Atherosclerosis is a disease in which the inside of an artery narrows
due to the build up of plaque. Initially, there are generally no
symptoms. When severe, it can result in coronary artery disease,
stroke, peripheral artery disease, or kidney problems depending on the
arteries affected. Symptoms, if they occur, generally do not begin
until middle age.
The exact cause is not known. Risk factors include high blood
pressure, diabetes, smoking, obesity, family history, and an unhealthy
diet. Plaque is made up of fat, cholesterol, calcium, and other
substances found in the blood. The narrowing of arteries limits the
flow of oxygen-rich blood to parts of the body. Diagnosis is based
upon a physical exam, electrocardiogram, and exercise stress test,
Prevention is generally by eating a healthy diet, exercising, not
smoking, and maintaining a normal weight. Treatment of established
disease may include medications to lower cholesterol such as statins,
blood pressure medication, or medications that decrease clotting, such
as aspirin. A number of procedures may also be carried out such as
percutaneous coronary intervention, coronary artery bypass graft, or
Atherosclerosis generally starts when a person is young and worsens
with age. Almost all people are affected to some degree by the age
Atherosclerosis is the number one cause of death and
disability in the developed world.
Atherosclerosis was first
described in 1575. There is evidence, however, that the condition
occurred in people more than 5,000 years ago.
2 Signs and symptoms
3 Risk factors
3.3 Lesser or uncertain
Calcification and lipids
4.3 Visible features
4.4 Rupture and stenosis
4.5 Accelerated growth of plaques
12 External links
The following terms are similar, yet distinct, in both spelling and
meaning, and can be easily confused: arteriosclerosis,
arteriolosclerosis, and atherosclerosis.
Arteriosclerosis is a general
term describing any hardening (and loss of elasticity) of medium or
large arteries (from Greek ἀρτηρία (artēria), meaning
'artery', and σκλήρωσις (sklerosis), meaning 'hardening');
arteriolosclerosis is any hardening (and loss of elasticity) of
arterioles (small arteries); atherosclerosis is a hardening of an
artery specifically due to an atheromatous plaque. The term
atherogenic is used for substances or processes that cause formation
Signs and symptoms
Atherosclerosis is asymptomatic for decades because the arteries
enlarge at all plaque locations, thus there is no effect on blood
flow. Even most plaque ruptures do not produce symptoms until
enough narrowing or closure of an artery, due to clots, occurs. Signs
and symptoms only occur after severe narrowing or closure impedes
blood flow to different organs enough to induce symptoms. Most of
the time, patients realize that they have the disease only when they
experience other cardiovascular disorders such as stroke or heart
attack. These symptoms, however, still vary depending on which artery
or organ is affected.
Typically, atherosclerosis begins in childhood, as a thin layer of
white-yellowish streaks with the inner layers of the artery walls (an
accumulation of white blood cells, mostly monocytes/macrophages) and
progresses from there.
Clinically, given enlargement of the arteries for decades, symptomatic
atherosclerosis is typically associated with men in their 40s and
women in their 50s to 60s. Sub-clinically, the disease begins to
appear in childhood, and rarely is already present at birth.
Noticeable signs can begin developing at puberty. Though symptoms are
rarely exhibited in children, early screening of children for
cardiovascular diseases could be beneficial to both the child and
his/her relatives. While coronary artery disease is more prevalent
in men than women, atherosclerosis of the cerebral arteries and
strokes equally affect both sexes.
Marked narrowing in the coronary arteries, which are responsible for
bringing oxygenated blood to the heart, can produce symptoms such as
the chest pain of angina and shortness of breath, sweating, nausea,
dizziness or light-headedness, breathlessness or palpitations.
Abnormal heart rhythms called arrhythmias (the heart is either beating
too slow or too fast) are another consequence of ischemia.
Carotid arteries supply blood to the brain and neck. Marked
narrowing of the carotid arteries can present with symptoms such as a
feeling of weakness, not being able to think straight, difficulty
speaking, becoming dizzy and difficulty in walking or standing up
straight, blurred vision, numbness of the face, arms, and legs, severe
headache and losing consciousness. These symptoms are also related to
stroke (death of brain cells).
Stroke is caused by marked narrowing or
closure of arteries going to the brain; lack of adequate blood supply
leads to the death of the cells of the affected tissue.
Peripheral arteries, which supply blood to the legs, arms, and pelvis,
also experience marked narrowing due to plaque rupture and clots.
Symptoms for the marked narrowing are numbness within the arms or
legs, as well as pain. Another significant location for the plaque
formation is the renal arteries, which supply blood to the kidneys.
Plaque occurrence and accumulation leads to decreased kidney blood
flow and chronic kidney disease, which, like all other areas, are
typically asymptomatic until late stages.
According to United States data for 2004, in about 66% of men and 47%
of women, the first symptom of atherosclerotic cardiovascular disease
is a heart attack or sudden cardiac death (death within one hour of
onset of the symptom). Cardiac stress testing, traditionally the most
commonly performed non-invasive testing method for blood flow
limitations, in general, detects only lumen narrowing of ≈75% or
greater, although some physicians claim that nuclear stress methods
can detect as little as 50%.
Case studies have included autopsies of U.S. soldiers killed in World
War II and the Korean War. A much-cited report involved autopsies of
300 U.S. soldiers killed in Korea. Although the average age of the men
was 22.1 years, 77.3 percent had "gross evidence of coronary
arteriosclerosis". Other studies done of soldiers in the Vietnam
War showed similar results, although often worse than the ones from
the earlier wars. Theories include high rates of tobacco use and (in
the case of the Vietnam soldiers) the advent of processed foods after
World War II.
Atherosclerosis and lipoproteins
The atherosclerotic process is not fully understood. Atherosclerosis
is initiated by inflammatory processes in the endothelial cells of the
vessel wall associated with retained low-density lipoprotein (LDL)
particles. This retention may be a cause, an effect, or both, of
the underlying inflammatory process.
The presence of the plaque induces the muscle cells of the blood
vessel to stretch, compensating for the additional bulk, and the
endothelial lining thickens, increasing the separation between the
plaque and lumen. This somewhat offsets the narrowing caused by the
growth of the plaque, but it causes the wall to stiffen and become
less compliant to stretching with each heart beat.
Western pattern diet
Lesser or uncertain
South Asian descent
The relation between dietary fat and atherosclerosis is controversial.
Writing in Science,
Gary Taubes detailed that political considerations
played into the recommendations of government bodies. The USDA, in
its food pyramid, promotes a diet of about 64% carbohydrates from
total calories. The American
Heart Association, the American Diabetes
Association and the National
Cholesterol Education Program make
similar recommendations. In contrast, Prof
Walter Willett (Harvard
School of Public Health, PI of the second Nurses' Health Study)
recommends much higher levels of fat, especially of monounsaturated
and polyunsaturated fat. These differing views reach a consensus,
though, against consumption of trans fats.
The role of dietary oxidized fats/lipid peroxidation (rancid fats) in
humans is not clear. Laboratory animals fed rancid fats develop
atherosclerosis. Rats fed DHA-containing oils experienced marked
disruptions to their antioxidant systems, and accumulated significant
amounts of phospholipid hydroperoxide in their blood, livers and
Rabbits fed atherogenic diets containing various oils were found to
undergo the greatest amount of oxidative susceptibility of LDL via
polyunsaturated oils. In another study, rabbits fed heated soybean
oil "grossly induced atherosclerosis and marked liver damage were
histologically and clinically demonstrated." However, Fred
Kummerow claims that it is not dietary cholesterol, but oxysterols, or
oxidized cholesterols, from fried foods and smoking, that are the
Rancid fats and oils taste very bad even in small amounts, so people
avoid eating them. It is very difficult to measure or estimate the
actual human consumption of these substances. Highly unsaturated
omega-3 rich oils such as fish oil are being sold in pill form so that
the taste of oxidized or rancid fat is not apparent. The health food
industry's dietary supplements are self-regulated and outside of FDA
regulations. To properly protect unsaturated fats from oxidation,
it is best to keep them cool and in oxygen-free environments.
Atherogenesis is the developmental process of atheromatous plaques. It
is characterized by a remodeling of arteries leading to subendothelial
accumulation of fatty substances called plaques. The buildup of an
atheromatous plaque is a slow process, developed over a period of
several years through a complex series of cellular events occurring
within the arterial wall and in response to a variety of local
vascular circulating factors. One recent hypothesis suggests that, for
unknown reasons, leukocytes, such as monocytes or basophils, begin to
attack the endothelium of the artery lumen in cardiac muscle. The
ensuing inflammation leads to formation of atheromatous plaques in the
arterial tunica intima, a region of the vessel wall located between
the endothelium and the tunica media. The bulk of these lesions is
made of excess fat, collagen, and elastin. At first, as the plaques
grow, only wall thickening occurs without any narrowing.
Stenosis is a
late event, which may never occur and is often the result of repeated
plaque rupture and healing responses, not just the atherosclerotic
process by itself.
Micrograph of an artery that supplies the heart showing significant
atherosclerosis and marked luminal narrowing. Tissue has been stained
using Masson's trichrome.
Early atherogenesis is characterized by the adherence of blood
circulating monocytes (a type of white blood cell) to the vascular bed
lining, the endothelium, then by their migration to the
sub-endothelial space, and further activation into monocyte-derived
macrophages. The primary documented driver of this process is
oxidized lipoprotein particles within the wall, beneath the
endothelial cells, though upper normal or elevated concentrations of
blood glucose also plays a major role and not all factors are fully
understood. Fatty streaks may appear and disappear.
Low-density lipoprotein (LDL) particles in blood plasma invade the
endothelium and become oxidized, creating risk of cardiovascular
disease. A complex set of biochemical reactions regulates the
oxidation of LDL, involving enzymes (such as Lp-LpA2) and free
radicals in the endothelium.
Initial damage to the endothelium results in an inflammatory response.
Monocytes enter the artery wall from the bloodstream, with platelets
adhering to the area of insult. This may be promoted by redox
signaling induction of factors such as VCAM-1, which recruit
circulating monocytes, and M-CSF, which is selectively required for
the differentiation of monocytes to macrophages. The monocytes
differentiate into macrophages, which proliferate locally, ingest
oxidized LDL, slowly turning into large "foam cells" – so-called
because of their changed appearance resulting from the numerous
internal cytoplasmic vesicles and resulting high lipid content. Under
the microscope, the lesion now appears as a fatty streak. Foam cells
eventually die and further propagate the inflammatory process.
In addition to these cellular activities, there is also smooth muscle
proliferation and migration from the tunica media into the intima in
response to cytokines secreted by damaged endothelial cells. This
causes the formation of a fibrous capsule covering the fatty streak.
Intact endothelium can prevent this smooth muscle proliferation by
releasing nitric oxide.
Calcification and lipids
Calcification forms among vascular smooth muscle cells of the
surrounding muscular layer, specifically in the muscle cells adjacent
to atheromas and on the surface of atheroma plaques and tissue. In
time, as cells die, this leads to extracellular calcium deposits
between the muscular wall and outer portion of the atheromatous
plaques. With the atheromatous plaque interfering with the regulation
of the calcium deposition, it accumulates and crystallizes. A similar
form of an intramural calcification, presenting the picture of an
early phase of arteriosclerosis, appears to be induced by a number of
drugs that have an antiproliferative mechanism of action (Rainer
Cholesterol is delivered into the vessel wall by
cholesterol-containing low-density lipoprotein (LDL) particles. To
attract and stimulate macrophages, the cholesterol must be released
from the LDL particles and oxidized, a key step in the ongoing
inflammatory process. The process is worsened if there is insufficient
high-density lipoprotein (HDL), the lipoprotein particle that removes
cholesterol from tissues and carries it back to the liver.
The foam cells and platelets encourage the migration and proliferation
of smooth muscle cells, which in turn ingest lipids, become replaced
by collagen and transform into foam cells themselves. A protective
fibrous cap normally forms between the fatty deposits and the artery
lining (the intima).
These capped fatty deposits (now called 'atheromas') produce enzymes
that cause the artery to enlarge over time. As long as the artery
enlarges sufficiently to compensate for the extra thickness of the
atheroma, then no narrowing ("stenosis") of the opening ("lumen")
occurs. The artery becomes expanded with an egg-shaped cross-section,
still with a circular opening. If the enlargement is beyond proportion
to the atheroma thickness, then an aneurysm is created.
Severe atherosclerosis of the aorta.
Although arteries are not typically studied microscopically, two
plaque types can be distinguished:
The fibro-lipid (fibro-fatty) plaque is characterized by an
accumulation of lipid-laden cells underneath the intima of the
arteries, typically without narrowing the lumen due to compensatory
expansion of the bounding muscular layer of the artery wall. Beneath
the endothelium there is a "fibrous cap" covering the atheromatous
"core" of the plaque. The core consists of lipid-laden cells
(macrophages and smooth muscle cells) with elevated tissue cholesterol
and cholesterol ester content, fibrin, proteoglycans, collagen,
elastin, and cellular debris. In advanced plaques, the central core of
the plaque usually contains extracellular cholesterol deposits
(released from dead cells), which form areas of cholesterol crystals
with empty, needle-like clefts. At the periphery of the plaque are
younger "foamy" cells and capillaries. These plaques usually produce
the most damage to the individual when they rupture. Cholesterol
crystals may also play a role.
The fibrous plaque is also localized under the intima, within the wall
of the artery resulting in thickening and expansion of the wall and,
sometimes, spotty localized narrowing of the lumen with some atrophy
of the muscular layer. The fibrous plaque contains collagen fibers
(eosinophilic), precipitates of calcium (hematoxylinophilic) and,
rarely, lipid-laden cells.
In effect, the muscular portion of the artery wall forms small
aneurysms just large enough to hold the atheroma that are present. The
muscular portion of artery walls usually remain strong, even after
they have remodeled to compensate for the atheromatous plaques.
However, atheromas within the vessel wall are soft and fragile with
little elasticity. Arteries constantly expand and contract with each
heartbeat, i.e., the pulse. In addition, the calcification deposits
between the outer portion of the atheroma and the muscular wall, as
they progress, lead to a loss of elasticity and stiffening of the
artery as a whole.
The calcification deposits, after they have become sufficiently
advanced, are partially visible on coronary artery computed tomography
or electron beam tomography (EBT) as rings of increased radiographic
density, forming halos around the outer edges of the atheromatous
plaques, within the artery wall. On CT, >130 units on the
Hounsfield scale (some argue for 90 units) has been the radiographic
density usually accepted as clearly representing tissue calcification
within arteries. These deposits demonstrate unequivocal evidence of
the disease, relatively advanced, even though the lumen of the artery
is often still normal by angiography.
Rupture and stenosis
Progression of atherosclerosis to late complications.
Although the disease process tends to be slowly progressive over
decades, it usually remains asymptomatic until an atheroma ulcerates,
which leads to immediate blood clotting at the site of atheroma ulcer.
This triggers a cascade of events that leads to clot enlargement,
which may quickly obstruct the flow of blood. A complete blockage
leads to ischemia of the myocardial (heart) muscle and damage. This
process is the myocardial infarction or "heart attack".
If the heart attack is not fatal, fibrous organization of the clot
within the lumen ensues, covering the rupture but also producing
stenosis or closure of the lumen, or over time and after repeated
ruptures, resulting in a persistent, usually localized stenosis or
blockage of the artery lumen. Stenoses can be slowly progressive,
whereas plaque ulceration is a sudden event that occurs specifically
in atheromas with thinner/weaker fibrous caps that have become
Repeated plaque ruptures, ones not resulting in total lumen closure,
combined with the clot patch over the rupture and healing response to
stabilize the clot is the process that produces most stenoses over
time. The stenotic areas tend to become more stable despite increased
flow velocities at these narrowings. Most major blood-flow-stopping
events occur at large plaques, which, prior to their rupture, produced
very little if any stenosis.
From clinical trials, 20% is the average stenosis at plaques that
subsequently rupture with resulting complete artery closure. Most
severe clinical events do not occur at plaques that produce high-grade
stenosis. From clinical trials, only 14% of heart attacks occur from
artery closure at plaques producing a 75% or greater stenosis prior to
the vessel closing.
If the fibrous cap separating a soft atheroma from the bloodstream
within the artery ruptures, tissue fragments are exposed and released.
These tissue fragments are very clot-promoting, containing collagen
and tissue factor; they activate platelets and activate the system of
coagulation. The result is the formation of a thrombus (blood clot)
overlying the atheroma, which obstructs blood flow acutely. With the
obstruction of blood flow, downstream tissues are starved of oxygen
and nutrients. If this is the myocardium (heart muscle) angina
(cardiac chest pain) or myocardial infarction (heart attack) develops.
Accelerated growth of plaques
The distribution of atherosclerotic plaques in a part of arterial
endothelium is inhomogeneous. The multiple and focal development of
atherosclerotic changes is similar to that in the development of
amyloid plaques in the brain and that of age spots on the skin.
Misrepair-accumulation aging theory suggests that misrepair
mechanisms play an important role in the focal development of
atherosclerosis. Development of a plaque is a result of repair of
injured endothelium. Because of the infusion of lipids into
sub-endothelium, the repair has to end up with altered remodeling of
local endothelium. This is the manifestation of a misrepair. Important
is this altered remodeling makes the local endothelium have increased
fragility to damage and have reduced repair-efficiency. As a
consequence, this part of endothelium has increased risk to be injured
and to be misrepaired. Thus, the accumulation of misrepairs of
endothelium is focalized and self-accelerating. In this way, the
growing of a plaque is also self-accelerating. Within a part of
arterial wall, the oldest plaque is always the biggest, and is the
most dangerous one to cause blockage of local artery.
The plaque is divided into three distinct components:
The atheroma ("lump of gruel", from Greek ἀθήρα (athera),
meaning 'gruel'), which is the nodular accumulation of a soft, flaky,
yellowish material at the center of large plaques, composed of
macrophages nearest the lumen of the artery
Underlying areas of cholesterol crystals
Calcification at the outer base of older or more advanced lesions.
Atherosclerotic lesions, or atherosclerotic plaques, are separated
into two broad categories: Stable and unstable (also called
vulnerable). The pathobiology of atherosclerotic lesions is very
complicated, but generally, stable atherosclerotic plaques, which tend
to be asymptomatic, are rich in extracellular matrix and smooth muscle
cells. On the other hand, unstable plaques are rich in macrophages and
foam cells, and the extracellular matrix separating the lesion from
the arterial lumen (also known as the fibrous cap) is usually weak and
prone to rupture. Ruptures of the fibrous cap expose thrombogenic
material, such as collagen, to the circulation and eventually
induce thrombus formation in the lumen. Upon formation, intraluminal
thrombi can occlude arteries outright (e.g., coronary occlusion), but
more often they detach, move into the circulation, and eventually
occlude smaller downstream branches causing thromboembolism.
Apart from thromboembolism, chronically expanding atherosclerotic
lesions can cause complete closure of the lumen. Chronically expanding
lesions are often asymptomatic until lumen stenosis is so severe
(usually over 80%) that blood supply to downstream tissue(s) is
insufficient, resulting in ischemia. These complications of advanced
atherosclerosis are chronic, slowly progressive and cumulative. Most
commonly, soft plaque suddenly ruptures (see vulnerable plaque),
causing the formation of a thrombus that will rapidly slow or stop
blood flow, leading to death of the tissues fed by the artery in
approximately five minutes. This event is called an infarction.
Microphotography of arterial wall with calcified (violet color)
atherosclerotic plaque (hematoxylin and eosin stain)
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.
Plaques that have ruptured are called complicated plaques. The
extracellular matrix of the lesion breaks, usually at the shoulder of
the fibrous cap that separates the lesion from the arterial lumen,
where the exposed thrombogenic components of the plaque, mainly
collagen will trigger thrombus formation. The thrombus then travels
downstream to other blood vessels, where the blood clot may partially
or completely block blood flow. If the blood flow is completely
blocked, cell deaths occur due to the lack of oxygen supply to nearby
cells, resulting in necrosis. The narrowing or obstruction of blood
flow can occur in any artery within the body. Obstruction of arteries
supplying the heart muscle results in a heart attack, while the
obstruction of arteries supplying the brain results in an ischaemic
Doppler ultrasound of right internal Carotid artery with calcified and
non-calcified plaques showing less than 70% stenosis
Lumen stenosis that is greater than 75% was considered the hallmark of
clinically significant disease in the past because recurring episodes
of angina and abnormalities in stress tests are only detectable at
that particular severity of stenosis. However, clinical trials have
shown that only about 14% of clinically debilitating events occur at
sites with more than 75% stenosis. The majority of cardiovascular
events that involve sudden rupture of the atheroma plaque do not
display any evident narrowing of the lumen. Thus, greater attention
has been focused on "vulnerable plaque" from the late 1990s
Besides the traditional diagnostic methods such as angiography and
stress-testing, other detection techniques have been developed in the
past decades for earlier detection of atherosclerotic disease. Some of
the detection approaches include anatomical detection and physiologic
Examples of anatomical detection methods include coronary calcium
scoring by CT, carotid IMT (intimal media thickness) measurement by
ultrasound, and intravascular ultrasound (IVUS). Examples of
physiologic measurement methods include lipoprotein subclass analysis,
HbA1c, hs-CRP, and homocysteine. Both anatomic and physiologic methods
allow early detection before symptoms show up, disease staging and
tracking of disease progression. Anatomic methods are more expensive
and some of them are invasive in nature, such as IVUS. On the other
hand, physiologic methods are often less expensive and safer. But they
do not quantify the current state of the disease or directly track
progression. In recent years, developments in nuclear imaging
techniques such as PET and SPECT have provided ways of estimating the
severity of atherosclerotic plaques.
Up to 90% of cardiovascular disease may be preventable if established
risk factors are avoided. Medical management of
atherosclerosis first involves modification to risk factors–for
example, via smoking cessation and diet restrictions. Additionally, a
controlled exercise program combats atherosclerosis by improving
circulation and functionality of the vessels. Exercise is also used to
manage weight in patients who are obese, lower blood pressure, and
decrease cholesterol. Often lifestyle modification is combined with
medication therapy. For example, statins help to lower cholesterol,
antiplatelet medications like aspirin help to prevent clots, and a
variety of antihypertensive medications are routinely used to control
blood pressure. If the combined efforts of risk factor modification
and medication therapy are not sufficient to control symptoms, or
fight imminent threats of ischemic events, a physician may resort to
interventional or surgical procedures to correct the obstruction.
Combinations of statins, niacin and 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. In the
many secondary prevention and several primary prevention trials,
several classes of lipoprotein-expression-altering (less correctly
termed "cholesterol-lowering") agents have consistently reduced not
only heart attack, stroke and hospitalization but also all-cause
mortality rates. The first of the large secondary prevention
comparative statin/placebo treatment trials was the Scandinavian
Simvastatin Survival Study (4S) with over fifteen more studies
extending through to the more recent ASTEROID trial published in
2006. The first primary prevention comparative treatment trial was
AFCAPS/TexCAPS with multiple later comparative statin/placebo
treatment trials including EXCEL, ASCOT and SPARCL.
While the statin trials have all been clearly favorable for improved
human outcomes, only ASTEROID and SATURN showed evidence of
atherosclerotic regression (slight). Both human and animal trials that
showed evidence of disease regression used more aggressive combination
agent treatment strategies, which nearly always included niacin.
Medical treatments often focus on alleviating symptoms. However
measures which focus on decreasing underlying atherosclerosis—as
opposed to simply treating symptoms—are more effective.
Non-pharmaceutical means are usually the first method of treatment,
such as stopping 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.
The key to the more effective approaches is to combine multiple
different treatment strategies. In addition, for those approaches,
such as lipoprotein transport behaviors, which have been shown to
produce the most success, adopting more aggressive combination
treatment strategies taken on a daily basis and indefinitely has
generally produced better results, both before and especially after
people are symptomatic.
Changes in diet may help prevent the development of atherosclerosis.
Tentative evidence suggests that a diet containing dairy products has
no effect on or decreases the risk of cardiovascular disease.
A diet high in fruits and vegetables decreases the risk of
cardiovascular disease and death. Evidence suggests that the
Mediterranean diet may improve cardiovascular results. There is
also evidence that a
Mediterranean diet may be better than a low-fat
diet in bringing about long-term changes to cardiovascular risk
factors (e.g., lower cholesterol level and blood pressure).
The group of medications referred to as statins are widely prescribed
for treating atherosclerosis. They have shown benefit in reducing
cardiovascular disease and mortality in those with high cholesterol
with few side effects.
These data are primarily in middle-age men and the conclusions are
less clear for women and people over the age of 70.
Monocyte counts, as well as cholesterol markers such as LDL:HDL ratio
and apolipiprotein B: apolipoprotein A-1 ratio can be used as markers
to monitor the extent of atherosclerotic regression which proves
useful in guiding patient treatments.
When atherosclerosis has become severe and caused irreversible
ischemia, such as tissue loss in the case of peripheral artery
disease, surgery may be indicated.
Vascular bypass surgery can
re-establish flow around the diseased segment of artery, and
angioplasty with or without stenting can reopen narrowed arteries and
improve bloodflow. Coronary artery bypass grafting without
manipulation of the ascending aorta has demonstrated reduced rates of
postoperative stroke and mortality compared to traditional on-pump
There is evidence that some anticoagulants, particularly warfarin,
which inhibit clot formation by interfering with Vitamin K metabolism,
may actually promote arterial calcification in the long term despite
reducing clot formation in the short term.
This section needs expansion. You can help by adding to it. (December
Diabetics, despite not having clinically detectable atherosclerotic
disease, have more severe debility from atherosclerotic events over
time than non-diabetics who have already had atherosclerotic events.
Thus diabetes has been upgraded to be viewed as an advanced
atherosclerotic disease equivalent.[clarification needed]
An indication of the role of HDL on atherosclerosis has been with the
rare Apo-A1 Milano human genetic variant of this HDL protein. A small
short-term trial using bacterial synthetized human Apo-A1 Milano HDL
in people with unstable angina produced fairly dramatic reduction in
measured coronary plaque volume in only six weeks vs. the usual
increase in plaque volume in those randomized to placebo. The trial
was published in JAMA in early 2006. Ongoing work
starting in the 1990s may lead to human clinical trials—probably by
about 2008.[needs update] These may use synthesized Apo-A1 Milano HDL
directly, or they may use gene-transfer methods to pass the ability to
synthesize the Apo-A1 Milano HDLipoprotein.
Methods to increase high-density lipoprotein (HDL) particle
concentrations, which in some animal studies largely reverses and
remove atheromas, are being developed and researched.
However, increasing HDL by any means is not necessarily helpful. For
example, the drug torcetrapib is the most effective agent currently
known for raising HDL (by up to 60%). However, in clinical trials it
also raised deaths by 60%. All studies regarding this drug were halted
in December 2006. See
CETP inhibitor for similar approaches.
The actions of macrophages drive atherosclerotic plaque progression.
Immunomodulation of atherosclerosis is the term for techniques that
modulate immune system function to suppress this macrophage
Research on genetic expression and control mechanisms is progressing.
PPAR, known to be important in blood sugar and variants of lipoprotein
production and function;
The multiple variants of the proteins that form the lipoprotein
transport particles.
Involvement of lipid peroxidation chain reaction in atherogenesis
triggered research on the protective role of the heavy isotope
(deuterated) polyunsaturated fatty acids (D-PUFAs) that are less prone
to oxidation than ordinary PUFAs (H-PUFAs). PUFAs are essential
nutrients – they are involved in metabolism in that very form as
they are consumed with food. In transgenic mice, that are a model for
human-like lipoprotein metabolism, adding D-PUFAs to diet indeed
reduced body weight gain, improved cholesterol handling and reduced
atherosclerotic damage to aorta.
MicroRNAs (miRNAs) have complementary sequences in the
3' UTR and 5'
UTR of target mRNAs of protein-coding genes, and cause mRNA cleavage
or repression of translational machinery. In diseased vascular
vessels, miRNAs are dysregulated and highly expressed. miR-33 is found
in cardiovascular diseases. It is involved in atherosclerotic
initiation and progression including lipid metabolism, insulin
signaling and glucose homeostatis, cell type progression and
proliferation, and myeloid cell differentiation. It was found in
rodents that the inhibition of miR-33 will raise HDL level and the
expression of miR-33 is down-regulated in humans with atherosclerotic
miR-33a and miR-33b are located on intron 16 of human sterol
regulatory element-binding protein 2 (SREBP2) gene on chromosome 22
and intron 17 of SREBP1 gene on chromosome 17. miR-33a/b regulates
cholesterol/lipid homeostatis by binding in the 3’UTRs of genes
involved in cholesterol transport such as ATP binding cassette (ABC)
transporters and enhance or represses its expression. Study have shown
that ABCA1 mediates transport of cholesterol from peripheral tissues
to Apolipoprotein-1 and it is also important in the reverse
cholesterol transport pathway, where cholesterol is delivered from
peripheral tissue to the liver, where it can be excreted into bile or
converted to bile acids prior to excretion. Therefore, we know
that ABCA1 plays an important role in preventing cholesterol
accumulation in macrophages. By enhancing miR-33 function, the level
of ABCA1 is decreased, leading to decrease cellular cholesterol efflux
to apoA-1. On the other hand, by inhibiting miR-33 function, the level
of ABCA1 is increased and increases the cholesterol efflux to apoA-1.
Suppression of miR-33 will lead to less cellular cholesterol and
higher plasma HDL level through the regulation of ABCA1
The sugar, cyclodextrin, removed cholesterol that had built up in the
arteries of mice fed a high-fat diet.
Aging is the most important risk factor for cardiovascular problems.
The causative basis by which aging mediates its impact, independently
of other recognized risk factors, remains to be determined. Evidence
has been reviewed for a key role of
DNA damage in vascular
aging. 8-oxoG, a common type of oxidative damage in
DNA, is found to accumulate in plaque vascular smooth muscle cells,
macrophages and endothelial cells, thus linking
DNA damage to
DNA strand breaks also increased in atherosclerotic
Werner syndrome (WS) is a premature aging condition in
humans. WS is caused by a genetic defect in a
RecQ helicase that
is employed in several repair processes that remove damages from DNA.
WS patients develop a considerable burden of atherosclerotic plaques
in their coronary arteries and aorta: calcification of the aortic
valve is also frequently observed. These findings link excessive
DNA damage to premature aging and early atherosclerotic
plaque development (see
DNA damage theory of aging).
Microorganisms, living in the body (all together called microbiome),
can contribute to atherosclerosis in many ways: modulation of the
immune system, changes in metabolism, processing of nutrients and
production of certain metabolites that can get into blood
circulation. One of such metabolites, produced by gut bacteria,
is trimethylamine-N-oxide (TMAO). Its levels have been associated with
atherosclerosis in human studies and animal research suggest that
there can be a causal relation. An association between the bacterial
genes encoding trimethylamine lyases — the enzymes involved in TMAO
generation — and atherosclerosis has been noted.
Some controversial research has suggested a link between
atherosclerosis and the presence of several different nanobacteria in
the arteries, e.g., Chlamydophila pneumoniae, though
trials of current antibiotic treatments known to be usually effective
in suppressing growth or killing these bacteria have not been
successful in improving outcomes.
In 2011, coronary atherosclerosis was one of the top ten most
expensive conditions seen during inpatient hospitalizations in the US,
with aggregate inpatient hospital costs of $10.4 billion.
^ a b c d e f "What Are the Signs and Symptoms of Atherosclerosis? -
NHLBI, NIH". www.nhlbi.nih.gov. 22 June 2016. Retrieved 5 November
^ a b "What Causes Atherosclerosis? - NHLBI, NIH". www.nhlbi.nih.gov.
22 June 2016. Retrieved 6 November 2017.
^ a b c "Who Is at Risk for Atherosclerosis? - NHLBI, NIH".
www.nhlbi.nih.gov. 22 June 2016. Retrieved 5 November 2017.
^ a b "How Can
Atherosclerosis Be Prevented or Delayed? - NHLBI, NIH".
www.nhlbi.nih.gov. 22 June 2016. Retrieved 6 November 2017.
^ a b c "How Is
Atherosclerosis Treated? - NHLBI, NIH".
www.nhlbi.nih.gov. 22 June 2016. Retrieved 6 November 2017.
^ a b Aronow, Wilbert S.; Fleg, Jerome L.; Rich, Michael W. (2013).
Tresch and Aronow's Cardiovascular Disease in the Elderly, Fifth
Edition. CRC Press. p. 171. ISBN 9781842145449.
^ a b c "What Is Atherosclerosis? - NHLBI, NIH". www.nhlbi.nih.gov. 22
June 2016. Retrieved 6 November 2017.
^ "How Is
Atherosclerosis Diagnosed? - NHLBI, NIH". www.nhlbi.nih.gov.
22 June 2016. Retrieved 6 November 2017.
^ Topol, Eric J.; Califf, Robert M. (2007). Textbook of Cardiovascular
Medicine. Lippincott Williams & Wilkins. p. 2.
^ a b Shor, Allan (2008). Chlamydia
Atherosclerosis Lesion: Discovery,
Diagnosis and Treatment. Springer Science & Business Media.
p. 8. ISBN 9781846288104.
^ Ross R (April 1993). "The pathogenesis of atherosclerosis: a
perspective for the 1990s". Nature. 362 (6423): 801–9.
^ Atherosclerosis. Harvard Health Publications Harvard Health
Publications. Health Topics A – Z, (2011)
^ a b c Atherosclerosis. National Heart, Lung and
^ Flora, G., Baker, A.B., Loewenson, R.B., and Klassen, A. C. A
Comparative Study of Cerebral
Atherosclerosis in Males and Females.
Circulation 38, 859-869
^ a b Arrhythmia.
Stroke Foundation. "Archived copy".
Archived from the original on 2014-02-03. Retrieved 2014-01-31.
^ Sims N.R.; Muderman H. (2010). "Mitochondria, oxidative metabolism
and cell death in stroke". Biochimica et Biophysica Acta. 1802 (1):
80–91. doi:10.1016/j.bbadis.2009.09.003. PMID 19751827.
^ Enos WF, Holmes RH, Beyer J (1953). "Coronary disease among United
States soldiers killed in action in Korea: Preliminary Report". JAMA.
152 (12): 1090–93. doi:10.1001/jama.1953.03690120006002. The
average age was calculated from the ages of 200 of the soldiers. No
age was recorded in nearly 100 of the men.
^ Li X, Fang P, et al. (April 2016). "Mitochondrial Reactive Oxygen
Species Mediate Lysophosphatidylcholine-Induced Endothelial Cell
Activation". Arteriosclerosis, Thrombosis, and Vascular Biology. 36
(6): 1090–100. doi:10.1161/ATVBAHA.115.306964. PMC 4882253 .
^ Williams, KJ; Tabas, I (May 1995). "The Response-to-Retention
Hypothesis of Early Atherogenesis". Arteriosclerosis, Thrombosis, and
Vascular Biology. 15 (5): 551–61. doi:10.1161/01.ATV.15.5.551.
PMC 2924812 . PMID 7749869.
^ Aviram M, Fuhrman B (1998). "LDL oxidation by arterial wall
macrophages depends on the oxidative status in the lipoprotein and in
the cells: role of prooxidants vs. antioxidants". Mol Cell Biochem.
188 ((1-2)): 149–59. doi:10.1023/A:1006841011201.
^ a b c d e f g h i j k l m n o p q r
^ Enas EA, Kuruvila A, Khanna P, Pitchumoni CS, Mohan V (October
2013). "Benefits & risks of statin therapy for primary prevention
of cardiovascular disease in Asian Indians - a population with the
highest risk of premature coronary artery disease & diabetes".
Indian J Med Res. 138 (4): 461–491. PMC 3868060 .
Heart Association Why South Asians Facts Web. 30 April 2015.
^ Borissoff JI, Spronk HM, Heeneman S, ten Cate H (June 2009). "Is
thrombin a key player in the 'coagulation-atherogenesis' maze?".
Cardiovasc. Res. 82 (3): 392–403. doi:10.1093/cvr/cvp066.
^ Borissoff JI, Heeneman S, Kilinç E, et al. (August 2010). "Early
atherosclerosis exhibits an enhanced procoagulant state". Circulation.
122 (8): 821–30. doi:10.1161/CIRCULATIONAHA.109.907121.
^ Borissoff JI, Spronk HM, ten Cate H (May 2011). "The hemostatic
system as a modulator of atherosclerosis". N. Engl. J. Med. 364 (18):
1746–60. doi:10.1056/NEJMra1011670. PMID 21542745.
^ Food and nutrition board, institute of medicine of the national
academies (2005). Dietary Reference Intakes for Energy, Carbohydrate,
Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids
(Macronutrients). National Academies Press. pp. 481–484.
^ Mozaffarian D, Rimm EB, Herrington DM (November 2004). "Dietary
fats, carbohydrate, and progression of coronary atherosclerosis in
postmenopausal women". Am. J. Clin. Nutr. 80: 1175–84.
doi:10.1093/ajcn/80.5.1175. PMC 1270002 .
PMID 15531663. CS1 maint: Multiple names: authors list
^ Bhatt DL, Topol EJ (July 2002). "Need to test the arterial
inflammation hypothesis". Circulation. 106 (1): 136–40.
doi:10.1161/01.CIR.0000021112.29409.A2. PMID 12093783.
^ Griffin M, Frazer A, Johnson A, Collins P, Owens D, Tomkin GH
(1998). "Cellular cholesterol synthesis—the relationship to
post-prandial glucose and insulin following weight loss".
Atherosclerosis. 138 (2): 313–8. doi:10.1016/S0021-9150(98)00036-7.
^ King, Cr; Knutson, Kl; Rathouz, Pj; Sidney, S; Liu, K; Lauderdale,
Ds (December 2008). "Short sleep duration and incident coronary artery
calcification". JAMA: The Journal of the American Medical Association.
300 (24): 2859–66. doi:10.1001/jama.2008.867. PMC 2661105 .
^ Provost, EB; Madhloum, N; Int Panis, L; De Boever, P; Nawrot, TS
(2015). "Carotid intima-media thickness, a marker of subclinical
atherosclerosis, and particulate air pollution exposure: the
meta-analytical evidence". PLoS ONE. 10 (5): e0127014.
doi:10.1371/journal.pone.0127014. PMC 4430520 .
^ Adar, Sara D.; Lianne Sheppard; Sverre Vedal; Joseph F. Polak; Paul
D. Sampson; Ana V. Diez Roux; Matthew Budoff; David R. Jacobs Jr; R.
Graham Barr; Karol Watson; Joel D. Kaufman (April 23, 2013). "Fine
Particulate Air Pollution and the Progression of Carotid Intima-Medial
Thickness: A Prospective Cohort Study from the Multi-Ethnic Study of
Atherosclerosis and Air Pollution". PLoS Medicine. 10 (4): e1001430.
doi:10.1371/journal.pmed.1001430. PMC 3637008 .
PMID 23637576. Retrieved May 4, 2013. This early analysis from
MESA suggests that higher long-term PM2.5 concentrations are
associated with increased IMT progression and that greater reductions
in PM2.5 are related to slower IMT progression.
^ Chih-Hao Wang. "Biological Gradient Between Long-Term Arsenic
Exposure and Carotid Atherosclerosis". ahajournals.org.
^ Taubes G (March 2001). "Nutrition. The soft science of dietary fat".
Science. 291 (5513): 2536–45. doi:10.1126/science.291.5513.2536.
^ "Food Pyramids: Nutrition Source, Harvard School of Public Health".
Archived from the original on 26 December 2007. Retrieved
^ Song JH, Fujimoto K, Miyazawa T (2000). "Polyunsaturated (n-3) fatty
acids susceptible to peroxidation are increased in plasma and tissue
lipids of rats fed docosahexaenoic acid-containing oils". J. Nutr. 130
(12): 3028–33. PMID 11110863.
^ Yap SC, Choo YM, Hew NF, et al. (1995). "Oxidative susceptibility of
low density lipoprotein from rabbits fed atherogenic diets containing
coconut, palm, or soybean oils". Lipids. 30 (12): 1145–50.
doi:10.1007/BF02536616. PMID 8614305.
^ Greco AV, Mingrone G (1990). "Serum and biliary lipid pattern in
rabbits feeding a diet enriched with unsaturated fatty acids". Exp
Pathol. 40 (1): 19–33. doi:10.1016/S0232-1513(11)80281-1.
^ "Scientist, 98, challenges orthodoxy on causes of heart disease".
^ Mattes RD (2005). "Fat taste and lipid metabolism in humans".
Physiol. Behav. 86 (5): 691–7. doi:10.1016/j.physbeh.2005.08.058.
PMID 16249011. The rancid odor of an oxidized fat is readily
^ Dobarganes C, Márquez-Ruiz G (2003). "Oxidized fats in foods".
Current Opinion in Clinical Nutrition and Metabolic Care. 6 (2):
^ supplements, FDA. "Dietary Supplements".
^ Schwartz, CJ; Valente AJ; Sprague EA; Kelley JL; Cayatte AJ; Mowery
J. (Dec 1992). "Atherosclerosis. Potential targets for stabilization
and regression". Circulation. 86 (6 Suppl): III117–123.
^ Robbins, Clinton S.; Hilgendorf, Ingo; Weber, Georg F.; Theurl,
Igor; Iwamoto, Yoshiko; Figueiredo, Jose-Luiz; Gorbatov, Rostic;
Sukhova, Galina K.; Gerhardt, Louisa M.S. (September 2013). "Local
proliferation dominates lesional macrophage accumulation in
atherosclerosis". Nature Medicine. 19 (9): 1166–1172.
doi:10.1038/nm.3258. ISSN 1078-8956. PMC 3769444 .
^ Miller J.D. (2013). "Cardiovascular calcification: Orbicular
origins". Nature Materials. 12: 476–478.
^ Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ
(May 1987). "Compensatory enlargement of human atherosclerotic
coronary arteries". N. Engl. J. Med. 316 (22): 1371–5.
doi:10.1056/NEJM198705283162204. PMID 3574413.
^ "Coronary atherosclerosis — the fibrous plaque with
calcification". www.pathologyatlas.ro. Retrieved 2010-03-25.
^ Janoudi, Abed; Shamoun, Fadi E.; Kalavakunta, Jagadeesh K.; Abela,
George S. (1 July 2016). "
Cholesterol crystal induced arterial
inflammation and destabilization of atherosclerotic plaque". European
Heart Journal. 37 (25): 1959–1967.
^ Maton, Anthea; Roshan L. Jean Hopkins; Charles William McLaughlin;
Susan Johnson; Maryanna Quon Warner; David LaHart; Jill D. Wright
(1993). Human Biology and Health. Englewood Cliffs, NJ: Prentice Hall.
ISBN 0-13-981176-1. OCLC 32308337.
^ Wang, Jicun; Michelitsch, Thomas; Wunderlin, Arne; Mahadeva, Ravi
Aging as a consequence of Misrepair –a novel theory of
aging". 0904 (0575). arXiv:0904.0575 .
^ Wang-Michelitsch, Jicun; Michelitsch, Thomas (2015). "
Aging as a
process of accumulation of Misrepairs". 1503 (07163).
arXiv:1503.07163 . Bibcode:2015arXiv150307163W.
^ Wang-Michelitsch, Jicun; Michelitsch, Thomas (2015). "Misrepair
mechanism in the development of atherosclerotic plaques". 1505
(01289). arXiv:1505.01289 . Bibcode:2015arXiv150501289W.
^ Ross R; Ross, Russell (January 1999). "
Atherosclerosis — An
Inflammatory Disease". New England Journal of Medicine. 340 (2):
115–26. doi:10.1056/NEJM199901143400207. PMID 9887164.
^ Finn AV, Nakano M, Narula J, Kolodgie FD, Virmani R (July 2010).
"Concept of vulnerable/unstable plaque". Arterioscler. Thromb. Vasc.
Biol. 30 (7): 1282–92. doi:10.1161/ATVBAHA.108.179739.
^ Didangelos A, Simper D, Monaco C, Mayr M (May 2009). "Proteomics of
acute coronary syndromes" (PDF). Current atherosclerosis reports. 11
(3): 188–95. doi:10.1007/s11883-009-0030-x.
^ Maseri A, Fuster V (2003). "Is there a vulnerable plaque?".
Circulation. 107 (16): 2068–71.
doi:10.1161/01.CIR.0000070585.48035.D1. PMID 12719286.
^ McGill, Henry C.; McMahan, C. Alex; Gidding, Samuel S. (2008-03-04).
Heart Disease in the 21st Century". Circulation. 117 (9):
ISSN 0009-7322. PMID 18316498.
^ McNeal, Catherine J.; Dajani, Tala; Wilson, Don; Cassidy-Bushrow,
Andrea E.; Dickerson, Justin B.; Ory, Marcia (2010-01-01).
"Hypercholesterolemia in youth: opportunities and obstacles to prevent
premature atherosclerotic cardiovascular disease". Current
Atherosclerosis Reports. 12 (1): 20–28.
doi:10.1007/s11883-009-0072-0. ISSN 1534-6242.
^ "Unit 6: Cardiovascular, Circulatory, and Hematologic Function."
Suzane C. Smeltzer, Brenda G. Bare, Janice L Hinkle, Kerry K Cheever.
Brunner & Suddarth's Textbook of Medical-Surgical Nursing.
Philadelphia: Lippincott Williams & Wilkins, 2010. 682-900.
^ T. E. Strandberg; S. Lehto; K. Pyörälä; A. Kesäniemi; H. Oksa
Cholesterol lowering after participation in the
Scandinavian Simvastatin Survival Study (4S) in Finland". European
Heart Journal. 18 (11): 1725–7;.
doi:10.1093/oxfordjournals.eurheartj.a015166. PMID 9402446.
^ Nissen SE, Nicholls SJ, Sipahi I, et al. (2006). "Effect of very
high-intensity statin therapy on regression of coronary
atherosclerosis: the ASTEROID trial" (PDF). JAMA. 295 (13): 1556–65.
doi:10.1001/jama.295.13.jpc60002. PMID 16533939. Archived from
the original (PDF) on 2007-09-29.
^ Downs JR, Clearfield M, Weis S, et al. (May 1998). "Primary
prevention of acute coronary events with lovastatin in men and women
with average cholesterol levels: results of AFCAPS/TexCAPS. Air
Atherosclerosis Prevention Study". JAMA: The
Journal of the American Medical Association. 279 (20): 1615–22.
doi:10.1001/jama.279.20.1615. PMID 9613910.
^ Bradford RH, Shear CL, Chremos AN, et al. (1991). "Expanded Clinical
Evaluation of Lovastatin (EXCEL) study results. I. Efficacy in
modifying plasma lipoproteins and adverse event profile in 8245
patients with moderate hypercholesterolemia". Arch. Intern. Med. 151
(1): 43–9. doi:10.1001/archinte.151.1.43. PMID 1985608.
^ Sever PS, Poulter NR, Dahlöf B, et al. (2005). "Reduction in
cardiovascular events with atorvastatin in 2,532 patients with type 2
diabetes: Anglo-Scandinavian Cardiac Outcomes Trial—lipid-lowering
Diabetes Care. 28 (5): 1151–7.
doi:10.2337/diacare.28.5.1151. PMID 15855581.
^ Linda Brookes, MSc. "SPARCL:
Stroke Prevention by Aggressive
Cholesterol Levels". Medscape. Archived from the original
on January 16, 2008. Retrieved 2007-11-19.
^ Amarenco P, Bogousslavsky J, Callahan AS, et al. (2003). "Design and
baseline characteristics of the stroke prevention by aggressive
reduction in cholesterol levels (SPARCL) study". Cerebrovascular
diseases. 16 (4): 389–95. doi:10.1159/000072562.
^ Blankenhorn DH, Hodis HN (August 1993). "Atherosclerosis--reversal
with therapy". The Western journal of medicine. 159 (2): 172–9.
PMC 1022223 . PMID 8212682.
^ a b Fonarow G (2003). "Aggressive treatment of atherosclerosis: The
time is now". Cleve. Clin. J. Med. 70: 431–434.
^ Ambrose J. A.; Barua R. R. (2004). "The pathophysiology of cigarette
smoking and cardiovascular disease". J Am Coll Cardiol. 43 (10):
^ Pigozzi F.; et al. (2011). "Endothelial (dys)function: the target of
physical exercise for prevention and treatment of cardiovascular
disease". J. Sports Med. Phys. Fitness. 51: 260–267.
^ Koh K.K.; et al. (2010). "Combination therapy for treatment or
prevention of atherosclerosis: focus on the lipid-RAAS interaction".
Atherosclerosis. 209: 307–313.
^ Rice, BH (2014). "Dairy and Cardiovascular Disease: A Review of
Recent Observational Research". Current nutrition reports. 3:
130–138. doi:10.1007/s13668-014-0076-4. PMC 4006120 .
^ Kratz, M; Baars, T; Guyenet, S (Feb 2013). "The relationship between
high-fat dairy consumption and obesity, cardiovascular, and metabolic
disease". European Journal of Nutrition. 52 (1): 1–24.
doi:10.1007/s00394-012-0418-1. PMID 22810464.
^ Wang, X; Ouyang, Y; Liu, J; Zhu, M; Zhao, G; Bao, W; Hu, FB (Jul 29,
2014). "Fruit and vegetable consumption and mortality from all causes,
cardiovascular disease, and cancer: systematic review and
dose-response meta-analysis of prospective cohort studies". BMJ
(Clinical research ed.). 349: g4490. doi:10.1136/bmj.g4490.
PMC 4115152 . PMID 25073782.
^ Walker C, Reamy BV (April 2009). "Diets for cardiovascular disease
prevention: what is the evidence?". Am Fam Physician. 79 (7): 571–8.
^ Nordmann, AJ; Suter-Zimmermann, K; Bucher, HC; Shai, I; Tuttle, KR;
Estruch, R; Briel, M (September 2011). "Meta-analysis comparing
Mediterranean to low-fat diets for modification of cardiovascular risk
factors". The American Journal of Medicine. 124 (9): 841–51.e2.
doi:10.1016/j.amjmed.2011.04.024. PMID 21854893.
^ Taylor, F; Huffman, MD; Macedo, AF; Moore, TH; Burke, M; Davey
Smith, G; Ward, K; Ebrahim, S (Jan 31, 2013). "
Statins for the primary
prevention of cardiovascular disease". The Cochrane Database of
Systematic Reviews. 1: CD004816. doi:10.1002/14651858.CD004816.pub5.
^ Vos E, Rose CP (November 2005). "Questioning the benefits of
statins". CMAJ. 173 (10): 1207; author reply 1210.
doi:10.1503/cmaj.1050120. PMC 1277053 .
^ Shanmugma N., Román-Rego A., Ong P., Kaski J.C. (2010).
"Atherosclerotic plaque regression fact or fiction?". Cardiovasc.
Drugs Ther. 24: 311–317. CS1 maint: Multiple names: authors
^ Zhao, Dong Fang (February 28, 2017). "Coronary
Grafting With and Without Manipulation of the Ascending Aorta: A
Network Meta-Analysis". Journal of the American College of Cardiology.
69 (8): 924–936. doi:10.1016/j.jacc.2016.11.071.
^ Price PA, Faus SA, Williamson MK (February 2000). "Warfarin-induced
artery calcification is accelerated by growth and vitamin D".
Arteriosclerosis, Thrombosis, and Vascular Biology. 20 (2): 317–27.
doi:10.1161/01.ATV.20.2.317. PMID 10669626.
^ Geleijnse JM, Vermeer C, Grobbee DE, et al. (November 2004).
"Dietary intake of menaquinone is associated with a reduced risk of
coronary heart disease: the Rotterdam Study". J. Nutr. 134 (11):
3100–5. doi:10.1093/jn/134.11.3100. PMID 15514282.
^ "Linus Pauling Institute at Oregon State University".
lpi.oregonstate.edu. Archived from the original on 7 April 2010.
^ Barter PJ, Caulfield M, Eriksson M, et al. (November 2007). "Effects
of torcetrapib in patients at high risk for coronary events". N Engl J
Med. 357 (21): 2109–22. doi:10.1056/NEJMoa0706628.
^ Jan Nilsson; Göran K. Hansson; Prediman K. Shah (2005).
Atherosclerosis – Implications for Vaccine
Development—ATVB In Focus". Arteriosclerosis, Thrombosis, and
Vascular Biology. 25 (1): 18–28.
doi:10.1161/01.ATV.0000149142.42590.a2. PMID 15514204.
^ Spiteller G (2005). "The relation of lipid peroxidation processes
with atherogenesis: a new theory on atherogenesis". Mol Nutr Food Res.
49: 999–1013. doi:10.1002/mnfr.200500055. PMID 16270286.
^ Berbée JFP, Mol IM, Milne GL, Pollock E, Hoeke G, Lütjohann D,
Monaco C, Rensen PCN, van der Ploeg LHT, Shchepinov MS (2017).
"Deuterium-reinforced polyunsaturated fatty acids protect against
atherosclerosis by lowering lipid peroxidation and
hypercholesterolemia". Atherosclerosis. 264: 100–107.
PMID 28655430. CS1 maint: Multiple names: authors list
^ Tsikas D (2017). "Combating atherosclerosis with heavy PUFAs:
Deuteron not proton is the first. (Editorial)". Atherosclerosis. 264:
^ a b Chen WJ, Yin K, Zhao GJ, et al. The magic and mystery of
microRNA-27 in atherosclerosis.
^ Sacco J, Adeli K. MicroRNAs: emerging roles in lipid and lipoprotein
metabolism. Curr Opin Lipidol 2012;23:220e5.
^ Bommer GT, MacDougald OA. Regulation of lipid homeostasis by the
bifunctional SREBF2-miR33a locus. Cell Metab 2011;13:241e7.
^ Rayner KJ, Sheedy FJ, Esau CC, et al. Antagonism of miR-33 in mice
promotes reverse cholesterol transport and regression of
atherosclerosis. J Clin Invest 2011;121:2921e31.
^ Rayner KJ, Esau CC, Hussain FN, et al. Inhibition of miR-33a/b in
non-human primates raises plasma HDL and lowers VLDL triglycerides.
^ Iwakiri Y. A role of miR-33 for cell cycle progression and cell
proliferation. Cell Cycle 2012;11:1057e8.
^ Singaraja RR, Stahmer B, Brundert M, et al. Hepatic ATP-binding
cassette transporter A1 is a key molecule in high-density lipoprotein
cholesteryl ester metabolism in mice. Arterioscler Thromb Vasc Biol
^ Zimmer S (2016). "
Cyclodextrin promotes atherosclerosis regression
via macrophage reprogramming". Science Translational Medicine. 8:
^ A sugar can melt away cholesterol. Science News
^ Wu H, Roks AJ (2014). "Genomic instability and vascular aging: a
focus on nucleotide excision repair". Trends Cardiovasc. Med. 24 (2):
61–8. doi:10.1016/j.tcm.2013.06.005. PMID 23953979.
^ a b Bautista-Niño PK, Portilla-Fernandez E, Vaughan DE, Danser AH,
Roks AJ (2016). "
DNA Damage: A Main Determinant of Vascular Aging".
Int J Mol Sci. 17 (5): 748. doi:10.3390/ijms17050748.
PMC 4881569 . PMID 27213333.
^ Shah AV, Bennett MR (2017). "
DNA damage-dependent mechanisms of
ageing and disease in the macro- and microvasculature". Eur. J.
Pharmacol. doi:10.1016/j.ejphar.2017.03.050. PMID 28347738.
^ a b Martinet W, Knaapen MW, De Meyer GR, Herman AG, Kockx MM (2002).
"Elevated levels of oxidative
DNA damage and
DNA repair enzymes in
human atherosclerotic plaques". Circulation. 106 (8): 927–32.
doi:10.1161/01.cir.0000026393.47805.21. PMID 12186795.
^ Ishida T, Ishida M, Tashiro S, Yoshizumi M, Kihara Y (2014). "Role
DNA damage in cardiovascular disease". Circ. J. 78 (1): 42–50.
^ a b Barrington William T., Lusis Aldons J. (2017). "Atherosclerosis:
Association between the gut microbiome and atherosclerosis". Nature
Reviews Cardiology. 14: 699–700.
^ Jie Z.; et al. (2017). "The gut microbiome in atherosclerotic
cardiovascular disease". Nat. Commun. 8: 845. CS1 maint: Explicit
use of et al. (link)
^ M Stitzinger (2007). "Lipids, inflammation and atherosclerosis"
(pdf). The digital repository of Leiden University. Archived (PDF)
from the original on 27 November 2007. Retrieved 2007-11-02. Results
of clinical trials investigating anti-chlamydial antibiotics as an
addition to standard therapy in patients with coronary artery disease
have been inconsistent. Therefore, Andraws et al. conducted a
meta-analysis of these clinical trials and found that evidence
available to date does not demonstrate an overall benefit of
antibiotic therapy in reducing mortality or cardiovascular events in
patients with coronary artery disease.
^ Pfuntner A, Wier LM, Steiner C (December 2013). "Costs for Hospital
Stays in the United States, 2011". HCUP Statistical Brief #168.
Rockville, MD: Agency for Healthcare Research and Quality.
Wikimedia Commons has media related to Atherosclerosis.
Atherosclerosis at Curlie (based on DMOZ)
V · T · D
ICD-9-CM: 440, 414.0
Patient UK: Atherosclerosis
Cardiovascular disease (vessels) (I70–I99, 440–456)
Peripheral artery disease
Critical limb ischemia
Carotid artery stenosis
Renal artery stenosis
Aortoiliac occlusive disease
Aneurysm / dissection /
torso: Aortic aneurysm
Abdominal aortic aneurysm
Thoracic aortic aneurysm
Aneurysm of sinus of Valsalva
Coronary artery aneurysm
head / neck
Intracranial berry aneurysm
Carotid artery dissection
Vertebral artery dissection
Familial aortic dissection
Hereditary hemorrhagic telangiectasia
Venous thrombosis /
primarily lower limb
Deep vein thrombosis
Hepatic veno-occlusive disease
Portal vein thrombosis
Renal vein thrombosis
upper limb / torso
Cerebral venous sinus thrombosis
Chronic venous insufficiency
Chronic cerebrospinal venous insufficiency
Superior vena cava syndrome
Inferior vena cava syndrome
Arteries or veins
Hypertensive heart disease
White coat hypertension