I Crushed My ApoB to 38. Nobody Measured My Small Vessels.

My cardiologist was content. I'm not. That difference is the reason I'm about to let someone thread a wire into my heart, again.

On paper, my case is closed. Eighty percent blockage in the right coronary artery at 44, stented. A year of work since: ApoB, the protein that actually carries cholesterol into the artery wall, driven down to 38, a number most people never see. Blood pressure controlled. Lp(a) checked and ruled out. Systemic inflammation bottomed out at an hsCRP of 0.45. My repeat CT angiogram came back clean, the little bit of leftover plaque in a non-stented vessel maybe even shrinking, still soft, still uncalcified. By every metric that guides a normal post-stent patient, I am a success story.

Except I still get chest tightness. Not dramatic, a 3 or 4 out of 10, but it is there. My heart throws an occasional off-rhythm beat that three different people have called benign but that I feel every time, because I run a 6-lead ECG on myself and I have watched it happen. And nobody has ever given me a straight answer for the thing that actually scared me: why my arteries went bad that fast, that young, when I was doing almost everything right.

I am a scientist, a clinician, and trained as a computational biologist. I spent years in a cancer lab watching how the machinery inside a cell breaks and now I spend all my spare time studying the biology of aging for my PhD program. So when a standard workup says "fine" and the patient on the other end of it says "I'm not fine", my instinct is to not trust that readout. It is to ask what layer the readout might be missing, which angle hasn't been explored, and which bridge is uncrossed. In the coronary arteries, there is a whole layer the standard workup almost never measures. That is where this post lives.

You do not need a stent or a frightening scan for this to be about you. If you are in your forties or fifties, watching your labs, doing the work, and quietly wondering whether the standard numbers really have you covered, this is the exact layer those numbers do not measure. My case is just where it got loud enough to force the question. The biology underneath it belongs to everybody.

The Bottom Line

Most heart testing is built to find one thing: a major artery with a big blockage. That is the plumbing you can see on an angiogram, the dye-and-X-ray movie of the large coronary vessels. But the large arteries are a small fraction of the coronary system. Below them sits a vast network of vessels too small for any angiogram to resolve, and when that network of small vessels stops working properly, you get something called coronary microvascular dysfunction. It is real, it is common, and it can drive symptoms and events while every big-artery picture and standard workup looks just fine.

Here is the part that matters for me, and probably for a fair majority of the people whose cases look handled but that are still dealing with discomfort and ongoing issues: microvascular dysfunction is substantially an inflammation problem. Chronic, low-grade, body-wide inflammation injures the lining of those small vessels. Which is why a skin disease, psoriasis, turns out to be a window into the coronary circulation, and why "I got my cholesterol perfect" is not the same sentence as "I fixed my risk." Localized, chronic inflammation is a different animal than systemic inflammation that shows up on a standard blood panel. We will be exploring this here.

The Read: A clean angiogram tells you that the major coronary arteries are open. It tells you almost nothing about the tiny microvasculature that branches off of them.

Vocabulary that matters

• Coronary microvascular dysfunction (CMD): when the smallest heart vessels, the ones an angiogram cannot see, fail to open on demand.
• Coronary flow reserve (CFR): how much the heart can boost its blood flow under stress versus at rest. A healthy heart roughly triples it; a stiff microcirculation cannot.
• Stress PET / stress cardiac MRI: scans that measure blood flow to the heart muscle at rest and under stress. Both can put an actual number on flow reserve; MRI also reads the state of the muscle tissue.
• Inflammaging: the slow, chronic, body-wide inflammation that builds with age and drives a long list of supposedly separate diseases. Hallmark 11 of the canonical hallmarks-of-aging framework, and the crux of how I now look at every disease, supplement, and intervention that exists.

Why I am the one pushing for this

My cardiology team did nothing wrong, I've visited three different cardiologists and they all went exactly by the book. But, as a scientist, an ER nurse, and an APRN student with a cardiology focus, I have studied enough of my own field to know that "no obstructive disease in the major arteries" and "problem solved/no disease" are different claims, and with my life at stake, I am not willing to let the difference between those statements remain unexamined.

The angle I am using to get looked at is my psoriasis. Mine is very mild, just a few patches on my knees nowadays. I haven't had a major outbreak for nearly a decade, after a period of intense life stress and the loss of a business and the place we called home in the US Virgin Islands following several back to back category 5 hurricanes. For most of my life I filed it under "annoying skin thing." I was wrong about what it is. Psoriasis most definitely goes further than skin deep. It is a systemic inflammatory disease that happens to surface on the skin, but that same inflammation does not politely stop there.

The evidence: clean picture, real disease

Lets start with whether the connection between a skin disorder, psoriasis, and cardiovascular dysfunction is even a real thing. It is real, and the evidence is not soft. In the WISE study, women with chest pain and mostly clean angiograms who had low coronary flow reserve had roughly double the rate of adverse cardiovascular events over about five years, 27 percent versus 12 percent, and that flow-reserve number predicted outcomes independent of how their arteries looked on the angiogram.¹ Clean picture, real disease, real risk.

It is also treatable, which is what turns it from an academic research exercise into something worth diagnosing. The CorMicA trial took patients with angina and no obstructive disease, ran an invasive test of their small-vessel function, and used the result to choose their medications. That group's angina improved meaningfully at six months versus a sham-controlled comparison.² The honest caveat: that trial measured symptoms and quality of life, not heart attacks prevented, and it covered a somewhat broader group than microvascular dysfunction alone. But it establishes the thing that counts: this is a diagnosable, actionable condition, with formal international criteria to define it.³

And the flow-reserve number is also not just an academic curiosity. It is one of the strongest risk markers in cardiology that most people have never heard of. A 2022 meta-analysis pooling 79 studies and nearly 60,000 patients found that an abnormal coronary flow reserve was associated with roughly triple the rate of death and major cardiac events (hazard ratios near 3.8 and 3.4, meaning that scale of higher event rate across the study periods).⁴ That is not a subtle signal.

Where my skin and my heart stop being two appointments

Now the inflammation piece. Young patients with severe psoriasis and no known heart disease have measurably lower coronary flow reserve than matched controls, and in one study the severity of the skin disease was the only independent predictor of how impaired the small vessels were.⁵ Follow psoriasis patients over time, and the ones with microvascular dysfunction have clearly worse event-free survival.⁶ And you do not need severe disease to see it: even mild-to-moderate psoriasis is associated with more inflammation in the wall of the aorta on imaging, independent of the usual risk factors.⁷ This last statement lands for me personally, because this annoying skin thing was only a mild case, so therefore it's something I kept waving off as unrelated until I did this digging.

The most convincing evidence that inflammation is doing the driving, not just riding along, comes from turning it off. Treat psoriasis patients with a TNF-inhibitor, a drug that blocks a specific inflammatory signal, and their coronary flow reserve improves, from about 2.2 to 3.0, and the gain tracks the drop in inflammatory markers rather than the clearing of their skin.⁸ Treat them with a biologic and their non-calcified coronary plaque, the soft and dangerous kind, measurably regresses over a year.⁹ These are small and mostly observational studies, so I hold them as promising rather than proven. But the skin was never the point. The inflammation was.

The Read: If treating the inflammation improves the artery wall, then the inflammation was the culprit all along.

Here is the part that should land even if your labs are pristine and you have never been near a cath lab: getting your cholesterol perfect is not the same thing as fixing your risk. If your entire heart plan is a good lipid panel, you are running half the race, and the other half is the one nobody handed you a number for.

This is also the answer to the question that has actually been eating at me: was crushing my ApoB to 38 enough? The uncomfortable data says lipids are only half the story. In CANTOS, a large randomized trial in people after a heart attack, a drug that blocked inflammation and did nothing to cholesterol still reduced cardiovascular events.¹⁰ And when you pool statin-treated patients and ask what predicts their remaining risk, it is the leftover inflammation, not the leftover LDL, that tracks with events and death.¹¹ I lowered the cholesterol. I have no evidence I touched the inflammation. And, my rock bottom systemic inflammation measured via hsCRP is a different beast than the inflammation caused by conditions like psoriasis, which is local and tissue specific and does not always raise a systemic marker like hsCRP.

The upstream layer, and the aging framing

Underneath all of this is one cell layer: the endothelium, the living, single-cell lining of every blood vessel, the thing that actually tells a vessel to relax and open. Inflammation injures it. When it is injured, the small vessels stop dilating the way they should, and you get microvascular dysfunction. That endothelial layer, and the nitric oxide it uses to do its job, is the real upstream story here, and it is a story deserving of its own article, which I will be delivering in just a few weeks. I will leave it here for now: the lining of the artery is where this whole process of cardiovascular dysfunction starts, and we will dissect and analyze it all soon.

Step back and the framing is the whole point of what I write. This is not a random cardiology footnote. Microvascular dysfunction driven by chronic inflammation IS inflammaging, Hallmark 11 of aging,¹² showing up in the coronary circulation specifically. The stent fixed a plumbing problem. It did nothing for the aging process that made the plumbing fail early. Read the mechanism instead of the label, and "coronary microvascular disease" and "my body's inflammatory aging" turn out to be nearly the same sentence.

And this was never only about my arteries. The same inflammaging that aged my small vessels early is the process aging everybody's body, and my read is that it simply picks a different first target in each of us. In me it surfaced in the coronary microcirculation, because that is where my weakest link happened to be. In you it may be surfacing somewhere you have not thought to look yet.

How you actually find it

So how do you find this, when the standard angiogram is blind to it? Three tools, in rough order of how invasive they are.

Stress PET measures blood flow to the heart muscle and can put a real number on flow reserve. I have had one, and it is a good lesson in the limits of a scan. Mine showed no stress-induced lack of blood flow anywhere they could see, a normal-sized heart, normal pumping. Reassuring. But the inferior wall, the territory fed by my stented right coronary artery, was blacked out by motion on the images, and they could not confidently quantify my flow reserve. Which means the single most useful number, the flow-reserve value that all of that outcome data hangs on, is the one number my scan did not produce. It turns out this is a relatively common occurrence for this type of scan, especially in men. A microvascular problem does not announce itself as a bright spot on a picture. It hides in the number, not the picture. The muscle can image perfectly while the flow reserve comes back low. If you do not get the number, a normal-looking scan has not ruled anything out.

Stress cardiac MRI does the same flow measurement at higher resolution and adds a read on the tissue itself. It is not a fringe test. In a randomized trial of over 900 patients, an MRI-perfusion strategy performed as well as invasive pressure-wire testing for guiding care, while sending fewer people to the cath lab.¹³ Newer quantitative MRI can map flow pixel by pixel across the heart and separate small-vessel disease from big-vessel disease, validated against the invasive standard,¹⁴ and it catches microvascular dysfunction in exactly the population that frustrates everyone: symptomatic patients with clean arteries (the cohort in this study was women).¹⁵

The gold standard, and the road I am most likely taking, is an invasive coronary angiogram with functional testing: a wire in the artery that measures flow reserve and small-vessel resistance directly. It also confirms my stent is still wide open, and it can check a few other things while it is in there. It carries real, if small, procedural risk, and for someone like me who does not love the cath table, that is not nothing. But it is the one test that answers the small-vessel question with a hard number instead of an inference.

What to do with this if you are not me

If you have no symptoms and no stent, the takeaway here is not to go demand an invasive test. It is to ask better questions at your next appointment, and to stop treating a couple of normal results as a finished conversation.

Ask what your inflammation actually looks like, because hsCRP is a cheap test and a lot of standard panels never bother with it. Ask whether a clean picture of your large arteries says anything at all about the small vessels underneath, because the honest answer is that it does not. And if you are someone with real symptoms that nobody can explain against clean-looking arteries, ask whether measuring your flow reserve is on the table, because that conversation is not happening in most offices and it should be.

None of that is exotic, and none of it requires a specialist. It mostly just never gets offered. What I am deliberately not doing here is handing you a list of supplements or habits to lower your inflammation, because that deserves its own evidence review rather than a paragraph of hand-waving at the end of somebody else's story. Those posts are coming.

Where this leaves me

Without a clean answer, yet. The invasive test is scheduled. I do not have a result to report or a protocol to sell you, and I would be suspicious of anyone in my position who did. What I changed is narrower, and I think more useful, than a supplement recommendation: I stopped treating my cholesterol number as the finish line. Getting ApoB to 38 was worth doing. It was never going to be the whole story, because the inflammatory, small-vessel, endothelial layer was always the part my lipid panel could not see. Cholesterol is just part of the picture here, and as with all chronic disease, the real culprit can be assigned to the biology of aging, and the framework known as the hallmarks of aging that allow us to systematically examine it. As stated earlier, this will be the crux of my writing and videos going forward. Allowing you to see how disease works through the lens of the biology of aging.

The other thing I did was go after more data on the plaque I already have. I have asked for a Cleerly analysis, an AI read that characterizes plaque far beyond a standard report, on the two CT scans I have already had. I may pay for it out of pocket just to own the data. The reason I've done this is two fold. First, I am genuinely curious how much more data these scans deliver. Second, I am positioning myself for the reality that I may have microvascular dysfunction. If I do, then one way I will be able to tell if the treatments assigned and my own longevity routine is moving the needle or not is to see how my arteries are responding to this routine. And improvement in the large arteries, the two spots of soft, non-calcified plaque, can help to show that inflammation is dying down. And although I will only see this in the large arteries with coronary artery CT scans that Cleerly is based on, one can use this to assign weight to the improvement in their microvasculature as well. That is its own story, and it is the next post.

The Final Signal

• What is real: the small vessels can be diseased while every big-artery picture looks clean, and it carries real risk.
• What drives it: chronic inflammation, the same inflammaging that ages the rest of the body, which is why my mild psoriasis is relevant and not a footnote.
• What I got wrong: treating a perfect cholesterol number as a solved case.
• What I changed: I stopped reading a clean angiogram as an all-clear, and I am chasing the flow-reserve number directly.
• What this means for you: you do not need my psoriasis or my stent to be carrying this. If your heart plan stops at a good cholesterol number and a clean picture, the inflammatory, small-vessel layer is the part still unaccounted for.
• What is next: a Cleerly deep-read of my existing scans, then the article this one kept pointing at, the endothelium and nitric oxide, where this whole story actually starts.

References

1. Pepine CJ, et al. Coronary microvascular reactivity to adenosine predicts adverse outcome in women evaluated for suspected ischemia (WISE). J Am Coll Cardiol. 2010. PMID 20579539 [Finding: In women with mostly non-obstructive angiograms, low coronary flow reserve roughly doubled 5-year adverse events (27% vs 12%) and predicted risk independent of how the arteries looked.]
2. Ford TJ, et al. Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina: The CorMicA Trial. J Am Coll Cardiol. 2018. PMID 30266608 [Finding: Diagnosing and treating microvascular and vasospastic angina by invasive function testing improved angina at 6 months versus sham. Symptom and quality-of-life endpoints, not hard outcomes.]
3. Ong P, et al. International standardization of diagnostic criteria for microvascular angina (COVADIS). Int J Cardiol. 2018. PMID 29031990 [Finding: Expert consensus establishing formal diagnostic criteria for microvascular angina, defining it as a real, diagnosable condition rather than a diagnosis of exclusion.]
4. Kelshiker MA, et al. Coronary flow reserve and cardiovascular outcomes: a systematic review and meta-analysis. Eur Heart J. 2022. PMID 34849697 [Finding: Across 79 studies and roughly 60,000 patients, abnormal coronary flow reserve was associated with about triple the rate of all-cause mortality and major cardiac events.]
5. Osto E, et al. Impaired coronary flow reserve in young patients affected by severe psoriasis. Atherosclerosis. 2012. PMID 22236480 [Finding: Young patients with severe psoriasis and no known heart disease had lower coronary flow reserve than matched controls, with skin-disease severity the only independent predictor of impairment.]
6. Piaserico S, Osto E, et al. Long-term prognostic value of coronary flow reserve in psoriasis patients. Atherosclerosis. 2019. PMID 31476732 [Finding: In psoriasis patients with no known cardiovascular disease, those with microvascular dysfunction had markedly worse event-free survival over long-term follow-up.]
7. Naik HB, et al. Severity of Psoriasis Associates With Aortic Vascular Inflammation Detected by FDG PET/CT. Arterioscler Thromb Vasc Biol. 2015. PMID 26449753 [Finding: Even mild-to-moderate skin severity tracked with more aortic-wall inflammation on imaging, independent of age, sex, and standard risk score.]
8. Piaserico S, et al. Treatment with tumor necrosis factor inhibitors restores coronary microvascular function in young patients with severe psoriasis. Atherosclerosis. 2016. PMID 27236353 [Finding: In a small self-controlled study, anti-TNF therapy raised coronary flow reserve, and the gain tracked falling inflammatory markers rather than skin clearance.]
9. Elnabawi YA, et al. Coronary artery plaque characteristics and treatment with biologic therapy in severe psoriasis. Cardiovasc Res. 2019. PMID 30721933 [Finding: One year of biologic therapy for the skin was associated with reduced non-calcified coronary plaque burden and necrotic core on CT angiography. Observational.]
10. Ridker PM, et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease (CANTOS). N Engl J Med. 2017. PMID 28845751 [Finding: In post-heart-attack patients, an anti-inflammatory drug reduced cardiovascular events with no effect on cholesterol, showing inflammation is a causal, independent driver.]
11. Ridker PM, et al. Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy. Lancet. 2023. PMID 36893777 [Finding: In pooled statin-treated patients, residual inflammation predicted events and death while residual LDL cholesterol was essentially neutral.]
12. López-Otín C, et al. Hallmarks of aging: an expanding universe. Cell. 2023. PMID 36599349 [Finding: The framework paper defining the hallmarks of aging, including chronic inflammation (inflammaging) as Hallmark 11.]
13. Nagel E, et al. Magnetic Resonance Perfusion or Fractional Flow Reserve in Coronary Disease (MR-INFORM). N Engl J Med. 2019. PMID 31216398 [Finding: In over 900 patients, a stress-perfusion MRI strategy was non-inferior to invasive pressure-wire testing for 1-year outcomes while sending fewer patients to the cath lab.]
14. Kotecha T, et al. Automated Pixel-Wise Quantitative Myocardial Perfusion Mapping by CMR. JACC Cardiovasc Imaging. 2019. PMID 30772231 [Finding: Quantitative stress-perfusion MRI detected obstructive disease and distinguished microvascular dysfunction from multivessel epicardial disease, validated against invasive coronary physiology.]
15. Thomson LEJ, et al. Cardiac magnetic resonance myocardial perfusion reserve index is reduced in women with coronary microvascular dysfunction (WISE). Circ Cardiovasc Imaging. 2015. PMID 25801710 [Finding: Stress MRI perfusion reserve was reduced in invasively-confirmed microvascular dysfunction, catching it in symptomatic women whose arteries looked clean.]