Chemotherapy boosts heart disease risk
Mon, 08 Oct 2007 19:52:34 GMTBy LAURAN NEERGAARD, AP Medical Writer
WASHINGTON - Breast cancer survivors may face increased risk of heart disease — and doctors are debating if it's time to largely abandon a chemotherapy mainstay that is one reason for the problem.
Drugs called anthracyclines are a breast chemo staple despite a well-known risk: They weaken some women's hearts. What's new is research suggesting the drugs work no better than safer alternatives for most women.
It's a controversy born of success: Treatment advances are enabling more women than ever before to beat breast cancer, and some 2.4 million survivors are alive today. Now a move is under way to determine just how many women are vulnerable to heart disease because of their cancer battle, and how to help them.
Chemo is only one cardiac culprit. Other factors play a role, too: Chest radiation, the weight gain that plagues many survivors, physical inactivity during treatment and stress.
"In the process of curing their breast cancer, we've exposed them to some pretty nasty things. And it's not just one nasty thing, it's a sequence of nasty things," explains Dr. Pamela Douglas, a Duke University cardiologist who is planning research into how to protect these women's hearts.
"This is really coming at you from all sides," says Douglas, who outlined the "multiple hits" in this month's Journal of the American College of Cardiology.
But much of the debate centers on who should use anthracyclines, including the best-known Adriamycin, that can damage heart muscle, sapping its pumping strength.
Dr. Dennis Slamon of UCLA's Jonsson Cancer Center cites nine studies, here and abroad, that conclude that only the 20 percent of patients whose tumors have an overactive gene called Her2 are specifically sensitive to anthracyclines.
Then Slamon's closer inspection found that not all Her2 patients are alike — and only those who have a second overactive gene, called TopoII, derive special benefit from anthracyclines. That's about 8 percent of breast cancer patients.
The powerful Her2-targeting drug Herceptin — key for women with Her2-positive tumors — also comes with a heart-damage warning. But adding it to anthracyclines increases the heart risk fivefold, with no extra benefit, Slamon found.
Outright heart failure during chemo is rare, around 2 percent of patients. But Douglas cites research that anywhere from 10 percent to half of anthracycline users experience more subtle heart weakening, making them more vulnerable to aging's usual rigors, like high blood pressure and cholesterol.
And in this month's Journal of Clinical Oncology, researchers tracked breast cancer survivors ages 66 to 70 who had undergone chemo 10 years earlier. Those who had received an anthracycline were 26 percent more likely to have developed heart failure in the following decade than those on different chemo.
"It's almost like the perfect storm," Slamon says of all the research. "We're adding no incremental benefit with plenty of incremental toxicity."
Now the influential National Breast Cancer Coalition is lobbying oncologists and government regulators to reconsider treatment guidelines.
"These are very strong, very real data that they need to pay attention to," says coalition president Fran Visco.
But many oncologists aren't convinced, and want more evidence that other chemos work as well.
Indeed, Duke University is beginning a major study funded by the Defense Department to do additional genetic testing on Her2-negative women, to compare Adriamycin to the non-anthracycline Taxotere.
"It's fair to say I'm using less Adriamycin for truly early stage" cancer, says lead researcher Dr. Kelly Marcom, Duke's breast oncology chief.
"But there are still patients that I think have cancers that may be more sensitive to Adriamycin," Marcom adds. The jury is still out."
However that controversy ends, a bigger question is how to find and help survivors with heart damage from any cause. As Jane Sartin of Providence, N.C., learned, symptoms are sneaky.
Sartin underwent a mastectomy for side-by-side breast tumors, and took Adriamycin followed by Herceptin. She was warned about heart side effects, and knew as an overweight smoker she already was at risk. Yet she blamed the surgery when she got winded.
"I had never said anything to my doctor about it. I'd say, 'I'm tired, I think from the surgery,'" recalls Sartin, 45.
Twice her ejection fraction — a measure of blood pumped per beat — dropped well below normal. It bounced back with treatment changes, and Sartin believes her cancer therapy's benefit justified the side effect.
"I really felt like, hey, I can deal with anything as long as I'm alive," says Sartin, who now is dieting and weaning herself from cigarettes.
For now, never shrug off heart-related symptoms, stresses Dr. Ann Bolger of the University of California, San Francisco, an American Heart Association spokeswoman. Early care can be lifesaving.
Duke's Douglas recommends that all breast cancer patients get a formal heart risk assessment before oncologists decide final treatment. It might sway cancer therapy, or signal who'll need extra heart care later.
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EDITOR's NOTE — Lauran Neergaard covers health and medical issues for The Associated Press in Washington.
Studies Stored blood lacks nitric oxide
Mon, 08 Oct 2007 21:18:29 GMTBy RANDOLPH E. SCHMID, AP Science Writer
WASHINGTON - Much of the stored blood given to millions of people every year may lack a component vital for it to deliver oxygen to the tissues. Nitric oxide, which helps keep blood vessels open, begins breaking down as soon as blood goes into storage, two research teams report in separate studies in this week's online edition of Proceedings of the National Academy of Sciences.
In recent years, doctors have become increasingly concerned about levels of heart attack and stroke in patients receiving transfusions and the new findings may help explain that.
"It doesn't matter how much oxygen is being carried by red blood cells, it cannot get to the tissues that need it without nitric oxide," said Dr. Jonathan Stamler of Duke University, leader of one of the research groups.
Blood vessels relax and constrict to regulate blood flow and nitric oxide opens up blood vessels, allowing red blood cells to deliver oxygen, he explained.
"If the blood vessels cannot open, the red blood cells back up in the vessel and tissues go without oxygen. The result can be a heart attack or even death," he said.
"The issue of transfused blood being potentially harmful to patients is one of the biggest problems facing American medicine," said Stamler.
Several of the researchers, including Stamler, have consulting and/or equity relationships with Nitrox/N30, a company developing nitric oxide based therapies.
The second research team, led by Dr. Timothy McMahon, also at Duke, studied the changes in stored blood over time. Currently blood is allowed to be kept in blood banks for up to 42 days. After that it must be discarded. An estimated 14 million units of red blood cells are administered to about 4.8 million Americans annually.
"We were surprised at how quickly the blood changes — we saw clear indications of nitric oxide depletion within the first three hours," McMahon said in a statement.
Stamler said in a telephone interview that the researchers knew that nitric oxide is responsible for opening up small blood vessels, but had not previously measured the amount of that chemical in stored blood.
"Surprisingly, we found blood depleted profoundly by day one and it remained depleted through day 42," he said.
But if they restored the nitric oxide at any point, the red blood cells were again able to open blood vessels and deliver oxygen to tissues, they said. They tested the blood with added nitric oxide both in the laboratory and in dogs.
"This is an important observation and it needs to be followed up," said Dr. Louis Katz, a past president of America's Blood Centers, which provides about half the nation's blood.
"If you are going to store red cells, is there a way to make sure appropriate nitric oxide levels are maintained?" said Katz, who was not part of the research teams.
It is possible that these findings may make the public concerned about transfusions, Katz said: "There is no doubt, if you are bleeding to death from a trauma" you need a transfusion.
Stamler agreed that "physicians need to be able to give blood if people are bleeding profusely."
Overall, Katz said: "This is neat research. It needs to be proven that it's clinically relevant."
Stamler agreed on the need for clinical trials.
"Banked blood is truly a national treasure that needs to be protected," Stamler said. "Blood can be life saving, only it is not helping the way we had hoped and in many cases it may be making things worse. In principle, we now have a solution to the nitric oxide problem — we can put it back — but it needs to be proven in a clinical trial."
The research was supported by the National Institutes of Health, Duke Anesthesiology Fund, the American Heart Association and N30 Pharma, which has a license agreement with Duke to develop nitric oxide-based therapies.
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On the Net:
PNAS: http://www.pnas.org
Study ties marital strife heart disease
Mon, 08 Oct 2007 20:15:21 GMTBy LINDSEY TANNER, AP Medical Writer
CHICAGO - A lousy marriage might literally make you sick. Marital strife and other bad personal relationships can raise your risk for heart disease, researchers reported Monday.
What it likely boils down to is stress — a well-known contributor to health problems, as well as a potential byproduct of troubled relationships, the scientists said.
In a study of 9,011 British civil servants, most of them married, those with the worst close relationships were 34 percent more likely to have heart attacks or other heart trouble during 12 years of follow-up than those with good relationships. That included partners, close relatives and friends.
The study, in Monday's Archives of Internal Medicine, follows previous research that has linked health problems with being single and having few close relationships. In the new study, researchers focused more on the quality of marriage and other important relationships.
"What we add here is that, 'OK, being married is in general good, but be careful about the kind of person you have married.' The quality of the relationship matters," said lead author Roberto De Vogli, a researcher with University College in London.
De Vogli said his research team is doing tests to see if study participants with bad relationships have any biological evidence of stress that could contribute to heart disease. That includes inflammation and elevated levels of stress hormones.
Another recent study also looked at quality of relationships but had different results. There was no association between marital woes in general and risks for heart disease or early death. But it did find, over a 10-year follow-up, that women who keep silent during marital arguments had an increased risk of dying compared with wives who expressed their feelings during fights. What appeared to matter more for men was just being married; married men were less likely to die during the follow-up than single men.
That study, of nearly 4,000 men and women, was published online in July in the journal Psychosomatic Medicine.
In De Vogli's study, men and women with bad relationships faced equal risks. Volunteers filled out questionnaires asking them to rate the person to whom they felt closest on several measures. These included questions about to what extent does that person "give you worries, problems and stress?"
They also were asked about whether they felt they could confide in that person, or whether talking with that person made them feel worse.
Over the following 12 years, 589 participants had heart attacks or other heart problems. Those with the highest negative scores on the questionnaire had the highest risks, even taking into account other factors related to heart disease such as obesity, high blood pressure and smoking.
James Coyne, a University of Pennsylvania psychology professor who also has examined the health impact of social relationships, said De Vogli's results "make intuitive sense." But he said the study found only a weak association that doesn't prove bad relationships can cause heart disease.
"It is still not clear what to recommend," Coyne said.
"Do we tell people who have negative relationships to get therapy? They may have other reasons to do so, but I see no basis for them doing so only to avoid a heart attack," Coyne said.
Ending a bad marriage is not necessarily the answer either, he said, given evidence that being unmarried also could be a risk.
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On the Net:
Archives: http://www.archinternmed.com
Study Disabled less likely to be online
Mon, 08 Oct 2007 20:05:36 GMTBy ANICK JESDANUN, AP Internet Writer
NEW YORK - Americans with disabilities and other chronic conditions are less likely to use the Internet, but those who are online are among the most avid consumers of health-related information, a new study finds.
Half of those with chronic conditions use the Internet, compared with three-quarters of those without, the Pew Internet and American Life Project said Monday.
That's partly because those with chronic conditions tend to be older and less educated, two factors linked with lower Internet usage overall, said Susannah Fox, an associate director at Pew and the study's main author. Other barriers include difficulties navigating the Web for those with, say, poor vision or motion control.
But when they are online, those with chronic conditions are more apt to seek health information online — at least for some tasks.
"It's an indication of what could happen in the future if there were more universal access to the Internet," Fox said. "This population is just as likely as anyone else to take advantage of the technology's promises."
The telephone study of 2,928 American adults was conducted in August 2006 and has a margin of sampling error of plus or minus 2 percentage points. Results based on the 268 Internet users with chronic conditions have an error margin of plus or minus 7 percentage points.
Pew said 86 percent of Internet users with chronic conditions have looked online for information on at least one of 17 health topics, compared with 79 percent of those without such conditions. The difference, however, falls within the error margin.
The study found the chronic population far more likely to look for information about medication, specific treatments and procedures and alternative treatments and medicines — all by margins exceeding the potential sampling error.
