Cardiovascular Disease Risk Factors

Atherosclerosis and Ischemic Heart Disease

• Familial predisposition to atherosclerosis and ischemic heart disease is likely polygenic.
• Hyperlipidemia is a major risk factor for atherosclerosis, with LDL cholesterol being the main component associated with increased risk.
• HDL cholesterol has an inverse relationship with symptomatic atherosclerosis, meaning higher levels of HDL lower the risk of ischemic heart disease.
• Hypertension is a major risk factor for atherosclerosis at all ages.
• Cigarette smoking is a well-established risk factor for atherosclerosis, particularly in men, and accounts for the recent increase in incidence and severity in women.
• Diabetes mellitus induces hypercholesterolemia and increases the predisposition to atherosclerosis, with the incidence of myocardial infarction being twice as high in diabetics as in non-diabetics.

Morphology of Atherosclerosis

• Fatty streaks are precursors to atheromatous plaques, composed of lipid-filled foam cells, T lymphocytes, and extracellular lipid.
• Atheromatous plaques are raised focal lesions within the intima, consisting of a core of lipid and a covering fibrous cap.
• Atherosclerotic plaques have three principal components: cells, connective tissue extracellular matrix, and intracellular and extracellular lipid deposits.

Complications of Atherosclerosis

• Patchy or massive calcification of arteries, leading to virtual pipe stems and brittle aortas.
• Focal rupture or gross ulceration of atheromatous plaques, resulting in thromboembolic events.
• Hemorrhage into a plaque, especially in coronary arteries.
• Aneurysm formation.

Pathogenesis of Atherosclerosis

• Focal regions of chronic endothelial injury lead to endothelial dysfunction.
• Increased endothelial permeability and leukocyte adhesion occur.
• Migration of monocytes into the intima and transformation into macrophages and foam cells.
• Adhesion of platelets to focal areas and migration of smooth muscle cells from the media into the intima.
• Enhanced accumulation of lipids both within cells and extracellularly.

Aneurysms

• Atherosclerotic aneurysms usually occur in the abdominal aorta and can rupture, causing retroperitoneal hemorrhage.
• Dissecting aneurysms occur in the thoracic aorta and can cause vascular occlusion and hemopericardium.
• Berry aneurysms occur within the brain and can rupture, causing subarachnoid hemorrhage.
• Capillary microaneurysms can occur in the retina, leading to diabetic retinopathy, or in the brain, leading to intracerebral hemorrhage.
• Syphilitic aneurysms are associated with syphilis and affect the thoracic aorta.
• Mycotic aneurysms result from weakening of the arterial wall due to fungal or bacterial infection, mainly affecting the cerebral arteries.

Giant Cell (Temporal) Arteritis

• Giant cell arteritis is an acute and chronic, often granulomatous, inflammation of medium-sized and small arteries.
• It affects the arteries in the head, particularly the temporal arteries, and can lead to blindness.
• Characteristically, short segments of one or more affected arteries develop nodular thickenings with reduction of the lumen, which may become thrombosed.
• Histologically, there is granulomatous inflammation of the inner half of the media, centered on the internal elastic membrane, with a mononuclear infiltrate, multinucleate giant cells, and fragmentation of the internal elastic lamina.

Buerger's Disease (Thrombo-Angiitis-Obliterans)

• Buerger's disease is a disease that affects medium-sized and small arteries, mainly the tibial and radial arteries.
• It is characterized by a heavy mixed inflammatory cell infiltrate, thrombosis of the lumen, and microabscesses.
• Complications include chronic ulcerations and gangrene to the toes and fingers.

Benign Tumors

• Hemangioma is a benign tumor characterized by an increased number of normal or abnormal vessels.
• Capillary hemangioma is composed of blood vessels that resemble capillaries, narrow, thin-walled, and lined by thin endothelium.
• Cavernous hemangioma is less common and is distinguished by the formation of large, dilated vascular channels.
• Pyogenic granuloma is a polypoid form of capillary hemangioma that occurs as a rapidly growing exophytic red nodule.
• Lymphangioma is the lymphatic analogue of hemangioma, with simple (capillary) and cavernous forms.

Angiosarcoma (Malignant Tumor)

• Angiosarcoma is a malignant endothelial neoplasm that can occur in both sexes and at any age, but is more common in older adults.
• It can arise in the skin, soft tissue, breast, and liver, and can also occur in the setting of lymphedema.
• Grossly, cutaneous angiosarcoma may begin as deceptively small, sharply demarcated, asymptomatic red nodules, but eventually becomes large, fleshy masses of pale gray-white soft tissue.