The #1 Killer Is Finally Being Attacked At Its Root. The Obvious Investment Angle May Be the Weakest.

This is an educational publication, not investment or medical advice. Full disclosures are at the bottom.

Here is the idea that reorganized how I look at the world's number one killer, and I think it will do the same for you: heart disease is really two problems, not one, and they are at very different stages.

There is the problem of new damage, the cholesterol particles still entering your artery walls, and the problem of old damage, the plaque already lodged there. The first problem, lowering, is where nearly all the money and attention is going. A wave of drugs now targets the causal particles directly, and some lower them dramatically. The second problem, clearing out plaque that has already formed, draws far less funding and has far less clinical progress.

My view, after mapping this field through a scoring framework I'll describe, is that this imbalance is the whole story for an investor. The lowering race is crowded and, as you'll see, dominated by companies so large that even an important success may barely move their stock. The clearing race is early, sparse, and mostly private, which is precisely where asymmetric opportunity tends to hide, and also precisely where the risk of total failure is highest. I'm not going to tell you the second wall is a sure thing. I'm going to show you why it's where I'm actually looking, and why the obvious bets on the first wall may disappoint.

I research longevity biotech for a living, and I track two companies on the second front, the clearing side, with my own money in one of them. I'll mention my personal motivation once and then set it aside: heart disease runs through both sides of my family and I carry higher LDL than I'd like, so this isn't abstract to me. That's the why. What follows is the work, including a fresh re-review of those two against the same standard as any new name.

First, one piece of genuinely useful information, because most people reading this, however successful and well-insured, have probably never had it measured.

The cholesterol panel you get at a physical reports LDL, the "bad" cholesterol. The prevention-focused physicians, Peter Attia prominent among them, argue that LDL is an estimate and that a particle count called ApoB more directly reflects how many atherogenic particles you carry. The 2026 ACC/AHA dyslipidemia guidelines treat ApoB as a useful selective confirmatory test in certain higher-risk patients, worth knowing about and asking your doctor whether it applies to you.

The more striking one is lipoprotein(a), said "L-P-little-a." Here are the verifiable facts, and they're remarkable on their own without any embellishment. It is a genetically determined, independent risk factor for heart attack, stroke, and aortic valve disease. Diet and exercise do not meaningfully change it, and statins do not lower it. Roughly one in five people, about 20% of the global population, carry it at elevated levels. There is, as of today, no FDA-approved drug that specifically lowers it.

And here is the fact that should genuinely bother you. As of 2026, the American College of Cardiology, the American Heart Association, and the National Lipid Association all now recommend that every adult have Lp(a) measured at least once in their lifetime. Yet a study of US testing trends found that in 2024 only about a quarter of one percent of the population was actually tested. Recommended for everyone. Done for almost no one. That is not a science problem, the test is cheap and you only need it once. It's a gap between what the guidelines say and what actually happens at a routine visit, and it means a great many people, including wealthy, health-conscious, well-doctored people, are walking around having never checked a risk factor their own cardiology guidelines say they should.

So here is the free, practical takeaway before any ticker below: ask your physician whether you should have your Lp(a) measured, given that current guidelines recommend it once for every adult, and whether ApoB testing applies to your situation. That's not medical advice, it's a prompt to have a more complete conversation than a standard physical usually produces. If you stop reading here, you've gotten the most useful thing in this letter.

But understanding the problem only sharpened the question that is actually my job: if a risk factor this common still has no approved treatment, who is racing to build one, and is any of it investable? I expected an obvious winner. What I found is why the obvious bet is usually the wrong one, which brings us back to the two walls, and to the names.

Below the line: the companies I ruled out and why, the public names I'm watching, the private ones I've scored, the catalysts that matter, and the specific triggers that would move me from wait to act. That map, kept current, is what a membership is.