Women & heart health: from prevention to intervention.

You don't have to tell Helen Rehak how treatment for heart disease has changed over the past quarter of a century. The 77-year-old woman, who lives in Indialantic, FL, has had three open-heart surgeries during her 25-year battle with genetically related heart disease and more angioplasties and angiograms than she can count.

She's had new blood vessels created to reroute blood around blocked arteries, arteries opened with balloons, plaque cleared out with rotor-rooter-like instruments and, in 2001, two tiny mesh scaffolds called stents inserted into her arteries to keep the darn things open.

Within a year, however, the arteries were nearly fully blocked again. Frustrated and desperate, her cardiologist arranged for her to have a still-experimental, drug-eluting stent implanted, hoping that the new device, designed to prevent arteries from clogging up again, would make a difference.

It did.

Three years later, Ms. Rehak's arteries remain clear, leaving her without the constant chest pain, or angina, that formerly haunted her. Today, she continues to do her own housework, play cards with friends and goes out to eat with her husband of 56 years.

Ms. Rehak is one of 33.3 million women in the United States, about one out of every five, diagnosed with some form of cardiovascular disease (CVD). This disease could be high blood pressure, a heart attack, chest pain, congestive heart failure, stroke or congenital heart defects. Overall, CVD accounts for nearly half of all deaths in the U.S., and costs the country about $368 billion in direct and indirect costs. (1)

Like many chronic illnesses, CVD strikes African-American women particularly hard, in part because they are more likely to have risk factors such as high blood pressure and be overweight, and in part because they tend to receive poorer care than Caucasian women. The result? Higher death rates--376.6 per 100,000 for African-American women in 2001 compared to 273.6 per 100,000 for Caucasian women. (1)

Regardless of their race, however, the majority of women remain unaware of their risk for heart disease, says Lori Mosca, MD, PhD, director of the preventive cardiology program at New York-Presbyterian Hospital and the Columbia University Center for Heart Disease Prevention in Manhattan. Dr. Mosca chaired the National Expert Panel that developed "Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women." That's why she's a major supporter of the American Heart Association's Go Red campaign, designed to make women more aware of their health risks in this area. "Women need to understand that heart disease is a health issue they need to be concerned with," she says.

Yet a 2003 survey of 204 women with heart disease conducted by researchers at the Mayo Clinic in Rochester, MN, found that many considered their condition "a man's disease." Almost half had been unaware they were at risk of coronary artery disease until after their diagnosis.

"I think one of the underlying reasons for women's misperception or the myth that heart disease is a man's disease is related to the fact that women's physicians often don't ask them about their heart disease risk or talk to them about it," Dr. Mosca notes.

In fact, the same Mayo Clinic survey noted above found that when women reported their cardiovascular symptoms to their doctors, nearly one-third of the physicians failed to recognize the symptoms as heart-related. (2)

"There's a lack of awareness of women's cardiac risk among physicians," says Dr. Mosca. One reason is that women have been excluded from so many cardiology research trials over the years. "So there's a perception that heart disease is not a problem for women," she says.

Another reason relates to how the media portrays heart attacks--nearly always in men. "The face of heart disease is often a male face," says Dr. Mosca.

That's true even when it comes to marketing drugs to treat heart disease. When Angela Cheung, MD, associate director of the women's health program at the University of Toronto, evaluated print advertising for cardiovascular drugs directed at physicians, she and her colleagues found the ads portrayed male patients 80 percent of the time. When women were depicted, they usually looked very young, quite unlike the postmenopausal woman most likely to get heart disease.

These findings are disturbing, she says, because other research shows that such advertising can affect physician actions. "Would they recognize a woman having a heart attack when she came in? Would they even prescribe the appropriate medications?" she asks.

If history is any indication, the answer is probably not. Numerous studies find significant gender-based differences in the way women with heart disease are treated. For instance, a study published in the journal Circulation in February 2005 found that women with heart disease are less likely than men to receive recommendations from their doctors for preventive therapies such as low-dose aspirin therapy, cholesterol-lowering drugs and cardiac rehabilitation. (3) (For more information on the benefits of low-dose aspirin therapy for women with heart disease, see "What to Know About Aspirin Therapy" on page 5.)

Another major study published in the February 1999 issue of the New England Journal of Medicine found women were less likely to be referred for cardiac catheterization, a procedure to unclog arteries, than men. (4) Furthermore, research presented at the American Heart Association's national meeting in late 2004 found that women who have heart attacks wait longer than men to receive an emergency angioplasty to open blocked arteries. (5)

Once women do undergo interventional procedures such as angioplasty, they're more likely to experience short-term complications. They're also twice as likely to die in the hospital following bypass surgery, she notes. "We believe much of this is related to the fact that women are older, have more numerous health conditions, and their disease is farther advanced when they finally do come to our attention," says Dr. Mosca.

Such data led the American Heart Association to recommend in February 2005 that physicians should diagnose and provide referrals to women for procedures like balloon angioplasty and stenting sooner than they do. Currently, just 35 percent of such procedures are performed on women. (6)

Newer, More Effective Treatments for Heart Disease

Perhaps nothing since the advent of the heart transplant has affected the treatment of heart disease as much as the introduction of cardiac catheterization in the late 1970s, notes Cindy L. Grines, MD, who directs the cardiac catheterization lab at William Beaumont Hospital in Royal Oak, MI. There are two main catheterization procedures: angiograms, a diagnostic procedure to identify artery blockages; and coronary angioplasty, similar to an angiogram but involving a treatment component as well.

Angioplasty, first performed in 1977, involves threading a balloon-tipped catheter through the groin artery to the blocked cardiac artery, inflating the balloon to unclog the artery, deflating it and removing the catheter. Unfortunately, the arteries often "recoiled" after the procedure, explains Dr. Grines, and became blocked again.

Researchers thought they had the recoil problem fixed when stents--tiny metal scaffolds used to prop the artery open--came on the scene in the 1990s. But while the stents eliminated the artery recoil, they irritated the lining of the artery. That, in turn, triggered a chemical cascade that resulted in the formation of scar tissue, a condition called "restenosis." Today, about 15 to 30 percent of patients undergoing angioplasty develop restenosis within a year, requiring a repeat angioplasty or bypass surgery. (7)

Enter drug-eluting stents, stents coated with medication that is slowly released into the coronary artery to keep plaque from reforming. The U.S. Food and Drug Administration (FDA) approved the first drug-eluting stent, Cypher, in 2003. The Cypher stent, developed and manufactured by Johnson & Johnson, is covered with sirolimus, a medication traditionally used to prevent transplant rejection. It works by keeping the artery open while also releasing small amounts of the drug inside the artery, which helps prevent blockage from recurring inside the vessel. Clinical studies funded by the Cypher stent's manufacturer, Johnson & Johnson, find that 94 percent of patients who have received the Cypher stent avoid a repeat cardiac procedure. (28)

In March 2004, the FDA approved a second drug-eluting stent, Taxus, which is coated with the chemotherapy drug paclitaxel (Taxol). This drug inhibits cell growth by killing cells inside the artery. (8)

One recent analysis conducted by Cypher's manufacturer found that women who received the Cypher stent, including high-risk women with diabetes and those who smoked, were five times more likely to avoid a repeat reblockage in the treated arteries than women who received a plain metal stent. (9)

The success of the stents, both drug-eluting and conventional bare metal, hasn't meant the demise of the traditional bypass surgery. During this procedure, surgeons fashion a new blood vessel from veins taken from the leg or another part of the body, and reroute blood flow around the blocked vessel. In 2001, an estimated 516,000 coronary bypasses were performed. (1) "Right now, there are certain subsets of patients we still routinely send for bypass surgery," says Dr. Grines, "including those with diabetes and those with blockages in multiple vessels." Studies show these patients live longer with bypass than angioplasty, she says.

That may change. Earlier studies comparing bypass to angioplasty were performed prior to the approval of drug-eluting stents. Studies are now underway comparing the surgical procedure to angioplasty performed with the drug-coated stents, she said.

There's also evidence that drug-eluting stents might have particular benefits for women, who are more likely to have blockages in very small vessels. A study published in the Journal of the American Medical Association in late 2004 found that the Cypher stent was successful in opening very small coronary vessels, which typically have up to a 50 percent restenosis rate. (10) "This is important for women, who have smaller vessels than men's," says Dr. Grines.

Also, she notes, restenosis is particularly common in small vessels. "Because there is so little room inside the vessel, any little bit of growth will plug the vessel," she explains. "By using a drug-eluting stent, the physician is more likely to open small vessels that they would have previously left alone."

Looking into the near future, Dr. Grines doesn't envision anything as dramatic as the drug-eluting stents emerging any time soon. One promising technology is the use of high frequency vibration from ultrasounds to break up plaque, she says, and coating stents with medications that could affect plaque clusters farther down in the artery, a common condition in women.

While such high-tech approaches for treating heart disease are all well and good, says Dr. Mosca, more attention needs to be paid to the low-tech aspects of preventing heart disease. "We need to find ways to help women lead heart-healthy lifestyles, because that is the root cause of the CVD epidemic," she says.

"We also need to evaluate the impact of women having multiple roles, taking care of aging parents, spouse, children, career. This delicate life-balancing act is no doubt going to play havoc with our hearts."

MEDICATING HEART DISEASE

Along with interventional procedures, health care professionals
prescribe medication to eliminate chest pain, angina attacks and
prevent heart attacks in patients with coronary artery disease. Most
drug therapy is designed to decrease the amount of  oxygen the heart
needs while increasing its oxygen supply, as well as preventing future
blood clotting that can close off vessels. (11) Several classes of drugs
are used either alone or in combination.

Medication       Medication Name                  How it Helps Your
Class                                             Heart

Nitrates         These include the commonly used  Provides an
                 nitroglycerine.                  external source of
                                                  nitric oxide, a
                                                  chemical that
                                                  relaxes blood
                                                  vessels and keeps
                                                  blood cells from
                                                  becoming sticky,
                                                  preventing clotting
                                                  and blockages. (11)

Calcium channel  Verapamil (Calan), diltiazem     Prevents calcium
blockers         (Cardizem), amlodipine           from entering heart
                 (Norvasc) and nifedipine         and vascular
                 (Adalat)                         muscles. Relaxes
                                                  heart muscle,
                                                  increases blood
                                                  vessel dilatation,
                                                  and improves oxygen
                                                  delivery. (11)

Beta blockers    Acebutolol (Sectral), atenolol   Decreases the force
                 (Tenormin), betaxolol            of the heart's
                 (Kerlone), metoprolol            contraction and its
                 (Lopressor), atenolol            overall heart rate,
                 (Tenormin), bisoprolol (Concor)  thus reducing the
                 and pindolol (Visken)            heart's demand for
                                                  oxygen. (11)

Platelet         Aspirin and clopidogrel          Helps keep blood
inhibitors       bisulfate (Plavix)               platelets from
                                                  sticking together
                                                  and forming clots,
                                                  thus maintaining
                                                  blood flow and
                                                  preventing another
                                                  stroke or heart
                                                  attack. (11)

Angiotensin      Enalapril (Vasotec), ramipril    Prevents formation
converting       (Altace) and captopril           of angiotensin II
enzyme (ACE)     (Capoten)                        hormone, which
inhibitors                                        normally causes
                                                  blood vessels to
                                                  narrow. ACE
                                                  inhibitors cause
                                                  the vessels to
                                                  relax, reducing
                                                  blood pressure. (11)

Angiotensin II   Losartan (Cozaar), valsartan     Works by blocking
receptor         (Diovan), irbesartan (Avapro),   angiotensin II
blockers         and candesartan (Atacand)        receptors on cells,
                                                  helping reduce
                                                  blood pressure.

Thrombolytics    tPA, TNKase (Tenecteplase),      Given intravenously
(clot busters)   alteplase (Activase) and         to dissolve
                 urokinase (Abbokinase)           existing blood
                                                  clots. (12)

Statins          Atorvastatin (Lipitor),          Lowers high blood
                 fluvastatin (Lescol),            cholesterol levels
                 lovastatin (Mevacor),            by reducing LDL
                 pravastatin (Pravachol),         ("bad") cholesterol
                 simvastatin (Zocor) and          levels; helps to
                 rosuvastatin (Crestor)           increase HDL
                                                  ("good")
                                                  cholesterol and
                                                  reduce triglyceride
                                                  levels.

Resources

American Heart Association

7272 Greenville Avenue

Dallas, TX 75231

1-800-242-8721

http://www.americanheart.org

Provides heart disease prevention, treatment and management information.

American Diabetes Association

ATTN: National Call Center

1701 North Beauregard Street

Alexandria, VA 22311

1-800-342-2383 (English and Spanish)

http://www.diabetes.org

Offers diabetes-related information in a variety of formats.

Association of Black Cardiologists

6849 B2 Peachtree Dunwoody Road, NE

Atlanta, GA 30328

1-800-753-9222

http://www.abcardio.org

Professional organization dedicated to eliminating the disparities related to cardiovascular disease in all people of color. Consumer publications available.

NHLBI Health Information Center

PO Box 30105

Bethesda, MD 20824-0105

301-592-8573

http://www.nhlbi.nih.gov

Web site offers wide range of information on diseases of the heart, blood vessels, lungs and blood, and sleep disorders.

U.S. Food and Drug Administration

Heart Health Online

http://www.fda.gov/hearthealth

Lists and defines cardiac procedures; also has current drug/product recall information related to heart disease.

WomenHeart

The National Coalition for Women with Heart Disease

818 18th Street, NW, Suite 730

Washington, DC 20006

202-728-7199

http://www.womenheart.org

National organization founded by women with heart disease; dedicated to reducing death and disability among women living with heart disease.

References

(1) American Heart Association. Heart Disease and Stroke Statistics-2004 Update. Dallas, TX.: American Heart Association. 2004.

(2) Marcuccio E, Loving N, Bennett SK, et al. A survey of attitudes and experiences of women with heart disease. Women's Health Issues. 2003 Jan-Feb;13(1):23-31.

(3) Mostal, Linfante AH, Benjamin El et al. National study of physician awareness and adherence to cardiovascular disease prevention guidelines. Circulation. 2005 Feb l;111(4):499-510.

(4) Shulman KA, Berlin JA, Harless W, Kerner et al. The effect of race and sex on physicians' recommendations for cardiac catheterization. N Engl J Med. 1999 Feb 25;340(8):618-26.

(5) Women wait longer for emergency heart treatment, study finds. University of Michigan health system. [press release]. November 9, 2004.

(6) Mieres JH, Shaw U, Arai A, et. al. Cardiac Imaging Committee: Role of non-Invasive testing in the clinical evaluation of women with suspected coronary artery disease: consensus statement from the Cardiac Imaging Committee, Council on Clinical Cardiology, and the Cardiovascular Imaging and Intervention Committee, Council on Cardiovascular Radiology and intervention, American Heart Association. Circulation. 2005 Feb 8;111(5):682-96.

(7) FDA Approves Drug-Eluting Stent for Clogged Heart Arteries. US Food and Drug Administration. [press release]. April 24, 2003

(8) TAXUS Express2 Paclitaxei-Eluting Coronary Stent System - P030025. New Device Approval. US Food and Drug Administration. September 9, 2004. http://www.fda.gov/cdrh/mda/docs/p030025.html.

(9) Analysis shows CYPHER Sirolimus-Eluting Coronary Stent Significantly Reduces Incidence of reblocked Heart Arteries in Women, Including Diabetics and Smokers. [press release]. Miami: Cordis Corporation; September 23, 2004.

(10) Ardissino D, Cavallini C, Bramucci E, et. al. Sirolimus-eluting vs uncoated stents for prevention of restenosis in small coronary arteries: a randomized trial. JAMA. 2004 Dec 8;292(22):2727-34.

(11) Zanger DR, Solomon AJ, Gersh BJ. Contemporary management of angina: part II. Medical management of chronic stable angina. Am Fam Physician. 2000 Jan 1;61(1):129-38. Review.

(12) Ryan TJ, Antman EM, Brooks NH, et al. 1999 update; ACC/AHA guidelines for the management of patients with acute myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). J Am Coll Cardiol. 1999 Sep;34(3):890-911.

(28) Monroe MC. Semays PW, Sousa JF, et. al RAVEL Study Group. Randomized Study with the Sirolimus Coated Bx Velocity Balloon-Expandable Stent in the Treatment of Patients with de Novo Native Coronary Artery Lesions. Related Articles. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med. 2002 Jun 6:346(23);1773-80.