US Pharm. 2016;41(9)44-47.
ABSTRACT: Myocardial infarction (MI), a major cause of cardiovascular disease morbidity and mortality, affects approximately 2.7 million women in the United States. Due to an increased prevalence rate of MI among older women and women of minority populations, differences between men and women regarding the management of MI should be considered. Women tend to experience atypical symptoms of MI and are often misdiagnosed or diagnosed too late, due to physiologic differences in a woman’s heart that may pose a challenge to clinicians. Identifying sex differences in the etiology, epidemiology, and pathophysiology of MI can assist healthcare providers in developing individualized action plans for women with MI. Overall, the management of MI encompasses a multidisciplinary team approach that necessitates effort from the patient, provider, family, and healthcare system.
Myocardial infarction (MI), also known as a heart attack, is a major cause of morbidity and mortality. Although overall mortality rates are trending down, coronary heart disease (CHD) currently affects approximately 6.6 million women in the United States. Of this population, 2.7 million have a history of MI.1 Prevalence rates of MI have been reported to be higher among older women and women of minority populations.2 Mehta et al state that black women have a higher prevalence of acute MI compared with other women, including higher rates of sudden cardiac death. Asian Indian women have higher mortality rates, which may be associated with higher rates of cardiovascular disease (CVD) risk factors.3 Differences in the management and treatment of MI in men and women may be associated with the rates of morbidity and mortality related to cardiovascular events. Therefore, when managing the cardiovascular health of women, it is important to take into account the significant differences between men and women regarding the epidemiology, risk factors, diagnosis, treatment, and prognosis of CHD.4,5
Epidemiology of MI in Women
CHD, including MI, continues to be the leading cause of death among women in the U.S.2 Although the prevalence of CHD increases with age for women and men, the incidence of MI in women increases dramatically following menopause, with rates 3 times those of women the same age who remain premenopausal.6-8 Data from 44 years of follow-up in the original Framingham Study cohort shows that the incidence of MI at ages 65 to 94 years compared with ages 35 to 64 years more than doubles in men and triples in women, respectively.7 Depending on clinical outcome and prognosis, women >65 years have a higher risk of death within one year after a first MI compared with younger women.2
Cardiovascular Risk Factors in Women
There are various risk calculators and estimators available to assess cardiovascular risk. Risk calculators such as the Reynolds or Framingham Risk Scores can assist providers in predicting a woman’s risk of developing CVD, MI, or stroke in the future. The Framingham risk calculator, which utilizes information from the Framingham Heart Study, is designed for adults >20 years who do not have a history of heart disease or diabetes.9 A person’s age, gender, cholesterol, smoking status, and blood pressure (BP) reading are required in order to assess risk. The Reynolds Risk Score is slightly different from the Framingham tool in that in addition to obtaining a person’s age, BP, cholesterol, and smoking status, it uses a person’s high-sensitivity C-reactive protein (hsCRP) levels to measure inflammation.10 The tool also assesses a person’s genetic risk by asking the question, “Did your mother or father have a heart attack before age 60?”10 The use of additional biomarkers such as hsCRP may be more useful in women, especially if specific risk factors are unclear.10
There are several cardiovascular risk factors that women have in common with men: age, family history, comorbid conditions, cigarette smoking, and other lifestyle factors.6 However, researchers have noted several differences in risk factors between women and men. Several studies have found that the impact of smoking is larger in women than in men.11-13 In the Tromsø study, the incidence of an MI was 18.3% in women >68 years (n=453; hazard ratio [HR]=2.5 [1.9-3.2] who actively smoked 10-19 cigarettes per day compared with 21.2% in men >60.7 years (n=769; HR=1.9 [1.5-2.4]).12 Negative cardiovascular effects associated with MI have also been found in passive smokers, or in non-smokers who involuntarily inhale cigarette smoke. The INTERHEART study showed that passive smoking accounted for 10.8% of MIs in women who had never smoked cigarettes; Iversen et al reported that there was a 52.1% incidence of MI among women >68 years versus an incidence of 36.2% among men >60.7 years who lived with a smoker >30 years.12,14 However, most of the increased risk of CVD events is drastically reduced within two to three years of smoking cessation.15
Hip fracture surgery in elderly women has been linked with an increased risk of MI, known as perioperative MI (PMI). PMI often remains unrecognized, and mortality is higher in elderly women. PMI symptoms are often masked by analgesia, sedation, and transient and subtle ECG changes. Gupta et al, in a cohort study of 1,212 elderly patients, found that PMI is associated with a 15-fold increased risk of in-hospital death and a 4.3-fold increased risk of 30-day mortality in the elderly. Measurement of the cardiac biomarker troponin can promote the early detection of a silent PMI in postoperative elderly women and can decrease PMI-associated short- and long-term mortality in this population.16
Postmenopausal status has been associated with an increased risk of CHD; however, there have been conflicting views on whether surgical or natural menopause affects cardiovascular risk.6,17,18 The Women’s Health Initiative trial found that predominantly healthy women who took estrogen plus progestin oral contraceptives experienced a 29% increase in CHD events compared to placebo; CHD events were defined as an acute MI requiring overnight hospitalization, silent MI diagnosed with an electrocardiogram (ECG), or CHD death.19 It is important to note that hormone replacement therapy is not recommended for CHD prevention.6
A history of pregnancy complications, such as gestational hypertension and diabetes, preeclampsia, and spontaneous pregnancy loss, has been associated with an increased future risk of CVD.6,20,21 Additional risk factors for CHD are shown in Table 1.
Clinical Presentation of MI in Women
Prompt recognition of symptoms is the first step in managing women patients with CHD.22 Patients may present with chest pain, MI, heart failure, or sudden cardiac death. At the time of presentation, women are generally older than men. Women may not recognize initial symptoms of heart disease and, therefore, may not seek immediate medical attention.5,23-26 Studies report that providers may not even evaluate symptoms of myocardial ischemia as early in women as they do in men owing to misdiagnosis, atypical symptoms, comorbidities, or underestimation of risk factors.26-28 Differences in acute MI pathophysiology have also been noted between women and men. Men have higher rates of plaque rupture in the setting of acute MI, while plaque erosion is more common in women compared to men.3
Although chest pain is one of the most common symptoms of an MI, the symptoms of women may be subtler than those of men and can sometimes be confusing. Women can experience an MI without chest pressure, and may instead experience shortness of breath, pressure or pain in the lower chest or upper abdomen, sweating, dizziness, lightheadedness or fainting, upper back pressure, nausea, or extreme fatigue.2,29 It is often more common for women to attribute the symptoms of MI to less life-threatening conditions, such as acid reflux, influenza, and normal aging.29 Also, women presenting with a first symptomatic MI, according to a report by Wilson and Douglas, are “more likely to have a history of diabetes, hypertension, hyperlipidemia, heart failure, and an unstable angina pattern than their male counterpart.”7
Morphologic Differences in the Female Heart
Morphologic differences in the female heart may contribute to disparities in the diagnosis, treatment and prognosis of MI and other cardiovascular events among women. Westerman and Wenger report a longer QT interval and a faster resting heart rate in women, which may be attributed to the smaller size of the female heart and differences in hormones and autonomic tone. According to the authors, the hormones estrogen and progesterone are both present in cardiac myocytes, which may be associated with the QT interval length and cardiovascular event risk. Furthermore, differences in the heart’s anatomic structures among women may cause increased surgical risks and an increase in the prevalence of heart-valve disorders. Surgical procedures such as angioplasty and stenting may not be as effective in women compared to men due to variations of arterial plaque build-up. Women are more likely to experience diastolic dysfunction of the heart, which may pose additional treatment challenges.30
Treatment Considerations for Women
There are several therapeutic agents available for the management of CHD. Treatment goals for acute coronary syndromes are aimed at relieving symptoms, preventing future secondary myocardial events, and preventing sudden cardiac death.31,32 Acute management therapies, including nitroglycerin and supplemental oxygen, are aimed at symptom control and restoring oxygen supply and demand in MI.31,32 Immediate antiplatelet therapy with aspirin has been shown to reduce mortality after an acute coronary event.33 Additionally, aspirin as secondary prevention has been proven to reduce recurrent ischemia in both men and women similarly in clinical trials.33,34
Regarding adverse effects, female patients usually have higher rates of bleeding from antiplatelets and thrombolytic drugs. The standards of care identify female sex as a risk factor for bleeding complications after an ST-elevated MI (STEMI).32 However, weight- and kidney-function monitoring may be beneficial in lowering the bleeding risk among women.3
Beta-receptor antagonists (beta-blockers) have been shown to reduce the rate of death from MI by reducing myocardial oxygen demand during periods of physical and mental stress and assisting in prevention of recurrent ischemia and life-threatening ventricular arrhythmias.35 However, a study in 2005 by Blomkalns et al demonstrated that among female patients, beta-blockers were actually less likely to be administered compared to males presenting with MI.36 Statins were also less likely to be administered for treatment of MI in women.5,37 ACE inhibitors have been shown to be beneficial after an acute MI in several studies; however, their efficacy in women has not been specifically studied.3,5 In a study conducted by Pregler et al, women were more likely to be inappropriately assigned to low-risk categories than men and were less likely to receive appropriate recommendations for lifestyle change and preventive pharmacotherapy.37
Reperfusion therapy such as percutaneous coronary intervention (PCI) aims to restore blood flow to coronary arteries after an MI.32 Although this cardiovascular intervention has been proven to reduce mortality and have better outcomes regardless of gender, evidence indicates that reperfusion therapy is more commonly performed in male patients.38 Disparities in gender also exist in the management of patients with non-ST-segment elevation (NSTE) and ST-segment elevation acute coronary syndromes (ACS). Additional studies have reported discrimination in the provision of medical care for women, noting that they were less likely to be admitted to the coronary care unit, less likely to undergo invasive procedures, and less likely than men to be treated for cardiovascular events; older women, in particular, are less likely to receive further treatment.39-41
Role of the Pharmacist
Pharmacists should play a key role in increasing patient awareness and knowledge about CHD, while assisting healthcare providers in identifying sex-specific barriers and factors among patients with MI and those at risk for CHD. Pharmacists can also utilize their medication expertise to provide evidence-based treatment recommendations, improve medication adherence, and assist in the development of tools that will be beneficial in improving CVD morbidity and mortality.
It is important that healthcare providers take into account physiologic, clinical, psychosocial, and health management differences among women compared to men when diagnosing MI, and in treating and monitoring patients with a history of MI. The use of risk calculators such as the Reynolds Risk Score, specifically developed for women, and the Framingham Risk Score may assist providers in assessing women for early signs of heart disease. Women also should be aware of the signs and symptoms of MI, and have an understanding of the disease, the appropriate management of medications, and ways of self-monitoring and incorporating healthy lifestyle behaviors. Furthermore, efforts from a multidisciplinary team that might include a cardiology specialist, pharmacist, nutritionist, and exercise physiologist as well as psychiatric and family support are vital in improving the quality of life and the cardiovascular health of older women.42
1. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation. 2015;131(4):e29-e322.
2. Writing Group Members, Mozaffarian D, Benjamin EJ, et al. Heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation. 2016;133(4):e38-e60.
3. Mehta LS, Beckie TM, DeVon HA, et al. Acute myocardial infarction in women: a scientific statement from the American Heart Association. Circulation. 2016;133(9):916-947.
4. Lee PY, Alexander KP, Hammill BG, et al. Representation of elderly persons and women in published randomized trials of acute coronary syndromes. JAMA. 2001;286(6):708-713.
5. Douglas P. Management of coronary heart disease in women. UpToDate.com. Updated April 28, 2015. www.uptodate.com/contents/management-of-coronary-heart-disease-in-women. Accessed May 31, 2016.
6. Douglas P, Poppas A. Overview of cardiovascular risk factors in women. UpToDate.com. Updated January 22, 2016. www.uptodate.com/contents/overview-of-cardiovascular-risk-factors-in-women. Accessed June 2016.
7. Wilson P, Douglas P. Epidemiology of coronary heart disease. Uptodate.com. Updated January 23, 2015. www.uptodate.com/contents/epidemiology-of-coronary-heart-disease. Accessed May 2016.
8. Gordon T, Kannel WB, Hjortland MC, McNamara PM. Menopause and coronary heart disease. the Framingham Study. Ann Intern Med. 1978;89(2):157-161.
9. D’Agostino RB Sr., Vasan RS, Pencina MJ, et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 2008;117(6):743-753.
10. Ridker PM, Buring JE, Rifai N, Cook NR. Development and validation of improved algorithms for the assessment of global cardiovascular risk in women: the Reynolds Risk Score. JAMA. 2007;297(6):611-619.
11. Huxley RR, Woodward M. Cigarette smoking as a risk factor for coronary heart disease in women compared with men: a systematic review and meta-analysis of prospective cohort studies. Lancet. 2011;378(9799):1297-1305.
12. Iversen B, Jacobsen BK, Lochen ML. Active and passive smoking and the risk of myocardial infarction in 24,968 men and women during 11 years of follow-up: The Tromsø study. Eur J Epidemiol. 2013;28(8):659-667.
13. Njolstad I, Arnesen E, Lund-Larsen PG. Smoking, serum lipids, blood pressure, and sex differences in myocardial infarction. A 12-year follow-up of the Finnmark study. Circulation. 1996;93(3):450-456.
14. Teo KK, Ounpuu S, Hawken S, et al. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study. Lancet. 2006;368(9536):647-658.
15. Rosenberg L, Palmer JR, Shapiro S. Decline in the risk of myocardial infarction among women who stop smoking. N Engl J Med. 1990;322(4):213-217.
16. Gupta BP, Huddleston JM, Kirkland LL, et al. Clinical presentation and outcome of perioperative myocardial infarction in the very elderly following hip fracture surgery. J Hosp Med. 2012;7(9):713-716.
17. Mondul AM, Rodriguez C, Jacobs EJ, Calle EE. Age at natural menopause and cause-specific mortality. Am J Epidemiol. 2005;162(11):1089-1097.
18. Hu G, Jousilahti P, Qiao Q, et al. The gender-specific impact of diabetes and myocardial infarction at baseline and during follow-up on mortality from all causes and coronary heart disease. J Am Coll Cardiol. 2005;45(9):1413-1418.
19. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288(3):321-333.
20. Ahmed R, Dunford J, Mehran R, et al. Pre-eclampsia and future cardiovascular risk among women: a review. J Am Coll Cardiol. 2014;63(18):1815-1822.
21. Kharazmi E, Dossus L, Rohrmann S, Kaaks R. Pregnancy loss and risk of cardiovascular disease: a prospective population-based cohort study (EPIC-Heidelberg). Heart. 2011;97(1):49-54.
22. Reeder G, Kennedy H, Rosenson R. Overview of the acute management of ST elevation myocardial infarction. UpToDate.com. Updated January 14, 2016. www.uptodate.com/contents/overview-of-the-acute-management-of-st-elevation-myocardial-infarction. Accessed May 31, 2016.
23. Stangl V, Witzel V, Baumann G, Stangl K. Current diagnostic concepts to detect coronary artery disease in women. Eur Heart J. 2008;29(6):707-717.
24. Orencia A, Bailey K, Yawn BP, Kottke TE. Effect of gender on long-term outcome of angina pectoris and myocardial infarction/sudden unexpected death. JAMA. 1993;269(18):2392-2397.
25. Kannel WB, Vokonas PS. Demographics of the prevalence, incidence, and management of coronary heart disease in the elderly and in women. Ann Epidemiol. 1992;2(1-2):5-14.
26. Douglas P. Clinical features and diagnosis of coronary heart disease in women. UpToDate.com. Updated August 19 2014. www.uptodate.com/contents/clinical-features-and-diagnosis-of-coronary-heart-disease-in-women. Accessed May 31, 2016.
27. Mosca L, Linfante AH, Benjamin EJ, et al. National study of physician awareness and adherence to cardiovascular disease prevention guidelines. Circulation. 2005;111(4):499-510.
28. Foa C, Artioli G. Gender differences in myocardial infarction: health professionals’ point of view. Acta Biomed. 2016;87 Suppl 2:7-18.
29. American Heart Association. Heart attack symptoms among women. Updated July 2015. www.heart.org/HEARTORG/Conditions/HeartAttack/WarningSignsofaHeartAttack/Heart-Attack-Symptoms-in-Women_UCM_436448_Article.jsp#.V3O6eKKPaeE. Accessed May 31, 2016.
30. Westerman S, Wenger NK. Women and heart disease, the underrecognized burden: sex differences, biases, and unmet clinical and research challenges. Clin Sci (Lond). 2016;130(8):551-563.
31. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130(25):e344-e426.
32. O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127(4):e362-e425.
33. Baigent C, Collins R, Appleby P, et al. ISIS-2: 10 year survival among patients with suspected acute myocardial infarction in randomised comparison of intravenous streptokinase, oral aspirin, both, or neither. the ISIS-2 (second international study of infarct survival) collaborative group. BMJ. 1998;316(7141):1337-1343.
34. Hennekens CH, Hollar D, Baigent C. Sex-related differences in response to aspirin in cardiovascular disease: an untested hypothesis. Nat Clin Pract Cardiovasc Med. 2006;3(1):4-5.
35. Nohria A, Vaccarino V, Krumholz HM. Gender differences in mortality after myocardial infarction: why women fare worse than men. Cardiol Clin. 1998;16(1):45-57.
36. Blomkalns AL, Chen AY, Hochman JS, et al. Gender disparities in the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: large-scale observations from the CRUSADE (can rapid risk stratification of unstable angina patients suppress adverse outcomes with early implementation of the American College of Cardiology/American Heart Association guidelines) national quality improvement initiative. J Am Coll Cardiol. 2005;45(6):832-837.
37. Pregler J, Freund KM, Kleinman M, et al. The heart truth professional education campaign on women and heart disease: needs assessment and evaluation results. J Womens Health (Larchmt). 2009;18(10):1541-1547.
38. Vaccarino V, Rathore SS, Wenger NK, et al. Sex and racial differences in the management of acute myocardial infarction, 1994 through 2002. N Engl J Med. 2005;353(7):671-682.
39. Pilgrim T, Heg D, Tal K, et al. Age- and gender-related disparities in primary percutaneous coronary interventions for acute ST-segment elevation myocardial infarction. PLoS One. 2015;10(9):e0137047.
40. Ayanian JZ, Epstein AM. Differences in the use of procedures between women and men hospitalized for coronary heart disease. N Engl J Med. 1991;325(4):221-225.
41. Medina HM, Cannon CP, Zhao X, et al. Quality of acute myocardial infarction care and outcomes in 33,997 patients aged 80 years or older: findings from Get With the Guidelines-Coronary Artery Disease (GWTG-CAD). Am Heart J. 2011;162(2):283-290.e2.
42. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation. 2016;133(4):e38-e360.
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