May 22, 2025 • 28 mins
In this episode of The Health Pulse Podcast, we go beyond the outdated “cholesterol clogs arteries” model and explore the modern science of atherosclerosis—a dynamic process involving oxidized LDL, inflammation, immune activation, and metabolic dysfunction.
Learn how damaged arteries, oxidized LDL particles, and foam cell formation drive plaque buildup, and why markers like ApoB, hs-CRP, and triglyceride-to-HDL ratio offer a more accurate picture of cardiovascular risk than total cholesterol alone. We also highlight how insulin resistance and poor metabolic health contribute to unstable plaque and higher heart disease risk.
🎧 Tap play to understand the full picture of heart health—and how lifestyle and advanced testing can help you protect it.
🚀 Brought to you by Quick Lab Mobile – Your Convenient Lab Testing Solution.
🔗 Learn more at www.quicklabmobile.com
📞 Need lab work done from the comfort of home? QLM offers fast, reliable mobile phlebotomy services—no clinic visit required.
📅 Book your appointment or learn more at:
👉 Quick Lab Mobile
📧 Contact us: info@quicklabmobile.com
💬 Enjoyed the episode? Leave us a review and let us know what topics you'd like us to cover next! Your feedback helps us bring you the content that matters most.
Disclaimer: The information provided in this podcast is for informational purposes only and should not be considered medical advice. The content discussed is based on research, expert insights, and reputable sources, but it does not replace professional medical consultation, diagnosis, or treatment. We strive to present accurate and up-to-date information, medical research is constantly evolving. Listeners should always verify details with trusted health organizations, before making any health-related decisions. If you are experiencing a medical emergency, such as severe pain, difficulty breathing, or other urgent symptoms, call your local emergency services immediately. By listening to this podcast, you acknowledge that The Health Pulse and its creators are not responsible for any actions taken based on the content of this episode. Your health and well-being should always be guided by the advice of qualified medical professionals.
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Nicolette (00:01):
Welcome to the Health Pulse, your go-to source for
quick, actionable insights onhealth, wellness and diagnostics
.
Whether you're looking tooptimize your well-being or stay
informed about the latest inmedical testing, we've got you
covered.
Join us as we break down keyhealth topics in just minutes.
Let's dive in.
Rachel (00:25):
You know, for the longest time, the story we all
heard about heart health waswell, pretty simple, wasn't it?
High cholesterol clogs yourarteries.
End of story.
Mark (00:34):
Right, like it was just plumbing.
Rachel (00:35):
Exactly, but lately the science seems to be pointing to,
I guess, a much more dynamicpicture, maybe even surprising.
Mark (00:43):
Absolutely yeah.
We're doing a deep dive todaybased on this really fascinating
article the Truth AboutCholesterol and Atherosclerosis
Debunking Old Myths with NewScience.
Rachel (00:54):
Okay.
Mark (00:55):
And it really does challenge that old simple idea
and brings out some crucial newinsights.
Rachel (01:01):
So if you're listening and you want to really get
what's going on with heartdisease, you know beyond just
that one cholesterol number, butwithout needing a PhD.
Mark (01:09):
Yeah, without getting totally bogged down in medical
jargon.
Rachel (01:12):
Then you're definitely in the right place.
Our goal today, our mission, isto pull out the key knowledge
from this piece what reallydrives atherosclerosis,
according to this newer science?
Mark (01:22):
And I think the most important thing to grab right
off the bat is thisAtherosclerosis isn't just about
how much cholesterol is likefloating around.
It's about the bigger picture.
It's about inflammation levelsin your body, how your body is
actually handling the fats, thelipids.
Nicolette (01:37):
Yeah.
Mark (01:38):
That context, it's everything.
Rachel (01:40):
Okay, so let's break that down.
Atherosclerosis 101.
And it sounds like it's waymore involved than just, you
know, pipes getting clogged withgunk.
Mark (01:48):
Precisely yeah, the article really stresses that
it's an active process.
It's deeply tied intoinflammation and your immune
system's response.
It's not just passive buildup.
Often the first domino to fallis some kind of problem with the
inner lining of your arteries.
That's called the endothelium.
Think of it like the smoothnonstick coating inside a pan
(02:10):
getting scratched up Right.
Rachel (02:12):
And what does the scratching?
What damages that lining?
Well, a few things.
Mark (02:15):
High blood pressure is a big one.
Insulin resistance, you knowwhere your body isn't responding
well to insulin.
Okay, smoking, obviously, andeven just sort of general wear
and tear from the things likeoxidative stress happening in
the body.
Rachel (02:26):
Oxidative stress like rust.
Mark (02:28):
Kind of yeah, it's chemical damage, and when this
lining, this endothelium, getsdamaged, it becomes leakier,
more permeable, and that allowscertain fat carrying particles
from your blood, especially theones that have a protein called
ApoB on them, to kind of slipthrough into the artery wall
itself.
Rachel (02:47):
ApoB.
Okay, we'll need to circle backto that one we will, and LDL,
the one everyone calls badcholesterol.
Mark (02:53):
that's a major type of these ApoB particles.
Rachel (02:55):
So, okay, these LDL particles get inside the artery
wall.
That's the cholesterol we'vealways been told is the bad guy.
Mark (03:02):
Well, ldl's actual job is just carrying cholesterol around
, which your body needs.
It's essential.
The trouble really kicks offwhen those LDL particles get
trapped in there, in thatsubendothelial space Trapped,
and then they undergo thisprocess called oxidation.
Basically, they get damaged.
They react with other molecules.
It's like metal rusting whenit's exposed to air and moisture
.
Nicolette (03:21):
Gotcha.
Mark (03:22):
And this oxidation gets ramped up by things like
inflammation and just poormetabolic health overall.
Rachel (03:27):
And this stuff, the oxidized LDL or ox LDL.
That's the real problem, child.
Mark (03:32):
That's what the article really highlights.
Yes, ox LDL isn't just, youknow, inert fat.
Sitting there it becomes highlyactive, it triggers
inflammation, it promotes thewhole atherosclerosis process.
Rachel (03:42):
How does it do that?
Mark (03:43):
Well, what's really interesting is how it acts.
Like a flare signal, itattracts your immune cells,
specifically macrophages, a typeof white blood cell, to come to
the site of injury.
Rachel (03:54):
Okay, so the body's trying to clean it up.
Mark (03:56):
Right, but that's where things go wrong.
These macrophages startgobbling up the oxidized LDL,
and in doing that they transforminto these things called foam
cells.
Rachel (04:06):
You might have heard of them.
Foam cells yeah, I think so.
Mark (04:09):
They're a key feature, a hallmark of the very early
stages of plaque development inthe arteries.
Okay, but it doesn't stop there.
This ox LDL also signals smoothmuscle cells in the artery wall
to migrate and lay down moresort of structural material
which helps those early fattystreaks grow into more complex,
hardened plaques.
(04:29):
Wow, the article even mentionedsome research identifying ox
LDL as a key initiator andactually a pretty strong marker
of cardiovascular risk.
Rachel (04:38):
Okay, so we've got the damage lining LDL gets in, it
rusts, gets oxidized and thenattracts the cleanup crew, the
macrophages which turn into foamcells and build up plaque.
Okay, but the article alsomentioned red blood cells.
That felt like it came out ofleft field.
Mark (04:56):
Yeah, that's a more recently understood part of the
story.
It seems red blood cells becomeparticularly important later on
, in the more advanced stages.
We're talking about plaquesthat are more vulnerable, the
ones that might become unstableand rupture.
Sometimes bleeding can happeninside these plaques.
It's called intraplaquehemorrhage.
Rachel (05:15):
Bleeding inside the plaque.
Mark (05:16):
Exactly, and when that happens, red blood cells get
into the plaque structure.
Rachel (05:20):
And why is that a problem?
They just carry oxygen, right.
Mark (05:24):
Normally, yes, but when they break down and the term is
hemolyzes, they release stuffthat makes the situation worse.
Rachel (05:31):
Like what.
Mark (05:32):
Well, one thing is free hemoglobin.
That actually contributes tomore oxidative stress right
there on the plaque.
Rachel (05:38):
More rust.
Mark (05:39):
Pretty much.
They also release iron, andiron is a big deal because it
acts like a catalyst, like aturbocharger for oxidizing even
more LDL through these thingscalled Fenton reactions.
Rachel (05:52):
OK, so it speeds up the bad process.
Mark (05:54):
Massively.
And finally, the membranes ofthose broken down.
Red blood cells releasephospholipids which can attract
even more macrophages to thearea, leading to more foam cells
.
Rachel (06:04):
So it's like a feedback loop from hell almost.
The plaque gets damaged, itbleeds, the red blood cells
break down, releasing stuff thatcauses more damage and
oxidation.
Mark (06:12):
Which then weakens the plaque further.
Rachel (06:14):
Exactly.
The article really emphasizeshow these processes amplify the
oxidative damage and, crucially,weaken the fibrous cap.
Mark (06:22):
The fibrous cap.
That's like the protectiveshell on the plaque.
That's right.
Rachel (06:26):
It's the layer holding it all together, keeping it
stable.
If that cap gets weak and thin,it's much more likely to
rupture, and that rupture iswhat triggers heart attacks and
strokes.
Mark (06:35):
Yeah, there was some important work cited that really
brought this red blood cellconnection to light.
It just underscores again thatatherosclerosis isn't simple.
It's this complex, multi-stepthing involving lipids, yes, but
also inflammation, oxidativestress, immune cells, even red
blood cells and vascular injury.
Rachel (06:54):
Man, that old clogged pipes idea really does miss
almost all of that complexity.
So, given all this, where didthe traditional focus on just
total cholesterol or LDL-Cactually come from?
What did it get right, maybe,and where did it fall short?
Mark (07:09):
Well, the article does acknowledge that focusing on
LDL-C, especially lowering it,has definitely helped.
It has reduced cardiovascularevents, particularly for people
already considered high risk.
Rachel (07:18):
Wait, so it wasn't totally wrong.
It helped some people.
Mark (07:21):
Not totally wrong.
No, it correctly identifiedthat LDL can be atherogenic,
meaning it can contribute toplaque, especially, as we now
know, when it gets oxidizedRight.
And yeah, plenty of studiesshowed that lowering LDL-C,
often with statins, does reducethe risk of future events,
especially in what we callsecondary prevention, people
who've already had an event.
Rachel (07:41):
Okay, so that's the what it got right.
Column.
Now the big question OK, sothat's the what it got right.
Column.
Now the big question what didit miss?
What are the key things thisnew science highlights?
Mark (07:50):
OK, this is where our understanding has really shifted
.
The article points out severalcritical things.
First, the number of LDLparticles in your blood might
actually be more important thanthe total amount of cholesterol
inside those particles, theLDL-C number.
Rachel (08:06):
The number of particles versus the amount of cholesterol
, explain that.
Mark (08:10):
So you could have someone whose LDL-C level looks, you
know, normal or even good, butthey might have a really high
concentration of small dense LDLparticles.
Rachel (08:19):
Ah, smaller particles, but lots of them.
Mark (08:21):
Exactly Each one of those particles.
Even if it's carrying lesscholesterol than a big fluffy
one can still get into theartery wall, get oxidized and
contribute to plaque.
Rachel (08:29):
And a standard test wouldn't show that.
Mark (08:31):
Not usually.
Your LDL-C might look fine.
You'd need to measure somethinglike ApoB, which we mentioned.
Rachel (08:35):
The protein marker Right , or the actual LDL particle
number, ldl-p, to see thathidden risk.
That makes a lot of sense.
Mark (08:47):
More potential troublemakers, even if they're
smaller.
What else did the old modelkind of overlook?
Another big one is the ratio ofyour triglycerides to your HDL
cholesterol.
Rachel (08:52):
Triglycerides to HDL.
Mark (08:54):
Okay, a high ratio there often signals underlying
metabolic stress, things likeinsulin resistance, maybe
elevated levels of other fattyparticles called VLDL remnants,
and often an overproduction ofthose small dense LDL particles
we just talked about.
This whole metabolic picture isreally pro-atherogenic.
It fuels the fire.
Rachel (09:14):
And HDL itself, the so-called good cholesterol.
Is it always good?
Mark (09:19):
Well, that's another nuance.
The article really stressesthat just having a high level of
HDL cholesterol, a high HDLCnumber, isn't automatically
protective.
Rachel (09:28):
Really.
Mark (09:28):
Yeah, what matters more is how well that HDL is
functioning.
Is it actually doing its jobeffectively?
Rachel (09:33):
Which is.
Mark (09:34):
Its main job is reverse cholesterol transport, basically
grabbing cholesterol from theartery walls and taking it back
to the liver.
But if your HDL isdysfunctional, how does it get
dysfunctional?
Things like oxidative stress,again damage from high blood
sugar, glycation or just generalinflammation can make HDL less
effective.
So the quantity on the reportmight look good, but the quality
(09:54):
might be poor.
It's not doing its protectivejob well.
Rachel (09:57):
OK, quality over quantity for HDL Got it and we
keep dancing around it, butinflammation seems like a
massive piece.
The traditional model maybedidn't emphasize enough.
Mark (10:07):
Absolutely huge, you could argue.
Cholesterol, or maybe oxidizedLDL gets the process started,
but inflammation is what reallydrives the plaque's progression
and, critically, its instability.
Rachel (10:18):
Instability, meaning likelihood to rupture.
Mark (10:21):
Exactly Markers in your blood like HSCRP, high
sensitivity C-reactive protein,or others like IL-6, TNF-alpha.
Studies show these correlatewith higher risk of heart
attacks and strokes, even inpeople whose LDL-C is
technically well controlled.
Rachel (10:34):
Wow, okay, and we talked about red blood cells earlier.
How did the old model misstheir contribution?
Mark (10:39):
Yeah, for a long time they just weren't really seen as
part of the atherosclerosisstory directly.
But, like we discussed, whenthey break down inside those
unstable plaques, the hemoglobinand iron get released Right and
that massively promotes LDLoxidation and foam cell
formation.
Plus, the leftover membranesfrom those broken red blood
cells can actually stimulatemore inflammation and even
(11:01):
encourage new leaky bloodvessels to grow within the
plaque itself.
Rachel (11:06):
Which just makes it even more unstable.
Mark (11:08):
Precisely it adds fuel to the fire.
Rachel (11:10):
And what about the structure, the physical
structure of the plaque itself?
Did the old model misssomething there too?
Mark (11:15):
It didn't really get into the why of plaque rupture as
much.
Now we understand thatinflammation activates certain
enzymes, like MMP9 is a key one.
Rachel (11:24):
MMP9.
Mark (11:25):
These enzymes basically act like molecular scissors.
They chew up the collagen andelastin, the stuff that gives
that fibrous cap its strengthand integrity.
Rachel (11:34):
So inflammation weakens the cap from the inside out.
Mark (11:37):
That's a good way to put it Makes the plaque fragile,
much more likely to break open.
Rachel (11:41):
And one last thing the article mentioned was
phytosterols plant sterolsAren't they supposed to be good?
You see them added to foods.
Mark (11:47):
That's a more nuanced point.
They can help lower LDLcholesterol for many people,
that's true, but but there'ssome emerging evidence,
according to the article,suggesting that for certain
individuals maybe people with agenetic condition called
cytosterolemia, or just peoplewho absorb these plant sterols
unusually well high levels ofspecific ones, like campesterol
(12:08):
and sidosterol, might actuallyget incorporated into the vessel
walls.
Uh-oh and potentiallycontribute to endothelial
dysfunction and maybe evenplaque instability.
It's a complex area still beingresearched.
Rachel (12:19):
So even good things aren't always universally good
for everyone.
Mark (12:23):
It's a reminder that biology is complicated and
context matters.
Rachel (12:27):
Definitely so.
Okay, it's abundantly clear.
The picture is way moreintricate than just high
cholesterol is bad.
This brings in particles,inflammation, metabolism,
structure.
It's a lot.
Let's really dig into one keypiece you mentioned.
Nicolette (12:40):
Yeah.
Rachel (12:40):
ApoB.
The article called it a bettermarker of risk.
Why?
What makes ApoB so important?
Mark (12:46):
Right, apob or apoliprotein B.
It's such an insightful markerbecause it's basically a protein
tag found on every singlepotentially harmful atherogenic
fat-carrying particle in yourblood.
Rachel (12:56):
Every single one, like LDL, VLDL.
Mark (12:59):
LDL, yes, but also VLDL, IDL, which are sort of
intermediate particles, and LPA,another important one, all the
ones that can contribute toplaque.
Rachel (13:08):
Okay.
Mark (13:08):
And here's the crucial part Each one of these
potentially harmful particlescarries exactly one molecule of
ApoB on its surface.
Just one.
Rachel (13:19):
Ah, so it's like a direct count.
Mark (13:20):
Exactly when you measure ApoB in the blood, you're
essentially getting a directcount of the total number of
these atherogenic particlesfloating around.
Rachel (13:28):
OK, so LDL-C measures the amount of cholesterol inside
the LDL particles.
Mark (13:32):
Right the cargo.
Rachel (13:33):
But APOB tells you how many actual vehicles, how many
particles are out there thatcould potentially deliver that
cargo into the artery wall.
Mark (13:41):
That's a perfect analogy and that's why it's often
considered a more accurate, moredirect measure of your actual
risk than LDL-C alone.
Rachel (13:48):
Because someone could have normal LDL-C.
Mark (13:50):
Right, but still have a very high number of those
smaller, denser LDL particles.
Each one carries lesscholesterol, so the LDL-C might
look OK.
Rachel (13:58):
But the ApoB count would be high because there are just
so many particles.
Mark (14:02):
Precisely, the ApoB test would likely pick up that
increased particle burden, thathigher traffic, whereas the
standard LDL-C might give falsereassurance.
Rachel (14:12):
And is there research backing this up?
Does ApoB predict risk better?
Mark (14:17):
Oh, yes, the article mentions.
Numerous large studies haveconsistently shown that ApoB is
a stronger predictor of futureheart attacks and strokes
compared to LDL-C or evennon-HDL cholesterol.
Rachel (14:28):
That makes sense.
Intuitively.
It's the particle getting inthat starts the problem.
Right, it's the particle numberin that starts the problem.
Mark (14:32):
Right, it's the particle number, the concentration, that
dictates the likelihood ofhitting the artery wall and
getting trapped.
Rachel (14:38):
And is the medical world catching on to this?
Is ApoB testing becoming morecommon?
Mark (14:43):
It definitely is gaining traction.
The article cites a 2021consensus statement from the
American College of Cardiology.
Ok, that actually recommendedconsidering ApoB as a primary
target for assessment,especially in people with
insulin resistance metabolicsyndrome or high triglycerides
situations where LDL-C can beparticularly misleading.
Rachel (15:01):
Right, those situations where you might have lots of
small dense particles.
Exactly so.
How does ApoB compare to thatother test you mentioned, LDL-P,
the particle number test?
Do they tell you the same thing?
Mark (15:17):
They're both aiming for the same goal of testing the
number of LDL particles andgenerally, both are better
predictors of risk than justLDLC.
Okay, but APOPE often has somepractical advantages it tends to
be less expensive.
It's more widely available onstandard lab panels.
Now, good points Doesn't alwaysrequire fasting, which is
convenient, and it'sincreasingly being built into
risk calculators and treatmentguidelines.
Rachel (15:38):
So easier to access and use clinically often.
Mark (15:42):
Often yes.
Rachel (15:42):
And the article specifically mentioned times
when checking ApoB is reallycrucial.
Mark (15:46):
Yes, it emphasizes its value, particularly if you have
normal or even low LDL-C, butyour triglycerides are high.
Rachel (15:53):
Okay, the discordant pattern.
Mark (15:54):
Exactly Also for anyone with metabolic syndrome or type
2 diabetes.
People with elevated LPA.
Rachel (16:00):
Which is that other genetic risk factor particle.
Mark (16:02):
Right, and just generally, anytime there seems to be a
mismatch between someone's LDL-Clevel and their other risk
factors or family history.
If things don't seem to add up,APOV can provide a lot of
clarity.
Rachel (16:14):
Are there target levels for ApoB?
Mark (16:16):
The article mentioned general targets, ideally aiming
for below 80 mL of GDL for manypeople and perhaps even lower,
like below 65 mL of GDL, forthose considered at very high
risk.
Rachel (16:27):
Okay, that really clarifies the ApoB story.
Now let's pivot back toinflammation.
The article didn't mince wordscalling it the real catalyst of
plaque formation.
Why such a strong focus oninflammation?
Mark (16:39):
It's a strong statement, yeah, but the science really
backs it up.
Think of it this wayCholesterol, maybe, specifically
oxidized LD, the gasolinepoured on the fire.
It's what transforms arelatively stable plaque into
something dangerous, somethingprone to growing rapidly and,
most importantly, rupturing.
Rachel (16:58):
So how does inflammation do that?
What's the mechanism?
Mark (17:00):
Well, we touched on parts of it.
Remember the damaged arterylining lets LDL in.
Once that LDL gets oxidized,it's a huge red flag for the
immune system.
It attracts those monocyteswhich become macrophages.
Rachel (17:12):
The cleanup crew that turns into foam cells.
Mark (17:20):
Exactly.
But as they engulf the ox LDL,they don't just sit there
quietly, they start churning outa whole bunch of inflammatory
signals, molecules calledcytokines, things like IL-6,.
Rachel (17:26):
TNF-alpha MCP-1.
Glyndals that call inreinforcements.
Mark (17:29):
Pretty much.
It creates thisself-perpetuating cycle More
inflammation attracts moreimmune cells.
It promotes the growth of thoseleaky new blood vessels within
the plaque which can bleed Right, causing more problems.
It fuels more oxidative stressand, as we discussed, it
activates those MMP enzymes.
Rachel (17:45):
The molecular scissors.
Mark (17:47):
That degrade the plaque's protective cap, making it weak
and unstable.
Rachel (17:50):
So inflammation is really driving the danger aspect
of the plaque's protective cap,making it weak and unstable.
So inflammation is reallydriving the danger aspect of the
plaque.
Mark (17:54):
That's the key insight.
It's less about the sheer sizeof the plaque sometimes and more
about how inflamed and unstableit is.
Rachel (18:00):
And can we measure this inflammation?
Are there tests?
Mark (18:03):
Yes, definitely.
The article mentions severalkey ones.
High sensitivity C-reactiveprotein, HSCRP, is probably the
most common.
Rachel (18:10):
H-CRP.
Mark (18:11):
Elevated levels, say above 2.0 mL, signal higher
cardiovascular risk, even ifyour LDL looks great.
Rachel (18:18):
Wow Okay.
Mark (18:19):
Interleukin-6, IL-6 is another important one.
Higher levels predict futureheart disease and it's actually
being explored as a therapeutictarget, itself Interesting.
And there's another calledLPPLA-2, which seems more
specific to inflammationhappening within the blood
vessels and unstable plaques.
So HSTRP gives a generalsystemic inflammation picture,
(18:40):
while IL-6 and LPLA2 might offermore targeted insights.
Rachel (18:44):
And wasn't there a big study mentioned that really
drove this inflammation pointhome.
Mark (18:48):
Absolutely the CANTOS trial from 2017.
It was a real landmark.
Rachel (18:52):
What did they do?
Mark (18:53):
They used a drug called canakinumab, which specifically
blocks one of those inflammatorycytokines, il-1.
They gave it to people who'dalready had a heart attack and
still had high HSCRP levelsindicating ongoing inflammation.
And the result.
The remarkable finding was thatthe drug significantly reduced
their risk of having anotherheart attack or stroke.
And here's the kicker.
Rachel (19:13):
Yeah.
Mark (19:13):
It did this without lowering their cholesterol or
lipid levels significantly.
Rachel (19:18):
Whoa how it was purely targeting the inflammation.
Mark (19:26):
Exactly.
It was really powerful proof ofconcept that targeting
inflammation directly couldreduce cardiovascular risk
independent of cholesterollowering.
Rachel (19:30):
That really changes everything, doesn't it?
So what are the implications?
How should this change how wethink about our risk?
Mark (19:36):
Well, the article strongly suggests that if you have, say,
normal LDL numbers but yourHSCRP is high, or if you have
metabolic syndrome or diabetes.
Right, or even chronicinflammatory conditions like
rheumatoid arthritis or lupus.
You might actually have asignificantly higher vascular
risk than a standard cholesterolpanel would suggest.
Rachel (19:56):
So the standard panel could be misleadingly reassuring
for those people.
Mark (19:59):
It could be.
The recommendation is thatthese individuals could really
benefit from a broader riskassessment, looking at
inflammatory markers alongsidelipids and focusing on lifestyle
changes that tackle both.
Rachel (20:10):
This really drives home that it's not just the stuff
floating in the blood but thewhole environment which leads
perfectly into the next pieceDiet, insulin resistance and
overall metabolic health.
How do these tie in?
Mark (20:23):
Fundamentally, the article frames the metabolic
environment as basically settingthe stage shaping your
cardiovascular risk, and insulinresistance is a key player here
.
Rachel (20:35):
How does being resistant to insulin mess with our lipids
and inflammation?
Mark (20:39):
It throws a lot of things out of whack.
Your liver starts pumping outmore VLDL.
Rachel (20:43):
Which raises triglycerides.
Mark (20:44):
Exactly and also promotes the formation of those small
dense LDL particles we keeptalking about.
Okay, insulin resistance alsotends to lower your HDL levels,
the good cholesterol and makesthe HDL you do have less
functional.
Impairs that reversecholesterol transport.
Rachel (20:58):
Double whammy.
Mark (20:59):
Yeah, and high insulin levels themselves can contribute
to other problems likeactivating the sympathetic
nervous system, causing sodiumretention and directly damaging
that endothelial lining.
Rachel (21:10):
So it hits on multiple fronts and you mentioned a
marker for this earlier.
Mark (21:13):
Yes, that triglyceride to HDL ratio.
The article highlights thatagain.
A ratio over 2.0 using MGDLunits is a really potent
indicator of underlying insulinresistance and higher
cardiovascular risk, even ifyour LDL-C looks perfect.
Rachel (21:29):
So simple yet powerful, and diet obviously must be a
huge lever here.
Mark (21:33):
Absolutely massive.
The types of food you eatdirectly influence these lipid
dynamics and inflammation.
Rachel (21:38):
What kind of diets are problematic according to the
article?
Mark (21:41):
Diets high in refined carbs, added sugars, processed
seed oils.
These tend to crank uptriglycerides, promote those
small LDLs and fuel inflammation.
Rachel (21:51):
Makes sense.
Mark (21:51):
Also, getting too many omega-6 fats without enough
balancing omega-3s cancontribute to oxidative stress
and endothelial issues.
Rachel (21:58):
Yeah.
Mark (21:59):
And just consistently eating too many calories overall
, regardless of source, tends toraise insulin and ramp up fat
production in the litter.
Rachel (22:06):
Okay, so that's the bad news.
What about the good news ondiet?
What helps?
Mark (22:09):
Definitely good news too.
The article mentions patternslike low-carbohydrate diets or
Mediterranean-style diets.
Rachel (22:15):
Why those?
Mark (22:15):
They've generally been shown to lower triglycerides,
improve HDL function, reducethose small dense LDLs and lower
inflammatory markers.
Things like time-restrictedeating or intermittent fasting
can also be beneficial for somepeople.
They can help lower fastinginsulin, improve lipid profiles,
reduce oxidative stress and, ofcourse, focusing on fiber-rich
(22:36):
whole foods, healthy fats likemonounsaturated fats from olive
oil, avocados, getting enoughomega-3s these all support
better lipid balance and helpkeep that endothelial lining
healthy.
Rachel (22:47):
So, bottom line, the same LDL-C number on a lab
report could mean very differentthings depending on someone's
insulin sensitivity, theirinflammation levels, their diet.
Mark (22:57):
Precisely.
That's why looking at LDL-C inisolation can be so incredibly
misleading.
You really need to assess forinsulin resistance.
Maybe look at inflammationmarkers.
Understand the dietary context,especially if the numbers are
kind of in that borderline zone.
Rachel (23:11):
Which brings us right to personalized risk.
How do we put all these piecestogether?
When should an elevated LDLreally worry us, and what are
the key tests beyond the basicsto get that fuller picture?
Mark (23:23):
Right.
The article stresses that asingle cholesterol number just
isn't enough.
Risk is contextual pull.
It depends on that wholemetabolic, inflammatory and even
structural picture in yourarteries.
Rachel (23:34):
So when does a high LDL become more concerning?
Mark (23:37):
It's more concerning if it's paired with other warning
signs, for example, high ApoBlevel, say over 100 milligdl, or
a high LDL particle count LDL-P.
That tells you the particleburden is high.
If you also have insulinresistance, metabolic syndrome
or type 2 diabetes, that's amajor red flag.
Rachel (23:54):
Makes sense.
Mark (23:55):
Elevated inflammatory markers like HSCRP or IL-6, a
high LPA level.
That genetic factor Got it Astrong family history of early
heart disease or personalhistory and, importantly, if
there's already evidence ofplaque held up on imaging like a
coronary artery calcium or TACscore over 100, that shows the
process is already underway.
Rachel (24:14):
So what are the key tests the article recommends to
get this deeper insight?
Let's recap those.
Mark (24:19):
Okay, beyond the standard lipids, apob is probably top of
the list for measuring thattotal atherogenic particle
number.
Rachel (24:25):
ApoB got it.
Mark (24:26):
LDL particle count.
Ldlp is another way to look atparticle quantity.
The triglyceride to HDL ratiois crucial for metabolic risk,
ideally aiming below 2.0.
Rachel (24:36):
DGHDL ratio.
Mark (24:37):
Check high-sensitivity CRP .
Hscrp for systemic inflammationideally below 1.0 mil-GO.
Rachel (24:45):
HSCRP.
Mark (24:46):
Fasting insulin and maybe a home IR calculation to
specifically check for insulinresistance.
Rachel (24:52):
Insulin and HMI.
Mark (24:53):
Lepoprotein or LPA to assess that genetic risk.
Maybe even things like ferritinand GGT which can give clues
about oxidative stress and liverissues impacting lipids.
Rachel (25:03):
Ferritin GGT.
Mark (25:05):
And then there's imaging the coronary artery calcium CAT
scan that directly measuresplaque burden and is a very
strong predictor of futureevents.
Rachel (25:12):
CAT scan.
Wow, that's a comprehensivelist.
Mark (25:15):
It gives you a much, much clearer picture than just LDL-C
alone.
Rachel (25:18):
And the article had an example to drive this home right
, Comparing two people.
Mark (25:22):
Yeah, it painted a picture .
Imagine two 48-year-old men,same LDL-C level on their report
.
Looks identical.
Rachel (25:29):
Okay.
Mark (25:29):
But man A has a much higher ApoB level, a poor TGHDL
ratio, high HSCRP and highfasting insulin.
Man-b has good levels for allthose other markers.
Rachel (25:40):
So even with the same LDL-C.
Mark (25:42):
MAN-A is at significantly higher risk.
The article makes that pointvery clearly.
Their underlying metabolic andinflammatory health is
completely different.
That's why this personalizedapproach, looking beyond just
one number, is so critical foraccurately understanding risk
and tailoring the rightinterventions.
Rachel (26:00):
This has been incredibly eye-opening really changes the
perspective.
So let's try and wrap this up.
What are the absolute keymessages, the main takeaways
from this deep dive into thenewer science?
Mark (26:09):
I think the biggest one is yes, cholesterol is involved in
atherosclerosis, but it's notjust about the amount, it's
about the form, like oxidizedLDL, the particle number, apob,
small dense LDL.
The overall context,inflammation, metabolic health,
those are way more critical.
Rachel (26:22):
Context is king.
Mark (26:23):
Exactly.
High ApoB, or lots of smallparticles, means high particle
burden.
Oxidized LDL is what reallytriggers the inflammation.
Inflammation is what makesplaques dangerous and likely to
rupture.
Rachel (26:36):
And underlying issues like insulin resistance fuel the
whole fire.
Mark (26:40):
They absolutely accelerate the whole process, and we even
learned that red blood cells inadvanced plaques can contribute
significantly to oxidativestress and instability through
hemoglobin and iron release.
Rachel (26:52):
So for people listening, what's the actionable thought
here?
What should we be thinkingabout differently?
Mark (26:57):
It really comes down to looking beyond that standard
lipid panel.
Talk to your doctor, ask aboutmeasuring ApoB.
Ask about HSCRP.
Understand your insulinsensitivity, maybe through
fasting insulin or that TGH dealratio.
Rachel (27:09):
Get the broader picture.
Mark (27:10):
Get the broader picture and never underestimate the
power of diet and lifestyle.
Those are your primary toolsfor influencing not just your
lipid numbers but that wholecrucial inflammatory and
metabolic environment.
Rachel (27:21):
So the provocative thought for everyone listening
might be stop fixating on justthat one cholesterol number.
Mark (27:27):
Yeah, ask yourself what's the rest of my story.
What's my ApoB, what's myinflammation level, what's my
metabolic health really like?
Rachel (27:33):
Exploring those other markers can give you a much
truer sense of your actualcardiovascular risk.
Mark (27:39):
Absolutely.
That empowers you to take moretargeted action.
Rachel (27:42):
This has been just fantastic A really important
discussion, I think.
Thank you so much for breakingdown all that complexity.
Mark (27:49):
My pleasure.
It's crucial information.
Rachel (27:50):
And just a final essential reminder for everyone
listening the information we'vegone over today is purely for
educational purposes.
It's crucial information.
And just a final essentialreminder for everyone listening
the information we've gone overtoday is purely for educational
purposes.
It is definitely not asubstitute for professional
medical advice.
Mark (28:02):
Absolutely Always.
Always consult with your owndoctor or qualified health care
provider for any questions orconcerns about your specific
health situation.
Rachel (28:12):
Couldn't agree more.
Get personalized advice fromyour trusted professional.
Nicolette (28:22):
Thanks for tuning into the Health Pulse.
If you found this episodehelpful, don't forget to
subscribe and share it withsomeone who might benefit.
For more health insights anddiagnostics, visit us online at
wwwquicklabmobilecom.
Stay informed, stay healthy andwe'll catch you in the next
episode.
Welcome to the Health Pulse, your go-to source for
quick, actionable insights onhealth, wellness and diagnostics
.
Whether you're looking tooptimize your well-being or stay
informed about the latest inmedical testing, we've got you
covered.
Join us as we break down keyhealth topics in just minutes.
Let's dive in.
Rachel (00:25):
You know, for the longest time, the story we all
heard about heart health waswell, pretty simple, wasn't it?
High cholesterol clogs yourarteries.
End of story.
Mark (00:34):
Right, like it was just plumbing.
Rachel (00:35):
Exactly, but lately the science seems to be pointing to,
I guess, a much more dynamicpicture, maybe even surprising.
Mark (00:43):
Absolutely yeah.
We're doing a deep dive todaybased on this really fascinating
article the Truth AboutCholesterol and Atherosclerosis
Debunking Old Myths with NewScience.
Rachel (00:54):
Okay.
Mark (00:55):
And it really does challenge that old simple idea
and brings out some crucial newinsights.
Rachel (01:01):
So if you're listening and you want to really get
what's going on with heartdisease, you know beyond just
that one cholesterol number, butwithout needing a PhD.
Mark (01:09):
Yeah, without getting totally bogged down in medical
jargon.
Rachel (01:12):
Then you're definitely in the right place.
Our goal today, our mission, isto pull out the key knowledge
from this piece what reallydrives atherosclerosis,
according to this newer science?
Mark (01:22):
And I think the most important thing to grab right
off the bat is thisAtherosclerosis isn't just about
how much cholesterol is likefloating around.
It's about the bigger picture.
It's about inflammation levelsin your body, how your body is
actually handling the fats, thelipids.
Nicolette (01:37):
Yeah.
Mark (01:38):
That context, it's everything.
Rachel (01:40):
Okay, so let's break that down.
Atherosclerosis 101.
And it sounds like it's waymore involved than just, you
know, pipes getting clogged withgunk.
Mark (01:48):
Precisely yeah, the article really stresses that
it's an active process.
It's deeply tied intoinflammation and your immune
system's response.
It's not just passive buildup.
Often the first domino to fallis some kind of problem with the
inner lining of your arteries.
That's called the endothelium.
Think of it like the smoothnonstick coating inside a pan
(02:10):
getting scratched up Right.
Rachel (02:12):
And what does the scratching?
What damages that lining?
Well, a few things.
Mark (02:15):
High blood pressure is a big one.
Insulin resistance, you knowwhere your body isn't responding
well to insulin.
Okay, smoking, obviously, andeven just sort of general wear
and tear from the things likeoxidative stress happening in
the body.
Rachel (02:26):
Oxidative stress like rust.
Mark (02:28):
Kind of yeah, it's chemical damage, and when this
lining, this endothelium, getsdamaged, it becomes leakier,
more permeable, and that allowscertain fat carrying particles
from your blood, especially theones that have a protein called
ApoB on them, to kind of slipthrough into the artery wall
itself.
Rachel (02:47):
ApoB.
Okay, we'll need to circle backto that one we will, and LDL,
the one everyone calls badcholesterol.
Mark (02:53):
that's a major type of these ApoB particles.
Rachel (02:55):
So, okay, these LDL particles get inside the artery
wall.
That's the cholesterol we'vealways been told is the bad guy.
Mark (03:02):
Well, ldl's actual job is just carrying cholesterol around
, which your body needs.
It's essential.
The trouble really kicks offwhen those LDL particles get
trapped in there, in thatsubendothelial space Trapped,
and then they undergo thisprocess called oxidation.
Basically, they get damaged.
They react with other molecules.
It's like metal rusting whenit's exposed to air and moisture
.
Nicolette (03:21):
Gotcha.
Mark (03:22):
And this oxidation gets ramped up by things like
inflammation and just poormetabolic health overall.
Rachel (03:27):
And this stuff, the oxidized LDL or ox LDL.
That's the real problem, child.
Mark (03:32):
That's what the article really highlights.
Yes, ox LDL isn't just, youknow, inert fat.
Sitting there it becomes highlyactive, it triggers
inflammation, it promotes thewhole atherosclerosis process.
Rachel (03:42):
How does it do that?
Mark (03:43):
Well, what's really interesting is how it acts.
Like a flare signal, itattracts your immune cells,
specifically macrophages, a typeof white blood cell, to come to
the site of injury.
Rachel (03:54):
Okay, so the body's trying to clean it up.
Mark (03:56):
Right, but that's where things go wrong.
These macrophages startgobbling up the oxidized LDL,
and in doing that they transforminto these things called foam
cells.
Rachel (04:06):
You might have heard of them.
Foam cells yeah, I think so.
Mark (04:09):
They're a key feature, a hallmark of the very early
stages of plaque development inthe arteries.
Okay, but it doesn't stop there.
This ox LDL also signals smoothmuscle cells in the artery wall
to migrate and lay down moresort of structural material
which helps those early fattystreaks grow into more complex,
hardened plaques.
(04:29):
Wow, the article even mentionedsome research identifying ox
LDL as a key initiator andactually a pretty strong marker
of cardiovascular risk.
Rachel (04:38):
Okay, so we've got the damage lining LDL gets in, it
rusts, gets oxidized and thenattracts the cleanup crew, the
macrophages which turn into foamcells and build up plaque.
Okay, but the article alsomentioned red blood cells.
That felt like it came out ofleft field.
Mark (04:56):
Yeah, that's a more recently understood part of the
story.
It seems red blood cells becomeparticularly important later on
, in the more advanced stages.
We're talking about plaquesthat are more vulnerable, the
ones that might become unstableand rupture.
Sometimes bleeding can happeninside these plaques.
It's called intraplaquehemorrhage.
Rachel (05:15):
Bleeding inside the plaque.
Mark (05:16):
Exactly, and when that happens, red blood cells get
into the plaque structure.
Rachel (05:20):
And why is that a problem?
They just carry oxygen, right.
Mark (05:24):
Normally, yes, but when they break down and the term is
hemolyzes, they release stuffthat makes the situation worse.
Rachel (05:31):
Like what.
Mark (05:32):
Well, one thing is free hemoglobin.
That actually contributes tomore oxidative stress right
there on the plaque.
Rachel (05:38):
More rust.
Mark (05:39):
Pretty much.
They also release iron, andiron is a big deal because it
acts like a catalyst, like aturbocharger for oxidizing even
more LDL through these thingscalled Fenton reactions.
Rachel (05:52):
OK, so it speeds up the bad process.
Mark (05:54):
Massively.
And finally, the membranes ofthose broken down.
Red blood cells releasephospholipids which can attract
even more macrophages to thearea, leading to more foam cells
.
Rachel (06:04):
So it's like a feedback loop from hell almost.
The plaque gets damaged, itbleeds, the red blood cells
break down, releasing stuff thatcauses more damage and
oxidation.
Mark (06:12):
Which then weakens the plaque further.
Rachel (06:14):
Exactly.
The article really emphasizeshow these processes amplify the
oxidative damage and, crucially,weaken the fibrous cap.
Mark (06:22):
The fibrous cap.
That's like the protectiveshell on the plaque.
That's right.
Rachel (06:26):
It's the layer holding it all together, keeping it
stable.
If that cap gets weak and thin,it's much more likely to
rupture, and that rupture iswhat triggers heart attacks and
strokes.
Mark (06:35):
Yeah, there was some important work cited that really
brought this red blood cellconnection to light.
It just underscores again thatatherosclerosis isn't simple.
It's this complex, multi-stepthing involving lipids, yes, but
also inflammation, oxidativestress, immune cells, even red
blood cells and vascular injury.
Rachel (06:54):
Man, that old clogged pipes idea really does miss
almost all of that complexity.
So, given all this, where didthe traditional focus on just
total cholesterol or LDL-Cactually come from?
What did it get right, maybe,and where did it fall short?
Mark (07:09):
Well, the article does acknowledge that focusing on
LDL-C, especially lowering it,has definitely helped.
It has reduced cardiovascularevents, particularly for people
already considered high risk.
Rachel (07:18):
Wait, so it wasn't totally wrong.
It helped some people.
Mark (07:21):
Not totally wrong.
No, it correctly identifiedthat LDL can be atherogenic,
meaning it can contribute toplaque, especially, as we now
know, when it gets oxidizedRight.
And yeah, plenty of studiesshowed that lowering LDL-C,
often with statins, does reducethe risk of future events,
especially in what we callsecondary prevention, people
who've already had an event.
Rachel (07:41):
Okay, so that's the what it got right.
Column.
Now the big question OK, sothat's the what it got right.
Column.
Now the big question what didit miss?
What are the key things thisnew science highlights?
Mark (07:50):
OK, this is where our understanding has really shifted
.
The article points out severalcritical things.
First, the number of LDLparticles in your blood might
actually be more important thanthe total amount of cholesterol
inside those particles, theLDL-C number.
Rachel (08:06):
The number of particles versus the amount of cholesterol
, explain that.
Mark (08:10):
So you could have someone whose LDL-C level looks, you
know, normal or even good, butthey might have a really high
concentration of small dense LDLparticles.
Rachel (08:19):
Ah, smaller particles, but lots of them.
Mark (08:21):
Exactly Each one of those particles.
Even if it's carrying lesscholesterol than a big fluffy
one can still get into theartery wall, get oxidized and
contribute to plaque.
Rachel (08:29):
And a standard test wouldn't show that.
Mark (08:31):
Not usually.
Your LDL-C might look fine.
You'd need to measure somethinglike ApoB, which we mentioned.
Rachel (08:35):
The protein marker Right , or the actual LDL particle
number, ldl-p, to see thathidden risk.
That makes a lot of sense.
Mark (08:47):
More potential troublemakers, even if they're
smaller.
What else did the old modelkind of overlook?
Another big one is the ratio ofyour triglycerides to your HDL
cholesterol.
Rachel (08:52):
Triglycerides to HDL.
Mark (08:54):
Okay, a high ratio there often signals underlying
metabolic stress, things likeinsulin resistance, maybe
elevated levels of other fattyparticles called VLDL remnants,
and often an overproduction ofthose small dense LDL particles
we just talked about.
This whole metabolic picture isreally pro-atherogenic.
It fuels the fire.
Rachel (09:14):
And HDL itself, the so-called good cholesterol.
Is it always good?
Mark (09:19):
Well, that's another nuance.
The article really stressesthat just having a high level of
HDL cholesterol, a high HDLCnumber, isn't automatically
protective.
Rachel (09:28):
Really.
Mark (09:28):
Yeah, what matters more is how well that HDL is
functioning.
Is it actually doing its jobeffectively?
Rachel (09:33):
Which is.
Mark (09:34):
Its main job is reverse cholesterol transport, basically
grabbing cholesterol from theartery walls and taking it back
to the liver.
But if your HDL isdysfunctional, how does it get
dysfunctional?
Things like oxidative stress,again damage from high blood
sugar, glycation or just generalinflammation can make HDL less
effective.
So the quantity on the reportmight look good, but the quality
(09:54):
might be poor.
It's not doing its protectivejob well.
Rachel (09:57):
OK, quality over quantity for HDL Got it and we
keep dancing around it, butinflammation seems like a
massive piece.
The traditional model maybedidn't emphasize enough.
Mark (10:07):
Absolutely huge, you could argue.
Cholesterol, or maybe oxidizedLDL gets the process started,
but inflammation is what reallydrives the plaque's progression
and, critically, its instability.
Rachel (10:18):
Instability, meaning likelihood to rupture.
Mark (10:21):
Exactly Markers in your blood like HSCRP, high
sensitivity C-reactive protein,or others like IL-6, TNF-alpha.
Studies show these correlatewith higher risk of heart
attacks and strokes, even inpeople whose LDL-C is
technically well controlled.
Rachel (10:34):
Wow, okay, and we talked about red blood cells earlier.
How did the old model misstheir contribution?
Mark (10:39):
Yeah, for a long time they just weren't really seen as
part of the atherosclerosisstory directly.
But, like we discussed, whenthey break down inside those
unstable plaques, the hemoglobinand iron get released Right and
that massively promotes LDLoxidation and foam cell
formation.
Plus, the leftover membranesfrom those broken red blood
cells can actually stimulatemore inflammation and even
(11:01):
encourage new leaky bloodvessels to grow within the
plaque itself.
Rachel (11:06):
Which just makes it even more unstable.
Mark (11:08):
Precisely it adds fuel to the fire.
Rachel (11:10):
And what about the structure, the physical
structure of the plaque itself?
Did the old model misssomething there too?
Mark (11:15):
It didn't really get into the why of plaque rupture as
much.
Now we understand thatinflammation activates certain
enzymes, like MMP9 is a key one.
Rachel (11:24):
MMP9.
Mark (11:25):
These enzymes basically act like molecular scissors.
They chew up the collagen andelastin, the stuff that gives
that fibrous cap its strengthand integrity.
Rachel (11:34):
So inflammation weakens the cap from the inside out.
Mark (11:37):
That's a good way to put it Makes the plaque fragile,
much more likely to break open.
Rachel (11:41):
And one last thing the article mentioned was
phytosterols plant sterolsAren't they supposed to be good?
You see them added to foods.
Mark (11:47):
That's a more nuanced point.
They can help lower LDLcholesterol for many people,
that's true, but but there'ssome emerging evidence,
according to the article,suggesting that for certain
individuals maybe people with agenetic condition called
cytosterolemia, or just peoplewho absorb these plant sterols
unusually well high levels ofspecific ones, like campesterol
(12:08):
and sidosterol, might actuallyget incorporated into the vessel
walls.
Uh-oh and potentiallycontribute to endothelial
dysfunction and maybe evenplaque instability.
It's a complex area still beingresearched.
Rachel (12:19):
So even good things aren't always universally good
for everyone.
Mark (12:23):
It's a reminder that biology is complicated and
context matters.
Rachel (12:27):
Definitely so.
Okay, it's abundantly clear.
The picture is way moreintricate than just high
cholesterol is bad.
This brings in particles,inflammation, metabolism,
structure.
It's a lot.
Let's really dig into one keypiece you mentioned.
Nicolette (12:40):
Yeah.
Rachel (12:40):
ApoB.
The article called it a bettermarker of risk.
Why?
What makes ApoB so important?
Mark (12:46):
Right, apob or apoliprotein B.
It's such an insightful markerbecause it's basically a protein
tag found on every singlepotentially harmful atherogenic
fat-carrying particle in yourblood.
Rachel (12:56):
Every single one, like LDL, VLDL.
Mark (12:59):
LDL, yes, but also VLDL, IDL, which are sort of
intermediate particles, and LPA,another important one, all the
ones that can contribute toplaque.
Rachel (13:08):
Okay.
Mark (13:08):
And here's the crucial part Each one of these
potentially harmful particlescarries exactly one molecule of
ApoB on its surface.
Just one.
Rachel (13:19):
Ah, so it's like a direct count.
Mark (13:20):
Exactly when you measure ApoB in the blood, you're
essentially getting a directcount of the total number of
these atherogenic particlesfloating around.
Rachel (13:28):
OK, so LDL-C measures the amount of cholesterol inside
the LDL particles.
Mark (13:32):
Right the cargo.
Rachel (13:33):
But APOB tells you how many actual vehicles, how many
particles are out there thatcould potentially deliver that
cargo into the artery wall.
Mark (13:41):
That's a perfect analogy and that's why it's often
considered a more accurate, moredirect measure of your actual
risk than LDL-C alone.
Rachel (13:48):
Because someone could have normal LDL-C.
Mark (13:50):
Right, but still have a very high number of those
smaller, denser LDL particles.
Each one carries lesscholesterol, so the LDL-C might
look OK.
Rachel (13:58):
But the ApoB count would be high because there are just
so many particles.
Mark (14:02):
Precisely, the ApoB test would likely pick up that
increased particle burden, thathigher traffic, whereas the
standard LDL-C might give falsereassurance.
Rachel (14:12):
And is there research backing this up?
Does ApoB predict risk better?
Mark (14:17):
Oh, yes, the article mentions.
Numerous large studies haveconsistently shown that ApoB is
a stronger predictor of futureheart attacks and strokes
compared to LDL-C or evennon-HDL cholesterol.
Rachel (14:28):
That makes sense.
Intuitively.
It's the particle getting inthat starts the problem.
Right, it's the particle numberin that starts the problem.
Mark (14:32):
Right, it's the particle number, the concentration, that
dictates the likelihood ofhitting the artery wall and
getting trapped.
Rachel (14:38):
And is the medical world catching on to this?
Is ApoB testing becoming morecommon?
Mark (14:43):
It definitely is gaining traction.
The article cites a 2021consensus statement from the
American College of Cardiology.
Ok, that actually recommendedconsidering ApoB as a primary
target for assessment,especially in people with
insulin resistance metabolicsyndrome or high triglycerides
situations where LDL-C can beparticularly misleading.
Rachel (15:01):
Right, those situations where you might have lots of
small dense particles.
Exactly so.
How does ApoB compare to thatother test you mentioned, LDL-P,
the particle number test?
Do they tell you the same thing?
Mark (15:17):
They're both aiming for the same goal of testing the
number of LDL particles andgenerally, both are better
predictors of risk than justLDLC.
Okay, but APOPE often has somepractical advantages it tends to
be less expensive.
It's more widely available onstandard lab panels.
Now, good points Doesn't alwaysrequire fasting, which is
convenient, and it'sincreasingly being built into
risk calculators and treatmentguidelines.
Rachel (15:38):
So easier to access and use clinically often.
Mark (15:42):
Often yes.
Rachel (15:42):
And the article specifically mentioned times
when checking ApoB is reallycrucial.
Mark (15:46):
Yes, it emphasizes its value, particularly if you have
normal or even low LDL-C, butyour triglycerides are high.
Rachel (15:53):
Okay, the discordant pattern.
Mark (15:54):
Exactly Also for anyone with metabolic syndrome or type
2 diabetes.
People with elevated LPA.
Rachel (16:00):
Which is that other genetic risk factor particle.
Mark (16:02):
Right, and just generally, anytime there seems to be a
mismatch between someone's LDL-Clevel and their other risk
factors or family history.
If things don't seem to add up,APOV can provide a lot of
clarity.
Rachel (16:14):
Are there target levels for ApoB?
Mark (16:16):
The article mentioned general targets, ideally aiming
for below 80 mL of GDL for manypeople and perhaps even lower,
like below 65 mL of GDL, forthose considered at very high
risk.
Rachel (16:27):
Okay, that really clarifies the ApoB story.
Now let's pivot back toinflammation.
The article didn't mince wordscalling it the real catalyst of
plaque formation.
Why such a strong focus oninflammation?
Mark (16:39):
It's a strong statement, yeah, but the science really
backs it up.
Think of it this wayCholesterol, maybe, specifically
oxidized LD, the gasolinepoured on the fire.
It's what transforms arelatively stable plaque into
something dangerous, somethingprone to growing rapidly and,
most importantly, rupturing.
Rachel (16:58):
So how does inflammation do that?
What's the mechanism?
Mark (17:00):
Well, we touched on parts of it.
Remember the damaged arterylining lets LDL in.
Once that LDL gets oxidized,it's a huge red flag for the
immune system.
It attracts those monocyteswhich become macrophages.
Rachel (17:12):
The cleanup crew that turns into foam cells.
Mark (17:20):
Exactly.
But as they engulf the ox LDL,they don't just sit there
quietly, they start churning outa whole bunch of inflammatory
signals, molecules calledcytokines, things like IL-6,.
Rachel (17:26):
TNF-alpha MCP-1.
Glyndals that call inreinforcements.
Mark (17:29):
Pretty much.
It creates thisself-perpetuating cycle More
inflammation attracts moreimmune cells.
It promotes the growth of thoseleaky new blood vessels within
the plaque which can bleed Right, causing more problems.
It fuels more oxidative stressand, as we discussed, it
activates those MMP enzymes.
Rachel (17:45):
The molecular scissors.
Mark (17:47):
That degrade the plaque's protective cap, making it weak
and unstable.
Rachel (17:50):
So inflammation is really driving the danger aspect
of the plaque's protective cap,making it weak and unstable.
So inflammation is reallydriving the danger aspect of the
plaque.
Mark (17:54):
That's the key insight.
It's less about the sheer sizeof the plaque sometimes and more
about how inflamed and unstableit is.
Rachel (18:00):
And can we measure this inflammation?
Are there tests?
Mark (18:03):
Yes, definitely.
The article mentions severalkey ones.
High sensitivity C-reactiveprotein, HSCRP, is probably the
most common.
Rachel (18:10):
H-CRP.
Mark (18:11):
Elevated levels, say above 2.0 mL, signal higher
cardiovascular risk, even ifyour LDL looks great.
Rachel (18:18):
Wow Okay.
Mark (18:19):
Interleukin-6, IL-6 is another important one.
Higher levels predict futureheart disease and it's actually
being explored as a therapeutictarget, itself Interesting.
And there's another calledLPPLA-2, which seems more
specific to inflammationhappening within the blood
vessels and unstable plaques.
So HSTRP gives a generalsystemic inflammation picture,
(18:40):
while IL-6 and LPLA2 might offermore targeted insights.
Rachel (18:44):
And wasn't there a big study mentioned that really
drove this inflammation pointhome.
Mark (18:48):
Absolutely the CANTOS trial from 2017.
It was a real landmark.
Rachel (18:52):
What did they do?
Mark (18:53):
They used a drug called canakinumab, which specifically
blocks one of those inflammatorycytokines, il-1.
They gave it to people who'dalready had a heart attack and
still had high HSCRP levelsindicating ongoing inflammation.
And the result.
The remarkable finding was thatthe drug significantly reduced
their risk of having anotherheart attack or stroke.
And here's the kicker.
Rachel (19:13):
Yeah.
Mark (19:13):
It did this without lowering their cholesterol or
lipid levels significantly.
Rachel (19:18):
Whoa how it was purely targeting the inflammation.
Mark (19:26):
Exactly.
It was really powerful proof ofconcept that targeting
inflammation directly couldreduce cardiovascular risk
independent of cholesterollowering.
Rachel (19:30):
That really changes everything, doesn't it?
So what are the implications?
How should this change how wethink about our risk?
Mark (19:36):
Well, the article strongly suggests that if you have, say,
normal LDL numbers but yourHSCRP is high, or if you have
metabolic syndrome or diabetes.
Right, or even chronicinflammatory conditions like
rheumatoid arthritis or lupus.
You might actually have asignificantly higher vascular
risk than a standard cholesterolpanel would suggest.
Rachel (19:56):
So the standard panel could be misleadingly reassuring
for those people.
Mark (19:59):
It could be.
The recommendation is thatthese individuals could really
benefit from a broader riskassessment, looking at
inflammatory markers alongsidelipids and focusing on lifestyle
changes that tackle both.
Rachel (20:10):
This really drives home that it's not just the stuff
floating in the blood but thewhole environment which leads
perfectly into the next pieceDiet, insulin resistance and
overall metabolic health.
How do these tie in?
Mark (20:23):
Fundamentally, the article frames the metabolic
environment as basically settingthe stage shaping your
cardiovascular risk, and insulinresistance is a key player here
.
Rachel (20:35):
How does being resistant to insulin mess with our lipids
and inflammation?
Mark (20:39):
It throws a lot of things out of whack.
Your liver starts pumping outmore VLDL.
Rachel (20:43):
Which raises triglycerides.
Mark (20:44):
Exactly and also promotes the formation of those small
dense LDL particles we keeptalking about.
Okay, insulin resistance alsotends to lower your HDL levels,
the good cholesterol and makesthe HDL you do have less
functional.
Impairs that reversecholesterol transport.
Rachel (20:58):
Double whammy.
Mark (20:59):
Yeah, and high insulin levels themselves can contribute
to other problems likeactivating the sympathetic
nervous system, causing sodiumretention and directly damaging
that endothelial lining.
Rachel (21:10):
So it hits on multiple fronts and you mentioned a
marker for this earlier.
Mark (21:13):
Yes, that triglyceride to HDL ratio.
The article highlights thatagain.
A ratio over 2.0 using MGDLunits is a really potent
indicator of underlying insulinresistance and higher
cardiovascular risk, even ifyour LDL-C looks perfect.
Rachel (21:29):
So simple yet powerful, and diet obviously must be a
huge lever here.
Mark (21:33):
Absolutely massive.
The types of food you eatdirectly influence these lipid
dynamics and inflammation.
Rachel (21:38):
What kind of diets are problematic according to the
article?
Mark (21:41):
Diets high in refined carbs, added sugars, processed
seed oils.
These tend to crank uptriglycerides, promote those
small LDLs and fuel inflammation.
Rachel (21:51):
Makes sense.
Mark (21:51):
Also, getting too many omega-6 fats without enough
balancing omega-3s cancontribute to oxidative stress
and endothelial issues.
Rachel (21:58):
Yeah.
Mark (21:59):
And just consistently eating too many calories overall
, regardless of source, tends toraise insulin and ramp up fat
production in the litter.
Rachel (22:06):
Okay, so that's the bad news.
What about the good news ondiet?
What helps?
Mark (22:09):
Definitely good news too.
The article mentions patternslike low-carbohydrate diets or
Mediterranean-style diets.
Rachel (22:15):
Why those?
Mark (22:15):
They've generally been shown to lower triglycerides,
improve HDL function, reducethose small dense LDLs and lower
inflammatory markers.
Things like time-restrictedeating or intermittent fasting
can also be beneficial for somepeople.
They can help lower fastinginsulin, improve lipid profiles,
reduce oxidative stress and, ofcourse, focusing on fiber-rich
(22:36):
whole foods, healthy fats likemonounsaturated fats from olive
oil, avocados, getting enoughomega-3s these all support
better lipid balance and helpkeep that endothelial lining
healthy.
Rachel (22:47):
So, bottom line, the same LDL-C number on a lab
report could mean very differentthings depending on someone's
insulin sensitivity, theirinflammation levels, their diet.
Mark (22:57):
Precisely.
That's why looking at LDL-C inisolation can be so incredibly
misleading.
You really need to assess forinsulin resistance.
Maybe look at inflammationmarkers.
Understand the dietary context,especially if the numbers are
kind of in that borderline zone.
Rachel (23:11):
Which brings us right to personalized risk.
How do we put all these piecestogether?
When should an elevated LDLreally worry us, and what are
the key tests beyond the basicsto get that fuller picture?
Mark (23:23):
Right.
The article stresses that asingle cholesterol number just
isn't enough.
Risk is contextual pull.
It depends on that wholemetabolic, inflammatory and even
structural picture in yourarteries.
Rachel (23:34):
So when does a high LDL become more concerning?
Mark (23:37):
It's more concerning if it's paired with other warning
signs, for example, high ApoBlevel, say over 100 milligdl, or
a high LDL particle count LDL-P.
That tells you the particleburden is high.
If you also have insulinresistance, metabolic syndrome
or type 2 diabetes, that's amajor red flag.
Rachel (23:54):
Makes sense.
Mark (23:55):
Elevated inflammatory markers like HSCRP or IL-6, a
high LPA level.
That genetic factor Got it Astrong family history of early
heart disease or personalhistory and, importantly, if
there's already evidence ofplaque held up on imaging like a
coronary artery calcium or TACscore over 100, that shows the
process is already underway.
Rachel (24:14):
So what are the key tests the article recommends to
get this deeper insight?
Let's recap those.
Mark (24:19):
Okay, beyond the standard lipids, apob is probably top of
the list for measuring thattotal atherogenic particle
number.
Rachel (24:25):
ApoB got it.
Mark (24:26):
LDL particle count.
Ldlp is another way to look atparticle quantity.
The triglyceride to HDL ratiois crucial for metabolic risk,
ideally aiming below 2.0.
Rachel (24:36):
DGHDL ratio.
Mark (24:37):
Check high-sensitivity CRP .
Hscrp for systemic inflammationideally below 1.0 mil-GO.
Rachel (24:45):
HSCRP.
Mark (24:46):
Fasting insulin and maybe a home IR calculation to
specifically check for insulinresistance.
Rachel (24:52):
Insulin and HMI.
Mark (24:53):
Lepoprotein or LPA to assess that genetic risk.
Maybe even things like ferritinand GGT which can give clues
about oxidative stress and liverissues impacting lipids.
Rachel (25:03):
Ferritin GGT.
Mark (25:05):
And then there's imaging the coronary artery calcium CAT
scan that directly measuresplaque burden and is a very
strong predictor of futureevents.
Rachel (25:12):
CAT scan.
Wow, that's a comprehensivelist.
Mark (25:15):
It gives you a much, much clearer picture than just LDL-C
alone.
Rachel (25:18):
And the article had an example to drive this home right
, Comparing two people.
Mark (25:22):
Yeah, it painted a picture .
Imagine two 48-year-old men,same LDL-C level on their report
.
Looks identical.
Rachel (25:29):
Okay.
Mark (25:29):
But man A has a much higher ApoB level, a poor TGHDL
ratio, high HSCRP and highfasting insulin.
Man-b has good levels for allthose other markers.
Rachel (25:40):
So even with the same LDL-C.
Mark (25:42):
MAN-A is at significantly higher risk.
The article makes that pointvery clearly.
Their underlying metabolic andinflammatory health is
completely different.
That's why this personalizedapproach, looking beyond just
one number, is so critical foraccurately understanding risk
and tailoring the rightinterventions.
Rachel (26:00):
This has been incredibly eye-opening really changes the
perspective.
So let's try and wrap this up.
What are the absolute keymessages, the main takeaways
from this deep dive into thenewer science?
Mark (26:09):
I think the biggest one is yes, cholesterol is involved in
atherosclerosis, but it's notjust about the amount, it's
about the form, like oxidizedLDL, the particle number, apob,
small dense LDL.
The overall context,inflammation, metabolic health,
those are way more critical.
Rachel (26:22):
Context is king.
Mark (26:23):
Exactly.
High ApoB, or lots of smallparticles, means high particle
burden.
Oxidized LDL is what reallytriggers the inflammation.
Inflammation is what makesplaques dangerous and likely to
rupture.
Rachel (26:36):
And underlying issues like insulin resistance fuel the
whole fire.
Mark (26:40):
They absolutely accelerate the whole process, and we even
learned that red blood cells inadvanced plaques can contribute
significantly to oxidativestress and instability through
hemoglobin and iron release.
Rachel (26:52):
So for people listening, what's the actionable thought
here?
What should we be thinkingabout differently?
Mark (26:57):
It really comes down to looking beyond that standard
lipid panel.
Talk to your doctor, ask aboutmeasuring ApoB.
Ask about HSCRP.
Understand your insulinsensitivity, maybe through
fasting insulin or that TGH dealratio.
Rachel (27:09):
Get the broader picture.
Mark (27:10):
Get the broader picture and never underestimate the
power of diet and lifestyle.
Those are your primary toolsfor influencing not just your
lipid numbers but that wholecrucial inflammatory and
metabolic environment.
Rachel (27:21):
So the provocative thought for everyone listening
might be stop fixating on justthat one cholesterol number.
Mark (27:27):
Yeah, ask yourself what's the rest of my story.
What's my ApoB, what's myinflammation level, what's my
metabolic health really like?
Rachel (27:33):
Exploring those other markers can give you a much
truer sense of your actualcardiovascular risk.
Mark (27:39):
Absolutely.
That empowers you to take moretargeted action.
Rachel (27:42):
This has been just fantastic A really important
discussion, I think.
Thank you so much for breakingdown all that complexity.
Mark (27:49):
My pleasure.
It's crucial information.
Rachel (27:50):
And just a final essential reminder for everyone
listening the information we'vegone over today is purely for
educational purposes.
It's crucial information.
And just a final essentialreminder for everyone listening
the information we've gone overtoday is purely for educational
purposes.
It is definitely not asubstitute for professional
medical advice.
Mark (28:02):
Absolutely Always.
Always consult with your owndoctor or qualified health care
provider for any questions orconcerns about your specific
health situation.
Rachel (28:12):
Couldn't agree more.
Get personalized advice fromyour trusted professional.
Nicolette (28:22):
Thanks for tuning into the Health Pulse.
If you found this episodehelpful, don't forget to
subscribe and share it withsomeone who might benefit.
For more health insights anddiagnostics, visit us online at
wwwquicklabmobilecom.
Stay informed, stay healthy andwe'll catch you in the next
episode.
Popular Podcasts
Amy Robach & T.J. Holmes present: Aubrey O’Day, Covering the Diddy Trial
Introducing… Aubrey O’Day Diddy’s former protege, television personality, platinum selling music artist, Danity Kane alum Aubrey O’Day joins veteran journalists Amy Robach and TJ Holmes to provide a unique perspective on the trial that has captivated the attention of the nation. Join them throughout the trial as they discuss, debate, and dissect every detail, every aspect of the proceedings. Aubrey will offer her opinions and expertise, as only she is qualified to do given her first-hand knowledge. From her days on Making the Band, as she emerged as the breakout star, the truth of the situation would be the opposite of the glitz and glamour. Listen throughout every minute of the trial, for this exclusive coverage. Amy Robach and TJ Holmes present Aubrey O’Day, Covering the Diddy Trial, an iHeartRadio podcast.
Dateline NBC
Current and classic episodes, featuring compelling true-crime mysteries, powerful documentaries and in-depth investigations. Follow now to get the latest episodes of Dateline NBC completely free, or subscribe to Dateline Premium for ad-free listening and exclusive bonus content: DatelinePremium.com
The Breakfast Club
The World's Most Dangerous Morning Show, The Breakfast Club, With DJ Envy And Charlamagne Tha God!