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American Heart Association's Top Research Advances For 1997

January 5, 1998
American Heart Association
Gene therapy to restore blood flow, preventing stroke in children with sickle cell anemia, and the emergence of common bacteria as a potential "smoking gun" in heart disease are among the top research advances in cardiovascular disease during 1997, according to Martha Hill, R.N., Ph.D., president of the American Heart Association.

Gene therapy to restore blood flow, preventing stroke in children with sickle cell anemia, and the emergence of common bacteria as a potential "smoking gun" in heart disease are among the top research advances in cardiovascular disease during 1997, according to Martha Hill, R.N., Ph.D., president of the American Heart Association.

"The list is designed to recognize the achievements this year in the laboratory, clinical and behavioral sciences that should have the greatest impact in the prevention and treatment of heart disease and stroke," says Hill.

Heart disease and stroke claim more lives - and cost the national more economically - than any other health disorder.

This is the second year that this list has been developed. But unlike the 1996 list of 10 advances, this year's announcement contains 11 accomplishments. "For the 1997 list, we wanted to include Dolly, the first cloned mammal, even though neither she or the technology used to create her have yet to benefit the treatment or elimination of cardiovascular disease," said Hill.

"When we look back on 1997 in the years to come, we expect that Dolly will have proven to be major accomplishment for heart disease and stroke," she said. "So for the 1997 list, she will be number 11 on the list - a bonus."

Following are the top advances of the year in heart disease and stroke research.

1. Gene therapy restores blood flow in atherosclerotic leg blood vessels - and key genetic factors are identified

People with atherosclerosis often undergo bypass surgery to restore blood flow in leg or heart vessels obstructed by cholesterol-laden plaque. In this surgery, a vessel from another part of the body is attached to the obstructed vessel to circumvent, or bypass, the blockage. However, many of these surgeries have to be repeated because blockages develop in the attached vessels. At one laboratory, researchers are using gene therapy to grow new blood vessels, a "natural bypass," around blockages in the leg. The gene is injected into the patient's leg, near the obstructed blood vessel. The newly grown blood vessels route blood flow around the obstruction in much the same way that a grafted vessel does. At another laboratory, scientists are using gene therapy to keep the attached vessel in the leg open after bypass surgery. The researchers "treat" the vessel before it is -more- attached by bathing it in a solution containing a gene. This treatment prevents the type of new cell growth that can cause obstructed blood vessels. Both research groups plan to test their gene therapy approaches in people who have atherosclerosis in their coronary arteries, the blood vessels to the heart.

This year scientists also identified hereditary clues to several types of cardiovascular disease - opening the door to research on new approaches to prevention and treatment. During the past year, scientists located: -- Genes that cause congenital heart defects in children - defects that once were regarded as random flukes of nature, not influenced by heredity; -- Two types of genes involved in dilated cardiomyopathy, a form of heart muscle disease. Dilated cardiomyopathy can help initiate congestive heart failure; and -- The chromosome that contains the genetic defect that may contribute to atrial fibrillation, or irregular heart beat, the cause of about one third of strokes in people over age 65.

2. Long-lasting, low-grade inflammation of blood vessels that feed the heart and brain may precede and help trigger heart attacks and stroke

For some time, scientists have known that high blood levels of a protein that is a marker for inflammation characterize people who've had a heart attack, stroke or severe chest pain. Whether the inflammatory response that created this marker, called C-reactive protein, was a result or a cause of the atherosclerosis, the disease process that causes obstructed blood vessels, has been unknown. A new study, whose results were announced this year, found that high levels of C-reactive protein preceded by years the heart attack or stroke. These findings raise the question that the inflammatory response may be a trigger. In the study, blood samples of healthy men were analyzed. Men who subsequently suffered a heart attack or stroke were found to have had much higher levels of C-reactive protein than did males who did not have a heart attack or stroke. Males with high levels of the protein had three times as many heart attacks and twice as many strokes as men of the same age and heal! th status but with normal blood levels of the protein. Also of interest is the research finding that aspirin, which is anti-inflammatory as well as anti-blood clotting, can lower blood levels of C-reactive protein. Could aspirin's benefits as a treatment for heart disease be a result of both of these effects? Once the cause of the inflammatory response is understood, it may be possible to prevent it and thereby to reduce or even eliminate atherosclerosis in some people.

3. Chlamydia bacteria emerges as a potential "smoking gun" in heart disease

If heart disease is in part initiated by an infection, which of the bacteria or viruses are to blame? This year scientists provided intriguing evidence that the "smoking gun" may be Chlamydia pneumoniae (Cp) bacterium, which causes a common respiratory infection and which has been detected in the blood vessel wall in several recent studies. Scientists found that heart attack survivors who had the most Cp antibodies had a four-times-higher risk for suffering another -more- heart attack or needing treatment to restore blood flow to the heart than did survivors who had no detectable antibodies to Cp in their blood. Antibiotic treatment seemed to quickly nullify the risk for these heart disease problems. If future research shows that high blood levels of Cp characterize individuals who have heart disease but have not yet had a heart attack, Cp may be placed on a par with cigarette smoking as a lurking "trigger" for heart attack. Cp also may provide a useful yardstick for predicting whether survivors of heart attack are at high risk for another attack.

4. People who are depressed after surviving a heart attack are less likely to follow medical advice important to their health

The mental state of people who've had a heart attack or stroke influences the quality and length of their lives. For reasons not yet understood, a sixfold increase in deaths six months after heart attack characterizes depressed patients when compared to those who are not depressed. Also not understood is the complex interplay among depression, poor health, and failure to make the lifestyle changes needed to lower risk for disease and to take the medications prescribed by doctors. The neurohormonal and other mechanisms that may help explain how psychological disorders or stress could increase the risk of cardiovascular disease, and how these emotional states influence patient behavior require better understanding. Such intriguing and important questions remain much at issue, but studies announced this year suggest depression significantly raises one's risk of a heart attack or stroke. A new study of over 200 heart attack survivors (over 23 percent of whom were significantl! y depressed) showed depressed mood is strongly associated with failure to make lifestyle changes needed to avoid a second heart attack or stroke. Another study, a 27-year investigation of 730 Danish men and women, found that those who suffered long-term depression had a 70 percent greater risk of heart attack than those unaffected by the disorder. In another study, prolonged hopelessness, one major symptom of depression, was found to speed the progression of coronary artery disease, the cause of heart attack. The study of middle age Finnish men found that those who rated themselves high on hopelessness had a 20 percent greater increase in blood vessel plaques over 4 years than those who ranked themselves low.

5. A diet high in fiber, fruits, vegetables, minerals and low-fat dairy foods can help control blood pressure

A new study reaffirms the important role of diet in preventing and controlling high blood pressure, which affects one in four adults. When people have high blood pressure, or hypertension, they are at increased risk for developing heart disease and stroke. For individuals who want to prevent, eliminate or reduce the amount of drugs that they take to lower their blood pressure, this study indicates that diet can prove to be an effective "treatment." The volunteers in the study were individuals whose blood pressure readings were either high normal or early hypertensive. During the study, they lived at home and were provided diets composed of real foods, not supplements. The diet that resulted in a decrease in blood pressure was low in saturated fat, total fat and cholesterol and high in fiber, fruits, vegetables and dairy foods and had adequate amounts of protein. The study diet contained more minerals (calcium, magnesium and potassium) -more- than the typical diet of most Americans. Low-fat dairy products were the primary source of calcium. The study demonstrated that diet with typical sodium intake can lower blood pressure without weight loss and reinforced the important role of a well-balanced diet in health.

6. Study of 80,000 women improves understanding of different types of fats in diet

Margarine, commercially baked foods such as doughnuts and any food cooked with hardened vegetable oil - all of which are high in trans fatty acids - should be labeled "bad for the heart," suggests new research that examined the kinds of fats that put women at risk for heart attack. The research found that trans fatty acids posed a greater risk to the heart than the saturated fats, which are found in meats and dairy food. Including 80,000 nurses, the study found that women whose diets had the highest amounts of trans fatty acids - which result from the processing of vegetable oils into "hard" margarine and cooking fats - had the highest risk for heart attack. Indeed, those with the most trans fatty acids in their diets had 53 percent increased risk for heart attack, when compared to women whose diets had relatively low amounts of trans fatty acids. Research suggests that replacing "bad" fats with monounsaturated fats (olive oil, for example) that characterize the so-called M! editerranean diet lowers risk for heart disease.

7. Implantable cardioverter defibrillators improve survival of people with life threatening heartbeat irregularities.

For several years, physicians have known that implantable defibrillators - which are similar to pacemakers - could save lives of people with irregular heartbeats. But, are defibrillators, a costly treatment, as or more effective than the anti-arrhythmic drugs that have been the standard treatment for people with life-threatening heartbeat irregularities? A study, whose results were announced this year, showed that implantable defibrillators could correct irregular heartbeats, which can cause heart attack and cardiac arrest, more effectively than anti-arrhythmic drug treatment. A defibrillator recognizes irregular heart beats and then electrically shocks the heart to resume a more normal rhythm of beating. Thousands of people with irregular heartbeats could benefit.

8. Cholesterol-lowering drugs can reduce risk for heart attacks and stroke among healthy middle-aged men and women

Cholesterol-lowering drugs known as "statins" have proven effective in preventing another heart attack or a stroke in individuals who have already suffered a heart attack. This year, a new study showed that these drugs also could prevent the first heart attack. The study included both men and women without symptoms of cardiovascular disease and with near-normal levels of blood cholesterol. Each participant had one or two risk factors for cardiovascular disease. Such individuals have not been regarded at high risk for heart disease and stroke. But these results suggest that they may benefit from these drugs as well as from eating a low-fat diet and engaging in regular physical activity - two behaviors known to lower risk for cardiovascular disease. (The individuals in the study ate a healthy diet and engaged in regular physical activity.) -more- 9. Radiating blood vessels keeps them open after balloon angioplasty

This year scientists reported research results demonstrating the effectiveness of radiation as a treatment to keep blood vessels open following balloon angioplasty. Although highly successful in pushing aside the cholesterol-filled plaque that can block blood flow in vessels, angioplasty often injures the tissue lining the vessel. When the tissue is injured, the body's natural healing process sets in, often creating layers of new cells at the site. This cell growth can narrow the blood vessels, impeding blood flow. The new obstruction in blood vessels - called restenosis - occurs in about 30 percent of people who undergo angioplasty and can be life threatening for the individual. Another angioplasty - or the more costly coronary bypass surgery - often is needed to restore blood flow again in the vessel. Radiating the tissue inside the blood vessel has emerged as a treatment to prevent the cell growth and thereby restenosis from occurring.

10. Blood transfusions prevent strokes in children with sickle cell anemia

The "Stroke Prevention Trial in Sickle Cell Anemia" (STOP) was stopped this year, 16 months earlier than planned, because the study's results clearly showed that the experimental treatment -- administering blood transfusions every three-to-four weeks -- reduced the rate of stroke by 90 percent in children with sickle cell anemia who are at high risk for suffering a "brain attack." An ultrasound technique called transcranial doppler was used to identify children at risk for stroke. It measures the velocity of blood flow in the brain. A total of 130 children, ages 2 to 16, participated in the study which compared standard supportive care for sickle cell anemia with treatment by blood transfusions, which reduce the amount of abnormal or sickle hemoglobin in the blood. An estimated 10 percent of children with sickle cell anemia experience strokes, and once a child with this blood disorder has had a brain attack, his or her risk of suffering another one is about 80 percent.

11. A mammal is cloned: a sheep named Dolly

Earlier this year, Dolly was born, ranking as the first mammal cloned from her mother's tissue. Dolly's birth likely will be regarded in the future as a highly significant accomplishment that will have substantially influenced the course of research on cardiovascular disease. In years to come, research using cloned mammals may improve understanding of the genetic factors influencing susceptibility to heart disease and stroke. Cloning also may provide new approaches to treatment. Scientists at the research institute that cloned Dolly recently announced that cloned lambs had been genetically altered to include human genes for a blood-clotting protein - an advance important in the treatment of hemophilia. A protein to limit, not promote, blood clotting would be one advance in cardiovascular disease that may occur as a result of the technology that created Dolly.

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