Cardiovascular disease is the leading cause of death of both women and men. However, women are unnecessarily suffering and dying from heart disease.
In the light of the month with International Women’s Day, it is safe to say that our generation is getting close to gender equality – equal pay, rights and gender roles. But, when it comes to health, women are drastically and unknowingly suffering from heart failure. Women are at a greater risk than men of not having heart disease diagnosed and treated and due to their role as mothers, their pregnancy, menopause, and hormonal changes put them at a higher risk for heart attacks. For example, “1/3 of young women with premature heart attacks have a history of pregnancy disorders, such as gestational diabetes or hypertension that doubles their risk for heart disease.”
‘One of the major problem lays with the younger women’ states Dr. Paula, head of the cardiology division at Women’s College in Toronto. Interviewed on the issue of heart disease and women, Dr. Paula said that they are "observing heart disease in the younger women – women less than 60 – we are actually seeing the rates of heart disease and death going up”. She also adds that “these women if they have a heart attack, are morel likely than men to have a second heart attack or die within 12 months of that heart attack.” (Paula, CBC news, Feb 2018)
In addition to this, women are most likely not aware or expecting to experience heart disease symptoms and when they do, they do not report it. For example, a man with chest pain would immediately seek medical attention but most women experiencing chest pain would brush it off and blame it on the soreness of their breasts due to missed or an upcoming menstrual cycle.
Figure 1: Percentage of deaths in hospital from those admitted with heart attack, CIHI. ( This image was taken from the following article: www.cbc.ca/news/health/heart-disease-women-1.4513036
Looking at the figure 1, we can see that at a very young age (20 – 29), women are already experiencing heart attacks. The percentage of heart attacks in women exponentially grows indirectly to men. According to the Heart & Stroke organization, early heart attacks are missed in about 78% of women and when a woman has a heart attack she is less likely to have major plaques, rather she possesses more diffuse disease that involves smaller blood vessels – this is hard to interpret with diagnostic tests in women.
In the article, Proceedings from the Scientific Symposium: Sex Differences in Cardiovascular Disease and Implications for therapies, the authors pointed out that atherosclerosis is qualitatively and quantitatively different in men and women; women demonstrate more plaque erosion and more diffuse plaque with less focal artery lumen intrusion. From this, they concluded that the evaluation of Cardiovascular Disease strategies that include devices should be used to explore differing anatomical shapes and surfaces as well as differing drug coating and eluding strategies to cut down the misinterpretations.
Some social factors also place women at great risks.
Women from different ethnic, poor economical and financial backgrounds are more vulnerable to heart disease and are more at risk than those that have access to health care, transportation and education. This is also the case for indigenous people living in reserves – these areas lack proper cardiac specialists, causing their symptoms to go untreated. We can also look at the increasing percentage of refugees that arrived in Canada in the past 2-3 years, their lack of education in the Canadian health system, poor language skills and access to transportation also place them at a higher risk of getting their symptoms treated.To find the underlying mechanism of cardiovascular disease, gender, mechanistic pathways, and sociological factors needs to be evaluated.
Sex differences in cardiovascular disease outcomes exist, but knowledge of the mechanistic pathways underlying sex differences is limited. With mechanistic pathways, it is essential also to evaluate socio-economical factors that may contribute to an individuals’ risk for heart disease.
The institute of medicine in 2001 published a monograph, Exploring Biological Contributions to Health: Does Sex Matter?
The IOM shared three conclusions (1) sex does matter and should e considered when designing and analyzing studies in all already of health- related research, (2) the study of sex has predominately observational research, and the next step is to study of mechanisms and therapies related to sex differences when present, and (3) barriers to the advancement of knowledge about sex differences in health and illness must be eliminated.
Major sex differences in cardiovascular disease were pointed out in the article ‘Proceedings from the Scientific Symposium: Sex Differences in Cardiovascular Disease and Implications for therapies"
1. Sex Differences in CVD Prevalence and Risk Factors
Reproductive hormones play a role in cardiovascular disease in women. Low estrogen levels due to the disruption of ovulatory cycling in premenopausal women contribute to greater obstructive coronary artery disease (CAD). Moreover, sex hormones alternations have been associated with polycystic ovary syndrome, which is also a risk factor for individuals suffering from Type 2 Diabetes and the metabolic syndrome including hyperlipidemia, obesity and hyperglycemia. This suggests that the imbalance of endogenous sex hormones in women accelerated cardiovascular risk.
2. Sex Differences in Atherosclerosis in Response to Minimal Injury
The patho-anatomic substrate for coronary thrombosis difference between men and women. In men, 80% of coronary thrombi tend to occur due to plaque rupture, whereas in women, 20-40% of coronary thrombi occur on an intact atherosclerotic plaque with superficial atherosclerotic erosion. Basically, plaque erosion is observed in younger women – plaque erosion happens when there is thrombus over a base-rich in smooth muscle with proteoglycan-rich matrix. The plaque erosion is a common finding in sudden cardiac death in younger women. Whereas the plaque rupture is commonly found in men and older women – this is observed by a fibrous cap overlapping a necrotic core infiltrated by foamy macrophages.In conclusion, atherosclerosis is qualitatively and quantitatively different in women and men; women demonstrate more plaque erosion and more diffuse plaque with less focal artery lumen intrusion.
Figure 2: The difference between plaque erosion and rupture.
3.Sex Differences in Bone and Vascular Cellular and Tissue Engineering
Studies investigating the response of male and female cartilage cells to estrogen show that even though both sexes have receptors for estrogen, some of the response for estrogen is only seen in females. In contrast, although both men and women have testosterone receptors, male cartilage show a response to testosterone receptors that is not observed in female cells. Moreover, in response to the most prominent estrogen found in humans, estradiol, female cells produce large amounts of Transforming Growth Factor-β (TGF- β) compared to male cells, which do not respond to estrogen exposure. Huard’s group demonstrate that muscle derived mesenchymal stem cells (MScs) from females differentiate easily into female recipients and less into males. Male cells were less effective in differentiating into females and the less engrafted of muscle derived cells is that of the male. To conclude, these results point out the importance of sex differences in stem cells that are more complicated than a male to female difference.
4. Sex Difference in Medication Response and Pharmacogenetics
Secondary prevention studies of aspirin including both sexes demonstrate CVD prevention in both men and women. An all female low dose study showed that low dose aspirin did not prevent first heart attack yet prevented first stroke in women, conversely an all male physician study concluded that aspirin prevented first heart attack but not first stroke. The observed sex difference in aspirin medicinal trials suggest that there needs to be a re-examination of the pathophysiology sex differences in CVD. Women and men can have differences in pharmacological therefore, sex specific pharmacogenomic studies should be implemented in medicinal trials and pharmacological development.
There have been some major points summarizing the need to re-evaluate gender in Cardiovascular Disease. A range of observational data proves that sex differences in cardiovascular disease exist. However, mechanistic knowledge, cardiovascular pathophysiology understanding, and therapeutics is limited. Future research in cardiovascular disease should thrive to examine sex-specific mechanistic and metabolic pathways to improve the overall health of women suffering from CVD.
References
Bairey Merz CN(1), Mark S, Boyan BD, Jacobs AK, Shah PK, Shaw LJ, Taylor D, Marbán E.Proceedings from the scientific symposium: Sex differences in cardiovascular disease and implications for therapies.2010 Jun;19(6):1059-72.