Affairs of the Heart: Cardiovascular Disease in Women Vs Men

JUNE 26, 2018
Jeannette Y. Wick, RPh, MBA, FASCP,
Surprisingly to many people, heart disease is the No. 1 killer of American women. One-third of women also die from heart-related episodes. Atherosclerosis affects both genders, but its profile in women is unique. For example, 42% of women who have heart attacks die within a year, compared with 24% of men.1 Traditionally, clinicians and investigators thought that estrogen was cardioprotective. However, later research disproved this theory, and even premenopausal women can experience serious heart disease.2

In general, risk factors that increase the likelihood of symptomatic heart problems are similar for men and women (Table 1).1,3-6 Diabetes is a stronger contributor in women, doubling the likelihood of death.7 Smoking also accelerates heart disease in women faster than in men.8 Individuals who have 1 risk factor have twice the risk of heart disease as those who do not. Once an individual accumulates 3 risk factors, she has 10 times the risk. Addressing modifiable risk factors can slow or stop heart disease’s progression, and women’s hearts respond better to healthy lifestyle changes than men’s do.1



PATIENTS’ EXPECTATIONS ABOUT MI ARE OFTEN WRONG
Misdiagnosis of heart disease in women is common, which is why it is important to identify symptom differences (Table 2).1,3,9 An essential fact to remember is that most patients who experience a myocardial infarction (MI) report that their symptoms—the magnitude of pain and location of discomfort or associated symptoms—were different from what they expected.10 Among women who die from MI, nearly two-thirds had no history of chest pain.1



ASSESSMENT
The 2013 American College of Cardiology and American Heart Association Guideline on the Assessment of Cardiovascular Risk introduced a calculator that determines an individual’s 10-year risk of heart disease or stroke, and numerous organizations have online calculators on their websites. Use of these calculators is controversial, but they do set a threshold for intervention.11 Clinicians need to know that a common tool used to assess patients is less accurate in women than in men. To understand why, clinicians need to differentiate between atherosclerotic cardiovascular disease (ASCVD), which affects the large arteries, and microvascular (or ischemic or nonobstructive) disease (MVD), which affects cardiac arterioles. In ASCVD, plaque gradually occludes large coronary arteries and may eventually completely block blood flow. In MVD, plaque builds evenly within the walls of small arteries. Blockage may not occlude blood flow completely but cause ischemia. Women, especially younger ones, are more likely than men to have MVD. Between 2 million and 3 million women in the United States have MVD.11

Clinicians rely on conventional testing, such as coronary angiography and stress testing, to diagnose ASCVD. Coronary angiography uses dye and x-rays, graphically displaying the large coronary arteries. Coronary angiography will not identify MVD, however, making it less useful in women.11 One alternative screening method, the Duke Activity Status Index (DASI), is a better measure of MVD.6,12 MVD symptoms often occur during routine daily tasks, such as cooking, gardening, and shopping, and the DASI identifies patients whose angiography results are negative but who experience ischemia.

WHAT ABOUT ASPIRIN?
Aspirin is a mainstay of cardiac care, but its effects vary by gender also. Consider 2 studies:
  • The Physicians’ Health Study followed men from 1982 to 1988. In men older than 50 who had no evidence of coronary disease, 325 mg of aspirin every other day reduced the risk of MI by 44%. Aspirin had no apparent effect on mortality or stroke.
  • The Women’s Health Study (1992-2004) demonstrated that in women with similarly clean cardiovascular pictures who were older than 65, 100 mg aspirin every other day had no apparent effect on MI risk or mortality. But it did reduce the risk of ischemic stroke and overall stroke by 24% and 17%, respectively.13
It is difficult to compare these 2 studies precisely because participants differed in age, aspirin doses, baseline rates of MI, and time. Regardless, aspirin’s effects are different in men and women.

The underlying explanation is both apparent and elusive. Aspirin’s molecular pharmacology is identical, regardless of gender, which suggests that men and women would respond identically. But gender influences aspirin’s pharmacodynamic profile. After identical doses, women experience salicylate levels higher than men do, and platelets also behave differently, causing a less-than-predictable antithrombotic effect. Further, women’s vascular anatomy differs from men’s; women have smaller coronary arteries. (Interestingly, when a woman’s heart is transplanted into a male recipient, these arteries enlarge, even if the woman’s body surface area was larger than the man’s.) Additionally, atherosclerotic plaque distribution, carotid anatomy, electrical repolarization, and vascular reactivity differ based on gender. Some of these differences may be hormonal, as estrogen upregulates prostacyclin production.13

CONCLUSION
A last fact is sobering: Women with heart disease receive less aggressive treatment than do men.9 Current guidelines for heart disease do not include gender-based diagnostic approaches. Lipid-lowering drugs reduce risk and lower mortality rates in women with heart disease. Secondary prevention measures, including angiotensin-converting enzyme inhibitors, aspirin, beta-blockers, rehabilitation, and revascularization, also help.1,14 
 
Jeannette Y. Wick, RPh, MBA, FASCP, is the assistant director of the Office of Pharmacy Professional Development at the University of Connecticut School of Pharmacy in Storrs.


References
  1. Women and heart disease facts. Women’s Heart Foundation website. womensheart.org/content/HeartDisease/heart_disease_facts.asp. Accessed April 27, 2018.
  2. Howard BV, Rossouw JE. Estrogens and cardiovascular disease risk revisited: the Women’s Health Initiative. Curr Opin Lipidol. 2013;24(6):493-499. doi: 10.1097/ MOL.0000000000000022.
  3. Women and heart disease prevention. Centers for Disease Control and Prevention website. cdc.gov/women/heart/. Updated February 7, 2017. Accessed April 27, 2018.
  4. Mehta PK, Wei J, Wenger NK. Ischemic heart disease in women: a focus on risk factors. Trends Cardiovasc Med. 2015;25(2):140-151. doi: 10.1016/j.tcm.2014.10.005.
  5. Eaker ED, Sullivan LM, Kelly-Hayes M, D’Agostino RB Sr, Benjamin EJ. Marital status, marital strain, and risk of coronary heart disease or total mortality: the Framingham Offspring Study. Psychosom Med. 2007;69(6):509-513.
  6. Phillips L, Wang JW, Pfeffer B, et al. Clinical role of the Duke Activity Status Index in the selection of the optimal type of stress myocardial perfusion imaging study in patients with known or suspected ischemic heart disease. J Nucl Cardiol. 2011;18(6):1015-1020. doi: 10.1007/s12350-011-9456-y.
  7. Barrett-Connor EL, Cohn BA, Wingard DL, Edelstein SL. Why is diabetes mellitus a stronger risk factor for fatal ischemic heart disease in women than in men? The Rancho Bernardo Study. JAMA.1991;265(5):627-631.
  8. 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. doi: 10.1016/S0140- 6736(11)60781-2.
  9. Brewer LC, Svatikova A, Mulvagh SL. The challenges of prevention, diagnosis and treatment of ischemic heart disease in women. Cardiovasc Drugs Ther. 2015;29(4):355-368. doi: 10.1007/s10557-015-6607-4.
  10. King KB, McGuire MA. Symptom presentation and time to seek care in women and men with acute myocardial infarction. Heart Lung. 2007;36(4):235-243. doi: 10.1016/j.hrtlng.2006.08.008.
  11. Shaw LJ, Merz CN, Pepine CJ, et al; Women’s Ischemia Syndrome Evaluation (WISE) investigators. The economic burden of angina in women with suspected ischemic heart disease: results from the National Institutes of Health–National Heart, Lung, and Blood Institute–sponsored women’s ischemia syndrome evaluation. Circulation. 2006;114(9):894-904. doi: 10.1161/CIRCULATIONAHA.105.609990.
  12. Mieres JH, Heller GV, Hendel RC, et al. Signs and symptoms of suspected myo- cardial ischemia in women: results from the What Is the Optimal Method for Ischemia Evaluation in WomeN? trial. J Womens Health (Larchmt). 2011;20(9):1261-1268. doi: 10.1089/jwh.2010.2595.
  13. Levin RI. The puzzle of aspirin and sex. N Engl J Med. 2005;352(13):1366-8. doi: 10.1056/NEJMe058051.
  14. Bedinghaus J, Leshan L, Diehr S. Coronary artery disease prevention: what’s dif- ferent for women? Am Fam Physician. 2001;63(7):1393-1400, 1405-1406.


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