drive atherosclerosis”
Main Takeaways:
- Atherosclerosis is primarily driven by lipoproteins, particularly those carrying the ApoB protein.
- LDL, Lp(a), and VLDL are specific types of lipoproteins involved in the development of atherosclerosis.
Notes: Explaining the biochemical mechanisms behind atherosclerosis.
Tone: Technical
Relevance: 5/5
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