At the heart of the matter

Gender disparities in cardiovascular health


In keeping with the American Heart Month spirit, this blog post serves to take a closer look at heart disease in women, specifically the disparities women face in heart disease diagnosis, treatment and health outcomes.


As the leading cause of death for women worldwide,[1] cardiovascular disease (CVD) in women must be examined and improvements in diagnosis and treatment be explored. Upon our own examination of the literature, we found gender disparities at all points of the heart health spectrum beginning with CVD risk factors, which disproportionately affect women.[2] Diagnosis, treatment and therapies recommended to women upon presentation of a cardiac event can lead to poorer heart health outcomes as well. You may ask yourself, as we did, three key questions:

  1. What are the heart health disparities women face?

  2. What are the reasons for the disparities?

  3. What can we do to ameliorate the gender gap in heart health?

Since 1984, CVD mortality is on the rise in younger women aged 35-54 years.[3] This has been attributed to an increasing prevalence of CVD risk factors, which can portend disparate outcomes in women versus men. For example, a number of clinical conditions unique to women have been shown to increase CVD risks such as pre-eclampsia, gestational diabetes, polycystic ovary syndrome, early menopause and autoimmune diseases.[4] Autoimmune disorders are more prevalent in women and inflammatory disorders such as rheumatoid arthritis, psoriasis, and systemic erythematous lupus have robust associations with CVD.[5] Social determinants of health such as psychosocial stressors and poverty, both with higher prevalence in women, are also associated with increased cardiovascular risk.[6] In addition to increased risk factors, health outcomes for women who experience a cardiac event like acute myocardial infarction (AMI) are unfavorable. Why?


The VIRGO Study looked at 3,501 patients (2,349 women and 1,152 men) with AMI.[7] When you look at a woman with AMI, she’s more likely than a man to have a myriad of comorbidities like diabetes, congestive heart failure (CHF), stroke, chronic obstructive pulmonary disease (COPD), chronic renal failure, and thyroid disorders. A woman is also more likely to have higher BMI and to report insufficient physical activity.[7] Gupta et al. had similar findings: several comorbidities were more prevalent in women as compared with men across all age subgroups, including CHF, hypertension, renal failure, COPD, and diabetes mellitus.[8] VIRGO found significantly more women had >3 cardiovascular risk factors (diabetes, hypertension, hypercholesterolemia, smoking, and obesity). Women were also more likely to have a history of cancer, autoimmune disorders, and psychiatric disorders than men. The observations of this study suggest that young and middle-aged women with AMI represent a sicker population than men of the same age.[7] Therefore, when a woman enters the hospital with AMI she is more likely than a male patient to be living with any number of other health issues that will affect her CVD outcomes. It is interesting to note that among patients with AMI, there is a higher prevalence of nonobstructive coronary arteries among women, particularly young women. Nevertheless, the prognosis for young women with AMI is worse than that for young men.[9]


How women patients are treated when they present with CVD has been studied and treatment disparities play a critical role in the poor cardiovascular health outcomes of women. In numerous studies it’s been reported that women are less likely to receive evidence-based treatments or be managed by guideline-based acute coronary syndrome (ACS) medications.[2][3][6][9][10][11][12][13] Young women had a lower probability of receiving lipid-lowering therapies, non-aspirin antiplatelets, beta blockers, coronary angiography and coronary revascularization. For those that did receive reperfusion it was delayed.[10] For women undergoing percutaneous coronary intervention (PCI), women were more likely to exceed in-hospital and transfer-time guidelines than men, and more likely to exceed door-to-needle (DTN) and door-to-balloon (DTB) times.[12] Diabetic women are less likely to be treated with aspirin and have their hyperlipidemia and hypertension optimized than similarly affected men. Women are also less likely to have their hypertension controlled compared to men.[12]


The health disparities begin once a woman presents with a cardiac event. Women often have atypical symptoms from men such as abdominal pain or dizziness and may present without chest pain at all.[14] In the VIRGO trial, young women with AMI who were eligible for and received reperfusion therapy were more likely to present with atypical chest pain or no symptoms and to present greater than 6 hours after symptom onset. While most patients present with typical symptoms such as central chest pain or pressure, women are more likely to experience anginal equivalents such as fatigue, dyspnea, indigestion, or jaw pain.[14] Differences in presentation may explain some of the gender disparities in CVD outcomes. However, Jneid et al. concluded disparities in the use of early aspirin and β-blocker therapies and the disparities in DTB and DTN times are hard to attribute to anything but inappropriate treatment biases.[10]

Recognition of cardiovascular risk in female patients is lower than for male patients with similar risk profiles.[6] Intermediate risk women were more likely to be assessed as lower risk by primary care physicians, obstetricians/gynecologists, and cardiologists than men with identical risk profiles.[2] Lower risk could equate to more conservative therapies when more aggressive therapies are warranted, directly affecting health outcomes. For example, systemic autoimmune disorders occur predominantly in women, which predisposes them to chronic inflammation, endothelial dysfunction, and accelerated atherosclerosis. These are considered risk-enhancing factors and their presence in intermediate or select borderline risk patients should yield consideration of initiation or intensification of statin therapy.[15] Pre-eclampsia, early menopause and autoimmune diseases are additional 'risk enhancers' that if present should yield consideration of initiation or intensification of statin therapy as well.[4]


We postulate that the gender gap in cardiovascular health can be ameliorated with the help of clinicians, physicians and researchers. A common thread we came across in multiple research studies was the need for women-specific clinical research, as the majority of cardiovascular research trials have been in men.[6] As of 2020, women represent only 38% of participants in cardiovascular clinical trials.[16] To understand further the distinct cardiovascular risk profile and to define treatment pathways in women, clinical trials could be designed specifically for women.[6]


Updated guidelines on prevention of CVD in women are needed to assist with accurate clinical decisions and to optimize CVD prevention in women.[2][6] A woman who presents with CVD needs to be cared for appropriately. A focused clinical history with a detailed assessment of the presenting symptoms, along with a family and social history, may provide diagnostic clues.[9] Agarwala et al. asserts that cardiovascular risk stratification in women is incomplete without a thorough obstetrical and gynecologic history. In addition, careful screening and preventive measures should be utilized in women with a history of inflammatory diseases.[15] Given women’s impaired prognosis, additional testing should be considered to attempt to identify processes, such as endothelial and/or microvascular dysfunction, that may influence treatment and long-term outcomes.[17]

Expanding initiatives such as the American Heart Association Go Red for Women campaign to help increase awareness about CVD risk in women is also needed.[6] More than 90% of primary care physicians don’t know that heart disease kills more women each year than men[1] and many women believe breast cancer is their biggest health risk. It’s our hope that this blog post shines a light on heart disease in women and increases awareness of the severity of the disease and the poorer health outcomes women face.


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References

1.https://www.cdc.gov/heartdisease/facts.htm

2. Lee SK, Khambhati J, Varghese T, et al. Comprehensive primary prevention of cardiovascular disease in women. Clin Cardiol. 2017;40(10):832-838. doi:10.1002/clc.22767

3. Wenger NK. Women and coronary heart disease: a century after Herrick: understudied, underdiagnosed, and undertreated. Circulation. 2012 Jul 31;126(5):604-11. doi: 10.1161/CIRCULATIONAHA.111.086892. PMID: 22850362.

4. Young L, Cho L. Unique cardiovascular risk factors in women. Heart. 2019 Nov;105(21):1656-1660. doi: 10.1136/heartjnl-2018-314268. Epub 2019 Jul 17. PMID: 31315936.

5. Angum F, Khan T, Kaler J, Siddiqui L, Hussain A. The Prevalence of Autoimmune Disorders in Women: A Narrative Review. Cureus. 2020;12(5):e8094. Published 2020 May 13. doi:10.7759/cureus.8094

6. Arora S, Stouffer GA, Kucharska-Newton AM, et al. Twenty Year Trends and Sex Differences in Young Adults Hospitalized With Acute Myocardial Infarction. Circulation. 2019;139(8):1047-1056. doi:10.1161/CIRCULATIONAHA.118.037137

7. Leifheit-Limson EC, D'Onofrio G, Daneshvar M, et al. Sex Differences in Cardiac Risk Factors, Perceived Risk, and Health Care Provider Discussion of Risk and Risk Modification Among Young Patients With Acute Myocardial Infarction: The VIRGO Study. J Am Coll Cardiol. 2015;66(18):1949-1957. doi:10.1016/j.jacc.2015.08.859

8. Gupta A, Wang Y, Spertus JA, et al. Trends in acute myocardial infarction in young patients and differences by sex and race, 2001 to 2010. J Am Coll Cardiol. 2014;64(4):337-345. doi:10.1016/j.jacc.2014.04.054

9. Tamis-Holland JE, Jneid H. Myocardial Infarction With Nonobstructive Coronary Arteries (MINOCA): It's Time to Face Reality!. J Am Heart Assoc. 2018;7(13):e009635. Published 2018 Jun 28. doi:10.1161/JAHA.118.009635

10. Jneid H, Fonarow GC, Cannon CP, Hernandez AF, Palacios IF, Maree AO, Wells Q, Bozkurt B, Labresh KA, Liang L, Hong Y, Newby LK, Fletcher G, Peterson E, Wexler L; Get With the Guidelines Steering Committee and Investigators. Sex differences in medical care and early death after acute myocardial infarction. Circulation. 2008 Dec 16;118(25):2803-10. doi: 10.1161/CIRCULATIONAHA.108.789800. Epub 2008 Dec 8. PMID: 19064680.

11. Bucholz EM, Strait KM, Dreyer RP, et al. Editor's Choice-Sex differences in young patients with acute myocardial infarction: A VIRGO study analysis. Eur Heart J Acute Cardiovasc Care. 2017;6(7):610-622. doi:10.1177/2048872616661847

12. Perdoncin E, Duvernoy C. Treatment of Coronary Artery Disease in Women. Methodist Debakey Cardiovasc J. 2017 Oct-Dec;13(4):201-208. doi: 10.14797/mdcj-13-4-201. PMID: 29744012; PMCID: PMC5935279.

13. Bhatia PM, Daniels LB. Highly Sensitive Cardiac Troponins: The Evidence Behind Sex-Specific Cutoffs. J Am Heart Assoc. 2020 May 18;9(10):e015272. doi: 10.1161/JAHA.119.015272. Epub 2020 May 9. PMID: 32390494; PMCID: PMC7660872.

14. Mechanic OJ, Gavin M, Grossman SA. Acute Myocardial Infarction. [Updated 2021 Aug 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459269/]

15. Agarwala A, Michos ED, Samad Z, Ballantyne CM, Virani SS. The Use of Sex-Specific Factors in the Assessment of Women's Cardiovascular Risk. Circulation. 2020;141(7):592-599. doi:10.1161/CIRCULATIONAHA.119.043429

16. https://www.heart.org/

17. Pepine CJ, Ferdinand KC, Shaw LJ, et al.; ACC CVD in Women Committee Emergence of Nonobstructive Coronary Artery Disease: A Woman's Problem and Need for Change in Definition on Angiography. J Am Coll Cardiol. 2015. October 27; 66 17: 1918– 33.