I’ve noticed that with statistics and data projects it doesn’t come without learning about the topic, which I find quite interesting. In this particular case, learning a bit about the sex differences and cardiovascular and pulmonary health was the topic of interest in this case. Below is what I learnt about sex differences.
Sex Differences
There are both male and female specific biological conditions that affect cardiovascular and pulmonary health. Some of the biological processes specific to women occur at different stages of their life such as menarche, contraceptive pill, pregnancy and menopause. But beyond these biological differences there are also societal expectations, interaction with peers and other aspects covered by the wider term of gender that all affect cardiovascular health. Hypertension prevalence differs between the sexes. Hypertension is more prevalent in men until the fifth decade of life then hypertension becomes more prevalent in women. [1] Women have a similar hypertension prevalence as men in the 45-64 age group but have a higher prevalence than men for the above 65 years age group. [2]
Traditionally women have been under represented in cardiovascular trials which form the basis of guide line for treatment. This leads to sex differences in treatment. There has been an increase in spending on research of sex difference in hypertension from $0.5 million in 1991 to $18.3 million in 2014.[1, 2] In general, more women in studies has improved recent CVD prevention trials. [2] In [10] it is seen that gender research in CVD has results in nearly a 30% decline in the number of women dying from CVD. In 2014 was the first time since 1984 that more men than women died of CVD in the US. This decreased mortality rates due to ischemic heart disease, (IHD), has increased awareness, greater focus on women and their IHD risk and application of evidence-based treatments for established IHD. [10]
Hypertension is associated with increased risk of cardiovascular diseases (CVD) including stroke, heart failure and myocardial infarctions. In the US, the difference in hypertension prevalence can be seen with respect to gender where the overall prevalence being higher for women compared to men. By 2015, the worldwide prevalence of hypertension among women is expected to exceed that of men. [2]
Intensive pharmacological treatment for hypertension may also result in increased side effects and women may experience more adverse events than men. Gender specific conditions such as menopause and related treatments which may be associated with increase salt-sensitivity, endothelial dysfunction and visceral adiposity may be a possible cause of the disparity. Other traits that were noticed to be sex specific were women displayed lower pack-years of smoking compared to men, they were older in age, had a higher systolic blood pressure, higher body mass index and were more likely to live alone. Women also had a lower prevalence than men to modifiable factors such as use of statin and aspirin, both of which have been associated with lower rates of CVD in both sexes. [2]
Ischemic heart disease is the leading cause of morbidity and mortality in women in the US. It accounts for one third of all female deaths globally and affects nearly 48 million women in the US. There are two aspects to women’s health: sex differences due to biological factors; gender differences which are affected by a broader social, environmental and community factor.[10] Some of the persistent disparities in CVD among subgroups of women include women who are socially disadvantages because of race, ethnicity, income level and educational attainment. Women with IHD experience worse outcomes compared to men and younger women, (< 55 years). Men and women share more traditional risk factors for IHD, but there are additional sex specific/based risk factors that are shown to be important to women. These include, menopause shows a significant increase in C VD risk in women >= 55 years and equals the risk of men >= 45 years; estrogen loss has a negative effect on arterial function and adversely alters the cholesterol profile; menopause increases the prevalence of metabolic syndrome and truncal obesity.
In [12], Boczar and Coutino consider aneurysms and sex differences. There is more evidence showing that aneurysm behaviour differs based on sex. Most types of aneurysms are more common in men but growth rates and outcomes are worse in women. The potential underlying differences in the arteries of men and women may contribute to the difference in aneurysm prevalence and outcomes. Female specific outcomes are well described in cardiovascular conditions such as coronary artery disease, mitral valve pathologic conditions and heart transplantation. Some of the CVD sex differences observed outside the heart include more evidence showing that aneurysm behaviour differs based on sex. This may include differences in the hormonal milieu and underlying anatomic and structural difference in the arterial beds between men and women. The UK Small Aneurysm Trial showed that female sex was an independent risk factor for abdominal aortic aneurysms (AAA); the rupture rates in women was three times higher than in men despite smaller initial aneurysm diameter.
Arterial hypertension is a known risk factor for thoracic aortic aneurysms (TAA). It is also a known risk factor for TAA formation and aneurysm growth. TAA’s growth is twice as fast in women as in men. From [12] there is a potential underlying difference in the arteries and biology of men and women that contributes the pathophysiology. Studies have suggested a difference in the hormonal make up and underlying anatomy in the arterial beds with estrogen playing an important protective role in vascular health and estrogen withdrawal in the postmenopausal state potentially adds to aneurysm-related risks. [12]
Globally CVD is the number one killer of women and one third of female deaths are due to IHD and stroke. [13] CVD has historically been referred to as a man’s disease but this is largely due to clinical trial evidence being based on males thus affecting our treatment of CVD.
The definition of sex and gender is as follows: Sex is determined by biological attributes of humans and animals including physical features, chromosomes, gene expression, hormones and anatomy. Gender is determined by socially-constructed roles, behaviours, expressions and identities of girls, women, boys, men and gender diverse people. [13] The Framingham Heart Study began in the 1940s to examine the epidemiology of CVD and identify patient characteristics that contributes to the development of heart disease. Through this study it was identified that age, sex, smoking, high blood pressure, high blood cholesterol and diabetes were major cardiac risk factors. The Acute Myocardial Infarction (AMI) study held in 52 countries (INTERHEART study), identified 9 modifiable risk factors that were shown to explain more than 90% of the risks for AMI in men and women. Modifiable means that if these factors were eliminated then the risk of AMI could be reduced by more than 90%. These factors were found to be, smoking, hypertension, abnormal lipid, diabetes, abdominal obesity, high risk diet, psychosocial factors, lack of physical activity, absence of alcohol use compared to moderate use. Diabetes and smoking were shown to have a strong association with CVD developing in women than in men. [13]
Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation associated with chronic inflammation of the bronchi, pulmonary parenchyma and vascular system. It is an irreversible, diffuse, peripheral small airway disease. The irreversibility if mostly due to fibrosis and stenosis of the small airways caused by chronic inflammation. Smoking is a major risk factor for COPD. The increase of incidence of COPD in women in recent years has surpassed that in men. This may be related to the increased smoking rate in women; speculation that women may be more susceptible to the effects of smoking and have a higher risk of smoking induced pulmonary function impairment. While smoking is a major cause of COPD, COPD has a higher incidence in men than women most likely due to the fact that more men smoke. While women usually smoke less than men, more women develop airflow limitations symptoms. Smoking women experience more sever lung damage than smoking men. [3]
In [6] Ekstrom et al. considered the sex difference in breathlessness. Since breathlessness is usually associated with major adverse health outcomes is twice as common in women as in men. Ekstrom et al. looks at whether this is due to their absolute lung volume. Some of the prevailing yet unproven possibilities of the differences in breathlessness between men and women is due to differences in the following areas: anxiety or depression; sociocultural differences in symptom report; hormonal changes related to menopause; women have smaller airways than men matched for lung size, knowns as dysanapsis. The results of the paper showed that people with breathlessness had a higher smoking exposure; higher body mass index (BMI), lower absolute and relative lung function; higher rates of asthma; chronic bronchitis; anxiety and depression. The other factors that were associated with breathlessness were, age, number of pack year of smoking, chronic airway limitations, comorbid diagnosis of asthma, chronic bronchitis, anxiety and depression. Upon a secondary analysis, being taller was associated with having less breathlessness. This association was the similar for men and women. The sex difference in breathlessness was not decreased when adjusting for anxiety, depression, menopause or dysanapsis. In general, there is a higher prevalence of breathlessness in women in relation to their smaller absolute lung volumes. [6]
Higher breathlessness may be exacerbated by smoking. Sorheim et al. in [8] examined how smoking behaviour and resulting lung function reduction differed by gender. The number of women with COPD is increasing and for the first time the number of deaths from COPD in women has surpassed those in men in the USA. A possible reason for this development is that the differences in smoking behaviour in men and women is changing. Some differences between men and women are women are more likely to report a history of asthma compared to men while more men report occupational exposure to dust or gas. Females with COPD have lower educational levels compared to males. The gender effect seems most pronounced when the level of smoking exposure is low, decreasing in magnitude as the number of pack years of smoking increases. After puberty, the number of cases of asthma is higher in women than men. It was also seen that women are less likely to be diagnosed with COPD than men. Other possible reasons for gender differences include occupational exposure, second-hand smoke, inhalation patterns, selection bias and reporting bias, work related exposure to dust or gas was higher in men than women. The results of Sorheim et al. found that female sex was associated with lung function reduction and the disease COPD was more severe in people with early onset COPD or low smoking exposure.[8]
Pulmonary arterial hypertension (PAH) is characterized by an elevated resting mean pulmonary arterial pressure of ≥25 mmHg in the presence of a normal pulmonary capillary wedge pressure of ≤ 15 mmHg. Most PAH registries report and overall female predominance of 2-4 over men. [4] From the findings of Batton et al. more studies to analyze data on individual PAH subgroups by sex is needed.
In the past COPD was considered a disease that mainly affected elderly men. This was a reflection of the high prevalence of smoking among men. However this is changing and COPD is now more commonly seen in women. The prevalence of smoking in women has grown in particular in developing countries. In general, women smoke less than men however, COPD Is more commonly seen in women. This suggests that women may be more susceptible to developing COPD in response to cigarette smoke than men. Women with severe COPD have a higher risk of hospitalization and death from respiratory failure and comorbidities. Some possible reasons for the greater susceptibility in women to develop COPD may be, relatively smaller airways for females than males for same lung volume surface; metabolism of cigarette smoke may be different in women due to sex difference; patterns between men and women may differ. [5]
Maggi and Torre [7] look at sex differences in a more general health setting. They noted that because the liver is sexually dimorphic, it may be relevant to explain the lower susceptibility to hepatic diseases and liver-derived metabolic disturbances such as cardiovascular diseases.
Casey and Mumma in [11] consider sex, race and insurance status differences with regards to hospital treatment following out of hospital cardiac arrest (OHCA). In the US, OHCA is the leading cause of death from CVD with <10% of 350 000 adults who suffer from OHCA each year surviving to hospital discharge. They also showed that female sex was associated with worse neurologic recovery; decreased odds of cardiac catheterization; decreased odds of treatment at a 24/7 PCI centre (percutaneous coronary intervention, (PCI)); increased odds of receiving a do not resuscitate (DNR) order within one day of admission. Among the results, female sex was a predictor of less aggressive treatment and worse clinical outcomes for patients admitted following OHCA. What was found relating to the female sex was that female patients were less likely to receive guideline-recommended treatments for OHCA in pre hospital settings; sex differences in pathophysiology of ischemic heart disease and the presence of ST-segment elevation myocardial infarction (STEMI), heart attack, may contribute to the lower rates of cardiac catheterization in women. Women underwent cardiac catheterization at lower rates than men. [11]
Regiz-Zagrosek considers the gender and sex differences in health in [9]. She remarks that the sex and gender is holding back more efficient health care as gender-based prevention measures or therapies are probably more effective than the one-size-fits-all approach to health. Sex influences health by modifying behaviour. For example, testosterone causes aggressive behaviours associated with risk-seeking and neglecting personal health. Gender related behaviour can modify biological factors and thus health. For example exposure to stress, environmental toxins, poor nutrition or lifestyle choices can induce genomic and epigenetic modifications. These modifications being different in women and men. Gender-sensitive medicine isn’t the same as considering the specific needs of women such as during pregnancy or menopause. The aim of gender medicine is to include biological and socio-cultural dimensions. More data is needs in particular situations. For example, more data on men in regards to osteoporosis and depression while more data for women in the areas of CVD. Sex and gender affect a wide range of physiological functions and disorders including cardiovascular and pulmonary diseases. Sex and gender difference in CVD: The incidence of myocardial infarctions is in decline worldwide except in young women. This group faces greater risks of CVD due to lifestyle changes such as smoking, greater job stress. This group has a higher rate of mortality after the first myocardial infarction and coronary bypass graft surgery than men in the same age group. However, men in all age groups have a higher risk of ischaemic sudden death. The psychological factors are a greater factor in women for myocardial infarctions. Heavy exercise is the more common cause in men for myocardial infarctions. A main cause of re-infarction in women is social stress. Women receive less guideline based diagnosis and less invasive treatment of myocardial infarction than men due to the habits of physicians. The average age of female sufferers of coronary artery disease is about 10 years older than male sufferers but women live 6-8 years longer than men. Hypertension is more common in young men than young women however this changes as men and women age. The incidence of hypertension increasing in women after menopause. Hypertension is one of the great risk factors of heart failure in women than in men. [9] Diabetes increases the risk for coronary artery diseases to higher degree in women. It is also associated with greater risk of death after myocardial infarction in women.
There are also clear gender differences in pulmonary diseases. There is higher incidence of asthma in young boys but these changes in young and older adults. In adulthood, women seem to be mostly affected by asthma. The smoking prevalence in women is increasing as thus the sensitivity to tobacco toxicity is rising and will soon reach the same level as men. In Germany it is shown that women are less frequently treated with evidence-based therapies. This is most pronounced when the physician is male and dealing with CVD and diabetes. In Europe it is observed that women receive less echocardiography, less angiography to diagnose coronary artery disease and less percutaneous coronary intervention of bypass surgery if needed. The justification of this lack of treatment is the higher age of women. However, this neglects the fact that on average women live longer than men. So, older women are similar to men 6-8 years younger than them biological age and life expectancy. [9]
The sex differences between men and woman are great and worth considering. For example, the limited mobility of older women as they own less cars. Women have constraints on their time due to being the primary care giver in a family. They have different preferences in exercise. In terms of disease management, ischaemic heart disease, symptoms of myocardial infarction, sensitivity to some cardiovascular drugs, different forms of prediabetes in women are not adequately considered. However, the female sex as a risk factor is taken into account by physicians in the management guidelines of atrial fibrillation as is guidelines for CVD during pregnancy resulting in focused treatment specific to women. [9]
Other sex differences that play a factor are:
Women are on average shorter in stature; kidney function between men and women are different; drug reabsorption and metabolism by hepatic enzymes and excretion causing difference in parmocokinetics. Ion channels in kidney and heart tissue are different in men and women possibly causing sex-specific effects of drugs that are used to modify kidney function or heart rhythm.
Many studies have come to the conclusion that women are still no sufficiently included in mixed-sex CV trials to properly reflect the disease prevalence among the general population. There was a study of 300 new drugs between 1995-2005. The study showed that there are substantial differences in how the drugs are absorbed, metabolized and excreted by men and women. There were also no sex-specific dosage recommendations on the labels. The may be a contributing factor as to why women are 1.5-2 times more likely to develop adverse reactions to prescriptions drugs than men. [9]
While gender-medicine is positive step forward there are obstacles against promotion of gender medicine. It has been mistaken for feminism; attached as “biologistic” and assumed to generate higher costs by doubling the amount of animal work and increasing the number of patients needed for clinical studies without adequate payback. None of this is true. The aim of gender medicine is to improve the health of women and men considering sociological aspects and biological facts.[9]
Glossary
Hypertension is an abnormally high blood pressure’ a state pf great psychological stress. Hypertension is another name of high blood pressure. It can lead to severe complications and increases the risk of heart disease, stroke and death. What is blood pressure? It is the force exerted by the blood against the walls of the blood vessels. The pressure depends on the work being done by the heart and the resistance of the blood vessels. Medically it is defined as 130 over 80 millimetres of mercury (mmHg). Hypertension and heart disease are global health concerns. [14]
A myocardial infarction is more commonly known as a heart attack. This occurs when the blood flow decreases or stops to part of the heart causing damage to the heart muscle. Common symptoms include chest pain, discomfort which may travel into the shoulder, arm, back, neck or jaw. [15]
Menarche is the time when menstruation first begins. During this time menstruation may be irregular and unpredictable. This time is also known as puberty. [16]
An aneurysm is an enlargement of an artery caused by weakness in the arterial wall. Usually no symptoms but a ruptured aneurysm can lead to fatal complications. [17]
ST-segment elevation myocardial infarction (STEMI) is the term used to describe a classic heart attack. It is one type of myocardial infarction where part of the heart muscle (myocardium) has died due to obstruction of the blood supply. ST-segment refers to the flat section of an electrocardiogram (ECG) reading. It represents the interval between jagged heartbeats. When a person has a heart attack, this part will appear abnormally elevated. [18]
Cardiac catheterization is a procedure to examine how well your heart is working. This is done by inserting a thin, hollow tube or catheter, into a large blood vessel that leads to the heart. It is performed to find out if there is any disease in the heart muscle, valves or coronary arteries. It may also measure the pressure and blood flow in the heart. [19]
Sex differences are based on biological factors. These include reproductive function, concentration of sexual hormones, expression of genes on X and Y chromosomes and the higher percentage of body fat in women. [9]
Gender is associated with behaviour, lifestyle and life experience. [9]
Comorbidity is the coexistence of two or more chronic diseases or conditions in a patient. [20]
References
- Sex differences in hypertension and other cardiovascular diseases, Delles, Christian and Currie, Gemma, Editorial Comment, www.jhypertension.com, Volume 36, Number 4, April 2018, pp. 768-770.
- Gender, blood pressure, and cardiovascular and renal outcomes in adults in hypertension from the Systolic Blood Pressure Intervention Trial, Foy, Capri G. et al., www.jhypertension.com, Volume 36, Number 4, April 2018, pp. 904-915.
- Sex-related differences in bronchial parameters and pulmonary function test results in patients with chronic obstructive pulmonary disease based on three-dimensional quantitative computed tomography, Li, Yan et al., Journal of International Medical Research, Vol. 46, No. 1, 2018, pp. 135-142
- Sex differences in pulmonary arterial hypertension: role of infection and autoimmunity in the pathogenesis of disease, Batton, Kyle A. et al., Biology of Sex Difference, Vol. 9, No. 15, 2018.
- Sex Differences in Chronic Obstructive Pulmonary Disease Mechanisms, Barnes, Peter J., American Journal of Respiratory and Critical Care Medicine, Editorials, Volume 193, Number 8, April 2016, 813-814.
- Absolute lung size and the sex difference in breathlessness in the general population, Ekstrom, Magnus et al., PLoS ONE, Vo. 13, No. 1, Jan 2018.
- Sex, metabolism and health, Maggi, Adriana and Torre, Sara Della, Molecular Metabolism, 2018, pp. 1-5.
- Gender differences in COPD: are women more susceptible to smoking effects than men?, Sorheim, Inga-Cecilie et al., Thorax, Vol. 65, 2010, pp. 480-485.
- Sex and gender differences in health, Regiz-Zagrosek, Vera, EMBO reports, Vol. 13, No. 7, 2012, pp. 596-603.
- Sex Differences in Ischemic Heart Disease, Advances, Obstacles, and Next Steps, Aggarwal, Niti R., Circ Cardiovasc Qual Outcomes, Feb 2018.
- Sex, race, and insurance status differences in hospital treatment and outcomes following out-of-hospital cardiac arrest, Casey, Scott D., Mumma, Bryn E., Resuscitation, Vol . 126, 2018, pp. 125-129.
- Sex Considerations in Aneurysm formation, Progression, and Outcomes, Boczar, Kevin E., Coutinho, Thais, Canadian Journal of Cardiology, Vol. 34, 2018, pp. 362-370.
- Sex differences in cardiovascular diseases – Impact on care and outcomes, Humphries, K. H. et al., Frontiers in Neuroendocrinology, Vol. 46, 2017, pp. 46-70.
- Everything you need to know about hypertension, Markus MacGill, December 2017, URL: https://www.medicalnewstoday.com/articles/150109.php
- Myocardial infarction, Wikipedia, URL: https://en.wikipedia.org/wiki/Myocardial_infarction
- Medical Definition of Menarche, MedicineNet.com, URL: https://www.medicinenet.com/script/main/art.asp?articlekey=4345
- Causes and treatments of aneurysm, MacGill, Markus, November 2017, URL: https://www.medicalnewstoday.com/articles/156993.php
- ST-Segment Elevation Myocardial Infarction, The Most Sever Type of Heart Attack, Fogoros, Richard N., Feb 2018, URL: https://www.verywellhealth.com/stemi-st-segment-elevation-myocardial-infarction-1746032
- Cardiac Catheterization, American heart Association, URL: http://www.heart.org/HEARTORG/Conditions/HeartAttack/DiagnosingaHeartAttack/Cardiac-Catheterization_UCM_451486_Article.jsp#.W1dm9dVKiM8
- Comorbidity, Wikipedia, URL: https://en.wikipedia.org/wiki/Comorbidity
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