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February 27, 2006

High death rate for women after heart surgery may be due to infection, U-M research finds

Mystery of why women die more often than men after bypass operations may be rooted in preventable or treatable causes

ANN ARBOR, MI – For years, experts have puzzled over the fact that women who have heart bypass surgery are far more likely than their male counterparts to die within days or weeks of their operation. This gender gap means many “extra” female deaths among the 270,000 Americans who have bypass surgery each year.

Mary A. M. Rogers, Ph.D., M.S.Now, a new University of Michigan study suggests that the answer to the mystery may lie with infections, regardless of their location in the body.

In a paper in the Archives of Internal Medicine, U-M Health System researchers report that 96 percent of the gender difference in death risk within 100 days of coronary artery bypass surgery may be explained by differences in infection. They used hospital and post-hospital data from 9,218 Michigan residents who had bypass surgery in a 15-month period. All were Medicare beneficiaries age 65 years or older.

“Overall, we found that women’s increased risk of mortality after coronary artery bypass surgery may be due to differences in infection,” says lead author Mary A. M. Rogers, Ph.D., M.S., research director of the Patient Safety Enhancement Program of the U-M Health System and the Veterans Affairs Ann Arbor Healthcare Center. “We found that 16 percent of women patients had an infection, compared with 10 percent of men.” This difference persisted after taking into account age, race, urgency of the operation, length of hospital stay, most co-existing medical conditions, and the number of bypass operations performed at each hospital or by each surgeon.

“We suspect that there may be a systemic, or body-wide, response to infection, making infection at any site a concern in elderly patients,” Rogers continues. She notes that women in the study were more likely than men to have infections of the urinary, respiratory and digestive tracts. Women were also more likely than men to have skin and post-operative infections.

But this was not the study’s only finding. Although women who had heart surgery were much more likely to have an infection than their male counterparts, women with an infection were less likely to die than men who had an infection. “This finding was a surprise since, overall, women had greater mortality,” says Rogers. “But when we looked closer, we found that there were two underlying relationships here: a greater prevalence of infection in women, and a higher mortality once infected for men.”

This pattern of greater morbidity in women but greater mortality for men has been observed before in elderly populations, Rogers notes. “Women tend to live with their disease; men die of it,” she says. In this case, the overall mortality was higher in women because infections were so much more prevalent among them.

Click on image for larger viewIn all, about 12 percent of patients in the study who had infections during their hospital stay died before leaving the hospital, compared with 4 percent of those without infections. And when the researchers looked at who had died in the first 30 and 100 days after their operation, those who had had an infection in the hospital were still far more likely to die.

Now, Rogers says, further research is needed to determine if any patient-related factors not analyzed in the study, such as blood-sugar control, nutritional status, smoking and genetic factors related to infection susceptibility, may account for these findings — and what role hospital-related factors such as the use of catheters might play. “There has been research indicating that, in patients undergoing heart surgery, small body size is a risk factor for mortality,” says Rogers. “So, there is a need for additional studies in this area.”

Until the new results can be confirmed and the precise role of infection in the bypass surgery “gender gap” determined, Rogers and her co-authors say there is much that heart patients of both sexes can do to prevent pre- and post-operation infections. Elderly Americans should keep up-to-date with their yearly influenza vaccination and, every five years, be vaccinated against bacterial pneumonia. Both vaccinations could be life-saving.

While in the hospital, bypass patients should heed their doctors’ advice to get up and start walking the hospital floor after their operation, because staying in bed for long periods of time may encourage respiratory infections. Frequent hand-washing by patients and their hospital caregivers is a good idea, and patients might also consider asking friends and family members who have colds to send their wishes by phone or computer instead of visiting.

Appropriate use of antibiotics is also important in patients undergoing bypass surgery. In fact, current national guidelines for bypass surgery call for patients to receive antibiotics an hour before their operation begins and to stay on them for at least a day afterward. The data used by Rogers and her colleagues did not include information regarding medications, so any differences among men and women in antibiotics use could not be evaluated.

Rogers, a faculty member in the General Medicine division of the U-M Department of Internal Medicine, works with a range of U-M physicians and researchers who study various aspects of patient safety and health care quality. That cooperation is what led to the current study. She had been working with Sanjay Saint, M.D., MPH, director of the Patient Safety Enhancement Program and associate professor of general medicine at the U-M and VA, on projects related to urinary tract infections among hospitalized patients with catheters. At the same time, she was working with heart-care quality researchers Brahmajee Nallamothu, M.D., MPH, and Catherine Kim, M.D., MPH, to examine differences among women and men in heart disease and care.

Curious to see if research had ever been done on the role of infection in heart-related gender differences, Rogers explored the medical literature — and found little. So, she embarked on the study with her colleagues, using Medicare data from a project led by Ken Langa, M.D., Ph.D., assistant professor of general medicine and a member of the U-M Institute for Social Research.

The study was funded by the U-M/VA Patient Safety Enhancement Program and by the John A. Hartford Foundation. Additional authors include Laurence McMahon Jr., M.D., MPH, professor and chief of the Division of General Medicine and professor of public health; Preeti Malani, M.D., a clinical assistant professor of internal medicine and VA research scientist; Brant Fries, Ph.D., professor of public health and gerontology at U-M and chief of health systems research at the VA Ann Arbor Healthcare System’s Geriatric Research, Education and Clinical Center; and Samuel Kaufman, M.Sc., of PSEP.

Reference: Archives of Internal Medicine, February 27, 2006; Vol. 166; pp. 437-443

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