Ep. 20: Got LDL Cholesterol? Let’s Play Cholesterol Marbles! — with Dr. Regina Druz, MD, MBA, FACC, FMCP-M, integrative cardiologist

What do ancient Egyptian mummies and modern humans have in common? Stick around for the answer. In this ‘Friday fun-day’ solo episode, Dr. Regina Druz literally plays with marbles to make sense of your cholesterol. Instead of the tired ‘good vs. bad’ framing, she walks you through your whole lipidome — the interconnected universe of lipid particles — using differently sized and colored marbles for chylomicrons, VLDL, LDL, small dense LDL, and HDL. Along the way she explains her 40-30-20-10 rule for why LDL lowering matters, the crucial difference between relative and absolute risk, why non-HDL cholesterol and ApoB predict risk better than LDL alone, and how all of it combines into your atherogenic lipid phenotype. (This episode is highly visual — best watched on YouTube.)

Watch on YouTube: A video version of this episode is available on the Own Your Heart Health YouTube channel. Subscribe to be notified of new episodes.

Episode Chapters

[00:00] Introduction: A Friday Fun-Day Question
[01:30] Your Lipidome: Cholesterol Doesn’t Live in a Silo
[03:30] The Biggest Marbles: Chylomicrons (ApoB48)
[05:30] From Liver to Bloodstream: VLDL → LDL
[08:00] Is LDL Important? The 40-30-20-10 Rule
[12:00] Relative vs. Absolute Risk
[15:30] Beyond LDL: Non-HDL Predicts Better
[17:30] The Most Worrisome Marble: Small Dense LDL
[22:00] Your Atherogenic Lipid Phenotype (ALP)
[25:00] The Pastel Marbles: HDL & Reverse Cholesterol Transport
[29:00] Mummies, Aging & What’s Next + For Clinicians

Transcript

[00:00] Introduction: A Friday Fun-Day Question

Dr. Regina Druz (00:02): Welcome to Own Your Heart Health. I’m Dr. Regina Druz, your holistic cardiologist. This week we’ll dive into common heart health concerns, uncovering root causes and unpacking scientific discoveries and controversies. The information provided does not constitute medical advice. Please contact your healthcare practitioner before making any changes that may impact your health.

Dr. Regina Druz (00:35): It’s Friday fun day, so let me ask you a question: what do ancient Egyptian mummies and modern humans have in common? Stick around to the end for the answer. I recently came back from the annual international conference of the Institute for Functional Medicine, where I served as faculty and co-led a discussion on a deeper understanding of cardiovascular risk. It inspired me to create a little game I call cholesterol marbles — because patients so often pick and choose what they consider ‘good’ and ‘bad’ about their cholesterol without putting the pieces together.

[01:30] Your Lipidome: Cholesterol Doesn’t Live in a Silo

Dr. Regina Druz (01:30): You’ve probably heard of the microbiome — the collection of microbes in our gut that shape digestion, immunity, and even mood, gut, brain, heart, and skin health. Cholesterol works similarly: it doesn’t exist in a separate silo but as part of a whole universe of lipid metabolism that many lipidologists call the lipidome — a collection of cholesterol, triglycerides, cholesterol esters, and apolipoproteins. By studying a person’s lipidome, we can give them actionable steps — nutrition, supplements, lifestyle, and sometimes medication — to shift that balance in a way that lowers vascular risk.

Dr. Regina Druz (02:45): So let me show you the marbles. If you’re on audio, please drop into our YouTube channel for the visual part — it really brings the points home. Yes, I’m an adult cardiologist playing with marbles, and each size and color represents a different particle.

[03:30] The Biggest Marbles: Chylomicrons (ApoB48)

Dr. Regina Druz (03:30): These biggest marbles represent chylomicrons. As we eat, nutrients are broken down into triglycerides, free fatty acids, cholesterol, and cholesterol esters, and after they traverse the stomach, duodenum, and gut they’re packaged into these very large particles. Chylomicrons are ApoB-containing particles — specifically ApoB48, one per particle — which is a component of the ApoB we detect on bloodwork. But because chylomicrons are so large, they exit the circulation quickly, so most of the ApoB we measure is actually ApoB100, with only a small share from ApoB48.

Dr. Regina Druz (04:45): Where do chylomicrons go? Blood flow delivers them to muscle and fat tissue, where they’re a rich source of triglycerides — broken down into free fatty acids for energy in muscle, or stored as triglycerides in fat. The rest is delivered to the liver, some directly and some via the portal circulation tied to bile acids.

[05:30] From Liver to Bloodstream: VLDL → LDL

Dr. Regina Druz (05:30): In the liver, those big triglyceride-rich chylomicrons get repackaged into very low-density lipoproteins (VLDL) — I made these marbles a bit smaller, because repackaging removed triglycerides and brought in cholesterol esters, so VLDL is richer in cholesterol than its parent. VLDL is also an ApoB-containing particle, now in a one-to-one relationship: one ApoB per VLDL. The liver releases VLDL into the circulation, where enzymes keep unloading triglycerides and swapping in cholesterol esters, so the particles shrink — and as they shrink they become low-density lipoprotein, or LDL. These little red spheres are my LDL marbles.

[08:00] Is LDL Important? The 40-30-20-10 Rule

Dr. Regina Druz (08:00): Patients often ask whether LDL really matters. It does — it’s been studied extensively across primary prevention, secondary prevention, and many populations. I teach an easy 40-30-20-10 rule. From pooled studies, for roughly every 39 mg/dL drop in LDL (I round to 40), there’s about a 22% reduction in cardiovascular mortality (I round to 20) and about a 10% reduction in all-cause mortality — death from any cause. And across those trials, LDL lowering accounts for about a 30% relative risk reduction in events. So: 40 (the LDL drop), 30 (relative risk reduction), 20 (cardiovascular mortality), 10 (all-cause mortality). LDL is not the only important part of the lipidome, but it is genuinely important.

Dr. Regina Druz (10:30): Hi everyone, it’s Dr. Regina here. I know there are contradictory opinions about nutrition for heart health and longevity — the discussion gets heated and confusing. Some push low-fat, low-cholesterol; others are fans of a ketogenic diet; and there are many voices urging vegan or vegetarian eating. To cut through the clutter, my team and I created Holistic Heart University: on-demand courses, nutrition and lifestyle resources, and supplement guidance to make healthy choices for your heart easier to understand. I’m especially proud of our open office hours and the Q&A feature where you can put us in the hot seat. Head to the show notes for the link and use promo code OWNER20 for 20% off our annual subscription. I’ll see you in office hours.

[12:00] Relative vs. Absolute Risk

Dr. Regina Druz (12:00): That 30% needs context. Imagine 100 untreated patients in a trial, and 10 have a cardiovascular event — a 10% event rate. A similar group of 100 receives LDL-lowering treatment and reduces their events by 30%, so instead of 10 events they have about 7. The relative risk reduction is the big, impressive number — 30% — but the absolute risk reduction is just 3 percentage points (10% down to 7%).

Dr. Regina Druz (13:30): Why does that matter? Because absolute risk reduction translates into something called the number needed to treat, which we’ll cover in a future show. For now, remember two things: the 40-30-20-10 rule holds, and the benefit of LDL lowering tracks with your baseline risk. Patients higher on the vascular-risk scale get a greater impact from the same intervention than lower-risk patients — which makes intuitive sense.

[15:30] Beyond LDL: Non-HDL Predicts Better

Dr. Regina Druz (15:30): Is LDL the best marker? Over time we’ve learned we need the whole lipidome: VLDL, intermediate-density and remnant lipoproteins, LDL, and others like lipoprotein(a) and small dense LDL. Together, all the non-HDL particles make up non-HDL cholesterol (everything except HDL). When we tally all the ApoB-containing particles, we find that non-HDL cholesterol is a better predictor of vascular risk than LDL alone — because it captures the precursors and derivatives that LDL by itself misses.

[17:30] The Most Worrisome Marble: Small Dense LDL

Dr. Regina Druz (17:30): One LDL derivative deserves its own marble — these black-and-yellow spheres are small dense LDL. The liver normally scoops LDL back up via receptors and recycles the cholesterol, but if it isn’t cleared well — often under insulin resistance or an excess of free fatty acids (which can occur in some people on a ketogenic diet) — LDL converts into small dense LDL. The problem: it lingers in the circulation a long time, around 72 hours, almost three days.

Dr. Regina Druz (19:30): At the conference, someone asked which lipid marker concerns me most. People reasonably said ApoB or lipoprotein(a). But most people with cardiovascular disease have normal lipoprotein(a) — and about 96% of genetic evaluations for elevated Lp(a) find no variant. Under insulin resistance or excess free fatty acids, though, people make a lot of small dense LDL — and it’s an independent risk factor for cardiovascular events, ischemic strokes, peripheral arterial disease, and cardiac mortality, even when LDL itself is optimized. That’s why it worries me. It also explains why non-HDL cholesterol and ApoB predict events better than LDL: they include Lp(a), small dense LDL, remnants, and more. And by the way, saying ‘LDL doesn’t matter, it’s all about ApoB’ is too simplistic — LDL is itself an ApoB-containing particle, usually the most numerous one.

Dr. Regina Druz (21:00): Why does cardiology focus on LDL at all? Because LDL is small enough to be incorporated into atherosclerotic plaque: it gets taken up by foam cells — derived from immune cells called macrophages — at sites of vessel injury, where the body uses cholesterol as a building block trying to repair the damage. So LDL is a central character even though, in modern data, non-HDL and ApoB carry greater predictive power.

[22:00] Your Atherogenic Lipid Phenotype (ALP)

Dr. Regina Druz (22:00): When we combine all the ApoB-containing particles with triglycerides, we can discern your atherogenic lipid phenotype, or ALP. At Holistic Heart Centers we do this for every patient, to characterize the lipidome and find the levers — medication, supplements, lifestyle — that will shift the balance in your favor. It’s not one-size-fits-all: much depends on your baseline risk, your age, and any specific conditions that make us more or less stringent.

Dr. Regina Druz (23:30): Hi everyone, it’s Dr. Regina here. Many of my colleagues and I are seeing patients arrive with self-ordered blood tests. When this trend started, I thought it would help — who doesn’t want more access to their health data? But too often self-ordered labs lead to more confusion and frustration: patients come in with a pile of results and are no better off. That’s why we created HeartWell Toolkits — a curated collection of at-home blood and genetic markers focused on heart and brain health that gives you the data you need to make informed, actionable decisions. You can order them at the shop on holisticheartcenters.com — the link is in the show notes. Use code TESTING10 for 10% off and free shipping.

[25:00] The Pastel Marbles: HDL & Reverse Cholesterol Transport

Dr. Regina Druz (25:00): Now the pretty pastel spheres — HDL cholesterol. HDL particles carry a different apolipoprotein, ApoA1 (not ApoB). Conveniently, my HDL marbles came in different colors but the same size, which is fitting: unlike ApoB particles, there isn’t a clean one-to-one relationship between an HDL particle and its ApoA1, so HDL is more variable. HDL’s job is reverse cholesterol transport: it scoops up cholesterol from areas of plaque formation and injury and carries it back to the liver for recycling — the opposite direction from LDL.

Dr. Regina Druz (26:45): But here’s the catch: reverse cholesterol transport can be defective. Some people have high HDL and feel a false sense of security — ‘my HDL is high, so I don’t care about my LDL.’ Yet high HDL isn’t always fully functional. Advanced lab testing can characterize beneficial HDL subfractions, and genetic profiling can reconstruct the metabolic pathways that move us from VLDL to LDL to small dense LDL, and govern how well HDL does its scooping. So a high HDL number alone is not a green light.

[29:00] Mummies, Aging & What’s Next + For Clinicians

Dr. Regina Druz (29:00): So skip the simplistic ‘good and bad cholesterol’ at your next visit; what matters is how your specific lipidome raises or lowers your vascular risk, and which internal pathways we can influence through diet, exercise, supplements, or medication to de-risk it. And the answer to my opening question: what do ancient Egyptian mummies and modern humans share? Atherosclerosis. In a 2013 whole-body CT study, investigators scanned mummies from Egypt and elsewhere and found that about 37% of these ancient humans had evidence of coronary artery calcification.

Dr. Regina Druz (30:30): We tend to think of heart disease as a modern phenomenon — the Framingham Heart Study, which shaped our understanding of risk factors, began in the late 1940s — yet heart disease was clearly present 4,000 years ago. As I always say, atherosclerosis is the fundamental process of aging. So whether your concern is brain health, cancer prevention, heart-attack prevention, or kidney health, the root causes overlap: inflammation, immune activation, oxidative stress, metabolic inflexibility, and insulin resistance. Maximizing vascular health is job number one. In future shows we’ll play cholesterol marbles again — diving deeper into ApoB, LDL particles and sizes, HDL subfractions, and remnant lipoproteins — and into where diet, supplements, and medications actually work. For context, lipid guidelines come from bodies I belong to — the American College of Cardiology, the European Society of Cardiology, and the National Lipid Association; the U.S. guidance dates to 2018, and the European Society of Cardiology is releasing an update this year.

Dr. Regina Druz (32:30): To the professionals listening: if you’re thinking of launching a cardiometabolic or integrative cardiology program in your practice, we can help. Holistic Heart Centers helps physicians expand into hybrid or concierge services — head to the show notes and click the application link; your intro call is entirely free. Ready to schedule a practice review? Use code DOC10 for 10% off our Practice Power Hour, a 60-minute coaching session. Thank you for tuning in to Own Your Heart Health with Dr. Regina Druz. This podcast is powered by Holistic Heart Centers. If you enjoyed the show, please rate and review us on your favorite platform, and visit holisticheartcenters.com and subscribe to our YouTube channel. See you next week.

Frequently Asked Questions

Is LDL cholesterol actually important?

Yes. Dr. Druz is emphatic that, while LDL is not the only thing that matters, it has been studied extensively and is genuinely important. She teaches a ‘40-30-20-10 rule’ drawn from pooled trial data: for roughly every 39 mg/dL drop in LDL (rounded to 40), there’s about a 22% reduction in cardiovascular mortality (rounded to 20) and about a 10% reduction in all-cause mortality, while LDL lowering accounts for roughly a 30% relative risk reduction in events across trials. She also stresses that the benefit scales with baseline risk — higher-risk patients gain more from the same LDL reduction. Importantly, she pushes back on the popular claim that ‘LDL doesn’t matter, only ApoB does,’ noting LDL is itself an ApoB-containing particle and usually the most numerous one. These figures are teaching approximations from the research; discuss your own targets with your clinician.

Why is non-HDL cholesterol (or ApoB) a better predictor than LDL alone?

Because they capture more of the picture. Non-HDL cholesterol is everything except HDL — it includes LDL plus the precursors and derivatives LDL alone misses: VLDL, intermediate-density and remnant lipoproteins, lipoprotein(a), and small dense LDL. ApoB counts the actual number of atherogenic, artery-damaging particles (each VLDL, IDL, and LDL carries one ApoB100; chylomicrons carry ApoB48). Because these markers reflect the total burden of harmful particles rather than just one fraction, modern data show non-HDL and ApoB predict cardiovascular risk better than LDL by itself. Dr. Druz combines all the ApoB-containing particles with triglycerides to define a patient’s ‘atherogenic lipid phenotype.’ This is educational information; the right markers and targets for you should be determined with a qualified clinician.

What is small dense LDL, and why is it dangerous?

Small dense LDL is a downstream product of regular LDL. Normally the liver scoops LDL back up via receptors and recycles the cholesterol, but when clearance is poor — often under insulin resistance or an excess of free fatty acids (which can occur in some people on a ketogenic diet) — LDL converts into small dense LDL. The trouble is that it lingers in the bloodstream for around 72 hours (almost three days) and is an independent risk factor for cardiovascular events, ischemic strokes, peripheral arterial disease, and cardiac mortality — even when standard LDL is optimized. Dr. Druz names it the lipid marker that concerns her most, more than lipoprotein(a) (which is usually normal in most people with heart disease). It can be measured with advanced lipid testing. This is general education, not personalized medical advice.

If my HDL (“good cholesterol”) is high, am I protected?

Not necessarily. HDL’s job is ‘reverse cholesterol transport’ — scooping cholesterol from areas of plaque and injury and carrying it back to the liver for recycling. But Dr. Druz cautions that this function can be defective, so a high HDL number can create a false sense of security. Unlike ApoB particles, HDL doesn’t have a clean one-to-one relationship with its apolipoprotein (ApoA1), making it more variable, and high HDL isn’t always fully functional. Advanced lab testing can characterize the more beneficial HDL subfractions, and genetic profiling can map the pathways involved. The bottom line: a high HDL alone is not a green light to ignore an elevated LDL or the rest of your lipidome. Interpret your full lipid picture with your physician.

Show Notes & Resources

Host: Dr. Regina Druz, MD, FACC

Dr. Regina Druz is a board-certified holistic cardiologist and the founder and CEO of Holistic Heart Centers. With a background in cardiac imaging and nearly 25 years in practice, she blends conventional cardiology with integrative, functional, root-cause medicine. She is a member of the American College of Cardiology, the European Society of Cardiology, and the National Lipid Association, and serves as faculty for the Institute for Functional Medicine. Her focus is cardiometabolic health, advanced lipid and genetic testing, and cardiovascular longevity — characterizing each patient’s lipidome and ‘atherogenic lipid phenotype’ to personalize prevention. She is the host of Own Your Heart Health and the creator of Holistic Heart University, the HeartWell Toolkits, and the Statin Overprescribing Solution program.

Resources Mentioned in This Episode

Atherogenic lipid phenotype (ALP) / lipidome analysis at Holistic Heart Centers — characterizing all ApoB-containing particles plus triglycerides
HeartWell Toolkit — at-home blood and genetic markers to map your lipidome (use code TESTING10 for 10% off and free shipping)
The 40-30-20-10 teaching rule — a mnemonic for the LDL-lowering evidence (approximate figures pooled from statin trials)
Horus study (2013) — whole-body CT of ancient mummies that found atherosclerosis in roughly a third of ancient humans
Framingham Heart Study — foundational cardiovascular risk-factor research (begun in the late 1940s)
Lipid guidelines — 2018 ACC/AHA guideline, the National Lipid Association, and the European Society of Cardiology (update due in 2025)
Cholesterol-marbles series — upcoming deep dives on ApoB, LDL particles and sizes, HDL subfractions, and remnant lipoproteins; plus a future episode on ‘number needed to treat’
Holistic Heart University — on-demand courses and resources (use code OWNER20 for 20% off annual)
For clinicians: Practice Power Hour coaching with Holistic Heart Centers (use code DOC10 for 10% off)

Holistic Heart Centers

holisticheartcenters.com
HeartWell.ai — AI-powered cardiovascular risk assessment
Address: 55 Bryant Avenue, Suite #6, Roslyn, NY 11576
Phone: 877-511-5166
YouTube: @reginadruzmd
Instagram: @dr.reginadruz
Podcast: Own Your Heart Health — available on Apple Podcasts, Spotify, and all major platforms

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