B vitamins fail to help heart
The radical idea that the amino acid homocysteine might play an important role in the onset of heart disease was first proposed three decades ago by Dr. Kilmer McCulley of Harvard Medical School.
His unorthodox theory, coming at a time when cardiologists were just beginning to focus on the adverse effects of cholesterol, earned McCulley a great deal of derision and got him ejected from the faculty of Harvard.
Over time, however, a series of studies has shown a strong link between high levels of homocysteine in the blood and a sharply increased risk of heart attacks and strokes. Many physicians have been advocating the use of vitamin B and folic acid supplements, which break down homocysteine in the body, to reduce levels of the amino acid and thereby cut the incidence of heart disease.
Now, three major studies, two of them released last week at an Atlanta meeting of the American College of Cardiology, offer at least partial support for the homocysteine theory. They show that the supplements do, in fact, bring homocysteine levels down sharply. But the reduced levels do not lead to any reduction in the risk for heart disease.
Other studies at the meeting indicate that two new drugs can reduce deaths in heart attack victims who receive clot-busting therapy, and that treating early signs of hypertension can delay onset of more severe problems. But the homocysteine research was especially surprising because of the many vocal proponents of the therapy. The results suggest “homocysteine could be a marker for, but not a cause of, vascular disease,” said Dr. Eva Lonn of McMaster University in Ontario, co-leader of one of the studies.
The supplement studies have brought McCulley, now at the VA Boston Health Care System, full circle. He conceded that the supplements are “not effective in reversing or benefiting advanced vascular disease.” But he and others continue to argue that they might help prevent the disease in healthy people.
“These studies did not test whether B vitamins used by healthy people can keep them healthy,” said Annette Dickinson, a past president of the Council for Responsible Nutrition, an organization of supplement manufacturers. “Vitamins should not be expected to perform like drugs. Their greatest promise is in prevention.”
Countered Lonn’s colleague, Salim Yusuf, a professor of medicine at McMaster: “Things that don’t work in sick people don’t work in less sick people either.”
Yusuf and Lonn studied 5,522 Americans and Canadians who had either heart disease or diabetes, which places patients at high risk of developing heart disease. Over a five-year period, half the patients were given the supplements and half a placebo.
Homocysteine levels fell by about one-third in the patients receiving the supplements -- more than enough to cause a reduction in heart attack risk if the homocysteine theory were correct. However, the team reported at the Atlanta cardiology meeting, the number of heart attacks and strokes in the two groups were virtually identical.
In the second study, Dr. Kaare Bonaa of the University of Tromso in Norway and colleagues gave either supplements or a placebo to patients who had suffered a heart attack. After three years, those receiving the supplements were no less likely to have a second heart attack or to die from heart disease.
In the third study, published two years ago in the Journal of the American Medical Assn., researchers at Wake Forest University’s School of Medicine gave supplements or a placebo to 3,680 people who had survived a stroke. The more supplements that were administered, the greater the reduction in homocysteine levels, but there was no change in the incidence of recurrent strokes at any level.
“The consistency among the results leads to the unequivocal conclusion that there is no clinical benefit of the use of folic acid and vitamin B12 (with or without the addition of vitamin B6) in patients” with heart disease, Dr. Joseph Loscalzo of Brigham and Women’s Hospital in Boston wrote in an accompanying editorial in the New England Journal of Medicine, where the studies will be published next month. Dr. Steven E. Nissen of the Cleveland Clinic, president of the American College of Cardiology, concluded that the findings should end the debate about the homocysteine theory.
In other study results reported at the meeting, researchers examined new drugs that might be able to save the lives of heart attack victims.
Currently, the gold standard for treating heart attack patients is angioplasty, in which a catheter is inserted into the coronary artery and a balloon is inflated to compress the clot that blocks blood flow.
If a patient cannot get to a hospital for angioplasty soon enough, however, the alternative is to use clot-busting drugs, such as tPA and streptokinase. Such patients are typically also given injections of the blood-thinner heparin to prevent the formation of new clots that can cause repeat heart attacks.
Three large studies presented at the meeting show that two new drugs are safer than heparin and more effective at preventing subsequent heart attacks and strokes in patients who have ST-elevation myocardial infarctions, which account for nearly half of all heart attacks.
One of the drugs, Lovenox, or enoxaparin, is a purified form of heparin. The second, Arixtra, or fondaparinux, is a synthetic compound that works at a different location in the biochemical cascade that leads to clotting.
One study involved 20,000 heart attack patients who were treated with a clot-buster and then randomly assigned to receive either enoxaparin or heparin. Dr. Eliot Antman of Brigham and Women’s Hospital reported that, after 30 days, 4.5% of the patients receiving heparin had a second, nonfatal heart attack, compared with 3% of those receiving enoxaparin. The new drug reduced deaths by 17%.
Patients receiving enoxaparin were more likely to suffer major bleeding, but Antman said that was offset by the outcome.
In the second trial, nearly 12,000 heart attack patients receiving clot-busting therapy and heparin also received either fondaparinux sodium or a placebo. McMaster’s Yusuf reported that those receiving fondaparinux sodium had a 35% reduction in second heart attacks and a 17% reduction in deaths -- about the same as with enoxaparin.
But there was no increased bleeding associated with use of the drug, he said, indicating that it is a safer alternative. Treatment with fondaparinux sodium showed no benefit, and was perhaps even somewhat harmful, in patients undergoing angioplasty.
In still another study reported at the meeting, researchers examined the potential benefits of treating early signs of hypertension.
About 70 million Americans have a condition now known as pre-hypertension -- formerly called high-normal blood pressure or borderline hypertension. These people have a blood pressure between 120/80 and 139/89. In many such patients, the condition is stable for long periods, but in others it proceeds to full-blown hypertension relatively rapidly. Hypertension is a major risk factor for heart disease.
Studies in mice by Dr. Stevo Julius of the University of Michigan Medical School have shown that treating pre-hypertensive animals with blood pressure-lowering drugs called ACE inhibitors for a short period could substantially delay the transition to hypertension.
Julius then organized a trial of 800 humans with pre-hypertension. Half took the hypertension drug candesartan or Atacand for two years, and half took a placebo. All were then monitored for another two years.
Julius told the meeting that 240 of those who took the placebo developed hypertension over the four years of the study, compared with 208 of those who took candesartan. The average time to development of hypertension was 2.2 years in the placebo group and 3.3 years in the candesartan group.
“There is a significant effect,” Julius told a news conference at the meeting. “It is not an overwhelming effect. It is a modest effect. But it has been proven.” He called for more research, possibly using other drugs.
