Understanding the gender divide (AHA Scientific Sessions 2006)

Studies find mechanisms for the well-documented gap between outcomes for men and women with heart disease and suggest strategies for narrowing it.

By Victoria Stagg Elliott — Posted Jan. 1, 2007

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When it comes to heart health, preventive strategies and treatment outcomes, men and women are not the same. Researchers are attempting to quantify the differences and disparities and determine how to address them, according to several studies and panel discussions at the American Heart Assn. Scientific Sessions in Chicago, Nov. 12-15, 2006.

"There's a huge gap in our science and our clinical practice," said Ann Bolger, MD, chair of the AHA's Council on Clinical Cardiology and William Watt Kerr Professor of Clinical Medicine at the University of California, San Francisco. "Women are different from men, and the outcomes, the risk factors and the responses to very particular therapies are probably different. We need to understand this."

These variations seem to start before heart disease becomes apparent. For example, women are less likely than men to be concerned about heart disease risk and to take steps to reduce it. Researchers from the University of Texas Southwestern Medical Center found that women with a family history of heart disease were more likely to smoke, were less active and had more risk factors than men with a similar background.

In the area of primary prevention, recognition is growing that the commonly used Framingham risk assessment tool may not be as good for women -- especially those younger than 70 -- as it is for men. "A majority of women are classified as low risk by traditional risk factor assessment and thus are not considered for more aggressive interventions to prevent the disease that kills the most," said Susan G. Lakoski, MD, a cardiology fellow at Wake Forest University School of Medicine, Winston-Salem, N.C.

Some physicians advocated placing greater emphasis on risk factors outside the Framingham model that are more common among females, such as obesity, sedentary behavior and hypertension. Many also would like to see more consideration given to family history and called for additional research to determine how gender-specific levels of C-reactive protein and coronary artery calcium can inform the risk assessment.

Women also seem to require different treatment strategies.

A study conducted at the Emory University Heart Center in Atlanta found that women did better with off-pump coronary artery bypass surgery than they did with the on-pump version. Researchers analyzed data on 11,413 patients gathered by the Society of Thoracic Surgeons Adult Cardiac Database from 1997 to 2005. Women had a 60% increased risk of death after any form of coronary artery bypass surgery than men, but the off-pump version eliminated this gender gap. An analysis of national data and similar results will be presented at the Society of Thoracic Surgeons meeting in San Diego in January.

"Why can't a woman be more like a man? Well, they can if they have off-pump bypass," said John D. Puskas, MD, study presenter and chief of cardiac surgery at the Emory Crawford Long Hospital in Atlanta. "Our data set confirms the historic belief that there is a gender disparity in clinical outcomes after CABG, but female patients benefited more from avoidance of cardio-pulmonary bypass during CABG than did their male counterparts."

In addition, women appear to need different strategies during the initial recovery period. High levels of anxiety during hospitalization have been shown to increase the risk of complications and death after an acute myocardial infarction in both genders, but a study from the University of Kentucky found that women were far more anxious than men in this situation. Anti-anxiety drugs reduced their complications.

"Treating anxiety in the immediate post-MI period is important to consider in order to decrease morbidity and mortality," said Debra K. Moser, DNSc, one of the authors and a professor in the university's College of Nursing.

Once out of acute care, differences persist. Another study found that women get less-aggressive secondary prevention. This paper followed 2,462 patients over a seven-year period presenting to the Cleveland Clinic Foundation. Women tended to be older and more likely to be hypertensive but were less likely to be taking anti-platelet therapy or statin drugs. They also were more likely to die during the study period.

"Everybody's very focused on the new and the latest and the greatest devices in medicine, but we're still far away from doing things that we know have a proven benefit," said Leslie Cho, MD, lead author and director of the Women's Cardiovascular Center at the Cleveland Clinic.

One treatment possibility has not lived up to its promise. A combination of folic acid, vitamin B6, and B12 lowered homocysteine levels by an average of 18% in women who already had cardiovascular disease or at least three risk factors. But this did not translate to a reduction in the number of heart attacks, strokes and death.

"Our study does not suggest that taking folic acid, B6 or B12 primarily to prevent cardiovascular disease would be worthwhile. Women who are taking them solely for that purpose may want to discontinue," said Christine M. Albert, MD, MPH, lead author and director of the Center for Arrhythmia Prevention at Brigham and Women's Hospital in Boston.

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Women vs. men

A study that followed 2,462 patients from 1997 to 2004 at the Cleveland Clinic's Preventive Cardiology Clinic found several gender-based variations.

Men Women
Age at presentation 59.4 62.2
Hypertensive 56.1% 68.1%
C-reactive protein 4.9 6.1
LDL cholesterol 116 135
HDL cholesterol 41 52
Total cholesterol 202 238
On antiplatelet therapy 85.0% 76.6%
On lipid-lowering drugs 67.1% 62.6%
Died from any cause within
7 years from an event
17.8% 21.5%

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Attention turns to young adults with high lifetime risk of heart disease

With tools to quantify a person's 10-year heart disease risk well established, physicians are seeking strategies to assess and reduce lifetime risk. This is particularly the case for patients younger than those usually considered to be candidates for most preventive measures, according to a presentation at the American Heart Assn.'s scientific sessions in Chicago in November 2006.

"There's a focus on chronologic age that reduces the likelihood of identifying young adults with a high lifetime risk," said Roger Blumenthal, MD, director of the Johns Hopkins University Ciccarone Preventive Cardiology Center in Baltimore. "[But] chronologic age does not necessarily correlate with biologic age."

This expansion of prevention efforts to those who appear to be heading toward a cardiovascular event -- even more than a decade away -- follows data suggesting risk factors start developing early.

"At every life stage, identifying the major risk factors is extremely useful, not only as a prediction of what's to come, but also to treat," said Neil J. Stone, MD, clinical professor of cardiology at Northwestern University's Feinberg School of Medicine in Chicago. "This doesn't necessarily mean giving them a medication, but every doctor should be comfortable looking a patient in the face and saying there are things we can do that make a difference."

Experts recommend such an assessment consider activity levels, obesity and any family history of premature cardiovascular disease, factors left out of most tools that measure short-term risk.

"Family history is a strong independent risk factor," said Christopher J. O'Donnell, MD, MPH, associate director of the Framingham Heart Study.

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Risks, benefits of aspirin and NSAIDs vary with patient problems

Risks, benefits vary with patient problems

Rather than a patient's genetic makeup, it may be co-morbidities that explain why some benefit less than others from aspirin therapy to reduce heart disease risk, according to several studies presented at the American Heart Assn. Scientific Sessions in Chicago.

Two studies, for instance, suggested that patients with diabetes and metabolic syndrome have a higher turnover rate of platelets that, in turn, may lead to an over-expression of cyclooxygenase-2 (COX-2). Whether these conditions or their treatment caused this was unclear, but the authors suggested the finding could explain why aspirin therapy is less likely to reduce cardiovascular events in these patients. Another paper found that genetics -- specifically a rare allele evidenced by variation in the thromboxane A2 synthase gene -- also may cause aspirin resistance.

These papers are the latest efforts to understand why regular aspirin use is not equally protective.

"The optimal effect in most patients is seen at a low dose of aspirin, but this raises the issue of whether selected patients would derive a benefit from higher doses," said Paul Gurbel, MD, director of the Center for Thrombosis Research at Baltimore's Sinai Hospital.

While several papers explored the mechanisms behind aspirin resistance, others attempted to quantify further the dangers of various nonsteroidal anti-inflammatories taken for pain control.

This issue has come up repeatedly since the September 2004 revelation of an increased risk of heart disease associated with the use of COX-2 inhibitor drugs. Physicians have since been looking for ways to ensure that patients get the pain relief they need while minimizing associated dangers.

One systematic review found that chronic use of nonselective NSAIDs increased the risk of hypertension, although this risk was highest with ibuprofen.

Another study concluded that rates of thrombotic cardiovascular events for patients taking the investigational, highly selective COX-2 inhibitor etoricoxib were comparable to those experienced by those who took the less-selective diclofenac. Patients who took etoricoxib had a higher rate of congestive heart failure and were more likely to discontinue the drug because of hypertension. The diclofenac group was more likely to stop taking this medication because of gastrointestinal and liver events.

"Our results do show that in these patients with arthritis that the COX-2 selective agent did not increase the risk relative to a traditional agent," said Christopher P. Cannon, MD, study leader and associate professor of medicine at Harvard Medical School in Boston.

A heart association statement issued in the wake of these results expressed caution and called for more long-term data that fully evaluates the risks and benefits of COX-2 inhibitors as well as the safety of traditional pain relievers.

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External links

Information about lectures, presentations and other developments at the American Heart Assn. 2006 Scientific Sessions (link)

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