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Women’s Heart Problems Found Distinct from Men’s
2/20/2006
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New findings clarify gender distinctions and reveal age-specific rewards from menopausal estrogen therapy; “Red” campaigns call for increased heart awareness
by Craig Weatherby


Many American women wore red on Friday, February 3rd in observance of National Wear Red Day: an event designed to help women send their gender sisters an urgent message about heart disease.

National Wear Red Day is intended to inspire women to take action to protect their heart health, and is part of the “Heart Truth” campaign created by the National Heart, Lung, and Blood Institute (NHLBI).

Like the American Heart Association’s companion “Go Red for Women” awareness campaign, the symbol of the Institute’s “Heart Truth” campaign is a red dress.

And, given the Heart Association’s recommendation to eat salmon, we propose deep-red wild salmon as a living symbol of all campaigns to help women avoid untimely death or disability via early detection and changes to lifestyle and diet.

Women and heart disease: a silent threat
Compared with middle-aged men, their female peers enjoy a lower risk of developing heart disease. But after age 65 the average woman's risk of heart problems rivals that of her male contemporaries.

The authors of a new study on gender differences in CVD attribute this increase in risk to normal hormonal changes, from high estrogen levels before menopause to decreasing estrogen and progesterone levels after menopause.

Women over 65 are more likely to suffer death or disability after a first heart attack, experience a second heart attack, and receive less aggressive treatment.

And instead of the classic chest and arm pain, women tend to have less obvious heart-attack symptoms such as nausea, fatigue, shortness of breath, or jaw, back, or shoulder pain, making proper diagnosis and appropriate treatment less likely.

Thanks to new research results we’ll review later (see “Estrogen therapy and heart-health” below), the reasons for these gender differences are becoming clearer, as are the risks and rewards of hormone replacement therapy (see “Women’s heart disease differs” below).

Heart disease by the numbers
These surprising statistics are found on the AHA’s Go Red Web site:
  • CVD is the No. 1 killer of women over age 25.
  • American women are 12 times more likely to die from CVD than from breast cancer.
  • Sixty-four percent of women who died suddenly of CVD had no previous symptoms.
  • Heart disease rates in post-menopausal women are 2 to 3 times higher than in same-age pre-menopausal women.
  • Stroke kills more women than men.
  • Stroke is the No. 3 cause of death for American women, and a leading cause of serious, long-term disability.
“Go Red” for women’s heart health
These are the American Heart Association’s Go Red guidelines for women, which place fish, fish oil, and highly monounsaturated olive and macadamia nut oils on a preventive-health pedestal. As we suggested, the deep red color of wild salmon makes it the perfect symbol of heart-friendly food:
  • Address the big issues. High cholesterol*, high blood pressure, and diabetes all increase the chances of heart disease, and women may be more sensitive to these risk factors than men. If you have any of these conditions, get them under control with lifestyle changes and, if necessary, medication.
  • Take diet to heart. Follow a heart-protective eating plan that's low in saturated and trans fats and animal foods and high in fruits, vegetables, whole grains, monounsaturated fat (found in olive oil), and omega-3 fatty acids (in salmon**, sardines, and other fish).
  • Don't smoke. More than half of heart attacks in younger women are related to smoking, and smokers who take birth control pills are at even higher risk. If you quit now, you'll reduce your risk of heart attack by one-third within just two years.
  • Stay trim. Women who are overweight are more likely to develop heart disease even if they have no other risk factors, because extra pounds strain the heart and arteries. You can lower your risk by losing even just 5 to 10 percent of your current weight.
  • Move more. Your heart is a muscle and needs exercise to stay in shape, just like any other body part. Regular physical activity can help regulate cholesterol levels, lower blood pressure, prevent diabetes, and reduce stress. Aim for at least 30 minutes a day on most days of the week.
  • Ask about aspirin. Daily low dose aspirin therapy can lower the risk of heart problems in some people at high risk; ask your physician if it's right for you.
*Research indicates that high blood cholesterol per se is not always the key risk factor, and that other problems—especially the ratio of types of cholesterol, and chronic “silent” inflammation—are the chief causes of concern.

** Not all salmon is equally good for your heart. As we reported just last month (see “Farmed Salmon's Diet Yields Unhealthful Cardiovascular Effects”), the results of a recent clinical test suggest that eating farmed salmon actually raises consumers’ blood levels of chemicals associated with dangerous vascular inflammation.

To learn more about women, heart disease, and the two companion awareness campaigns, click here for the Heart Truth Web site, and click here for the Go Red Web site.

Women’s heart disease differs from men’s and defies detection
Even though the reduction of blood flow that can lead to heart attacks is often considered a man's disease, it takes the lives of more women than men each year (see the statistical sidebar titled “Women and heart disease, by the numbers”).

New research finding show that cardiovascular disease in women differs from men’s in important ways. As a consequence, women's heart disease often evades traditional diagnostic techniques and continues to cause symptoms until it progresses to a dangerous degree.

These findings come from The Women's Ischemia Syndrome Evaluation (WISE) Study, a large, long-term investigation whose results were reported in a supplement to the Feb. 7, 2006 issue of the Journal of the American College of Cardiology. (“Ischemia” means “constricted blood supply”: a condition characteristic of cardiovascular disease.)

When people experience chest pain, doctors usually look for signs of fatty, calcified arterial plaque in arteries. This phenomenon, called atherosclerosis, characterizes heart disease in men.

But in many women, problems in two other areas—the lining of coronary arteries and tiny blood vessels within the heart itself—combine to rob the heart’s muscles of oxygen.

The WISE study’s findings provide the first detailed picture of the circulatory problems specific to heart disease in women.  Although the "diffuse atherosclerosis" that many women experience is not apparent on the coronary angiograms normally used to look for arterial clogs, it results in reduced blood flow to the heart’s own tissues.

Absent any evidence of a blocked artery, a woman's symptoms are likely to be dismissed as signs of something unknown and far less dangerous than heart disease.

Making diagnosis harder, women's symptoms frequently differ from men's. Women may report fatigue, sleep disturbances and shortness of breath, all of which may be dismissed as irrelevant to heart disease or mistakenly attributed to benign conditions.

Other CVD risk factors in women include anemia and inflammation in the arteries. Accordingly, the most promising early-detection test options include testing for blood levels of C-reactive protein—a key inflammatory chemical—and monitoring of hemoglobin levels (blood iron-carrying capacity).

In addition, physicians may look for narrowing of the retinal artery and calcification in coronary arteries, conduct stress tests that can reveal the blood flow problems characteristic of women’s heart disease, and administer questionnaires regarding daily diet and activities (Sedentary women suffer a significantly higher risk of CVD).

Risks are also increased among women who are diabetic, obese, or have three or more of the cluster of five predisposing physical characteristics and biochemical risk factors called “metabolic syndrome” (e.g., obesity, unhealthful blood fat or cholesterol profile, high blood pressure, and high blood sugar).

Estrogen therapy and heart-health: a reversal of fortune?
For years, menopausal women were told that estrogen replacement therapy could be heart-protective.

However, part of the Women's Health Initiative (WHI) study—a comprehensive investigation conducted among 10,739 women ages 50 to 79—was stopped in March of 2004 when early findings raised health alarms.

The sudden halt was called when preliminary results indicated that post-menopausal estrogen use increased the participating women’s risk of strokes and deep-vein blood clots, but did not reduce their risk of heart attacks.

This unexpected, disturbing finding cut sales of hormone replacement therapy drugs by more than half.

The authors of the suspended part of the WIH study reported the following impacts of estrogen-alone therapy versus placebo. The results, which reflect the number of adverse events per 10,000 women, did not differ by race, ethnicity, or body mass index (BMI):

Increased risks
  • Fatal and non-fatal strokes: 44 cases in those on estrogen alone and 32 in those on placebo.
  • Venous thrombosis*: 21 cases in those on estrogen alone and 15 in those on placebo.
Reduced risks or no difference
  • Bone fractures—reduced risk: 11 cases in those on estrogen alone and 17 cases in those on placebo.
  • Breast cancer—uncertain (statistically insignificant) effect: 26 cases in those on estrogen alone and 33 in those on placebo.
  • Coronary heart disease—no significant risk difference versus placebo.
  • Colorectal or total cancer—no significant risk difference versus placebo.
  • All deaths—no significant risk difference versus placebo.
*blood clots, usually in one of the deep veins of the legs

Now, the results of a new analysis of data from the Women's Health Initiative (WHI) study indicate that estrogen supplements do not appear to reduce the heart attack risks among menopausal women aged 50 to 59, and do not raise their risks of developing heart disease.

The new WHI study involved 3,310 women between the ages of 50 to 59 who had previously undergone a hysterectomy (removal of the uterus) for various medical reasons.

Because the bodies of women without uteri cannot produce significant amounts of estrogen, studying the effects of estrogen supplements in this group enabled researchers to isolate the heart effects of supplemental estrogen.

About half were given estrogen and the rest took a placebo pill. After seven years, the group taking estrogen experienced one-third fewer heart attacks, compared with the placebo group.

While the estrogen group did not enjoy any overall protection against heart attacks or heart-related deaths, the data indicated a reduced risk of CVD symptoms among participants aged 50 to 59 years when estrogen therapy began.

In other words, it appears safe for women to start estrogen supplements between the ages of 50 and 59, since the estrogen group were less likely to manifest clinical signs of cardiovascular disease (CVD), and died from heart-related problems at no greater rate than the participants who took placebo pills.


Sources
  • National Heart, Lung, and Blood Institute. Women's Health Initiative. Questions and answers about the estrogen-alone study. Accessed online February 18, 2006 at http://www.nhlbi.nih.gov/whi/e-a_faq.htm#q1.
  • Bairey Merz CN, Shaw LJ, Reis SE, Bittner V, Kelsey SF, Olson M, Johnson BD, Pepine CJ, Mankad S, Sharaf BL, Rogers WJ, Pohost GM, Lerman A, Quyyumi AA, Sopko G; WISE Investigators. Insights from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study: Part II: gender differences in presentation, diagnosis, and outcome with regard to gender-based pathophysiology of atherosclerosis and macrovascular and microvascular coronary disease. J Am Coll Cardiol. 2006 Feb 7;47(3 Suppl):S21-9.
  • Gierach GL, Johnson BD, Bairey Merz CN, Kelsey SF, Bittner V, Olson MB, Shaw LJ, Mankad S, Pepine CJ, Reis SE, Rogers WJ, Sharaf BL, Sopko G; WISE Study Group. Hypertension, menopause, and coronary artery disease risk in the Women's Ischemia Syndrome Evaluation (WISE) Study. J Am Coll Cardiol. 2006 Feb 7;47(3 Suppl):S50-8.
  • Handberg E, Johnson BD, Arant CB, Wessel TR, Kerensky RA, von Mering G, Olson MB, Reis SE, Shaw L, Bairey Merz CN, Sharaf BL, Sopko G, Pepine CJ. Impaired coronary vascular reactivity and functional capacity in women: results from the NHLBI Women's Ischemia Syndrome Evaluation (WISE) Study. J Am Coll Cardiol. 2006 Feb 7;47(3 Suppl):S44-9.
  • Shaw LJ, Bairey Merz CN, Pepine CJ, Reis SE, Bittner V, Kelsey SF, Olson M, Johnson BD, Mankad S, Sharaf BL, Rogers WJ, Wessel TR, Arant CB, Pohost GM, Lerman A, Quyyumi AA, Sopko G; WISE Investigators. Insights from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study: Part I: gender differences in traditional and novel risk factors, symptom evaluation, and gender-optimized diagnostic strategies. J Am Coll Cardiol. 2006 Feb 7;47(3 Suppl):S4-S20.
  • Shaw LJ, Olson MB, Kip K, Kelsey SF, Johnson BD, Mark DB, Reis SE, Mankad S, Rogers WJ, Pohost GM, Arant CB, Wessel TR, Chaitman BR, Sopko G, Handberg E, Pepine CJ, Bairey Merz CN. The value of estimated functional capacity in estimating outcome: results from the NHBLI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study. J Am Coll Cardiol. 2006 Feb 7;47(3 Suppl):S36-43.
  • Pepine CJ, Kerensky RA, Lambert CR, Smith KM, von Mering GO, Sopko G, Bairey Merz CN.  Some thoughts on the vasculopathy of women with ischemic heart disease. J Am Coll Cardiol. 2006 Feb 7;47(3 Suppl):S30-5.
  • Cote S, Dodin S, Blanchet C, Mulvad G, Pedersen HS, Blanchet C, Holub BJ, Dewailly E. Very high concentrations of n-3 fatty acids in peri- and postmenopausal Inuit women from Greenland. Int J Circumpolar Health. 2004;63 Suppl 2:298-301.
  • Saldeen P, Saldeen T. Women and omega-3 Fatty acids. Obstet Gynecol Surv. 2004 Oct;59(10):722-30; quiz 745-6. Review.
  • Hsia J et al. Conjugated Equine Estrogens and Coronary Heart Disease. Arch Intern Med. 2006;166:357-365.
  • Erkkila AT, Lichtenstein AH, Mozaffarian D, Herrington DM. Fish intake is associated with a reduced progression of coronary artery atherosclerosis in postmenopausal women with coronary artery disease. Am J Clin Nutr. 2004 Sep;80(3):626-32.
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