Well hey!

Welcome back.

This is Part 2 of my Gen X Heart Guide. If you missed Part 1 last week, or this is your first week reading (welcome!), you should read through Part 1, which you can find here.

Did you ever think you’d be thinking seriously about heart disease and how to avoid it? When did we get this old? 🤯

But… If you can’t help but think of heart disease as something that happens when you are older, what you are actually saying is: the deadly consequences of heart disease pop up later in life.

The ice water splash to the face reality is: The causes of these deadly consequences start in your teenage years and accelerate in midlife.

BTW - If you have kids, there is one heart-related blood test they need to get as teens. Read on for more on that.

Before you add a shot of bourbon to your morning coffee, thinking this newsletter is going to be a depressing review of how your body is falling apart, here is what I find so encouraging:

Unlike other major disease categories (especially cancer and dementia), we have the tools to see if heart disease is coming our way and the means to counteract it. Many of these are innovations of the past 20 years, gifts of modern science ready for your use.

Here’s an overview of what I cover below:

• The heart scan everyone in Gen X should have done, even if you are totally healthy. It takes less than 30 minutes and costs about $100 (or free).

• How to quickly read and fully understand the results of your lipid panel (cholesterol test) by focusing on just one number.

• Why your LDL cholesterol target should be lower than you think.

• The primary way to hit your LDL cholesterol target (it isn’t diet or exercise).

• The one blood test everyone needs one time in their lives (if you have kids, they should get this test in their teenage years).

I’m ready to go if you are!

1️⃣ ONE BIG THING

Gen X Heart Guide: Part 2

In Part 1 last week, you learned the foundations of atherosclerosis (the process where your blood vessels get clogged—the primary source of heart disease that leads to heart attacks and strokes) and its connection to cholesterol.

Here is a refresher:

• Cholesterol is essential to life; it isn’t bad.

• There is one type of cholesterol. There is no "good cholesterol" or "bad cholesterol." There are good and bad versions of lipoprotein particles that shuttle cholesterol (and triglycerides) around your bloodstream, which I compared to buses carrying passengers.

• There are fundamentally two major types of these “lipoprotein buses”:

  • Higher density + wrapped in molecules called “apoA” – includes HDL particles.

  • Lower density + wrapped in a molecule called “apoB” – includes several particle types, such as VLDL, LDL, and Lp(a).

• Clogging or blocking of your blood vessels begins when these buses crash into the one-cell lining of your blood vessels and get stuck there. It is mainly the “apoB buses” that crash and get stuck.

• When these buses get stuck, your immune system first tries to patch the crash sites up with fibrous "plaques." Over time, these plaques get a harder calcium coating over them. Remember this part.

• The good news: This process happens very slowly (over decades).

• The sobering news: This process starts early in life (your teenage years or earlier).

Let’s dive into how to get greater insight on where you stand today. 🔬👀

Heart disease is often called the silent killer. The ideas below can turn silence into understanding and action. Don’t look back in 15 years wishing you had acted sooner.

One no-brainer heart scan.

Every Gen X-er reading this should get a Coronary CT calcium scan.

Think of this as the colonoscopy of heart disease.

OK, maybe that is not the most appealing comparison. This scan takes less that 30 minutes and doesn’t involve…. well, you know.

But Kevin, last week you noted you’re not a doctor, don’t play one on TV, and don’t have any doctors as friends. Why are you telling me to get a scan that my primary care physician has never even mentioned?

Let me tackle that in three parts: (1) what is this scan, (2) why your doctor hasn’t recommended it, and (3) why it is a no-brainer to do.

A coronary CT calcium scan looks at the blood vessels around your heart to see if there are any of the calcium deposits I mentioned in Part I (and above). Remember, if there is a lipoprotein “bus crash” site somewhere, your body tries to seal this up over time with a layer of calcium.

This scan looks for any signs of this type of calcium and gives you a score to understand your current situation (a score of zero means no calcium).

Traditional, reactive doctors typically don’t suggest this scan unless you are at higher risk for heart disease. This is madness.

Why don’t doctors recommend it to everyone over the age of 40? Here are three explanations and the reasons they are dumb. 😂

1. The broader health system: It is not currently set up for everyone over 40 to get this scan, but that is a society-wide consideration. Your top concern is you, not the wider health system. Your doctor looks out for the system (which makes sense), but you are looking out for yourself.

2. Radiation: Back in the day, these scans used a lot of radiation. Today, the radiation exposure from this scan is the same as you get standing outside in the sun.

3. Cost: Most insurance will cover this scan, but let’s assume you have to pay for this out of pocket. When I did it, I paid $79. The average is $100-400.

In Part I last week, you learned that atherosclerosis happens very slowly but starts very early in life. If there are places in your arteries (near your heart) where lipoprotein bus crashes have festered long enough to form calcium deposits, then things have progressed very far. Yet, you may not have a single symptom.

Take a moment to read this story of a man in his early 40s. He had no cardiovascular risk factors. He ate well and participated in triathlons. After blood tests (which I will cover below) and a CT calcium scan showed red flags, an imaging scan showed he had a 90% blockage of the major coronary artery long known as the “widow-maker.” He had no symptoms. Scans and blood tests saved his life.

You can visibly see this blockage below (white arrow):

Sure, that is one person.

However, this 2024 study put statistical validity around this idea. It looked at atherosclerosis in adults without any traditional risk factors. Researchers examined data from 1,033 adults from the Miami Heart Study with no risk factors (they did not have high blood pressure, diabetes, or use tobacco).

Of this low-risk group, researchers found that 36% had coronary plaque and 25% had calcification (the thing the CT calcium scan tests for).

The choice is yours, but if you decide to get this quick scan done, you can ask your doctor for a referral. But you don’t even need a doctor to get this scan.

To find a test in your area:

• Google “coronary CT calcium scan near me”, or

• Use this search tool from MD Save.

Great. You get the test done and get your score. What should you make of the results?

If you get a score that is not zero (meaning the scan shows you have calcification), this is not a cause for undue alarm. Remember, this is a very slow-moving disease. But it should be a wake-up call. You will know you need to start taking more aggressive action to reduce your risk (more below).

Personally, if my score were over zero, I would book an appointment with a progressive cardiologist. I say progressive because it took me three tries to find a cardiologist actively interested in discussing prevention strategies.

You want to fire-proof your house, not wait until a big fire breaks out.

A cardiologist may suggest a more advanced scan, such as a CT angiogram. I had this test done. It is far superior to the calcium scan. However, it is more costly (closer to $800-1,000) and more involved. If you have any existing risk factors (blood pressure, smoking history, family history) I would get this scan first (skipping the calcium scan).

I chose to spend more time on the CT calcium scan here in this newsletter, as it seems to me the most straightforward starting point (which means you are more likely to get it done). But if you want to be more proactive or get a more accurate view of your current risk profile, get a CT angiogram.

If you get a score of zero (no calcium), you don’t have any “bus crash sites” that have progressed far enough to be calcified. It does not mean you don’t have any underlying issues (the scan cannot see the formation of plaques or other precursors). If you are healthy in your 40s and 50s, your score should be zero. Think of a score of zero as a minimum baseline score. It is not like getting a medal for an exceptional achievement.

Ultimately, please make your own decisions and consult with (a progressive) doctor.

But more than anything else, as Dr. Peter Attis says, get in the driver’s seat. 

OK! Let’s more on to blood tests! We’re having a good time.

But before we do, let me take a final step back and deepen your understanding of the root problem.

Why did the bus crash in the first place?

Why might one of the lipoprotein buses randomly crash and get stuck in the inner wall of your blood vessel?

There are two primary answers (and they can work together): 

1. Too many buses. At some point, if there are too many buses, the odds that one of them will crash increases. Researchers believe there are “threshold concentrations” above which the odds an “apoB” type of bus will crash into your artery wall and get stuck are high.

2. Low-quality walls. If the one-cell inner lining of your blood vessel starts to degrade, it will likely attract a bus crash. Some of the primary things that do this are:

   • Age (not much we can do here).

   • Smoking – chemically degrades the inside wall over time.

   • High blood pressure – mechanically degrades the inside wall over time.

The key idea in #1 above is "threshold concentrations." Like how a street functions, everything is fine if you have a few buses traveling along the road. As you add more and more buses to the street, eventually, there is a tipping point where back-ups and crashes increase exponentially.

Let's look at the blood tests that can tell you whether your concentration of problematic lipoprotein buses is over or under this threshold concentration.

Understanding your lipid panel.

My guess is you have already “had your cholesterol tested,” which means you have the blood test known as a lipid panel. Great.

While the categories reported can vary, your results probably look something like this:

Look at the LDL cholesterol (LDL-C) value in the table (90.6).

What is this number counting?

Using my bus analogy, this value is counting the volume of cholesterol passengers inside of all your LDL "buses." It is not a measure of how many buses there are.

You now know that the problems that lead to heart disease are caused by the concentration of particles (the buses), not by the concentration of cholesterol (number of passengers). This is a subtle but key point to understand.

Most testing companies report on LDL cholesterol concentration (rather than particle counts) because it is a cheaper test to run.

There are several flaws with this shortcut:

• The LDL buses/particles are not all the same size. Knowing the number of bus passengers, in this analogy, does not tell you how many buses there are.

• There are health scenarios where a person can have a low LDL-C number (the total number of passengers on the bus), but have a dangerously high number of particles (buses).

With that said, when it comes to blood tests, there are two possible ways for you to proceed:

#1. Get a better test, the apoB test. Last week you learned that all of the disease causing particles (e.g., LDL, VLDL) have a single apoB protein wrapped around the outside. Therefore, counting apoB is an elegant way to count the number of problematic particles moving around your bloodstream.

Here are two ways to get this test:

• Labcorp’s “Complete Heart Health Test (with ApoB)." This is simply a variation of the standard lipid panel your doctor typically orders. It should be covered by insurance. So, you can simply request that your next lipid panel include an apoB count. (It doesn’t have to be LabCorp.)

• A direct apoB test. If you just want to test your apoB now, you can order this test without any doctors involved for $28.

I can imagine this might sound too simple to be correct, but tracking your apoB particle count will tell you just about all you need to know about your "cholesterol-related" risk for atherosclerosis. It gives you a single number to see if you are below the threshold concentration of problem-causing particles.

Warning: Do not be surprised if your primary care physician does not know what apoB is. There is a better than 50% chance (conservatively) they do not. And if they don't know what it is, prepare for their defensive reaction to be, "You don't need to worry about that."

If you want to better educate your doctor (yes, you can do this), here is the official statement on apoB from the National Lipid Association. Print this out and take it with you.

#2. Continue to use the LDL-C number. Listen, if you were to say: Nice try, Kevin, but there is no way I am asking my doctor anything like this, and honestly, I don't see myself spending $28 once a year to understand my current risk level. Then I would say: OK, all good, use the LDL-C number that you are already getting. Is it better than nothing? Absolutely.

What targets am I shooting for?

In a blood test result, let's cover your target levels for apoB and LDL-C.

First, you probably have seen that most blood tests include your result (e.g., 90 mg/dL) a then a "reference range" to compare your result to population averages (e.g, 100-190).

What do these ranges mean?

Imagine you have a child in college (maybe you do!). Her first-year biology class has 500 students. They take an exam, and the 500 students get test scores that range from 42 to 100 (on a typical 0-100 scale). 95% of the students get scores somewhere between 45-98. If your child got a 55 on the exam, would you consider that a good result? Probably not.

When you see reference ranges on blood test results, this is what you are looking at. For some tests, perhaps kidney function, this is helpful. You want your result to be "somewhere in the middle" or basically, normal.

This is not the case for lipid tests. You do not want a result that fits within the typical range of, for example, the average American.

How low should my LDL / apoB number be? 

The consensus answer is “as low as possible." No total is considered "too low."

Targets are still helpful. So here are today’s standard targets:

• LDL-C: Under 100 mg/dL if you have zero risk factors; under 70 mg/dL if you have any risk factors (e.g., hypertension, smoking, family history).

• apoB: Under 130 mg/dL if you have zero risk factors; under 65-80 mg/dL if you have any risk factors.

But the real goal is "as low as possible."

Here are the targets that Peter Attia has for his patients:

• apoB: He believes the ‘ceiling’ should be 60 mg/dL, including for people with no risk factors. (I think this implies a similar target number for LDL-C.)

Note, he calls that the ceiling—as high as you want to be.

I believe there are psychological flaws in the way test results are often illustrated:

If your LDL-C level comes back at 117 mg/dL, you may look at this chart and think: Well, I’m in decent shape.

However, researchers believe the threshold concentration level is 100 mg/dL. This means that at 100, you are beginning to play with fire. You have the maximum number of lipoprotein buses cruising down the street. They are not crashing yet, but they are at the tipping point.

However, if you operate with a true risk-reducing ceiling of 60 mg/dL, suddenly, your score of 117 feels more problematic, and you will be more inclined to take action.

How do I reduce LDL and apoB?

The first approach is the more traditional: eat healthy food, avoid junk food, avoid alcohol, boost your metabolic health (insulin resistance, prediabetes, type 2 diabetes), and exercise.

The best way to think about these approaches is that they help your liver function better (and kidneys to a degree). The liver plays a significant role in clearing cholesterol and triglycerides from your system. If your liver works double-time solving other problems, its ability to clear cholesterol and triglycerides is degraded.

Now, there are few things I hate more than useless advice like “eat better”. Here are five more specific things to do to reduce LDL-C and apoB:

1. Reduce your intake of saturated fats. These are primarily found in animal sources (butter, fatty meats) and in fast and fried food.

2. Eat more fiber, such as oats, beans/lentils, chia seeds, etc. Aim for 25-30g a day. 5-10g of soluble fiber daily can lower LDL-C by 5-10%.

3. Reduce refined carbs and sugar. White bread, pasta, sugary drinks, juice.

4. Lose excess body fat (especially in your midsection). A 5-10% weight loss can lower LDL-C/ApoB by 10-20%.

5. Exercise regularly. Regular endurance exercise (150+ minutes a week) can reduce ApoB by up to 15%.

Here’s where this gets more surprising.

There is a good chance that you can do all five of the above and still have LDL-C and apoB counts that are too high. This was true for me.

The direct way to reduce LDL-C and apoB with drugs.

My sense is a lot of people see drugs as a secondary, back-stop solution:

Let me first try to tackle this by eating better and exercising more. If that doesn’t work, then maybe I will investigate drug options.

I believe this is backwards logic that exposes you to unnecessary risk.

Why?

• As we learned, atherosclerosis is a slow-moving disease of cumulative risk. The more years you live with elevated lipids, the greater your cumulative lifetime risk. Spending two years trying to lower your LDL-C from 140 to 110 with a new diet is two years you live with levels above the concentration thresholds.

• I believe in you and your determination, but can you consistently sustain these diet and exercise behaviors until you are 75?

• Most importantly, lifestyle changes alone are very unlikely to bring LDL-C and apoB numbers under 60 mg/dL. It's not you; it is just the way the body works.

As you likely know, statins are the most common drugs for lowering LDL-C and apoB. Many are on the market, and nearly all are generic, so they are affordable. In the early days of statins, muscle soreness was a common side effect. This can still happen, but most people can test 1-2 different statins before they find one that does not produce any side effects.

I started taking rosuvastatin (brand name Crestor), with no side effects, in June 2023.

Here is a chart of my lipid panel blood tests between October 2022 and October 2024.

You can see that in May 2023, my LDL-C was 101, and my apoB was 96.

After starting the 10mg rosuvastatin daily, my LDL-C was 56, and my apoB was 66.

If you do not tolerate any type of statin for any reason, other drug types can also do the job. These include PCSK9 inhibitors, ezetimibe, bempedoic acid, and (coming soon) ASOs (antisense oligonucleotides).

I am not quick to take medications in most cases. For example, I never take any medication when I get a common cold. But I believe it’s worth realizing the areas of life where the drugs available to us are something close to a gift. The first statin hit the market in 1987. We are among the first generation of adults hitting midlife with so many ways to substantially control risk factors for heart disease.

Before we wrap things up here, I want to cover two final blood test topics:

• Total cholesterol, HDL, and triglycerides.

• Lp(a).

What about all the other numbers in my lipid panel?

To reiterate what I covered above, LDL cholesterol (or, better yet, apoB) is the primary contributor to your risk for atherosclerosis.

What about the other numbers?

The easy one is "total cholesterol." In Outlive, Dr. Attia says, “And your 'total cholesterol,' the first number people offer up when talking about heart disease, is only slightly more relevant to your cardiovascular risk than the color of your eyes.” I’ll let that speak for itself.

HDL is more interesting and much, much more complex. I listened to nearly two hours of detailed discussion of HDL and cardiovascular disease with Peter Attia and Dan Rader, MD, who has done extensive research on HDL. They both agreed that the HDL family of particles is exponentially more complex than the apoB family (LDL, VLDL, etc.) and that there is still much that researchers do not understand.

However, here are a few key things to know:

• The origin of HDL as the “good cholesterol” dates back to the Framingham heart studies from the early 1980s. These found higher levels of HDL were associated with a lower risk of heart disease. In tandem, this led to the notion that the ratio of HDL to LDL was also important. The thinking at the time went: Even if you have higher LDL, as long as you have higher HDL, you are OK. But that was almost 50 years ago.

• Specialists no longer think either of these things is true (though, once again, your primary care physician may still believe this).

• In summary, Having high HDL is not protective. And the HDL-LDL ratio is irrelevant. Here are two quotes from Dan Rader, MD, on this topic:

  • “The HDL cholesterol itself is not directly and causally protective against atherosclerotic cardiovascular disease.”

  • “High HDL is never a reason not to treat someone who would’ve otherwise merited treatment.” For example, due to high LDL.

• One caveat: Very low HDL numbers may, in fact, be a red flag in some cases. Key genetic factors are at play here, and in people of African descent, low HDL may not mean the same thing.

Finally, there is a lot of interesting research on the interactions between HDL and triglycerides (and the ratio between these two things). Much of this is beyond my current comprehension, so I won’t dive too far into this here.  

However, here is one quick note on triglycerides that I find helpful.

As we have seen, alongside cholesterol, triglycerides are the other major passengers inside of our lipoprotein buses. Triglycerides are the primary way your body moves fat around the body. Like cholesterol, fat is essential for your body. Your muscles burn fat as their most efficient energy source. You store fat as a critical energy reserve. Triglycerides are the currency of this whole fat energy system.

Therefore, high triglyceride numbers in a lipid panel are often considered a proxy measure for poor metabolic health (insulin resistance, prediabetes, or type 2 diabetes). Poor metabolic functioning can mean your muscles are no longer efficient at burning fat for energy—you are no longer soaking up triglycerides for daily energy production (or you are but at a reduced rate). This means you are not clearing triglycerides from your system, which leads to more storage of triglycerides as fat and higher triglyceride blood levels.

In this way, higher triglycerides in your blood increase your heart disease risk, but via the cascade of problems resulting from metabolic syndrome rather than the more direct problem of “lipoprotein buses” crashing into the lining of your blood vessels.

In terms of reading your blood test results:

• Healthy triglyceride numbers would be less than 80-100 mg/DL.

• Many doctors also consider the ratio of HDL/triglycerides a strong predictor of insulin resistance. This ratio is triglyceride divided by HDL, and an optimal ratio is under 1.5. Above 3.0 is considered high risk (a red flag for metabolic problems).

And finally, what the heck is this Lp(a)?

I left this for last, but I find it the most fascinating part of this whole story.

Lp(a)—said el pee little A—is a strange variant of the LDL particle. I like to think of it like Saturn, the planet. It carries around with it an odd extra protrusion dangling around the outside of the particle. Here is a good view:

This added appendage makes it much easier for this particle to stick to the inside of your blood vessel—quite literally getting snagged there. This article has a nice overview.

Lp(a) is considered 8-10x more dangerous (on a per particle basis) than LDL.

If anyone in your family has ever died tragically early in life from a heart attack or stroke, there is a decent chance Lp(a) was the cause. If someone had best-in-class LDL-C numbers and still had a heart attack or stroke, there is a decent chance that Lp(a) was the cause.

Here are some additional facts:

• Whether you produce Lp(a) is entirely genetic.

• About 20% of the population produces Lp(a).

• You only need to be tested once for Lp(a). The number you get in a test when you are 15 years old will be the same as the number you get at 55.

• Lifestyle changes (eating, exercise, etc.) do not change Lp(a) levels.

Is Lp(a) included in any tests your primary care physician gives you? No.

There is literally nothing crazier to me than this fact. It is mind-blowing.

You should get your Lp(a) level tested this year. Do not wait.

If you have children, get their level tested, perhaps in their teens.

Again, it only needs to be done once in a lifetime.

Again, this is something your primary care physician may not be aware of. They may try to claim it is really not that important. Once again, if you would like to educate them, here is the July 2024 guidance from the National Lipid Association: "Lp(a) should measured at least once in all adults.” Take the PDF with you.

Or, as with the apoB test, you can bypass your doctor and get this test yourself for $39. Here is a link. 

Here is a summary of what you will be looking for when you get your results:

For example, my Lp(a) total was 127, just into the high-risk area. I have several members of my extended family who had heart attacks early in life. Unfortunately, the Lp(a) production genes passed down to me.

What can you do if lifestyle factors do not alter Lp(a)?

You want to get maximally aggressive in all the other modifiable risk factors, reducing LDL / apoB to very low levels.

Atherosclerosis is a cumulative disease over time, which is why I think testing children for Lp(a) is so important. Lowering LDL / apoB levels early in life can reduce cumulative risk.

There are no drugs currently on the market specifically to lower Lp(a). However, PCSK9 inhibitors (Rapatha is the most common) are used off-label and have been shown to reduce Lp(a) by 20-30%.

Let me close with some great news.

Many therapeutics are currently in clinical trials to tackle Lp(a). The furthest along (Pelacarsen) is in a Phase 3 trial now, with results expected this year. The most exciting (Lepodisiran) is in a Phase 2 trial now. Preliminary results show this drug can reduce Lp(a) to undetectable levels and may only need to be administered once or twice a year.

But there is no reason to wait. Understand your Lp(a) today. If it is high, like mine, reread these emails and dig into aggressive reductions in the risk factors you can control today.

I heart you.

See you next Sunday.