Atherosclerosis

Atherosclerosis Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Atherosclerosis from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Assessment of Cardiovascular Risk
Diagnosis
Diagnostic Study of Choice
History and Symptoms
Physical Examination
Laboratory Findings
Electrocadiogram
X-ray
Echocardiography and Ultrasound
CT scan
MRI
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
ACC/AHA Guideline Recommendations
Assessment of cardiovascular risk
Secondary prevention
Case Studies
Case #1
Atherosclerosis On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Atherosclerosis All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Atherosclerosis
CDC on Atherosclerosis
Atherosclerosis in the news
Blogs on Atherosclerosis
Directions to Hospitals Treating Atherosclerosis
Risk calculators and risk factors for Atherosclerosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]

Treatment

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. However, medicines are criticized for their expense, patented control and occasional undesired effects.

Lipoprotein imbalances, upper normal and especially elevated blood sugar, i.e. diabetes, high blood pressure, homocysteine, stopping smoking, taking anticoagulants (anti-clotting agents) which target clotting factors, taking omega 3 oils from fatty fish or plant oils such as flax or canola oils, exercising and losing weight are the usual focus of treatments which have proved to be helpful in clinical trials. The target serum cholesterol level is ideally equal or less than 4mmol/L (160 mg/dL) and triglycerides equal or less than 2mmol/L 180 (mg/dL).

In general, the group of medications referred to as statins has seen popularity yet they are not approved in most jurisdictions for treating atherosclerosis. They have relatively few short-term undesirable side-effects and have shown some effect in reducing atherosclerotic disease 'events' in some but not all studies such as ALLHAT.

The newest statin, rosuvastatin, has been the first to demonstrate regression of atherosclerotic plaque within the coronary arteries by IVUS evaluation, see the Effect of Very High-Intensity Statin Therapy reference below. The study was not set up to demonstrate clinical benefit or harm. However, for most people, changing their physiologic behaviors, from the usual high risk to greatly reduced risk, requires a combination of several compounds, taken on a daily basis and indefinitely. More and more human treatment trials have been done and are ongoing which demonstrate improved outcome for those people using more complex and effective treatment regimens which change physiologic behaviour patterns to more closely resemble those humans exhibit in childhood at a time before fatty streaks begin forming.

Lowering lipoprotein little a, a genetic variant of LDL, can be achieved with large daily doses of vitamin B3, niacin. Niacin also tends to shift LDL particle distribution to larger particle size and improve HDL functioning. Work on increasing HDL particle concentration and function, beyond the niacin effect, perhaps even more important, is slowly advancing. Combinations of statins, niacin, intestinal cholesterol absorption inhibiting supplements (ezetimibe and others, and to a much lesser extent fibrates have been the most successful in changing dyslipidemia patterns and but, in the case of inhibitors and fibrates without improving clinical outcomes in secondary prevention. In primary prevention, cholesterol lowering agents have not reduced the mortality rates, for example the AFCAPS/TexCAPS and EXCEL trials and the 2 main trials with atorvastatin, Lipitor, as in the ASCOT and SPARCL studies. Dietary changes to achieve benefit have been more controversial, generally far less effective and less widely adhered to with success.

Evidence has increased that people with diabetes, despite not having clinically detectable atherosclotic 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 disease equivalent.

Lowering homocysteine levels, including within the normal range and dietary supplements of Omega 3 oils, especially those from the muscle of some deep salt water living fish species, also have clinical evidence of significant protective effects as confirmed by 6 double blind placebo controlled human clinical trials.

Medical treatments often focus predominantly on the symptoms. However, over time, the treatments which focus on decreasing the underlying atherosclerosis processes, as opposed to simply treating the symptoms resulting from the atherosclerosis, have been shown by clinical trials to be more effective.

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 additional blood supply connections which go around the more severely narrowed areas.

High dose supplements of vitamin E or C, with the goal of improving antioxidant protection, have failed to produce any beneficial trends in human, double blind, clinical research trials. However, these trials have consistently used lower doses than those claimed to be effective and have ignored the short half life of high intakes of vitamin C in the body.

On the other hand, the statins, and some other medications have been shown to have antioxidant effects, possibly part of their basis for some of their therapeutic success in reducing cardiac 'events'.

The success of statin drugs in clinical trials is based on some reductions in mortality rates, however never in women or people over the age of 70 CMAJ. For example, in 4S, the first large placebo controlled, randomized clinical trial of a statin in people with advanced disease who had already suffered a heart attack, the overall mortality rate reduction for those taking the statin, vs. placebo, was 30%. For the subgroup of people in the trial who had Diabetes Mellitus, the mortality rate reduction between statin and placebo was 54%. 4S was a 5.4 year trial which started in 1989 and was published in 1995 after completion. There were 3 more dead women at trial's end on statin than in the group on placebo drug. The |ASTEROID trial, mentioned above and in reference 3, has been the first to show actual disease volume regression (see page 8 of the paper which shows cross-sectional areas of the total heart artery wall at start and 2 years of rosuvastatin 40 mg/day treatment); however, its design was not able to "prove" the mortality reduction issue since it has no placebo group.

In summary, the key to the more effective approaches has been better understanding of the widespread and 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, adopting more aggressive combination treatment strategies has generally produced better results, both before and especially after people are symptomatic. However, treating asymptomatic people remains controversial in the medical community.

Patients at risk for atherosclerosis-related diseases are increasingly being treated prophylactically with low-dose aspirin and a statin. The high incidence of cardiovascular disease led Wald and Law to propose a Polypill, a once-daily pill containing these two types of drugs in addition to an ACE inhibitor, diuretic and beta blocker and folic acid. They maintain that high uptake by the general population by such a Polypill would reduce cardiovascular mortality by 80%. It must be emphasized however that this is purely theoretical, as the Polypill has never been tested in a clinical trial.

Recent research

Methods to increase high density lipoprotein (HDL) particle concentrations, which in some animal studies largely reverses and remove atheromas, are being developed and researched. Niacin has HDL raising effects (by 10 - 30%) and showed clinical trial benefit in the Coronary Drug Project, however, the drug torcetrapib most effectively raising HDL (by 60%) also raised deaths by 60% and all studies regarding this drug were halted in December 2006.[3]

An indication of the role of HDL on atherosclerosis has been with the rare Apo-A1 Milano human genetic variant of this HDL protein. Ongoing work starting in the 1990s may lead to human clinical trials probably by about 2008, on using either synthesized Apo-A1 Milano HDL directly or by gene-transfer methods to pass the ability to synthesize the Apo-A1 Milano HDL protein.

The ASTEROID trial used a high-dose of a powerful statin, rosuvastatin, and found plaque (intima + media volume) reduction; see the Effect of Very High-Intensity Statin Therapy reference below. No attempt has yet been made to compare this drug with placebo regarding clinical benefit.

Since about 2002, progress in understanding and developing techniques for modulating immune system function so as to significantly suppress the action of macrophages to drive atherosclerotic plaque progression are being developed with considerable success in reducing plaque development in both mice and rabbits. Plans for human trials, hoped for by about 2008, are in progress. Generally these techniques are termed immunomodulation of atherosclerosis.

Genetic expression and control mechanism research, including (a) the PPAR peroxisome proliferator activated receptors known to be important in blood sugar and variants of lipoprotein production and function and (b) of the multiple variants of the proteins which form the lipoprotein transport particles, is progressing.

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.

The immunomodulation approaches mentioned above, because they deal with innate responses of the host to promote atherosclerosis, have far greater prospects for success.

Pathological Findings

Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

• 
  Atherosclerosis: Gross, close-up of fatty streak and intimal thickening
• 
  Atherosclerosis: Gross, very good example of fibrous plaques with ulceration and thrombosis
• 
  Atherosclerosis: Gross, proximal left anterior descending artery showing faint fatty streaks and penetrating arteries
• 
  Atherosclerosis: Gross, close-up view of aorta. A plaque with ulceration and thrombosis

• 
  Atherosclerosis: Gross, good example of plaques in aorta
• 
  Atherosclerosis: Coronary artery: Gross, close-up view of excellent plaque lesion causing more than 90% occlusion
• 
  Atherosclerosis: Gross, good example of advanced calcific atherosclerosis in aorta.
• 
  Atherosclerosis: Gross, very good example of calcified and ulcerated atheromatous plaques in aorta

• 
  Atherosclerosis: Dissecting Aortic Aneurysm: Gross, shows dilated aorta with extensive atherosclerosis dissection is seen. A small abdominal aorta, atherosclerotic aneurysm is present. A good picture for association of dilation with dissection
• 
  Atherosclerosis: Gross, close-up, an excellent view but appearance much like that of syphilitic aortitis
• 
  Atherosclerosis: Gross, an excellent example of ulcerated lesions with many mural thrombi
• 
  Atherosclerosis: Gross, very good example of plaque lesion and small mural thrombi

• 
  Atherosclerosis: Coronary artery: Gross, an excellent example of plaque, 80% occlusion, uncomplicated lesion.
• 
  Atherosclerosis: Coronary artery: Atherosclerosis and thrombotic occlusion: Gross, (an excellent example) in situ on heart
• 
  Atherosclerosis: Coarctation: Gross, adult lesion with dramatic demonstration of accelerated atherosclerosis
• 
  Atherosclerosis: Coronary artery: Gross, cross section well shown hemorrhage into plaque and thrombosis

• 
  Atherosclerosis: Aorta: Gross, good example of fibrous plaques
• 
  Atherosclerosis: Aorta: Gross, an excellent example of fibrous plaques and mural thrombi
• 
  Atherosclerosis: Aorta: Gross, thrombi at the origin of celiac axis and superior mesenteric arteries
• 
  Atherosclerosis: Aorta: Gross, thrombotic occlusion extending from just below renal arteries into iliac artery

• 
  Atherosclerosis: Abdominal Aneurysm Ruptured: Gross, a good example, opened kidneys in marked place. Atherosclerosis in lower thoracic aorta
• 
  Atherosclerosis: Adult type coarctation with atherosclerosis in aortic arch
• 
  Atherosclerosis: Abdominal Aneurysm Graft Repair: Gross natural color, close-up, an excellent example of Dacron graft that has been in place for years with pseudointima and atherosclerosis
• 
  Atherosclerosis: Renal Transplant: Gross, natural color, a close-up view of severe atherosclerosis in abdominal segment of aorta and fatty streaks in descending thoracic much advanced lesions for a 22 years old male with chronic glomerulonephritis

Saphenous Vein Graft

• 
  Saphenous vein coronary bypass graft: Atherosclerosis: Micro, an excellent demonstration of myofibroblastic type cells in thickened intima
• 
  Saphenous vein coronary bypass graft: Atherosclerosis: Micro, trichrome low mag, advanced plaque with hemorrhage into atheroma and complete lumen occlusion with fresh thrombus
• 
  Saphenous vein coronary bypass graft: Atherosclerosis: Micro, low mag, early atheromata consisting of subendothelial foam cells, whole graft and fibrous intimal thickening, (102 months after CABG)
• 
  Saphenous vein coronary bypass graft: Atherosclerosis: Micro, high mag, subendothelial foam cells

• 
  Saphenous vein coronary bypass graft: Atherosclerosis: Micro, trichrome, low mag, large athero plaque and recanalized thrombus in lumen
• 
  Saphenous vein coronary bypass graft: Atherosclerosis: Micro, H&E, low mag, large and ruptured atheromatous plaque with focal hemorrhage and calcification
• 
  Saphenous vein coronary bypass graft: Atherosclerosis: Micro, trichrome, low mag, very complicated hemorrhagic and necrotic plaque with lumen occlusion. A recanalized thrombus and a large aneurysm at side filled with old blood and atheroma crystals
• 
  Saphenous vein coronary bypass graft: Atherosclerosis: Micro, ald. fusch., complicated occlusive lesion with organized and recanalized thrombus and old hemorrhage into atheroma

Coronary Arteries

Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

• 
  Coronary artery: Atherosclerosis: Micro, H&E, low mag, injected artery, good demonstration of organized and recanalized thrombus
• 
  Coronary artery: Atherosclerosis: Micro, H&E, low mag, injected artery, very good example of marked lumen stenosis due to typical fibrous plaque with some calcifications
• 
  Coronary artery: Atherosclerosis: Micro, H&E, injected artery, marked large plaque with thin fibrous cap has eroded to adventitia, the start of an aneurysm
• 
  Coronary artery: Atherosclerosis: Micro, H&E, low mag, an excellent example of plaque with calcification and marked narrowing of lumen. 90% lumen is occluded by thrombus

• 
  Coronary artery: Atherosclerosis: Micro, low mag, an excellent example of atheromatous plaque causing marked lumen obstruction. An uncomplicated plaque
• 
  Coronary artery: Atherosclerosis: Micro, H&E, low mag, an excellent example of athero plaque. the lumen is completely occluded
• 
  Coronary artery: Atherosclerosis: Micro, H&E, low mag, a plaque with hemorrhage and organizing mural thrombus in lumen
• 
  Coronary artery: Atherosclerosis: Micro, H&E, low mag, a good example of plaque with old hemorrhage and marked lumen compensation

• 
  Coronary artery: Atherosclerosis: Micro, H&E, med mag, plaque rupture with thrombosis
• 
  Coronary artery: Atherosclerosis: Micro, H&E, low mag, injected artery, a good example of atheromatous plaque that appears to owe much of its mass to an organized mural thrombus
• 
  Coronary artery: Atherosclerosis: Micro, H&E, low mag, typical uncomplicated fibrous plaque
• 
  Coronary artery: Atherosclerosis: Micro, H&E, low mag, a good example of athero plaque with marked lumen narrowing. A small mural thrombus in lumen

• 
  Coronary artery: Atherosclerosis: Micro, low mag, hemorrhage into plaque and thrombosis
• 
  Coronary artery: Atherosclerosis: Recanalized Thrombus: Micro, low mag, H&E, lesion is nearly completely organized, small adventitial dissection probably related to bypass surgery about 24 hours before death (a good example)
• 
  Coronary artery: Atherosclerosis: Plaque Hemorrhage and Thrombosis: Micro, low mag, H&E, quite good photo, large plaque with hemorrhage, organizing thrombus in lumen
• 
  Coronary artery: Atherosclerosis, Severe: Micro, low mag, H&E, more than 90% stenosis, also shown a side branch

Aorta

Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

• 
  Kidney: Atheromatous Embolus: Gross, natural color, external view of kidney with typical scarring pattern of repeated infarction and aorta with severe atherosclerosis (quite good example)
• 
  Aorta, Atherosclerosis: Gross, natural color, opened thoracic segment showing sessile plaques covering intima with several mural thrombi
• 
  Aorta, Atherosclerosis: Gross natural color view of descending thoracic and abdominal segments with expected distribution of atherosclerotic lesions in subject over 60 years old. Not much in thoracic segment and extensive plaques in abdominal segment, some with ulceration
• 
  Thrombus: Gross natural color aorta with kidneys showing thrombotic occlusion due to atherosclerosis beginning just below renal arteries and extending into common iliac (very good example)

Carotid Artery

Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

• 
  Carotid artery: Atherosclerosis: Gross, internal carotid plaque with thrombosis
• 
  Carotid artery: Atherosclerosis: Gross, plaque with hemorrhage in carotid bulb
• 
  Carotid artery bifurcation, atherosclerosis
• 
  Carotid artery, atherosclerosis and thrombosis
• 
  Carotid artery: Atherosclerosis: Gross, good example of carotid bulb plaque with thrombus

Lung

Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

• 
  Lung: Pulmonary fibrosis and atherosclerosis of pulmonary artery
• 
  Lung: Pulmonary fibrosis and atherosclerosis of pulmonary artery
• 
  Lung: Pulmonary fibrosis and atherosclerosis of pulmonary artery
• 
  Lung: Atherosclerosis: Gross, natural color, arteries show atherosclerotic plaque lesions

Pulmonary Artery

Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

• 
  Pulmonary artery atherosclerosis in patient with pulmonary hypertension
• 
  Pulmonary Artery Atherosclerosis: Gross, essentially natural color, artery stained by hemolysis, small plaque lesions
• 
  Atherosclerosis: Gross, natural color, close-up fatty plaques in large pulmonary artery
• 
  Atherosclerosis: Micro, low mag, van Gieson, thickened intima with fatty streak type lesion and preservation of fetal medial structure, a large pulmonary artery, 4yo male with primary pulmonary hypertension

Brain

Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

• 
  Brain: Atherosclerosis: Gross, a good example of atherosclerosis in vessels at base of brain.
• 
  Brain: Basilar Artery Atherosclerosis: Gross, fixed tissue, an external view of base of brain (typical lesion)
• 
  Brain: Old Cystic Encephalomalacia: Gross, fixed tissue, frontal lobe lesion with frontal artery atherosclerosis
• 
  Brain: Watershed Infarct and Carotid Atherosclerosis

Liver

Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

• File:Atherosclerosis 65.jpg
• File:Atherosclerosis 66.jpg
• File:Atherosclerosis 67.jpg
• File:Atherosclerosis 68.jpg

Kidney

Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

• 
  Atherosclerosis: Kidney: Atheromatous Embolus: Gross, natural color, kidney with typical scarring pattern of repeated embolism and aorta with severe atherosclerosis (a quite good example)
• 
  Atherosclerosis: Kidney: Atrophy secondary to renal artery atherosclerosis: Gross, natural color, both kidneys one very atrophic the large left kidney weighed 220 grams and the small left one 90 gram

Spleen

Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

• File:Atherosclerosis spleen 1.jpg
• File:Atherosclerosis spleen 2.jpg
• File:Atherosclerosis spleen 3.jpg
• File:Atherosclerosis spleen 4.jpg

See also

• Monckeberg's arteriosclerosis
• Artery
• Atheroma
• Fatty streaks
• Heart
• Coronary circulation
• Coronary catheterization
• Angiogram
• IVUS
• Arterial stiffness

cs:Ateroskleróza da:Åreforkalkning de:Arteriosklerose ko:동맥경화 it:Aterosclerosi he:טרשת עורקים nl:Atheromatose no:Åreforkalkning fi:Ateroskleroosi sv:Åderförkalkning