Complications of Atherosclerosis

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Complicated Atherosclerotic Plaques:  A complicated plaque is characterized by erosion, ulceration or fissuring of the surface of the plaque; plaque hemorrhage; mural thrombosis; calcification; and/or aneurysm formation.

         Aneurysm formation:  A complicated plaque extends into the media of an elastic artery and so weakens the wall to result in the formation of an aneurysm, typically in the abdominal aorta. At a certain size, these aneurysms may suddenly rupture and cause a vascular catastrophe.

         Calcification occurs in areas of necrosis and elsewhere in the plaque. Calcification in the artery is thought to depend on focal mineral deposition and resorption, which is regulated by osteoblast-like and osteoclast-like cells in the vessel wall.

         Mural thrombosis results from abnormal laminar and/or turbulent blood flow around the plaque that protrudes into the lumen. The disturbance in flow causes damage to the endothelial lining, which may become dysfunctional or locally denuded and is no longer an effective thromboresistant surface. Thrombi often form at sites of erosion and fissuring on the surface of the fibrous cap of the plaque. Mural thrombi may embolize to more distal sites.     A thrombus formed over an atherosclerotic plaque may detach, become an embolism and lodge in a distal vessel. Ulceration of an atherosclerotic plaque may also dislodge atheromatous debris and produce so-called cholesterol crystal emboli, which appear as needle-shaped spaces in affected tissues, most commonly in the kidney.

         Vulnerable atheroma has structural and functional alterations that predispose the fibroinflammatory lipid plaque to plaque destabilization.

         Atheroma destabilization, resulting often in acute coronary syndromes, may occur at any time when the dynamic balance of opposing biological and physical processes is disrupted, leading to occlusive thrombosis, fibrous cap rupture, and occlusive thrombosis, or intraplaque hemorrhage and rupture. Clinically silent ruptures have been demonstrated, indicating that they can heal.  Once the fibrous cap ruptures, the thrombogenic material in the plaque will usually promote thrombosis in the lumen, resulting in the formation of an occlusive thrombus.  Most plaques that rupture show less than 50% luminal stenosis, and over 95% display less than 70% stenosis. Plaque rupture often occurs at the shoulder of the plaque, suggesting that hemodynamic shear stress plays a role in weakening and tearing the fibrous cap. If not repaired, endothelial loss leads to erosion of the plaque, thereby weakening the fibrous cap and exposing the plaque to blood constituents. Plaque rupture has been associated with (1) areas of inflammation, (2) large lipid core size, (3) thin fibrous cap, (4) reduced number of smooth muscle cells owing to apoptosis, and (5) imbalance of proteolytic enzymes and their inhibitors in the fibrous cap, (6) calcification in the plaque, (7) intraplaque hemorrhage leading to inside-out rupture of the fibrous cap.  

         Acute coronary syndromes:  Coronary artery disease is the leading cause of mortality in the western world.  Acute coronary syndromes (ACS) are characterized clinically  into three groups, patients with unstable angina, those with non-ST elevation myocardial infarction (non-STEMI) and those with ST elevation myocardial infarction (STEMI).  These conditions have similar pathophysiology although each has different clinical features, therapies, and prognosis.  The presence of atherothrombotic coronary artery occlusion due to plaque rupture and superimposed thrombosis with our without distal embolization is the common pathophysiology of ACS.  The extent of lumen occlusion and the role of vasospasm is variable, so that patients with unstable angina may only have non-occlusive thrombi leading to reduced myocardial perfusion while those with acute myocardial infarction may have a thrombotic occlusion of the coronary artery. 

         Plaque rupture may also heal without clinical complications. Plaque hemorrhage due to rupture of thin, newly formed vessels within the plaque, may occur within the plaque with or without a subsequent rupture of the fibrous cap. In the latter case the hemorrhage may result in expansion of the size of the plaque, thus narrowing the lumen further. The hemorrhage will be resorbed over time within the plaque, and residual hemosiderin-laden macrophages persist as evidence of a previous hemorrhage.

         Several circulating markers have been associated with plaque burden, including C-reactive protein, fibrinogen, soluble VCAM, IL-1, IL-6, and TNF.