Atheroembolization

Atherosclerosis

The process of atherosclerosis may begin as early as childhood, developing slowly with effects rarely manifesting before the fourth or fifth decades of life. Traditional risk factors include hypertension, diabetes, smoking, and hypercholesterolemia.

Atherosclerosis can affect any artery, but the most frequently affected are the large and medium-sized arteries. Intravascular sites of blood turbulence, such as bifurcations, favor the development of atherosclerotic lesions. Initial changes in arterial wall morphology result in the formation of fatty streaks that consist of lipid-engorged macrophages in the arterial intima. Progression of such precursor lesions occurs secondary to an inflammatory process initiated by endothelial injury and dysfunction. Insufficient nitric oxide production results in increased adhesion and aggregation of platelets. Up-regulation of the expression of endothelial adhesion molecules and selectins leads to the accumulation of monocytes and T lymphocytes. These cells become activated and produce growth factors, cytokines, and chemokines. Smooth muscle cells migrate from the media into the intima and proliferate. In time, these lesions develop into raised, fibrous plaques consisting of a fibrous cap covering a core containing necrotic material, lipids, and cholesteryl esters. This advanced plaque forms the base onto which the complex plaque develops, consisting of fissures, erosions, or ulceration. Interest has increased in the role of monocytes and macrophages in the pathogenesis of plaque progression and rupture, processes that are related to thrombosis, embolism, and clinical manifestations.

Atheromatous embolization

Atheromatous embolization is a descriptive term for embolization of any atheromatous material. Atheroembolization refers to the dislodgment of vascular plaque material that contains cholesterol crystals, red blood cells, and fibrin. This “cholesterol emboli” syndrome comprises renal failure, skin lesions, blue toes, and neurologic manifestations. It can develop spontaneously (because of plaque rupture) or after the use of thrombolytics or anticoagulants, or result from arterial manipulation (during surgical procedures, cardiac catheterization, insertion of an intraaortic balloon pump [IABP], percutaneous aortic valve replacements [transcatheter aortic valve implantation (TAVI)], and aortic endo-stent placements [thoracic endovascular aortic repair/endovascular aortic repair (TEVAR/EVAR)]). Disruption of a vascular plaque results in the release of cholesterol crystals with subsequent downstream vascular obstruction and initiation of an inflammatory process with lymphocytic and mononuclear cell infiltration. Biopsy specimens of affected organs such as skin or kidneys are usually diagnostic.

Plaque morphology and embolic risk

Severe atherosclerosis of the ascending aorta appears to be the most important morphologic indicator of an increased risk of atheromatous embolization. The French Aortic Plaque in Stroke group identified a plaque thickness of 4 mm or greater on transesophageal echocardiogram (TEE) as an independent predictor of recurrent embolization. ^, Plaque ulceration and morphology may contribute to an increased risk of embolic events, with evidence of pedunculated, mobile plaques and the absence of calcium conferring a higher risk. ^, The cerebral embolic risk is also influenced by plaque location; as complex plaques are more frequent distal to the ascending aorta, there is increased risk to the left cerebral hemisphere and the peripheral circulation.

Macroembolization and microembolization

Emboli can be divided into macroemboli and microemboli, also described as thromboembolism and atheroembolism . Despite sharing the same underlying pathophysiology, clinical manifestations differ. Thromboemboli affect arteries larger than 200 μm in diameter, whereas atheroemboli affect smaller arteries, arterioles, and capillaries. Macroemboli may cause overt clinical presentations (e.g., stroke or peripheral ischemia), whereas microemboli tend to be more occult in their manifestations of end-organ injury or dysfunction (e.g., renal injury, neuropsychological impairment). Embolization may arise spontaneously or be related to vascular interventions and cardiovascular surgery. The complex aortic plaque–related 3-year mortality is reported to be as high as 20%.

Cerebral

As the prevalence of aortic atherosclerotic disease increases with age, so does the rate of atheromatous embolization. Postmortem studies indicate that it affects 20% of patients in their fifth decade, increasing to 80% in those in their eighth decade. Emboli from the atherosclerotic thoracic aorta commonly result in stroke (50%) and transient ischemic attack (35%), with the middle cerebral artery being the most frequent site of arterial embolism. Stroke has profound effects; outcomes from acute stroke are measured in terms of survival, functional independence, and financial cost. Survival after stroke is significantly poorer than after myocardial infarction (MI) or most cancers and is the leading cause of disability in developed countries.

Cholesterol emboli (atheroembolization) are an important and frequently unrecognized cause of stroke. Microembolization is a recognized cause of more subtle, sometimes subclinical neurologic injury. ^, This injury is manifested by subtle changes in cognitive function that may only be evident on detailed neuropsychological testing ^, and include amaurosis fugax, transient ischemic attack, and confusional state. Rarely, embolization to the spinal cord can lead to lower extremity paralysis. The importance of microembolization has increased over recent years, particularly in patients undergoing coronary artery bypass surgery (CABG); nevertheless, the evidence suggests that the late cognitive decline between 1 and 5 years after surgery may be secondary to high rates of cerebrovascular disease among patients who need CABG. A history of hypertension and other cardiovascular risk factors are known to be associated with increased risk for long-term cognitive decline.

Cardiac

Atherosclerotic disease is the leading cause of death in developed countries. Every year it results in over 19 million deaths worldwide, and coronary heart disease accounts for the majority of those. Most acute coronary syndromes are caused by plaque rupture. Distal embolization of cholesterol and atheromatous material may be important in the pathogenesis of some acute coronary syndromes. The occurrence of distal coronary embolization in the setting of acute coronary syndromes has been followed using serum levels of cardiac troponins to detect small degrees of myocardial necrosis. Embolization after percutaneous coronary interventions is well recognized, and elevated troponins are seen in up to 44% of patients. ^,

Peripheral

Peripheral emboli most frequently lodge in the lower extremities. Cholesterol atheroembolization may be subclinical or result in systemic effects. Although renal, neurologic, and cutaneous manifestations tend to dominate the clinical picture, involvement of most organs has been reported.

Cholesterol embolization frequently manifests as acute kidney injury ^, and can even lead to renal failure. ^, In those cases, renal biopsy is diagnostic. Cutaneous manifestations, including livedo reticularis and “blue-toe” syndrome, are the most common signs of atheroembolism, occurring in up to 34% of cases. Atheroemboli from the carotid vessels give rise to retinal emboli, resulting in visual symptoms. The mesenteric circulation may also be affected, resulting in small bowel bleeding and intestinal infarction. The pancreas, spleen, liver, and gallbladder may also be involved. More rarely, involvement of transplanted viscera such as the kidney may result in renal failure.