Focus on THIS Instead: Poor Metabolic Health and Low HDL is a Greater Predictor of Coronary Artery Calcium than LDL Cholesterol
A new study finds poor metabolic health and low HDL is a greater predictor of coronary artery calcium than LDL cholesterol.
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Link to study: https://bit.ly/3Zj56fA
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—————————————-Show Notes————————————-
0:00 Intro
0:30 LDL does not correlate with the degree of coronary artery plaque.
1:02 HDL is protective against coronary artery disease and plaquing.
2:10 Triglycerides correlate with diabetes, coronary artery disease and plaquing.
3:45 HDL size is highly predictive.
5:15 LDL, vLDL, and IDL had no strong association.
8:00 LDL may be lower with prediabetes and diabetes, reflecting imbalance.
12:10 HDL is increased by lifestyle.
13:00 Plaquing is more common in diabetics.
15:47 High triglycerides increase odds of metabolic disease by 100%.
18:00 The smaller HDL particles become, the less protective they are.
19:13 Coronary artery calcium is associated with HDL size, concentration and composition.
21:20 High HDL with low triglycerides is linked with better metabolic health.
23:10 Exercise increases the size and number of your protective HDL.
Transcript
Intro
0:00a new study found that LDL cholesterol
0:02does not strongly correlate with the
0:04degree of coronary artery
0:06atherosclerosis this is a very important
0:08study I’m going to talk slow
0:10intentionally so that no messages Get
0:12Lost in Translation this is a study that
0:15was just published in the international
0:16Journal of Cardiology involving 5,000
0:19patients that were normal glycemic
0:21pre-diabetic or diabetic and that was
0:24the first part of the study they wanted
0:25to investigate and see whether the
0:28degree of diabetes ore diabetes
LDL does not correlate with the degree of coronary artery plaque.
0:30correlated with coronary artery calcium
0:33scores they also then wanted to see
0:35which diabetic related biomarkers and
0:38lipid related biomarkers were linked
0:39with the degree of coronary artery
0:42calcium scores so this is really
0:44fascinating now what they found is that
0:46LDL cholesterol was not correlated with
0:50the degree of coronary artery calcium uh
0:53plaing now this is really important
0:55because again most doctors like to monom
0:57manically focus on lowering your LDL
1:00cholesterol but it turned out that HDL
HDL is protective against coronary artery disease and plaquing.
1:03cholesterol the so-called good
1:05cholesterol that is increased when you
1:07exercise when you have a low carb diet
1:09when you have healthier fats and less
1:11processed sugar in your diet your HDL
1:14generally increases HDL specifically the
1:17larger buoyant HDL particles were more
1:21protective against both metabolic
1:23disease as well as the degree of
1:25coronary artery plaing and again they
1:28used a CT scan to look at the degree of
1:31severity and calcification in the
1:33coronary arteries including the left
1:36anterior descending coronary artery the
1:37one that is known as the Widowmaker and
1:39highly susceptible to becoming plaqued
1:41and atherosclerotic and again is
1:44correlated with major Adverse
1:45cardivascular Events but let’s dive into
1:48this this is a really important study I
1:50strongly suggest you take some notes
1:51because we’re going to dive into some
1:53aspects of lipoprotein particles and I
1:56think this is important because again
1:58most doctors are measuring the
2:00cholesterol content in your particles
2:02not the particles themselves and this is
2:04a very important distinction and this is
2:06what the investigators used Beyond just
2:09looking at the cholesterol content of
Triglycerides correlate with diabetes, coronary artery disease and plaquing.
2:11the particles and it turns out that your
2:13HDL particles your vldl particles your
2:15LDL particles traffic phospholipids
2:19triglycerides and cholesterol but as you
2:22become more prone to developing diabetes
2:24and are on the path of insulin
2:26resistance the composition of your LDL
2:29HDL and vldl particles becomes enriched
2:32in
2:33triglycerides and guess what that is
2:35correlated with Corry artery
2:38atherosclerosis and plaing as well as a
2:42higher propensity to develop diabetes
2:45and so this is really important stuff
2:46we’re going to dive into this so the
2:48title of this study is lipoproteins and
2:50lipoprotein lipid composition are
2:53associated with stages of dis glycemia
2:55and subclinical coronary atherosclerosis
2:58as I mentioned this is actually ahead of
3:00print this is going to be published in
3:022025 probably January in the the
3:05international Journal of Cardiology
3:07there were 5,000 study participants that
3:09were part of a big cohort I think of the
3:11bioimaging cohort in uh Sweden and they
3:14also looked using a CT uh Scan Imaging
3:18to enumerate coronary artery calcium
3:20scores and that is going to give us
3:23better insights into the degree of
3:25subclinical coronary artery AOS
3:28sclerosis and so I think this is
3:29important and they looked at
3:31225 biomarkers okay so 32 biomarkers
3:35were associated with pre-diabetes and
3:37diabetes and were further investigated
3:39for their associations with coronary
3:41artery calcium scores here’s what they
3:44found the HDL diameter the size of the
HDL size is highly predictive.
3:48HDL now you’re very familiar with HDL
3:50because it’s known as the so-called good
3:52cholesterol but there’s different
3:53flavors of HL you have small HL
3:56particles and large big bigger larger
3:59diameter HL particles as you are become
4:02more metabolically healthy you lose the
4:03visceral fat you exercise more your V2
4:06Max increases you’re cutting out hyper
4:08palatable processed carbohydrates and
4:10sugars and Seed Wells and things like
4:11that guess what happens your liver
4:13starts making bigger more protective
4:15more Health promoting HL particles it
4:17turns out that this was the most
4:20sensitive and specific biomarker that
4:22not only predicted the degree of
4:24metabolic Health but the presence or
4:27lack thereof of coronary artery calcium
4:29I which is a direct reflection of
4:33atherosclerosis and so this was uh the
4:36size of HDL was among all the different
4:39biomarkers that they looked at was the
4:40most strongly tethered with a lower odds
4:44of having coronary artery calcium so
4:46this is really important and they want
4:47to say that there was no consistent
4:50Association for non-hdl lipoproteins non
4:55HDL such as vldl LDL Remnant lipoprotein
4:58or IDL Etc and coronary artery calcium
5:02scoring so what does this mean this
5:03doesn’t mean that in all individuals
5:05that HL is never a problem but in this
5:08analysis of 5,000 people the
5:12lipoprotein the the cholesterol if you
LDL, vLDL, and IDL had no strong association.
5:15will the the HDL was most strongly
5:17tethered inversely correlated with corn
5:21artery calcium scores there was not a
5:23strong statistical association with vldl
5:26or LDL or IDL with Corner artery calcium
5:31scoring and I want to really dive into
5:33this because this is very important but
5:35first I want to thank you for being here
5:37if you’re enjoying this content hit that
5:38like button be sure to share this video
5:40with a friend because we’re going to
5:41dive into the weeds in this study I
5:42think you’ll really find some value from
5:45this so that you can better stratify
5:47your risk uh of cardiovascular disease
5:49and also optimize your prevention
5:51because it’s the number one leading
5:52cause of mortality in this country now
5:54since we’re talking about metabolic
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6:41below as well as videos on berberin but
6:43getting back to the study again the
6:44study is really good because it helps us
6:46better understand how blood sugar
6:48disregulation and even having
6:50pre-diabetes is linked with higher risk
6:52of getting coronary artery uh
6:55atherosclerosis and increasing our our
6:57likelihood of developing a major a heart
7:00attack and or a stroke down the road so
7:02the investigators say derangements in
7:04both glucose and lipid metabolism
7:06characterize the clinical course of
7:08diabetes and increase the risk of aosc
7:10cardiovascular disease the most common
7:12cause of death in persons with diabetes
7:14so again it’s not only the most common
7:16cause of death here in the US and
7:18throughout the world for all people but
7:20especially in people with pre and
7:23diabetes individuals with both
7:25pre-diabetes and diabetes have different
7:27degree of dysliidemia typically High
7:29circulating triglycerides low HL
7:32cholesterol and high amounts of small
7:34dense LDL with normal or slightly
7:37elevated total cholesterol and LDL
7:40cholesterol levels are observed in
7:42individuals with diabetes however lipids
7:44and lipoprotein circulating levels and
7:46their composition differ greatly in
7:48individuals with diabetes depending upon
7:50the stage of the disease metabolic
7:52compensation and type of treatment
7:55here’s where it gets really interesting
7:56and this may be new to you but this has
7:58been long known in the literature
LDL may be lower with prediabetes and diabetes, reflecting imbalance.
8:01observational and Interventional Studies
8:02have shown in fact that LDL cholesterol
8:04levels may be lower in individuals with
8:08diabetes as compared to individuals
8:10without diabetes I’m going to show you a
8:11table soon but let’s just pause here
8:13let’s just go back and reread what they
8:15said I know you heard me but I just want
8:17to solidify this point because it’s
8:18really important observational and
8:20Interventional Studies have shown in
8:22fact that LDL cholesterol levels may be
8:24even lower in individuals with diabetes
8:27as compared to individuals without
8:30diabetes now here’s what’s interesting
8:32as we just learned the number one cause
8:35of death in individuals who have
8:37diabetes is heart disease okay this is
8:40long this is well known well established
8:42at this point but it’s also now well
8:44established that even in diabetics their
8:47LDL cholesterol levels are actually
8:49lower than you might see in normal
8:52glycemic individuals which is quite
8:54perplexing and this is why going back in
8:572007 2008 2009 I actually sold Advanced
9:00lipoprotein particle testing to doctors
9:02for this very reason to help them better
9:04stratify risk assessment for their
9:06pre-diabetic patients because it turns
9:09out that you can really see the
9:12arthrogenic changes in the lipids using
9:15Advanced lipoprotein particle testing
9:18above and beyond what you normally get
9:20from commercial Labs now it’s
9:22embarrassing to say this was a hard sell
9:24to cardiologists at the time to Family
9:26Medicine doctors to Internal Medicine
9:28doctors that would look at me now
9:30everyone uses NMR or Berkeley heart Labs
9:32or Ultra scentific there’s a lot of
9:35different modalities to uh enumerate the
9:37composition of LDL and vldl and HL
9:40particles now this is years later common
9:43practice but back then a lot of doctors
9:44were like how was this going to change
9:46my clinical decision making because
9:49there wasn’t apparently a lot of
9:50emphasis in medical school on the idea
9:53that as you become more pre-diabetic and
9:56diabetic and more insulin resistant the
9:58composition of particles actually change
10:01if I just have a book here for reference
10:03Imagine This Is A lipoprotein particle
10:06that’s trafficking phospholipids
10:08cholesterol vitamins like vitamin K2 or
10:10co-enzyme Q10 as well as cholesterol as
10:13you get more insulin resistant let’s
10:15just say in a healthy metabolically
10:17healthy individual there’s roughly 5050
10:20if you look at this little border here
10:22uh 50% triglycerides and 50% cholesterol
10:25in the lipoprotein particles such as an
10:27LDL or vldl particle
10:29as you become more insulin resistant
10:32that act the cholesterol content in the
10:34particle becomes reduced and there’s
10:35more triglycerides in the particle and
10:38that’s linked with increased
10:40atherosclerosis and that might be
10:42reflected in the serum as a lower LDL
10:45cholesterol level but that doesn’t
10:47necessarily reflect an improvement in
10:49metabolic Health it reflects actually uh
10:52disease in terms of metabolic health and
10:54so this is why looking at the
10:55lipoprotein particles is so important
10:57and that’s exactly what these investig
10:59found is that the composition of the
11:01particles shift in the wrong direction
11:04they become triglyceride enriched and
11:06that’s problematic and that’s why we
11:08often see and hear about these j-shaped
11:10associations with LDL cholesterol and
11:12coronary artery disease where
11:14individuals with really low LDL
11:15cholesterol levels actually have advance
11:18or at are at higher risk often times for
11:21major adverse cardiovascular events and
11:22having coronary artery plaque and high
11:25coronary artery calcium scores because
11:27the cholesterol content of the particles
11:30becomes reduced in relation to the
11:32triglyceride content does that make
11:34sense let me know in the comments I hope
11:36hope I hope I explain that and again I
11:38think doctors are now finally waking up
11:40to this it took a better part of a
11:42decade for this to become mainstream
11:43clinical practice and this is why the
11:46investigators say to this end we aim to
11:48identify a dyslipidemic profile based on
11:51lipid and lipoprotein concentration
11:53lipoprotein lipid content again that
11:55would mean the amount of cholesterol
11:57versus triglyceride in the particles and
11:59metabolites able to discern individuals
12:02across three glycemic categories defined
12:04as normal glycemic pre-diabetic or
12:06diabetic okay that was a lot of jargon
12:09let’s get to the simple tables the
HDL is increased by lifestyle.
12:11tables I think tell the story so we see
12:14the normal glycemic patients the
12:15pre-diabetic patients and the diabetic
12:17patients here uh in table one now what
12:21what I think is interesting about this
12:22table uh is first of all the relative
12:25proportions of normal glycemic
12:27individuals who do moderate or vigor R
12:29physical activity compared to the people
12:31who have diabetes and do really low
12:33amounts of all types of exercise and so
12:35I think that’s really important we know
12:37that exercise is a great way to increase
12:39your HDL this is the thing so HDL is
12:43increased by lifestyle and that’s why we
12:45don’t hear a lot of M mainstream doctors
12:47talking about this because there’s not a
12:48pill there’s not a drug there’s not a
12:50Statin that will increase HDL you have
12:52to earn it by way of exercise so I think
12:54that’s really interesting now going to
12:56table two this is where things get even
12:58a little bit more curious as you can see
Plaquing is more common in diabetics.
13:00here the coronary artery calcium scoring
13:03uh meaning the degree of plaing uh was
13:06much more common in diabetics it was
13:08present in 62% of diabetics compared to
13:11just 44% of individuals with
13:13pre-diabetes and only 37% of individuals
13:17with normal glycemia isn’t that
13:19interesting now let’s go on and look at
13:21LDL as you can see here low density
13:25lipoprotein the so-called bad
13:27cholesterol as you can imagine it is
13:31going down in individual so remember 62%
13:36of the
13:37diabetics had high corner re artery
13:40calcium scores but when we compare LDL
13:43cholesterol in the normal glycemic Group
13:46which only had 30 37% of these
13:48individuals had high coronary re artery
13:50calcium scores the individuals had
13:53higher LDL cholesterol in the normal
13:55normal glycemic group compared to the
13:57pre and full-on diabetic group you can
14:00see the LDL cholesterol and this is
14:02nanal per liter goes from 3.5 nanal per
14:06liter in the normal glycemic group and
14:08it drops down to 2.7 in the diabetic
14:11group but remember coronary artery
14:14calcium scoring was significantly higher
14:17in 62% of the diabetics compared to only
14:1937% of the non-diabetics and 44% of the
14:23pre-diabetics and so there is not a
14:25strong relationship with LDL cholesterol
14:28and you and we’ll see that on the next
14:29slide which is what I think is
14:31interesting and we also see an inverse
14:35Association uh if you look at the
14:37characteristics here uh eight shell
14:39cholesterol is much higher in the normal
14:41glycemic group compared to the
14:42pre-diabetic group canted protein is
14:44much lower in the normal glycemic group
14:46compared to the uh diabetic group and
14:49you can see here the calcium scoring of
14:51the um different corn arteries and so
14:54forth and and I think that’s very
14:56interesting blood pressure uh was much
14:58higher in the diabetics compared to the
14:59non-diabetics Weist ratio is much higher
15:02than the diabetics compared to the
15:03non-diabetics so again if we’re trying
15:05to optimize cardiovascular health and
15:07prevent a major adverse cardiovascular
15:08event we need to focus on metabolic
15:11Health on visceral adapost tisue on
15:13waste to hip ratios on blood pressure uh
15:15on increasing HL and also it’s worth
15:18noting here that triglycerides actually
15:21were significantly higher in the
15:23diabetics and pre-diabetics compared to
15:25the normal glycemic group how often do
15:27we hear doctors focusing on
15:29triglycerides they often focus on LDL
15:30cholesterol so I know by now you’re
15:32getting the story you’re understanding
15:33that there’s this correlation with non
15:36LDL particles and and corn artery
15:39atherosclerosis and so forth okay so
15:41let’s look at this figure here this is
15:42the odds ratio this is what I think is
15:45really interesting and it goes back to
15:46the composition of the particles
High triglycerides increase odds of metabolic disease by 100%.
15:49remember we’re just using this book as a
15:51as a easy way to visualize this this is
15:53either an HDL or a vldl or an LDL
15:56roughly in in metabolically healthy
15:58people might be relatively evenly split
16:01between the cholesterol content in the
16:03particle because again your blood is
16:04water-based so you need these
16:06lipoprotein particles to travel in the
16:08water and and in the the water-based uh
16:11plasma and blood and inside them is the
16:14fats because if you’ve ever made pasta
16:16you put olive oil in your pasta or
16:18butter uh in you make your Mac and
16:20Cheese it floats to the top it doesn’t
16:22disperse well well it it it it uh
16:25separates and so that’s why you need
16:26these particles and as you become more
16:29metabolically unhealthy they become
16:30triglyceride enriched and that’s what
16:32we’re seeing on this figure right here
16:35in the individuals who are diabetic or
16:37pre-diabetic you see the ratio of
16:40triglycerides within the vldl uh and the
16:43LDL particles is significantly increased
16:46and they’re only able to figure this out
16:48using NMR and so you see here there’s
16:51the odds uh of the correlation with
16:55triglyceride enriched vldl increases the
16:58odds of the presence of metabolic
17:00Disease by 100% so the odds the odds
17:02ratio here is two uh so 100% increase
17:06and and this is even if go on down the
17:08list I mean you see um the cholesterol
17:11content of the particles uh is linked
17:13with a lower odds of diabetes as well as
17:16Corner artery artherosclerosis so
17:18basically this is confirming what we
17:20just talked about that the composition
17:23of the hlv LDL and LDL particles tends
17:25to Pivot to be L cholesterol enriched to
17:28more triglyceride enriched and that’s
17:31why triglycerides I think are a great
17:32biomarker because when you see
17:34triglycerides increase in the blood you
17:36can also reasonably assume that they are
17:39increasing in the uh particles and that
17:41is increasing the arthrogenic nature of
17:43the particles Mak meaning that they’re
17:45more prone to causing the coronary
17:48artery calcium deposition in
17:50atherosclerosis so I think this figure
17:53uh is quite interesting and let’s
17:55further dive into this the investigators
17:57say increasing circul levels of small
The smaller HDL particles become, the less protective they are.
18:00HCL is associated with diabetes with an
18:03odge ratio of 1.37 so the smaller your
18:07protective HCL become the less
18:09protective those HCL particles are and
18:11so they are linked with a greater odds
18:13of developing not only diabetes but also
18:16developing coronary artery
18:17atherosclerosis which is bad they also
18:19say among the HL lipid components
18:22phospholipids in the HDL in the small HL
18:25excuse me was associated with diabetes
18:27on the contrary the large lipid enriched
18:30HCL was associated with a lower risk of
18:33diabetes they say lipid components in
18:35large and extra-large hgl were highly
18:37correlated uh with a lower risk of
18:40diabetes they say an increase in the
18:43vldl mean diameter was associated with
18:45diabetes with an odds ratio of 1.42
18:47which means a 42% greater odds of
18:50developing diabetes if you have a big
18:53vldl or high vldl I think that’s
18:55important because vldl is something that
18:58we should be measuring and we’ve talked
18:59about the vl2 triglyceride ratio before
19:02and how that’s problematic so they they
19:04go on to talk about some other
19:05lipoproteins here but let’s get to the
19:08conclusion because I think this is
19:10really important the investigators say
19:12the occurrence of coronary artery
Coronary artery calcium is associated with HDL size, concentration and composition.
19:13calcium was associated with HCL size
19:16concentration and composition
19:19consistently with previous observations
19:21in normoglycemic study participants
19:23circulating levels of small HDL were
19:25slightly increased in those treated with
19:27statins as compared to non-treated which
19:29we also observed in the group with
19:30pre-diabetes the investigators say in
19:32conclusion we identified 32 biomarkers
19:35mirroring circulating levels of
19:37lipoproteins lipoprotein components and
19:39metabolites associated with pre-diabetes
19:41diabetes in a small contemporary Swedish
19:43population among these 32 biomarkers an
19:46excess of small circulating HDL
19:49particles not good you want your HDL to
19:50be bigger was associated with the
19:52occurrence of subclinical coronary
19:54atherosclerosis estimated by the
19:56coronary artery calcium score by way of
19:58a CT scan further we show that if lipid
20:00lowering drugs were dispensed the
20:02association of small AG shell with the
20:05occurrence of coronary artery calcium
20:06scoring was modified although the
20:09interaction analysis did not attain a
20:10formal statistical significance in
20:12conclusion they say consistently we
20:14observed larger vldl levels in
20:16individuals with pre-diabetes and
20:18diabetes but also a relative increase in
20:20triglyceride concentrations of the vdl
20:23IDL and LDL regardless of the
20:25concentration and diameter of the single
20:27like lipoprotein I’m going to explain
20:29that in just a moment diabetes
20:31Associated dysliidemia was commonly
20:33defined by the presence of high
20:34triglycerides low HDL and elevated
20:37levels of small dense LDL total and LDL
20:40cholesterol levels are commonly reported
20:42as normal or slightly higher as compared
20:44to the normal glycemic population in our
20:47study we observe that total as well as
20:50LDL cholesterol levels were consistently
20:52lower in pre-diabetes and diabetes than
20:56in normal glycemic individuals in the
20:58presence and absence of dispensed lipid
21:01lowering drugs lower LDL cholesterol
21:03levels have been reported in individuals
21:05with diabetes in both observational and
21:08Interventional studies with low LDL
21:10cholesterol levels being associated with
21:12an increased risk of coronary events in
21:14the presence of high triglycerides and
21:16low HDL recently biomarkers associated
21:19with LDL cholesterol were found to be
High HDL with low triglycerides is linked with better metabolic health.
21:21inversely related to the risk of
21:23developing diabetes in the UK biobank
21:27data set okay what does this all mean
21:30clearly there is a strong association
21:33with metabolic disease and the presence
21:35of coronary artery calcium scoring which
21:37reflects the degree of atherosclerosis
21:40which then reflects the risk of
21:42developing a major adverse carvas event
21:45which as you know is the number one
21:46leading cause mortality we know that
21:49having high hgl low triglycerides
21:53irrespective of LDL is linked with
21:56better metabolic Health it turns out
21:58that in individuals who are on the
22:00trajectory or path of developing
22:02diabetes their LDL cholesterol levels
22:05can actually go down so if we monom
22:07manically focus on lowering LDL or using
22:10LDL as the sinic quinon biomarker of
22:12risk for coronary artery atherosclerosis
22:14we are missing the boat we need to
22:16further expand our repertoire of lipid
22:20species that we look at and look at
22:22triglycerides look at HCL look at
22:25vldl knowing because the composition of
22:29the particles can shift as you become
22:31more inso resistant your L the the
22:34cholesterol concentration of your
22:36lipoprotein particles goes down and
22:38because the freed wal equation which is
22:41the way that your LDL cholesterol is
22:43enumerated when you go and get your
22:44physical or common blood work it’s
22:46looking at the cholesterol content not
22:48the particles themselves so that can
22:50give you a false positive and that’s why
22:53we are seeing statistically there’s a
22:55large percentage of people who have
22:56fatal heart attacks with normal or low
22:58LDL cholesterol levels so it’s time that
23:01we broaden our scope just you know if
23:03you’re looking through a telescope just
23:04move out a little bit and look more at
23:06the bigger picture here so where does
23:08this leave us this leaves us knowing
Exercise increases the size and number of your protective HDL.
23:11that exercise is really important
23:12because it it can increase the size of
23:15your protective HDL and increase the
23:17total number of HDL particles that you
23:19have and it can lower your blood
23:21triglycerides which can obviously are a
23:24strong reflection of optimal metabolic
23:26health and therefore
23:28reduce the odds that you will develop
23:31calcified arteries and and increase the
23:34presence of
23:36atherosclerosis so download our blood
23:39Retreat sheet go to high-intensity
23:40health.com definitely opt in for that
23:41because on page one we talk all about
23:43this along with LP little a we talk
23:45about fibrinogen we talk about other
23:47apob to A1 ratios in this but I think
23:50this study is incredibly fascinating I
23:52really hope you got some value from this
23:53I know we talked about some jargonistic
23:54terms and things like that um but
23:57hopefully the figures the tables will
23:59really help you better understand the
24:01significance of this study and better
24:04help us make strategic lifestyle changes
24:07to optim or lower our chasar risk and
24:10optimize metabolic Health we’ll catch
24:13you on a future video down the road
24:15until then be well
