Understanding Atherosclerosis - The Leading Cause of Death and Disability

About Preventive Cardiology Center Disease Prevention Know Your Risks Healthy Heart Information

Atherosclerosis is a treacherous disease of arteries which causes stroke, heart attack, aneurysms and loss of circulation to the legs. It is like a cancer growing and spreading in the walls of an artery. It begins as little tumors called plaques. They grow, become confluent, form thick scars and accumulate calcium.

Atherosclerosis eventually narrows the opening or lumen of the artery to such a degree that symptoms occur. However, the small, asymptomatic plaques are the most dangerous. They are inflamed and actively growing and prone to suddenly rupture. This causes a blood clot, cuts off blood flow, and can result in a heart attack.

Atherosclerosis Causes Death and Disability

Heart disease and stroke are the leading causes of death in this country. Each year some 1.5 million people will have a heart attack and one-third of these will die. 41% of all deaths are due to cardiac and vascular diseases.1

These problems cause serious ongoing illness in those who survive. They are responsible for 6 million hospitalizations each year.2 Four million Americans have survived a stroke and live disabled lives. 13.5 million have survived a heart attack and live with symptomatic heart disease.3

The Importance of Early Diagnosis and Identifying Risk Factors

Establishing a diagnosis of early atherosclerosis, before complications or disability develop, is very important. Identifying conditions predisposing you to develop atherosclerosis can lead to tests identifying it in the earliest stages. Intervention can then begin.

These predisposing conditions are called Risk Factors. They are listed below in the section titled "Atherosclerotic Disease Risk Factor Assessment". Some can be changed and to the extent they are altered, future risk is reduced.

Many of these risk factors run in families. The search for increased genetic risk should extend to families of persons who develop atherosclerotic disease at a young age. The future health and well being of these family members can be improved

Understanding the Disease

One must first understand the disease process to properly appreciate the importance of early detection, the diagnostic tests employed, the treatments used and the possibility of control or regression. The progression of atherosclerosis can be artificially divided into six stages illustrated below.4

Phase 0: No symptoms. Normal artery. Normal blood flow.

Phase 1: No symptoms. Fatty streak in the artery wall and beginning plaque growth.

Phase 2: No symptoms. Plaque grows like a boil or tumor in the artery wall. It accumulates cholesterol in little lakes like swiss cheese. Surrounding the cholesterol are inflammatory pus cells. Over the top of the plaque is connective tissue forming a cap. At this stage the plaque is soft and inflamed. Over time this plaque may evolve into a mass of scar tissue and even calcify.

Phase 3: No symptoms. The weak border of the plaque cap ruptures, exposing angry tissue beneath. A small clot forms, eventually scars over and the plaque continues to grow. These small cap ruptures and small clots probably happen frequently in atherosclerotic arteries.

Phase 3b: Angina, unstable angina. Plaque margin rupture occurs and a large clot accumulates. The artery diameter is suddenly reduced by 70% and the artery area for blood flow is likewise reduced. The heart muscle cannot get enough blood and chest pain occurs with activity (stable angina) or is unprovoked and occurs at rest (unstable angina).

Phase 4: Heart attack, ischemic sudden death. Plaque rupture and clot suddenly occludes the artery totally. Heart muscle dies if the clot persists for 2-3 hours or more and a heart attack results. The heart muscle forms a scar. If the occluded artery induces the muscle to produce certain abnormal heart rhythms (ventricular tachycardia or ventricular fibrillation), the circulation collapses and death occurs.

Phase 5: Heart failure, arrhythmias or no symptoms. The artery is chronically occluded and a heart attack has been survived. A weakened heart muscle may lead to enlargement and heart failure which is a syndrome of poor pumping performance. Scarred heart attacks can cause a variety of abnormal heart rhythms. Lucky hearts heal well and have few subsequent symptoms.

Diagnosis After the Fact

Atherosclerosis is easy to diagnose after an atherosclerotic "event". These events are:

Stroke: A stroke can be due to a number of causes including bleeding, embolism and atherosclerotic obstruction of the carotid artery in the neck or an artery in the brain. The usual tests done at the time of the stroke would point to atherosclerotic arterial disease. Heart attack or angina.
Heart Attack or Angina: Heart attack or the development of angina is almost always due to atherosclerotic disease of the coronary arteries. It is very rarely a congenital artery problem or an inflammatory connective tissue disease of arteries. Essentially everyone who has had angina, a heart attack, angioplasty or coronary bypass surgery has atherosclerosis.
Arterial Vascular Insufficiency of the Legs: This condition causes pain in the calves and thighs while walking and this symptom is called claudication. Almost all with this problem have advanced atherosclerosis.
Aneurysm: Aneurysms of the aorta are usually due to a type of atherosclerosis, although there are other causes. These most commonly occur in the abdomen but can be seen in the chest or elsewhere. The danger posed by an aneurysm is that the wall weakens as the aneurysm enlarges and rupture can occur leading to death.

Early Detection of Atherosclerosis

Prior to symptoms,the earlier symptoms of atherosclerosis can be diagnosed by detecting obstruction to flow using a functional test or by imaging certain arteries:

Functional tests.
These detect asymptomatic obstruction of arteries through exercise or other stress. Examples are the exercise treadmill test, stress echocardiogram, pharmacologic stress test, or nuclear stress test. These can identify coronary artery disease before symptoms develop during ordinary daily activity. However, arteries must be blocked up to 50-70% before these tests become abnormal or symptoms occur.

Carotid artery duplex scanning.
Ultrasound to image the carotid artery in the neck and detect small plaques long before they cause a problem.5

Electron Beam CT Scanning (EBCT or UltraFast CT).
EBCT is a special x-ray test which can identify calcium in the heart's coronary arteries.6 Older, scarred plaques calcify. Most of us accumulate some degree of coronary calcification as we age. However, extensive calcium can be present in asymptomatic individuals who have normal stress tests. This obstruction is usually less than 50% and is not yet severe. An abnormally high amount for age can indicate advancing atherosclerosis and constitute one of the "new risk factors" for heart attack listed below. Such a high score establishes a diagnosis of atherosclerotic disease and justifies aggressive treatment to prevent progression.

Atherosclerotic Disease Risk Factor Assessment

Certain conditions accelerate development of atherosclerosis. These are called Risk Factors. They are divided into traditional risk factors and newly recognized risk factors.

Traditional Risk Factors:
1. Family history of premature coronary heart disease or stoke in a first degree relative under the age of 60.
2. Tobacco abuse.
3. Diabetes.
4. High blood pressure.
5. Left ventricular hypertrophy (thickened heart muscle)
6. High cholesterol.

New Risk Factors (* signifies preliminary findings):
7. Small, dense LDL cholesterol.
8. Abnormal Electron Beam CT Scan.
9. Abnormal HDL Subclass.
10. Elevated Lipoprotein(a).
11. Elevated Homocysteine.
12. Elevated Fibrinogen*
13. Elevated C-Reactive Protein*
14. Elevated Antibody Titer to certain infections*

Specific medical treatments are available for all the standard risk factors listed above, excluding family history. Treatments are also available for all the newer risk factors although the benefit remains speculative for the last three on the list.

Aggressive Treatment to Decelerate Atherosclerosis

Atherosclerosis has momentum. When discovered it has been present for decades, relentlessly progressing. It cannot be slowed or stopped immediately. A runaway train going 90 miles per hour down the track will not suddenly stop because the engineer stops shoveling coal into the burner.

Likewise, treating risk factors will not slow atherosclerosis right away. The disease already present (called the "atherosclerotic burden") will progress through its natural history. New, young plaque will evolve to scarred, calcified plaque. Some young plaques may rupture and cause symptoms because they were there before treatment began. A treatment effect seems to begin at about six months.

Aggressive treatment is designed to stop the appearance of new, dangerous atherosclerotic plaques. While treating all risk factors helps, driving down circulating LDL cholesterol helps prevent the deposition of this key building block of new plaque. It has proven very effective in reducing future atherosclerotic events such as heart attack and stroke. 7, 8

Aggressive lipid reduction to an average LDL of 106 in patients with documented coronary atherosclerosis resulted in a remarkable 1.3% death rate at 10 years versus 19.8% in a usual care group without such lipid reduction (FATS Study). 9 Likewise, patients with one or two vessel coronary stenoses who were treated with aggressive LDL reduction to an average value of 76 did just as well over an 18 month follow-up as those treated with balloon angioplasty (AVERT Study). 10

Thus the key component of aggressive treatment to decelerate and stop atherosclerosis is reduction of LDL cholesterol to goal levels, usually 85 to 100. All other risk factors require goal-directed treatment as well, particularly diabetes and hypertension. Target glucose values in diabetics and blood pressures in hypertensives should be lower than the usual goal in patients without known atherosclerosis.

Non-Medical (Non-Prescription) Treatments

Diet.

Changes in dietary fat intake combined with exercise can result in lowering of cholesterol, improved blood pressure, and better regulation of diabetes. However, the cholesterol benefit of diet is modest and usually not enough to lower cholesterol levels to the targets now recommended. 11

Vitamins.

The use of antioxidant vitamins is now standard medical practice in atherosclerosis for all those with elevated LDL cholesterol. These vitamins are E and C.12

Aspirin.

One single aspirin a day is also almost universally prescribed. It has proven benefit in preventing certain kinds of strokes and reducing the number of heart attacks.13

Lifestyle modification.

Diet and exercise combined with efforts to alleviate stress are well established recommendations from physicians. The additional value of special programs to achieve these goals such as the Ornish Program 14 or the Pritikin Plan 15 remain speculative. Some of these programs are too expensive and time consuming for most working people.

Chelation.

There has never been any scientific evidence that chelation "reverses" atherosclerosis by removing calcium as was once claimed.16 However, certain current intravenous "chelation therapies" now use vitamins rather than EDTA and make no claim to remove calcium from arteries. In reality, they may act as antioxidants like oral vitamins and may improve artery function without reducing the amount of plaque.17

Regression of Atherosclerosis

Aggressive treatment can stabilize and in some cases reverse atherosclerosis.8 The older, scared and calcified arteries will never improve. Only the smaller, younger and more dangerous plaque appears to resolve.18, 19 However, this can provide the most benefit by reducing the probability of future heart attack.

Your Doctor and a Supervised Treatment Plan

After reading the above documents, it must be clear that the diagnosis of atherosclerosis and its treatment are complex matters. They should be supervised by your personal physician with the help of specialists when necessary. A diagnosis of atherosclerosis implies a lifelong medical problem requiring intervention and long term follow-up. Specialty consultation, dietary and exercise counseling, regular follow-up and treatment of risk factors will be necessary. All of this should be supervised by a physician whom you know well and who can coordinate all aspects of your care.

References - Understanding Athlerosclerosis

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2. Graves, EJ. National Hospital Discharge Survey: Annual Summary, 1992. Vital Health Statistics (13) 1994; 119.

3. Breslow, JL. Cardiovascular Disease Myths and Facts. Clev Clin J Med 1998; 65:286-287.

4. Fuster, V. Mechanisms leading to myocardial infarction: Insights from Studies of Vascular Biology. Circ 1994; 90: 2126-2146.

5. Furberg, CD et al. Effect of Lovastatin on Early Carotid Atherosclerosis and Cardiovascular Events: Asymptomatic Carotid Artery Program Study (ACAPS). Circ 1994; 90: 1679-1687.

6. Brundage, BH. Beyond Perfusion with Ultrafast Computed Tomography. Am J Cardiol 1995; 75: 69D - 73D.

7. Crouse, JR et al. Pravastatin, Lipids and Atherosclerosis in the Carotid Arteries (PLAC II) AM J Cardiol 1995; 75: 455 - 459.

8. Superko, HR et al. Coronary Artery Disease Regression: Convincing Evidence for the Benefit of Aggressive Lipoprotein Management. Circ 1994; 90: 1056 - 1069.

9. Brown, BG et al. Very Intensive Lipid therapy with lovastatin, Niacin and Colestipol for Prevention of Death and Myocardial Infarction: A Ten Year Familial Atherosclerosis Treatment Study (FATS) Follow-up 1998. Sirc; I-635.

10. Pitt, B et al. AVERT Study 1998.

11. Denke, MA. Cholesterol Lowering Diets: A Review of the Evidence. Arch Int Med 1995; 155: 17-26.

12. Mosca, L et al. Antioxidant Nutrient Supplementation Reduces the Succeptibility of Low Density Lipoprotein to Oxidation in Patients with Coronary Artery Disease. J Am Coll Cardiol 1997; 30: 392-399.

13. Lewis, HD et al. Protective Effects of Aspirin Against Acute Myocardial Infarction and Death in Men With Unstable Angina. NEJM 1983; 309: 396-403.

14. Ornish, D. Can Life-Style Changes Reverse Coronary Atherosclerosis? Hosp Practice 1991; May: 123-132.

15. Barnard, RJ. Effects of Life-Style Modification on Serum Lipids. Arch Int Med 1991; 151: 1389-1394.

16. Van Rij et al. Chelation Therapy for Intermittent Claudication. A Double Blind, Randomized Controlled Trial. Circ 1994: 90: 1194-1199.

17. Plotnick, GD et al. Effect of Antioxidant Vitamins on the Transient Impairment of Endothelium-Dependent Brachial Artery Vasoactivity Following a Single High Fat Meal. JAMA 1997; 278: 1682-1686.

18. Blankenhorn, DH et al. For the MARS Group. Coronary Angiographic Changes with Lovastatin Therapy. Ann Intern Med 1993; 119: 969-976.

19. Waters, D et al for the CCAIT Group. Effects of Monotherapy with an HMG-CoA Reductase Inhibitor on the Progression of Coronary Atherosclerosis as Assessed by Serial Quantitative Angiography. Circ 1994; 89: 959-968.