Healthy Ageing of the Heart

Early cultures were already aware that the heart plays an important role in the human body. In various cultures, the spirit or soul was believed to reside in the heart; for the Aztecs, the heart played a central role in sacrificial rituals; and for the Egyptians, the heart was favoured by Anubis, the god of the rites of the dead, to determine whether the soul of the deceased would be destroyed. For us, the heart is mainly associated with love and emotions. We are delighted when someone makes our heart beat faster; we are frightened when our heart sinks; and when we pour our heart out to someone, we confide everything to that person. Let us shift our focus from the cultural to the medical and biological aspects of the heart: within the chest, this organ fulfils a completely different, yet equally central, role. The cardiovascular system is essential for practically all functions of the human body. It ensures that every cell receives the nutrients necessary for its function. Whether the brain requires energy for complex thought processes or the nutrients absorbed in the gut need to be transported to the liver for further processing: without the heart’s pumping action, nothing in the human body works.

The central role of the heart becomes particularly clear when the heart and circulatory system no longer function optimally. Cardiovascular diseases are the leading cause of death in Austria. They account for around one third of all deaths. This is a trend that can also be observed among our neighbours in Germany, Switzerland and worldwide. Even though scientific progress is yielding ever-better treatment options, lifestyle factors play a significant role – particularly in the Western world – in the development of cardiovascular diseases, some of which are fatal. A lack of exercise, unhealthy eating habits, being overweight, smoking and alcohol consumption are among the key factors responsible for the widespread prevalence of cardiovascular diseases in Austria. High cholesterol levels are also a factor that can have a negative long-term impact on the health of the heart and our blood vessels.

At the Medical University of Graz, intensive research is being carried out into the heart and the prevention and treatment of cardiovascular diseases. One of these research groups is led by Simon Sedej, who is investigating a specific form of heart failure.

When the heart does not beat properly

In heart failure, the heart is no longer able to supply the body adequately with blood and thus with nutrients, or can only do so at the cost of increased filling pressures. A general distinction is made between two types of heart failure:

heart failure with reduced ejection fraction (HFrEF):
in this form of heart failure, the heart’s ejection fraction is reduced. This can be caused, amongst other things, by calcification of the coronary arteries (coronary heart disease), heart valve disorders or cardiac arrhythmias such as atrial fibrillation. In addition, there are also hereditary heart muscle disorders.

Heart failure with preserved ejection fraction (HFpEF):
In this form of heart failure, the heart’s ejection fraction is preserved, but higher pressures are required to ensure adequate filling of the heart. For patients over the age of 65, heart failure is the most common cause of hospital admissions, which is why the condition also poses a particular challenge for the healthcare system, especially in light of demographic change – Austrians are living longer and longer and are getting older as a result. Treatment options for HFpEF are limited, which is due to the mechanisms underlying this multi-organ disease not yet being fully understood. Research is being carried out at the Medical University of Graz to
address this challenge.

Research for the future

“HFpEF is a systemic condition that affects more than just the heart. It arises primarily from the interplay of ageing, physical inactivity and associated metabolic disorders such as overweight or obesity, high blood pressure and metabolic syndrome. These conditions, which are among the greatest risk factors for HFpEF, lead to a vicious circle of metabolic dysfunction and progressively impaired heart function,” explains Simon Sedej. The issue of excess weight was the focus of the working group led by Simon Sedej and Alina Stockner, the lead author of the study ‘Inhibition of Adipose Tissue Lipolysis Treats Obesity-Related HFpEF’. The study analysed the role that adipose tissue may play in the development of heart failure and how its negative consequences can be prevented. Among other things, it focused on fatty acid mobilisation (also known as lipolysis).

Alina Stockner summarises the research findings as follows: “Adipose tissue does indeed play a central role in HFpEF by contributing to the development of chronic systemic inflammation (i.e. an inflammatory response that occurs continuously throughout the body). Despite the significant role of adipose tissue in the progression of the disease, there is currently no evidence that direct modulation of adipose tissue metabolism alone is sufficient to treat obesity-related HFpEF. In this study, however, we provide compelling evidence that the genetic or drug-induced inhibition of fatty acid mobilisation specifically within adipose tissue is sufficient to prevent or even treat HFpEF associated with obesity.” The research focused on a compound called atglistatin. It inhibits a protein molecule that breaks down fat, known as adipose triglyceride lipase (ATGL). 

In a mouse model of HFpEF, Alina Stockner was able to demonstrate that atglistatin protects the heart. Pro-inflammatory factors, which in turn promote the progression of heart failure, were also reduced by the use of this compound in adipose tissue. In the mouse model, the administration of atglistatin blocked fat breakdown in adipose tissue, but not in the heart or other organs where the lipase is also present. This aspect is important, as inhibiting lipase in other organs would lead to harmful fat accumulations. The inhibitor atglistatin could now open up a new therapeutic approach for this condition as well. Scientists from the University of Graz and Graz University of Technology have developed an inhibitor that is effective in human cells. This research is still in the preclinical phase.

Facts and figures about the (healthy) heart

• The heart is roughly the size of a fist. In newborns, it is the size of a walnut.
• Depending on gender and body size, the heart weighs between 250 and 350 grams.
• The heart beats approximately 60 to 80 times per minute. This means the heart beats just under 100,000 times a day.
• At rest, the heart pumps just under 5 to 6 litres of blood per minute.
• Blood vessels form a vast, branching network stretching some 150,000 kilometres in length, reaching every part of the body, no matter how remote. This is almost four times as long as the equator, which measures just under 40,000 kilometres.

In Austria, there are approximately 250,000 to 300,000 people living with heart failure. Around half of these are affected by heart failure with preserved ejection fraction. The symptoms of HFrEF and HFpEF are similar:

» Shortness of breath
»Lack of energy» Tiredness
»Exhaustion» Palpitations
»Dizziness
»Fluid retention
»Loss of appetite

Simon Sedej and his research group are conducting research into heart failure with preserved ejection fraction. The causes of this condition can be varied:

»Smoking
»High blood pressure
»Obesity
»Type 2 diabetes mellitus
»Chronic kidney disease
»Lack of physical activity