Etiology

Coronary atherosclerotic disease is the underlying cause in nearly all patients with acute myocardial ischemia. The most common cause of unstable angina(UA) is coronary artery narrowing caused by a thrombus that develops on a disrupted atherosclerotic plaque and is usually nonocclusive.[2]

A less common cause is intense vasospasm of a coronary artery (variant or Prinzmetal angina, ischemia and no obstructed arteries [INOCA], or secondary to cocaine use). This intense vasospasm is caused by vascular smooth muscle or by endothelial dysfunction in INOCA.

Pathophysiology

The initiating lesion in coronary artery disease (CAD) is a fissure in the vessel endothelial lining over an underlying cholesterol plaque, which results in a loss in the integrity of the plaque cap. Plaques that fissure or rupture tend to have a thin fibrous cap, a high lipid content, few smooth muscle cells, and a high proportion of macrophages and monocytes.[16][17]

The fissure or plaque rupture leads to exposure of subendothelial matrix elements (e.g., collagen), stimulating platelet activation and thrombus formation. Release of tissue factor directly activates the coagulation cascade and promotes the formation of fibrin.

If an occlusive thrombus forms, the patient may develop an acute ST-segment elevation myocardial infarction unless the affected myocardium is richly collateralized. If the thrombus formation is not occlusive, the patient may develop non-ST-elevation myocardial infarction/UA with nonspecific ST changes on the ECG (ST depression or T-wave changes).

Arterial inflammation caused by or related to infection may cause plaque destabilization and rupture and precipitate acute coronary syndrome (ACS). Activated macrophages and T lymphocytes located at the shoulder of a plaque increase the expression of enzymes such as metalloproteinase that may cause thinning and disruption of the plaque, leading to ACS.[18]

Myocardial supply and demand mismatch may cause ischemia without significant CAD. These include:

  • Increased myocardial oxygen requirements such as fever, tachycardia, thyrotoxicosis

  • Reduced coronary blood flow: for example, hypotension

  • Reduced myocardial oxygen delivery such as anemia or hypoxemia

In patients with prior ACS with coronary stents, stent thrombosis or in-stent restenosis may cause ST-elevation myocardial infarction, non-ST-elevation myocardial infarction, or UA. Both stent thrombosis and restenosis have complex causes, triggers, pathophysiology, and risk factors. Of importance, premature cessation of antiplatelet agents in patients with stents (drug-eluting and bare-metal) may trigger an ACS.[1][2]

Classification

Classification of acute coronary syndrome (ACS)[1]​​[2]

The term ACS is used to describe the spectrum of conditions that includes UA, non-ST-elevation myocardial infarction (non-STEMI), and ST-elevation myocardial infarction (STEMI).

The classification of patients is based on ECG findings. Patients are divided into two categories:

  1. Chest pain with persistent ST segment elevation (>20 minutes) on ECG is classified as STEMI.

  2. Chest pain with no persistent ST segment elevation is classified as non-ST-elevation ACS. The ECG changes may include transient ST segment elevation, ST depression, T wave inversion, or pseudonormalization of T wave, or the ECG may be normal.

Further categorization of non-ST-elevation ACS is by measurement of cardiac biomarkers:

  • Elevated: non-STEMI

  • Nonelevated: UA

Specific clinical findings in UA include prolonged (>20 minutes) angina at rest, new onset of severe angina; angina increasing in frequency, longer in duration or lower in threshold; or angina that occurs after a recent episode of myocardial infarction.[1]

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