In my recent post, we delved into the fascinating insights of Dr. Peter Attia on APOB and its implications for heart disease. This exploration opened a window into the intricate world of cardiovascular health and sparked a newfound curiosity in me.
It led me further into Dr. Attia’s extensive work, particularly his nine-part series on a closely related and equally vital topic: Cholesterol.
In this follow-up post, I aim to break down each of Dr. Attia’s detailed blog posts into digestible bullet points for easy understanding. This is mainly for my personal reference, as I found the 9-part series to be overwhelming, albeit very in-depth and useful.
Cholesterol Concepts Simplified
Concept #1: What is Cholesterol?
– Cholesterol is a molecule made of 27 carbon atoms.
– It has two forms:
– Free Cholesterol (UC): Active in the body.
– Esterified Cholesterol (CE): Stored form.
– Cholesterol is produced only by animals (zoosterol).
Concept #2: Dietary vs. Body Cholesterol
– Daily intake: 300-500 mg from food, 800-1200 mg produced by the body.
– Most cholesterol is in cell membranes (30-40 grams total in the body).
– Liver makes 20% of cholesterol, other cells make 80%.
– Body regulates cholesterol production and levels tightly.
How Cholesterol is Absorbed
– NPC1L1 protein in the gut helps absorb cholesterol.
– ABCG5 and ABCG8 proteins in the gut remove excess cholesterol.
– Only unesterified cholesterol (UC) is absorbed from food.
– Most dietary cholesterol (esterified) is not absorbed directly.
Concept #3: Misconceptions About Cholesterol
– Cholesterol is essential for life, not inherently “bad.”
– It’s a key part of cell membranes and helps make hormones and vitamins.
– Problems occur when cholesterol accumulates in arteries, leading to blockages.
Summary
– Cholesterol is a crucial molecule in the body, needed in all cells.
– Body cholesterol is regulated through synthesis, absorption, and excretion.
– Dietary cholesterol has little effect on cholesterol levels in the body.
– It’s important to understand cholesterol’s role and regulation for overall health.
Concept #4: How Cholesterol Moves Around Our Body
Hydrophobic vs. Hydrophilic:
– Hydrophobic molecules repel water.
– Hydrophilic molecules attract water.
Cholesterol’s Transport:
– Blood is mostly water; cholesterol is hydrophobic.
– Cholesterol needs transporters (lipoproteins) to move in blood.
Types of Lipoproteins:
– Apoproteins: Proteins that transport lipids.
– Apolipoproteins: Apoproteins bound to lipids.
– Lipoproteins: Spherical structures carrying lipids, bound by phospholipid membrane.
Key Apolipoproteins:
– ApoA-I: Found in high-density lipoprotein (HDL).
– ApoB: Found in low-density lipoprotein (LDL).
Lipoprotein Structure:
– Composed of cholesterol, phospholipids, cholesteryl esters, and triglycerides.
– Density varies based on lipid-to-protein ratio.
– Five main classes: HDL, LDL, IDL, VLDL, chylomicrons.
Cholesterol’s Journey:
– Carried by lipoproteins through blood.
– From liver, lipoproteins mature, shedding triglycerides and becoming cholesterol-rich.
– Transport occurs in both directions: to and from the liver.
Concept #5: Measuring Cholesterol
Early Methods:
– Initially, only total cholesterol (TC) in blood was measurable.
LDL-C Estimation:
– Friedewald Formula: LDL-C estimated as TC – HDL-C – (TG/5).
Direct Measurements:
– VAP Panel: Measures cholesterol in various lipoproteins directly.
– NMR (Nuclear Magnetic Resonance): Counts and measures LDL and HDL particles.
Insights from Particle Count and Size:
– Particle count and size can indicate early signs of insulin resistance.
– Small LDL and HDL particles are markers for insulin resistance.
Summary:
– Cholesterol doesn’t travel freely in blood, it’s carried by lipoproteins.
– Measuring cholesterol involves calculating or directly measuring the cholesterol content in different lipoprotein types.
– Advances like NMR provide a more detailed analysis of cholesterol and its carriers.
Concept #6: How Does Cholesterol Cause Problems?
Key Metric for Heart Disease Risk:
– ApoB particle count in plasma is crucial.
– Two ways to measure: directly measure apoB concentration or LDL particle count using NMR technology.
Role of HDL and LDL Particles:
– High number of LDL particles (apoB) indicates risk of atherosclerosis.
– HDL particle functionality is important but secondary to LDL particle count.
Mechanism of Atherosclerosis:
– Sterols accumulate in artery walls, transported by apoB-containing lipoproteins (mainly LDL).
– LDL particles penetrate the endothelium, leading to atherosclerosis.
– LDL retention and inflammatory response in arteries cause plaque buildup.
Atherosclerosis Progression:
– LDL particles enter sub-endothelial space, initiating immune response.
– Progressive accumulation leads to plaque formation, narrowing arteries or causing ruptures.
– Advanced stages result in myocardial infarction or heart attacks.
Concept #7: Does the Size of an LDL Particle Matter?
Debate on LDL Particle Size:
– LDL particle size (large vs. small) has been a contentious topic in lipidology.
Comparing Large vs. Small LDL Particles:
– Statistically, large LDL particles are less harmful than small ones.
– Small LDL particles are associated with higher atherosclerosis risk.
Impact of Particle Size vs. Number:
– The number of LDL particles is a more significant risk factor than size.
– Small LDL particle size is a marker for other metabolic issues.
Studies and Findings:
– Studies show once LDL particle number is accounted for, the size’s impact on atherosclerosis risk is minimal.
– Large LDL particles can also increase atherosclerosis risk if the particle number is high.
Conclusion on LDL Particle Size:
– LDL particle number (LDL-P or apoB) is a more important predictor of heart disease risk than particle size.
– Small LDL particles indicate metabolic problems, but risk assessment requires knowing particle number.
Concept #8: Why Measure LDL-P Instead of Just LDL-C?
Statistical Concordance and Discordance
– Concordance: When two metrics predict the same outcome.
– Discordance: When two metrics predict different outcomes.
– LDL-P (number of LDL particles) and LDL-C (cholesterol content in LDL) can be discordant, meaning they don’t always indicate the same cardiovascular risk.
Predicting Cardiovascular Risk:
– LDL-P is a more accurate predictor of heart disease than LDL-C.
– Studies show LDL-P’s superiority in predicting adverse cardiac events.
Case of Discordance in LDL Measurements:
– High LDL-P with low LDL-C can indicate higher risk than anticipated.
– This discordance is particularly prevalent in patients with metabolic syndrome or diabetes.
Importance of LDL Particle Number:
– LDL particle number, rather than cholesterol content, drives atherosclerosis risk.
– High number of LDL particles increases the probability of them penetrating arterial walls, leading to atherosclerosis.
The Problem with Solely Relying on LDL-C:
– LDL-C measurement can be misleading, underestimating cardiovascular risk, especially when discordant with LDL-P.
– LDL-C doesn’t always reflect the actual number of LDL particles in the blood.
Why LDL-P is Critical to Measure:
– LDL-P provides a more comprehensive picture of cardiovascular risk.
– It accounts for both the number and size of LDL particles.
– LDL-P is crucial for accurate risk assessment, especially in patients with metabolic syndrome or diabetes.
Clinical Implications:
– LDL-P measurement should be considered for more accurate cardiovascular risk assessment.
– Relying solely on LDL-C may overlook individuals at high risk of heart disease.
– LDL-P is a crucial marker for guiding treatment and preventive measures for cardiovascular diseases.
In conclusion, LDL-P measurement is essential for a more accurate assessment of cardiovascular risk, especially in cases where LDL-C and LDL-P are discordant. This emphasizes the need for comprehensive lipid profiling in clinical practice to better identify and manage individuals at risk for heart disease.
Concept #9: Does “HDL” Matter After All?
Debunking the HDL Hypothesis:
– Recent studies challenge the belief that high HDL cholesterol (HDL-C) levels are always “good.”
– Major drug trials targeting HDL-C (e.g., torcetrapib, niacin) failed to show benefits in reducing heart disease risk, despite increasing HDL-C levels.
HDL-C vs. HDL-P:
– HDL-C: Amount of cholesterol carried by HDL particles.
– HDL-P: Number of HDL particles in blood.
– Recent focus on the importance of HDL particle number (HDL-P), not just cholesterol content (HDL-C).
Understanding HDL Functionality:
– HDL participates in reverse cholesterol transport (RCT), moving cholesterol from arteries to the liver.
– HDL’s protective role may be more about the function and number of particles (HDL-P) rather than just the cholesterol amount (HDL-C).
HDL Particle Size and Function:
– Small to medium-sized HDL particles might offer more protection (antioxidant, anti-inflammatory, cholesterol efflux capacity) than larger ones.
– HDL particle size and number are dynamic and interdependent, influencing cardiovascular risk.
Rethinking HDL-C as a Marker:
– Studies suggest that high HDL-C does not necessarily imply lower heart disease risk, especially in the presence of discordant LDL-P and LDL-C levels.
– HDL-C is not a reliable standalone marker for heart health or disease prediction.
Implications for Treatment and Research:
– Targeting HDL-C alone with drugs has not proven effective in reducing heart disease risk.
– Research suggests focusing on HDL particle number (HDL-P) and functionality might be more relevant for heart health.
– Understanding the complex role of HDL in cholesterol transport and cardiovascular disease requires more nuanced approaches.
In conclusion, while HDL-C has traditionally been seen as “good cholesterol,” recent research emphasizes the importance of HDL particle number (HDL-P) and function over just cholesterol content. This shift in understanding necessitates a more complex approach to evaluating and treating cardiovascular risk, moving beyond simple HDL-C measurements.
Concept #10: Dietary Strategies for Delaying Cardiovascular Disease
Understanding Aging and Cardiovascular Risk:
– Age is a critical risk factor in developing cardiovascular disease.
– The risk increases with age due to prolonged exposure to apoB particles, essential in atherosclerosis.
Diet’s Role in Cardiovascular Health:
– While direct long-term studies linking diet to heart disease are lacking, current evidence shows diet’s significant impact on cardiovascular risk markers.
– Dietary changes, especially in sugar and fat intake, have shown effects on heart health in short-term studies.
Sugar Intake and Heart Disease:
– High consumption of sugar, particularly fructose and high fructose corn syrup, raises harmful blood lipids like triglycerides.
– Reducing sugar intake, including fructose and glucose, can positively alter cardiovascular risk factors.
Insulin Resistance, Metabolic Syndrome, and Heart Health:
– Addressing insulin resistance and reducing metabolic syndrome symptoms can decrease the risk of heart disease and other related conditions.
– Dietary choices significantly impact insulin resistance and metabolic syndrome.
Dietary Recommendations for Heart Health:
– Minimize sugar intake, especially sources like fructose and high fructose corn syrup.
– Consider a low-carbohydrate diet to improve heart health markers.
– Focus on improving insulin resistance through diet to reduce cardiovascular risk.
Future Research and Considerations:
– Long-term studies are needed to fully understand the impact of different diets on heart disease risk.
– Research should continue to explore how dietary changes affect detailed lipid profiles, including LDL particle numbers and sizes.
In conclusion, emerging research suggests that dietary strategies focusing on reducing sugar intake and managing carbohydrates could delay the onset of cardiovascular disease, especially in those with insulin resistance or metabolic syndrome.
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