Heart Attack (Myocardial Infarction)

Heart attack facts

• A heart attack results when a blood clot completely obstructs a coronary artery supplying blood to the heart muscle and heart muscle dies.
• The blood clot that causes the heart attack usually forms at the site of rupture of an atherosclerotic, cholesterol plaque on the inner wall of a coronary artery.
• The most common symptom of heart attack is chest pain.
• The most common complications of a heart attack are heart failure and ventricular fibrillation.
• The risk factors for atherosclerosis and heart attack include elevatedcholesterol levels, increased blood pressure, tobacco use, diabetes, male gender, and a family history ofheart attacks at an early age.
• Heart attacks are diagnosed with electrocardiograms and measurement of cardiac enzymes in blood.
• Treatment guidelines emphasize treatment at a hospital capable of doing PCI (percutaneous coronary intervention) also termed as stenting or stent placement.
• Early reopening of blocked coronary arteries reduces the amount of damage to the heart and improves the prognosis for a heart attack.
• Medical treatment for heart attacks may include antiplatelet, anticoagulant, and clot dissolving drugs as well as angiotensin converting enzyme (ACE) inhibitors, beta blockers, and oxygen.
• Interventional treatment for heart attacks may include coronary angiography with percutaneous transluminal coronary angioplasty (PTCA), coronary arterystents, and coronary artery bypass grafting (CABG).
• Patients suffering a heart attack are hospitalized for several days to detect heart rhythm disturbances, shortness of breath, and chest pain.
• Further heart attacks can be prevented by aspirin, beta blockers, ACE inhibitors, discontinuing smoking, weight reduction, exercise, good control of blood pressure and diabetes, following a low cholesterol and low saturated fat diet that is high in omega-3-fatty acids, taking multivitamins with an increased amount of folic acid, decreasing LDL cholesterol, and increasing HDL cholesterol.

What is a heart attack?

A heart attack (also known as a myocardial infarction or MI) is the damage and death of heart muscle from the sudden blockage of a coronary artery by a blood clot. Coronary arteries are blood vessels that supply the heart muscle with blood and oxygen. Blockage of a coronary artery deprives the heart muscle of blood and oxygen, causing injury to the heart muscle. Injury to the heart muscle causes chest pain and chest pressure sensation. If blood flow is not restored to the heart muscle within 20 to 40 minutes, irreversible death of the heart muscle will begin to occur. Muscle continues to die for six to eight hours at which time the heart attack usually is "complete." The dead heart muscle is eventually replaced by scar tissue.

What causes a heart attack?

Atherosclerosis

Atherosclerosis is a gradual process by which plaques (collections) of cholesterol are deposited in the walls of arteries. Cholesterol plaques cause hardening of the arterial walls and narrowing of the inner channel (lumen) of the artery. Arteries that are narrowed by atherosclerosis cannot deliver enough blood to maintain normal function of the parts of the body they supply. For example, atherosclerosis of the arteries in the legs causes reduced blood flow to the legs. Reduced blood flow to the legs can lead to pain in the legs whilewalking or exercising, leg ulcers, or a delay in the healing of wounds to the legs. Atherosclerosis of the arteries that furnish blood to the brain can lead to vascular dementia (mental deterioration due to gradual death of brain tissue over many years) or stroke(sudden damage and death of brain tissue).

In many people, atherosclerosis can remain silent (causing no symptoms or health problems) for years or decades. Atherosclerosis can begin as early as the teenage years, but symptoms or health problems usually do not arise until later in adulthood when the arterial narrowing becomes severe. Smoking cigarettes, high blood pressure, elevated cholesterol, anddiabetes mellitus can accelerate atherosclerosis and lead to the earlier onset of symptoms and complications, particularly in those people who have a family history of early atherosclerosis.

Coronary atherosclerosis (or coronary artery disease) refers to the atherosclerosis that causes hardening and narrowing of the coronary arteries. Diseases caused by the reduced blood supply to the heart muscle from coronary atherosclerosis are called coronary heart diseases (CHD). Coronary heart diseases include heart attacks, sudden unexpected death, chest pain (angina), abnormal heart rhythms, and heart failure due to weakening of the heart muscle.

Atherosclerosis and angina pectoris

Angina pectoris (also referred to as angina) is chest pain or pressure that occurs when the blood and oxygen supply to the heart muscle cannot keep up with the needs of the muscle. When coronary arteries are narrowed by more than 50 to 70 percent, the arteries may not be able to increase the supply of blood to the heart muscle during exercise or other periods of high demand for oxygen. An insufficient supply of oxygen to the heart muscle causes angina. Angina that occurs with exercise or exertion is called exertional angina. In some patients, especially in people with diabetes, the progressive decrease in blood flow to the heart may occur without any pain or with just shortness of breath or unusually early fatigue.

Exertional angina usually feels like a pressure, heaviness, squeezing, or aching across the chest. This pain may travel to the neck, jaw, arms, back, or even the teeth, and may be accompanied by shortness of breath, nausea, or a cold sweat. Exertional angina typically lasts from one to 15 minutes and usually is relieved by rest or by placing a tablet ofnitroglycerin under the tongue. Both resting and nitroglycerin decrease the heart muscle's demand for oxygen, thus relieving angina. Exertional angina may be the first warning sign of advanced coronary artery disease. Chest pains that just last a few seconds rarely are due to coronary artery disease.

Angina also can occur at rest. Angina at rest more commonly indicates that a coronary artery has narrowed to such a critical degree that the heart is not receiving enough oxygen even at rest. Angina at rest infrequently may be due to spasm of a coronary artery (a condition called Prinzmetal's or variant angina). Unlike a heart attack, there is no permanent muscle damage with either exertional or rest angina although the angina is a warning sign that there is an increased chance of a heart attack in the future.

Atherosclerosis and heart attack

Occasionally the surface of a cholesterol plaque in a coronary artery may rupture, and a blood clot forms on the surface of the plaque. The clot blocks the flow of blood through the artery and results in a heart attack (see picture below). The cause of rupture that leads to the formation of a clot is largely unknown, but contributing factors may include cigarette smoking or other nicotine exposure, elevated low-density lipoprotein (LDL) cholesterol, elevated levels of blood catecholamines (adrenaline), high blood pressure, and other mechanical and biochemical stimuli.

Unlike exertional or rest angina, heart muscle dies during a heart attack and loss of the muscle is permanent, unless blood flow can be promptly restored, usually within one to six hours.

Heart Attack illustration - Myocardial Infarction

While heart attacks can occur at any time, more heart attacks occur between 4 A.M. and 10 A.M. because of the higher blood levels of adrenaline released from the adrenal glands during the morning hours. Increased adrenaline, as previously discussed, may contribute to rupture of cholesterol plaques.

Only half of patients who develop heart attacks have warning signs such as exertional angina or rest angina prior to their heart attacks, but these signs may be mild and ignored as unimportant.

What are the symptoms of a heart attack?

Although chest pain or pressure is the most common symptom of a heart attack, heart attack victims may experience a variety of conditions including:

• Pain, fullness, and/or squeezing sensation of the chest
• Jaw pain, toothache, headache
• Shortness of breath
• Nausea, vomiting, and/or general epigastric (upper middle abdomen) discomfort
• Sweating
• Heartburn and/or indigestion
• Arm pain (more commonly the left arm, but may be either arm)
• Upper back pain
• General malaise (vague feeling of illness)
• No symptoms (Approximately one quarter of all heart attacks are silent, without chest pain or new symptoms. Silent heart attacks are especially common among patients with diabetes mellitus.)

Even though the symptoms of a heart attack at times can be vague and mild, it is important to remember that heart attacks producing no symptoms or only mild symptoms can be just as serious and life-threatening as heart attacks that cause severe chest pain. Too often patients attribute heart attack symptoms to "indigestion," "fatigue," or "stress," and consequently delay seeking prompt medical attention. One cannot overemphasize the importance of seeking prompt medical attention in the presence of new symptoms that suggest a heart attack. Early diagnosis and treatment saves lives, and delays in reaching medical assistance can be fatal. A delay in treatment can lead to permanently reduced function of the heart due to more extensive damage to the heart muscle. Death also may occur as a result of the sudden onset of arrhythmias such as ventricular fibrillation.

What are the complications of a heart attack?

Heart Failure

When a large amount of heart muscle dies, the ability of the heart to pump blood to the rest of the body is diminished, and this can result in heart failure. The body retains fluid, and organs, for example, the kidneys, begin to fail.

Ventricular fibrillation

Injury to heart muscle also can lead to ventricular fibrillation. Ventricular fibrillation occurs when the normal, regular, electrical activation of heart muscle contraction is replaced by chaotic electrical activity that causes the heart to stop beating and pumping blood to the brain and other parts of the body. Permanent brain damage and death can occur unless the flow of blood to the brain is restored within five minutes.

Most of the deaths from heart attacks are caused by ventricular fibrillation of the heart that occurs before the victim of the heart attack can reach an emergency room. Those who reach the emergency room have an excellent prognosis; survival from a heart attack with modern treatment should exceed 90%. The 1% to 10% of heart attack victims who later die frequently had suffered major damage to the heart muscle initially or additional damage at a later time.

Deaths from ventricular fibrillation can be avoided bycardiopulmonary resuscitation (CPR) started within five minutes of the onset of ventricular fibrillation. CPR requiresbreathing for the victim and applying external compression to the chest to squeeze the heart and force it to pump blood. In 2008, the American Heart Association modified the mouth-to-mouth instruction of CPR, and recommends that chest compressions alone are effective if a bystander is reluctant to do mouth-to-mouth. When paramedics arrive, medications and/or an electrical shock (cardioversion) can be administered to convert ventricular fibrillation back to a normal heart rhythm and allow the heart to pump blood normally. Therefore, prompt CPR and a rapid response by paramedics can improve the chances of survival from a heart attack. In addition, many public venues now have automatic external defibrillators (AEDs) that provide the electrical shock needed to restore a normal heart rhythm even before the paramedics arrive. This greatly improves the chances of survival.

What are the risk factors for atherosclerosis and heart attack?

Factors that increase the risk of developing atherosclerosis and heart attacks include increased blood cholesterol, high blood pressure, use of tobacco, diabetes mellitus, male gender (although women may still be very much at risk -- see section at end of article), and a family history of coronary heart disease. While family history and male gender are genetically determined, the other risk factors can be modified through changes in lifestyle and medications.

• High Blood Cholesterol (Hyperlipidemia). A high level of cholesterol in the blood is associated with an increased heart attack risk because cholesterol is the major component of the plaques deposited in arterial walls. Cholesterol, like oil, cannot dissolve in the blood unless it is combined with special proteins called lipoproteins. (Without combining with lipoproteins, cholesterol in the blood would turn into a solid substance.) The cholesterol in blood is either combined with lipoproteins as very low-density lipoproteins (VLDL), low-density lipoproteins (LDL) or high-density lipoproteins (HDL).

The cholesterol that is combined with low-density lipoproteins (LDL cholesterol) is the "bad" cholesterol that deposits cholesterol in arterial plaques. Thus, elevated levels of LDL cholesterol are associated with an increased risk of heart attack.

The cholesterol that is combined with HDL (HDL cholesterol) is the "good" cholesterol that removes cholesterol from arterial plaques. Thus, low levels of HDL cholesterol are associated with an increased risk of heart attacks.

Measures that lower LDL cholesterol and/or increase HDL cholesterol (losing excess weight, diets low in saturated fats, regular exercise, and medications) have been shown to lower the risk of heart attack. One important class of medications for treating elevated cholesterol levels (the statins) have actions in addition to lowering LDL cholesterol which also protect against heart attack. Most patients at "high risk" for a heart attack should be on a statin no matter what the levels of their cholesterol.

• High Blood Pressure (Hypertension). High blood pressure is a risk factor for developing atherosclerosis and heart attack. Both high systolic pressure (the blood pressure as the heart contracts) and high diastolic pressure (the blood pressure as the heart relaxes) increase the risk of heart attack. It has been shown that controlling hypertension with medications can reduce the risk of heart attack.
• Tobacco Use (Smoking). Tobacco and tobacco smoke contain chemicals that cause damage to blood vessel walls, accelerate the development of atherosclerosis, and increase the risk of heart attack.
• Diabetes (Diabetes Mellitus). Both insulin dependent and noninsulin dependent diabetes mellitus (type 1 and 2, respectively) are associated with accelerated atherosclerosis throughout the body. Therefore, patients with diabetes mellitus are at higher risk for reduced blood flow to the legs, coronary heart disease,erectile dysfunction, and strokes at an earlier age than nondiabetic subjects. Patients with diabetes can lower their risk through rigorous control of their bloodsugar levels, regular exercise, weight control, and proper diets.
• Male Gender. Men are more likely to suffer heart attacks than women if they are less than 75 years old. Above age 75, women are as likely as men to have heart attacks.
• Family History of Heart Disease. Individuals with a family history of coronary heart diseases have an increased risk of heart attack. Specifically, the risk is higher if there is a family history of early coronary heart disease, including a heart attack or sudden death before age 55 in the father or other first-degree male relative, or before age 65 in the mother or other female first-degree female relative.

How to diagnose a heart attack

When there is severe chest pain, suspicion that a heart attack is occurring usually is high, and tests can be performed quickly that will confirm the heart attack. A problem arises, however, when the symptoms of a heart attack do not include chest pain. A heart attack may not be suspected, and the appropriate tests may not be performed. Therefore, the initial step in diagnosing a heart attack is to be suspicious that one has occurred so that the appropriate tests can be done.

Electrocardiogram. An electrocardiogram (ECG) is a recording of the electrical activity of the heart. Abnormalities in the electrical activity usually occur with heart attacks and can identify the areas of heart muscle that are deprived of oxygen and/or areas of muscle that have died. In a patient with typical symptoms of heart attack (such as crushing chest pain) and characteristic changes of heart attack on the ECG, a secure diagnosis of heart attack can be made quickly in the emergency room and treatment can be started immediately. If a patient's symptoms are vague or atypical and if there are pre-existing ECG abnormalities, for example, from old heart attacks or abnormal electrical patterns that make interpretation of the ECG difficult, the diagnosis of a heart attack may be less secure. In these patients, the diagnosis can be made only hours later through blood tests.

Blood tests. Cardiac enzymes are proteins that are released into the blood by dying heart muscles. These cardiac enzymes are creatine phosphokinase (CPK), special sub-fractions of CPK (specifically, the MB fraction of CPK), and troponin, and their levels can be measured in blood. These cardiac enzymes typically are elevated in the blood several hours after the onset of a heart attack. Currently, troponin levels are considered the preferred lab tests to use to help diagnose a heart attack, as they are indicators of cardiac muscle injury or death. A series of blood tests for the enzymes performed over a 24-hour period are useful not only in confirming the diagnosis of heart attack, but the changes in their levels over time also correlates with the amount of heart muscle that has died.

The most important factor in diagnosing and treating a heart attack is prompt medical attention. Rapid evaluation allows early treatment of potentially life-threatening abnormal rhythms such as ventricular fibrillation and allows early reperfusion (return of blood flow to the heart muscle) by procedures that unclog the blocked coronary arteries. The more rapidly blood flow is reestablished, the more heart muscle that is saved. At this time, mechanical reperfusion with angioplasty and/or stenting to increase the flow of blood to the heart is the preferred way to preserve heart muscle if it can be performed within 90 minutes of arrival to the hospital; if there will be a delay, thrombolytic agents (clot busters) are preferred.

Large and active medical centers often have a "chest pain unit" where patients suspected of having heart attacks are rapidly evaluated. If a heart attack is diagnosed, prompt therapy is initiated. If the diagnosis of heart attack is initially unclear, the patient is placed under continuous monitoring until the results of further testing are available.

What is the treatment for heart attack?

The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) task force recommends a treatment guideline that they consider as a preferred strategy to treat heart attacks; PCI (Percutaneous Coronary Intervention) or stenting is emphasized. For details about PCI, please see reference 2.

The 2013 ACCF/AHA guidelines for treatment of a heart attack are summarized as follows:

1. Ideally, transport patient to a PCI capable hospital; if not PCI capable, transfer patient as soon as possible and less than 120 min; if anticipated transfer is more than 120 min, give fibrinolytic agent within 30 min of arrival
2. Send to cath lab
3. Diagnostic angiogram
4. PCI (Percutaneous Coronary Intervention) also termed stenting or stent placement
5. If reocclusion occurs or perfusion fails in a patient given a fibrinolytic, arrange transfer to a PCI capable facility; for other patients treated with a fibrinolytic, transfer to a PCI facility within about 3-24hrs
6. If step 5 occurs, step 3 should follow at a PCI capable facility were either medical therapy, a PCI or a CABG should be done Patients who are not candidates for PCI therapy usually undergo medical or surgical (CABG) therapy. For a more detailed presentation of the medical treatments and CABG, read the heart attack treatment article.

What are the risk factors for heart attack in women?

Coronary artery disease (CAD) and heart attacks are erroneously believed to occur primarily in men. Although it is true that the prevalence of CAD among women is lower before menopause, the risk of CAD rises in women after menopause. At age 75, a woman's risk for CAD is equal to that of a man's. CAD is the leading cause of death and disability in women after menopause. In fact, a 50-year-old woman faces a 46% risk of developing CAD and a 31% risk of dying from coronary artery disease. In contrast, her probability of contracting and dying from breast cancer is 10% and 3%, respectively.

The risk factors for developing CAD in women are the same as in men and include:

• increased blood cholesterol,
• high blood pressure,
• smoking cigarettes,
• diabetes mellitus, and a
• family history of coronary heart disease at a young age.

Smoking cigarettes

Even "light" smoking raises the risk of CAD. In one study, middle-aged women who smoked one to 14 cigarettes per day had a twofold increase in strokes (caused by atherosclerosis of the arteries to the brain) whereas those who smoked more than 25 cigarettes per day had a risk of stroke 3.7 fold higher than that of nonsmoking women. Furthermore, the combination of smoking and the use of birth control pills increase the risk of heart attacks even further, especially in women over 35.

Quitting smoking immediately begins to reduce the risk of heart attacks. The risk gradually returns to the same risk of nonsmoking women after several years of not smoking.

Cholesterol treatment guidelines in women

Current NCEP (National Cholesterol Education Program) treatment guidelines for undesirable cholesterol levels are the same for women as for men.

What are the symptoms of heart attack in women and how is heart attack diagnosed?

Women are more likely to encounter delays in establishing the diagnosis of heart attack than men. This is in part because women tend to seek medical care later than men, and in part because diagnosing heart attacks in women can sometimes be more difficult than diagnosing heart attacks in men. The reasons include:

1. Women are more likely than men to have atypical heart attack symptoms such as:
   • neck and shoulder pain,
   • abdominal pain,
   • nausea,
   • vomiting,
   • fatigue, and
   • shortness of breath.
2. Silent heart attacks (heart attacks with little or no symptoms) are more common among women than among men.
3. Women have a higher occurrence than men of chest pain that is not caused by heart disease, for example chest pain from spasm of the esophagus.
4. Women are less likely than men to have the typical findings on the ECG that are necessary to diagnose a heart attack quickly.
5. Women are more likely than men to have angina (chest pain due to lack of blood supply to the heart muscle) that is caused by spasm of the coronary arteries or caused by disease of the smallest blood vessels (microvasculature disease). Cardiac catheterization with coronary angiograms (X-ray studies of the coronary arteries that are considered the most reliable tests for CAD) will reveal normal coronary arteries and therefore cannot be used to diagnose either of these two conditions.
6. Women are more likely to have misleading, or "false positive" noninvasive tests for CAD then men that don't disclose the arterial disease that is present.

Because of the atypical nature of symptoms and the occasional difficulties in diagnosing heart attacks in women, women are less likely to receive aggressive thrombolytic therapy or coronary angioplasty, and are more likely to receive it later than men. Women also are less likely to be admitted to a coronary care unit. 

How is heart attack in women treated?

Thrombolytic (fibrinolytic or clot dissolving) therapy has been shown to reduce death from heart attacks similarly in men and women; however, the complication of strokes from the thrombolytic therapy may be slightly higher in women than in men.

Emergency percutaneous transluminal coronary angioplasty (PTCA) or coronary stenting for acute heart attack is as effective in women as in men; however women may have a slightly higher rate of procedure-related complications in their blood vessels (such as bleeding or clotting at the point of insertion of the PTCA catheter in the groin) and death. This higher rate of complications has been attributed to women's older age, smaller artery size, and greater severity of angina. The long-term outcome of angioplasty or stenting however, is similar in men and women, and should not be withheld due to gender. This is still the preferred mode of therapy if it can be performed in a timely fashion.

The immediate mortality from coronary artery bypass graftsurgery (CABG) in women is higher than that for men. The higher immediate mortality rate has been attributed to women's older age, smaller artery size, and greater severity of angina (the same as for PTCA). Long-term survival, rate of recurrent heart attack and/or need for reoperation, however, are similar in men and women after CABG.

What about hormone therapy and heart attack in women?

After menopause, the production of estrogen by the ovaries gradually diminishes over several years. Along with this reduction, there is an increase in LDL ("bad" cholesterol) and a small decrease in HDL ("good" cholesterol). These changes in lipid levels are believed to be one of the reasons for the increased risks of developing CAD after menopause. Women who have had their ovaries surgically removed (oophorectomy) or experience an early menopause, also have an accelerated risk of CAD.

Since treatment with estrogen hormone results in higher HDL and lower LDL cholesterol levels, doctors thought for many years that estrogen would protect women against CAD (as well protect against dementia and stroke). Many studies have found thatpostmenopausal women who take estrogen have lower CAD rates than women who do not. Unfortunately many of the studies were observational studies (studies in which women are followed over time but decide on their own whether or not they wish to take estrogen). Observational studies have serious shortcomings because they are subject to selection bias; for example, women who choose to take estrogen hormones may be healthier and have a lower risk of heart attacks than those who do not. In other words, something else in the daily habits of women who take estrogen (such as exercise or healthier diet) may make them less likely to develop heart attacks. Therefore, only a randomized trial (a study in which women agree to be assigned to estrogen or a placebo or sugar pill at random but are not told which pills they took until the end of the study) can establish whetherhormone therapy after menopause can prevent CAD.

HERS trial results

The Heart and Estrogen/progestin Replacement Study (HERS), was a randomized placebo-controlled trial of the effect of the daily use of estrogens plus medroxyprogesterone(progestin) on the rate of heart attacks in postmenopausal women who already had CAD. The HERS trial did not find a reduction in heart attacks in women who took hormone therapy. This lack of benefit in preventing heart attacks occurred despite an 11% lower LDL and a 10% higher HDL cholesterol level in the women treated with hormones. The study also found that more women in the hormone-treated group experienced blood clots in the veins and gallbladder disease than women in the placebo-treated group. (Blood clots in the veins are dangerous because these clots can travel to the lungs and cause pulmonary embolism, a condition with chest pain, shortness of breath, and even shock and death.) However, the increase in gallbladder disease and blood clots among healthy users of estrogen who do not have heart disease is very small.

Based on the results of this study, researchers concluded that estrogen is not effective in preventing coronary artery disease and heart attacks in postmenopausal women who already have CAD. It should be noted, however, that the results of the HERS trial only apply to women who have known CAD prior to starting hormone therapy and not to women without known coronary artery disease.

WHI trial results

The Women's Health Initiative (WHI) was the first randomized controlled trial designed to determine the long-term benefits and risks of treatment with estrogens plus medroxyprogesterone (progestin) in healthy menopausal women (women without CAD). The results were reported in a series of articles in 2002, 2003, and 2004. The estrogen + progestin portion of the WHI study had to be stopped earlier than planned, after just 5.2 years, because the increase in coronary heart disease, stroke, and pulmonary embolismamong women who use estrogen + progesterone outweighed the benefits of reduced bonefractures and colon cancer. The estrogen-alone portion of the WHI was stopped because women who took estrogen alone had no reduction in heart attack risk, yet there was a significant increase in stroke risk.

An increase in breast cancer became apparent after three to five years, but the increase in heart disease and pulmonary emboli occurred early on, in the first year.

Recommendations for the use of estrogens plus medroxyprogesterone (progestin) in women

MedicineNet Medical Editors believe that:

• Decisions regarding use of hormone therapy have to be individualized, and all women should discuss with their physicians what is best for them.
• Estrogens plus medroxyprogesterone (progestin) is still the best therapy for hot flashes. Despite the WHI study, many women remain good candidates for estrogens plus medroxyprogesterone (progestin) therapy (or estrogen alone if they have had hysterectomy). This is especially true if hormone therapy is limited to the shortest duration, optimally less than five years.
• Estrogens with or without medroxyprogesterone (progestin) should not be used to prevent or treat either Alzheimer's disease, heart disease, or stroke.
• While estrogens plus medroxyprogesterone (progestin) are effective in preventing osteoporosis and related bone fractures, women concerned about the risk of hormone therapy should discuss their concerns with their doctors, the use of other nonhormonal alternatives to prevent and treat osteoporosis

What is new in heart attack?

Greater public awareness about heart attacks and changes in lifestyle have contributed to a dramatic reduction in the incidence of heart attacks during the last four decades. The role of the "super aspirins" (abciximab [Reopro] and eptifibatide [Integrilin]) has been established to be of benefit in selected patients.

More effective versions of clot-busting drugs have been developed. Increasingly, paramedics can do ECGs in the field, diagnose a heart attack, and take patients directly to hospitals that have the ability to do PTCA and stenting. This can save time and reduce damage to the heart. At present, the accepted best treatment for a heart attack is identification promptly of the diagnosis, and transport to a hospital that can perform prompt catheterization and PTCA or stenting within the first 90 minutes of the cardiac event (see 2013 guidelines above).

Recent data has shown that lowering blood LDL levels even further than previously suggested may further decrease the risk of heart attacks.

Research also has shown that inflammation may play a role in the development of atherosclerosis, and this is an active area of current investigation. There also is early evidence that with genetic engineering it may be possible to develop a drug that can be administered to clear plaques from arteries (a "scavenger molecule").

Ovarian Cancer (Cancer of the Ovaries)

Ovarian cancer facts

• Ovarian cancer is a relatively uncommon type of cancer that arises from different types of cells within the ovary.
• The most common ovarian cancers are known as epithelial ovarian cancers (EOC).
• Other types of ovarian cancer include ovarian low malignant potentialtumor (OLMPT), germ cell tumors, and sex cord-stromal tumors.
• Inherited mutations in the BRCA1 and BRCA2 genes greatly increase a woman's risk of developing ovarian cancer.
• A gynecologic oncologist is a specialist with expertise in the management of ovarian cancer.
• Most ovarian cancers are diagnosed in advanced stages because there are no reliable early symptoms and signs of ovarian cancer. Even in more advanced tumors, symptoms and signs are vague and nonspecific.
• There are no reliable screening tests for ovarian cancer.
• Treatment of ovarian cancer involves surgery to remove as much of the tumor as possible and chemotherapy.

What is ovarian cancer?

The term "ovarian cancer" includes several different types of cancer that all arise from cells of the ovary. Most commonly, tumors arise from the epithelium, or lining cells, of the ovary. These include epithelial ovarian (from the cells on the surface of the ovary), fallopian tube, and primary peritoneal (the lining inside the abdomen that coats many abdominal structures) cancer. These are all considered to be one disease process. There is also an entity called ovarian low malignant potential tumor; these tumores have some of the microscopic features of a cancer, but tend not to spread like typical cancers.

There are also less common forms of ovarian cancer that come from within the ovary itself, including germ cell tumors and sex cord-stromal tumors. All of these diseases as well as their treatment will be discussed.

Epithelial ovarian cancer (EOC)

Epithelial ovarian cancer (EOC) accounts for a majority of all ovarian cancers. It is generally thought of as one of three types of cancer that include ovarian, fallopian tube, and primary peritoneal cancer. All three tumors behave, and are treated the same way, depending on the type of cell that causes the cancer. The four most common cell types of epithelial ovarian cancer are serous, mucinous, clear cell, and endometrioid. These cancers arise due to DNA changes in cells that lead to the development of cancer. The serous cell type is the most common variety. It is now thought that many of these cancers actually come from the lining in the fallopian tube, and fewer of them from the cells on the surface of the ovary, or the peritoneum. However, it is often hard to identify the sources of these cancers when they are found at advanced stages, which is very common. 

Ovarian low malignant potential tumor (OLMPT; borderline tumor)

Ovarian tumors of low malignant potential (OLMPT; formerly referred to as borderline tumors) account for about 15% of EOC. They are most often serous or mucinous cell types. They often develop into large masses that may cause symptoms, but they only rarely metastasize, that is, spread to other areas. Often, removal of the tumor, even at more advanced stages, can be a cure.

Germ cell ovarian cancers

Germ cell tumors arise from the reproductive cells of the ovary. These tumors are uncommon and are seen most commonly in teens or young women. This type of tumor includes different categories: dysgerminomas, yolk sac tumors, embryonal carcinomas, polyembryomas, non-gestational choriocarcinomas, immature teratomas, and mixed germ cell tumors.

Stromal ovarian cancers

Another category of ovarian tumor is the sex cord-stromal tumors. These arise from supporting tissues within the ovary itself. As with germ cell tumors, these are uncommon. These cancers come from various types of cells within the ovary. They are much less common than the epithelial tumors. Stromal ovarian cancers include granulosa-stromal tumors and Sertoli-Leydig cell tumors. 

According to the National Cancer Institute (NCI), in 2015 there were an estimated 21,290 new cases of ovarian cancer and 14,180 deaths from the disease. The vast majority of the cases are EOC and are found at stage 3 or later, meaning the cancer has spread beyond the pelvis or to the lymph nodes. This is mostly due to the lack of definite symptoms at the early stages of cancer growth. Around 1.3% of women will be diagnosed with cancer of the ovary at some point in life, thus it is relatively rare. The median age of diagnosis is 63. However, approximately 25% of cases are diagnosed between ages 35 and 54. Caucasian women have the highest rate of diagnosis.

Like many other cancers, when ovarian cancer is found at an early stage (for example, localized to the ovary or fallopian tube) the survival at 5 years is very good (about 92%); most women at stage 1 will still be alive at 5 years. However, the 5-year survival for all women diagnosed with ovarian cancer is only 45%. This is because it is often found at an advanced stage in which the disease has already spread within the abdomen.

Survival is also dependent on the type of care the patient receives. Women suspected of having ovarian cancer should be referred to a gynecologic oncologist. These are physicians with special training in gynecologic (ovarian, uterine, cervical, vulvar, and vaginal) cancers. If a woman does not involve a doctor with this specialized training in her care, then studies show that her survival is significantly worse, often by many years. For this reason, every woman with this disease ideally will obtain a referral to a gynecologic oncologist before she starts any treatment or has any surgery.

What are ovarian cancer risk factors?

Risk factors are related to two major categories: menstrual cycles (ovulation) and family history. The more a woman ovulates (cycles) over her lifetime, the higher her risk of ovarian cancer. Thus starting her period (menarche) at a younger age, ending her period (menopause) at a late age, and never getting pregnant (nulliparity) are all risk factors. It was once thought that infertility patients who underwent preparation for IVF (ovarian stimulation for in vitro fertilization) were at increased risk, but this has since been shown not to be the case in a large comprehensive review of the subject.

Approximately 15% of ovarian cancers are genetically related. Because of this, current guidelines suggest that all women with ovarian cancer should undergo testing for BRCA1 and BRCA2 gene changes (mutations). All patients with ovarian cancer will ideally discuss this topic with their doctor. These gene mutations can affect males as well as females. If a patient is positive for one of these, then her siblings and her children can be tested as well. Testing involves a simple blood test that can be drawn at many offices and laboratories. The results of this test can greatly affect how family members are monitored for various cancers, and family members of both sexes are encouraged to be tested.

When compared with the general population risk (1.3% of women will develop ovarian cancer), women with BRCA1 and BRCA2 genetic mutations have a 39% (BRCA1) or 11% to 17% (BRCA2) chance of developing ovarian cancer in their lifetime. Lynch syndrome (typically colon and uterine cancer), Li-Fraumeni syndrome, and Cowden's syndrome are also associated with ovarian cancer but are less common.

The less common varieties of ovarian cancer (borderline, germ cell, and stromal tumors) have few definable risk factors. The germ cell tumors often seen at younger ages and are treated very differently both surgically and chemotherapeutically.

What are ovarian cancer symptoms and signs?

Screening tests are used to test a healthy population in an attempt to diagnose a disease at an early stage. Unfortunately, there are no good screening tests for ovarian cancer, despite extensive ongoing research. Imaging (ultrasound, X-rays, and CT scans), and blood tests should not be used as a screen, as they are inaccurate and lead many women to surgery who do not need it (they are false positive tests).

Diagnosis of ovarian cancer is often suspected based on symptoms and physical exam, and these are followed by imaging. The signs and symptoms, when present, are very vague. These can include fatigue, getting full quickly (early satiety), abdominal swelling, clothes suddenly not fitting, leg swelling, changes in bowel habits, changes in bladder habits,abdominal pain, and shortness of breath. As mentioned above, these symptoms can be very subtle and vague, as well as very common. This only makes diagnosing the disease that much more difficult. Some studies suggest that the average patient with ovarian cancer sees up to three different doctors prior to obtaining a definitive diagnosis. Often, it is the persistence of the patient that leads to a diagnosis. OLMPT and some benign tumors can present with similar symptoms. In addition, they are often seen with very large masses in the ovary. Often these masses are large enough to cause bloating, abdominal distension, constipation, and changes in bladder habits.

In the more uncommon ovarian types (stromal and germ cell tumors), symptoms are similar. Sometimes, granulosa cell tumors can occur with severe pain and blood in the belly from a ruptured tumor. These can often be confused with a ruptured ectopic pregnancy, as they tend to be found in women of reproductive age. 

How is ovarian cancer diagnosed?

Often vague symptoms eventually lead to a clinical diagnosis, or one based on suspicion generated by exams, laboratory tests, and imaging. However, an accurate diagnosis requires some of the tumor to be removed, either by biopsy (less often), or preferably, surgery to verify the diagnosis. Often a high clinical suspicion can trigger a referral to a gynecologic oncologist.

Various types of imaging studies can be used to diagnose this disease and lead to tissue sampling. Ultrasound and CT scans are the most commonly done studies. These often can give images that show masses in the abdomen and pelvis, fluid in the abdominal cavity (ascites), obstructions of the bowels or kidneys, or disease in the chest or liver. Many times this is all that is necessary to trigger a referral to a specialist, as the suspicion for ovarian cancer can be quite high. PET scans can be used, but often are not necessary if a CT scan is able to be performed.

Blood work can be helpful as well. The CA-125 is a blood test that is often, but not always, elevated with ovarian cancer. If apostmenopausal woman has a mass and an elevated CA-125, she has an extremely high risk of having a cancer. However, in younger women, CA-125 is extraordinarily inaccurate. It is elevated by a large number of disease processes, including but not limited to, diverticulitis, pregnancy, irritable bowel syndrome,appendicitis, liver disease, stomach disease, and more. No one should get this test done unless they actually have a mass, or their doctor has some reason to get it. It should not be drawn just to see the level since it is not a reliable screening test for ovarian cancer.

HE4 is another blood test that is used in the U.S. to monitor patients with ovarian cancer to see if their cancer has recurred. Like CA-125, the HE4 test does not always detect cancer.

OVA-1 is a test that is performed by a private company. This test uses a series of blood tests, and then incorporates the results into an equation that then gives the doctor a result about the likelihood that a mass is cancerous. A high value for the test has been shown in some studies to increase the probability that a cancer is present. This test aids a doctor in planning for surgery when a mass is found.

How is ovarian cancer staging determined?

Staging is the process of classifying a tumor according to the extent to which it has spread in the body at the time of diagnosis.

Ovarian cancer staging:

• Stage 1: Limited to one or both ovaries
• Stage 2: Limited to the pelvis
• Stage 3: Disease outside of the pelvis, but limited to the abdomen, or lymph node involvement, but not including the inside of the liver
• Stage 4: Disease spread to the liver or outside of the abdomen

Complete staging of an ovarian cancer includes hysterectomy, removal of the ovaries, tubes, pelvic and aortic lymph node biopsies or dissection, biopsies of the omentum (a large fatty structure that provides support for abdominal organs), and peritoneal (lining tissue of the abdomen) biopsies.

Ovarian cancer staging is determined surgically, unless it is stage 4 (metastasis outside of the abdomen, or metastasis to the liver -- not on the surface of the liver). If it is stage 4, or very advanced stage 3, then often this is proven with biopsy, and chemotherapy is begun neoadjuvantly (before surgery). If the disease is not obviously stage 4, then aggressive surgical staging and debulking (see next section) often is considered. This decision is based on the health of the patient, as well as the judgment of the surgeon as to the chance of achieving an optimal debulking (see treatment below).

What is the treatment for ovarian cancer?

Epithelial ovarian cancer treatment most often consists of surgery and chemotherapy. The order is best determined by a gynecologic oncologist.

Surgical treatment

Surgery consists of an effort to remove all visible disease in the abdomen, commonly called surgical debulking. If one imagines a handful of wet sand thrown on the ground, you will see small piles and bigger piles. This is often how the abdomen looks when in surgery. It is the job of the surgeon to remove, (also known as debulking) as many of these masses as possible. This surgery usually results in removal of both tubes and ovaries, the uterus (hysterectomy), removal of the omentum (omentectomy -- a large fat pad that hangs off of the colon), lymph node biopsies and any other organ involved in the disease. This can mean a portion of the small bowel, large bowel, liver, the spleen, the gallbladder, a portion of the stomach, a portion of the diaphragm, and removal of a portion of the peritoneum (a thin lining in the abdomen that covers many of the organs and the inside of the abdominal wall). Done properly, this can be a very extensive surgery. The patients who live the longest have all of the visible nodules taken out at time of surgery. To accomplish an “optimal debulking,” at minimum, no individual nodule greater than 1 cm should be left behind. If this cannot be done, the patient is brought back to the operating room for a second surgery after a few rounds of chemotherapy (neoadjuvant chemotherapy and interval debulking surgery).

It should be noted that now many gynecologic oncologists believe that “optimal debulking” should mean that there is no visible disease left at the time of surgery. This has been a shift over the last years. Historically the goal was to leave no individual nodule greater than 2 cm behind. This has steadily progressed to the point where the term “optimal debulking” is now accepted by many to mean that there is no disease left to remove. As we have progressed to this point, surgery has become more involved, on a more routine basis. This has led to a concern about undertreatment of elderly patients due to a fear that they cannot survive the surgical risks.

There has recently been new research indicating that if all visible disease cannot be removed at the time of surgery, that giving chemotherapy for three cycles before surgery may be just as beneficial as up front surgery. When this is done, the amount of surgery needed to optimally debulk a patient is significantly less. This is a concept that has been used historically, but it was always felt to be substandard. With recent research as well as ongoing research, more information is coming out that supports the use of this strategy in some circumstances.

Chemotherapy

Any patient healthy enough to tolerate chemotherapy will often benefit greatly from its use. The drugs used in ovarian cancer tend to have fewer side effects, and thus are easier to tolerate than many other chemotherapy drugs. Currently, there are two ways to give chemotherapy in ovarian cancer. Traditionally, it is given into the vein intravenously (IV). When initially diagnosed, the two most common drugs are carboplatin and paclitaxel(Taxol). Most commonly, the carboplatin is given every 21 days and the paclitaxel is given every 21 days, or every 7 days.

Another way of giving the chemotherapy is to place it directly into the abdomen (intraperitoneal or IP). In many studies, intraperitoneal administration has been shown to significantly increase survival. This is most often used after optimal surgical debulking. Currently the drugs used are cisplatin and paclitaxel. In a 21 day cycle, the paclitaxel is given IV on day 1, followed by cisplatin IP on day 2, and paclitaxel IP on day 8. This regimen is the current standard in IP ovarian cancer chemotherapy. There are studies that are looking at substituting carboplatin for the cisplatin, because the side effects are less. We do not have an answer for this yet.

The drug bevacizumab has also been used experimentally in the initial treatment of ovarian cancer. When used in the initial rounds of chemotherapy and then used for 12 months after the initial six cycles of chemotherapy, there is research indicating that the cancer, if not cured, will come back at a later date than would be expected with traditional chemotherapy regimens (increased progression-free survival). This has not yet been shown to increase survival however. Bevacizumab is a very good drug to use in ovarian cancer; however, the timing of its use is still being determined.

Some centers are starting to experiment with heated intraperitoneal chemotherapy (HIPEC). However, at this time, HIPEC is still experimental. There are significant risks and complications from surgery with HIPEC, and it has not yet been shown to extend survival over standard chemotherapy. Until a trial is done proving its usefulness, HIPEC should be used with caution.

Maintenance chemotherapy is a concept that gives long-term chemotherapy, often for a year, of a single drug. The idea is that, if the patient is not cured, then this may prevent the recurrence from occurring for an extended amount of time. Drugs that have been studied with this approach include paclitaxel and bevacizumab. We have yet to show an increased survival using this method of treatment. This creates controversy, because if the patient will not live longer, then why subject them to 12 months of chemotherapy? As of now, there is no definitive answer on whether or not this should be done. Each patient can discuss this with her treating physician to get information.

When epithelial ovarian cancer recurs, the timing of the recurrence dictates how it is treated. Sometimes, a patient may be a good candidate for surgery again. If not, then chemotherapy is used. The type of drugs used are determined by how long it has been since the last time a patient has taken a drug containing platinum (carboplatin or cisplatin). If it has been less than 6 months, then the patient is termed platinum resistant. If it has been more than 6 months since the last day of platinum-based chemotherapy, then often a platinum-containing drug will be used again.

If the patient is still platinum sensitive, then often she will receive a platinum drug with another drug. This can be paclitaxel again, or another taxane type drug, such as docetaxel. Also, another class of drugs, such as gemcitabine or pegylated liposomal doxorubicin (PLD) may be used. Often the combination is chosen based on how a patient tolerated her previous chemotherapy, as well as the side effect profile that will best suit the patient. If the patient is platinum resistant, then often a single drug is used. These can include drugs that have previously been used. Agents used include pegylated liposomal doxorubicin, docetaxel, paclitaxel, topotecan, gemcitabine, etoposide, and bevacizumab. The order, schedule and dosing are quite variable, depending on many factors.

The Gynecologic Oncology Group is a national organization that sponsors clinical trials in gynecologic cancers. Patients can ask their physician if they are eligible for a trial that may help them, as this is how new drugs are discovered. If a doctor or hospital does not participate in the GOG trials, a doctor can often contact a regional center that does.

Stromal and germ cell ovarian tumors are most often treated with a combination of bleomycin, etoposide, and cisplatin. There is much less research on these as they are more curable and much less common than epithelial tumors. Because of their rarity, it will be very difficult to find effective new treatments. 

What is the survival rate and prognosis of ovarian cancer?

Epithelial ovarian cancer is the most deadly of the gynecologic cancers. Approximately 80% of patients will eventually die of the disease. However, survival in the short term is quite good, meaning many years. With the addition of IP chemotherapy, the survival of ovarian cancer has been significantly extended. According to recent studies, if a patient undergoes optimal debulking, followed by IP chemotherapy, then they have a greater than 50% chance to still be alive in six years. This is quite good compared to other advanced stage cancers. Even in the recurrent setting, epithelial ovarian cancer is often very sensitive to chemotherapy. The disease can often go in to complete remission (no detectable disease) many times. However, once it recurs, it is not curable and will continue to come back.

Germ cell and stromal tumors have a much better prognosis. They are often cured because they are more often detected at early stages.

Can ovarian cancer be prevented?

There is no way to truly prevent ovarian cancer. One would think that removal of the fallopian tubes and ovaries would prevent the disease but this is not always the case (primary peritoneal cancer can arise in the pelvis even after the ovaries have been removed). However, there are ways to significantly reduce your risk. If a woman takes birth control pills for more than 10 years, then her risk of ovarian cancer drops significantly. Tubal ligation has long been known to decrease the risk of ovarian cancer. Recently, removal of the entire tube has been shown to further decrease the risk. This procedure, called a salpingectomy, can be considered by any woman considering a tubal ligation. Removal of the ovaries does decrease the risk of cancer, but at the cost of increasing death due to heart disease and other causes. Currently this procedure is often saved for specific situations (genetic risk, family history) in patients under 60 to 65 years of age and is not used in the general population. Until recently, if a woman was close to menopause and was undergoing surgery, then the ovaries and tubes would be removed. The recent studies indicating that many of these cancers actually come from the fallopian tube, and the studies indicating that removal of even postmenopausal ovaries causes other problems has caused a significant shift in this philosophy. Certainly, the tubes should be removed at the time of hysterectomy for any woman. The need for removal of the ovaries is much more uncertain.

Genetic abnormalities are an exception to this recommendation. If a patient is positive for a BRCA or Lynch syndrome genetic defect (mutation), then the patient should strongly consider removal of her tubes and ovaries to decrease the chance of her getting a cancer. Women with these mutations are at a very high risk of ovarian cancer, and in this situation the risk of heart disease is not as significant as dying of one of these cancers. This can be planned at the end of child bearing, or at age 35. Each patient is recommended to discuss this with her doctor, or a genetic counselor.

How does one cope with ovarian cancer?

A diagnosis of cancer is often accompanied by the emotional side effects of anxiety, fear, and depression. Just as treatments are designed to help fight cancer growth and spread, self-care and support measures to help one handle the emotional aspect of the diagnosis can be extremely valuable.

Many hospitals and cancer treatment centers offer cancer support groups and counseling services to help manage the trying emotional side effects of cancer and its treatment. There are also a number of valuable online resources for both patients and families.

For example, the American Cancer Society offers tips on coping with cancer in everyday life; coping checklists for patients and caregivers; managing anger, fear, and depression; and a series of online "I can cope" classes through their website.

The National Ovarian Cancer Coalition (NOCC) also offers online resources on coping with ovarian cancer.

The National Cancer Institute offers a variety of patient education publications about coping with the effects of cancer and its treatment on everyday life, including materials for caregivers and family.