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Why LDL cholesterol is only part of the cardiovascular story—and what coronary plaque, insulin resistance, ApoB, lipoprotein(a), cell membrane health, and emerging research reveal about preventing heart attacks and strokes

Robert’s Note: Before You Begin

First, thank you for making time to read this article.

I have to tell you, this started with what I thought would be a short, simple overview of cholesterol, statins, and cardiovascular health. Well, that short overview turned into what now feels like a small book!

But the more I researched, the more I realized just how much information deserves to be shared.

Regardless of where you are in your cardiovascular health journey, I want you to understand something about my approach. After more than three decades working in nutrition and metabolic health, I have rarely, if ever, recommended that someone start taking a statin. That’s not because I believe statins have no place in medicine. They may, particularly for certain individuals at elevated cardiovascular risk. Rather, my approach has always been to look at the bigger picture before focusing on medication.

There’s a tremendous amount being said about cholesterol, particularly low-density lipoprotein cholesterol (LDL-C), and its relationship to heart attacks and strokes. But I believe we’ve become so focused on cholesterol numbers that other important aspects of cardiovascular health often receive too little attention.

What about the actual condition of your arteries? What about insulin resistance, inflammation, endothelial function, inherited risk factors, and the health of your cell membranes? And how do we know whether someone already has cardiovascular disease without realizing it?

These are questions worth exploring.

And here’s something else I want you to take away from this article.

You’re going to learn about three important blood tests that are often missing from routine laboratory work—and why you may want to discuss requesting them with your healthcare provider.

✅ Lipoprotein(a), or Lp(a): A largely inherited cardiovascular risk factor that can help identify people at increased risk for heart attacks and other cardiovascular complications, even when their conventional cholesterol numbers appear acceptable.

✅ Apolipoprotein B (ApoB): A measurement that helps estimate the number of potentially artery-clogging lipoprotein particles circulating in your bloodstream. It can provide valuable information beyond LDL cholesterol alone.

✅ Fasting insulin: A measurement that can provide additional insight into insulin regulation and possible insulin resistance, sometimes before conventional blood glucose measurements become abnormal. Its usefulness depends on the clinical context, and it is not a universally recommended screening test.

Lp(a) is generally recommended at least once in adulthood, while ApoB and fasting insulin testing can be considered based on individual risk factors and clinical circumstances.

My point is simple: If we’re serious about preventing heart attacks and strokes, shouldn’t we be looking beyond a routine cholesterol panel?

My goal with this article isn’t to convince you to take a statin or avoid one. It’s to help you become better informed, ask better questions, and understand that preventing a heart attack or stroke involves much more than simply lowering a cholesterol number.

I encourage you to take your time reading this article. There’s a lot to unpack, but I believe the information is worth your time.

Because ultimately, it’s not about winning an argument over cholesterol or statins. It’s about helping you make informed decisions that could protect your health and potentially save your life.

Imagine three people sitting in a doctor’s office.

The first person has cholesterol numbers that don’t appear particularly alarming. They exercise, feel reasonably healthy, and have never experienced chest pain. They assume their arteries must be in good condition.

The second person has been told for years that their cholesterol is too high. Yet nobody has investigated whether they have coronary plaque, how insulin-resistant they might be, or whether they carry an inherited cardiovascular risk factor.

The third person walks into the doctor’s office feeling perfectly fine but leaves frightened.

Their doctor reviews their blood work, points to an elevated low-density lipoprotein cholesterol (LDL-C) level, and says something along the lines of, “Your bad cholesterol is too high. If you want to avoid a heart attack and live longer, you need to start taking a statin.”

And just like that, fear enters the conversation.

The patient doesn’t ask about their actual risk of experiencing a heart attack or stroke. They don’t ask whether they already have coronary artery plaque, whether additional testing might help clarify their risk, or how much the medication is expected to reduce their chances of experiencing a cardiovascular event.

They simply accept the prescription.

Not necessarily because they understand the science, but because they’re afraid of what might happen if they don’t.

And here’s something I believe we need to talk about more openly.

Many patients don’t ask questions because they don’t know what questions to ask.

They trust their doctor, as they should be able to. But trust should never mean that patients are discouraged from understanding their diagnosis, their treatment options, or the potential benefits and risks of a medication.

Now, let’s return to our first two patients.

Imagine discovering that the first person, whose cholesterol numbers appeared relatively reassuring, actually has extensive coronary artery disease.

Meanwhile, the second person, who has been concerned about elevated cholesterol for years, undergoes a coronary artery calcium scan and has no detectable coronary calcium.

Which person is at greater risk?

The answer isn’t as simple as looking at their cholesterol numbers. The first person has documented coronary atherosclerosis, while the second person’s risk still depends on age, genetics, other risk factors, and the possibility of noncalcified plaque.

And what about the third person?

Was a statin the right decision? Possibly. It might even be lifesaving. But shouldn’t that person understand why the medication was recommended, what benefits they can reasonably expect, and whether additional information could help guide their care?

This is not an argument against statins. It’s an argument for better cardiovascular risk assessment, informed decision-making, and conversations that educate patients rather than leave them frightened.

For decades, much of the public conversation has centered on lowering LDL-C. Yet cardiovascular disease involves much more than a single laboratory measurement.

We need to understand what happens inside the artery wall, how insulin resistance affects vascular health, why certain cholesterol-carrying particles contribute to plaque formation, and how the fatty acid composition of our cell membranes may influence the function of blood vessels.

We also need to understand why someone can have relatively favorable cholesterol numbers and still experience a heart attack—and why someone with elevated LDL-C may have a different level of near-term cardiovascular risk than another person with the same result.

And we need to ask a question that matters far more than whether a laboratory result improves:

Does the intervention actually reduce heart attacks, strokes, and premature deaths—and by how much for someone with my risk profile?

In this article, I’m going to explain the science behind atherosclerosis, why apolipoprotein B (ApoB) and lipoprotein(a) [Lp(a)] deserve attention, what research reveals about the prevalence of poor metabolic health, and how omega-3 fatty acids influence endothelial function and nitric oxide production.

We’ll also examine coronary artery calcium testing, the benefits and limitations of statins, alternatives to statins, and the difference between improving a biomarker and preventing a cardiovascular event.

Along the way, I want to equip you with something many patients never receive during a brief medical appointment: the knowledge to ask better questions about your cardiovascular health.

Most importantly, I’ll share what I believe a more comprehensive approach to cardiovascular prevention should look like.

Because the goal should never be to frighten someone into taking a medication—or frighten them away from one.

The goal should be to help people make informed decisions that genuinely reduce their risk of a heart attack, stroke, or premature death.

 

First, What Exactly Is Atherosclerosis?

Before discussing cholesterol or statins, we need to understand the disease we’re trying to prevent.

Atherosclerosis is a chronic disease in which plaque develops within the walls of arteries.

These plaques can contain cholesterol, inflammatory cells, connective tissue, calcium, and other materials.

Atherosclerosis is not simply a matter of eating fat and having that fat clog a blood vessel like grease accumulating inside a kitchen drain.

It is a complex biological process.

Certain cholesterol-carrying particles enter the artery wall and become retained. This can trigger inflammatory responses that contribute to the development and progression of plaque.

Over time, plaques may grow, develop fibrous coverings, or accumulate calcium.

Some plaques narrow arteries enough to restrict blood flow, particularly during physical activity.

Others may not produce significant narrowing but can still become dangerous.

A heart attack often occurs when a coronary plaque ruptures or its surface erodes, triggering the formation of a blood clot that obstructs blood flow to heart muscle.

A similar process in arteries supplying the brain can cause an ischemic stroke.

This distinction matters because a person may have coronary atherosclerosis without experiencing obvious symptoms.

The absence of chest pain does not necessarily mean the absence of coronary artery disease.

And a cholesterol panel, by itself, cannot tell us whether someone already has plaque.

Cholesterol Is Essential to Life

Cholesterol has acquired a terrible reputation.

Yet cholesterol is indispensable to human biology.

Our bodies use cholesterol to build and maintain cell membranes, produce steroid hormones, synthesize vitamin D, and manufacture bile acids needed for digestion and absorption of dietary fats.

Every cell depends on cholesterol for important structural and functional processes.

The liver produces cholesterol because our bodies need it.

But the fact that cholesterol is essential does not mean that every concentration or distribution of cholesterol-carrying particles in the bloodstream is harmless.

This is where we must distinguish cholesterol itself from the particles transporting it.

Cholesterol is a substance.

Lipoproteins are the transportation system.

And the number, type, and behavior of those particles can influence cardiovascular risk.

LDL and HDL: Understanding the Transportation System

Cholesterol and triglycerides cannot travel freely through the bloodstream in substantial quantities because they are not readily soluble in water.

Instead, they are transported within structures called lipoproteins.

These particles contain varying proportions of cholesterol, triglycerides, phospholipids, and proteins.

The liver releases very-low-density lipoprotein (VLDL) particles, which transport triglycerides and can eventually give rise to intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) particles.

LDL particles deliver cholesterol to tissues and participate in normal cholesterol transport.

High-density lipoprotein (HDL) particles participate in cholesterol transport and other biological processes, including pathways involved in returning cholesterol toward the liver.

But here’s an important distinction:

LDL-C measures the amount of cholesterol carried within LDL particles. It does not directly count the particles themselves.

Two people can have the same LDL-C concentration but different numbers of LDL particles.

Why does that matter?

Because each potentially plaque-forming particle represents another opportunity for a particle to enter and become retained in the artery wall.

This brings us to one of the most important cardiovascular measurements that many people have never heard of.

Why ApoB Deserves More Attention

Apolipoprotein B (ApoB) is a structural protein found on several types of cholesterol- and triglyceride-carrying lipoproteins.

These include VLDL, IDL, LDL, and Lp(a).

These particles are described as atherogenic.

What Does Atherogenic Mean?

The word atherogenic comes from two parts:

• • Athero- refers to fatty plaque or deposits that develop within the walls of arteries.
  • -genic means producing, causing, or giving rise to something.

Put them together, and atherogenic means capable of promoting plaque formation inside your arteries.

This is important because atherosclerosis—the disease responsible for most heart attacks and many strokes—involves the buildup of plaque within artery walls.

When scientists describe certain cholesterol-carrying particles as atherogenic, they’re referring to particles capable of entering the artery wall, becoming trapped, and contributing to the biological processes that produce atherosclerotic plaque.

These include low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and lipoprotein(a) [Lp(a)].

Here’s something especially important to understand.

Each of these circulating atherogenic lipoprotein particles contains one molecule of apolipoprotein B (ApoB).

That means measuring ApoB provides a useful estimate of the total number of potentially plaque-forming lipoprotein particles circulating in your bloodstream.

Think of It This Way

Imagine your bloodstream is a highway filled with delivery trucks.

LDL cholesterol (LDL-C) tells us how much cholesterol cargo is being transported inside the LDL trucks.

ApoB helps us estimate how many potentially plaque-forming trucks are traveling on the highway.

Now imagine two people.

Both have an LDL-C level of 100 mg/dL.

However, the first person has fewer LDL particles carrying more cholesterol per particle.

The second person has more LDL particles, but each carries less cholesterol.

Their LDL-C results look identical.

Yet the second person may have a higher ApoB level because more potentially plaque-forming particles are circulating in their bloodstream.

Why does that matter?

Because each of those particles represents another opportunity for a particle to enter the artery wall and become retained.

In other words, it’s not just how much cholesterol is being transported. The number of particles transporting it matters, too.

This becomes particularly important when LDL-C and ApoB are discordant—meaning the two measurements don’t tell the same story.

What does discordant mean?

Simply put, discordant means that two measurements do not agree or tell the same story.

In cardiovascular testing, discordance occurs when the amount of cholesterol carried by LDL particles does not align with the number of potentially plaque-forming particles reflected by ApoB.

For example, someone may have an LDL-C level that appears relatively normal but an elevated ApoB level because they have a large number of LDL particles, each carrying relatively little cholesterol.

LDL-C tells us how much cargo is being transported, while ApoB helps estimate how many vehicles are carrying that cargo.

You can have less cargo in each vehicle but still have a lot of vehicles on the road.

And because each atherogenic particle has the potential to enter and become trapped in the artery wall, having more particles can mean greater cardiovascular risk than LDL-C alone might suggest.

This is especially relevant in people with insulin resistance, elevated triglycerides, obesity, or type 2 diabetes.

Research has established that ApoB-containing lipoproteins play a causal role in atherosclerosis (Borén et al., 2020; Ference et al., 2017).

The 2026 American College of Cardiology/American Heart Association (ACC/AHA) dyslipidemia guideline also recognizes the value of selective ApoB testing and measuring Lp(a) at least once during adulthood (Blumenthal et al., 2026).

However, ApoB is not the only factor determining whether a person experiences a heart attack.

The condition of the artery wall, blood pressure, inflammatory processes, inherited risk factors, smoking, diabetes, and existing plaque burden all matter.

ApoB helps us understand exposure to plaque-forming particles. It does not, by itself, tell us how much plaque is already present.

The Artery Wall: Where Cardiovascular Disease Develops

When we talk about heart disease, heart attacks, and strokes, most people immediately think about cholesterol. But there’s another important part of the conversation: the health of the cells lining the inside of our arteries.

These are called endothelial cells, and together they form the endothelium, a thin, protective lining that helps regulate blood flow, inflammation, blood clotting, and the movement of substances into the artery wall.

Every endothelial cell is surrounded by a cell membrane, also called the plasma membrane. This membrane consists of a phospholipid bilayer containing fatty acids, cholesterol, and proteins. The fatty acid composition of the membrane can influence its fluidity, organization, and the way cells communicate and respond to signals.

This is where omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), become especially interesting.

EPA and DHA can become incorporated into endothelial cell membrane phospholipids, influencing membrane properties and cellular signaling. Experimental research suggests these fatty acids can also affect pathways involved in nitric oxide production, inflammation, and vascular function.

When endothelial function becomes impaired, it can contribute to conditions that promote atherosclerosis, including inflammation and changes in how cholesterol-carrying particles interact with the artery wall. Over time, atherosclerotic plaques can contribute to heart attacks and certain types of strokes.

So, protecting cardiovascular health isn’t just about what’s circulating in your blood. It’s also about the health and function of the cells lining your blood vessels—and the membranes surrounding those cells.

Understanding the Endothelium, Cell Membrane, and Glycocalyx

Before we explore the connection between omega-3 fatty acids and cardiovascular health, let’s understand three structures that work together inside our blood vessels.

First, the endothelium.

The endothelium is a continuous, single-cell-thick layer of endothelial cells lining the inside of our blood vessels.

These cells help regulate blood flow, blood vessel relaxation, inflammation, and clotting.

Second, the endothelial cell membrane.

Every endothelial cell is surrounded by a cell membrane, also called the plasma membrane.

This membrane consists primarily of a phospholipid bilayer containing fatty acids, with cholesterol and proteins incorporated into its structure.

The membrane helps regulate what enters and leaves the cell, how the cell communicates with its environment, and how it responds to signals.

This is where EPA and DHA become particularly interesting.

Both fatty acids can become incorporated into the phospholipids of endothelial cell membranes.

Their presence can influence membrane organization, physical properties, and cellular signaling.

Experimental research suggests that these effects may influence pathways involved in endothelial nitric oxide production, inflammation, and vascular function.

Third, the endothelial glycocalyx.

Attached to the blood-facing surface of endothelial cells is a delicate, carbohydrate-rich coating called the endothelial glycocalyx.

It is composed of structures including proteoglycans, glycosaminoglycans, and associated molecules.

The glycocalyx helps protect the endothelial surface, regulate interactions with circulating blood components, and transmit signals generated by blood flow.

Importantly, the glycocalyx is not a separate cell membrane. It is a specialized coating anchored to and associated with the endothelial cell surface.

How These Structures Fit Together

Imagine moving from the bloodstream toward the interior of an endothelial cell.

You would encounter these structures in the following order:

Bloodstream → Endothelial glycocalyx → Endothelial cell membrane → Interior of the endothelial cell

This relationship matters because the glycocalyx, cell membrane, and internal cellular signaling systems work together to help endothelial cells respond to their environment.

One important response involves the production of nitric oxide (NO), a signaling molecule that helps blood vessels relax and supports normal vascular function.

And this brings us back to nutrition.

EPA and DHA are not simply fats circulating in the bloodstream. They can become structural components of endothelial cell membranes, where they influence the cellular environment in which important signaling processes occur.

That does not mean omega-3 supplementation automatically increases nitric oxide production in every person or reverses existing coronary plaque.

But it helps explain why scientists are investigating the relationship between omega-3 status, membrane biology, endothelial function, and cardiovascular health.

What Do Omega-3 Fatty Acids and Cell Membrane Fluidity Have to Do with Your Arteries?

One important characteristic of a cell membrane is its fluidity.

Cell membrane fluidity refers to how freely lipids and certain proteins can move within the membrane.

Think of the membrane as a flexible, constantly moving surface rather than a rigid shell.

Its composition and physical properties affect membrane protein function, cellular signaling, and interactions with the surrounding environment.

Because of their chemical structures, EPA and DHA can influence membrane organization, flexibility, and the behavior of proteins associated with the membrane.

DHA contains six double bonds, giving it a highly flexible molecular structure that can affect how surrounding membrane lipids are arranged.

EPA contains five double bonds and also participates in membrane organization and cellular signaling.

However, membrane fluidity is not simply a matter of making a membrane as fluid as possible.

Different cell membranes require different physical properties to function normally.

The biological objective is appropriate membrane composition and function, not maximum fluidity.

Experimental research has shown that DHA can influence the membrane environment associated with endothelial nitric oxide synthase, an enzyme involved in nitric oxide production (Li et al., 2007).

But the biological roles of EPA and DHA extend beyond their effects on membrane structure.

These fatty acids also participate in pathways involved in inflammation, oxidative stress, and vascular function.

And that brings us back to nitric oxide.

The Connection Between Omega-3s and Nitric Oxide

Endothelial cells produce nitric oxide, which helps blood vessels relax and maintain healthy circulation.

One of the enzymes responsible for producing nitric oxide is called endothelial nitric oxide synthase (eNOS).

The activity of this enzyme is influenced by cellular signaling pathways, membrane-associated proteins, and the biochemical environment within endothelial cells.

Experimental research suggests that EPA and DHA can influence some of these pathways, including mechanisms involved in endothelial nitric oxide production and availability.

Omega-3 fatty acids may also influence inflammatory and oxidative processes that affect endothelial health.

Why is this important?

Because nitric oxide is essential for normal vascular function.

When nitric oxide availability is reduced, blood vessels may become less able to relax appropriately, and endothelial dysfunction can develop.

This is one reason researchers have investigated whether improving omega-3 status can support endothelial function.

And importantly, we now have human clinical research to consider.

What Human Studies Reveal About Omega-3s and Endothelial Function

A 2024 systematic review and meta-analysis published in the European Journal of Clinical Investigation examined 32 randomized studies involving 2,385 participants.

The researchers investigated the effects of omega-3 fatty acid supplementation on flow-mediated dilation (FMD).

FMD is a test used to evaluate how effectively an artery widens in response to increased blood flow.

It provides information about endothelial function.

The analysis found that omega-3 supplementation improved FMD by an average of approximately 0.8 percentage points compared with control treatments (Arabi et al., 2024).

That finding is encouraging.

But it is important to understand what it means.

The study did not demonstrate that 0.8% fewer people experienced heart attacks.

It demonstrated an improvement in a measurement of vascular function.

The researchers also reported substantial differences among the studies, meaning the size of the effect varied considerably.

Then, in 2026, another systematic review and meta-analysis examined omega-3 supplementation and several vascular health measurements.

Published in the Journal of the American Nutrition Association, the study by Norouzzadeh and colleagues (2026) included 20 randomized trials involving 1,208 participants.

The researchers reported improvements in certain vascular function measurements, but not all outcomes improved.

In particular, they did not find a statistically significant overall improvement in pulse-wave velocity, a measurement commonly used to assess arterial stiffness.

The certainty of the evidence varied from moderate to low.

So, what should we take away from these findings?

Human clinical research suggests that omega-3 fatty acids can improve certain measurements of endothelial function.

That supports further attention to EPA and DHA in cardiovascular health.

However, improvements in FMD, membrane properties, or nitric oxide signaling do not automatically establish that a supplement prevents heart attacks, reverses coronary plaque, or prolongs life.

Those questions require clinical outcome trials.

Are Most People Getting Enough EPA and DHA?

Here’s another question worth asking.

How do you know whether your body has adequate amounts of EPA and DHA incorporated into its cell membranes?

Taking a fish oil supplement doesn’t necessarily answer that question.

Neither does occasionally eating fish.

And here’s something many people don’t realize: Just because a supplement label says it contains omega-3 fatty acids doesn’t mean you know what your body’s fatty acid profile looks like.

Research suggests that low blood levels of EPA and DHA are widespread, particularly in populations with limited intake of omega-3-rich seafood.

A global review by Stark and colleagues (2016) examined 298 studies reporting blood levels of EPA and DHA.

The researchers identified substantial geographic differences in omega-3 status, with many populations showing low or very low levels.

North America was among the regions where relatively low EPA and DHA levels were commonly observed.

This does not mean that a specific percentage of Americans has a clinically diagnosed omega-3 insufficiency.

There is no universally accepted blood concentration that defines clinical EPA and DHA deficiency in every adult.

Nevertheless, these findings suggest that many people may have room to improve their omega-3 nutritional status.

And that brings us to something I believe deserves far more attention in preventive healthcare.

Why guess about your omega-3 status when you can measure it?

This is one reason I encourage people to consider fatty acid profile testing.

My At-Home Cellular Health Test is designed to provide measurable information about a person’s fatty acid status, including their omega-6-to-omega-3 ratio, Omega-3 Index, and individual fatty acid levels such as EPA and DHA.

Rather than simply assuming that eating fish or taking an omega-3 supplement is producing the intended nutritional response, testing provides an opportunity to establish a baseline and monitor changes over time.

And when it comes to cardiovascular health, understanding what’s happening at the cellular level may add useful information to the bigger picture.

Measuring Omega-3 Status Rather Than Assuming

How do you know whether your body has adequate amounts of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)?

Taking an omega-3 supplement doesn’t necessarily answer that question. Neither does occasionally eating fish.

One way to assess longer-term omega-3 status is through the Omega-3 Index, which measures EPA and DHA as a percentage of total fatty acids in red blood cell membranes.

The Omega-3 Index was proposed as a potential cardiovascular risk marker by Harris and von Schacky (2004).

Researchers have suggested that an Omega-3 Index of 8% or higher may represent a favorable range for cardiovascular health. However, this threshold is not a universally established treatment target, and randomized clinical trials have not demonstrated that raising everyone’s Omega-3 Index above 8% necessarily prevents heart attacks or strokes.

Nevertheless, knowing your omega-3 status can provide useful information about your nutritional health and how your body responds to dietary changes or supplementation.

What Does a Fatty Acid Profile Test Actually Tell You?

This is where my At-Home Cellular Health Test comes into the conversation.

Unlike a conventional cholesterol panel, which measures circulating lipids and lipoprotein-related markers, this test evaluates selected fatty acids and their relative proportions.

The results provide three particularly useful measurements.

1. Omega-6-to-Omega-3 Ratio

This measurement compares the relative amounts of omega-6 and omega-3 fatty acids in the tested sample.

Both families of fatty acids are essential to human health. They contribute to cell membrane structure and participate in biological pathways involved in cellular signaling and inflammation.

A higher omega-6-to-omega-3 ratio may reflect relatively lower omega-3 status, greater omega-6 representation, or both.

Why does this matter?

Because the relative amounts of these fatty acids help describe the composition of cell membrane lipids and the availability of fatty acids involved in important biological processes.

However, the ratio does not directly measure inflammation or diagnose cardiovascular disease. Although researchers and laboratories have proposed desirable ranges, no single omega-6-to-omega-3 ratio has been conclusively established as a threshold that guarantees protection against heart attacks, strokes, or other chronic diseases.

2. Omega-3 Index

The Omega-3 Index measures the combined amount of EPA and DHA as a percentage of total fatty acids in red blood cell membranes.

Because red blood cells circulate for approximately 120 days, their fatty acid composition provides information about longer-term omega-3 status rather than simply reflecting what someone ate yesterday.

This measurement can help establish a baseline and evaluate whether changes in diet or supplementation are producing a measurable response over time.

3. Individual EPA and DHA Levels

Although EPA and DHA belong to the same omega-3 family, they have distinct biological roles.

EPA participates in pathways involved in lipid mediator production, inflammatory regulation, and cellular signaling.

DHA is especially important for cell membrane structure and function, including membranes in the brain, retina, and other tissues.

Both fatty acids can influence the physical properties and signaling activities of cell membranes, including those of endothelial cells.

Measuring EPA and DHA individually provides more detailed information than simply knowing that someone takes a product labeled “fish oil.”

Why I Believe Testing Matters

Imagine two people who take an omega-3 supplement every day.

One person has an Omega-3 Index of 8.5%.

The other has an Omega-3 Index of 3.5%.

These are hypothetical examples, but they illustrate an important point.

Taking an omega-3 supplement does not guarantee that two people will have similar fatty acid profiles.

Differences in EPA and DHA dosage, supplement formulation, consistency of use, dietary intake, absorption, and individual biology can all influence the results.

Without testing, both individuals may assume they’re getting enough omega-3 fatty acids.

But their measured status tells a different story.

This is why I developed my approach around measuring rather than guessing.

The At-Home Cellular Health Test provides a baseline of fatty acid status, allowing individuals to see their omega-6-to-omega-3 ratio, Omega-3 Index, and individual EPA and DHA levels.

When appropriate, repeat testing can help determine whether nutritional changes are producing the intended measurable response.

The goal is to replace assumptions with information that can help guide more personalized nutritional decisions.

An Important Distinction About Cell Membranes

Earlier, we discussed the importance of endothelial cells—the cells lining the inside of blood vessels—and how their membranes participate in nitric oxide signaling and vascular function.

But here’s something important to understand.

Red blood cells are not endothelial cells.

Although both have cell membranes containing fatty acids, they perform very different functions.

The Omega-3 Index measures EPA and DHA in red blood cell membranes. It does not directly measure endothelial cell membrane fluidity, nitric oxide production, or the condition of the coronary artery wall.

Likewise, the omega-6-to-omega-3 ratio provides information about fatty acid proportions, not a direct measurement of arterial inflammation or coronary plaque.

A person can have a favorable Omega-3 Index and still have elevated apolipoprotein B (ApoB), high lipoprotein(a) [Lp(a)], insulin resistance, or extensive coronary atherosclerosis.

Conversely, an unfavorable fatty acid profile does not automatically mean someone has cardiovascular disease.

This is why fatty acid testing should complement—not replace—established cardiovascular risk assessment.

We must also distinguish between three different outcomes:

• • Measuring a biomarker: Knowing your current fatty acid profile.
  • Improving a biomarker: Demonstrating a measurable change in your fatty acid status.
  • Preventing a cardiovascular event: Demonstrating that an intervention reduces heart attacks, strokes, or premature deaths.

These are not interchangeable.

I believe understanding nutritional status is an important part of preventive healthcare. But no fatty acid profile test, by itself, can guarantee healthy arteries or freedom from cardiovascular disease.

The strongest approach combines food as medicine, nutritional assessment, metabolic health evaluation, and evidence-based cardiovascular prevention.

The Endothelial Glycocalyx: Your Blood Vessels’ Protective Coating

Now that we’ve explored endothelial cell membranes and fatty acid status, there’s another structure worth understanding.

It’s called the endothelial glycocalyx.

What Does Glycocalyx Mean?

The word glycocalyx comes from two parts:

• • Glyco- refers to sugars or carbohydrates.
  • -calyx means a covering or protective structure.

Put them together, and glycocalyx refers to a carbohydrate-rich coating that covers the surface of cells.

In blood vessels, the endothelial glycocalyx forms a delicate, gel-like layer on the blood-facing surface of endothelial cells.

It contains specialized molecules, including proteoglycans and glycosaminoglycans, that help maintain the normal functioning of the vascular lining.

Think of it as a protective coating that helps endothelial cells interact with flowing blood.

Why Is the Glycocalyx Important?

The endothelial glycocalyx performs several important functions.

It helps regulate what moves between the bloodstream and the artery wall, influences interactions between blood cells and the endothelium, and participates in the biological signals that help blood vessels respond to changing conditions.

One particularly important function involves detecting the mechanical forces created by flowing blood.

This process is called mechanotransduction.

What Does Mechanotransduction Mean?

Let’s break the word down:

• • Mechano- refers to mechanical forces, such as pressure, stretching, or movement.
  • Transduction means converting one type of signal into another.

In simple terms, mechanotransduction is how cells convert physical forces into biological signals.

For example, as blood flows through an artery, it creates frictional force along the endothelial surface. This is called shear stress.

The glycocalyx and associated cellular structures help endothelial cells detect these forces and activate signaling pathways that influence vascular function.

Some of these pathways help regulate nitric oxide production, allowing blood vessels to respond appropriately to changes in blood flow.

Research by Askari and colleagues (2023) describes how the glycocalyx interacts with membrane proteins and internal cellular structures to transmit mechanical signals.

What Happens When the Glycocalyx Becomes Damaged?

Researchers have found that conditions involving elevated blood glucose, oxidative stress, and inflammation can damage or alter the endothelial glycocalyx.

Metabolic dysfunction may contribute to these processes.

When the glycocalyx becomes compromised, some of its normal protective and signaling functions may be impaired.

This can contribute to an unhealthy vascular environment associated with endothelial dysfunction and atherosclerosis.

Why does this matter?

Because cardiovascular disease is influenced not only by the cholesterol-carrying particles circulating in the blood, but also by the condition of the cells and protective structures lining our blood vessels.

An unhealthy endothelium may become more susceptible to inflammatory activity and processes involved in plaque development.

Where Do EPA and DHA Fit Into This Picture?

EPA and DHA can become incorporated into endothelial cell membranes and influence pathways involved in inflammation, cellular signaling, and nitric oxide production.

Researchers are investigating whether these effects may contribute to healthier vascular function.

However, an important scientific distinction remains.

We do not yet have strong clinical evidence demonstrating that EPA or DHA supplementation directly restores the human endothelial glycocalyx or prevents heart attacks through this particular mechanism.

Nor should we assume that elevated insulin alone destroys the glycocalyx or that improving someone’s omega-3 status guarantees its repair.

The relationship between fatty acid composition, metabolic health, endothelial signaling, and atherosclerosis is complex.

But understanding these connections helps explain why cardiovascular health deserves a broader discussion than cholesterol alone.

Why This Changes the Cardiovascular Conversation

When evaluating cardiovascular health, we should be interested in more than the amount of cholesterol circulating in the bloodstream.

We should also consider the condition and function of the cells lining our arteries.

Are endothelial cells responding appropriately to blood flow?

Is nitric oxide signaling functioning normally?

Are metabolic dysfunction, oxidative stress, and inflammation contributing to vascular injury?

And could nutritional status, including EPA and DHA levels, be one of several modifiable factors influencing vascular health?

These are important questions.

They reinforce why food as medicine, metabolic health, and nutritional assessment deserve a place alongside conventional cardiovascular risk testing.

And they explain why I believe measuring fatty acid status can provide useful additional information, even though it cannot diagnose coronary disease or replace established cardiovascular testing.

Healthy arteries depend on more than cholesterol levels. The number of atherogenic particles, existing plaque burden, metabolic health, endothelial function, nitric oxide signaling, and cell membrane composition all contribute to the larger cardiovascular picture.

Insulin Resistance: A Cardiovascular Risk Factor We Shouldn’t Ignore

Now we come to a subject that has been central to my work for decades: metabolic health.

Insulin is a hormone produced by the pancreas that helps regulate blood glucose and coordinates how the body stores and uses nutrients.

When cells become less responsive to insulin, the pancreas often compensates by producing more of it.

This condition is called insulin resistance.

For years, insulin resistance may develop before someone receives a diagnosis of type 2 diabetes.

During this period, fasting glucose and hemoglobin A1c (HbA1c)—a measure reflecting average blood glucose over approximately two to three months—may not fully reveal the underlying metabolic dysfunction.

But before examining how insulin resistance contributes to cardiovascular risk, I want to share something that should get everyone’s attention.

How Widespread Is Poor Metabolic Health in America?

Research from two respected American universities suggests that the overwhelming majority of U.S. adults are not achieving optimal metabolic health.

In a study conducted by researchers at the University of North Carolina at Chapel Hill, published in 2019, investigators analyzed data from 8,721 adults participating in the National Health and Nutrition Examination Survey (NHANES) between 2009 and 2016.

They examined five important markers: waist circumference, blood glucose, blood pressure, triglycerides, and HDL cholesterol.

Their finding?

Only 12.2% of American adults met all five criteria for optimal metabolic health.

That means approximately 87.8%—nearly nine out of ten adults—did not (Araújo et al., 2019).

Then came another eye-opening study.

In 2022, researchers from Tufts University’s Friedman School of Nutrition Science and Policy published findings in the Journal of the American College of Cardiology after analyzing data from more than 55,000 American adults.

Using a comprehensive assessment of cardiometabolic health, including body fatness, blood glucose, blood lipids, blood pressure, and cardiovascular disease status, they found that only 6.8% of American adults had optimal cardiometabolic health in 2017–2018.

Think about that.

Approximately 93.2% of American adults failed to meet all the criteria for optimal cardiometabolic health (O’Hearn et al., 2022).

Now, an important distinction: these findings do not mean that 93% of American adults have clinically confirmed insulin resistance.

The researchers evaluated multiple metabolic and cardiovascular risk factors, not insulin resistance alone.

Furthermore, failing to meet every optimal criterion does not necessarily mean someone has a metabolic disease.

However, insulin resistance is closely associated with several of the abnormalities these studies examined.

And that raises an important question:

If poor metabolic health is this widespread, why aren’t we paying more attention to identifying metabolic dysfunction before someone develops type 2 diabetes, coronary artery disease, or experiences a heart attack?

This is one reason I believe cardiovascular prevention must extend beyond LDL cholesterol.

We should be looking at blood glucose regulation, insulin sensitivity, triglycerides, HDL cholesterol, blood pressure, abdominal fat, and other indicators of metabolic health.

Because preventing cardiovascular disease should begin long before someone develops symptoms.

How Insulin Resistance Affects Cardiovascular Risk

Insulin resistance is commonly associated with several cardiovascular risk factors:

• • Elevated triglycerides
  • Low HDL cholesterol
  • Increased abdominal fat
  • Higher blood pressure
  • Fat accumulation in the liver
  • Abnormal glucose regulation
  • Changes in lipoprotein particle concentrations and sizes

These abnormalities often occur together.

They can influence vascular health, inflammation, and cardiovascular risk.

But I want to make an important distinction.

Insulin resistance is a major contributor to cardiovascular risk. It is not the single explanation for every case of atherosclerosis or heart disease.

Some people develop coronary disease despite relatively favorable insulin sensitivity.

Others have significant insulin resistance without having detectable coronary plaque.

Genetics, ApoB exposure, Lp(a), blood pressure, smoking, age, and other factors still matter.

This is why I advocate addressing metabolic dysfunction without ignoring the other mechanisms involved in cardiovascular disease.

What Should We Measure?

A standard metabolic assessment may include fasting glucose, HbA1c, triglycerides, HDL cholesterol, blood pressure, and waist circumference.

In selected cases, fasting insulin can offer additional context, although there is no universally accepted fasting insulin cutoff that independently diagnoses insulin resistance in every individual.

Another useful calculation is the triglyceride-to-HDL cholesterol ratio.

For example, someone with triglycerides of 180 mg/dL and HDL cholesterol of 40 mg/dL has a ratio of 4.5.

This pattern can suggest metabolic dysfunction, although its interpretation depends on factors including ethnicity, sex, and the units used.

The ratio is not a definitive diagnostic test.

Still, these measurements can help identify a metabolic pattern that deserves attention.

And now there’s another measurement worth discussing.

Fasting Insulin and HOMA-IR: Are We Overlooking Early Insulin Resistance?

One of the most overlooked measurements in metabolic health is fasting insulin.

Most people are familiar with fasting blood glucose and hemoglobin A1c (HbA1c).

But here’s something important to understand.

Your blood glucose can remain within the normal range even when your body is producing more insulin than it should need to maintain that level.

This can occur during the early development of insulin resistance.

As cells become less responsive to insulin, the pancreas may compensate by producing additional insulin to help maintain normal blood glucose levels.

Consequently, a person can have reassuring glucose results while already experiencing metabolic dysfunction.

This is why I believe fasting insulin deserves greater attention.

What Is HOMA-IR?

HOMA-IR stands for Homeostatic Model Assessment of Insulin Resistance.

It uses fasting insulin and fasting glucose to estimate insulin resistance.

The calculation is straightforward:

HOMA-IR = (Fasting Insulin × Fasting Glucose) ÷ 405

This formula applies when fasting insulin is measured in µIU/mL and fasting glucose in mg/dL.

For example, imagine someone has:

• • Fasting glucose: 95 mg/dL
  • Fasting insulin: 15 µIU/mL

Their HOMA-IR would be approximately 3.5.

Although their fasting glucose is within the normal range, the elevated insulin requirement and HOMA-IR result may suggest insulin resistance.

Generally, higher HOMA-IR values indicate greater estimated insulin resistance.

However, there is no single universally accepted cutoff for diagnosing insulin resistance in every individual. Results can vary with insulin assay methods, age, population characteristics, and underlying metabolic conditions.

Why Does This Matter for Your Arteries?

One of the biggest misconceptions about insulin resistance is that it must be accompanied by elevated blood glucose or triglycerides.

That’s simply not true.

A person can have normal fasting glucose, normal hemoglobin A1c (HbA1c), and normal triglycerides while still being insulin resistant.

In fact, during the early stages of insulin resistance, the pancreas may compensate by producing additional insulin to keep blood glucose within the normal range.

This means metabolic dysfunction can be developing even when conventional blood tests appear reassuring.

Although insulin resistance is frequently associated with elevated triglycerides, altered lipoprotein metabolism, high blood pressure, and endothelial dysfunction, these abnormalities do not have to be present for insulin resistance to exist.

Research has demonstrated that normal triglycerides and a favorable triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio do not reliably exclude insulin resistance, particularly in certain populations (Sumner et al., 2005; Kim-Dorner et al., 2010).

This is particularly important because insulin resistance can contribute to an unfavorable cardiovascular environment through several biological pathways.

These include impaired endothelial function, altered nitric oxide signaling, increased oxidative stress, and changes in inflammatory activity.

Over time, these processes may contribute to vascular dysfunction and the development or progression of atherosclerosis.

However, insulin resistance does not automatically mean someone has coronary plaque, and improving insulin sensitivity does not, by itself, prove that existing plaque has regressed.

This is why I believe fasting insulin and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) deserve greater attention when evaluating metabolic and cardiovascular health.

These measurements can help identify metabolic dysfunction that may not be apparent from glucose and triglyceride results alone.

Neither test is perfect, and neither has a universally accepted diagnostic cutoff. But they can provide valuable information when interpreted alongside blood pressure, waist circumference, lipid measurements, glucose regulation, and the person’s overall clinical picture.

Normal triglycerides do not rule out insulin resistance. Normal glucose does not rule out insulin resistance. And waiting until these measurements become abnormal may mean missing an earlier opportunity to intervene.

My position is simple: We should not wait for someone to develop diabetes before taking insulin resistance seriously—especially when our goal is to prevent cardiovascular disease before a heart attack or stroke occurs.

LP-IR: Can Advanced Lipoprotein Testing Reveal Metabolic Dysfunction?

Most people are familiar with a standard lipid panel.

It typically reports total cholesterol, LDL-C, HDL cholesterol, and triglycerides.

But advanced lipoprotein testing can reveal additional information about particle concentrations and sizes.

One example is the lipoprotein insulin resistance (LP-IR) score.

LP-IR is derived from nuclear magnetic resonance (NMR) lipoprotein testing.

It uses six lipoprotein-related measurements, including particle concentrations and particle sizes, to estimate a pattern associated with insulin resistance.

The score generally ranges from 0 to 100.

Lower scores indicate a more insulin-sensitive lipoprotein pattern, while higher scores indicate a more insulin-resistant pattern.

In 2014, Shalaurova and colleagues published research evaluating LP-IR as a lipoprotein-derived measure of insulin resistance.

Their findings supported an association between specific lipoprotein characteristics and insulin resistance.

Why might this be useful?

Because insulin resistance can influence the way the liver produces, processes, and clears triglyceride-rich lipoproteins.

It can also affect HDL particles and other aspects of lipoprotein metabolism.

An individual may therefore have a metabolic disturbance that is not fully captured by LDL-C alone.

LP-IR has been investigated as a marker of insulin resistance and a predictor of future type 2 diabetes.

However, we need to understand its limitations.

LP-IR is not a direct measurement of insulin action, and a favorable score does not guarantee that someone is free of coronary artery disease.

Nor has a particular LP-IR threshold been established as proof that a person has little or no chance of developing a heart attack.

It is not a replacement for ApoB, Lp(a), coronary artery calcium imaging, or a comprehensive clinical risk assessment.

For people with suspected metabolic dysfunction, LP-IR may offer additional information.

But it should be interpreted in context, not treated as a cardiovascular safety certificate.

Coronary Artery Calcium: Seeing Evidence of Disease

Here’s where our discussion becomes especially important.

A cholesterol test estimates certain risk-related factors circulating in the blood.

A coronary artery calcium (CAC) scan provides information about calcified atherosclerotic plaque already present in the coronary arteries.

The scan uses computed tomography (CT) to identify and quantify coronary calcium.

The result is commonly reported as an Agatston score.

A score of zero means no coronary calcium was detected.

A higher score generally indicates a greater burden of calcified coronary atherosclerosis.

A score above 300 is commonly associated with substantially elevated cardiovascular risk.

And a score of 1,000 or higher identifies a particularly high-risk group.

In the Multi-Ethnic Study of Atherosclerosis (MESA), ten-year atherosclerotic cardiovascular event rates ranged from approximately 1.3% to 5.6% among people with CAC scores of zero, compared with approximately 13.1% to 25.6% among those with scores above 300, depending on demographic subgroup (Budoff et al., 2018).

These are absolute event rates, not simply relative comparisons.

They demonstrate why measuring existing plaque burden can add important information beyond conventional risk factors.

However, CAC testing has limitations.

It detects calcified plaque, not all noncalcified or so-called soft plaque.

A score of zero does not guarantee that the coronary arteries are free of atherosclerosis.

This is particularly important in younger adults and in people with certain high-risk characteristics.

A CAC scan also does not tell us whether a particular coronary artery has a flow-limiting narrowing.

For that, other testing may be appropriate depending on symptoms and clinical circumstances.

CAC is a risk-assessment tool, not a universal screening test for everyone.

But in appropriately selected individuals, it can meaningfully influence cardiovascular prevention decisions.

The 2026 ACC/AHA dyslipidemia guideline further recognizes the role of CAC scoring in refining cardiovascular risk assessment (Blumenthal et al., 2026).

John Doe: A CAC Score of 1,276

Let me introduce an anonymized case that illustrates why we must look beyond cholesterol numbers.

I’ll refer to this individual as John Doe.

On October 1, 2026, John underwent a coronary artery calcium scan.

His total Agatston score was:

1,276.

The calcium was distributed across multiple coronary arteries:

Coronary artery	CAC score
Left main	151
Left anterior descending (LAD)	468
Left circumflex	93
Right coronary artery (RCA)	564
Total	1,276

His report classified the findings as indicating very high coronary artery disease risk.

This is not a borderline result.

It represents extensive calcified coronary atherosclerosis.

John’s laboratory findings also revealed important risk factors.

His LDL-C was approximately 146 mg/dL, HDL cholesterol was 43 mg/dL, and triglycerides were 105 mg/dL.

His triglyceride-to-HDL ratio was approximately 2.44.

But another result caught my attention.

His lipoprotein(a), or Lp(a), exceeded 233 nmol/L.

That is substantially elevated.

His ApoB had not yet been measured.

What Happened When John Saw the Cardiologist?

John subsequently attended a cardiology appointment.

He reported that the visit was brief and that he was told he was asymptomatic.

The cardiologist prescribed rosuvastatin 20 mg daily, ordered a stress test, and reportedly recommended follow-up in one year.

Rosuvastatin 20 mg is a high-intensity statin dose, and prescribing lipid-lowering therapy was a reasonable step given John’s cardiovascular risk.

However, another detail in John’s clinical summary deserves attention.

He had reported mild left arm or biceps discomfort when beginning a walk, with the discomfort subsiding after approximately five to ten minutes.

That symptom does not necessarily mean he has obstructive coronary artery disease.

Musculoskeletal explanations are possible.

But exertional arm discomfort can sometimes be an anginal equivalent—a symptom of inadequate blood flow to the heart occurring without typical chest pain.

And in someone with a CAC score of 1,276, it deserves prompt clinical attention rather than waiting for an annual visit.

John should ensure that his cardiology team is aware of the symptom, clarify the timing of the ordered stress test, and obtain individualized guidance about exercise while the symptom is being evaluated.

New, worsening, persistent, or severe symptoms—particularly when accompanied by chest discomfort, breathlessness, sweating, nausea, or faintness—warrant emergency evaluation.

The ordered stress test may help assess whether exertion produces evidence of reduced blood flow to the heart muscle.

But even a normal stress test would not eliminate the significance of his existing plaque burden.

The cardiologist also needs to consider John’s elevated Lp(a), blood pressure history, and previously reported episode of a very rapid heart rhythm requiring electrical cardioversion.

His exact arrhythmia diagnosis remains important, particularly because certain rhythm disorders require a separate assessment of stroke risk.

What Does This Case Teach Us?

First, a favorable triglyceride level does not erase extensive coronary plaque.

Second, a cholesterol panel cannot substitute for direct evidence of coronary atherosclerosis.

Third, a person may have significant cardiovascular risk even when symptoms are absent or subtle.

Fourth, prescribing a medication is only one part of a comprehensive prevention strategy.

For John, an appropriate plan should also include timely evaluation of his exertional symptoms, assessment of treatment response, consideration of ApoB testing, and clear follow-up.

The response to lipid-lowering treatment is generally reassessed within approximately four to twelve weeks rather than waiting an entire year to determine whether the medication achieved its intended effect.

A favorable fasting insulin, glucose, triglyceride level, or LP-IR score would not erase a CAC score of 1,276.

That is a point I want every reader to understand.

Lipoprotein(a): A Risk Factor Many People Have Never Had Measured

Lp(a) is one of the most important inherited cardiovascular risk factors that remains unfamiliar to much of the public.

It is an LDL-like particle containing ApoB and an additional protein called apolipoprotein(a).

Lp(a) concentrations are largely determined by genetics.

Elevated levels are associated with greater risk of atherosclerotic cardiovascular disease and calcific aortic valve disease (Kronenberg et al., 2022).

Unlike triglycerides or glucose, Lp(a) levels generally do not change dramatically in response to ordinary dietary modifications.

This is why someone can eat well, exercise regularly, and maintain favorable metabolic measurements yet still have elevated inherited cardiovascular risk.

The 2026 American College of Cardiology (ACC) and American Heart Association (AHA) guideline recommends measuring lipoprotein(a) [Lp(a)] at least once during adulthood. An elevated result does not mean a heart attack is inevitable.

It means the overall prevention strategy may need to be more intensive, particularly when other risk factors or established plaque are present.

For someone like John Doe, knowing the Lp(a) level adds valuable context.

And it underscores why a single laboratory marker should never dominate the entire cardiovascular conversation.

Why a CAC Score of Zero Is Not a Lifetime Guarantee

Before moving on to treatment, there’s one more point about coronary calcium that deserves attention.

A CAC score of zero is generally reassuring, particularly when interpreted in the context of a person’s age and other risk factors.

But zero calcium does not mean zero cardiovascular risk.

Some plaques have not yet accumulated enough calcium to be detected.

This is particularly relevant in younger adults, whose plaques may be less calcified.

Certain high-risk individuals may therefore have noncalcified coronary plaque despite a CAC score of zero.

And because coronary disease changes over time, a zero score today does not guarantee a zero score years from now.

This is why CAC results should be interpreted alongside symptoms, diabetes status, smoking, family history, and other clinical factors.

No single cardiovascular test tells the entire story.

What Statins Actually Do

Now let’s address one of the most debated subjects in cardiovascular medicine.

What exactly do statins do inside the body, and how does that translate into reducing the risk of a heart attack or stroke?

Statins are medications that inhibit an enzyme called 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase).

That’s a complicated name, but the process is relatively straightforward.

This enzyme plays a central role in the production of cholesterol, particularly in the liver.

The medical term hepatic simply means relating to the liver.

By inhibiting HMG-CoA reductase, statins reduce the liver’s ability to manufacture cholesterol.

But here’s where the process becomes especially interesting.

How Does Lowering Cholesterol Production Affect the Bloodstream?

When cholesterol availability inside liver cells decreases, the liver responds by increasing the number of low-density lipoprotein (LDL) receptors on its surface.

Think of these receptors as docking stations that capture LDL particles circulating in the bloodstream.

The liver takes up these particles and processes their contents.

As a result, fewer LDL particles remain circulating in the blood.

This is why statins generally lower both:

• • LDL cholesterol (LDL-C): The amount of cholesterol carried inside LDL particles.
  • Apolipoprotein B (ApoB): A marker of the number of circulating potentially plaque-forming lipoprotein particles.

Some statins also produce modest reductions in triglycerides.

And because ApoB-containing particles play an important causal role in atherosclerosis, reducing their concentration can help lower cardiovascular risk.

But Lower Cholesterol Is Not the Same as Preventing a Heart Attack

This is where I believe the conversation needs to become more meaningful.

The central question should not simply be:

“How much did the medication lower my cholesterol?”

It should also be:

“How much does this medication reduce my actual risk of having a heart attack, stroke, or other cardiovascular event?”

And in appropriately selected patients, randomized clinical trials have demonstrated that statins can reduce these events.

However, the magnitude of benefit depends heavily on a person’s baseline cardiovascular risk.

Someone who has already experienced a heart attack or has extensive coronary atherosclerosis is not in the same risk category as a younger adult with no known plaque and otherwise favorable cardiovascular risk factors.

Even when two people experience a similar percentage reduction in LDL-C, the absolute benefit they receive from statin treatment may be very different.

This is why I believe statin decisions should be based on an individual’s overall cardiovascular risk—not simply whether one cholesterol measurement falls above a particular number.

The goal should always be to prevent cardiovascular events, not merely to produce a more favorable laboratory report.

Relative Risk Versus Absolute Risk: The Numbers Everyone Should Understand

This may be one of the most important sections of this article.

When people hear that a medication reduces heart attacks by 25%, they may imagine that 25 out of every 100 people taking it will avoid a heart attack.

That is not what a 25% relative risk reduction means.

To understand why, let’s examine two hypothetical five-year clinical trials involving people with different levels of cardiovascular risk.

Example 1: People With Lower Cardiovascular Risk

Imagine a five-year study involving 2,000 people, divided equally into two groups.

• • Among 1,000 people not receiving the medication, 20 experience a heart attack.
  • Among 1,000 people receiving the medication, 15 experience a heart attack.

That means:

• Without medication: 2% experienced a heart attack.
• With medication: 1.5% experienced a heart attack.

How Do Researchers Calculate the Relative Risk Reduction?

Relative risk reduction tells us how much the risk decreased compared with the original risk.

The formula is:

Relative Risk Reduction = (Untreated Event Rate − Treated Event Rate) ÷ Untreated Event Rate × 100

Using our numbers:

(2% − 1.5%) ÷ 2% × 100 = 25%

That’s where the 25% relative risk reduction comes from.

But here’s what I want you to understand.

How Do We Calculate the Absolute Risk Reduction?

Absolute risk reduction tells us how much the actual chance of experiencing a heart attack decreased.

The formula is:

Absolute Risk Reduction = Untreated Event Rate − Treated Event Rate

Using the same numbers:

2% − 1.5% = 0.5 percentage points

That’s an absolute risk reduction of 0.5% of the population over five years.

In other words, the medication prevented approximately 5 additional heart attacks for every 1,000 people treated over five years, compared with the untreated group.

So, in this example:

Relative risk reduction: 25%

Absolute risk reduction: 0.5% (0.5 percentage points)

Both numbers are correct, but they describe different aspects of the same benefit.

Here’s another way to look at it.

Of the 1,000 people who did not receive the medication, 980 did not experience a heart attack.

Of the 1,000 people who received the medication, 985 did not experience a heart attack.

That’s a difference of just five people.

Example 2: People With Higher Cardiovascular Risk

Now imagine another five-year study, but this time involving people with a much higher risk of experiencing a cardiovascular event.

Once again, the study includes 2,000 people divided equally into two groups.

• Among 1,000 people not receiving the medication, 200 experience a cardiovascular event.
• Among 1,000 people receiving the medication, 150 experience a cardiovascular event.

That means:

• Without medication: 20% experienced a cardiovascular event.
• With medication: 15% experienced a cardiovascular event.

How Do We Calculate the Relative Risk Reduction?

Remember, relative risk reduction tells us how much the risk decreased compared with the original risk.

(20% − 15%) ÷ 20% × 100 = 25%

Once again, the medication produced a 25% relative risk reduction.

Exactly the same relative risk reduction as Example 1.

How Do We Calculate the Absolute Risk Reduction?

Now let’s calculate the actual difference in risk.

20% − 15% = 5 percentage points

That’s an absolute risk reduction of 5% of the population over five years.

In practical terms, the medication prevented approximately 50 additional cardiovascular events for every 1,000 people treated over five years.

So, in this example:

Relative risk reduction: 25%

Absolute risk reduction: 5% (5 percentage points)

And here’s the important distinction.

In Example 1, the medication prevented 5 additional heart attacks per 1,000 people.

In Example 2, the medication prevented 50 additional cardiovascular events per 1,000 people.

Same Relative Risk Reduction. Very Different Absolute Benefit.

Both examples produced the same 25% relative risk reduction.

But the absolute benefit was dramatically different.

In the lower-risk group, the absolute reduction was 0.5%, representing 5 fewer heart attacks per 1,000 people over five years.

In the higher-risk group, the absolute reduction was 5%, representing 50 fewer cardiovascular events per 1,000 people over five years.

Same 25% relative risk reduction. Ten times the absolute reduction in event probability.

Why?

Because the second group had a much higher risk of experiencing a cardiovascular event to begin with.

Here’s the simplest way I can explain it:

Relative risk reduction tells you how much your risk decreases proportionally compared with where it started.

Absolute risk reduction tells you how much your actual chance of experiencing an event decreases.

If your starting risk is low, a 25% relative reduction may translate into a relatively small absolute benefit.

If your starting risk is high, that same 25% relative reduction may translate into a much larger absolute benefit.

The relative percentage sounds the same. The number of events prevented can be very different.

That’s why I believe patients deserve to hear both numbers.

What Is the Number Needed to Treat?

There’s another measurement I want you to understand.

It’s called the number needed to treat (NNT).

This tells us approximately how many people would need to receive a medication over a specific period to prevent one additional cardiovascular event.

And we can calculate it using percentages without converting anything into decimals.

The formula is:

NNT = 100 ÷ Absolute Risk Reduction (percentage-point value)

Example 1: Lower-Risk Group

The absolute risk reduction was 0.5 percentage points.

100 ÷ 0.5 = 200

That means approximately 200 people would need to take the medication for five years to prevent one additional heart attack.

Example 2: Higher-Risk Group

The absolute risk reduction was 5 percentage points.

100 ÷ 5 = 20

That means approximately 20 people would need to take the medication for five years to prevent one additional cardiovascular event.

Think about that.

In the lower-risk group, approximately 200 people needed treatment to prevent one additional event.

In the higher-risk group, approximately 20 people needed treatment to prevent one additional event.

Same relative risk reduction. But substantially different absolute benefits and numbers needed to treat.

These are hypothetical examples designed to explain the mathematics. They are not actual clinical trial results or predictions of an individual patient’s benefit.

Actual results depend on the medication, the population being treated, the outcome being measured, and the duration of follow-up.

Why This Matters When Discussing Statins

Now let’s bring this back to statins.

Imagine two people sitting in their doctor’s office.

One has already experienced a heart attack or has extensive coronary artery plaque.

The other has no known coronary artery disease and relatively few cardiovascular risk factors.

Should we assume both people will receive the same absolute benefit from a statin?

No.

Their starting cardiovascular risks may be very different.

Someone with established cardiovascular disease or substantial plaque burden may have considerably more to gain from an effective treatment than someone whose risk of a heart attack is already very low.

That doesn’t mean statins are unnecessary for everyone at lower risk.

Nor does it mean everyone at higher risk should automatically receive the same treatment.

It means treatment decisions should consider a person’s overall cardiovascular risk, expected absolute benefit, possible adverse effects, and personal preferences.

A relative risk reduction without the corresponding absolute risk reduction can create a misleading impression of the size of a treatment’s benefit.

My position is simple:

Don’t just tell me a medication reduces cardiovascular events by 25%. Tell me my estimated starting risk, how much that risk may decrease with treatment, and over what period of time.

That’s the information that helps patients make informed decisions about their cardiovascular health.

What Clinical Trials Tell Us About Statin Benefits

A major systematic review conducted for the U.S. Preventive Services Task Force examined statin therapy for primary prevention—that is, prevention among people without a prior cardiovascular event.

Across the included studies, statin treatment was associated with several benefits (Chou et al., 2022).

For myocardial infarction, the pooled relative risk reduction was approximately 33%, accompanied by an absolute risk reduction of approximately 0.85 percentage points, or 8.5 fewer events per 1,000 participants.

For stroke, the relative risk reduction was approximately 22%, with an absolute reduction of approximately 0.39 percentage points, or 3.9 fewer events per 1,000 participants.

For composite cardiovascular outcomes, the relative risk reduction was approximately 28%, with an absolute reduction of approximately 1.28 percentage points, or 12.8 fewer events per 1,000 participants.

For all-cause mortality, the relative risk reduction was approximately 8%, with an absolute reduction of approximately 0.35 percentage points, or 3.5 fewer deaths per 1,000 participants.

These were pooled findings from studies with varying follow-up periods, approximately six months to six years, and differing participant risk profiles.

They should not be interpreted as precise five-year estimates for every individual.

Nevertheless, they demonstrate something important.

Statins can prevent cardiovascular events.

But the absolute benefit varies.

That is why decisions should consider the patient’s overall risk, existing disease, preferences, treatment tolerance, and alternative options.

What About Statin Side Effects?

Statins can cause adverse effects, and patients deserve to have those concerns taken seriously.

Some people report muscle pain, weakness, fatigue, or other symptoms while taking these medications.

However, muscle symptoms are also common among people who are not taking statins.

A large analysis of randomized, blinded trials found that statin therapy caused a relatively small excess of muscle symptoms compared with placebo, particularly during the first year of treatment (Cholesterol Treatment Trialists’ Collaboration, 2022).

Rarely, statins can cause serious muscle injury.

Statins can also increase the likelihood of developing diabetes, particularly among individuals already predisposed to it.

A 2024 individual-participant-data analysis confirmed a dose-dependent increase in diabetes diagnoses associated with statin therapy (Cholesterol Treatment Trialists’ Collaboration, 2024).

That risk needs to be weighed against cardiovascular benefit, especially in patients with substantial atherosclerotic risk.

Other issues, including potential drug interactions and changes in liver enzymes, may require evaluation.

Statins also inhibit a pathway involved in the synthesis of coenzyme Q10 (CoQ10), but reduced circulating CoQ10 does not establish that supplementation prevents statin-related muscle symptoms. Clinical trial results have not consistently demonstrated such a benefit.

What should happen when someone experiences side effects?

They deserve an individualized assessment.

Depending on the circumstances, a clinician may consider a different statin, a lower dose, an adjusted regimen, or a nonstatin medication.

The important point is that medication intolerance should not automatically result in abandoning cardiovascular risk reduction.

This is particularly true for people with established atherosclerosis or very high cardiovascular risk.

10 Questions to Ask Your Doctor Before Starting a Statin

Remember the third person from the beginning of this article?

The individual who walked into the doctor’s office feeling fine but left frightened after being told their LDL cholesterol was too high?

This section is for that person—and for anyone who wants to understand their cardiovascular health before making a medication decision.

I believe patients should be encouraged to ask questions, understand their risk, and participate in decisions about their care.

These questions are not intended to challenge a physician’s expertise or suggest that statins are unnecessary.

They’re intended to make sure patients understand why a medication is being recommended and what they can reasonably expect from it.

1. What is my actual risk of having a heart attack or stroke over the next 10 years?

Ask your doctor to explain your estimated cardiovascular risk using an appropriate risk assessment method.

Age, blood pressure, smoking, diabetes, cholesterol measurements, and other factors can influence that estimate.

A risk calculator is not perfect, but it can help provide context.

If you already have cardiovascular disease, your risk may need to be assessed differently.

2. How much will this statin reduce my risk in absolute numbers—not just percentages?

This may be the most important question on the list.

If your doctor says a statin could reduce your risk by 25%, ask what that means in absolute terms.

For example, does it mean reducing your estimated five-year risk from 20% to 15%, or from 2% to 1.5%?

Both represent a 25% relative reduction, but the absolute benefits are very different.

Ask about the expected time frame and whether the estimate comes from patients with risk profiles similar to yours.

3. Do I already have evidence of coronary artery plaque, and would a CAC scan help clarify my risk?

A coronary artery calcium scan may provide valuable information about existing calcified plaque.

For some adults, particularly when the decision to begin medication is uncertain, CAC testing can help refine risk assessment.

However, not everyone needs a CAC scan.

People with established cardiovascular disease, very high LDL-C, certain inherited conditions, or other high-risk features may already have a strong indication for treatment without additional imaging.

And a CAC score of zero does not exclude noncalcified plaque.

Ask whether the test would actually change your treatment plan.

4. Should we measure ApoB and lipoprotein(a) before making a decision?

ApoB provides information about the number of potentially plaque-forming lipoprotein particles.

Lp(a) is an inherited cardiovascular risk factor that many people have never had measured.

These tests can provide information beyond LDL-C.

Ask whether your existing results and risk profile make ApoB testing useful.

And if you’ve never had Lp(a) measured, ask about obtaining it at least once during adulthood.

5. Have we evaluated my metabolic health and possible insulin resistance?

Ask your doctor to review your triglycerides, HDL cholesterol, fasting glucose, HbA1c, blood pressure, waist circumference, and other relevant measurements.

In selected cases, fasting insulin or advanced lipoprotein testing may provide additional context.

Insulin resistance and related metabolic abnormalities can influence cardiovascular risk.

But favorable metabolic results do not rule out atherosclerosis.

6. Is my elevated LDL-C the only reason you’re recommending a statin, or are there other risk factors?

This question encourages a more complete conversation.

Your doctor may be considering age, diabetes, blood pressure, smoking, family history, chronic kidney disease, Lp(a), existing plaque, or other factors.

An LDL-C level of 190 mg/dL or higher, for example, may warrant treatment even without a CAC scan because of the potential for substantial lifetime exposure to atherogenic lipoproteins.

Ask which findings are driving the recommendation in your particular case.

7. What are the potential side effects, and what should I do if I experience them?

Ask about muscle symptoms, changes in blood glucose, medication interactions, and any monitoring that may be appropriate.

If you have previously experienced statin-related symptoms, explain exactly what happened.

There may be options involving a different statin, an adjusted dose, or another medication.

Do not stop a prescribed cardiovascular medication without discussing the decision with your healthcare professional.

8. What alternatives or additional treatments are available if I cannot tolerate a statin?

Ezetimibe, PCSK9 inhibitors, bempedoic acid, and other therapies may be appropriate in selected situations.

These medications work through different mechanisms and have different evidence bases, costs, and administration requirements.

Ask which options are supported by cardiovascular outcome trials for people with your risk profile.

Also ask whether combination therapy could provide better risk reduction with a tolerable regimen.

9. What lifestyle and nutritional changes should I make alongside treatment?

Medication should not replace attention to nutrition, physical activity, smoking, blood pressure, sleep, or metabolic health.

Ask what dietary changes could help improve your ApoB, LDL-C, triglycerides, blood pressure, and glucose regulation.

Discuss whether your current eating pattern provides adequate protein, dietary fiber, and essential nutrients.

If you’re interested in supplements, ask about their potential benefits, limitations, and interactions with your medications.

Remember that improving a nutritional biomarker does not automatically establish protection against cardiovascular events.

10. What is our follow-up plan, and how will we know whether the treatment is working?

Before leaving the appointment, make sure you understand the next steps.

Ask when your cholesterol and other relevant markers should be rechecked.

After starting or changing lipid-lowering medication, reassessment is commonly recommended within approximately four to twelve weeks.

Ask what treatment targets are appropriate for your risk level, whether ApoB should be monitored, and what would prompt a change in treatment.

Also clarify which symptoms require urgent evaluation.

The purpose of these questions is not to talk someone out of taking a statin. It’s to make sure the decision is informed, individualized, and supported by an appropriate assessment of cardiovascular risk.

For someone with extensive coronary plaque, a previous heart attack, or another high-risk condition, delaying proven treatment while pursuing unnecessary testing can be harmful.

But for someone whose treatment decision is less clear, additional discussion and selected testing may help clarify the most appropriate approach.

You deserve to understand your cardiovascular risk—not simply be frightened by a laboratory number.

Beyond Statins: Ezetimibe and PCSK9 Inhibitors

One reason I want to expand this discussion is that many people assume the only choices are taking a statin or taking nothing.

That is not the case.

Several evidence-based medications can reduce circulating atherogenic lipoproteins.

Ezetimibe: Reducing Intestinal Cholesterol Absorption

Ezetimibe works by inhibiting a cholesterol transporter called Niemann-Pick C1-Like 1 (NPC1L1) in the small intestine.

This reduces absorption of cholesterol from both dietary sources and bile.

The liver responds by increasing the clearance of circulating LDL particles.

Ezetimibe is often used with a statin when additional LDL-C lowering is needed.

It may also be considered when a patient cannot tolerate statin therapy.

But does it actually reduce cardiovascular events?

The IMPROVE-IT trial examined patients who had recently experienced an acute coronary syndrome, such as a heart attack or unstable angina.

Over approximately seven years, the primary composite cardiovascular event rate was 34.7% with simvastatin alone, compared with 32.7% with simvastatin plus ezetimibe.

That represents an absolute reduction of 2.0 percentage points, or approximately 20 fewer composite events per 1,000 patients over seven years (Cannon et al., 2015).

The relative reduction in the event rate was approximately 5.8%.

That is a modest but meaningful additional benefit in the studied population.

And it demonstrates why the clinical context matters.

The results do not mean every healthy adult should take ezetimibe.

They demonstrate that adding the medication can reduce events in an appropriately selected high-risk population.

PCSK9 Inhibitors: Helping the Liver Clear LDL Particles

Another treatment category involves proprotein convertase subtilisin/kexin type 9 (PCSK9).

PCSK9 is a protein involved in regulating the number of LDL receptors available on liver cells.

LDL receptors help remove LDL particles from the bloodstream.

When PCSK9 promotes the degradation of these receptors, fewer receptors remain available to clear LDL.

Medications such as evolocumab and alirocumab inhibit PCSK9, allowing more LDL receptors to remain active.

These injectable treatments can produce substantial reductions in LDL-C, often around 50% to 60% in appropriate treatment settings.

Importantly, major clinical trials have demonstrated reductions in cardiovascular events in selected high-risk populations.

In the FOURIER trial, researchers studied more than 27,000 patients with established cardiovascular disease who were receiving statin therapy.

Over a median follow-up of approximately 2.2 years, the primary composite cardiovascular event rate was 11.3% in the placebo group, compared with 9.8% in the evolocumab group.

That represents an absolute reduction of 1.5 percentage points, or approximately 15 fewer composite events per 1,000 patients over the study period (Sabatine et al., 2017).

The relative reduction was approximately 13.3% when calculated from those event percentages; the trial’s time-to-event analysis reported a hazard ratio of 0.85.

These medications do not make plaque disappear overnight.

And they do not replace the need to address blood pressure, smoking, metabolic dysfunction, nutrition, and physical activity.

But they can be valuable tools when cardiovascular risk is high or additional lipid lowering is necessary.

Other treatment options, including bempedoic acid, may also be appropriate in selected patients.

The goal should not be loyalty to a particular medication. The goal should be reducing cardiovascular events using interventions supported by evidence.

Cholesterol, the Gut Microbiome, and Emerging Research

The digestive system also participates in cholesterol metabolism.

Bile acids are produced from cholesterol in the liver and released into the intestine to help digest fats.

Much of this bile acid pool is normally reabsorbed and recycled.

The gut microbiome—the collection of microorganisms living in the digestive tract—can modify bile acids and produce metabolites that influence host metabolism.

Researchers are investigating how these interactions affect lipid regulation, inflammation, insulin sensitivity, and cardiovascular health.

But this remains an evolving field.

We should not claim that changing the microbiome alone reverses coronary plaque or prevents heart attacks.

What we can say is that dietary patterns rich in fiber-containing plant foods support several aspects of metabolic health and can influence cholesterol metabolism.

Soluble fibers, including psyllium and certain fibers found in oats, barley, beans, and other foods, can help reduce LDL-C.

These are practical nutritional strategies with measurable effects.

And they fit naturally into a food-as-medicine approach.

Food as Medicine: What Nutrition Can Contribute

Nutrition deserves a central role in cardiovascular prevention.

But we should be careful not to confuse dietary cholesterol with saturated fat, or individual nutrients with entire foods.

Dietary cholesterol generally has a smaller effect on blood LDL-C than many people assume, although individual responses vary.

Saturated fatty acids can raise LDL-C and ApoB in many individuals, especially when they replace unsaturated fats in the diet.

The effect also depends on the food source and the overall dietary pattern.

For example, foods containing saturated fat may differ substantially in their nutrient composition, processing, and food matrix.

This is why nutritional science must consider whole foods and dietary patterns rather than only isolated nutrients.

Research on the Portfolio dietary pattern is also relevant.

This approach emphasizes several cholesterol-lowering food components, including soluble fiber, plant proteins, nuts, and plant sterols.

In a controlled dietary trial, Jenkins and colleagues (2003) found that a dietary portfolio substantially lowered LDL-C over a short intervention period, with reductions comparable to those observed in the study’s low-dose lovastatin group.

That finding is interesting.

But we must distinguish a reduction in LDL-C from proof of equivalent protection against heart attacks and strokes.

The trial evaluated a cholesterol-related biomarker, not long-term cardiovascular outcomes.

Nevertheless, the findings reinforce the potential of nutrition to improve cardiovascular risk factors.

For me, this is where food as medicine belongs.

Not in promises that a particular food can dissolve plaque.

But in the consistent use of nutritional strategies that support metabolic health, blood pressure, vascular function, and healthier lipoprotein concentrations.

Can You Naturally Reduce Plaque in Your Arteries?

Here’s a question I believe deserves far more attention in cardiovascular education.

If plaque has already developed inside your arteries, can changes in nutrition and lifestyle actually reduce it?

For years, many people have been led to believe that once plaque develops, the damage is permanent.

But research suggests the story is more encouraging—and more complicated.

In some circumstances, intensive lifestyle changes have been associated with measurable improvements in atherosclerosis, including reductions in certain plaque measurements.

However, we need to understand what the research actually demonstrates.

First, Understand the Difference Between Plaque Regression and Plaque Stabilization

There are three important outcomes when discussing existing arterial plaque.

1. Slowing plaque progression

This means reducing the rate at which additional plaque develops.

2. Stabilizing existing plaque

This means changing plaque characteristics in ways that may make it less likely to rupture and trigger a blood clot.

3. Plaque regression

This means an actual reduction in plaque burden or a measurable improvement in the narrowing of an artery.

These outcomes are related, but they are not identical.

And here’s something especially important.

A person does not necessarily need to eliminate existing plaque to substantially reduce cardiovascular risk.

Preventing plaque rupture and the formation of a dangerous blood clot is one of the most important goals of cardiovascular prevention.

What Did Dr. Dean Ornish Discover?

One of the most frequently discussed studies on lifestyle interventions and coronary plaque was conducted by physician and researcher Dr. Dean Ornish.

In the Lifestyle Heart Trial, published in The Lancet in 1990, researchers investigated whether comprehensive lifestyle changes could influence existing coronary artery disease.

Participants in the intervention group followed an intensive program that included a very-low-fat vegetarian diet, regular physical activity, stress management, smoking cessation, and social support.

After one year, researchers observed something remarkable.

The average narrowing of the coronary arteries, measured as percentage diameter stenosis, decreased from approximately 40.0% to 37.8% in the intervention group.

Meanwhile, the control group’s average narrowing increased from approximately 42.7% to 46.1%.

In other words, the intervention group experienced a modest average improvement in arterial narrowing, while the control group experienced progression.

The five-year follow-up, published in JAMA in 1998, provided additional findings.

Among participants with follow-up angiography, average coronary stenosis decreased by approximately 3.1 percentage points from baseline in the intensive lifestyle group.

In the control group, it increased by approximately 11.8 percentage points.

These findings demonstrated that measurable improvement in coronary artery narrowing was possible in some patients through comprehensive lifestyle changes.

However, the study was relatively small, and the intervention involved several lifestyle changes simultaneously.

It does not establish that any single food, supplement, or dietary component can reverse coronary plaque.

Nor does it mean that every person with advanced coronary disease can achieve similar results.

But it challenges the idea that existing atherosclerosis must always progress.

What Does More Recent Research Show?

A 2021 randomized study published in JACC: Cardiovascular Imaging provides another important piece of evidence.

Researchers enrolled 92 individuals with nonobstructive coronary artery disease.

Participants received optimal medical therapy, but one group also received structured dietary counseling based on the Dietary Approaches to Stop Hypertension (DASH) eating pattern, along with encouragement to increase physical activity.

After approximately 67 weeks, researchers used coronary computed tomography angiography to examine changes in plaque.

The intensive lifestyle group experienced a larger reduction in noncalcified plaque volume than the group receiving medical therapy alone.

The average reductions were approximately:

• • 51.3 cubic millimeters in the lifestyle intervention group.
  • 21.3 cubic millimeters in the medical-treatment-only group.

The between-group difference was statistically significant.

However, total percentage plaque volume did not differ significantly between the groups.

This distinction matters.

The study supports the possibility that structured lifestyle intervention, when added to medical treatment, can favorably influence certain coronary plaque components.

It does not prove that lifestyle intervention alone produces the same results or that these imaging changes necessarily translate into fewer heart attacks.

The Mediterranean Diet: Evidence Beyond Cholesterol Numbers

Another important study is the CORDIOPREV randomized clinical trial.

Published in The Lancet in 2022, this study followed 1,002 adults with established coronary heart disease who were assigned to either a Mediterranean dietary pattern or a low-fat dietary pattern.

The Mediterranean approach emphasized foods such as vegetables, fruits, legumes, nuts, whole grains, and extra-virgin olive oil.

During approximately seven years of follow-up, the primary cardiovascular outcome occurred in:

• • 17.3% of participants assigned to the Mediterranean diet.
  • 22.2% of participants assigned to the low-fat diet.

That represents an absolute difference of approximately 4.9 percentage points over the study period.

Importantly, both groups received dietary intervention. This was not a comparison between a healthy diet and no dietary guidance.

The results suggest that the composition of a healthy eating pattern can matter for people who already have coronary artery disease.

A separate CORDIOPREV analysis published in Stroke in 2021 also found favorable changes in carotid artery measurements, including carotid plaque height, among participants assigned to the Mediterranean diet.

Carotid arteries supply blood to the brain, so these findings do not directly establish regression of coronary plaque.

Nevertheless, they add to the evidence that dietary patterns can influence the progression of atherosclerosis.

What Can You Do Through Food and Lifestyle?

This is where I believe the concept of food as medicine becomes especially important.

We cannot promise that changing your diet will dissolve existing plaque.

But there are several modifiable factors that influence the biological environment in which atherosclerosis develops.

1. Improve Insulin Sensitivity and Metabolic Health

Insulin resistance is associated with several cardiovascular risk factors, including elevated triglycerides, high blood pressure, abnormal lipoprotein metabolism, and metabolic dysfunction.

Improving metabolic health through food choices, physical activity, and appropriate weight management can help address these factors.

For someone with insulin resistance, I would pay particular attention to fasting glucose, hemoglobin A1c, triglycerides, high-density lipoprotein cholesterol (HDL-C), and, when appropriate, fasting insulin.

However, improving insulin sensitivity does not automatically demonstrate that existing coronary plaque has regressed.

2. Increase Dietary Fiber, Especially Soluble Fiber

Foods such as oats, barley, beans, lentils, fruits, and certain vegetables provide dietary fiber that supports digestive and metabolic health.

Soluble fiber can help lower low-density lipoprotein cholesterol (LDL-C), partly by influencing bile acid handling and cholesterol metabolism.

Fiber-rich foods also support beneficial activities of the gut microbiome.

This makes dietary fiber relevant to cardiovascular prevention, even though consuming more fiber has not been proven to directly remove existing coronary plaque.

3. Choose Fats That Support Cardiovascular Health

The type of fat consumed matters.

Replacing some saturated fats with unsaturated fats from foods such as olive oil, nuts, seeds, and fish can improve blood lipid profiles and support cardiovascular health.

EPA and DHA are also relevant to cell membrane structure, cellular signaling, and pathways involved in vascular function.

However, improving the Omega-3 Index or omega-6-to-omega-3 ratio does not, by itself, establish that coronary plaque is shrinking.

This is why I believe fatty acid testing can be useful for understanding nutritional status, but it should not be confused with coronary plaque imaging.

4. Make Physical Activity a Consistent Part of Life

Regular physical activity improves cardiovascular fitness, insulin sensitivity, blood pressure regulation, and several aspects of endothelial function.

It also supports skeletal muscle, which plays an important role in glucose disposal and metabolic health.

For many people, walking, resistance training, and other sustainable forms of movement are valuable components of prevention.

However, someone with known coronary disease and exertional chest, arm, jaw, or shoulder discomfort should receive medical evaluation before beginning or intensifying an exercise program.

5. Address Smoking, Blood Pressure, Sleep, and Stress

Smoking cessation, blood pressure management, adequate sleep, and stress management all contribute to a healthier cardiovascular environment.

These factors matter because atherosclerosis is influenced by more than cholesterol concentration alone.

It develops through interactions among circulating lipoproteins, the artery wall, inflammatory processes, and other biological influences.

What About Reducing ApoB and Lipoprotein(a)?

We also need to address something fundamental.

Atherosclerotic plaque develops in part because apolipoprotein B (ApoB)-containing particles enter and become retained within artery walls.

Reducing long-term exposure to these particles is an established strategy for reducing cardiovascular events.

Dietary changes can lower ApoB in many individuals, although the magnitude of improvement varies.

Lipoprotein(a), or Lp(a), is largely genetically determined and generally changes much less in response to lifestyle interventions.

Therefore, a person can improve their diet, insulin sensitivity, and fatty acid profile while still having substantial cardiovascular risk associated with elevated ApoB or Lp(a).

This is why I do not believe we should treat any one biomarker as the entire cardiovascular story.

Food as medicine and appropriate medical treatment are complementary tools—not competing philosophies.

For someone with extensive coronary plaque, dietary changes should not be used as a reason to delay indicated treatment.

Can Your Coronary Calcium Score Actually Go Down?

This is another area where people can become confused.

A coronary artery calcium (CAC) scan measures calcified plaque.

But calcified plaque is only one component of atherosclerosis.

Some treatments that reduce cardiovascular risk may increase the density or amount of calcification within existing plaque, even as other plaque characteristics improve.

Therefore, a rising CAC score does not always mean that treatment is failing.

Likewise, a lower cholesterol result does not prove that plaque has disappeared.

If the goal is to evaluate plaque composition or changes in plaque volume, other imaging techniques may provide different information, although repeat imaging is not routinely appropriate for everyone.

The 2026 American College of Cardiology/American Heart Association dyslipidemia guideline notes that repeat CAC testing is generally not indicated after lipid-lowering treatment has begun, partly because calcification may increase despite beneficial treatment effects.

This is especially important for someone with a very high CAC score.

The objective is not simply to make a calcium score smaller.

The objective is to prevent a heart attack, stroke, or premature cardiovascular death.

My Position: Prevention Should Begin Before the Heart Attack

When someone discovers they have coronary plaque, I don’t want them to feel that nothing can be done.

But I also don’t want them believing that a supplement, detox, or short-term dietary program can erase decades of atherosclerosis.

The evidence supports a more responsible and encouraging message.

Comprehensive lifestyle interventions can improve cardiovascular risk factors.

Some studies have demonstrated measurable improvements in arterial narrowing or plaque-related measurements.

And randomized dietary trials have shown that healthy eating patterns can reduce cardiovascular events in people with established heart disease.

But outcomes vary, and intensive lifestyle intervention is not a substitute for appropriate medical care when cardiovascular risk is high.

My approach is to address the whole person.

That means understanding existing plaque burden, ApoB, Lp(a), blood pressure, metabolic health, endothelial function, physical activity, and nutritional status—including EPA and DHA when appropriate.

It also means recognizing that a favorable nutritional biomarker does not guarantee that coronary arteries are free of disease.

The most important question isn’t simply, “Can I make the plaque disappear?”

It’s, “What can I do today to reduce the likelihood that existing plaque will cause a heart attack or stroke tomorrow?”

That is where food as medicine, lifestyle intervention, informed medical decisions, and evidence-based prevention come together.

Omega-3 Fatty Acids: What Cardiovascular Outcome Trials Actually Show—and What They May Be Missing

Earlier, we explored how eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can become incorporated into cell membranes and influence endothelial biology.

Now we need to address an equally important question.

Does taking omega-3 fatty acids actually prevent heart attacks and strokes?

The answer depends on the formulation, dose, population, and outcome being measured.

And the results from major randomized clinical trials have not all been the same.

But before examining those results, I want to raise another question that deserves serious scientific attention.

Were researchers measuring everything necessary to understand how omega-3 fatty acids influence cardiovascular health?

In particular, were they evaluating the quality and oxidation status of the oils, participants’ omega-6 to omega-3 fatty acid ratios, their Omega-3 Index, and their individual EPA and DHA levels—not just at baseline, but throughout treatment?

These distinctions matter because swallowing an omega-3 capsule is not the same as demonstrating that a person’s cellular fatty acid balance has improved.

REDUCE-IT: A Prescription EPA Formulation Demonstrated Benefit

The REDUCE-IT trial investigated a prescription formulation of purified EPA called icosapent ethyl.

The study included 8,179 patients who were already receiving statin therapy and had elevated triglycerides along with established cardiovascular disease or other qualifying risk factors.

Participants received either 4 grams per day of icosapent ethyl or a mineral-oil comparator.

Over a median follow-up of 4.9 years, the primary composite cardiovascular event rate was 22.0% in the comparator group, compared with 17.2% in the icosapent ethyl group.

That represents an absolute risk reduction of 4.8 percentage points, or approximately 48 fewer patients experiencing a first composite cardiovascular event per 1,000 treated over the study period.

The trial reported a hazard ratio of 0.75, corresponding to a 25% lower hazard of the primary composite outcome (Bhatt et al., 2019).

These are clinically meaningful results in the population studied.

Researchers also measured EPA concentrations. Reported median EPA levels increased substantially in the treatment group, from approximately 26 micrograms per milliliter at baseline to 144 micrograms per milliliter after one year.

That finding demonstrates that the intervention increased circulating EPA exposure.

However, increased circulating EPA does not, by itself, tell us everything about the participant’s broader fatty acid balance or cell membrane composition.

The published primary trial did not establish whether cardiovascular benefits differed according to a comprehensive baseline omega-6 to omega-3 ratio or a predefined red blood cell Omega-3 Index target.

Another question concerns the mineral-oil comparator. Subsequent analyses found increases in several inflammatory and atherosclerosis-related biomarkers in the comparator group, generating debate about whether the comparator influenced the observed treatment difference.

That debate does not erase REDUCE-IT’s findings, but it is relevant when interpreting why the results differed from other trials.

Importantly, REDUCE-IT studied a prescription EPA medication, not an ordinary over-the-counter fish oil supplement.

STRENGTH: A Different Omega-3 Formulation Did Not Reduce Events

The STRENGTH trial investigated a different high-dose omega-3 formulation containing both EPA and DHA.

It included 13,078 patients at high cardiovascular risk who were receiving statins.

Participants received 4 grams daily of an omega-3 carboxylic acid formulation or a corn-oil comparator.

The trial did not demonstrate a statistically significant reduction in its primary composite cardiovascular outcome.

The event rate was approximately 12.0% in the omega-3 group, compared with 12.2% in the comparator group, over a median follow-up of approximately 3.5 years (Nicholls et al., 2020).

The absolute difference was approximately 0.2 percentage points, or about 2 fewer events per 1,000 participants. This small difference was not statistically significant and should not be interpreted as an established protective effect.

But here’s something especially important.

STRENGTH did measure EPA and DHA levels in both plasma and red blood cells at baseline and after 12 months.

In a subsequent analysis involving 10,382 participants with available measurements, researchers examined whether achieving higher EPA or DHA concentrations was associated with fewer cardiovascular events.

They found no significant cardiovascular benefit associated with the highest achieved concentrations.

That is an important result that deserves to be acknowledged.

It also means we should not assume that raising EPA and DHA levels automatically guarantees fewer heart attacks or strokes.

However, the trial’s primary published conclusions were not organized around whether participants achieved a specified omega-6 to omega-3 ratio or red blood cell Omega-3 Index target.

This raises a legitimate question for future research:

Would cardiovascular outcomes differ if participants were evaluated according to their complete fatty acid profile, baseline imbalance, and changes in membrane fatty acid composition—not simply the assigned omega-3 dose?

We do not yet have enough evidence to answer that question definitively.

The Overlooked Question: Was the Omega-3 Oil Fresh or Oxidized?

Omega-3 fatty acids are polyunsaturated fats, which makes them susceptible to oxidation when exposed to oxygen, heat, light, and other conditions.

As oils oxidize, they can develop primary and secondary oxidation products.

This process is commonly described as rancidity.

Researchers can evaluate oxidation using measurements such as:

✅ Peroxide value (PV): A measure of primary oxidation products.

✅ Para-anisidine value (p-AV): A measure of certain secondary oxidation products.

✅ Total oxidation value (TOTOX): A combined indicator of primary and secondary oxidation.

Independent investigations have found that some commercially available omega-3 supplements exceed recommended voluntary oxidation limits.

That is not a trivial quality-control concern.

A 2017 randomized study also compared high-quality and deliberately oxidized fish oil and found differences in certain lipoprotein-related outcomes, demonstrating that oil quality can influence biological responses.

But we need to be careful not to overstate what this proves.

These findings do not establish that oxidized omega-3 products cause heart attacks, nor do they prove that oxidation explains why STRENGTH failed to demonstrate cardiovascular benefit.

Furthermore, REDUCE-IT and STRENGTH used pharmaceutical formulations rather than typical retail supplements. We should not assume those products had the same oxidation problems identified in some consumer supplements.

What we can reasonably ask is whether future omega-3 outcome trials should more consistently report independent measurements of product oxidation, stability, storage conditions, and quality throughout the study.

If we’re investigating the cardiovascular effects of fatty acids, shouldn’t we also know the condition of the fatty acids being administered?

Why Baseline Omega-3 Status and Fatty Acid Balance Matter

Here’s where I believe the scientific conversation needs to expand.

Imagine enrolling two people in an omega-3 trial.

One person begins with a very low Omega-3 Index and a substantially elevated omega-6 to omega-3 ratio.

The other begins with a considerably higher Omega-3 Index and a more balanced fatty acid profile.

Both receive the same omega-3 dose.

But are we certain they will experience the same biological response?

Not necessarily.

Their baseline fatty acid status, diet, absorption, metabolism, and changes in red blood cell fatty acid composition could differ.

This is why I believe future research should more consistently evaluate:

✅ Omega-6 to omega-3 ratio: What was the participant’s starting balance, and how did it change?

✅ Omega-3 Index: What percentage of red blood cell fatty acids consisted of EPA and DHA at baseline and throughout treatment?

✅ Individual EPA and DHA levels: How much of each fatty acid was present, and how did each respond to supplementation?

✅ Arachidonic acid (AA) and EPA balance: Did the relationship between these fatty acids change?

✅ Supplement oxidation and stability: Was the intervention product independently evaluated for oxidation throughout the study?

✅ Clinical outcomes: Were changes in these measurements associated with actual reductions in cardiovascular events?

These questions are especially relevant to understanding how omega-3 fatty acids interact with cell membranes and cardiovascular physiology.

However, we must distinguish between a promising biomarker and a clinically validated treatment target.

Although the Omega-3 Index and omega-6 to omega-3 ratio can provide information about fatty acid status, randomized outcome trials have not yet established that treating everyone to a particular target—such as an Omega-3 Index of 8–12% or an omega-6 to omega-3 ratio of 3:1 or lower—will necessarily prevent heart attacks or strokes.

Those targets warrant investigation, but they should not be presented as proven cardiovascular outcome thresholds.

What REDUCE-IT and STRENGTH Actually Teach Us

REDUCE-IT demonstrated that a specific prescription EPA formulation reduced major cardiovascular events in a selected high-risk population already receiving statins.

STRENGTH demonstrated that a different formulation containing EPA and DHA did not significantly reduce cardiovascular events in its study population, even though EPA and DHA concentrations increased.

Both findings matter.

Together, they tell us that omega-3 cardiovascular benefits cannot be assumed to be identical across formulations, doses, populations, and clinical circumstances.

They also raise important questions about the role of fatty acid status, cellular incorporation, product quality, and other biological factors.

For me, the next generation of omega-3 research should move beyond asking only:

“How many grams of omega-3 did participants take?”

We should also ask:

“What was their fatty acid status before treatment, how did their cellular fatty acid profile change, what was the quality of the oil, and did those changes translate into better cardiovascular outcomes?”

That is the kind of research that could help us better understand the relationship between omega-3 fatty acids, cell membrane biology, and cardiovascular disease prevention.

A Safety Issue That Deserves Attention: Atrial Fibrillation

When discussing omega-3 fatty acids and cardiovascular health, we also need to address a potential safety concern associated with higher-dose formulations.

Atrial fibrillation (AF) is a heart rhythm disorder in which the upper chambers of the heart beat irregularly.

AF can increase the risk of stroke because irregular blood flow within the heart can contribute to blood clot formation.

Several randomized clinical trials have reported an increased incidence of atrial fibrillation among participants receiving high-dose omega-3 formulations.

REDUCE-IT: Increased Atrial Fibrillation Hospitalizations

In REDUCE-IT, hospitalization for atrial fibrillation or atrial flutter occurred in:

✅ 3.1% of participants receiving 4 grams daily of icosapent ethyl.

✅ 2.1% of participants receiving the comparator.

That represents an absolute increase of 1.0 percentage point, or approximately 10 additional hospitalizations per 1,000 participants over a median follow-up of 4.9 years.

STRENGTH: Increased Atrial Fibrillation Events

In STRENGTH, atrial fibrillation occurred in approximately:

✅ 2.2% of participants receiving the high-dose EPA and DHA formulation.

✅ 1.3% of participants receiving the comparator.

That represents an absolute increase of approximately 0.9 percentage points, or 9 additional cases per 1,000 participants over approximately 3.5 years.

These findings deserve attention.

However, they do not mean that everyone who takes omega-3 fatty acids will develop atrial fibrillation.

Nor do they establish that consuming omega-3-rich foods or taking lower supplemental doses produces the same risk observed with these prescription-strength formulations.

The concern is particularly relevant at higher doses, especially in people with a history of atrial fibrillation or other heart rhythm disorders.

An Important Question: Does Baseline Fatty Acid Status Matter?

This brings us back to a question raised earlier.

Were the participants who experienced atrial fibrillation already deficient in EPA or DHA?

Did they have an elevated omega-6 to omega-3 ratio?

What was their Omega-3 Index before treatment?

And did their risk of atrial fibrillation differ according to how much their fatty acid status changed during the trial?

These are scientifically relevant questions.

The trials provide evidence that certain high-dose omega-3 formulations can increase atrial fibrillation risk, but they do not establish whether correcting a documented omega-3 deficiency or achieving a particular fatty acid balance would prevent that risk.

We should not assume that improving an omega-3 biomarker eliminates the possibility of an adverse effect.

The cardiovascular benefits and potential risks of higher-dose omega-3 treatment must be considered together.

What About the Omega-6 to Omega-3 Ratio?

This is where I believe cardiovascular nutrition research deserves a more comprehensive discussion.

Omega-6 and omega-3 fatty acids are essential components of human biology.

The omega-6 family includes linoleic acid (LA) and arachidonic acid (AA).

The omega-3 family includes eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA).

These fatty acids contribute to cell membrane structure and function.

They also participate in cellular signaling and serve as precursors for molecules involved in inflammation, its resolution, and other physiological processes.

But here’s what I want readers to understand.

The amount of omega-3 someone consumes is not necessarily the same as the amount incorporated into their cell membranes.

Two individuals could take the same omega-3 supplement, at the same dose, for the same period and experience different changes in their fatty acid profiles.

Their baseline status, diet, metabolism, absorption, and individual biological responses may differ.

That is one reason I believe measuring fatty acid status deserves more attention.

Why the Omega-6 to Omega-3 Ratio Interests Me

A high omega-6 to omega-3 ratio may indicate a relative imbalance in fatty acid intake or tissue composition.

Researchers continue to investigate how these patterns relate to inflammation, cardiovascular health, and other chronic conditions.

However, omega-6 fatty acids are not inherently harmful.

For example, linoleic acid is an essential fatty acid, and replacing saturated fat with polyunsaturated fat, including linoleic acid, has been associated with cardiovascular benefits in clinical research.

The objective should not be to eliminate omega-6 fatty acids.

The objective is to better understand the individual’s fatty acid status and whether changes in that status translate into improved health outcomes.

It is also important to recognize that the omega-6 to omega-3 ratio can differ depending on whether it is measured in whole blood, plasma, or red blood cells. The testing method must be considered when interpreting results.

The Omega-3 Index: Another Piece of the Puzzle

The Omega-3 Index measures EPA and DHA as a percentage of total fatty acids in red blood cell membranes.

Unlike simply asking whether someone takes fish oil, this measurement provides information about the fatty acids actually present in their red blood cells.

That distinction is meaningful.

For example, someone might report taking an omega-3 supplement every day while still having a relatively low Omega-3 Index.

Conversely, someone who regularly consumes omega-3-rich seafood might have a higher index without taking a supplement.

This is why I believe testing can provide information that supplement labels and self-reported intake cannot.

An Omega-3 Index of approximately 8% or higher has been proposed as a favorable cardiovascular biomarker target, while an omega-6 to omega-3 ratio of 3:1 or lower is sometimes used as a nutritional balance goal.

However, neither target has been established through randomized cardiovascular outcome trials as a universally validated threshold that guarantees protection against heart attacks, strokes, or atrial fibrillation.

These are promising areas for additional research—not guarantees of disease prevention.

Three Things We Must Never Confuse

When interpreting omega-3 research, we need to distinguish between three different levels of evidence.

✅ 1. Measuring a biological marker. Establishing someone’s omega-6 to omega-3 ratio, Omega-3 Index, and individual EPA and DHA levels.

✅ 2. Improving that marker. Demonstrating that dietary changes or supplementation produce measurable improvements in fatty acid status.

✅ 3. Demonstrating better clinical outcomes. Showing through appropriate clinical research that those improvements reduce heart attacks, strokes, cardiovascular deaths, or other meaningful health outcomes.

These are not the same thing.

A person can improve a laboratory measurement without necessarily experiencing a proven reduction in cardiovascular events.

At the same time, a clinical trial that fails to reduce cardiovascular events does not automatically mean the intervention had no biological effects.

Both distinctions matter.

Where I Believe Omega-3 Research Should Go Next

I would like to see more cardiovascular outcome trials that incorporate comprehensive fatty acid testing and carefully documented product quality.

Specifically, researchers should examine whether baseline fatty acid status and changes during treatment help explain differences in both benefits and adverse effects.

That includes investigating whether the risk of atrial fibrillation differs according to achieved EPA and DHA concentrations, Omega-3 Index, or other fatty acid measurements.

The goal is not to assume that correcting an imbalance will prevent every cardiovascular problem.

The goal is to determine whether more personalized nutritional assessment can improve how we evaluate omega-3 interventions.

Because ultimately, cardiovascular prevention is not about achieving a particular laboratory number.

It’s about preventing heart attacks, strokes, disability, and premature death.

Can Supplements Reverse Coronary Plaque?

This question deserves a careful answer.

Several supplements are frequently promoted for cardiovascular health.

Among them are aged garlic extract, vitamin K2, nattokinase, and various antioxidant formulations.

Some have been studied for effects on blood pressure, lipids, vascular measurements, or imaging markers.

For example, small studies have investigated aged garlic extract and changes in coronary plaque characteristics.

But preliminary imaging findings do not establish that a supplement prevents heart attacks or reverses advanced coronary disease.

Vitamin K2 participates in biological processes involving calcium regulation, but evidence does not establish that supplementation removes calcium already deposited in coronary arteries.

Nattokinase has been promoted for its effects on blood clotting and fibrinolysis, but robust clinical evidence showing that it prevents heart attacks or safely treats coronary plaque is lacking.

It may also create bleeding concerns, especially when combined with antiplatelet or anticoagulant medications.

For someone with extensive coronary atherosclerosis, supplements should never be presented as substitutes for appropriate cardiovascular care.

I support examining nutritional deficiencies, improving dietary quality, and evaluating supplements when there is a sound reason to use them.

But I also believe we must resist the temptation to promise outcomes that clinical trials have not demonstrated.

A supplement that improves a laboratory value is not automatically a supplement that saves lives.

What Should a Comprehensive Cardiovascular Assessment Include?

If we truly want to reduce heart attacks and strokes, we need to look beyond total cholesterol.

The appropriate evaluation will vary from person to person, but several categories deserve consideration.

Lipoprotein-Related Risk

LDL-C, non-HDL cholesterol, ApoB, and Lp(a) can help clarify exposure to atherogenic particles and inherited risk.

ApoB may be especially useful when LDL-C and metabolic risk markers appear discordant.

Lp(a) should generally be measured at least once during adulthood.

Metabolic Health

Fasting glucose, HbA1c, triglycerides, HDL cholesterol, blood pressure, waist circumference, and other relevant measurements help identify metabolic dysfunction.

Fasting insulin or LP-IR may offer additional information in selected cases, although neither replaces established cardiovascular risk assessment.

Existing Atherosclerosis

Coronary artery calcium testing can be valuable in appropriately selected adults when the results are likely to influence preventive decisions.

People with symptoms or known cardiovascular disease may require different diagnostic approaches.

Nutritional and Cellular Health

Dietary quality, essential fatty acid intake, and nutritional status may also deserve consideration.

Omega-3 fatty acid testing can provide information about longer-term EPA and DHA status, although it does not replace cardiovascular imaging or established risk markers.

Other Major Risk Factors

Smoking history, family history of premature cardiovascular disease, kidney function, age, physical activity, sleep, and certain chronic inflammatory conditions all deserve consideration.

Some individuals may benefit from additional evaluation of vascular function or inflammatory markers.

But no single test should be portrayed as a universal solution.

The goal is to assemble a clearer picture of the person’s actual cardiovascular risk.

What About People Who Already Have Extensive Plaque?

This is where prevention becomes especially urgent.

Someone with a CAC score above 1,000 is not in the same situation as someone with no known coronary plaque.

The presence of extensive calcified atherosclerosis indicates a substantial burden of established disease.

In these cases, I believe it is particularly important to avoid false reassurance from favorable results in other areas.

A person might improve glucose control, lower triglycerides, lose excess body fat, and increase physical activity.

Those improvements are valuable.

But they do not erase existing coronary plaque or eliminate the need to address ApoB-related risk.

A comprehensive plan may involve:

• • Prompt cardiovascular evaluation and appropriate follow-up
  • Evidence-based lowering of atherogenic lipoproteins
  • Blood pressure management
  • Evaluation and treatment of diabetes or insulin resistance
  • Smoking cessation when applicable
  • Sustainable improvements in nutrition and physical activity
  • Review of medications, supplements, and possible interactions
  • Individualized decisions about antiplatelet treatment and other therapies

Not everyone with a high CAC score needs aspirin, anticoagulation, or invasive coronary procedures.

Those decisions depend on clinical circumstances, including symptoms, bleeding risk, cardiac history, and the presence of other conditions.

An anticoagulant, for example, is not routinely prescribed merely because someone has a high CAC score.

But a person with certain documented heart rhythm disorders may have an entirely separate reason to undergo stroke-risk assessment.

This is why individualized care matters.

The presence of extensive plaque should lead to a more comprehensive prevention strategy—not to the assumption that a single supplement, diet, or laboratory target can solve the problem.

Are We Measuring the Right Things?

After examining cholesterol biology, insulin resistance, ApoB, Lp(a), coronary calcium, cell membrane health, and medication outcomes, I return to the question that inspired this article.

Are we measuring the right things?

My answer is that we’re measuring some of the right things, but too often we’re interpreting them in isolation.

LDL-C matters.

ApoB matters.

Lp(a) matters.

Insulin resistance matters.

Blood pressure matters.

Endothelial health matters.

Cell membrane composition matters to normal cellular function.

Existing plaque burden matters.

And the person’s overall clinical history matters.

None of these measurements should be treated as the entire cardiovascular story.

Consider the individual with normal glucose but genetically high Lp(a).

Or the individual with favorable LDL-C but elevated ApoB.

Or someone with insulin resistance and an unfavorable triglyceride-to-HDL ratio.

Or someone who takes omega-3 supplements but has never measured their omega-3 status.

Or John Doe, whose coronary calcium score of 1,276 revealed extensive existing atherosclerosis.

Each person may need a different combination of evaluation and intervention.

This is precisely why cardiovascular prevention should be personalized.

We need to move away from arguments that insist cholesterol is everything or cholesterol is nothing.

Both positions are too simplistic.

The strongest scientific evidence indicates that ApoB-containing lipoproteins contribute causally to atherosclerosis.

At the same time, metabolic dysfunction, vascular health, inherited risk, and established plaque burden help determine who develops disease and who experiences clinical events.

And nutritional factors, including essential fatty acid status, may influence some of the cellular pathways involved in vascular function.

These mechanisms are not competing explanations.

They are parts of the same larger cardiovascular picture.

My Final Thoughts: Prevent the Heart Attack, Not Just the Laboratory Result

After more than three decades working in nutrition and metabolic health, one lesson continues to shape how I approach chronic disease prevention.

A laboratory number is not the person.

A cholesterol value is not an artery.

A fasting glucose result is not a complete metabolic assessment.

A favorable triglyceride-to-HDL ratio does not guarantee the absence of coronary plaque.

And taking a supplement does not automatically mean that the intended biological outcome has occurred.

I believe food as medicine should play a central role in cardiovascular prevention.

That includes eating patterns that provide adequate protein, dietary fiber, essential fatty acids, vitamins, minerals, and sufficient nourishment to support long-term health.

It includes improving insulin sensitivity, supporting healthier blood pressure, maintaining skeletal muscle, and reducing excess body fat when appropriate.

It also includes understanding the biological importance of the nutrients that become incorporated into our cell membranes.

EPA and DHA are not simply ingredients listed on a supplement label.

They are biologically active fatty acids that can influence membrane composition and cellular signaling.

And because endothelial cells depend on healthy membrane function and complex signaling pathways to regulate nitric oxide production, this is an area of cardiovascular biology that deserves continued research and attention.

The 2024 and 2026 meta-analyses examining omega-3 fatty acids and vascular function provide encouraging evidence.

But they also remind us of the difference between improving a physiological measurement and demonstrating fewer cardiovascular events.

That distinction is essential.

We must also recognize when nutrition alone is not enough.

For some people, particularly those with extensive atherosclerosis or very high inherited risk, medications can provide important additional protection.

Statins have demonstrated benefits in appropriate populations.

Nonstatin therapies have also expanded the options available to patients.

And advanced testing may help clinicians identify risk that conventional measurements overlook.

But we must continue to ask the right questions.

Are we reducing the number of atherogenic particles circulating in the bloodstream?

Are we identifying and addressing metabolic dysfunction?

Are we evaluating inherited risk factors such as Lp(a)?

Are we recognizing existing coronary plaque before it produces a catastrophic event?

Are we considering the health of the endothelial cells that regulate blood vessel function?

Are we assessing nutritional status rather than simply assuming that supplementation is achieving the intended result?

Are we considering both the potential benefits and risks of high-dose supplements, particularly in people with existing cardiovascular disease or heart rhythm disorders?

Are we choosing treatments based on evidence that they reduce heart attacks, strokes, and premature death?

And are we explaining both the potential benefits and the risks in a way patients can genuinely understand?

Those are the questions that should guide cardiovascular prevention.

Because the goal is not simply to achieve a better cholesterol report.

The goal is to protect the arteries, preserve cardiovascular function, and help people live longer, healthier lives without experiencing a preventable heart attack or stroke.

That’s what matters most.

Have Questions? Let’s Connect.

If you have questions about anything I’ve shared in this article, or you’d like to learn more about my nutrition and metabolic health programs and the At-Home Cellular Health Test, I’d welcome the opportunity to connect with you.

The At-Home Cellular Health Test can help you better understand your omega-6 to omega-3 fatty acid balance, Omega-3 Index, and other important markers of cellular fatty acid status.

Email me directly at robert@dietfreelife.com.

Because when it comes to your health, I believe the more informed you are, the better equipped you are to make decisions that support your long-term well-being.

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__________
Robert Ferguson is a California- and Florida-based single father of two daughters, clinical nutritionist, Omega Balancing Coach™, researcher, best-selling author, speaker, podcast and television host, health advisor, NAACP Image Award Nominee, creator of the Diet Free Life methodology, and Chief Nutrition Officer for iCoura Health. He also serves on the Presidential Task Force on Obesity for the National Medical Association and the Health and Product Advisory Board for Zinzino, Inc.

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