Atherosclerosis

Atherosclerosis is a disease process in which cholesterol accumulates in the walls of an artery. It is a chronic process, that gradually leads to stenosis, or narrowing, of the artery. The rupture of an atherosclerotic plaque can lead to the formation of a thrombus, which can occlude an artery, preventing the flow of blood. Depending on the location of the artery, this can lead to a variety of medical presentations.

Epidemiology

Atherosclerosis generally does not affect individuals below the age of 35. While cholesterol may be transiently deposited, it is quickly removed. Above the age of 35, reports of prevalence are highly variable. Some studies report ranges of between 2.5% and 31.7% in asymptomatic individuals.

Risk Factors

A number of risk factors predispose to the formation of atherosclerosis. These include:

• age (over the age of 40)
• male gender
• genetic predisposition/family history
• hypertension
• high total cholesterol, LDL and triglycerides
• low HDL and total cholesterol:LDL ratio
• obesity, particularly around the abdomen
• poor diet, high in saturated and trans-saturated fats
• lack of physical exercise

Disease Process

Cholesterol circulates in the bloodstream contained in molecules called lipoproteins. The two most common forms are high-density lipoproteins ("good cholesterol", which reduces atherosclerosis) and low-density lipoproteins ("bad cholesterol", which increases atherosclerosis).

The wall of an artery is made of up three layers - the innermost tunica intima, the muscular tunica media, and the outer tunica adventitia. Atherosclerosis affects the inner two layers. It is initiated by injury to the wall of an artery. In most cases, this is due to high blood pressure. This increases the permeability of the tunica intima, allowing the passage of lipoproteins and white blood cells called macrophages to the space between the tunica intima and media. Macrophages are responsible for engulfing debris through the process of phagocytosis, which allows its removal from the body. When they phagocytose lipoproteins, they trap the cholesterol in the artery wall, and become foam cells.

The macrophages release chemicals known as cytokines, which cause an inflammatory response. This results in the migration of smooth muscle cells, or myofibroblast, which lays a fibrous outer shell around the foam cells. The foams cells eventually die, resulting in the trapping of cholesterol and cellular debris inside the shell. The shell and its lipid core is known as a plaque, or atheroma. Occasionally cholesterol may crystallise within the plaque, forming cholesterol clefts.

Over time, a number of plaques may form within the wall of an artery, some of which may combine to form larger plaques. This leads to a narrowing of the lumen of the artery, constricting the flow of blood. Depending on the artery affected, this may present as a variety of symptoms, including ischemic heart disease (coronary arteries), syncope (carotid arteries) or hypertension (renal arteries). Plaques can be either stable or unstable depending on the ratio of their shell thickness to liquid core, with a lower ratio corresponding to a less stable plaque. Unstable plaques may be eroded or rupture into the lumen of an atery, spelling their contents into the blood. This can lead to the formation of a thrombus, which can further occlude the flow of blood. Large thrombi may completely prevent the passage of red blood cells, leading to ischemia and infarction of the supplied tissue.

Investigation

Atherosclerosis is not generally investigated unless it causes clinical symptoms/signs. While it is not possible to visualise the plaque within the wall of the artery, it is possible to measure its effects through either a doppler ultrasond or an angiogram. A doppler ultrasound measures the flow of blood through an artery using a probe which is placed on the skin. An angiogram involves injecting arteries with radioopaque dye, and then taking x-rays to identify any areas of constriction.

Serum cholesterol is often routinely measured. Elevated levels (hypercholesterolemia) can indicate an increased risk of atherosclerosis, and a need for lifestyle modification or pharmacological treatment.