The New Skinny on Lp(a)

When it [music] comes to heart health, my dad kind of screwed me because he passed down to me high levels of what's called LP little A. Maybe this is a

marker you've heard of, maybe not, but you should have because LP little A has suddenly become the new hot kid on the cardiology block.

LP little A.

Ever heard of LPA?

Lipoprotein little A.

Lipoprotein little A.

It's a genetically determined risk factor that can raise your risk for heart disease and a heart attack.

[music] You can think about it as LDL's more dangerous cousin. It's similar in structure to LDL particles, but with an extra sticky tail called apple

lipoprotein delay. That tail makes LP

lipoprotein delay. That tail makes LP little A more likely to clot and more likely to build up plaque in your arteries. [music] So in short, LP little

arteries. [music] So in short, LP little A is worse, far more dangerous than LDL.

And right now, this is the scary part.

We don't have any proven way to lower it. and reduce [music] heart disease

it. and reduce [music] heart disease risk, which is kind of depressing if you're in the boat with [music] me of having high LP delay. But here's where

things get interesting. Brand new 2025 data just dropped. And they gave [music] me heart and hope. Hope that the genetic hand my dad dealt me might not be as bad

as it looks [music] because of something else about me. Something I'm actually showing you right now. Something you

might share, too.

Let's find out. This is a striking and really encouraging finding. Appears to

elevate cardiovascular disease risk only in individuals with a high a clear pattern emerged. Genes aren't fake.

pattern emerged. Genes aren't fake.

Activates a protein that promotes clotting. Improve body composition.

clotting. Improve body composition.

Optimize waist to hippo ratio. Here's

another way to look at the data. Much of

the cardiovascular risk disappears. The

goal of this new 2025 study was to determine whether a measure of atyposity waist to hip ratio modifies the relationship between LP little A and

cardiovascular disease risk. So to

explore this the researchers analyzed data from 4,652 participants in the multithnic study of atherosclerosis the MESA cohort. They

followed them over a median time frame of 17.4 4 years and during this time 792 of the participants developed cardiovascular disease related events.

The study stratified individuals based on LP the delay levels. High LP delay being defined as greater than 50 mgs per deciliter. And you can see the

deciliter. And you can see the conversion to other units on the screen.

And the researchers investigated how this risk with high LP delay was modified by waist to hip ratio as a marker of central atyposity and visceral

fat. We're going to get to more details

fat. We're going to get to more details on that later. Anyway, the findings were striking. Among those with high LP

striking. Among those with high LP delay, individuals with a higher waist to hip ratio, so more central atyposopy, more appleshaped, less pear-shaped were

three times more likely to experience cardiovascular events compared to those with high LP little A but lower waist hip ratio. And remarkably, in

hip ratio. And remarkably, in individuals with lower waist to hip ratio, LP little A levels were not significantly associated with increased risk of cardiovascular disease related

events. In other words, if your waist to

events. In other words, if your waist to hip ratio is lower, even high LP delay levels may pose much less of a concern

for cardiovascular disease. So to drive the point home, look at this graph. It

shows the cumulative incidence of cardiovascular disease related events over about 20 years. Each line

represents a different combination of LP delay levels and waist tape ratio. So

the blue line is a lower waist hip ratio and a lower LP to delay. The black line is a high waist hip ratio but low LP to

delay. The red line is high waist tape

delay. The red line is high waist tape ratio and high LP to delay. And the

orange line is lower waist hip ratio and higher LP to delay. And what stands out is how closely the orange line and the blue line representing people with low

waist hip ratios but high versus low LP to delay. how closely they couple. This

to delay. how closely they couple. This

suggests that in leaner individuals with lower waist hip ratios, even genetically elevated LP to delay carries minimal to no additional risk for cardiovascular

disease. This is a striking and really

disease. This is a striking and really encouraging finding for those with high LPA like me who maintain a leaner, more metabolically healthy profile. Now,

here's another way to look at the data.

Look at these graphs. When the

researchers divided participants into turtiles, three equally sized groups based on waist hip ratios sampled in the study, a clear pattern emerged in both

the lowest off to the left and middle tiles of waist to hip ratio. High LP

delay did not confer a higher incidence of cardiovascular events compared to lower LP delay. The increase in cardiovascular disease events only

appeared in the high waist hip ratio tertile off to the right i.e those third of participants with the greatest central atyposity the greatest waist hip

ratio in that group elevated LP delay was clearly associated with an increased risk of cardiovascular disease related events. So the takeaway is simple.

events. So the takeaway is simple.

According to these data, LP delay appears to elevate cardiovascular disease risk only in individuals with a high waist hip ratio. Now I'm sure you

want to know what waist hip ratio values to aim for yourself. Well, in this study, participants were grouped based on percentiles of waist hap ratio.

However, the 90th percentile cut point used doesn't actually reflect modern population distributions. I know that's

population distributions. I know that's a little bit confusing. So that said, the specific values are more useful and they were as follows. 1.03

for men and 1.00 for women. And if you really want to target excellent waist hip ratios, even beyond those used in the study, a level of less than 0.85 for

men and less than 0.75 for females, is elite in the waist hip ratio category.

You can measure this pretty easily at home. Just measure your waist at its

home. Just measure your waist at its narrowest point, ideally in the morning, fasted and maybe after a bowel movement for a consistent measure, and then measure your hips at the widest point.

Divide your waist measurement by your hip measurement, and that's your waist to hip ratio. If you don't have a tape measure, that's not a problem. You can

just use a piece of string or a belt and mark it and then measure it with a ruler or a yard stick. So, for example, the math, my own measurements are about 26

to 26.5 in for waist and about 33.75 in for hips, giving me a waist taper ratio of about 0.78.

And given my LP delay is quite elevated.

This result I find reassuring based on the data. I likely face a far lower

the data. I likely face a far lower cardiovascular disease risk associated with high LP delay than I might have otherwise believed. So now let's tangent

otherwise believed. So now let's tangent or move on and get into the mechanisms. You guys know I love mechanisms. Why would a high waist to hip ratio have a

strong influence on LP little A related risk?

Well, waist hip ratio is a proxy for abdominal atyposity or visceral fat. The

inflammatory fat stored deep in the abdominal cavity. This kind of fat is

abdominal cavity. This kind of fat is biologically active and contributes to both inflammation and clot formation, two mechanisms behind atherosclerosis,

cardiovascular disease. So here's a few

cardiovascular disease. So here's a few things that we know and that are relevant to this conversation. LP the

delay activates plasmminogen activator inhibitor 1 or P AI1, a protein that promotes clotting. As a quick aside, P

promotes clotting. As a quick aside, P AI1 is coded by the Serpine1 gene. And I

share this in case you've heard this gene mentioned before and because honestly I think it's a fun word to say.

Serpine one and I love snakes. As a

random fact, as a kid I owned a python named Monty. Monty Python, anyone?

named Monty. Monty Python, anyone?

I'm invincible.

Also, visceral fat. Sorry, I like to jump off on tangents. Visceral fat also increases levels of the same protein the P AI1 and this creates potential synergy

a synergistic pro-thrombotic environment between LP little and visceral fat.

Additionally, visceral fat promotes chronic lowgrade inflammation which may further act via LP little to amplify cardiovascular risk. So with respect to

cardiovascular risk. So with respect to inflammation, now speaking practically, a marker you should know is your high sensitivity C reactive protein level, HSCRP, a general marker of inflammation.

You should target an HSCRP level less than two, although less than one is really ideal. Now, here's another

really ideal. Now, here's another important layer, oxidative stress, which kind of goes handinhand with inflammation. Fat, not just visceral

inflammation. Fat, not just visceral fat, but other forms of body fat, produce enzymes like myoparoxidase. We

actually reviewed it earlier on this channel. See this video for more.

channel. See this video for more.

Anyway, these enzymes made by body fat, they can oxidize fatty acids, especially polyunsaturated fatty acids, PUFAS, creating oxidized phospholipids. And

these oxidized lipids are actually carried around on LPA particles. These

are so-called ox pls on apple. And

they're directly involved in the development of atherosclerosis, cardiovascular disease. LPA actually

cardiovascular disease. LPA actually acts as a reservoir for these oxidized phosphoippids, these oxls. And studies

show that when you control for oxpls, much of the cardiovascular risk attributed to LP delay disappears. And

this suggests that LP delay's danger lies in part in its ability to transport and concentrate oxidized lipids. So to

simplify the cascade, body fat generates oxidative enzymes like mo that oxidized lipids. LPA collects these lipids,

lipids. LPA collects these lipids, oxidized phospholippids, and this can promote atherosclerosis.

Isn't that interesting?

Now, the protocol I mentioned, well, based on the data I just reviewed, you can start to piece the puzzle together, but there's a plethora of additional data that I can use to develop a protocol. In fact, I did based on the

protocol. In fact, I did based on the physiology of metabolism, what we know about LP the little light to turn insights into action. Now, if I were to review all the data that went into this protocol, this would be a 4-hour long video. But if you want access to the

video. But if you want access to the protocol, please check out the newsletter linked in the video notes.

Parts of all my letters are entirely free and available with additional bells and whistles like protocols available to the premium subscribers who really keep this community, the stay curious learning community here, my Substack, my

other socials afloat and vigorously growing. I'm really grateful for them.

growing. I'm really grateful for them.

So for what it's worth, if you do want to become a premium subscriber to the newsletter, it costs only 67 cents or less per letter for full access. Maybe

you can afford that, maybe not something to consider. Anyway, shameless plug

to consider. Anyway, shameless plug over. Now I want to summarize the key

over. Now I want to summarize the key points. One, LP delay primarily

points. One, LP delay primarily increases cardiovascular risk in those with a high waist hip ratio. Two, a high waist hip ratio suggests more visceral

fat which amplifies the pro-inflammatory and pro-thrombotic clotty environment and properties of LP delay. And three,

if you have high LP to delay but a low waist tape ratio, low inflammation like an HSCRP, and low oxidative stress like an MO marker, your actual cardiovascular

risk associated with an elevated LP delay may be much lower than previously assumed. And if you don't check all of

assumed. And if you don't check all of these boxes, that's an opportunity, not a cause for alarm. Focus on the fundamentals. Improve body composition.

fundamentals. Improve body composition.

Optimize waist hyper ratio. I know,

easier said than done, but still prioritize quality sleep, stay physically active, and for the elite, you can check out the protocol I mentioned in the notes. So, in

conclusion, my final words, genes aren't fate. Your genetically determined LP the

fate. Your genetically determined LP the delay isn't your cardiovascular fate.

Metabolic context matters. Knowledge is

power. And while binging on donuts won't help your visceral fat, binging on more stay curious metabolism content just might. Thank you. Stay curious. I really

might. Thank you. Stay curious. I really

do appreciate you.

Thanks.