Understanding Coronary Artery Disease

Medical Disclaimer: This content is for educational purposes only and does not constitute medical advice, diagnosis, or treatment. Information is based on current medical literature and clinical guidelines but may not apply to your specific situation. Individual responses vary based on personal medical history and concurrent conditions. Always consult qualified healthcare providers before starting new treatments and for all medical decisions. Never delay seeking medical care based on content you have read.

These articles provide education to enhance your healthcare partnership. All treatment decisions should involve your healthcare team. Use this knowledge to have informed discussions, not replace medical care.

In Brief: Clinical Overview of Coronary Artery Disease

The progression of coronary artery disease develops when lipid-rich lesions accumulate inside the epicardial vessels. This process is driven by chronic vascular inflammation, not passive mechanical blockage, that unfolds over decades before producing symptoms. The most clinically important feature of this disease is that the plaque most likely to cause a heart attack is often not the one causing chest pain: it is frequently a moderate-sized, biologically unstable lesion that was never severely narrowing blood flow. A normal stress test does not mean no risk. A stent treats one location, not the underlying disease. Risk-factor control matters most during the years when a person feels entirely well. This article explains how plaques form, why the disease stays hidden, what distinguishes a dangerous plaque from a stable one, and what happens when the disease finally declares itself.

The Anatomy and Mechanics of Coronary Circulation

The heart is unlike any other muscle in the body. It works continuously — without rest, without recovery — from before birth until death, and the consequences of even brief interruption to its own blood supply are immediate and often irreversible. What makes this uniquely demanding is not simply the workload, but the metabolic conditions under which the work is done.

At rest, the myocardium extracts approximately 60–75% of the oxygen delivered through its own vessels, meaning the baseline coronary circulation already operates near its maximum physiological ceiling.[1] Because the myocardium already operates at near-maximal oxygen extraction at baseline, increasing cardiac workload requires a corresponding increase in coronary blood flow rather than increased extraction from the same blood. During exertion, emotional stress, or illness, the heart must receive more blood. It cannot compensate by extracting more from what it already has. This dependency on increased flow — rather than increased extraction — means that even moderate coronary obstruction can become clinically limiting during physiological demand, and explains why the coronary circulation carries consequences so different from obstruction elsewhere in the body.

This is why symptoms of coronary disease so often appear first during exertion — and why the same obstruction that causes no trouble at rest can produce chest discomfort, breathlessness, or dangerous rhythm disturbances when the heart is working harder.

The heart supplies itself through the coronary arteries, which arise from the aorta just above the heart and penetrate the myocardium — delivering oxygenated blood during diastole, the relaxation phase between beats, when the myocardial wall releases compression of its own intramural vessels.[2] The anatomy is covered in Article 0.

What matters clinically is the territorial consequence of obstruction, as the location of a blockage determines its structural impact:

• Left Main Coronary Artery: Short, critical, and surgically feared, it divides into the left anterior descending (LAD) artery and the circumflex.
• Left Anterior Descending (LAD): Because the proximal LAD supplies a large proportion of the left ventricular myocardium, acute occlusion at this level places an extensive, poorly collateralised territory at immediate risk.
• Right Coronary Artery (RCA): Supplies the inferior wall and, in most people, the AV node and conduction system, which is why inferior infarctions frequently produce severe rhythm disturbances alongside myocardial injury.

Readers new to cardiac anatomy and physiology may wish to begin with Article 0 before proceeding; Article 2 in this series examines the risk factors that accelerate the disease process described here.

The Biology of Atherosclerotic Plaque Formation

The most consequential misconception about coronary artery disease is that it resembles cholesterol accumulating like grease in a pipe. This model leads to predictable errors: that a stent clears the problem, that the degree of narrowing is the central measure, that arteries either work or they don’t. None of these conclusions holds, because arteries are not pipes. They are living tissue — lined with cells that sense and respond to their biological environment, infiltrated by immune cells when injured, capable of adaptation and failure in ways no mechanical system could replicate.

Phase 1: Endothelial Injury and Vascular Inflammation

The innermost layer of every artery is the endothelium — a single-cell lining covering the entire vascular surface of the body across an area of several thousand square metres. In health, the endothelium maintains arterial tone, suppresses inflammation, prevents inappropriate clotting, and keeps the vessel wall impermeable to lipid accumulation. These are active, continuously maintained physiological functions. When the endothelium is injured, each of these properties degrades in ways that set the conditions for plaque formation.

The exposures that most reliably damage this barrier represent the primary drivers of endothelial injury and atherosclerosis encountered in clinical practice.

• Dyslipidaemia: Particularly elevated LDL, provides the lipid substrate that a damaged, permeable endothelium can no longer exclude from entering the vessel wall.
• Sustained Hypertension: Exposes the vascular wall to chronic mechanical stress — particularly at branch points and curves where flow becomes oscillatory and shear forces are abnormal — accelerating endothelial dysfunction and increasing wall permeability.[3]
• Chronically Elevated Blood Glucose: Drives glycation of endothelial proteins and generates reactive oxygen species that impair nitric oxide signalling and promote vascular inflammation.[20]
• Smoking: Delivers oxidants that deplete nitric oxide, activate inflammatory cascades, and produce measurable, dose-related endothelial dysfunction in a pattern associated with the degree of tobacco exposure.[4]

[Visual: Healthy endothelium vs injured endothelium — showing nitric oxide production, permeability barrier, and sites of LDL entry]

Phase 2: Lipid Retention and the Inflammatory Immune Response

What follows is not passive accumulation, but rather the active process of atherosclerotic plaque formation. When LDL particles cross a dysfunctional endothelium and become retained within the arterial wall, they undergo oxidative modification that marks them as biologically foreign.[5] The immune system responds as it does to any tissue injury: monocytes migrate into the wall, transform into macrophages, and engulf the modified lipid. As macrophages become saturated with cholesterol — foam cells — they lose normal function and eventually die, releasing their lipid contents into a growing inflammatory pool. Smooth muscle cells attempt to contain the damage by building a fibrous cap over this accumulation. The result, developing over years and decades, is an atherosclerotic plaque: a lipid-rich, inflamed necrotic core, covered by a fibrous shell, embedded within the arterial wall.

[Visual: Plaque formation sequence — LDL entry → oxidation → macrophage engulfment → foam cell death → necrotic core → fibrous cap]

Phase 3: Plaque Character and Stable vs Vulnerable Plaque

What determines clinical outcome is not primarily the degree of luminal narrowing but the distinction between a stable vs vulnerable atherosclerotic plaque. A plaque with a thick, fibrotic cap and a small lipid core may narrow an artery considerably while remaining structurally stable — causing symptoms during exertion through flow limitation, but unlikely to rupture. A plaque with a thin cap, a large lipid-rich core, and active inflammation degrading the cap from within may produce only moderate narrowing while remaining biologically volatile — capable of rupturing without warning and producing a myocardial infarction within minutes. The most dangerous plaque is not the most obstructive one. It is the one that is most biologically unstable.

[Visual: Stable plaque vs vulnerable plaque cross-section — thick fibrous cap with small lipid core vs thin cap with large necrotic core]

This is why a cardiologist may be more concerned about a 50% narrowing that is inflamed and biologically active than a 70% narrowing that is fibrotic and calcified. The most dangerous plaque is not necessarily the most obstructive one — and this is one of the most important things a patient with coronary disease can understand about their own condition. Percent narrowing, by itself, does not tell the whole clinical story.

This process begins long before middle age. The PDAY study examined coronary arteries from nearly 3,000 individuals aged 15–34 who died of external causes and found early atherosclerotic changes common even in adolescence, with more advanced lesions increasingly prevalent by the early 30s.[6] When a 55-year-old is diagnosed with three-vessel coronary disease, they are not seeing something that developed recently. They are seeing the cumulative product of decades of endothelial stress, lipid retention, and inflammatory activity — a process that was biologically active during years when they felt entirely well and had no clinical indication that anything was wrong.

Why Statins Do More Than Lower Cholesterol: Plaque Stabilization

The inflammatory nature of this process also explains why statins reduce cardiovascular events through mechanisms that extend well beyond standard LDL reduction. In addition to reducing the lipid substrate available for subendothelial retention, high-intensity statins and plaque stabilization protocols drive reductions in plaque lipid content, suppression of intra-plaque inflammation, and promotion of fibrous cap thickening — effects observed in intravascular imaging studies and consistent with the substantial reductions in cardiovascular events seen across major trials.[7,8] This plaque-stabilising biology is why statins remain central to secondary prevention even when LDL is already at target, and why abruptly stopping them after a cardiac procedure — when the coronary tree still harbours unstable lesions at multiple sites — exposes the patient to ongoing risk. They are not primarily treating a laboratory value. They are modifying the biology of an active, systemic disease.

Two trials confirmed what the plaque biology already implied. The CANTOS trial showed that canakinumab — an anti-inflammatory that targets interleukin-1β with no effect on LDL whatsoever — reduced major cardiovascular events by approximately 15% in patients with prior myocardial infarction.[9] The COLCOT trial showed that low-dose colchicine reduced subsequent events by approximately 23% when given after MI.[10] Inflammation is not merely a marker of coronary disease. It is a causal driver. Controlling it matters independently of controlling cholesterol.

Why Coronary Artery Disease Stays Hidden: Silent Ischemia Mechanisms

Coronary disease is, by design, a condition that conceals itself. The biological processes described above — endothelial injury, lipid retention, inflammatory plaque formation — produce no subjective experience in the person in whom they are occurring. There is no sensation of endothelial dysfunction, no symptom of LDL retention, no warning signal from years of plaque accumulation. By the time symptoms appear, the process has typically been active for two or three decades.

The cardiovascular system’s capacity for compensation deepens this concealment. As plaque develops within an arterial wall, the vessel remodels outward to preserve the inner channel — the Glagov phenomenon — a process known as the glagov phenomenon of arterial remodeling. This means that substantial plaque burden can accumulate without producing any narrowing on an angiogram and without limiting resting blood flow.11] As narrowing eventually progresses, collateral vessels — microscopic pre-existing connections between coronary territories — gradually enlarge to provide alternative perfusion routes around the developing obstruction. Some patients remain asymptomatic despite extensive three-vessel disease because years of gradual progression allowed this physiological adaptation to develop. The cardiovascular system compensates extraordinarily well. The clinical danger is precisely how well it compensates, and for how long.

[Visual: Glagov remodelling — arterial cross-section showing outward expansion preserving lumen diameter despite growing plaque burden]

This is why a patient can have a reassuring angiogram — one that shows no significant narrowing — and still carry substantial atherosclerotic plaque burden within the arterial wall. The imaging shows the channel. It does not show what is accumulating around it.

Not all concealment is purely anatomical. In patients with diabetes, autonomic neuropathy can blunt or abolish the anginal signal entirely, so that progressive ischaemia produces no chest discomfort — causing patients to experience only generalized fatigue, reduced exercise tolerance, or explicit symptoms of silent ischemia that warrant the same clinical attention as symptomatic conditions. Silent ischaemia — objectively demonstrable ischaemia without accompanying symptoms — is well recognised in this population and carries clinical significance that warrants the same attention as symptomatic disease.

Similarly, mapping coronary artery disease symptoms in women requires looking beyond classic substernal exertional pressure. Women more frequently experience atypical fatigue, dyspnea, nausea, or back and jaw discomfort, and more frequently develop microvascular dysfunction and vasospasm rather than epicardial obstructive disease.[13,14] Because these presentations diverged from the male-derived clinical standard from which cardiology developed its diagnostic frameworks, they were historically underestimated and underinvestigated. A normal epicardial angiogram in a woman with objective evidence of ischaemia does not close the clinical question — ischaemia with non-obstructive coronary arteries (INOCA) encompasses microvascular dysfunction, vasospasm, and related entities that require specific evaluation and management.[13,14]

In acute clinical events, identifying the difference in plaque rupture and plaque erosion is critical. While older males display high rates of cap rupture, younger individuals and female cohorts more frequently present with superficial plaque erosion than frank plaque rupture, and may produce acute thrombosis in lesions without a large necrotic core.[21] Older patients as a group frequently present atypically as well, with fatigue, confusion, or breathlessness rather than classic chest discomfort.

Furthermore, long-term cardiovascular prognosis depends on the cumulative total plaque burden cardiovascular risk distributed throughout the entire coronary tree. A patient with diffuse moderate disease throughout multiple vessels may carry substantially higher long-term risk than someone with a single severe narrowing — even when no individual lesion crosses an intervention threshold. Coronary artery calcium scoring — a CT measurement of calcified plaque — provides one window onto this total burden: current guidelines support its use for risk stratification in selected intermediate-risk individuals,[20] and higher scores reflect more years of atherosclerotic activity and a higher likelihood of coexisting non-calcified, potentially unstable plaque.[15] A score of zero lowers near-term risk estimates, though it does not mean zero risk. A high score is most usefully understood as a starting point for a clinical conversation about the intensity of preventive treatment, not a verdict, and not a substitute for sustained attention to the modifiable risk factors that drive the underlying biology.

Taken together, these mechanisms — compensatory arterial remodelling, collateral development, the supply-demand threshold for symptoms, neurological blunting in diabetes, atypical presentations in women, non-obstructive mechanisms, and the systemic distribution of plaque burden — explain why coronary disease often progresses silently for decades before becoming clinically visible. The cardiovascular system compensates until it cannot. And when compensation fails, the failure can be sudden.

When the Disease Declares Itself: Acute Heart Attack Symptoms

The clinical behaviour of coronary artery disease follows directly from its underlying cell biology. Plaques that have developed thick fibrous caps and small lipid cores tend to narrow arteries slowly and predictably. They produce symptoms through exertion-related flow limitation — the same discomfort, reliably triggered by the same activities, reliably relieved by rest. This is stable angina. It signals the presence of flow-limiting disease, and it is clinically important. But it does not signal where the next event will come from. The symptom-producing plaque is typically fibrotic and structurally stable. The dangerous lesion is often a moderate narrowing elsewhere in the same coronary tree — biologically unstable, producing no symptoms, and invisible to a stress test designed to detect flow limitation rather than assess biological instability.

Other plaques are biologically different. Thin caps. Large, lipid-rich cores. Active inflammation degrading the cap from within. These lesions may produce only 40–50% narrowing — insufficient to limit resting flow, insufficient to produce exertional symptoms, insufficient to produce a positive stress test. The patient is asymptomatic. A cardiology evaluation may be entirely reassuring. Then the thin cap ruptures, the lipid contents contact flowing blood, the clotting cascade activates, and within minutes a moderate narrowing becomes complete occlusion. Most acute myocardial infarctions arise from plaques that were not severely obstructing flow beforehand.[12] The dangerous plaque is frequently not the symptomatic one, and not the one a procedure would have been directed at. In some patients, the first clinical manifestation of coronary disease is the acute event itself — no preceding angina, no preceding positive evaluation, no preceding signal of any kind. Feeling well is not the same as being biologically safe.

If you believe you may be having a heart attack, call emergency services immediately. Suspected myocardial infarction is a time-critical emergency. Delayed presentation substantially increases irreversible myocardial injury. Do not drive yourself.

When a coronary artery is completely occluded, the myocardium it supplies begins to die. Cell death starts in the innermost muscle layer — the subendocardium, farthest from the epicardial blood supply and under the highest intracavitary pressure — and extends progressively outward in a time-dependent wavefront.[16] The duration of occlusion is the dominant determinant of how much muscle is lost permanently. A small infarction treated within the first hour may leave the left ventricle functionally intact. A large infarction treated hours later may leave substantial fibrotic scar, a reduced ejection fraction — the percentage of blood the ventricle pumps out with each beat — and a heart that must sustain the rest of life with diminished reserve.

[Visual: Myocardial wavefront — showing progressive cell death spreading outward from subendocardium over time with treatment at 1 hour vs 3 hours vs 6 hours]

This is why “time is muscle” is not a slogan. Every minute of sustained coronary occlusion converts recoverable, ischaemic muscle into permanent scar. Getting to a catheterisation laboratory quickly is among the most life-altering decisions a patient or bystander can make.

After an infarction, cardiac function is not a simple binary of dead versus unaffected. Stunned myocardium — viable muscle that survived ischaemia but is transiently dysfunctional — typically recovers over days to weeks.[17] Hibernating myocardium — chronically underperfused muscle that has downregulated its contractile activity to survive — may recover after revascularisation restores adequate supply, provided irreversible fibrosis has not already occurred.[18] Cardiologists reassess left ventricular function weeks after an acute event because initial measurements frequently underestimate the recovery that will follow.

Whether the artery was opened by emergency stenting or the heart recovered partially on its own, one thing does not change: the underlying disease that caused the event is still present throughout the coronary tree.

When a stent opens a blocked artery, blood flows and symptoms resolve. The procedure has accomplished what it was designed to do. It has not treated the underlying disease. The stented lesion was one site in a coronary tree that has been accumulating plaque for decades. The segments with moderate narrowing — not treated because they did not meet intervention thresholds — harbour the same endothelial injury, the same lipid retention, the same inflammatory activity, the same potential for rupture.

A stent treats anatomy; it does not alter the systemic biology that produced it. Post-intervention medications are required because the mechanical solution cannot address global vascular health:

• Statins: Modify plaque biology across the entire coronary tree, decreasing lipid core size, suppressing inflammation, and promoting fibrous cap thickening — not only at the treated site.[7,8]
• Antiplatelet Therapy: Prevents thrombosis at the stent surface before endothelial cells have covered it; premature discontinuation substantially increases the risk of stent thrombosis.[19]
• Glycemic and Blood Pressure Control: Directly reduce ongoing mechanical and metabolic endothelial injury throughout the entire vascular system.

Stopping medications because symptoms have resolved — or because a procedure was declared successful — leaves the biological process unmodified and the risk that produced the first event continuing to produce the conditions for the next.

The Disease That Hides: Long-Term Cardiovascular Risk Management

The systemic progression of coronary artery disease is dangerous in a unique way: it is most dangerous when it cannot be felt. The decades of plaque accumulation, the years of endothelial injury, the biologically unstable lesion building toward rupture — none of these produce a warning. The cardiovascular system compensates so effectively, for so long, that the first signal is often the event itself.

Two things follow from this that matter more than almost anything else in cardiovascular medicine.

The first is that a reassuring test is not the same as a safe biology. A normal stress test means no lesion is currently limiting blood flow enough to produce ischaemia on demand. It does not mean no dangerous plaque exists. Many heart attacks arise from plaques that would never have produced a positive stress test — moderate narrowings, biologically unstable, invisible to flow-based testing until the moment they rupture. Understanding this changes what a “normal” result actually means.

The second is that the most effective moment to intervene is not when symptoms appear. It is during the years before they do. Risk-factor control — blood pressure, LDL, glucose, smoking — works on the same biological processes this article has described: reducing endothelial injury, slowing lipid retention, stabilising developing plaques. This work is invisible. It produces no dramatic moment of confirmation. But it alters the trajectory of a process that, left unmodified, will eventually produce consequences that are neither invisible nor reversible.

Coronary disease is slow biology with fast consequences. The most dangerous phase is the one that cannot be felt — which is precisely when understanding it matters most.

Key Terms

Angina: Chest discomfort arising from myocardial ischaemia, typically produced by exertion and relieved by rest or nitrates.

Atherosclerosis: The inflammatory disease process characterised by plaque accumulation within arterial walls, driven by LDL retention, immune activation, and impaired repair.

Collateral circulation: Enlargement of pre-existing microscopic connections between coronary territories in response to progressive arterial narrowing, providing alternative perfusion routes.

Coronary artery calcium (CAC) score: A CT-derived measure of calcified plaque burden in the coronary arteries, used to refine cardiovascular risk stratification.

Ejection fraction: The percentage of blood volume ejected from the left ventricle with each systolic contraction; a measure of left ventricular systolic function. Normal is typically above 55%.

Endothelium: The single-cell inner lining of arteries, regulating vascular tone, inflammation, permeability, and thrombosis; the primary site where cardiovascular risk factors produce tissue injury.

Foam cells: Macrophages engorged with oxidised LDL cholesterol; their death contributes to necrotic core formation within vulnerable plaques.

Glagov phenomenon (compensatory arterial remodelling): The outward expansion of the arterial wall in response to accumulating plaque, which preserves luminal diameter and conceals disease burden from standard imaging during early and intermediate stages.

Hibernating myocardium: Chronically underperfused but viable myocardium that has downregulated contractile function to match its reduced oxygen supply; function may recover following revascularisation if fibrosis has not occurred.

INOCA (Ischaemia with Non-Obstructive Coronary Arteries): A clinical syndrome characterised by symptoms and objective evidence of myocardial ischaemia in the absence of obstructive epicardial coronary disease; encompasses microvascular dysfunction, vasospasm, and related entities.

Ischaemia: Insufficient blood flow to meet the oxygen and metabolic demands of a tissue.

Myocardial infarction: Irreversible death of myocardial cells resulting from sustained interruption of coronary blood supply. Also called heart attack.

Necrotic core: The soft, lipid-rich, inflammatory interior of a vulnerable plaque, formed from the accumulated debris of dead foam cells and associated inflammatory material.

Plaque erosion: Disruption of the endothelial surface overlying a plaque without frank fibrous cap rupture, producing thrombosis despite the absence of a large necrotic core; more prevalent in women and younger patients.

Plaque rupture: Disruption of the fibrous cap overlying the necrotic core, exposing lipid contents to flowing blood and triggering rapid thrombus formation and coronary occlusion.

Silent ischaemia: Objectively demonstrable myocardial ischaemia occurring in the absence of anginal symptoms; particularly common in diabetes, older adults, and some women.

Stunned myocardium: Viable but transiently dysfunctional myocardium following ischaemia and reperfusion; contractile function typically recovers over days to weeks.

Vulnerable plaque: A plaque characterised by a thin fibrous cap, large lipid-rich necrotic core, and active inflammation — prone to rupture regardless of the degree of luminal narrowing it produces.

References

1. Goodwill AG, Dick GM, Kiel AM, Tune JD. Regulation of coronary blood flow. Compr Physiol. 2017;7(2):321–382. https://doi.org/10.1002/cphy.c160016
2. Algranati D, Kassab GS, Lanir Y. Physiology of coronary circulation: physico-mechanical considerations. Physiology (Bethesda). 2011;26(4):205–216. https://doi.org/10.1152/physiol.00020.2010
3. Malek AM, Alper SL, Izumo S. Hemodynamic shear stress and its role in atherosclerosis. JAMA. 1999;282(21):2035–2042. https://doi.org/10.1001/jama.282.21.2035
4. Celermajer DS, Sorensen KE, Georgakopoulos D, et al. Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults. Circulation. 1993;88(5 Pt 1):2149–2155. https://doi.org/10.1161/01.CIR.88.5.2149
5. Williams KJ, Tabas I. The response-to-retention hypothesis of early atherogenesis. Arterioscler Thromb Vasc Biol. 1995;15(5):551–561. https://doi.org/10.1161/01.ATV.15.5.551
6. Strong JP, Malcom GT, McMahan CA, et al. Prevalence and extent of atherosclerosis in adolescents and young adults: implications for prevention from the Pathobiological Determinants of Atherosclerosis in Youth Study. JAMA. 1999;281(8):727–735. https://doi.org/10.1001/jama.281.8.727
7. Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366(9493):1267–1278. https://doi.org/10.1016/S0140-6736(05)67394-1
8. Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670–1681. https://doi.org/10.1016/S0140-6736(10)61350-5
9. Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377(12):1119–1131. https://doi.org/10.1056/NEJMoa1707914
10. Tardif JC, Kouz S, Waters DD, et al. Efficacy and safety of low-dose colchicine after myocardial infarction. N Engl J Med. 2019;381(26):2497–2505. https://doi.org/10.1056/NEJMoa1912388
11. Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med. 1987;316(22):1371–1375. https://doi.org/10.1056/NEJM198705283162204
12. Libby P. Mechanisms of acute coronary syndromes and their implications for therapy. N Engl J Med. 2013;368(21):2004–2013. https://doi.org/10.1056/NEJMra1216063
13. Beltrame JF, Crea F, Kaski JC, et al. International standardization of diagnostic criteria for vasospastic angina. Eur Heart J. 2017;38(33):2565–2568. https://doi.org/10.1093/eurheartj/ehv351
14. Pepine CJ, Anderson RD, Sharaf BL, et al. Coronary microvascular reactivity to adenosine predicts adverse outcome in women evaluated for suspected ischemia: results from the National Heart, Lung and Blood Institute WISE study. J Am Coll Cardiol. 2010;55(25):2825–2832. https://doi.org/10.1016/j.jacc.2010.01.054
15. Criqui MH, Denenberg JO, Ix JH, et al. Calcium density of coronary artery plaque and risk of incident cardiovascular events. JAMA. 2014;311(3):271–278. https://doi.org/10.1001/jama.2013.282535
16. Reimer KA, Lowe JE, Rasmussen MM, Jennings RB. The wavefront phenomenon of ischemic cell death. 1. Myocardial infarct size vs duration of coronary occlusion in dogs. Circulation. 1977;56(5):786–794. https://doi.org/10.1161/01.CIR.56.5.786
17. Braunwald E, Kloner RA. The stunned myocardium: prolonged, postischemic ventricular dysfunction. Circulation. 1982;66(6):1146–1149. https://doi.org/10.1161/01.CIR.66.6.1146
18. Rahimtoola SH. The hibernating myocardium. Am Heart J. 1989;117(1):211–221. https://doi.org/10.1016/0002-8703(89)90685-6
19. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization. Circulation. 2022;145(3):e18–e114. https://doi.org/10.1161/CIR.0000000000001038
20. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease. Circulation. 2019;140(11):e596–e646. https://doi.org/10.1161/CIR.0000000000000678
21. Partida RA, Libby P, Crea F, Jang IK. Plaque erosion: a new in vivo diagnosis and a potential major shift in the management of patients with acute coronary syndromes. Eur Heart J. 2018;39(22):2070–2076. https://doi.org/10.1093/eurheartj/ehx786