Epidemiology

CVD in General

  • Coronary heart disease (CHD), which includes myocardial infarction(MI; heart attack) and angina pectoris (AP), stroke, congestive heartfailure (CHF), and cardiac arrest are types of cardiovascular disease(CVD). CVD affects 25% of American women and men. 1
  • CVD is the leading killer in America, 1 but most women think that CVD is a “man’s disease.” 2 Since 1984, more women than men have died of CVD every year. 3 In 2002, CVD killed 493,623 women compared with 433,825 men. Fifty-three percent of CVD deaths occur in women. 3
  • In 2002, CVD killed nearly 500,000 women compared to approximately 41,500 deaths by breast cancer. 3 In 2002, nearly twice as many American women died of CVD than from all types of cancer combined. 3

Coronary Heart Disease (Myocardial Infarction and Angina Pectoris)

  • Women typically develop clinically evident CHD up to ten years later than men. 1 According to the Framingham Heart Study (FHS), the lifetime risk ofdeveloping CHD after age 40 is 49% and 32% in men and women,respectively. 1 While CHD deaths have decreased in men, studies indicate that CHD deaths in women have remained stable or even have increased. 4
  • Men have a greater risk of suffering from an MI and at earlier ages than women. 2 Women are more likely to suffer from MIs at older ages than men. 3 The average age of first MI is 65.8 and 70.4 in men and women, respectively. 1
  • After menopause, the rate of CHD is 2-3 times that of premenopausal women who are the same age. 3
  • Significantly more women than men (3.3 million vs 3.1 million) suffer from AP, which is chest pain due to myocardial ischemia. 3

Stroke

  • Each year, approximately 40,000 more women than men suffer from astroke. This is related to women’s greater life expectancy and thehigher rates of stroke in the oldest age groups. 3
  • Female stroke patients are more likely than male patients to haveatrial fibrillation, the most common form of irregular heartbeat. 5
  • Although stroke is uncommon in children, a study of over 2,000children demonstrated that boys were at a greater risk of suffering from stroke than girls. 6

Congestive Heart Failure

  • According to the FHS, at age 40, the lifetime risk of developing CHF is 1 in 5 in both sexes. 7
  • At younger ages, men have a higher prevalence of CHF, whereas after age 75, the prevalence is higher in women. 8
  • Women who present with CHF are more likely to have comorbid diabetes and hypertension than men. 9

Cardiac Arrest

  • Cardiac arrest is about 3 times greater in men than in women; however, women have lower recovery and survival rates than men. 10 A recent study showed that between 1989 and 1998, the rate of suddencardiac death decreased in men across all age groups but increased inwomen between the ages of 35-44 years. 11
  • Arrhythmias can occur in healthy people, but they also may indicateserious problems with the heart and lead to cardiac arrest. Women aremore likely than men to have certain types of cardiac arrhythmias(irregular heartbeat), drug-induced torsades de pointes, and long QTsyndrome. The mechanism for these sex differences may be related to thelonger QT interval on the electrocardiogram in women. 12

Risk

Alcohol

Women who consume one alcoholic drink (12 oz. beer or 5 oz. wine) per day have a lower risk of CVD than nondrinkers. However, excessive orbinge drinking can contribute to obesity and high triglycerides, raiseblood pressure, cause heart failure, and lead to stroke. 2

Cholesterol/Lipids

Studies have shown that low levels of HDL convey a higher risk for CVD in women. 3, 13 Women’s total cholesterol is higher than men’s cholesterol beginning at age 45. 3 As women go through menopause, their lipid profiles change and become more atherogenic. 13 High triglycerides may increase the risk of CVD for women more than for men. 14

C Reactive Protein (CRP)

The AHA currently recommends assessment of CRP as a marker forcardiovascular risk. A recent study demonstrated that women had higherCRP levels than men. 15 Levels were also higher in AfricanAmericans than in Caucasians. The authors caution that further studiesare necessary to determine if these differences in CRP levels lead todifferences in CVD outcomes.

Diabetes

For information on the effects of diabetes on CVD, see the “ Sex Differences in Diabetes ” section.

Ethnicity

  • African and Mexican-American women have a higher prevalence of CVD risk factors than Caucasian women. 1 Hypertension was shown to be a particularly strong risk factor for CHDin African American women. The greater likelihood of hypertension inAfrican American women increases their risk for developing heart disease and stroke. The death rate for heart disease and stroke is higher forAfrican American women than for white women.
  • One study showed that women who immigrate to the U.S. are morelikely to die from heart disease and stroke than women born in the U.S.Lower rates of hormone therapy or higher levels of dietary fat comparedto women born in the U.S. may explain the increased risk. 16

Hypertension

  • Before the age of 55, a higher percentage of men than women havehypertension; however, this relationship switches after age 55. 3 Hypertension affects 74% of women ages 65 to 74. In 2002, 59% of the deaths from hypertension were in women.
  • Several studies, including the FHS, have reported that hypertensionand diabetes are greater risk factors for CHF and stroke in women thanin men. 5, 8, 17

Mental Health

  • Studies have shown that depression may increase the risk of CHD inwomen. Women with MI suffer more severe and long-term depression thanmen, and d epression may even increase mortality after MI in women. 13
  • Depression 18 and phobic anxiety 19 have beenshown to increase the risk of cardiac arrest and sudden cardiac death in women. For example, 40% of women who had a cardiac arrest experiencedstress such as a divorce or depression beforehand, compared with only16% of men. Only 5% of the women reported physical exertion before acardiac arrest, compared with 40% of men. 18

Obesity

Although obesity is a known risk factor for CVD, how sex differencesin obesity relate to CVD is an area in need of further scientific study. According to the AHA, in 2002, the prevalence of obesity was higher inwomen than in men, and African and Mexican American women had a higherprevalence of obesity than Caucasian women. 3

Physiology

  • Observational studies of postmenopausal women taking estrogen forhormonal therapy documented a decrease in cardiovascular events. TheWomen’s Health Initiative, which analyzed thousands of postmenopausalwomen taking either estrogen/progestin or estrogen alone did not findsuch benefits. Both arms of the trial, which were stopped early,determined that hormonal therapy is not recommended for the primaryprevention of CVD and stroke in older women. 20, 21
  • Some studies have shown that the risk for certain types of strokewas increased during pregnancy and that the postpartum period wasassociated with increased risk. 1 Studies on the influence of oral contraceptives on stroke risk have had varied results; however,the data regarding women older than 35 appear consistent. These women,and especially those who smoke, have hypertension or migraine, may havean increased risk for stroke. 22
  • Approximately 5-10% of women of reproductive age have polycysticovarian syndrome (PCOS), which is a multifaceted disorder that involvesdysfunctions in the reproductive system, as well as in metabolism. Women with PCOS have an increased risk of cardiovascular complications. 23

Smoking

Studies have shown that women who smoke have a higher risk of developing or dying from heart disease, 24, 25 stroke, 22 and CHF 17 than men. Smoking was shown to increase the risk of MI in women younger than 55, a population that normally is at relatively low risk. 14

Symptoms

Coronary Heart Disease (Myocardial Infarction and Angina Pectoris)

  • Until recently, only men were considered to be at risk for MI, sotheir MI symptoms were defined as “typical”. These include chestdiscomfort, discomfort in the arms, back, neck, jaw, or stomach,shortness of breath, and other symptoms, such as cold sweat, nausea, orlight-headedness. 26 Chest pain is the most common symptom of MI for men. 27, 28
  • Several studies have indicated that women experience a wide varietyof prodromal and acute MI symptoms, which are often considered“atypical” because they differ from symptoms in men. Women do experience chest pain, but it is a more reliable symptom of CVD in women olderthan 65 than in younger women. 29 Women are more likely tohave subtle symptoms of MI such as nausea, vomiting, fatigue, shortnessof breath, dizziness, abdominal or mid-back pain, and indigestion. 27, 29 Unfortunately, because these symptoms differ from those typicallyreported by men, women may not receive appropriate and aggressivetreatment. 13 In fact, women experience delays in botharriving at the hospital after having MI symptoms and receiving timelytreatment for those symptoms. 30 Results of AHA surveys from1997 through 2003 demonstrate that women are becoming more aware of theatypical signs of heart disease. 31
  • Several studies have reported that women suffered more from atypical symptoms of unstable angina (UA) than men, including shortness ofbreath, nausea, difficulty breathing, loss of appetite, back pain, andweakness. 32
  • Typical symptoms of MI are the strongest indicators of acutecoronary syndromes (severe and sudden heart conditions that requireaggressive treatment but have not developed into a full blown MI) inwomen, and they are as important in women as in men. 33
  • Data from the FHS showed that 50% of men and 64% of women who died suddenly of CHD had no previous symptoms. 1

Stroke

One study showed that men with strokes had more traditional stroke warning signals than women. 34 Twenty percent of men reported imbalance, compared with only 15% ofwomen. More men reported weakness of one side of the body than women(24% versus 19%). Twenty-eight percent of women reported nontraditionalstroke symptoms such as pain and change in level of consciousness,compared with only 19% of men. More women reported non-neurologicsymptoms than men (21% vs 17%).

Congestive Heart Failure

A higher proportion of women suffer from diastolic heart failure (vssystolic), which is the inability of the left ventricle to fill properly with oxygenated blood. Diastolic heart failure is well correlated withone of the major symptoms of CHF in women – dyspnea on exertion, orshortness of breath during exercise. 35, 36

Diagnostics, Interventional Procedures, and Treatments

Most of the earlier studies in CVD were conducted in men, which left a gap in knowledge about appropriate diagnostics and therapies for womensuffering from CVD. In addition, recent studies that have included women have had inconsistent results, potentially due to variations in studydesign. 37 However, enough data have emerged to indicate that sex differences are likely to exist in the management of CVD, butfurther research is desperately needed.

Coronary Heart Disease (Myocardial Infarction and Angina Pectoris)

  • The AHA guidelines recommend initial evaluation of CHD with exercise electrocardiographic (ECG) testing. Despite these guidelines, studieshave demonstrated that men were more likely than women to undergo ECGtesting, and more men who underwent ECG testing were more likely toreport no CVD symptoms. 4, 38 An additional study showed that women younger than age 55 (both African American and Caucasian) wereless likely to have this test than same-aged Caucasian men. 39 The lower ECG referral rate may be due to a lower suspicion of CVD inyounger women. However, t he diagnostic ability of this test may belimited in women because of several reasons: lower prevalence of CHD inwomen, higher prevalence of single vessel disease, higher incidence ofmitral valve prolapse, differences in exercise capacity, and thedigoxin-like effects of estrogen. 13 Imaging techniques may aid in the diagnosis of CHD in women who are likely to have intermediate disease. 4, 13
  • Many studies have demonstrated that women are less likely to receive cardiac catheterization and revascularization procedures such ascoronary artery bypass surgery (CABG) and percutaneous coronaryintervention (PCI; angioplasty). 38, 40-44 One studydemonstrated that sex differences were apparent in the type ofrevascularization procedure offered; older women were less likely toundergo CABG but were more likely to undergo PCI than older men. 37 In studies of w omen who did undergo CABG, they were older than men and were more likely to have diabetes, high cholesterol, hypertension, UA,CHF, lower physical function, and depression. 45, 46 Lowerreferral rates for these procedures may result from the increasedhemorrhagic complications after CABG and the poorer recovery afterrevascularization in women compared to men. 13 Studiesconcluded that considering both sexes have comparable outcomes aftersimilar angioplasty-based treatments, sex alone should not be a factorin the decision to perform angioplasty. 47 Other factors that should be considered include age, co-morbidities, risk factors, patient preferences, and current health status. 38 However, anotherstudy found that elderly patients, particularly women, were less likelyto receive angiography and to see a heart specialist after an MI thanyounger patients. 48
  • The AHA guidelines indicate that thrombolytics be administered toall patients regardless of age, sex, or race, and who present withcertain CVD symptoms in the hospital. 49 However, several studies have demonstrated that women are less likely to undergo thromolytic therapy for reperfusion, 41, 49, 50 which may be due to age, medical history, symptoms, and women’s and physicians’ delay in seeking treatment for cardiac events. 38, 49 In addition, thrombolytic therapy may cause more serious bleeding in women than in men. 51 The effectiveness of thrombolytic drugs depends on their use withinminutes of an MI; however, even when women do not delay treatment, theymay be less likely to receive these drugs. 38 A randomizedtrial of patients who received either thrombolytic therapy orangioplasty demonstrated that women benefited greater from angioplastycompared with thrombolytic therapy. Women derived a greater absolutebenefit from angioplasty than did men. 51
  • In addition to thrombolytic agents, other drugs used to treat CVDare often administered differently in women and men. One studydemonstrated that women received aspirin and ACE inhibitors less oftenthan men; however, the authors stated that it was unclear whether thesex differences were due to sex bias by clinicians or due to truedifferences in eligibility to receive certain treatments. 52 A study in Australia showed that in elderly patients, the effectiveness of ACE inhibitors may be lower in women. 53
  • Although the original studies showing the benefits of aspirin in the prevention of CVD were performed predominantly in men, aspirin wasconsidered an important preventive therapy in both sexes. However,studies demonstrated that women with CVD took aspirin for prevention ofsubsequent CVD symptoms less than men. 54 The paucity ofinformation about the benefits of aspirin on cardiovascular health inwomen led to a primary-prevention trial of nearly 40,000 women. 55 Although aspirin is useful in the prevention of a first MI in men, this study determined that aspirin was not effective in preventing first MIin women. However, aspirin significantly decreased the risk of stroke in women. Prevention of CVD cholesterol-lowering therapies is another area where women have historically been overlooked. As recently as 1996, the American College of Physicians suggested women not be screened ortreated for high cholesterol as a primary means of CVD prevention; 56 however, it is now known that women benefit as much as men from cholesterol-lowering drug regimens. 13, 57, 58
  • Several studies have shown that women are less likely to enroll in cardiac rehabilitation despite its benefit. 13, 59, 60 A study by the Mayo Clinic found that after suffering an MI, women andthe elderly were 55% less likely to participate in cardiacrehabilitation than men. 59

Stroke

  • Not many studies evaluating sex differences in management of strokehave been performed; however, sex differences in diagnostics have beendemonstrated. In a study of approximately 4,500 first-time strokepatients in seven European countries, women presented with more severely compromised clinical conditions but were less likely to receive brainimaging, Doppler sonography, echocardiogram, and angiography than men. 61
  • Some studies indicate that women receive anticoagulants and antiplatelet therapies less often than men, 62-64 even though women who receive recombinant tissue plasminogen activator(rtPA) therapy for stroke may have better functional outcomes. 65 For example, in a study of over 2,000 patients who suffered from acuteischemic stroke, women benefited more from rtPA than men even thoughthere was no difference in severity of stroke between the sexes. 66 A small, retrospective study demonstrated that after rtPA,recanalization occurred more often in women than in men with vascularocclusive lesions. 65

Congestive Heart Failure

  • Several studies have indicated that women do not receivepharmacologic treatments for CHF as often as men in both the ambulatoryand hospital settings. 9 One study found modest sexdifferences in treatment, where women received therapies less often than men. Although the results were modest, the authors claim thatconsidering nearly 1 million people are hospitalized for CHF each yearin the U.S., the group of female patients who do not receive appropriate treatment is likely to be sizable.

Outcomes

Similar to diagnostics and treatments for CVD, studies investigatingpossible sex differences in outcomes of patients with various forms ofCVD have resulted in inconsistent data. However, many studies indicatethat sex differences exist.

Coronary Heart Disease (Myocardial Infarction and Angina Pectoris)

  • Studies have shown that women have worse in-hospital and long-term outcomes than men after MI. 4, 13, 40, 50, 67-69 For example, in a study of over 6,000 MI patients in Germany, womenwere more likely to experience recurrent AP and CHF during theirhospital stay. 41 Additional studies demonstrated that womenwere twice as likely to experience complications such as infection,bleeding, and irregular heartbeat during and after CABG compared to men. 45, 46 Women also experienced a higher readmission ratewithin 6 months of their MI and CABG. Results of the FHS demonstratedthat within 6 years of an MI, more women than men will have anotherheart attack (35% vs 18%), be disabled with CHF (46% vs 22%), and suffer a stroke (11% vs 8%). 1
  • According to the AHA, 38% of women who have had an MI will die within one year, compared with 25% of men. 3 This is partly because women have MIs at older ages than men and aremore likely to die from them within a few weeks. Higher mortality mayalso be due to women’s worse baseline characteristics and comorbidities. 69
  • Younger age at MI appears to be a stronger risk factor for mortality in women. 1, 50, 70 According to a Canadian study that analyzed administrative records ofalmost 23,000 patients with acute MI and over 8,000 patients with UA,women with UA had a survival advantage. 71
  • Studies have shown that the mortality rates after CABG are higher for women. 13, 72 One study showed that women younger than 50 were three times more likely to die after CABG compared to men. 73 Women 50-59 years of age were 2.4 times more likely to die. The smaller size of coronary arteries in women may make CABG more difficult. Otherstudies have shown that women who receive thrombolytic therapy after MIare more likely to die or develop complications than men. 51
  • Studies show that post-MI, women have more severe depression thatlasts longer than in men. Depression has been linked to an increase inpost-MI mortality in women. 13

Stroke

  • Two large, European, multi-center studies of stroke patientsdemonstrated that women were more likely to have been disabled, livingat home, or institutionalized prior to the stroke. 61, 64 Pre-stroke institutionalization was a significant determinant of post-stroke discharge destination and handicap. 61 Women were more physically and mentally impaired than men 3 months after their stroke. 64 A Canadian study found that in addition to the increased likelihood ofwomen being discharged to long-term care after stroke, women had longerhospital stays than men. 74
  • In 2002, stroke claimed the lives of 100,050 women, which represents 61.5% of the total stroke deaths. 3

Congestive Heart Failure

  • Multiple studies evaluating sex differences in CHF survival haveshown inconsistent results by demonstrating a survival advantage forboth sexes; however, many studies indicate that women have a survivaladvantage. 9, 17, 75 It is likely that the underlyingetiology of the disease differs in women and men, and depending on thestudy design, this could impact prognosis and study results. 8, 35
  • Based on the FHS, 80% of men and 70% of women who have CHF will die within 8 years. 1
  • According to the AHA, in 2001, 62.5% of the CHF deaths were in women. 1

Views of Female Patients and Physicians

  • The AHA and American Stroke Association have conducted severalsurveys to determine women’s perception of health threats. Compared toone-third of women surveyed in 1997 who knew that CVD was the leadingcause of death for women, in 2003, that number increased to 46%.Although the studies’ authors commended the trend in increased awareness of CVD risk, they remain concerned that only half of the 2003 studyparticipants recognized CVD as the leading cause of death. In addition,those women in the highest CVD risk groups, specifically AfricanAmerican and Hispanic women, showed the smallest improvement inawareness over the six years. 31 Similar results were seen regarding women’s awareness of stroke risk. 76 In 2003, awareness of the threat of stroke was low; only one-third ofrespondents stated they were well informed about stroke. Awareness ofstroke warning signs was also low, especially among African American and Hispanic women.
  • While 93% of the women surveyed by the AHA in 2003 stated that theywould feel comfortable discussing CVD issues with their health careprovider, only 38% reported discussing CVD with their doctors. 31 Compared to results of the 1997 AHA survey, this percentagesignificantly increased in 2003, but only for Caucasian women; thepercentage of women in racial/ethnic minorities who discussed CVD withtheir doctors decreased over the six years.
  • The AHA recently published the first evidence-based report of guidelines to prevent CVD in women. 77 This report discusses the clinical presentation of the four levels(optimal, low, intermediate, and high) of CVD risk in women, as well asthe clinical recommendations to help prevent CVD (lifestyle, riskfactor, and pharmacotherapeutic interventions). In 2005, a studyanalyzed physician adherence to these guidelines and found that compared to men, women were more likely to be assigned to a lower risk categoryalthough calculated risk was similar. 78
  • One in three physicians surveyed in 1995 did not know that CVD is the leading cause of death among women in the United States. 79 Fewer than 1 in 5 physicians surveyed in 2004 knew that more women than men die of CVD each year. 78
  • Physician’s lack of awareness of CVD in women may be attributed tomany factors: women have been excluded from CVD clinical trialsresulting in unclear diagnostic criteria and treatment for women withCVD, physicians may not recognize women’s symptoms of CVD, andphysicians may be more likely to minimize CVD symptoms in women andattribute them to emotional issues. 38 Gaps in physicianknowledge of CVD in women may be improved by targeted educationalprograms in medical schools, residency and fellowship programs, andcontinuing medical education courses.
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