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Women and Cardiovascular Diseases
in Latin America and the Caribbean

Palmira Pramparo*, Auris Flores de Finizola**,
Bartolomé Finizola**, Otavio Gebara***,
Ricardo Granero**, Martha Hill****,
J. Ricardo Loret de Mola****, Beatriz Marcet Champagne****,
Nilson Roberto de Melo***, Herman E. Schargrodsky*,
María Ema Urthiague*, Andreas T. Wielgoszª,
Elinor Wilsonª, Mary Winston****,
Elizabeth Barret-Connor****, Nanette Wenger****

*Argentina, **Venezuela, ***Brazil, ****USA, ªCanada
Epidemiology and Prevention Council, Argentine Society of Cardiology,
Buenos Aires, Argentina and the InterAmerican Heart Foundation, Dallas, Texas, USA

A RECOMMENDATION FOR HEALTH PROFESSIONALS FROM THE INTERAMERICAN HEART FOUNDATION
   Cardiovascular diseases (CVD) have become the leading cause of death and disability in men and women in most countries of the Americas. Widespread preventive measures and improved treatments for CVD appear to have had a positive effect in helping reduce cardiovascular and cerebrovascular mortality rates in countries such as the USA, Canada and some other nations where these measures have long been implemented and emphasized. However, women have not benefited to the same extent as men. Women tend to be concerned more with breast cancer than heart disease, failing to appraise adequately the severity of cardiovascular disease symptoms. Thus, careful consideration should be given to individual risk factor management prior to the onset of clinical symptoms of CVD in women.

   Although most risk factors for CVD are similar in men and women, gender differences have been documented particularly in diabetes and dyslipidemia. Whereas prevalence rates of heart diseases and stroke are similar in both sexes, the onset of the disease is usually delayed in women, probably due to the protective effect of estrogen. There is a significantly lower age-specific risk of coronary heart disease (CHD) in women than men. Risk of death due to CVD in women is roughly similar to that of men 10 years younger and the risk equalizes approximately between ages 65-70.

Cardiovascular Risk Factors: General considerations
   Risk factors for CHD in women are: cigarette smoking, hypertension (including isolated systolic hypertension), dyslipidemia, diabetes mellitus, obesity, sedentary life style, poor nutrition, age above 55 years and/or menopause (particularly early or surgical), and family history of premature coronary heart disease in first degree relatives.

   Cigarette smoking remains the leading preventable cause of CVD in women, with more than 50% of acute myocardial infarctions (MIs) among middle-aged women attributable to tobacco. Not only is tobacco use a cardiovascular risk factor, but it also increases the risk of lung cancer, emphysema and other related diseases in women as in men.

   Epidemiological studies document a strong association between high levels of both systolic and diastolic blood pressure and risk of CVD in both women and men. Of particular concern for older women is isolated systolic hypertension which is estimated to affect 30% of women older than 65.

   High levels of total cholesterol and LDL are an important risk factor also in women. Low levels of HDL are predictive of CHD in women, and appear to be a stronger risk factor for women over 65 years than men over 65 years. Elevated triglycerides may be a significant risk factor in women, especially when they are associated with low levels of HDL. Secondary and primary prevention trials with lipid-lowering therapy (statins) that included women show a substantial benefit in risk reduction. In spite of these findings, many surveys have shown a significant undertreatment of postmenopausal women with CHD.

   Diabetes is a major risk factor in women, increasing CHD risk 3 to 7 fold compared with 2 to 3 fold increase in risk in men. This difference may be due to the particularly deleterious effect of diabetes on lipids and blood pressure in women.

   Several studies have pointed to the importance of family history of cardiovascular disease. Risk is higher when a first degree relative has had or died from CVD at age <55 if male and/or at age <65 if female. Nonetheless, the degree of independence from other risk factors and the absolute magnitude of incremental risk remain uncertain.

   Pregnancy is an opportune time to review a woman's risk factor status and health behaviors to reduce future cardiovascular disease. Pregnant women should be strongly encouraged to discontinue smoking and not to relapse during the post-partum period. Avoidance of excess weight gain during pregnancy may reduce the risk of developing CHD in the future.

   The older a woman, the more likely she is to develop heart disease or have a stroke. Emphasis on prevention of CHD in post-menopausal women is particularly important because the incidence of CHD rises with age. The loss of natural estrogen may contribute to the higher risk after menopause. There is also evidence indicating that women who have had early or surgical menopause are at increased risk of CHD.

   Clarifying the role of estrogen in cardiovascular disease prevention is the subject of ongoing studies. Observational studies have demonstrated a beneficial effect of HRT in the primary prevention of heart disease. Many published studies show that estrogen raises HDL and lowers LDL cholesterol and has beneficial effects on vasodilatation and endothelial cell function, among others. The PEPI trial (Postmenopausal Estrogen Progestin Intervention) shows significant beneficial effects on lipid profiles in women treated with either estrogen replacement therapy (ERT) or hormonal replacement therapy (HRT). The HERS trial (Heart Estrogen/progestin Replacement Study), which evaluated the effect of HRT in women with diagnosed CHD, was the first randomized clinical trial to evaluate secondary prevention in an elderly population. The overall results of the study revealed that, after 4.1 years, no cardiovascular benefit was seen in the HRT group. During the first year an increase in CVD events was noted in the HRT group, but in years 4 and 5, fewer events occurred in the HRT arm than in the placebo arm. The Women's Health Initiative trial, which includes 27,000 participants, was designed to evaluate the long-term benefits as well as risks of ERT/HRT therapy. Data from this trial will be available in 2005 and will include an analysis of the effect of ERT/HRT on primary prevention of CVD.

   Interventions to prevent heart disease and stroke in women should involve the primary care physician, gynecologist and other health professionals. A major emphasis should be placed on lifestyle modifications, including not smoking, smoking cessation, regular physical activity, maintaining a healthy weight, and a diet low in saturated fat and high in fruits, vegetables, grains, fiber and an adequate protein intake. These recommendations should be an integral part of every medical visit to help women lower their own CVD risk and also because women are in an optimal position to influence changes in attitudes and lifestyle in their children and families.

   Most countries in Latin America and the Caribbean have limited and non-comparable information regarding cardiovascular diseases in women. This region is heterogeneous in economic development and health care policies, as well as the resources available for prevention and treatment of CVD. Its population is also highly diverse. Most countries have socioeconomic problems that deprive large sectors of the population from resources required to implement preventive measures.

   In addition, recent published data on women show that ethnicity and socioeconomic status have an important relationship to CVD risk factors. The striking differences by both ethnicity and socioeconomic status underscore the critical need to improve screening, early detection, and treatment of CVD-related conditions in minority women and in those with lower socioeconomic status.

   Table 1 presents guidelines for the early detection of cardiovascular risk factors and the prevention of CVD in women with recommendations for health professionals in Latin America and the Caribbean.

CONCLUSIONS
   In the next decades, nearly 40% of women in the Americas will be over 50 years of age. Many of them may manifest CHD or atherosclerotic disease. Efforts should be made to prevent cardiovascular risk factors in women and through education to dispel the misconception that women are not at risk of CHD. Women should have access to information and health care in order to adequately prevent, detect, and treat cardiovascular conditions.

   The InterAmerican Heart Foundation has set forth these recommendations in the hope that the cooperation of all the people involved will promote health education and the prevention of cardiovascular disease in women.

   Development of this statement on Women and CVD in Latin America and the Caribbean was made possible with an unrestricted educational grant from Wyeth-Ayerst to the InterAmerican Heart Foundation.

GUIDELINES FOR THE EARLY DETECTION OF CARDIOVASCULAR RISK FACTORS AND THE PREVENTION OF CORONARY HEART DISEASE IN WOMEN

Tobacco
Goal:
- Complete cessation
- Avoid passive cigarette smoke

Recommendations:
- Ask about current smoking status and exposure to others' cigarette smoke as part of routine evaluation. Assess prior attempts at quitting and readiness to stop smoking.
- Provide information about the risks of smoking, not only during pregnancy but throughout life.
- Explain the risk associated with oral contraceptive use in smoking women.
- Strongly encourage and support patient and family to stop smoking.
Provide counseling about cessation using proven interventions, including pharmacological approaches, or refer patient to specialized professionals.

Lipid Management
Primary Goal:
Women without CVD
Lower risk: (< 2 risk factors)
LDL < 160 mg/dl (optimal < 130 mg/dl)
Higher risk: (> 2 risk factors)
LDL goal < 130 mg/dl
Women with CVD
LDL < 100 mg/dl

Secondary goals:
HDL > 35 mg/dl
Triglycerides < 200 mg/dl

Note:
In women, the optimal level of triglycerides may be even lower (< 150 mg/dl) and the HDL even higher (> 45 mg/dl)

Recommendations:
In all women:
- Ask the patient about dietary habits as part of the routine evaluation.
- Promote lifestyle approach (heart healthy diet, weight management, physical activity and smoking avoidance).
- Rule out secondary causes of dyslipidemia.

Women without CVD:
- Measure nonfasting total and HDL cholesterol and assess nonlipid risk factors. Follow up is based on the following initial measurements (all cholesterol values in mg/dl):
TC < 200, HDL > 45: follow-up in 5 years
TC < 200, HDL < 45: follow-up with fasting lipoprotein analysis
TC 200-239, HDL > 45 and < 2 risk factors: follow-up in 1-2 years
TC 200-239, HDL < 45 and > 2 risk factors: follow-up with fasting lipoprotein analysis
TC > 240: follow-up with fasting lipoprotein analysis
- Promote a diet with < 30% fat, 8-10% saturated fat and < 300 mg/day cholesterol.

Women with CVD:
- Measure fasting lipoprotein analysis (may take 4-6 weeks to stabilize after CV events or bypass surgery).
- Promote a stricter diet with < 30% fat, < 7% saturated fat and < 200 mg/day cholesterol.

Add drug therapy to diet when:
a) LDL > 220 mg/dl in low risk premenopausal women
b) LDL > 190 mg/dl in postmenopausal women with < 2 risk factors
c) LDL > 160 mg/dl in women with > 2 risk factors
d) LDL > 100 mg/dl in all women with CVD
- Drug selection should be based on trygliceride levels.
- HRT is an option for postmenopausal women but treatment should be individualized and considered with other health risk.

High Blood Pressure
Goal:
Maintain blood pressure <140/90 mmHg (Optimal is < 120/80 mmHg

Recommendations:
- Measure blood pressure as part of routine evaluation.
- Reassess borderline blood pressure values in subsequent visits.
- Follow-up screening may be modified on the basis of prior history, symptoms, presence of other risk factors and end organ damage.
- Promote lifestyle modification (weight control, physical activity, sodium restriction, moderation in alcohol consumption).
- If blood pressures > 140/90 mmHg after 3 months of lifestyle modification or if initial value is > 160 mmHg systolic or > 100 mmHg diastolic, then initiate and individualize pharmaco-therapy.
- In pregnant women with hypertension, evaluate for preeclampsia.

Diabetes
Goal:
- Desirable fasting glucose level is < 125 mg/dl
For patients with diabetes:
- Maintain blood glucose: pre-prandial = 80-120 mg/dl and bedtime = 100-140 mg/dl
- Maintain Hb A1c < 7%
- LDL < 130 mg/dl (< 100 mg/dl if established CVD). Many authorities believe that LDL should be < 100 mg/dl in all patients with diabetes.
- Triglycerides < 150 mg/dl

Recommendations:
- Screen for diabetes as part of routine examination in women with risk factors for diabetes such as obesity or positive family history.
- Promote diabetic diet (< 30% fat, < 10% saturated fat, 6-8% polyunsaturated fat and < 300 mg/day cholesterol) and regular physical activity.
- Control other risk factors, i.e., hypertension, overweight, obesity.
- Monitor glucose and hemoglobin A1, as part of the routine periodic evaluation in women with diabetes.
- Pharmacotherapy with oral agents or insulin should be used when indicated

Physical Activity
Goal:
Accumulate at least 30 minutes of moderate intensity physical activity on most days of the week

Recommendations:
- Ask the patient about physical activity as part of routine evaluation.
- Encourage a minimum of 30 min. of moderate intensity dynamic exercise (e.g., brisk walking) daily. This may be performed in intermittent or shorter bouts (=10 min.) of activity throughout the day. Encourage incorporating physical activity in daily routine (e.g., using stairs).
- In women with symptoms suggestive of CVD or previously sedentary women >50 years old with at least 2 risk factors, consider stress test to establish safety of exercise and to guide the exercise prescription.
Recommend and facilitate cardiac rehabilitation program for women with known CVD particularly after a recent cardiovascular event or procedures, i.e., revascularization, angioplasty or bypass.

Weight Management
Goal:
- Desirable measurements are: waist-to-hip ratio < 0.8 and waist circumferences < 88 cm (35 inches)
- Desirable BMI is in the range 18.5 - 24.9 kg/m2

Recommendations:
- Measure waist circumference or hip-waist ratio and BMI as part of routine evaluation.
- Achieve and maintain the goal through diet and physical activity.
- Offer weight loss counseling to patients with hypertension, dyslipidemia, diabetes or family history of CVD.
The recommended weight gain during pregnancy is 25-35 lb. (11-16 kg) if the patient's prepregnancy weight is normal. Overweight women with BMI > 25 and < 30 should gain 15-25 lb. (7-11 kg). Obese women with BMI > 30 should gain < 15 lb. (7 kg).

Psycho-Social Factors
Goal:
- Positive adaptation to stressful situations
- Improved quality of life
Maintain or establish social connections

Recommendations:
- Assess presence of stressful situations and response to stress as part of routine evaluation.
- Encourage participation in social activities or volunteer work for socially isolated women.
- Evaluate for depression, especially in women with recent cardiovascular events.
- Consider treatment of depression and anxiety disorders where appropriate.

Antiplatelet Agents / Anticoagulants
Goal:
Prevention of clinical thrombotic and embolic events in women with established CVD

Recommendations:
- Determine if contraindications to therapy exist at the time of the initial cardiovascular event.
- If no contraindications, women with atherosclerotic CVD should use aspirin 80-325 mg/day.
- Evaluate ongoing compliance, risk and side effects as part of routine follow-up.
Other antiplatelet agents, such as newer thiopyridine derivatives, may be used to prevent vascular events in women who cannot take aspirin.

Beta Blockers
Goal:
To reduce the reinfarction rate, incidence of sudden death, and overall mortality in women after MI

Recommendations:
- Determine if contraindications to therapy exist at the time of the initial cardiovascular event.
- Start intravenously within hours of hospitalization in women with an evolving MI without contraindications. If not started acutely, treatment should begin within a few days of the event and continued indefinitely
- Evaluate ongoing compliance, risk and side effects as part of routine follow-up.

ACE Inhibitors
Goal:
To reduce morbidity and mortality among MI survivors and patients with LV dysfunction.

Recommendations:
- Determine if contraindications to therapy exist at the time of the initial cardiovascular event.
- Start early during hospitalization for MI unless hypotension or other contraindications exist.
- Continue indefinitely for all with LV dysfunction (ejection fraction < 40%) or symptoms of congestive heart failure; otherwise ACE inhibitors may be stopped at 6 weeks.
- Evaluate ongoing compliance, risk and side effects as part of routine follow-up.
- Discontinue ACE inhibitors if a woman becomes pregnant

Oral Contraceptives
Goal:
- Minimize the risk of adverse cardiovascular effects while preventing pregnancy
- Use the lowest effective dose of estrogen/progestin

Recommendations:
- Determine contraindications and cardiovascular risk factor status of women who are considering use of oral contraceptives.
- Use of oral contraceptives is relatively contraindicated in women > 35 years of age who smoke.
- Women with a family history of premature heart disease should have a lipid analysis before initiating oral contraception.
- Women with significant risk factors for diabetes should have their glucose tested before initiating oral contraception.
- If hypertension develops in a woman using an oral contraceptive, it is advisable to stop its use.

Hormone-Replacement Therapy
Goal:
Initiation or continuation of HRT in women for whom the potential benefits may exceed the potential risks of therapy
- Short-term therapy is indicated for treatment of menopausal symptoms
- Minimize risk of adverse side effects through careful patient selection and appropriate choice of therapy

Recommendations:
- Review menstrual status of women > 40 years old.
Combination therapy with progestin is usually indicated to prevent endometrial hyperplasia in women with an intact uterus and prescribed estrogen
- Individualize decision based on prior history and risk factors for CVD as well as risks of thromboembolic disease, gallbladder disease, osteoporosis, breast cancer and other health risks.

CVD = cardiovascular diseases; CHD = coronary heart disease; BMI = body mass index or weight in kg/ height in meters 2 ; TC = total cholesterol; LDL = low-density lipoprotein; HDL = high-density lipoprotein; TG = triglycerides; Hb A1c = glycosylated hemoglobin; HRT = hormone replacement therapy; ERT = estrogen replacement therapy.

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2nd Virtual Congress of Cardiology

Dr. Florencio Garófalo
Steering Committee
President
Dr. Raúl Bretal
Scientific Committee
President
Dr. Armando Pacher
Technical Committee - CETIFAC
President
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