Gender issues in cardiovascular medicine

Is there a difference?

If we search Medline for ‘gender difference’ we will find 28 089 references. Adding the term ‘cardiovascular’ decreases the number to 1965 references. With these two lines of introduction we may end this editorial. There must be a difference if 1965 colleagues have written papers about the topic. Without a gender difference it would have been impossible to publish all these papers. So where is the difference?

Physician gender

Does the association of physician gender with patient satisfaction differ for male and female patients? Having a female physician in an emergency room was positively associated with women's satisfaction, but physician gender was not associated with men's satisfaction in a recent study [1]. A British study [2] investigated the general preferences to see a male or female general practitioner (GP) either some or all of the time, and specific preferences to see a female primary healthcare worker for individual health issues. That study concluded that in order to meet women's expressed preferences, every GP practice should have at least one female GP available at least some of the time and every GP practice should employ a female primary healthcare worker. Actually male doctors may be quite unpleasant. Tabenkin and co-workers [3] concluded that outpatient visits by women differ from those of men in ways that reflect women's unique healthcare needs but also raise concern about unequal delivery of health habit counseling for diet and exercise. In another study female physicians had longer visit durations, and were more likely to perform female prevention procedures and make some follow-up arrangements and referrals, than male doctors [4]. Other groups have reported that physicians use fewer resources to treat the genital-specific conditions of patients who share their sex [5].

Myocardial infarction

Despite major advances in the diagnosis and treatment of heart disease, coronary artery disease remains the leading cause of morbidity and mortality in both men and women in developed countries. However, women suffer cardiovascular complications at older age, and more frequently fatal myocardial infarction, than men. In the Interheart study [6] female cases of myocardial infarction were 8 years older than male cases. Furthermore, hypertension and diabetes were found to confer higher risk in women. Moreover, the protective strategies evaluated in the Interheart study, exercise and moderate alcohol consumption, appeared to be more protective in women compared with men. The same study found that similar odds ratios were recorded in women and men for the association of acute myocardial infarction with smoking, raised lipids, abdominal obesity, composite of psychosocial variables, and vegetable and fruit consumption. Despite the observed gender differences, the authors of the Interheart study suggest that more than 90% of the risk of an acute myocardial infarction in a population can be predicted by the risk factors included in both genders. Other studies have reported that C-reactive protein confers higher cardiovascular risk in women [7],[8] than among men. The predictive value of C-reactive protein for a first myocardial infarction was even stronger than the predictive value of low-density lipoprotein cholesterol values in the Women's Health Study [9]. Subsequent cohort studies have shown that women's C-reactive protein concentrations are higher than men's, and this difference is larger when the metabolic syndrome is present [8].

Heart failure

Heart failure is multifactorial, and many risk factors have direct and indirect influence on its development. Coronary artery disease, hypertension, idiopathic dilated cardiomyopathy and valvular heart disease are the most common causes in both genders; however, the relative roles of these diseases are different in men and women. Chronic heart failure leads to significant morbidity and mortality in both genders, imposing a major burden on public health resources. Female recruitment in heart failure clinical trials had ranged between 20% and 30%, while epidemiological studies had indicated half of heart failure patients are female [10]. Overall, women had tended to be older, more likely to have preserved systolic function, more likely to develop heart failure post-myocardial infarction despite less prevalent coronary artery disease, and more often had history of hypertension, diabetes and prior heart failure [11],[12].

Is this determined in uterus?

Since David Barker reported (1989) an inverse relationship between birth weight and mortality due to adult ischemic heart disease, the role of prenatal programming as a determinant of adult diseases has become increasingly appreciated [13-15]. An excepted consensus has been that diseases such as type 2 diabetes, coronary heart disease, hypertension and stroke arise from the interactions between influences of adult lifestyle and a genetically determined susceptibility. This concept has been challenged by growing research indicating that conditions such as nutrition and endocrine environment during fetal life and in early childhood may have a profound impact on the risk to develop these diseases later in life. Animal studies demonstrate that there is an association between nutrient imbalance in fetal life and later development of hypertension, diabetes and obesity. It is also shown that impaired fetal growth followed by rapid catch-up in infancy is a predictor of cardiovascular and metabolic syndrome, and the relationships between the patterns of growth in early life and cardiovascular disease may differ between females and males. There is also a different impact of early nutritional manipulations on male and female offspring and the foundation for such outcomes is not well understood [16-18].

The ‘developmental origins’ hypothesis therefore proposes that alterations in nutrition and endocrine status in early life elicit developmental adaptations that may permanently alter the individual's structure, physiology and metabolism. As a consequence, the individual may be predisposed to develop cardiovascular, metabolic and endocrine disease in adult age. This development may also be influenced by postnatal growth patterns. Therefore studies that allow a better understanding of the growth trajectory and aspects of the hormonal milieu of the male and female infant are required to determine how early development is directly relevant to programmed health outcomes [16-20].

Until recently there has been little information as to whether the early environment is associated with altered behavior in humans. Some studies reported that low birth weight was associated with features of hyperactivity and reduced attention, and that this effect was observed across the range of birth weight [21],[22]. In a large cohort of Swedish army recruits, Nilsson and colleagues reported that there was a continuous relationship between size at birth and stress susceptibility in a psychological assessment of suitability for military combat duties [23]. The results are supported by a study of 106 young healthy males who were exposed to the Trier Social Stress Test, a psychological stress test involving a public speaking task [24]. Cortisol responses to the stress exposure were also significantly and inversely related to the subjects' birth weight. Ward and co-workers demonstrated that low birth weight is associated with enhanced blood pressure and heart rate responses to psychological stressors in women but not men, suggesting that there are potential sex differences in the nature of the relationship between size at birth and the stress response [25-27].

Perinatal medicine and cardiology

In the hospital the gynecologist and cardiologist never meet, except in rare cases when they both look for the ultrasound machine. They certainly work in different areas, but maybe they should meet? As mentioned above there are obvious links between fields of reproduction, perinatal medicine, neonatology and cardiovascular disease. They might need to discuss when it is appropriate to prescribe postmenopausal hormone therapy, but apart from these obvious clinical questions more research needs to be done to understand the process of cardiovascular disease in relation to gender.