DOCTOR'S VIEW ARCHIVE

Gene therapy designed to grow new blood vessels in the heart muscle led the list of the top 10 research advances in heart disease and stroke compiled by the American Heart Association. The list, first created in 1996, recognizes achievements in basic and clinical research that may have the most impact on the prevention and treatment of cardiovascular disease.

The most recent edition of the list is as follows:

1. Gene therapy to create a "natural" bypass around blockage
2. New drugs to prevent clots causing heart attacks and strokes
3. Relationship between inflammation and heart attacks
4. Detection of unstable plaques in vessels by imaging technology
5. Heart cells recover thanks to left ventricular assist device
6. Tobacco's effects from fewer than 10 cigarettes a day
7. Impact of diet and exercise on blood cholesterol levels
8. Education of people with heart symptoms to go to the emergency room
9. Epidemic of cardiovascular disease and stroke
10. Nobel Prize for discovery of nitric oxide (which relaxes blood vessels).

This list was issued at the end of 1999 by the American Heart Association and is based upon developments reported during 1998. We will comment upon each of these ten advances:

1. Gene therapy to create a "natural" bypass to circumvent plaques obstructing the heart's blood vessels.

People with heart disease may be routinely treated in the future by a genetically engineered technique that induces the growth of new blood vessels. The new vessels would help restore blood flow to the hearts of people whose arteries are obstructed by plaques. By impeding blood flow, these obstructions can cause severe chest pain (angina) and heart attacks.

Scientists reported that they had used a human growth factor called FGF-1 (fibroblast growth factor-1), obtained through genetic engineering, to induce the growth of new blood vessels in 20 patients with heart disease. In their three-year follow-up study of the patients, the scientists reported that the treatment resulted in a two to three times more blood flow to the heart.

Another growth factor called VEGF (vascular endothelial growth factor) also appears capable of inducing new blood vessel growth for the heart. Gene therapy may thus become an important part of the treatment of heart disease.

2. New drugs to prevent clots causing heart attacks and strokes.

Drugs called platelet blockers (or, more formally, IIb/IIIa receptor blockers) were found to keep blood platelets from clumping and forming blood clots that can trigger a heart attack or stroke. In this regard they are like aspirin. However, the platelet blockers -- eptifibatide (brand name: Integrilin), tirofiban (Aggrastatin) and abciximab (ReoPro) -- are more potent than aspirin. And they are administered intravenously (IV).

To test the usefulness of the platelet inhibitor drugs, a total of about 32,000 heart patients received a platelet blocker as part of their treatment for a heart attack or severe chest pain. Some individuals received only the platelet blockers while others were treated with a platelet blocker plus angioplasty -- a procedure that uses a balloon-tipped catheter to restore blood flow in the blood vessel. Those who received the platelet blockers had a 30 percent reduced risk of all-cause death than those who did not receive the drugs. The individuals who particularly benefited from the drugs were those who also were treated with angioplasty. In these individuals the drug was administered just as the coronary arteries were being opened by inflation of the balloon-tipped catheters used for the procedure.

3. Relationship between inflammation and heart attacks.

It is recommended that people at elevated risk for heart attack and stroke take aspirin because it helps prevent the blood clots that can cause heart attacks and strokes. Aspirin, however, may have another benefit for people at high risk for heart attacks and stroke. Aspirin is an anti-inflammatory drug, and research suggests that the body's inflammatory response may play a role in cardiovascular disease.

The area of the blood vessel where an obstructive plaque develops can become inflamed. The inflammatory response may not be localized to the blood vessel wall in that area. It also can occur throughout the bloodstream. This systemic inflammation may explain the development of blood clots on top of relatively stable plaques.

4. Detection of unstable plaques in vessels by imaging technology.

Most heart attacks and strokes are caused by blood clots unleashed by plaques in the blood vessels. The clots, which are formed when the plaques rupture, block blood flow to the heart and brain, thereby causing a heart attack or stroke. It was found that magnetic resonance imaging (MRI) can detect plaque obstructions that are prone to rupture in the carotid artery (a blood vessel in the neck that carries blood to the brain), and the thoracic aorta (the large blood vessel that carries blood from the heart to the body). MRI can be adapted to freeze-frame the beating heart so that "unstable" plaque in the coronary arteries can be detected.

MRI promises to provide a way to detect people at high risk of having a heart attack or stroke and to initiate treatment to stabilize the plaques and reduce the chance that a blood clot will form.

5. Heart cells recover thanks to left ventricular assist device.

The heart tissue of people with congestive heart failure can recover some of its function through treatment with what is called a left ventricular assist device (LVAD). The LVAD takes over the pumping action of the left side of the heart for patients with severe heart failure who are awaiting heart transplantation. Heart muscle cells, called myocytes, were found to recover their ability to contract and relax as a result of the heart's being supplemented by the LVAD. The heart cells had been obtained from patients who had been on LVADs but who were given heart transplants. In another study, scientists describe how they had weaned five patients from the LVAD. When they were placed on the LVAD, all had diagnosed irreversible end-stage heart failure. But their heart function was dramatically modified during the LVAD treatments. As a result, they did not need a heart transplant.

6. Tobacco's effects from fewer than 10 cigarettes daily.

About 13,000 men in the United States, Europe and Japan were monitored for 25 years. For men who had smoked 10 or more cigarettes a day, the risk of death from heart disease or lung cancer rose to 80 percent more than for men of the same age who did not smoke. However, what was perhaps even more stunning was the finding that men who had smoked fewer than 10 cigarettes daily had a 30 percent higher risk of death from heart disease or lung cancer than men of the same age who did not smoke. Smoking even "a few" cigarettes is clearly quite dangerous.

7. Impact of diet and exercise on blood cholesterol levels.

New research characterized people for whom a low-fat diet is most often effective in lowering elevated levels of "bad" cholesterol (low-density lipoprotein, or LDL). Individuals who benefited most from the effects of a low-fat diet, it was found, were those who had been at the highest risk for heart attack and stroke.

A low-fat diet effectively lowered the abnormally high LDL levels in people who have inherited what is called the E-4 variant of apolipoprotein E, a genetic variant that is typically associated with high LDL. About 15 percent of the population have the E-4 variant.

A low-fat diet was also effective in people who have a form of LDL that is called "pattern B." People with "pattern B" LDL characteristically have abnormally low levels of "good" cholesterol (high-density lipoprotein or HDL), which can rise to normal as a result of diet. About 25 percent of the population have "pattern B" LDL.

Diet should therefore usually be tried first before cholesterol- lowering drugs because diet can be effective in many people, especially those at particularly high risk. To lower LDL level, exercise should be added to the diet. Increased physical activity enhances the effects of a low-fat diet in reducing LDL levels. Exercise and diet should ideally be paired.

8. Education of people with heart symptoms to go to the emergency room.

Community campaigns have been designed to teach people about heart attack symptoms and the need for rapid action. The goal is to reduce the time people delay seeking emergency care for heart attacks because, the quicker that people seek treatment, the greater their chances of surviving the heart attack and reducing damage to the heart.

A study was conducted in 20 cities in the U.S. Half of the cities were sites of the community education campaign. In the remainder, the educational program was not conducted. In the cities with the education, more people with heart attack symptoms came to the emergency department. There also was a 10 to 15 percent increase in the number of people choosing to call Emergency Medical Service. In most U.S. cities, one-half to two-thirds of those with possible heart attack arrive in the emergency room by other means than by Emergency Medical Service, a particularly dangerous situation.

9. Epidemic of cardiovascular disease and stroke.

The way age-adjusted death rates from heart attack and stroke are calculated has been updated. Age-adjustment works like a currency so that different populations can be compared (or the same populations can be compared) over time to determine trends.

The new age-adjusted death rates have been adjusted to the age- distribution of the U.S. population in the year 2000, replacing the old standard that was based on the age-distribution of the 1940 population. The U.S. population in the year 2000 has more older people than the 1940 population. As a result, heart disease and stroke death rates adjusted to year 2000 are much higher than those adjusted to 1940 standard.

10. Nobel Prize for the discovery of nitric oxide (which relaxes blood vessels).

The discovery of nitric oxide and its function is one of the most important in the history of cardiovascular medicine. The 1998 Nobel Prize in Physiology or Medicine was awarded to three American scientists -- Robert F. Furchgott, Louis J. Ignarro and Ferid Murad -- for their discoveries concerning nitric oxide as a signaling molecule in the cardiovascular system.

Nitric oxide, a colorless gas, makes blood vessels dilate (widen) by relaxing the muscles in the vessel wall. Nitric oxide is therefore a key component in blood pressure. Levels of nitric oxide normally rise when someone is in a stressful situation. A lack of nitric oxide in the bloodstream, or a lack of reactivity by the blood vessels to nitric oxide, can narrow the vessel, thus raising the blood pressure. High blood pressure is a major risk factor for both heart disease and stroke.

For more, please visit the High Blood Pressure Center.