Pub Date: Monday, Sep 21, 2020
Author: Garima Sharma, MD, FACC (1), Roger S. Blumenthal, MD, FACC, FAHA (1) and Laxmi S. Mehta MD, FACC, FAHA (2)
Affiliation: 1. Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Division of Cardiology, The Johns Hopkins University School of Medicine 2. Division of Cardiology, Department of Medicine, The Ohio State University
Cardiovascular disease (CVD) is the leading cause of death for women (and men) in the United States (US), killing 385,943 women in in 2017—or about 1 in every 4 female deaths.1 It is also the leading cause of death for Black and White women in the US. Among American Indian and Alaska Native women, CVD and cancer cause roughly the same number of deaths each year. For Hispanic and Asian or Pacific Islander women, CVD is second only to cancer as a cause of death.2
This trend is even more concerning while accounting for the racial/ethnicity backgrounds and age of this patient population. According to the 2020 American Heart Association (AHA) Heart Disease and Stroke statistics, about 1 in 16 women age 20 and older (6.2%) have coronary heart disease: 6.1% White, 6.5% Black women, 6.0% Hispanic, 3.2% Asian women.3
Sex Based Differences in CVD Burden
Over the past 3 decades, we have learned that conventional coronary risk factors impact women differently (and generally more adversely) than men and we have identified a sizeable number of risk factors that are unique to or predominant in women.4-6 Admittedly, our understanding of anatomy, physiology and symptomatology of coronary heart disease in women has improved tremendously. Men are more likely to have plaque rupture associated with sudden onset of symptoms as compared with women in studies of plaques in acute coronary syndrome (ACS) patients. Women are still more likely to present with plaque rupture than plaque erosion in the setting of an ACS; however, autopsy studies have shown the frequency of plaque erosion is higher in younger patients and in women.7, 8
In spite of higher risk factor burden, atherosclerotic plaque burden in women presenting with ACS is different than men; women present with fewer non-culprit lesions, have smaller luminal area, thinner fibro-atheroma, and less dense calcium, necrotic core volume, and fibrofatty tissue as compared with men.9 In addition, there is growing recognition of sex specific risk factors for CVD, particularly those related to pregnancy and hormonal influences such as premature menopause.5, 10 Adverse pregnancy outcomes such as preeclampsia, and eclampsia, gestational hypertension, preterm delivery, small for gestational age infant and gestational diabetes increase the risk of future CVD for women.11-13
There are also certain CVD risk factors that are female predominant, particularly autoimmune disorders, including rheumatoid arthritis, systemic lupus erythematosus, and scleroderma. Breast cancer and its treatment increase the risk of CVD, manifesting just 7 years after the breast cancer diagnosis.14, 15 Due to these myriad differences, the scientific community recognizes that efforts should be made towards early identification of these risk factors and targeted primordial prevention interventions to reduce the excess burden of CVD in women and men. The 2019 ACC/AHA Primary Prevention of Cardiovascular Disease Guideline has also stressed the importance of incorporating a pregnancy history while assessing the CVD risk of women and addressing the sex-specific risks in our assessment.16
AHA Advocacy to Improve Awareness of CVD in Women
Since 1997, the AHA has conducted national surveys among US women to evaluate trends in awareness of CVD risk among women from differing racial/ethnic and age groups, as well as knowledge of CVD symptoms and preventive behaviors/barriers.17, 18 Between 1997 and 2012, the rate of CVD awareness as the leading cause of death nearly doubled (56% versus 30%; P<0.001). The rate of awareness among Black and Hispanic women in 2012 (36% and 34%, respectively) was similar to that of White women in 1997 (33%).
In 1997, women were more likely to cite cancer than CVD as the leading killer (35% versus 30%), but in 2012, the trend reversed (24% versus 56%). In 2013, about 15 years after focused interventions and advocacy campaigns, there were some encouraging trends; the awareness of atypical symptoms of CVD improved since 1997, but there was still a persistent racial/ethnicity knowledge gap in Black and Hispanic women.18
In this issue of Circulation, Cushman et al present the 2019 survey data on the 10–year differences in women’s awareness related to coronary heart disease. In addition to knowledge, behaviors, and awareness of coronary heart disease symptoms, the survey was exclusively online and included information on underlying CVD risk factors. Women were asked about the use of a technology-enabled device to monitor or improve health making this survey contemporary and reflective of current digitalization of patient care.
The survey should be commended for the very high rate of response (85%) and including a greater proportion of non-Hispanic Black and non-Hispanic Asian respondents than in 2009. The largest proportion of women reported incomes > $100,000, followed by the next largest < $35,000, making this sample population more representative of the dichotomous income disparity in the US today.
The findings of the survey raise some important considerations for clinicians, health policy analysts, and researchers. First, the recognition of heart disease as the leading cause of death (LCOD) in women declined as compared to 2009, (43.7% vs. 64.8%, p<0.05), particularly in the non-Hispanic Black, Hispanic and non-Hispanic Asian women (58%, 59% and 67% less likely respectively). This decline in awareness was most evident among women aged 25-34 years. Here in lies the most important consideration from the manuscript. While this age group has the lowest incidence of CVD, it stands to benefit the most from early preventive and educational strategies. Education and awareness in this group can change their health trajectory tremendously.
Second, it is alarming that the knowledge of heart disease as the LCOD decreased in those with CVD risk factors, including women with prior heart disease and stroke. Women with hypertension had 30% lower awareness than women without hypertension, while awareness in those with diabetes continued to be as low as 2009. Lastly, the recognition of a spectrum of symptoms related to heart attack also declined, where for nearly every heart attack symptom, fewer women in 2019 identified the possible warning sign as compared to 2009.
This concerning marked decline in awareness of heart disease as the LCOD especially in racial/ethnic minorities despite decades of educational and advocacy interventions, should spark a new conversation around providing culturally sensitive care and education particularly to those from the most vulnerable of socio-economic backgrounds. Clearly, understanding the impact of social determinants of health on cardiovascular disease risk factors is an important first step.
Sex based Disparities in CVD
The results of this survey have to be taken into context with the known sex disparities in CVD. Despite widespread efforts for the AHA and the National Institutes of Health and National Heart Lung Blood Institute to consistently examine and publish scientific data through a sex and gender perspective, some striking disparities in CVD management continue to persist. When presenting with an ACS, younger women, are less likely to receive guideline-recommended therapies, timeliness of care, or diagnostic and invasive therapies resulting in worse outcomes in comparison with men.7, 19
Recent literature has suggested a sex disparity, with women receiving bystander CPR at notably lower rates than men.20, 21 Specifically, only 39% of women receive bystander CPR in out of hospital cardiac arrests as compared to 45% of the men;21 this difference in resuscitation contributes to overall survival, where men were found to have better odds of survival to hospital discharge when compared with women (odds ratio, 1.29; 95% CI, 1.17–1.42; P<0.01).21
Additionally, there is also a sex disparity in the management of advanced heart failure. Although, women with heart failure with reduced ejection fraction (HFrEF) live longer than men, women with HFrEF are less likely to receive evidence-based therapies, including medications, implantable cardioverter defibrillators, ventricular assist devices, and heart transplant, despite improved survival and quality of life when receiving these therapies. Women live longer than men with HFrEF, although these additional years are of poorer quality with psychological and physical disability.22 Despite a clear mortality benefit seen with cardiac resynchronization therapy (CRT) in women, this life-saving therapy is still significantly underutilized in women. Additionally, the majority of the patients enrolled in the ICD and CRT trials are men, making determination of sex-specific mortality and clinical outcomes has often not been possible owing to the low numbers of women enrolled.23-25
Data from the PINNACLE registry, showed that women were significantly less likely than men to use any anticoagulation overall (56.7% versus 61.3%; P<0.001) and at all levels of CHA2DS2‐VASc score (adjusted risk ratio 9% to 33% lower, all P<0.001).26 Thus, women continue to be under-studied, under-represented in clinical trials, and under-treated even though they generally live about 7 years longer than men do. These disparities have persisted in our clinical practices and behoove us to continue to escalate efforts towards studying and examining sex based disparities in cardiovascular care.
A Call to Action
Knowledge of CVD among women continues to be suboptimal despite advances made in the last 20 years as a result of educational and public awareness efforts. We need to re-examine the factors that have long been established as reasons for this sex gap including decreased physician awareness of CVD risk in women, lack of focused curricula in cardiovascular training on sex specific risk factors for CVD, absence of competencies requirements in cardiovascular disease in pregnancy, and persistent knowledge gaps within the medical community in understanding the pathophysiological differences in CVD in women. These factors need to be addressed by renewed commitment of our scientific community and advocacy groups.
Our volunteer science organizations and government agencies should continue their strategically focused research networks in women’s cardiovascular health, and publish scholarship in sex based research. Medical institutions need to establish Preventive Cardiology programs where women and men with high 10-year and 30-year estimated ASCVD risk are seen by multidisciplinary teams, improving the educational experience of our trainees. Medical schools need to develop curricula that engage in a broader discussion of the impact of race/ethnicity, implicit bias, and social determinants of health on disparities in cardiovascular disease in women and men.
It is time to provide culturally competent care and social determinants of health must be considered in a complex equation, including known risk factors, poor health literacy, acculturation and economic challenges, which put under-represented minorities who live in at-risk communities at greater risk for disease. Our guidelines need to consistently examine the evidence for diagnostic and therapeutic adherence in CVD management in women.
Our clinical guidelines need to be translated into routine clinical practice. Lastly, creating public awareness and improving the sex disparities in cardiovascular care is a complex equation and will not happen overnight. This will need social reengineering and renewed efforts to educate women, particularly young women.
Finally, all of our female and male patients, as well as their clinicians, should remember the ABC’s of Prevention.27 A: Assessment of Risk – lifetime and 10-year ASCVD risk and take into account risk enhancing factors; Antithrombotic Rx- aspirin is rarely indicated in primary prevention but in secondary prevention the decision is between single vs dual antiplatelet therapy. A CHA2DS2-Vasc score can identify which patient should be considered for anticoagulant therapy; B: Blood Pressure – normal is < 130/80 mmHg; C: Cholesterol: optimize lifestyle therapy for all and statin therapy is first line pharmacologic therapy in those that qualify for treatment; C: Cigarette Cessation: both combustible and electronic cigarettes; D: Diet/Weight – need to make steady progress and review at each patient visit; D: Diabetes Prevention/Management; and E: Exercise. Knowing one’s ABC’s of Prevention is a key component of achieving good cardiovascular health.
Cushman M, Shay CM, Howard VJ, Jiménez MC, Lewey J, McSweeney JC, Newby LK, Poudel R, Reynolds HR, Rexrode KM, Sims M, Mosca LJ; on behalf of the American Heart Association. Ten-year differences in women’s awareness related to coronary heart disease: results of the 2019 American Heart Association National Survey: a special report from the American Heart Association [published online ahead of print September 21, 2020]. Circulation. doi: 10.1161/CIR.0000000000000907
- Centers for Disease Control and Prevention, National Center for Health Statistics. Underlying Cause of Death 1999-2018 on CDC WONDER Online Database, released in 2020. Data are from the Multiple Cause of Death Files, 1999-2018, as compiled from data provided by the 57 vital statistics jurisdictions through the Vital Statistics Cooperative Program. Accessed at http://wonder.cdc.gov/ucd-icd10.html on Aug 21, 2020 7:37:38 PM.
- Heron M. Deaths: Leading Causes for 2017. National vital statistics reports : from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System. 2019.
- Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Chang AR, Cheng S, Delling FN, Djousse L, Elkind MSV, Ferguson JF, Fornage M, Khan SS, Kissela BM, Knutson KL, Kwan TW, Lackland DT, Lewis TT, Lichtman JH, Longenecker CT, Loop MS, Lutsey PL, Martin SS, Matsushita K, Moran AE, Mussolino ME, Perak AM, Rosamond WD, Roth GA, Sampson UKA, Satou GM, Schroeder EB, Shah SH, Shay CM, Spartano NL, Stokes A, Tirschwell DL, VanWagner LB, Tsao CW, American Heart Association Council on E, Prevention Statistics C and Stroke Statistics S. Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association. Circulation. 2020;141:e139-e596.
- Garcia M, Mulvagh SL, Merz CN, Buring JE and Manson JE. Cardiovascular Disease in Women: Clinical Perspectives. Circ Res. 2016;118:1273-93.
- Agarwala A, Michos ED, Samad Z, Ballantyne CM and Virani SS. The use of sex-specific factors in the assessment of women's cardiovascular risk. Circulation. 2020.
- Gulati M. Improving the Cardiovascular Health of Women in the Nation: Moving Beyond the Bikini Boundaries. Circulation. 2017;135:495-498.
- Mehta LS, Beckie TM, DeVon HA, Grines CL, Krumholz HM, Johnson MN, Lindley KJ, Vaccarino V, Wang TY, Watson KE, Wenger NK, American Heart Association Cardiovascular Disease in W, Special Populations Committee of the Council on Clinical Cardiology CoE, Prevention CoC, Stroke N, Council on Quality of C and Outcomes R. Acute Myocardial Infarction in Women: A Scientific Statement From the American Heart Association. Circulation. 2016;133:916-47.
- Chandrasekhar J and Mehran R. Sex-Based Differences in Acute Coronary Syndromes: Insights From Invasive and Noninvasive Coronary Technologies. JACC Cardiovasc Imaging. 2016;9:451-64.
- Lansky AJ, Ng VG, Maehara A, Weisz G, Lerman A, Mintz GS, De Bruyne B, Farhat N, Niess G, Jankovic I, Lazar D, Xu K, Fahy M, Serruys PW and Stone GW. Gender and the extent of coronary atherosclerosis, plaque composition, and clinical outcomes in acute coronary syndromes. JACC Cardiovasc Imaging. 2012;5:S62-72.
- Sharma G, Lindley K and Grodzinsky A. Cardio-Obstetrics: Developing a Niche in Maternal Cardiovascular Health. J Am Coll Cardiol. 2020;75:1355-1359.
- Lane-Cordova AD, Khan SS, Grobman WA, Greenland P and Shah SJ. Long-Term Cardiovascular Risks Associated With Adverse Pregnancy Outcomes: JACC Review Topic of the Week. J Am Coll Cardiol. 2019;73:2106-2116.
- Mehta LS, Warnes CA, Bradley E, Burton T, Economy K, Mehran R, Safdar B, Sharma G, Wood M, Valente AM, Volgman AS, American Heart Association Council on Clinical C, Council on Arteriosclerosis T, Vascular B, Council on C, Stroke N and Stroke C. Cardiovascular Considerations in Caring for Pregnant Patients: A Scientific Statement From the American Heart Association. Circulation. 2020;141:e884-e903.
- Sharma G, Zakaria S, Michos ED, Bhatt AB, Lundberg GP, Florio KL, Vaught AJ, Ouyang P and Mehta L. Improving Cardiovascular Workforce Competencies in Cardio-Obstetrics: Current Challenges and Future Directions. J Am Heart Assoc. 2020;9:e015569.
- Bradshaw PT, Stevens J, Khankari N, Teitelbaum SL, Neugut AI and Gammon MD. Cardiovascular Disease Mortality Among Breast Cancer Survivors. Epidemiology. 2016;27:6-13.
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