Why Cholesterol Isn’t the Whole Story

What the New ACC Statement Admits About Heart Disease—and What It Doesn’t Say

In 2025, the American College of Cardiology (ACC) released a major Scientific Statement on Inflammation and Cardiovascular Disease.

It’s one of the most important updates in years—because for the first time, the ACC openly acknowledges something long observed in clinical practice:

Chronic inflammation—not LDL cholesterol—is the strongest predictor of heart attacks and cardiovascular disease progression.

This represents a quiet but profound shift in how we understand heart disease.

But the Statement also leaves out some critical upstream biology that deserves public attention.

Let’s break down what the ACC did say… and what remains missing.

1. The ACC now admits inflammation drives cardiovascular disease

For decades, heart disease has been framed as a cholesterol problem: LDL goes up → plaque builds → arteries clog.

But the ACC statement reviews decades of new evidence showing something different:

• Many heart attacks occur even when LDL is normal.

• A large portion occurs in people with no traditional risk factors (“SMuRF-less” heart attacks).

• Inflammation markers (especially hsCRP) predict future events better than LDL.

• Anti-inflammatory therapies reduce heart attacks without lowering cholesterol at all.

This is an astonishing acknowledgment:

LDL is not the main engine—chronic inflammation is.

2. But the ACC doesn’t say the uncomfortable part: our LDL-only focus has been misleading

For years, clinical practice has focused almost entirely on lowering LDL.

This has unquestionably saved lives, and LDL control still matters.

But the new evidence makes something clear:

Managing LDL alone does not fix the root cause of most cardiovascular events.

Yet the healthcare system:

• screens everyone for LDL,

• Rarely screens anyone for inflammation,

• and assumes LDL tells the whole risk story.

This doesn’t match the biology—or the outcomes.

The ACC doesn’t explicitly say this, but the implications are hard to miss.

3. The ACC focuses on “controlling inflammation,” not on why inflammation fails to turn off

This is perhaps the biggest gap in the Statement.

The focus is on downstream anti-inflammatory treatments, such as:

• low-dose colchicine

• IL-1 or IL-6 inhibitors

• statins (for their anti-inflammatory effects)

And while lifestyle is mentioned, it’s framed in broad strokes:

• “Exercise more”

• “Eat healthy”

• “Don’t smoke.”

What’s missing is the biology that controls immune resolution—the body’s natural ability to turn inflammation off.

Inflammation is not supposed to be chronic.

It’s meant to ignite, solve a problem, and then resolve.

Whether that resolution happens depends on something the ACC statement does not address:

Bioenergetic sufficiency — the energy needed to complete recovery

Immune resolution requires:

• adequate mitochondrial function

• sufficient cellular energy

• balanced redox state

• proper fission–fusion dynamics

• healthy metabolic flexibility

Chronic inflammation often persists not because the body “makes too much,” but because the body cannot afford the energy to complete the shutdown process.

This is a central idea of the Exposure-Related Malnutrition (ERM) framework:

When recovery is underfunded, inflammation becomes chronic.

4. What science knows—but the ACC did not discuss—about what drives failed immune resolution

Several upstream factors strongly influence whether inflammation resolves or becomes chronic, yet they receive no attention in the Statement:

Micronutrients required for immune resolution

These are not “supplements”—they are biochemical cofactors:

• Vitamin D → regulates immune tolerance, macrophage phenotype, and anti-inflammatory signaling

• Magnesium → required for activating vitamin D, binding ATP, and controlling inflammasomes

• Omega-3 fatty acids → precursors for specialized pro-resolving mediators (SPMs)

• Zinc, selenium, and B vitamins → crucial for antioxidant defenses, DNA repair, and mitochondrial function

Without these, the “off-switch” for inflammation doesn’t work.

Environmental toxicants that overwhelm energy and immune balance

Low-level exposure to:

• mercury

• lead

• cadmium

• air pollutants

can impair mitochondria, distort immune signaling, and create a persistent low-grade inflammatory state.

These exposures are common, measurable, and modifiable—yet missing from the ACC document.

5. If inflammation drives heart disease, we must ask: why can’t the body turn it off?

This is the question the ACC statement raises—but never answers.

The science points to a clearer picture:

• Inflammation becomes chronic when energy is insufficient.

• Energy becomes insufficient when micronutrient demands exceed supply.

• Resolution fails when mitochondria are stressed, starved, or toxicant-burdened.

• Lifestyle works not by “good behavior,” but by restoring energetic and metabolic capacity.

This is not alternative medicine—it's emerging biology.

And it leads to a new paradigm:

Heart disease is not just a lipid problem. It is an unresolved inflammation problem. And unresolved inflammation is an energy and nutrient availability problem.

6. Why this matters for the public

A cholesterol-only story gives people incomplete advice:

• Many believe their heart health is “fine” because their LDL is normal.

• Others struggle to improve risk because inflammation, not LDL, is driving their disease.

• People are rarely told that micronutrient deficiencies and low-grade toxic exposures can impair immune resolution.

• Clinicians have been trained to monitor LDL routinely—but not hsCRP, vitamin D, omega-3 status, or heavy-metal burden.

The ACC statement is a step forward.

But the next step is understanding how bioenergetic sufficiency, micronutrient status, and environmental exposures shape the immune system’s ability to resolve inflammation.

That is where the future of heart disease prevention lies.

Conclusion: Cholesterol matters — but it is not the master switch

The ACC’s 2025 statement finally acknowledges that inflammation—not LDL—is the central driver of cardiovascular disease.

But to truly prevent heart disease, we must expand the conversation beyond LDL control and beyond inflammation suppression.

We need to understand why inflammation stays on.

It stays on when:

• The body lacks the energy to finish the healing process,

• The resolution pathways lack the nutrients they need,

• Or environmental exposures keep reactivating danger signals.

This is the biology of immune resolution, and it explains the missing link between stress, lifestyle, modern exposures, and chronic disease.

The conversation has finally opened.

Now we must take it upstream.

Mensah, G. A., Ridker, P. M., Brooks, M., Dzau, V. J., Fuster, V., Libby, P., & Taqueti, V. R. (2025). Inflammation and cardiovascular disease: 2025 American College of Cardiology Scientific Statement. Journal of the American College of Cardiology, 85(3), 241–276. https://doi.org/10.1016/j.jacc.2024.11.015