By DR.S.SIVASUBRAMANIAN, M.D.
Asst.Professor of Paediatric
Cardiac Surgery
This is one of the most fascinating questions clinical epidemiologists are asking themselves. There is a well-defined gender gap when it comes to an analysis of risks, diagnosis and treatment of coronary heart disease. This article will attempt to reconstruct the factors responsible for this gender gap, and provide some hints on preventing heart disease for both sexes.
What are the causes of the gender gap ?
"Men are from Mars, Women from Venus" - Gray JM
Traditionally, men and women have played different roles in society. These roles result in exposure to a different set of influences. These in turn act on the organ systems in different ways.
Unhealthy behaviour patterns
Men have been exposed to a higher risk of unhealthy patterns in their lifestyles. Smoking, alcohol consumption, eating a lot of red meat and less of fruits and vegetables are more commonly seen in males. These factors however are only contributory, and not causative, of coronary disease.
Work outside home
While it has been suggested that work stresses are in a large part responsible for coronary heart disease, recent studies focussed on working women draw different conclusions. For instance, the heart disease risk has been shown to be higher only in subordinate, clerical posts. Successful working women are NOT at a higher risk.
Social supports and Community style
Men and women have differing socialization needs and skills. Men have a lesser propensity to share feelings, and the resultant inner anger releases increased amounts of stress hormones that accelerate the development of atherosclerosis. Men also have fewer social supports, and are more likely to name their spouse as their favorite confidant. Social supports are cardio-protective.
Coronary prone behaviour
The prototype of a behaviour pattern that is at high risk for coronary disease is more likely seen in males. The so called "type A" personality has aggressiveness, competitiveness, hostility, time urgency and is associated with coronary heart disease in both sexes.
Does the way studies are conducted have anything to do ?
Certainly there has been a bias involved in most studies published on coronary heart disease comparisons between the sexes. For instance, exercise has been reported not to benefit women as much as men. However, these studies that are based on questionnaires focussed on sports, and ignored energy expenditure in household work. Vacuuming a two story house is as energy intensive as playing nine holes of golf !
Hormones might have an effect, but it is as yet unproven. Dehydro-epi androsterone (DHEA) is a masculinizing hormone. Increased levels of DHEA have been shown to protect against coronary heart disease - but only in men ! The mechanism of this is unclear.
Another is estrogen, the feminizing hormone. Pharmacologic doses of estrogen have been shown to improve exercise tolerance levels in post-menopausal women. Perhaps a sex-specific estrogen receptor in the inner lining of coronary arteries responds to estrogens. This might explain the selective benefit for women over men.
More evidence for the protective nature of estrogen comes from the observation that men universally have higher risks of coronary artery disease and that, in women who have early menopause, the female advantage is lost. The cardioprotective action of estrogen may be due to its effect on the lipid profile (reduced LDL cholesterol levels).
Most of the risk factors are common to both sexes. Generally, though, men have a higher exposure rate to these factors. Cigarette smoking, dietary fiber lack, vitamin C deficiency, blood viscosity, uric acid levels, low HDL cholesterol and high triglycerides are all associated with high risk in both men and women. Perhaps the only factors that decrease the risk profile in men are exercise, alcohol consumption and lower serum fibrinogen levels.
Then why is there a gender gap ?
The clue may lie in three factors that have a greater effect - that is, they contribute more to coronary heart disease - in women than men. The short list of these factors is
diabetes
low HDL cholesterol
high triglycerides
These are a part of a metabolic syndrome that exists in association with insulin lack and lipid disorders (dyslipidemia).
Diabetes
The most striking risk factor in women is diabetes mellitus. Coronary heart disease risk in women diabetics is twice as high as diabetic males. No other common risk factor so nearly erases the female advantage. The mechanism for such a difference needs further evaluation.
Cholesterol and Triglycerides
Low HDL cholesterol and high triglyceride levels also have a more significant effect on causing heart disease in women than in men, but the magnitude is not as dramatic as diabetes. For each mg/dl rise in HDL levels, the risk of coronary disease is reduced by 2% in men, but by 3% in women.
Sex linked inheritance
Intrinsic genetic factors also are responsible for the gender gap. This is evidenced by the consistent coronary artery disease sex ratio in different countries, cutting across differences in lifestyle, diet, culture and habits. The mechanisms of this has however not been explored deeply. Behaviour pattern may be influenced as early as in fetal life, when hormone differences between sexes is first manifest. Also, women are more resistant to infections than men. This might explain a delayed development of atherosclerosis, since there is a theory that proposes coronary atherosclerosis to be a sequel of inflammation.
Other mechanisms
Other mechanisms may also play a role. Homocysteine levels are decreased by folic acid intake in fruits and vegetables, and thus coronary heart disease risk is brought down. Iron has also been proposed as a coronary risk factor. Women have a greater iron loss (from menstrual bleeding) than men and so might be at lower risk.
In conclusion, there are many factors that account for the gender difference in coronary heart disease risk. Women have a superior risk profile, but as they also have a longer life expectancy, the absolute number of deaths due to coronary heart disease are equal among sexes. Modifying lifestyle can help bring all these risk factors under control and reduce coronary risk profiles for both men and women.
For a more detailed account of the topic discussed in this article you can refer to the journal paper in Circulation. 1997;95:252-264.
A lot has been written about the role hormones play in causing or preventing heart disease and stroke in women. In this article, we will take a look at the still controversial issue of the role of hormones in heart disease in women.
The two major endogenous hormones (that is, hormones produced in the body itself) in women are estrogen and progesterone. Each has a specific physiologic role in growth and development, pregnancy, lactation and other functions. Levels of both hormones alter at different stages of growth - pre-pubertal, reproductive age and after menopause. The varying levels cause different changes in the organ systems including the heart and blood vessels, some of which may increase or decrease the risks of disease.
In addition, hormones may be exogenous (administered in medication). The most common source of exogenous hormones in women is in oral contraceptive pills.
We will discuss first the impact birth control pills have had on the epidemiology of heart disease and later the effect of hormone replacement therapy in post-menopausal women.
Ever since birth control pills were introduces in 1960, there have been reports suggesting an increased risk of heart attacks and stroke. The earlier pills contained high doses - around 150 micrograms - of estradiol (In contrast, pills in 1988 contain only 35 micrograms). Also, addition of progesterone derivatives further altered the effects of the pill. Recently, the addition of third-generation progesterones like desogestrel and gestodene lowers LDL cholesterol levels and raises HDL cholesterol - changes that reduce heart disease risk. For more on cholesterol effects, read my earlier article on heart disease prevention.
Prescribing patterns have also changed, following recognition that oral contraceptives raise blood pressure and pose additional risk in older women who smoke cigarettes. These changes in products and their use would be expected to reduce the cardiovascular risks associated with oral contraceptives.
A study carried out by the World Health Organization reported the association between current use of oral contraceptives and heart attack in more than 300 cases. The study suggested that the pill might be responsible for an increased risk of heart attacks. However, the absolute risk in nonsmoking women younger than 35 years was low. The risk was dramatically increased in older women who smoked, and in women with known hypertension whose blood pressure was not checked before prescription. Risk was not associated with dose or duration of use of estrogen and did not persist after oral contraceptives were discontinued.
In summary, new oral contraceptives carry a greatly reduced risk of cardiovascular complications compared with other high-dose preparations, but third-generation progestins appear to greatly increase risk of venous blood clots in the leg veins. Overall, the risk/benefit ratio is excellent except for women who smoke.
Several reviews have provided evidence that a remarkably consistent reduced risk of coronary heart disease (CHD) and a somewhat less consistent reduced risk of stroke is seen in women using postmenopausal estrogen in the United States and Europe.
Because the risk of CHD exceeds the risk of all other estrogen-associated conditions combined in the United States, and because estrogen use has been associated with reduced mortality from all causes combined, post-menopausal estrogen has been proposed as the standard of care in countries where heart disease is the leading cause of death and a major cause of morbidity in women. An analysis of many studies carried out earlier, most from the US, it has been shown that post-menopausal estrogen reduces the risk of CHD by 35% to 50%. This means that on the basis of a calculation of overall risks and benefits, a healthy woman at no particular increased risk for heart disease, cancer, or osteoporosis would gain on average one additional year of life !
How does estrogen protect against Coronary Heart Disease ?
Multiple mechanisms may be involved. These include:
including favorable changes in lipids
altered lipoprotein profile
changes in fibrinogen and PAI-1
effects on blood vessel reactivity
antioxidant effects
Are these findings biased ?
It has been postulated that the striking differences noticed with post-menopausal estrogen therapy may be an artifact produced by pre-selecting low-risk patients. Estrogen replacement therapy is more likely to be prescribed to higher income, highly educated groups, who for different reasons are more likely to have fewer risk factors for heart disease.
Recently this "healthy woman selection bias" has been strikingly documented by the Healthy Women's Study, which followed 355 premenopausal women through menopause. Women who later elected to take hormones were, when premenopausal, significantly more educated and had significantly more favorable levels of HDL cholesterol, blood pressure, fasting insulin, body weight, alcohol intake, and physical activity. Thus, the amount of protection attributed to estrogen may be exaggerated.
Two major US trials have been designed to quantitate the cardioprotective effect of postmenopausal estrogen unconfounded by healthy woman selection bias.
HERS is a 5-year randomized placebo-controlled secondary prevention trial of conjugated equine estrogen plus medroxyprogesterone acetate (a form of progesterone) in women who already have CHD. This study of 2673 postmenopausal women is planned to end in 1998. Unopposed estrogen is not being evaluated.
The Women's Health Initiative (WHI), a placebo-controlled primary prevention trial in 27,500 postmenopausal women, is scheduled to complete randomization in 1998. The three major outcomes are CVD, osteoporosis, and breast cancer. Active treatments are conjugated equine estrogen alone for women without a uterus or conjugated equine estrogen plus continuous medroxyprogesterone acetate for women with an intact uterus, as compared with placebo. The WHI is planned to end in 2006. This trial will be the first to provide disease data in ethnic minority women on hormone therapy.
In summary, ongoing research suggests that estrogen replacement therapy reduces risk of CVD but may increase the risk of other diseases, including breast cancer and venous blood clots. The potential benefits and risks need to be confirmed in clinical trials such as those now in progress. Until more definitive data are available, clinicians should individualize therapy based on a woman's baseline risk for CVD and should weigh the potential net benefit on overall health.
Emerging data suggest selective estrogen receptive modulators, also known as "designer" estrogens, may have beneficial effects on the cardiovascular system as well as bone without untoward effects on breast or uterus. However, the clinical effectiveness of newer hormonal agents for disease prevention remains to be established.
For a more detailed account of the topic discussed in this article you can refer to the journal paper in Circulation. 1997;96:2468-2482.
Heart disease mortality rates have been decreasing over the past several decades. However, the rate of decline is slower in women than in men. It is less in African-American women as compared to white women.
As women live longer, the aging population makes the absolute number of deaths due to cardiovascular disease (CVD) in women actually rise. In the year 2000 nearly 50 million American women will be older than 50 years. Because the risk of heart disease and stroke increases with age, there is a need for an increased awareness of the importance of CVD as a major public health issue for older women.
Cardiovascular disease, particularly coronary heart disease (CHD) and stroke, remains the leading killer of women in America and most developed countries. In 1994, the last year for which statistics are available, CVD claimed the lives of more than one half million women and accounted for 45.2% of all deaths in women, more than all forms of cancer combined ! The death rate due to CVD is 69% higher in black women than white women. It is estimated that 1 in 2 women will eventually die of heart disease or stroke, compared with 1 in 25 who will eventually die of breast cancer.
In this article, I will discuss recent advances in knowledge of the occurrence, determinants, and treatment of atherosclerotic CVD in women, including coronary artery disease, hypertension and stroke.
Women and Coronary Artery Disease
Women have a much lower risk of coronary artery disease than men. The risk of death due to CHD in women is roughly similar to that of men 10 years younger. However, as women have a higher likelihood of surviving to older ages, the actual number of deaths due to CHD are nearly equal in men and women.
In the Cardiovascular Health Study, the prevalence of heart attacks (myocardial infarction) in older women was 9.7% for those aged 65 through 69 years and 17.9% for those 85 years and older. What is more worrying from a public health perspective is that nearly two thirds of sudden deaths due to coronary artery disease in women in the Framingham Heart Study occurred in those patients with NO previous symptoms of heart disease. In contrast, almost one half of the men in that study had preceding signs or symptoms of heart disease. For these women, primary prevention is likely to be the only practical solution.
Just as in men, the major risk factors for coronary artery disease in women are
cigarette smoking
high blood pressure (including isolated systolic hypertension)
blood lipid disorders
diabetes
obesity
sedentary lifestyle
poor nutrition
However, gender differences have been documented, and I have discussed these in detail in another article.
Cigarette smoking
Cigarette smoking remains the leading preventable cause of coronary disease in women. More than one half of heart attacks among middle-aged women are attributable to tobacco. Risk of coronary events begins to decline within months of stopping smoking and reaches the level of persons who have never smoked within 3 to 5 years. Sadly, though, smoking cessation rates have declined more slowly among women than men.
The changing demographics of smoking, particularly the unfavorable smoking patterns among younger women, may contribute substantially to the future burden of coronary artery disease on women, as well as other smoking-related illnesses.
High Blood Pressure
Among US adults older than 45 years, 60% of white women and 79% of African-American women were classified as having hypertension (defined as either taking antihypertensive medication or having systolic BP over 140 mm Hg or diastolic BP over 90 mm Hg).
Of particular concern for older women is isolated systolic hypertension, which is estimated to affect 30% of women older than 65.
Lipid profile disorders
From 1980 to 1991 more than 50% of women older than 55 years had serum cholesterol levels that were considered high (over 240 mg/dL). A low level of high-density lipoprotein (HDL) cholesterol, however, was a risk factor for coronary artery disease in both younger and older women and was a stronger predictor of mortality related to heart disease in women than in men.
Obesity
The prevalence of obesity has increased among both men and women in the United States in the past decade; currently about one third of adult women (or 34 million) are classified as obese. Obesity, particularly abdominal adiposity, is an important risk factor in women.
Sedentary Lifestyle
Nearly 60% of both men and women have no regular physical activity. There may however be some element of bias in this observation, since most data are gathered by questionnaires which do not enquire about the amount of household work done by a woman. For instance, vacuuming two floors of a household consumes as much energy as playing nine holes of golf !
In any case, these findings support the 1995 federal exercise guidelines endorsing 30 minutes of moderately intense physical activity most days of the week, a program that should be feasible and safe for most of the population.
Diabetes
Diabetes is one of the most important gender-specific risk factors for coronary artery disease, and is associated with a threefold to sevenfold elevation in risk among women, compared with a twofold to threefold elevation among men; this gender-based difference may be due to a particularly deleterious effect of diabetes on lipids and blood pressure in women.
The epidemiological evidence is compelling: diets low in saturated fat and high in fruits, vegetables, whole grains, and fiber are associated with a reduced risk of coronary atherosclerosis.
Prevention of Coronary Events in Women
The use of drugs to control or reverse risk factors has proven successful to a variable extent. Anti-platelet therapy that aims to prevent platelets aggregating together and clogging coronary arteries is useful in some patients. Post-menopausal women benefit from hormone replacement with estrogens.
In primary prevention, the balance of benefits and risks of aspirin prophylaxis among women remains unknown and awaits the results of the ongoing Women's Health Study. Antioxidant vitamin supplements, particularly vitamin E, and homocysteine-lowering agents such as folate and B6, have promising roles in prevention of coronary artery disease, but conclusive evidence is still awaited. Early surgical menopause is linked to increased risk of coronary disease, which appears to be neutralized by the use of estrogen therapy.
In summary, clinical studies and trials provide compelling evidence that coronary artery disease is largely preventable. Pharmacological intervention has a role in primary prevention for selected patients. However, a major emphasis should be placed on lifestyle modifications, including smoking cessation, regular physical activity, maintenance of healthy weight, and consumption of a diet low in saturated fat and high in fruits and vegetables. Further studies on the potential benefits of stress reduction and psychosocial interventions can also provide valuable new information on heart disease prevention.
Our Menopause Update will keep you informed about any new developments in the following on-going studies:
ESPRIT -- Estrogen in the Prevention of Reinfarction Trial
HERS -- Heart and Estrogen-progestin Replacement Study
SEAS -- Soy Estrogen Alternative Study
SWAN -- Studies of Women's health Across the Nation
WISDOM -- Women's International Study of Long-Duration Estrogen after Menopause
WHI -- Women's Health Institute
Disclaimer - Menopause-Online is not intended as medical advice. Its intent is solely informational and educational. The information is not a substitute for talking with your health professional.
