COVER

HELP FOR THE HEART

A STUDY LINKING IRON IN BLOOD TO HEART DISEASE OFFERS HOPE FOR DETECTION AND PREVENTION

D’ARCY JENISH September 21 1992
COVER

HELP FOR THE HEART

A STUDY LINKING IRON IN BLOOD TO HEART DISEASE OFFERS HOPE FOR DETECTION AND PREVENTION

D’ARCY JENISH September 21 1992

HELP FOR THE HEART

A STUDY LINKING IRON IN BLOOD TO HEART DISEASE OFFERS HOPE FOR DETECTION AND PREVENTION

COVER

On a cold, blustery day in January, 1991, Peter Doig walked home from his office in downtown Halifax, poured himself a drink and began to change his clothes. The 62-year-old executive with National Sea Products Ltd. was unbuttoning his shirt when he collapsed into a chair, passed out—and nearly died of a heart attack. By the time ambulance attendants wheeled him out of his home, his heart had not functioned for about 10 minutes. Doctors revived him and 13 days later performed a life-saving bypass operation, taking blood vessels from other parts of his body to replace the clogged coronary arteries that had caused his heart attack. Doig says that since then, he has completely recovered. Still, the

experience has left him paying closer attention to his diet and staying abreast of medical research into heart disease. As a result, Doig said that he was intrigued to learn last week that Finnish researchers had reported a link between coronary heart disease and the buildup in some individuals of iron, a mineral long regarded as essential to human health. Said Doig, who has reduced his consumption of fatty foods but never considered iron to be a problem: “I’m skeptical. I need to be convinced.” Although many heart specialists and researchers were equally cautious, the Finnish study generated widespread public interest. Heart disease is the leading cause of death in most industrialized countries. In 1989, the latest year for which statistics are available, cardiovascular diseases, which include strokes and hardening of the arteries as well as heart attacks, killed more than 78,000 Canadians. Cancer, the number 2 cause of death, claimed 50,000. Cardiovascular diseases are also Canada’s single most expensive health problem. Officials at Health and Welfare Canada estimate that the direct and indirect costs linked to heart disease, including medical treatment, lost wages and reduced productivity, exceed $17 billion annually.

Vital: The Finnish study, which began in 1984 and involved 1,931 men, showed that men who had high levels of iron stored in their bodies were more likely to suffer from heart disease than men with smaller amounts of iron. By pointing to a link between iron levels in the body and the risk of heart disease, the study appeared to vindicate the work of Jerome Sullivan, an American researcher who claimed the existence of a link 11 years ago (page 46). The Finnish findings also indicated that scientists still have only a partial knowledge of the functioning of the vital organ that has the task of supplying oxygen-rich blood to the human body (page 48). As well, the Finnish findings focused attention on other promising lines of research that are being pursued internationally and by Canadian researchers (page 47).

After the results of the controversial study were published in Circulation, a monthly journal of the Dallas-based American Heart Association, Dr. Jukka Salonen, the Finnish doctor who directed the survey, told Maclean’s that his

group’s findings could eventually lead Europeans and North Americans to change their diets and eating habits. Salonen said that concerns about the levels of iron in the body could lead to reductions in consumption of red meats, the main dietary source of the mineral. As well, Salonen said that doctors may begin encouraging their patients to donate blood several times a year in order to keep their iron levels lower. Said Salonen of the apparent relationship between iron and heart attacks: “This is a totally new finding. It has already led to new research by other investigators.”

The study also appeared to challenge conventional medical ideas about the role of iron in the human body—and widely accepted theories about the causes of heart disease. Most doctors maintain that dietary iron is an essential source of energy for human beings, and sometimes recommend non-prescription iron supplements for patients suffering from anemia. As well, Health and Welfare Canada and the Food and Nutrition Board of the National Academy of Sciences in the United States both publish recommended daily levels of iron intake, which vary according to age, weight and sex. At the same time, the North American health-care industry has developed dozens of products, mostly in tablet form, aimed at providing the vitamins and minerals, including iron, considered necessary for good health.

According to Douglas Cox, vice-president of marketing services with Pittsburgh-based SmithKline Beecham Consumer Brands Co., which produces Geritol tablets, Americans spend about $550 million annually on those and similar products, which are known as multiple vitamin/ mineral supplements. Cox noted that Geritol, which has been on the market for more than 50 years, originally contained only iron, but now consists of about 30 vitamins and minerals, including iron, copper, zinc and magnesium. Cox said that the firm will wait for the results of further research before it considers removing iron from its Geritol tablets. Said SmithKline clinical research associate Charles Sloughfy: “We have absolutely no plans to reformulate Geritol in response to the Finnish study.”

For their part, most heart specialists said that the Finnish findings would have to be independently confirmed by other researchers before they will fully accept the suggestion that dietary iron can cause heart disease. Experts in the field said that previous research has demonstrated to the satisfaction of most experts that smoking, obesity and excessive consumption of fatty foods, including some meats and dairy products, are the principal behavioral causes of heart disease. Said Dr. Wilbert Keon, director-general of the University of Ottawa Heart Institute and one of Canada’s leading heart surgeons: “There is no question that the techniques involved in the study were sound and the results were published in a very, very good journal. But we have to have more research.”

Sharply: Most experts note that cardiovascular death rates have fallen sharply during the past three decades as a result of other research findings, improved diagnosis and treatment, and public education campaigns. During the early 1960s, the annual mortality rate among Canadian men from heart disease was 600 per 100,000, according to figures published by Statistics Canada. By the late 1980s, the rate had fallen to about 350 per 100,000. During the same period, the mortality rate for women with heart disease declined to 200 deaths for every 100,000 women from 450.

Most heart surgeons and researchers reacted cautiously to Salonen’s study not only because it enters new territory, but also because of an element of its methodology. Salonen’s subjects were all from eastern Finland, a region that happens to have one of the highest rates of heart disease in the world. As a result, some experts say that the outcome may only apply to that region. Said Dr. Ruth McPherson, an associate professor in the departments of cardiology and endocrinology at the University of Ottawa Heart Institute: “This theory has to be verified in a much, much larger population.”

For his part, Salonen said that he decided to carry out a major study after he developed a belief that there might be a relationship between iron levels in the body and heart disease. He said that when he launched the study in 1984, he focused on eastern Finland because of the high incidence of heart disease there and because the difference in the rates of heart disease among men and women is greater there than anywhere else in the world. Salonen said that he attributes the variation in male and female rates to the fact that women lose iron every month while menstruating.

Before launching his research, Salonen said, he studied scientific journals devoted to coronary research and discovered that his theory about iron and heart disease had never been tested. In fact, U.S. researcher Jerome Sullivan developed the same theory a decade ago. But funding agencies rejected his applications for research grants to examine it, and two prominent scientific journals turned down his articles on the subject before a British journal accepted one of his studies.

Indeed, the possibility that normal amounts of dietary iron may be harmful to human health injects a dramatically new element into theories about heart disease—and contradicts most conventional ideas about nutrition. Frances Berkoff, a nutritionist at Toronto’s Mount Sinai Hospital and co-author of the 1989 book Power Eating, said that iron is a necessary component in the production of hemoglobin, a protein in red blood cells that carries oxygen to various parts of the body. Shortages of iron can cause fatigue or even anemia. Berkoff added that women frequently need to adjust their diets and increase their iron intake to make up for losses of the mineral through menstruation. “We seldom have a case where a person has too much dietary iron,” she said. “I usually see people who don’t have enough.”

Nutritious: Dietary iron is readily available. Red meats, and particularly organ meats from kidneys and livers, are the primary dietary source for most North Americans. But iron is also found in eggs, such dried fruits as raisins and prunes, and in leafy green vegetables including spinach and broccoli. As well, flour and breakfast cereal producers frequently enrich their products by adding iron to make them more nutritious, and potentially appealing, to consumers. Berkoff said that she does not recommend the use of iron supplement pills. Instead, she said that people suffering from fatigue should have their iron levels assessed by a doctor, and then try to correct the problem by changing their diet.

Doctors have known for some time that extreme iron overload—in amounts beyond the levels involved in Salonen’s study—can cause fatal heart damage. Dr. Peter Liu, a cardiologist at The Toronto Hospital, said that for several years he has been involved in treating children and adults who suffer from congenital anemia and who require frequent blood transfusions. Liu said that in the past, the transfusions caused a buildup of iron in the recipient’s body. Almost invariably, the children died of heart failure in their midto late teens. Now, he said, drugs have been developed to remove the excess iron, and youngsters can expect to reach adulthood and live until at least 30.

Punch: Liu said that the children were suffering from heart failure because the body naturally deposits excess iron in the heart, liver or pancreas. He said that iron normally reacts with oxygen in the bloodstream in a process called oxidization. But when excess iron is present, the oxidization process occurs at a much higher rate than normal, leading to the formation of chemicals containing unpaired electrons called “free radicals.” Liu, who likened the stray electrons to “energetic and troublemaking humans,” said that they punch holes in the walls of cells to react with protein molecules inside. Those molecules, in turn, take on the character of the free radicals and begin destroying cell membranes. As a result, in children suffering from congenital anemia, the destruction of cells can eventually weaken the heart to the point where it can no longer function—causing death.

Still, Liu insisted that the deadly effects of iron overload did not amount to further evidence of a link between iron levels and heart

disease. He said that in congenital anemia cases, the iron directly caused damage to the heart cells, while Salonen’s study appeared to indicate that iron buildup in bodies could encourage the entry of cholesterol into artery

walls. Liu said that Salonen’s work has only established that there is a statistical correlation between levels of iron and heart attacks, because the men in the study who were most prone to heart disease usually had higher levels of stored iron in their bodies. But Liu and other experts said that it will take further research to determine whether excess iron in itself causes heart attacks.

In the past, much of the research on diet and heart disease has been focused on the production and effects of cholesterol, which has been generally regarded as the chief cause of clogged arteries and heart attacks. The University of Ottawa’s McPherson, who is currently conducting cholesterol research, said that the body naturally produces cholesterol, which it uses in the formation of several hormones, including those that lead to the expression of male and female sexual characteristics. But the consumption of such fatty foods as butter, cheese and certain meats also increases the level of cholesterol in the blood. She added that research has shown that, because of their diets, many Canadians have twice as much

According to Dr. Malcolm Arnold, a cardiologist at the Victoria Hospital in London, Ont., doctors have three main methods of treating patients who have suffered coronary heart disease, depending upon the severity of the problem.

cholesterol in their bloodstream as they require. The excess cholesterol tends to build up dangerously along the walls of arteries and blood vessels throughout the body, she said.

He said that most doctors conduct tests to determine if drug therapy alone is sufficient to promote healing of the damaged heart and to prevent a recurrence of an attack.

If drugs cannot solve the problem, the next step is to consider an angioplasty, a technique in which a tube is inserted into a coronary artery and a balloon is inflated to attempt to open it. Arnold said that coronary bypass surgery is another option, but doctors try to avoid the operation because it is costly, complex and traumatic for the patient.

During the past decade, angioplasty has become an increasingly

popular method of treating heart disease, and doctors across Canada now perform approximately 7,000 annually, compared with only 500 a in the early 1980s.

Scaffold: Dr. Ian Penn, another cardiologist at London’s Victoria Hospital, said that since 1989, cardiologists at six heart centres across Canada have been testing an implant device known as a stent, which was developed to overcome the shortcomings of angioplasty. Penn described the stent as a tiny mesh scaffold, which is implanted inside a cholesterollined artery to keep it open. He said that the benefits of angioplasty are frequently shortlived because arteries tear, or return to their original constricted condition.

Penn added that if the patient’s condition cannot be stabilized by repeated balloon inflations, then urgent bypass surgery is often the next step. But there is also a risk involved in using the stent: in up to 10 per cent of patients, blood clots form around the device and cause a heart attack.

Drill: Penn said that he is currently testing a technique that could be used in cases when cholesterol deposits are so hard that an angioplasty balloon cannot open the blood vessel. It is a tiny drill called a rotablator, which rotates at a speed of 160,000 revolutions per minute. A surgeon can insert it into a vessel where it can actually chip away at the hardened buildup of plaque laden with cholesterol without cutting into soft arterial tissue. Penn said that he has tested the rotablator on about 50 patients. He said that he plans to describe the results at a meeting of the Canadian Cardiovascular Society in Ottawa next month.

But if drug therapy or angioplasty are unsuccessful, heart surgeons have to perform the

coronary bypass operation. In 1988-1989, the latest year for which figures are available, there were 10,922 bypass operations in Canada, up from 7,825 in 1981-1982. Dr. Yves Leclerc, head of surgery at the Montreal Heart Institute, said that the eight surgeons on staff at the centre perform 1,100 bypasses annually, an average of almost five every working day.

Leclerc explained that before 1980, surgeons customarily would take a section of a blood vessel from a patient’s thigh or leg and use it to replace a clogged artery near the heart. But he said that now, doctors usually prefer an artery from the patient’s chest, because research and simple experience have shown that such vessels remain open longer than would a vein from the lower extremities. He added that most bypass patients at the Montreal hospital are over 60 and that most are able to resume a normal life eight to 10 weeks after their surgery.

There is another, more extreme, treatment for heart disease—the transplant, still relatively rare because of the difficulties in finding donors and matching them with appropriate patients. Keon said that the Ottawa Heart Institute performs about 30 transplants a year, more than any of the five other Canadian heart centres where the procedure is available. He added that since 1986, the Ottawa institute has been involved in a joint project with researchers at the University of Utah to develop an artificial heart. He said that they recently installed a working model, valued at close to $100,000, in a calf, and are testing it for durability, but that the device may not be ready for use in humans until the turn of the century.

Meanwhile, heart disease research will continue to consume hundreds of millions of dollars

annually as scientists try to gain new insights into the causes of the disease and develop new techniques for treating it. Many experts say that if the link between iron and heart disease is proved, it could lead to a whole new field of heart research. Despite the gains in prevention, diagnosis and treatment, heart disease can still strike with a suddenness, and a severity, that surprises even veteran surgeons. Said Keon: “We see many, many people who die of heart attacks every year who have nothing else wrong with them.” Indeed, for many surgeons, it is that tragic waste of human life that drives their search for the causes and cures of North America’s biggest killer.

D’ARCY JENISH

with

JOHN DeMONT

in Halifax and

SHARON DOYLE DRIEDGER

in Toronto