Does Putting Out Inflammation Stop Heart Attacks?

You'll see a lot of health influencers online claiming inflammation is "the real cause" of cardiovascular disease, and that apoB and LDL aren't really a concern if there's no inflammation present. The ZEUS trial results just came out, and they're a good example of why we should push back on that narrative.

The ZEUS Trial

Over 6,300 people with atherosclerotic disease, chronic kidney disease, and elevated inflammation were randomized to an IL-6 inhibitor or placebo. IL-6 is a signaling protein your immune system releases to help drive and coordinate inflammation. The drug did exactly what it was designed to do biologically, IL-6 and hsCRP both dropped as expected. But that didn't reduce cardiovascular events. The hazard ratio was 0.99. Completely neutral.

If inflammation were truly "the real cause" of atherosclerosis, or the upstream driver of these events, you'd expect turning it down to change outcomes, but it didn't.

The Alarm and the Burglar

IL-6 inhibition suppresses a downstream response to a problem. It doesn't effect what's generating that response in the first place, which in the arteries of this population is, at least partially, the apoB-containing particles getting into and retained in the artery wall, which then incites a whole cascade that includes inflammation.

So you can quiet the alarm. But if the burglar setting it off is still in the house, there's still a problem.

I think this is where a lot of the online debate goes sideways. Some people see that suppressing an inflammatory marker doesn't fix outcomes, and they treat that as proof inflammation was never important. But that's not really what a negative trial like this tells you. It tells you that suppressing one signal, later in the disease process, in people who already have established plaque, wasn't enough on its own. That's a narrower and much less dramatic claim than "inflammation doesn't matter."

This Isn't Just an IL-6 Problem

Here's the part I think gets missed the most though. A lot of drugs, across a lot of areas of medicine, work by suppressing a response rather than removing the cause. That's not a criticism of pharmacology, sometimes that's exactly what's needed. But it's worth being honest about what a given intervention is actually doing.

Even lipid-lowering therapy can fall into this category, depending on why someone's LDL is elevated in the first place. If someone's high LDL is driven by a poor diet and lifestyle pattern, and you put them on a statin without changing any of that, you're lowering the number. You're not addressing whatever upstream process is generating that number, and you're also not addressing whatever else that same upstream process might be doing elsewhere in the body. Is it really surprising, in that light, that some people on statins still have heart attacks? No, and this issue could be one potential contributing factor.

Genetics can create a different situation. With familial hypercholesterolemia, or some of the other mutations that keep LDL elevated even with a genuinely healthy diet and lifestyle, the elevated LDL itself is much closer to being the primary problem. There's no upstream lifestyle driver left to fix. Lowering it pharmacologically in that case is much closer to addressing the actual cause, rather than suppressing a response to something else.

And to be clear, there are also situations serious enough, regardless of the underlying cause, that we need LDL-lowering medications to directly treat plaque that's already there. That's not in conflict with anything I'm saying here. It's just a different job than removing a root cause. To use a different analogy, sometimes your house is already so on fire, and you don't have the luxury of only addressing why the fire started.

Order Matters

This actually connects to something I think about in just about every area of practice, not just cardiovascular disease. Naturopathic medicine principles state there is a therapeutic hierarchy to how interventions should be layered. You start with the least forceful, least invasive things, the foundational support that gives the body a real opportunity to do what it already knows how to do. You move up to more aggressive interventions when they're genuinely needed, but even then, the foundational piece doesn't get abandoned. It gets applied alongside the more aggressive things.

Drugs and procedures, even when they're necessary, aren't usually what does the actual healing. They're creating a better opportunity for the body to do that work, or in more urgent cases, they're managing a problem that's already outpaced what foundational support alone can handle in time. Either way, skipping the foundational piece and going straight to suppression, whether that's an inflammatory marker, an LDL number, or anything else, tends to leave the underlying process untouched, and the healing response potentially less complete.

Where This Leaves Us

I don't read the ZEUS trial as proof that inflammation doesn't matter in atherosclerosis. I read it as a reminder that suppressing a response, whether that's an inflammatory marker or a lipid number, isn't the same thing as addressing what's causing it. Sometimes you still need to do that suppression, plaque doesn't always wait around for lifestyle change to catch up. But it should never be instead of trying to treat the cause. It should be alongside it, or after you've genuinely tried the foundational approach first.

Order tends to matter more than we give it credit for.

In health, Daniel Chong, ND