Atherosclerosis, or athero for short, is the

progressive buildup of plaque fatty

deposits and other cells in the walls of
the arteries. Its name comes from the
Greek words athero (meaning gruel or
paste) and sclerosis (hardness).

There are two types of plaque that can

form in the artery walls:
Stable plaque has a thick fibrous
cap made of smooth muscle cells
covered by endothelial cells. As
plaque grows, it can reduce blood
flow to the brain, heart, or other
parts of the body.
Unstable plaque is more
dangerous because it has a thin
cap. As a result, it may rupture,
causing an acute, life-threatening
thrombosis when this occurs in
the heart it is termed a myocardial
infarction, or heart attack.

Atherosclerotic cardiovascular disease is the leading cause of death in the world. Atherosclerosis
typically begins in early adolescence, and is found in major arteries, yet is asymptomatic and not
detected by most diagnostic methods during life. Traditional risk factors for atherosclerosis are high
low density lipoprotein (LDL) cholesterol, high blood pressure, family history, diabetes, smoking,
obesity, being post-menopausal for women and being older than 45 for men. As the patient ages,
arterial plaque can build up and restrict blood flow. Over time this disease can eventually chronically
clog the arteries, or result in an acute thrombotic event, limiting or blocking blood flow. According to
United States data for the year 2004, for about 66% of men and 47% of women, the first sign of
atherosclerotic cardiovascular disease is heart attack or sudden cardiac death (death within one
hour of onset of the symptom).

Diagnosis
Areas of severe narrowing, stenosis, detectable by angiography, and to a lesser extent "stress
testing" have long been the focus of human diagnostic techniques for cardiovascular disease, in
general. However, these methods focus on detecting only severe narrowing, not the underlying
atherosclerosis disease. As demonstrated by human clinical studies, most severe events occur in
locations with heavy plaque, yet little or no lumen narrowing present before debilitating events
suddenly occur. Plaque rupture can lead to artery lumen occlusion within seconds to minutes, and
potential permanent debility and sometimes sudden death.
Consequences
Because plaque tends to build up slowly in the arteries, atherosclerosis may have no symptoms until
the artery becomes severely narrowed or completely blocked. The consequences of atherosclerosis
can be severe and far-reaching, including:
Coronary artery disease (CAD) can result when blood flow is restricted to parts of the heart.
Restricted blood flow may cause chest pain (also called angina) and heart attack, while other
complications include post-myocardial infarction heart failure.
Stroke and transient ischemic attack (TIA). Atherosclerosic plaques can rupture generating a
thrombus that can travel to the brain. TIAs can occur if blood supply to part(s) of the brain is
temporarily blocked but flow is restored before significant damage. Stroke can occur when
the blockage persists long enough to impart permanent damage, and can be very serious.
TIA often has some of the same symptoms as stroke, although symptoms normally pass
within one hour up to 24 hours. It may not be as serious as stroke, but it is considered a
warning for future attacks and stroke.
Peripheral arterial disease (PAD) occurs when blood flow to the arms or legs is limited. PAD
can cause pain and numbness and, if left unchecked, can result in tissue death or gangrene.
High blood pressure or kidney failure, if atherosclerosis happens in the arteries leading to
kidneys.

Treatment options
Living a healthy lifestyle that incorporates good nutrition, weight management and routine physical
activity can play a big role in avoiding atherosclerosis. However, for most people, pharmacologic
treatment of risk factors, described below, has proven to be a more effective strategy toward
cardiovascular disease risk reduction compared with lifestyle modification. If atherosclerosis leads to
symptoms, some symptoms such as angina pectoris can be treated. Non-pharmaceutical means are
usually the first method of treatment, such as cessation of smoking and practicing regular exercise. If
these methods do not work, medicines are usually the next step in treating cardiovascular diseases,
and, with improvements, have increasingly become the most effective method over the long term.

LDL-lowering agents
An elevated level of LDL is a major risk factor for atherosclerosis. Since 1987, statins, or HMG-CoA
reductase inhibitors, have been used to reduce LDL cholesterol levels in patients with
hypercholesterolemia. Statins have relatively few short- or long-term undesirable side-effects and
have become the standard-of-care for treatment of hypercholesterolemia and CAD risk reduction.
Several clinical trials comparing statin treatment with placebo have consistently shown strong
effects in reducing atherosclerotic disease 'events' (e.g., heart attack) and cardiovascular mortality
by about 25-35%.

Relatively newer drugs for hypercholesterolemia include cholesterol absorption inhibitors (e.g.,
ezetimibe), which modestly reduce LDL cholesterol levels when given as monotherapy, and
proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. The latter class of drugs include
therapeutic antibodies (Praluent, Repatha) and small interfering RNA (Leqvio). Both approaches
robustly reduce LDL cholesterol, with Leqvio offering the additional convenience of twice-yearly
dosing.

Anti-platelet medications.
Anti-platelet medications, such as aspirin, can reduce the likelihood that platelets will clump in
narrowed arteries, form a blood clot and cause further blockage.
Primary and secondary prevention
Combinations of statins, intestinal cholesterol absorption-inhibiting supplements (ezetimibe and
others, and to a much lesser extent fibrates) have been the most successful in changing common but
sub-optimal lipoprotein patterns and group outcomes (although fibrates have not yet been shown to
affect outcomes). Recently, a clinical trial with an antibody to the pro-inflammatory cytokine IL-1 ,
has proven that suppression of inflammation is beneficial in patients with cardiovascular disease and
high inflammation. Administration of the antibody, even in patients with good lipid levels, reduced
the frequency of cardiovascular events.

Surgical intervention
Other physical treatments, helpful in the short term, include minimally invasive angioplasty
procedures that may include stents to physically expand narrowed arteries and major invasive
surgery, such as bypass surgery, to create additional blood supply connections that go around the
more severely narrowed areas.

Diet and dietary supplements

Dietary, rather than pharmacologic, interventions to achieve benefit have been controversial,
generally far less effective and less widely adhered to with success. One reason for this is that most
cholesterol, typically 80-90%, within the body, is created and controlled by internal production by all
cells in the body (true of all animals), with typically slightly greater relative production by
hepatic/liver cells. From a dietary perspective, the primary driver of hypercholesterolemia is intake
of saturated fat.

Facts and Figures