What Keeps Plaque in Your Heart Arteries From Rupturing?

In 2025 a cardiologist put a stent, a small metal scaffold, in my right coronary artery because it was 80 percent blocked. The same angiogram, the dye X-ray of the heart's arteries, also found smaller narrowings that nobody stented, including 10 percent in the artery that runs down the front of my heart and 20 percent in a branch off the side. Leaving them alone was standard care. Stents are for narrowings that choke off blood flow, and small plaques like those get treated with medication instead, which in my case means a statin and a PCSK9 inhibitor, two drugs that lower LDL cholesterol. However, just because they didn't earn a stent doesn't mean those small numbers in my other arteries don't scare me. They scare the crap out of me. The plaque in my right coronary artery that earned the stent very likely started out as a 10 percent spot just like them, then ruptured and ballooned to the 80 percent found on the angiogram. As I've discussed in previous posts, not all plaque ruptures result in the dramatic scene you see on TV. Sometimes you don't even feel them at all.

So, what exactly keeps a plaque, even a tiny one, from rupturing? The answer depends heavily on its fibrous cap, the layer of living tissue between the plaque's fatty core and the blood. A thick cap over a small core is what pathologists call a stable plaque. A thin cap over a large, inflamed core is the unstable kind, the kind most likely to tear. The percentages on an angiogram don't measure any of that; they measure the channel, the space left for blood. The words "soft" and "hard" on a CT report don't measure the cap either. If your own report lists a small narrowing, that number is about the channel too, not the cap that stands between an ordinary day and a heart attack.

What happens to the small plaques that get left alone? A study called PROSPECT followed them forward in living patients. Researchers ran an ultrasound catheter through the upper and middle stretches of all three coronary arteries of 697 people who had just been stented for a heart attack or unstable angina, then followed them for a median of 3.4 years. Within three years, 20.4 percent had another major event, a count that included cardiac deaths, heart attacks, and readmissions for worsening chest pain. Those events were traced about equally to two sources: 12.9 percent of patients had one traced to the plaque that had been stented, and 11.6 percent had one traced to a plaque that had been left alone. The left-alone plaques that caused trouble were narrowed by 32.3 percent on average, and most had looked mild on the angiogram. What they had more often was plaque filling 70 percent or more of the artery's cross-section, a channel of 4 square millimeters or less, or an ultrasound pattern read as a thin cap over a large core. Each of those features came with three to five times the rate of events (hazard ratios from 3.21 to 5.03). Abbott Vascular and Volcano, the company that made the ultrasound catheter, paid for the study.¹

The Bottom Line

A plaque's risk is not the same as its narrowing. Whether a plaque tears depends heavily on its fibrous cap, a sheet of collagen-rich living tissue over a core of cholesterol and dead cells. Pathologists who studied plaques that had already torn found three features in common, which they read as likely signs of instability: a cap thinner than 65 micrometers, roughly the thickness of a human hair; a large core; and immune cells worked into the cap.² Imaging studies in living patients have since linked heavy plaque and thin caps to later coronary events, including heart attacks and cardiac deaths.¹³

Cells build the cap and keep rebuilding it, and inflammation breaks it down. When breakdown outpaces repair, the cap thins. Two hallmarks of aging map onto that balance: chronic inflammation on the breakdown side, and cellular senescence, cells that have stopped dividing, on the repair side.⁴ The evidence for the first link comes from human tissue in a dish, and for the second mostly from mice; both are below.

The good news is that there is something you can do about it. In a randomized trial after heart attack, a year of evolocumab, a PCSK9 inhibitor, on top of a statin thickened the thinnest point of the cap by 42.7 micrometers, against 21.5 micrometers with the statin and a placebo. The plaque was still there at the end of the year, with a thicker cap over it.⁵ Neither a calcium score, the CT number for how much calcium sits in the heart's arteries, nor the words "noncalcified" and "calcified" on a CT report measures a cap.

Vocabulary that matters

• Fibrous cap. The layer of collagen-rich living tissue covering a plaque's core, built and maintained mostly by cells that came from the artery's smooth muscle. It sits inside the artery wall, under the thin lining that faces the blood.
• Necrotic core. The pool of cholesterol, dead cells, and debris under the cap. Some papers call it the lipid core.
• Thin-cap fibroatheroma. The pathologists' name for a plaque with a large core under a cap thinner than 65 micrometers, the plaque type most ruptures come from.
• Stenosis and plaque burden. Stenosis is how narrow the channel is, the percent on your report. Plaque burden is how much of the artery's cross-section the plaque takes up. The two can disagree, which is how a large plaque can still look mild on an angiogram.
• Collagen, fibronectin, and fibrin. Collagen is the rope-like protein that gives the cap its strength. Fibronectin helps cells grip and organize the collagen around them. Fibrin is the mesh that holds a blood clot together. A cap is mostly collagen organized by cells; a clot is fibrin and platelets formed from blood.
• Rupture and erosion. A rupture is a tear through the cap. An erosion is a patch where the lining over an intact cap has worn away. Either one can set off a clot.

What is a fibrous cap?

Let's start in the blood and work outward into the wall. First the lumen, the channel blood flows through. Then the endothelium, a single layer of cells lining that channel. Beneath it, inside the wall, the plaque: the cap on top, the core underneath, and the artery's muscle layer around both. The cap is the only thing separating the core from the blood.

The cap is closer to a scar than to a lid. Cells that came from the artery's smooth muscle lay down its collagen the way a healing wound lays down collagen, and they keep laying it down for as long as the cap exists, while enzymes released by immune cells digest it. How thick the cap is at any moment depends on which side has been ahead.

How thin is too thin? The 65-micrometer number comes from autopsies. Pathologists studying ruptured plaques under a microscope named three features that likely mark a cap as unstable: a cap thinner than that, a large core, and macrophages, a type of immune cell, worked into the cap.² That describes what torn caps looked like after the fact. Optical coherence tomography, OCT, a catheter that images the artery wall with light, made it possible to measure caps in living people. In the CLIMA study, 1,003 patients had the first stretch of the artery down the front of the heart imaged with OCT during an angiogram they needed anyway, and were followed for a year. Plaques with a cap thinner than 75 micrometers came with 4.7 times the rate of cardiac death or of a heart attack traced to that stretch of artery (hazard ratio 4.7). The absolute numbers were small: 37 patients, 3.7 percent, had one of those events.³ A thin cap was linked to higher risk in that study; it did not identify which plaque would tear, or when.

What makes a plaque unstable?

A cap weakens in two ways: it loses the tissue holding it together, or the forces pulling on that tissue rise.

Immune cells digest the collagen. Macrophages, the immune cells that crowd into inflamed plaques, release enzymes called matrix metalloproteinases (MMPs) that cut collagen. In 1995, researchers dissected fibrous caps from human plaques and incubated them with human macrophages for two days. The fluid around the caps filled with collagen breakdown products, twenty times the amount around caps left without cells, and a drug that blocks MMPs stopped the breakdown completely.⁶ That was tissue in a dish, taken from the aorta and carotid arteries rather than the heart, but the cells and the caps were human.

The cells that rebuild the cap accumulate damage. Smooth muscle cells taken from human plaques carry more broken DNA than normal cells, with their damage-response machinery switched on. Researchers then engineered mice so that only those cells repaired DNA breaks badly, or unusually well. With poor repair, more of the cells stopped dividing or died, and the caps made up a smaller share of the plaque. With faster repair, the caps were larger and held more cells. The total amount of plaque did not change either way.⁷ DNA damage is one of the things that can push a cell into senescence, a state where it stops dividing and starts releasing inflammatory signals. I have written about senescent cells before. The human part of that study is observation of tissue; the cause-and-effect experiments were done in mice.

Chronic inflammation and cellular senescence are two of the twelve hallmarks of aging, the processes researchers have proposed as the shared biology of getting older.⁴ In a plaque cap, inflammation lines up with the breakdown side and senescence with the repair side; the first link rests on human tissue in a dish, the second mainly on mice.

The core grows from the inside. Bleeding inside the plaque is common in advanced coronary plaques, most likely from fragile new blood vessels that grow into them. In coronary arteries from 24 people who died suddenly, signs of old bleeding inside the plaque were scarce in early plaques and heavy in advanced ones, and the more bleeding a plaque showed, the larger its core and the more macrophages it held.⁸ Red blood cell membranes are rich in cholesterol, and the authors proposed that a plaque that bleeds into itself adds that cholesterol to its own core; a rabbit experiment reproduced the sequence.⁸ A large core is one of the three features pathologists read as a sign of an unstable plaque.

Microscopic calcium can concentrate stress. When researchers scanned the caps of 22 unruptured human coronary plaques at a resolution of 2.1 micrometers, they counted nearly 35,000 calcium specks 5 micrometers or larger, most of them too small for earlier scanners to see. A computer model of the forces on those caps found 193 pairs of specks close enough together to more than double the local stress on the tissue, and only 3 pairs close enough that the model estimated the stress could rise more than fivefold. The authors concluded that nearly all caps have microscopic calcium deposits, "but only a small subset has the potential for rupture."⁹ This calcium is far below anything a CT scanner can see, and it is a different thing from the calcium in a calcium score.

When a cap tears

When a cap tears, the core meets the blood. The core is packed with material that sets off clotting, and a clot builds on the tear. What happens next depends on the clot: whether it grows, whether it stays, and how badly it cuts off blood to the heart muscle downstream. A clot does not have to close the artery completely to damage heart muscle.

Many tears never cause symptoms. In PROSPECT, 14 percent of patients had a rupture that had caused no symptoms, in a plaque other than the one being treated. Over three years on standard medications, their rate of major events was not significantly different from that of patients without one.¹⁰

Silent tears can heal, and they leave a mark. In the hearts of 142 men who died suddenly of coronary disease, pathologists found healed ruptures in 61 percent. Many plaques held several healed tears stacked in layers, and the more healed sites a segment of artery had, the narrower its channel. The authors described silent rupture as "a form of wound healing that results in increased percent stenosis."¹¹ A plaque can grow in steps this way, one tear and one repair at a time, without the person ever feeling it.

My own artery most likely went this way, and I made that case in The Heart Attacks You Never Feel. A coronary CT in 2016, when I was 36, found no detectable plaque in any of my coronary arteries. I had no coronary scan again until early 2025, when the right coronary artery was 80 percent blocked. Since that post, a cardiology consult note from this July put it in writing, summarizing my 2025 angiogram as showing "a ruptured plaque with an approximately 80% lesion." The only imaging inside that artery was an ultrasound catheter, and I have written about what that probe could and could not answer. Nobody imaged the cap with OCT, so there is no picture of how thin it was or how it healed. A tear that clotted without closing the artery, then healed and left the plaque bigger, is the most plausible explanation I have for going from no plaque to 80 percent.

Not every coronary clot starts with a tear. In 50 sudden deaths from a coronary clot, 22 of the clots sat on plaques whose caps were intact; the lining over the cap had worn away instead. Those eroded plaques were rich in smooth muscle cells, less often held macrophages, were less often calcified, and came from younger people, more often women.¹² A 2019 review argued that as more people get their LDL cholesterol under control, erosion may account for a growing share of acute coronary syndromes, heart attacks and unstable angina. It also noted that clots on erosions seem to be richer in platelets, while clots on ruptures are built more from fibrin.¹³

Is soft plaque dangerous?

It can be. On a CT report, "soft" means noncalcified, and noncalcified covers both the dangerous kind and the stable kind. Every one of my reports that describes composition calls my plaque noncalcified.

CT sorts plaque mainly by whether it holds enough mineral to show up bright. Noncalcified plaque can be a lipid-rich core under a thin cap, or firm fibrous tissue over a small core. CT cannot measure the cap. It can flag features that predicted later heart attacks and unstable angina in follow-up studies, chiefly plaque of very low density and plaque that pushes the artery wall outward.¹⁴ A report graded on CAD-RADS, the scale radiologists use for coronary CT, adds "HRP," for high-risk plaque, when a plaque shows at least two of four features: those two, small specks of calcium, or a bright ring around a dark center.¹⁵ Calcified plaque contains mineral, and that says nothing about the cap over the rest of the plaque. A calcium score sees only the mineral, which is how it can read zero while noncalcified plaque sits in the wall.

So is hard plaque the safer kind? Only partly. MESA, a US study, followed 3,398 adults who had some coronary calcium for a median of 7.6 years. More calcium volume meant more coronary events, 1.81 times the rate for each one-standard-deviation step up in the logarithm of calcium volume, roughly a fivefold increase in calcium. A standard deviation is a statistician's unit of spread. At the same volume, denser calcium meant fewer events, 0.73 times the rate for each step up in density.¹⁶ That is an observational link measured across whole people, not a verdict on any single plaque, and the volume half of the same result means a big calcium score is not reassuring.

Stable, in this post, means relatively resistant to rupture. It does not mean the plaque is harmless, gone, or leaving plenty of room for blood.

Can plaque be stabilized?

Yes, at least on imaging. In Japan, 70 patients with unstable angina who were not yet on cholesterol treatment were randomized to 20 or 5 milligrams a day of atorvastatin for a year, and OCT measured the cap on a plaque that had not caused their symptoms. On the higher dose, LDL averaged 69 mg/dL against 78, and caps thickened by 69 percent against 17 percent. The thickening tracked the fall in LDL, in C-reactive protein, a blood marker of inflammation, and in MMP-9, a blood marker from the same enzyme family as the dish experiment above. Pfizer Japan, which sells atorvastatin, paid for the trial.¹⁷

The HUYGENS trial pushed LDL much lower. It gave 161 people who had just had a heart attack monthly evolocumab or a placebo for a year, all of them on a statin. LDL fell to 28.1 mg/dL on evolocumab and 87.2 on placebo. The thinnest point of the cap thickened by 42.7 micrometers against 21.5. The lipid-rich region, measured on OCT as the angle it covers around the artery, shrank by 57.5 degrees against 31.4, and the OCT signal from macrophages fell more on evolocumab. The share of the artery's volume taken up by plaque, measured by ultrasound, fell by 2.29 percentage points against 0.61. The groups did not differ in how their calcium changed.⁵ Amgen, which sells evolocumab, paid for the trial. It measured caps, not heart attacks, so it cannot say the thicker caps prevented any. Nine pooled OCT studies of statins point the same direction, with results that vary widely in size.¹⁸

Regression means less plaque. Stabilization means a change in what the plaque is made of that should make it harder to tear: a thicker cap, a smaller lipid-rich region, fewer macrophages. HUYGENS measured both and found both. A plaque does not have to disappear for its cap to get thicker.

The Read The percent narrowing on your report tells you the least about whether a plaque will tear. The cap and the core tell you the most, and nobody can see them without a catheter in your heart. Every trial in this post that measured caps under cholesterol-lowering treatment found them getting thicker.

What my tests can tell me

None of my scans has measured a cap. The ultrasound catheter run through my right coronary artery in 2025 described the segment as having "moderate atherosclerosis" and "discrete eccentric disease," which describes how much plaque there was and where, not how thick anything was. My cath in August was a spasm test, and nobody imaged a cap then either.

My CT angiogram this February looks better than the one from the year before. The 2025 scan was graded CAD-RADS 4A, the severe-narrowing category, because of the right coronary plaque that then got the stent. The February scan was graded 1, minimal narrowing, with the stent open. Most of that change is the stent doing its job. It does not show my other plaques shrinking, and the February report says "COMPARISON: None," meaning no radiologist read it against the earlier scan. Plaque numbers from CT also move between scans for reasons unrelated to the plaque; I have written about how much. And no CT can measure a cap.

My latest LDL was 28 mg/dL, about where the evolocumab group in HUYGENS finished, and my ApoB, the count of cholesterol-carrying particles in my blood, runs about 38. I take the two drug classes that thickened caps in those trials, a statin and a PCSK9 inhibitor. My inflammation markers have always run low, and my hsCRP, a blood test for low-grade inflammation, is 0.45 mg/L, well under the 2 mg/L the CANTOS trial below required to enroll.¹⁹ Nobody has measured what any of that did to my caps.

What to ask about your own plaque

Nobody can measure your cap without a catheter in your heart, but most of what thickens or thins one shows up in tests and habits you can do something about.

• Read your CT report past the percent. Look for the plaque burden grade, P1 to P4 on a CAD-RADS report, and for "HRP."¹⁵ In a study of 3,158 people who had a coronary CT angiogram, 16.3 percent of those with high-risk plaque features went on to a heart attack or unstable angina over an average of 3.9 years, against 1.4 percent of those without. But about as many of those events came from plaques without high-risk features as from plaques with them.¹⁴ An HRP flag is worth acting on. Its absence is not a pass: neither my 2025 nor my 2026 CT report carries one, including the 2025 scan of the plaque later described as a rupture.
• Push your ApoB down, and know the number. ApoB counts the particles that carry cholesterol into the artery wall, and it is the number I track. Caps thickened most in the groups where LDL fell furthest: to 69 mg/dL in one trial and 28.1 in the other. They thickened less in the comparison groups, at 78 and 87.2.¹⁷⁵ Ask for ApoB, not just LDL, and ask your cardiologist what target fits your disease.
• Get an hsCRP. High-sensitivity C-reactive protein is a cheap blood test for low-grade inflammation. In EASY-FIT, caps thickened more as CRP fell.¹⁷ In CANTOS, 10,061 heart-attack survivors with an hsCRP of 2 mg/L or higher were randomized to placebo or to an antibody that blocks an inflammatory signal and did not lower cholesterol. At 150 mg, the only dose that cleared the trial's statistical bar, the combined rate of nonfatal heart attack, nonfatal stroke, and cardiovascular death fell 15 percent in relative terms (hazard ratio 0.85; 3.86 against 4.50 events per 100 person-years), and the drug raised the rate of fatal infections.¹⁹ If your LDL is at target and your hsCRP is still high, that is a conversation to have with your cardiologist; I covered the anti-inflammatory options in the CHIP post.
• Don't smoke. In an autopsy series of 113 men who died suddenly with coronary disease, smoking was a risk factor in 75 percent of the men who died of a fresh clot, against 41 percent of the men whose narrowed arteries held no clot. A high ratio of total cholesterol to HDL went with ruptured caps; smoking went with the clot.²⁰
• Don't chase an OCT. It means a catheter threaded into your heart, and it is not a screening test. The cap measurements in living people in this post came from patients who were already having an angiogram for a medical reason.³⁵¹⁷
• Don't wait out chest pain. A plaque that looked minor on a scan can still set off a clot. New chest pressure or pain, pain spreading to the jaw, arm or back, or breathlessness that doesn't settle means calling 911, not driving yourself in.
• Ask what any plaque product actually measured. When a supplement or protocol promises to clear or stabilize plaque, ask which of these it measured in people: the cap, the core, the amount of plaque, the clot, or heart attacks. Each is a different result, and only the last one is the outcome you care about.

What I changed

I keep my ApoB under 40, and it runs about 38. I think under 40 should be the target for anyone with known coronary disease, especially disease severe enough to need a stent. I can't prove that number is the right one. My reasoning is the biology in this post: my own plaque most likely tore and healed, and lowering LDL, and with it the particles that carry cholesterol into the artery wall, is what correlated with thicker caps in the trials. What changed for me is how I read a scan report. The percent narrowing and the word "noncalcified" tell me nothing about the cap, so I look at plaque burden and at my ApoB, two things I can act on.

The Calibrated Claim Audit

Claim	Evidence	My read
A mild narrowing means a harmless plaque	Left-alone plaques that caused later events averaged 32.3% narrowing 1; thin caps on OCT were linked to higher event rates 3	Narrowing alone can't settle it.
Soft plaque is dangerous, hard plaque is safe	More calcium volume meant more events; at the same volume, denser calcium meant fewer 16	Neither label measures the cap.
A plaque has to shrink to get safer	Caps thickened on a statin 17 and a PCSK9 inhibitor; plaque share fell 2.29 percentage points (placebo, 0.61) 5	Stabilization and regression are different measurements.

Commercial distortion risk: low. The drug trials here were paid for by the company selling the drug: HUYGENS by Amgen, EASY-FIT by Pfizer Japan, CANTOS by Novartis. PROSPECT, a natural-history study rather than a drug trial, was paid for by Abbott Vascular and by Volcano, which made its imaging catheter. That is how this research gets done. The cath lab is an expensive place with a big, well-paid team, and the money to test something new has to come from somewhere. Who paid worries me less than who ran the trial and wrote it up. EASY-FIT's authors reported no relationships relevant to the paper. HUYGENS, CANTOS and PROSPECT are the ones to read with that in mind: HUYGENS's lead author consults for Amgen and three of its authors are Amgen employees who hold its stock; two CANTOS authors worked for Novartis; and PROSPECT's lead author reported grants and consulting fees from Abbott Vascular and grants from Volcano, and two of its authors were Abbott Vascular employees.

The Final Signal

• What the "stable plaque" idea gets right: what a plaque is made of matters, and a thick cap over a small core is harder to tear than a thin cap over a large one.
• What it gets wrong: percent narrowing and the words "soft" and "hard" don't measure a cap. Most left-alone plaques that caused later events in PROSPECT looked mild,¹ and some clots form on caps that never tore.¹²
• What I changed: an ApoB target under 40, which I can't prove is the right number, and a different way of reading a scan report.
• What would change my mind: outcome trials showing that treatments which thicken caps on OCT don't reduce heart attacks. That would make cap thickness a number that moves without telling anyone much about risk.
• What's next: the habits and routines at home that can affect your blood pressure and the health of your artery lining.

More on plaque and what drives it: the Cardiovascular Risk series, and the Diagnostic Toolkit posts on what each scan can and can't see.

The plaque that scares me most is the noncalcified one where my left main artery branches into the artery down the front of my heart. I would like it to calcify, and it hasn't. What these trials taught me is that calcium was never the only way a plaque gets safer. A cap can thicken with no change in calcium, and no scan I can get would show it. So I work on what that cap is exposed to: ApoB under 40 and inflammation kept low.

Where we head next

Next week is about your own house: the habits and routines at home that can affect your blood pressure and the health of your endothelium, the thin inner lining of your arteries. One of them is probably sitting on your bathroom counter right now. We'll go through the biology, what the studies actually show, and what I changed. Stay tuned.

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References

1. Stone GW, Maehara A, Lansky AJ, et al. A prospective natural-history study of coronary atherosclerosis. N Engl J Med. 2011;364:226-235. PMID: 21247313 [Finding: Among 697 patients imaged with ultrasound after being stented for an acute coronary syndrome and followed for a median 3.4 years, the 3-year cumulative major adverse event rate was 20.4%, a composite that includes readmission for unstable or progressive angina. Events were traced to the treated (culprit) lesion in 12.9% of patients and to untreated lesions in 11.6%; those untreated lesions were mostly angiographically mild (mean 32.3% stenosis). Plaque burden of 70% or more, a minimal lumen area of 4 mm² or less, and a radiofrequency-ultrasound thin-cap fibroatheroma classification each independently predicted them. The ultrasound classifies a pattern; it does not measure a 65-micrometer cap. Funded by Abbott Vascular and Volcano; the lead author reported grants and consulting fees from Abbott Vascular and grants from Volcano, and two authors were Abbott Vascular employees.]
2. Virmani R, Burke AP, Kolodgie FD, Farb A. Pathology of the thin-cap fibroatheroma: a type of vulnerable plaque. J Interv Cardiol. 2003;16:267-272. PMID: 12800406 [Finding: A pathology review describing the thin-cap fibroatheroma as the precursor of plaque rupture, with instability read from a large necrotic core, a fibrous cap under 65 microns, and numerous macrophages within the cap. A post-mortem description, not a threshold measured in living patients.]
3. Prati F, Romagnoli E, Gatto L, et al. Relationship between coronary plaque morphology of the left anterior descending artery and 12 months clinical outcome: the CLIMA study. Eur Heart J. 2020;41:383-391. PMID: 31504405 [Finding: In 1,003 patients whose untreated proximal LAD was imaged with OCT during a clinically indicated angiogram, 37 (3.7%) had cardiac death or target-segment heart attack within a year. Across 1,776 lipid plaques, a fibrous cap under 75 micrometers carried a hazard ratio of 4.7; a small lumen, a wide lipid arc, and OCT-defined macrophages were also associated with events, and all four together had a hazard ratio of 7.54. Observational, one artery, one year; a study-specific threshold, not a universal line. Funded by the CLI Foundation, a non-profit linked to the lead author's institution; the lead author discloses Amgen and Abbott Vascular consulting in a 2022 paper.]
4. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: an expanding universe. Cell. 2023;186:243-278. PMID: 36599349 [Finding: A framework review proposing twelve hallmarks of aging, including chronic inflammation and cellular senescence; it supplies the lens this post uses; a review with no original data, and its abstract does not mention plaques or caps.]
5. Nicholls SJ, Kataoka Y, Nissen SE, et al. Effect of evolocumab on coronary plaque phenotype and burden in statin-treated patients following myocardial infarction. JACC Cardiovasc Imaging. 2022;15:1308-1321. PMID: 35431172 [Finding: In statin-treated patients after a non-ST-elevation heart attack (80 on evolocumab, 81 on placebo), one year lowered LDL to 28.1 versus 87.2 mg/dL and increased minimum fibrous cap thickness on OCT by 42.7 versus 21.5 micrometers. Maximum lipid arc fell 57.5 versus 31.4 degrees, the macrophage index fell more, and percent atheroma volume on ultrasound fell 2.29 versus 0.61 percentage points; the groups did not differ in calcium change. Amgen-funded; the lead author consults for Amgen and three authors are Amgen employees; imaging endpoint; no event data.]
6. Shah PK, Falk E, Badimon JJ, et al. Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques. Potential role of matrix-degrading metalloproteinases and implications for plaque rupture. Circulation. 1995;92:1565-1569. PMID: 7664441 [Finding: Human fibrous caps incubated with human macrophages for 48 hours released twentyfold more hydroxyproline, a collagen breakdown product, than caps in cell-free medium, and an MMP inhibitor abolished the effect; the macrophages expressed MMP-1 and MMP-2. Human aortic and carotid tissue in culture, not a patient study.]
7. Gray K, Kumar S, Figg N, et al. Effects of DNA damage in smooth muscle cells in atherosclerosis. Circ Res. 2015;116:816-826. PMID: 25524056 [Finding: Smooth muscle cells from human plaques show increased DNA damage with an active damage response. In mice, impairing DNA repair in those cells increased growth arrest and cell death and reduced relative fibrous cap area; accelerating repair increased cap area and smooth muscle cell content; neither changed the extent of plaque. Human tissue observation plus a mouse mechanism.]
8. Kolodgie FD, Gold HK, Burke AP, et al. Intraplaque hemorrhage and progression of coronary atheroma. N Engl J Med. 2003;349:2316-2325. PMID: 14668457 [Finding: In coronary plaques from 24 sudden-death patients, markers of old intraplaque bleeding were scarce in early lesions and heavy in late-core and thin-cap plaques, and more bleeding tracked larger necrotic cores and more macrophages; a rabbit model reproduced the sequence. Autopsy plus animal; the authors proposed red-cell membranes as a cholesterol source for the core.]
9. Kelly-Arnold A, Maldonado N, Laudier D, Aikawa E, Cardoso L, Weinbaum S. Revised microcalcification hypothesis for fibrous cap rupture in human coronary arteries. Proc Natl Acad Sci U S A. 2013;110:10741-10746. PMID: 23733926 [Finding: Micro-CT at 2.1 micrometers found nearly 35,000 microcalcifications of 5 micrometers or more in the caps of 22 unruptured human coronary plaques. A simplified finite-element model found 193 particle pairs that more than doubled local tissue stress and 3 pairs where it could rise more than fivefold. The authors conclude nearly all caps have microcalcifications but only a small subset has the potential for rupture. Human specimens plus modeling, not a clinical frequency.]
10. Xie Y, Mintz GS, Yang J, et al. Clinical outcome of nonculprit plaque ruptures in patients with acute coronary syndrome in the PROSPECT study. JACC Cardiovasc Imaging. 2014;7:397-405. PMID: 24631511 [Finding: Among 660 PROSPECT patients with complete ultrasound data, 14.1% had a subclinical rupture in a nonculprit plaque, more often in fibroatheromas with heavy plaque burden; over three years on optimal medical therapy, their major adverse event rate did not differ significantly from patients without one. Not a count of how every rupture healed, and not proof of equivalence; a sub-analysis of an industry-funded cohort.]
11. Burke AP, Kolodgie FD, Farb A, et al. Healed plaque ruptures and sudden coronary death: evidence that subclinical rupture has a role in plaque progression. Circulation. 2001;103:934-940. PMID: 11181466 [Finding: In 142 men who died of sudden coronary death, healed ruptures were found in 61% of hearts, often as multiple layered repair sites, and luminal narrowing increased with the number of healed sites. The authors conclude that silent plaque rupture is a form of wound healing that results in increased percent stenosis. Autopsy series; NHLBI-funded.]
12. Farb A, Burke AP, Tang AL, et al. Coronary plaque erosion without rupture into a lipid core. A frequent cause of coronary thrombosis in sudden coronary death. Circulation. 1996;93:1354-1363. PMID: 8641024 [Finding: In 50 consecutive sudden deaths from coronary thrombosis, 22 (44%) had a clot on an eroded plaque with the cap intact and no exposed lipid core. Compared with ruptures, erosions came from younger people (44 versus 53 years), more often women (50% versus 18%), were less often calcified (23% versus 69%), and less often had macrophages in the cap (50% versus 100%). Autopsy series; compares rupture with erosion, not stable with unstable plaque; not a contemporary rate.]
13. Libby P, Pasterkamp G, Crea F, Jang IK. Reassessing the mechanisms of acute coronary syndromes. Circ Res. 2019;124:150-160. PMID: 30605419 [Finding: A review contrasting rupture (thin cap, large lipid pool, foam cells) with superficial erosion (matrix-rich, lipid-poor), noting that erosion thrombi seem more platelet-rich than the fibrinous clots on ruptures, and arguing that erosion may assume greater clinical importance as LDL control improves. No new data.]
14. Motoyama S, Ito H, Sarai M, et al. Plaque characterization by coronary computed tomography angiography and the likelihood of acute coronary events in mid-term follow-up. J Am Coll Cardiol. 2015;66:337-346. PMID: 26205589 [Finding: Of 3,158 patients who had coronary CT angiography, followed a mean 3.9 years, acute coronary syndrome occurred in 16.3% (48 of 294) of those with CT high-risk plaque (positive remodeling, low attenuation) and 1.4% (40 of 2,864) of those without; yet the number of events arising from lesions without high-risk features (43) was similar to the number from lesions with them (45). High-risk features predict; their absence does not exclude.]
15. Cury RC, Leipsic J, Abbara S, et al. CAD-RADS 2.0 - 2022 Coronary Artery Disease-Reporting and Data System: An Expert Consensus Document of the Society of Cardiovascular Computed Tomography (SCCT), the American College of Cardiology (ACC), the American College of Radiology (ACR), and the North America Society of Cardiovascular Imaging (NASCI). J Cardiovasc Comput Tomogr. 2022;16:536-557. PMID: 35864070 [Finding: The reporting standard for coronary CT: stenosis categories 0 to 5, plaque burden categories P1 to P4 (in the abstract), and modifiers including HRP, high-risk plaque, assigned when at least two of positive remodeling, low attenuation, spotty calcification, or the napkin-ring sign are present (full-text level; the same rule is printed in the legend of the author's own CT reports). An expert consensus document, not outcome data.]
16. Criqui MH, Denenberg JO, Ix JH, et al. Calcium density of coronary artery plaque and risk of incident cardiovascular events. JAMA. 2014;311:271-278. PMID: 24247483 [Finding: In MESA, 3,398 adults free of known cardiovascular disease with any coronary calcium, followed for a median 7.6 years: calcium volume was independently associated with coronary events (hazard ratio 1.81 per standard deviation of log volume), and at any given volume calcium density was inversely associated (hazard ratio 0.73 per standard deviation). Observational, person-level; NIH-funded.]
17. Komukai K, Kubo T, Kitabata H, et al. Effect of atorvastatin therapy on fibrous cap thickness in coronary atherosclerotic plaque as assessed by optical coherence tomography: the EASY-FIT study. J Am Coll Cardiol. 2014;64:2207-2217. PMID: 25456755 [Finding: In 70 statin-naive patients with unstable angina randomized to atorvastatin 20 versus 5 mg for a year, LDL averaged 69 versus 78 mg/dL and fibrous cap thickness on OCT rose 69% versus 17%; the thickening tracked falls in LDL, C-reactive protein, and serum MMP-9. Dual-center; surrogate endpoint; both arms treated. Funded by Pfizer Japan per the journal's footnote; the authors reported no relationships relevant to the paper.]
18. Ozaki Y, Garcia-Garcia HM, Beyene SS, et al. Effect of statin therapy on fibrous cap thickness in coronary plaque on optical coherence tomography: review and meta-analysis. Circ J. 2019;83:1480-1488. PMID: 31118354 [Finding: A meta-analysis of nine OCT studies (341 patients) found caps in statin-treated groups thickened by a pooled 67.7 micrometers from baseline, with the size differing by statin regimen and very high heterogeneity between studies; there was no untreated comparison group. Direction consistent; the size varies widely.]
19. Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377:1119-1131. PMID: 28845751 [Finding: In 10,061 patients with a prior heart attack and hsCRP of 2 mg/L or more, canakinumab, an antibody against interleukin-1 beta, did not lower lipids; at 150 mg every three months it cut the primary endpoint of nonfatal heart attack, nonfatal stroke, or cardiovascular death (hazard ratio 0.85; 3.86 versus 4.50 per 100 person-years), with more fatal infections and no difference in all-cause mortality. Funded by Novartis; two authors were Novartis employees.]
20. Burke AP, Farb A, Malcom GT, Liang YH, Smialek J, Virmani R. Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N Engl J Med. 1997;336:1276-1282. PMID: 9113930 [Finding: In 113 men with coronary disease who died suddenly, 59 had an acute clot (41 on a ruptured thin-cap plaque, 18 on an eroded plaque) and 54 had severe narrowing without a clot. Smoking was a risk factor in 75% of the men with a clot against 41% of those without, and a high total-to-HDL cholesterol ratio went with rupture. Autopsy series.]