Research

The Gebhard Lab is an interdisciplinary scientific research group, which aims to generate a better understanding of sex- and gender-specific disease mechanisms of cardiovascular diseases in order to improve the care of patients of all genders. 

Mission statement

At the Gebhard Lab, we bring gender equality together with cardiovascular medicine through cutting-edge research and
state-of-the-art education.

Read more about our research and education.

Projects

Gender Differences in Cardiac Function

Our recent findings show significant sex- and age-specific differences in baseline left ventricular ejection fraction (LVEF) with a strong age-dependent increase in LVEF in healthy women, but not in men.

The Heart-Brain Axis

The female cardiovascular system is more sensitive to stress.

Impact of Sex and Gender on COVID-19 Outcomes

Men are more susceptible to a severe disease course of COVID-19 than women, and worldwide data show that the disease is deadlier in men than in women. 

Identifying Sex- and gender-specific Predictors of Severe COVID-19

Current risk predictors are valuable tools to predict individual manifestations of COVID-19 since they combines different aspects of the disease, including biological sex. 

Cardiac Hypertrophy

Left ventricular hypertrophy (LVH) is an example of a heart disease with significant sex-specific differences.

Men and Stress

The association between diagnosed acute ST-elevation myocardial infarction (STEMI) and hockey games in the Canadian population is unknown.

Flurpiridaz

Assessment of sex-specific determinants of myocardial blood flow.

Gender differences in cardiac function

Since left ventricular ejection fraction (LVEF) is routinely used in clinical decision making, it is vital to understand the variables that control cardiac contractility and its vulnerability to injury in postmenopausal women and older men. These insights are critical for the development of personalized age- and gender-based therapies. We therefore assess the impact of (patho)physiological factors contributing to sex- and age-related differences in cardiac function. Specifically, we investigate whether these sex-differences can be attributed to sex hormones and their receptors, differences in genetic predisposition, neurohumoral signalling, and gender-based lifestyle factors. Our studies use murine experimental models and diverse imaging techniques like positron-emissions tomography (PET), echocardiography, and cardiovascular magnetic resonance (cMR) imaging. Our ultimate goal is to improve and personalise gender-based treatments for the aging population.

New_Variables_web_042021

The heart-brain axis

Using the latest imaging techniques, the Gebhard Lab has demonstrated that the amygdala, a part of the brain that controls emotional reactions (the so-called anxiety centre), is highly active in women with cardiac cardiovascular disorders, but not in men. It is hypothesized that increased rates of inflammatory markers in the blood and bone marrow form a link between the stress response in the brain and the heart disease in women. Therefore, stress reduction in women with heart disease should become a vital part of cardiovascular disease management. In a follow-up project, we are now investigating further control mechanisms at the molecular and cellular level that are responsible for the increased stress response in women with heart disease to develop specific and effective cardiovascular treatments.

The-Heart-Brain (1)_web_042021

More Information

Impact of Sex and Gender on COVID-19 outcomes

COVID-19 mortality is highest in aged men and men with pre-existing cardiovascular diseases. The mechanisms underlying these differences are currently unclear. We analyse available clinical and epidemiological data on ageing, co-morbidities and lifestyle in Switzerland to elucidate the role of sex and gender variables in the COVID-19 disease progression. In addition, the underlying mechanisms will be assessed in a murine model of hormone withdrawal. Our work aims to identify both the biological sex- and gender-related predictors for COVID-19 and in order to develop effective antiviral interventions.

Identifying Sex- and gender-specific Predictors of Severe COVID-19

For a more comprehensive understanding of the disease, the so-called ‘gender dimension’ (different from biological sex) which comprises psychosocial, cultural, and socioeconomic variables, should be included in COVID-19 risk models. Gender characterizes individuals as more feminine or masculine based on psychosocial and sociocultural variables, including their role in society. Gender is linked to disease exposure and occurrence, individual risk factors, access to health care and prevention, and therefore, it has a major impact on disease outcomes. Biological sex and gender (S&G) have recently been shown to drive disease outcomes in opposite directions: while female sex was shown to have a protective effect after a myocardial infarction in women, female gender was associated with adverse outcomes. Given its novelty as a unit of measurement and the challenges associated with its use in precision medicine, gender has not yet been considered in recent prediction tools for COVID-19. Researchers, including our own group, are now developing strategies to identify the most important gender-related variables in Western societies and have built gender scores that can be used in risk prediction models. These scores depend on the society under consideration but are largely independent of underlying diseases.

COVID_Score_web_042021

More Information

Cardiac hypertrophy

 

It is an independent risk factor for cardiovascular complications, including heart failure, sudden cardiac death, and stroke. Although women are at a higher risk for left ventricular hypertrophy (LVH)-associated complications, the unique sex-specific determinants remain unknown. We are investigating the role of cardiac fibrosis, inflammation and sympathetic activity in the progression of LVH in women. Given the increasing proportion of women dying from cardiovascular disease and the greater life expectancy of women in the developed world, it is imperative that we develop our knowledge about the role of cardiac hypertrophy in the ageing female heart. This helps to implement novel diagnostic strategies and a timely risk assessment in both men and women with LVH.

LVH_web_042021

Men and stress

The association between diagnosed acute ST-elevation myocardial infarction (STEMI) and hockey games in the Canadian population is unknown.

Methods

We retrospectively analyzed the association between hockey games of the National Hockey League Montreal Canadiens and daily hospital admissions for acute STEMI at the Montreal Heart Institute, Canada.

Results

Between June 2010 and December 2014, a total of 2199 patients (25.9% women; mean age, 62.6 ± 12.4 years) were admitted for acute STEMI. An increase in STEMI admissions was observed the day after a hockey game of the Montreal Canadiens in the overall population (from 1.3 ± 1.2 to 1.5 ± 1.3), however, this difference was not significant (P = 0.1). The number of STEMI admissions increased significantly from 0.9 ± 1.0 to 1.2 ± 1.0 per day in men (P = 0.04), but not in women (P = 0.7). The association between ice hockey matches and STEMI admission rates was strongest after a victory of the Montreal Canadiens. Accordingly, an increased risk for the occurrence of STEMI was observed in the overall population (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.0-1.3; P = 0.037) when the Montreal Canadiens won a match. This association was present in men (HR, 1.2; 95% CI, 1.03-1.4; P = 0.02) but not in women (P = 0.87), with a most pronounced effect seen in younger men (younger than 55 years; HR, 1.4; 95% CI, 1.1-1.8; P = 0.009).

Conclusions

Although a weak association between hockey games and hospital admissions for STEMI was found in our overall population, the event of a hockey game significantly increased the risk for STEMI in younger men. Preventive measures targeting behavioural changes could positively affect this risk.

Flurpiridaz

Flurpiridaz_web_042021

 

Despite remarkable advances in cardiovascular disease management, coronary artery disease remains the leading cause of death in the Western world. While clinical manifestations and outcomes of coronary artery disease differ substantially between the sexes, current therapeutic guidelines rely on data overrepresenting the male population. Accordingly, accurate cardiovascular risk-stratification in women is hampered by limitations of contemporary imaging modalities in women and the relatively high prevalence of visually non-detectable dysfunction of the coronary microvasculature in female patients. The latter can be assessed with functional myocardial perfusion imaging by using positron emission tomography. Hence, we envision to identify key sex determinants that affect microvascular dysfunction using the innovative and validated perfusion tracer 18F-flurpiridaz.