Atherosclerosis is a disease of arterial blood vessels. Veins are
not involved unless surgically moved to function as an artery.
Atherosclerosis is commonly referred to as a "hardening of blood
vessels", but this is not precise. Vascular lesions known as
atheromatous plaques or atheromata are formed in the vessel wall, which may
reduce or restrict blood flow in the inside of the artery. When the inner
covering of an unstable atheroma breaks, it may lead to excessive internal
bleeding into the plaque, very often leading to severe health conditions
and even death. ‘Athero’ is porridge in Latin, as the plaque changes have a
foamy appearance under high power light microscopy. ‘Sclerosis’ denotes
Atherosclerosis typically begins in later childhood, is usually
found in most major arteries, and yet is asymptomatic and not detected by
most diagnostic methods during life. It becomes serious when interfering
with the circulation of blood to the heart or the brain, and is considered
the most important underlying cause of strokes, heart attacks, various
heart diseases including congestive heart failure. For about 59% of men and
women, the first symptom of atherosclerosis is heart attack.
Most artery flow disrupting events occur at locations with less than
50% lumen narrowing. Cardiac stress testing, the most commonly performed
non-invasive testing method for blood flow limitations generally only
detects lumen narrowing of about 75% or greater, although some physicians
advocate that nuclear stress methods can detect as little as 50%.
Atherogenesis refers to the state of having many lesions present in
many arteries. It is characterized by remodeling of arteries involving an
accumulation of these atheromatous plaques, which contain an excess of
fatty cellular membranes within the arterial wall. The plaques are always
located between the epithelial lining and muscular portion of the artery
wall, typically without producing any narrowing of the artery opening.
The resident cells within the artery wall seem to signal an
intrusion and an inflammation response. Monocytes, one of the 5 main types
of white blood cells circulating in the blood, enter the artery wall.
Within tissues, monocytes change characteristics and are called
macrophages. The macrophages ingest oxidized cholesterol, slowly turning
into large "foam cells" – so described because of their appearance
to accommodate their high lipid content. Foam cells eventually die, and
further propagate the inflammatory process.
Small calcium deposits form within vascular smooth muscle cells of
the surrounding muscular layer, specifically in the muscle cells adjacent
to the atheromas. In time, as cells die, this leads to extracellular
calcium deposits between the muscular wall and outer portion of the
Cholesterol is delivered into the wall by minute LDL particles (low
density lipoprotein). To attract and stimulate macrophages, the cholesterol
must be released from the LDL particles and oxidized, a key step in the
ongoing inflammatory process. Additionally, the macrophages must be unable
to remove excess cholesterol fast enough, into functioning HDL particles
(high density lipoprotein) to avoid becoming foam cells and dying.
A protective fibrous cap normally forms between the fatty deposits
and the artery lining (the intima). These capped fatty deposits (atheromas)
produce enzymes, which cause the artery to enlarge. The artery becomes
expanded and egg shaped, still with a circular opening. If the enlargement
is beyond proportion to the atheroma thickness, then an aneurysm is
created. This process usually starts in childhood and continues, thereby
making the diagnosis very difficult.
However, atheromas within the vessel wall are soft and fragile with
little elasticity. Arteries constantly expand and contract with each
heartbeat. In addition, the calcification deposits between the outer
portion of the atheroma and the muscular wall, lead to a loss of
elasticity, stiffening, of the artery as a whole. Although the disease
process tends to be slowly progressive over decades, in later stages, it
also becomes unstable with repetitive sudden problems, most without obvious
symptoms at the time of occurrence. These problems result from instability
of the newer, soft atheromas.
If the fibrous cap separating a soft atheroma from the bloodstream
within the artery ruptures, atheroma tissue fragments are exposed and
released. Atheroma tissue fragments are very clot promoting; they attract
blood platelet accumulation and activate the blood clotting system
proteins. This leads to a temporary patch covering and partial narrowing
(stenosis) within the artery lumen. However, sometimes the combination of
atheroma material release, platelet accumulation and accumulation of blood
clotting proteins may suddenly create a near complete obstruction. The
obstruction, either at the site of rupture, or as a result of debris sent
downstream, prevents adequate blood flow to cells downstream. Cells starved
for adequate blood supply are injured and may die.
Areas of severe narrowing, detectable by angiography, and to a
lesser extent "stress testing" have long been the focus of human
diagnostic techniques for heart disease and cardiovascular diseases.
However, these methods focus only on detecting severe narrowing, not the
underlying atherosclerosis disease. Plaque rupture can lead to artery lumen
occlusion within seconds to minutes, and potential permanent debility and
sometimes sudden death.
75% lumen stenosis used to be considered by cardiologists as the
hallmark of clinically significant disease because it is only at this
severity of narrowing of the larger heart arteries that recurring episodes
of angina and detectable abnormalities by stress testing methods are seen.
However, clinical trials have shown that only about 14% of clinically
debilitating events occur at locations with this, or greater severity of
narrowing. The majority of events occur due to atheroma plaque rupture at
areas without narrowing sufficient enough to produce any angina or stress
test abnormalities. Though any artery in the body can be involved, usually
only severe narrowing or obstruction of some arteries, those that supply
more critically important organs, are recognized. Obstruction of arteries
supplying the heart muscle result in a heart attack while obstruction of
arteries supplying the brain result in a stroke.
These anatomic, physiological & behavioral risk factors for
atherosclerosis are known:
· Documented atheroma
in any artery (unfortunately not detected by most medical tests)
· Having diabetes or
just upper normal blood glucose and insulin levels
(cholesterol and triglyceride level disturbances):
· Having a high or
elevated blood concentration of low-density lipoprotein (LDL, "bad
· Having a low
concentration of functioning high-density lipoprotein (HDL, "good
· Higher fibrinogen
· Homocysteine in the
upper half of the normal range, and especially elevated levels
· Tobacco smoking,
even just once a day
· Having close
relatives who had heart disease or a stroke at a relatively young age
· Having high blood
· Having trouble
managing stress, especially anger
· Being obese
(especially central obesity, i.e. fat at waist level more than fat below
· Several internal
chemical markers indicating ongoing inflammation may also relate to
Most humans develop arteriosclerosis. Usually only
"high-risk" patients are advised to change dietary choices,
exercise, lose weight, take cholesterol-lowering mediation and lower blood
sugar levels. Most of the proven, more effective cholesterol medications
are only available by prescription. There is ongoing debate about what
dietary changes are wisest and how to adjust these for different people.
If arteriosclerosis leads to symptoms, the symptoms can be treated.
Medicines are usually the first step in treating cardiovascular diseases,
and with improvements, have increasingly become the most effective method
over the long term. However, medicines are criticized for their expense,
patented control and occasional undesired effects.
Lipoprotein imbalances, diabetes, high blood pressure, stopping
smoking, taking anticoagulants (anti-clotting agents) which target
platelets, taking Omega 3 oils from salt-water fish meats, exercising and
losing weight are the usual focus of treatments which have proved to be
helpful in clinical trials.
Dramatic lowering of lipoprotein levels, including to very
abnormally low levels for adults (and especially the smaller lipoprotein
particles), and elevating the large particle (HDL) can slow, stop, or even
partially reverse the buildup of plaque, as demonstrated in clinical
trials. This can be achieved with large daily doses of niacin (B3).
Combinations of statins, niacin, cholesterol absorption inhibiting
supplements (ezetimibe). Evidence has increased that people with diabetes,
though without clinically detectable atherosclerotic disease, have more
severe debility from atherosclerotic events over time than even
non-diabetics who have already suffered atherosclerotic events. Thus
diabetes has been upgraded to be viewed as an advanced atherosclerotic
Aerobic exercise, weight loss, and dietary changes can also help in
major ways, but are often more problematic for many to achieve and continue
Medical treatments often focus predominantly on the symptoms. Over
time, the treatments which focus on decreasing the underlying
atherosclerosis processes, as opposed to treating the symptoms resulting
from the atherosclerosis, have been shown by clinical trials to be more
Other physical treatments, helpful in the short term, include
minimally invasive angioplasty procedures to physically expand narrowed
arteries and major invasive surgery, such as bypass surgery, to create a
blood supply connection which goes around the more severely narrowed areas.
In summary, the key to more effective approaches has been better
understanding of the insidious nature of the disease and to combine
multiple different treatment strategies, not rely on just one or a few
approaches. Additionally, for those approaches, such as lipoprotein
transport behaviors, which have been shown to produce the most success,
being more treatment aggressive has generally produced better results, both
before and especially after people are symptomatic. However treating
asymptomatic people remains controversial.