Atherosclerosis: Not “Inflammation and CAD,” but One Metabolico-Inflammatory Disease

The ESC review, titled “Inflammation and coronary artery disease,” is timely and valuable. It correctly draws attention to inflammatory biology, biomarkers, imaging, and therapeutic opportunities in coronary disease. Yet the title itself reveals a conceptual separation that can mislead: it places inflammation and coronary artery disease beside one another as though they were two distinct processes.

This wording matters because it may encourage physicians to think of inflammation as an additional factor that accompanies or aggravates CAD. In fact, atherosclerosis is a single, chronic, systemic metabolico-inflammatory disease. Its metabolic and inflammatory components are inseparable parts of one unified pathological process, and coronary artery disease is one of its possible clinical manifestations.

The purpose of this discussion is therefore not to oppose the ESC article. On the contrary, it is to support its attention to inflammation while asking for a more accurate pathological frame: not inflammation and coronary artery disease, but systemic metabolico-inflammatory atherosclerosis, with CAD as one of its manifestations.

Where the Process Begins

Atherosclerosis begins with disturbed lipid metabolism — not merely with an elevated cholesterol value, but with failure of the dynamic system that synthesizes, packages, transports, recognizes, clears, and processes lipoproteins.

When this system is disturbed, atherogenic lipoproteins persist in the circulation and enter the arterial wall. Some become retained beneath the endothelium and cannot be adequately removed. This retained material is the fundamental biological problem to which the organism must respond.

Genetic dyslipidaemias, including familial hypercholesterolaemia and elevated lipoprotein(a), can create a high burden from early life. Acquired dyslipidaemias related to insulin resistance, diabetes, obesity, kidney disease, endocrine disorders, diet, inactivity, or chronic illness can produce the same arterial challenge through other routes.

Inflammation Is the Response

Inflammation is not something separate that descends upon coronary disease from outside. It is the organism’s protective and compensatory response to retained lipid material and injury within the arterial wall.

The body attempts to solve the problem. Endothelial cells signal injury. Monocytes enter the vessel wall and become macrophages. Macrophages attempt to take up and process modified lipoproteins. Smooth-muscle and connective-tissue responses attempt to isolate the material and rebuild a stable arterial surface.

The atherosclerotic plaque is therefore not merely a passive deposit of cholesterol. It is an organised structure formed through the body’s attempt to contain material that it cannot fully eliminate. The fibrous cap is part of that protective architecture: it separates the lipid-rich plaque core from circulating blood.

Why Disease Becomes Chronic

If retained lipoproteins could be processed, removed, and followed by complete restoration of the arterial wall, progressive atherosclerosis would not develop. The problem is that the metabolic burden persists.

As retained particles remain in the wall, macrophages can become overloaded, foam cells form, some cells die, and their contents may not be cleared efficiently. The organism must continue its inflammatory and reparative work because the original problem remains unresolved.

This is why atherosclerosis is chronic. Inflammation is maintained not because it is an independent disease existing beside CAD, but because the body continues to confront retained and modified material that it cannot completely remove.

Waves of Injury and Repair

Atherosclerosis does not develop as a smooth, constant progression. It has a wave-like course: periods of injury and inflammatory activation are followed by periods of containment, partial healing, remodelling, and relative quiet.

Some cycles end with effective repair. The plaque becomes more fibrous, more stable, and may remain clinically silent for years. Other cycles resolve incompletely, leaving behind additional lipid debris, damaged tissue, altered connective structure, impaired endothelial recovery, and less capacity to withstand the next episode.

Over decades, these incomplete cycles can gradually change a stable plaque into a vulnerable one. The important point is that the danger does not arise simply because inflammation is present. It arises when the normal compensatory processes of inflammation, containment, healing, and restoration can no longer maintain the integrity of the arterial wall.

Acute Events Are Failed Repair

Myocardial infarction, ischemic stroke, and acute limb ischemia should not be described simply as consequences of “inflammation.” They are clinical consequences of disturbed inflammation and failed repair in a plaque that has become structurally vulnerable.

When a fibrous cap ruptures or the endothelial surface erodes, plaque material is exposed to blood. Thrombosis then develops. Initially, this too can be understood as an emergency reparative response intended to cover an injured arterial surface.

The emergency becomes dangerous when the thrombotic response is excessive, unstable, poorly organised, obstructs blood flow, or sends emboli downstream. Thus, the acute event reflects a failure of long-term metabolico-inflammatory containment and repair — not the mere existence of inflammation.

CAD Is a Manifestation

Coronary artery disease is the manifestation of this process in the coronary arteries. In another patient, the same systemic disease may appear first in the carotid arteries, cerebral circulation, aorta, renal arteries, or lower-extremity arteries.

Atherosclerosis is systemic, although it is distributed unevenly. Local blood flow, branching patterns, arterial-wall structure, mechanical stress, endothelial biology, plaque composition, and the capacity for repair influence which arterial territory becomes clinically visible first.

Therefore, when atherosclerosis is identified in one arterial bed, the clinician should think systemically. Coronary disease should prompt consideration of disease elsewhere when symptoms, examination, risk, or clinical decisions justify further assessment; similarly, peripheral or carotid disease should raise concern for possible coronary involvement.

A Title That Shapes Understanding

The ESC article should be supported because it brings needed attention to inflammatory mechanisms, biomarkers, imaging, and therapeutic possibilities in coronary disease. Its focus on CAD is appropriate and should be retained.

At the same time, the wording “Inflammation and coronary artery disease” may unintentionally suggest that inflammation and CAD are separate processes. This is more than a semantic issue: titles influence how physicians understand disease mechanisms and therapeutic priorities.

A more coherent reading preserves the article’s coronary focus while recognizing that inflammation is not added to CAD from outside. Coronary atherosclerosis is a clinical manifestation of one systemic, chronic metabolico-inflammatory process. Thus, the article is best understood as addressing the inflammatory and reparative biology of coronary manifestations of systemic atherosclerosis, rather than two independent entities — inflammation and coronary artery disease.

Therapeutic Meaning

This framework changes the purpose of treatment. Therapy should not aim simply to suppress inflammation, because inflammation is necessary for defence, containment, and tissue repair. The goal is to reduce the persistent metabolic burden that forces the arterial wall into chronic inflammation, while supporting orderly repair and preventing its disturbance.

Clinical treatment of atherosclerosis, including CAD, should therefore:

• Reduce the burden of atherogenic lipoproteins and address the specific dyslipidaemic phenotype

• Identify familial hypercholesterolaemia, elevated Lp(a), and other inherited contributors where appropriate

• Correct acquired metabolic drivers such as diabetes, insulin resistance, obesity, hypertension, smoking, kidney disease, and endocrine disorders

• Use anti-inflammatory therapy selectively to modulate harmful, unresolved inflammatory activity rather than treating inflammation as an isolated disease

• Use antithrombotic treatment and revascularisation when clinically indicated, while recognising that neither removes the systemic process that produced the plaque

• Treat the patient over time, because atherosclerosis is a lifelong trajectory of metabolic burden, inflammation, repair, compensation, and possible decompensation

The central message is straightforward: atherosclerosis is not inflammation plus CAD. It is one systemic metabolico-inflammatory disease in which inflammation is the body’s attempt to solve a persistent arterial lipid problem. CAD is one clinical expression of that disease, and acute events occur when the mechanisms of containment and repair are disturbed or fail.

You can learn more by reading h=these our e-books: 1) Iabluchanskyi M., Yabluchanskiy A. Atherosclerosis: Bridging Genetics, Inflammation, and Clinical Realities, and 2)  Iabluchanskyi M., Shlyakhover V., Garkaviy P., Yabluchanskiy A. The Uncharted Architecture of Atherosclerosis: Beyond Lipid Panels — Functional Subspecies, Risk Stratification, and Targeted Therapy.

Mykola Iabluchanskyi together with Andriy Yabluchanskiy