The Role of Physical Activity in Cardiovascular Disease Risk Reduction – On the Way to Personalized Exercise Prescription (ACT-ON Study)

Non-communicable diseases (NCDs) are a major public health challenge worldwide, and physical exercise interventions (PEI) can play a crucial role in their prevention and management[1]. Compared to other methods of treatment, such as drugs, physical exercise has low implementation costs and few or no negative side effects. Some of the most common NCDs that can be managed with PEI include cardiovascular disease (CVD), diabetes, cancer, chronic respiratory diseases, and musculoskeletal disorders such as osteoarthritis, sarcopenia, etc.,[1–3]. According to the World Health Organization (WHO), NCDs are responsible for 71% of all deaths globally, with CVD alone accounting for 17.9 million deaths per year 32% of all deaths globally)[4]. Physical inactivity is one of the major risk factors for NCDs, and studies have shown that regular exercise can significantly reduce the risk of developing NCDs and improve outcomes in people already affected by these conditions[5,6]. The burden of NCDs varies across different regions and countries. However, globally, NCDs are responsible for a significant proportion of disability-adjusted life years lost[7,8].

PEI, such as aerobic exercise, resistance training, and high-intensity interval training, have been shown to be effective in reducing the risk of developing NCDs and improving health-related outcomes in people already affected by these conditions[6]. However, even engaged in high quality randomized controlled trials (RCTs) with high adherence to prescribed PEI, there is a high variability in response to PEI[9–13]. Often, there is a subset of people who do not respond to physical exercise in the same way as the general population. These individuals are commonly referred to as "non-responders" or "low- responders", as they do not experience significant improvements in their fitness level, body composition, or other health-related benefits after a period of structured exercise training[10].

This lack of response can be due to various factors, including genetic factors, age, sex, baseline fitness level, health status, exercise adherence and compliance, and lifestyle factors such as diet, stress, sleep habits, overall physical activity levels outside of formal exercise session etc[10]. However, even if someone is considered a non-responder in one specific aspect of fitness or health, they may still experience other benefits from exercise, such as improvements in mental health or overall well-being. Thus, it is very important to implement a multidimensional and interdisciplinary approach to investigate this issue and ultimately find the optimal exercise prescription for each individual.[14,15] This concept is known as personalized or precision medicine. It is an emerging field in healthcare that aims to tailor medicine treatments to individual patients based on their unique characteristics[16]. Thus, with the advancements in genetics, biomarkers, data analytics, AI, clinical decision support tools and disease-specific applications we will aim to increase scientific potential to transform healthcare by enabling tailored treatment approaches that can optimize patient outcomes and improve overall healthcare delivery. Therefore, we will include PEI, as a key component of personalized medicine model through 7 working packages.

The ACT-ON project will deliver several outcomes, including:

a)      Identifying factors that differentiate between responders and non-responders to exercise;

b)     Developing personalized training programs based on patients' characteristics, specifically factors confirmed through literature reviews and acute and longitudinal studies;

c)      Creating a valid physical fitness self-assessment tool that will enable researchers and health professionals to conduct decentralized clinical research and manage epidemiological studies with less effort and overall cost in different populations of interest.

Funding

This project was funded by the University of Ljubljana’s Development Fund (project IDs: 005-1/2023 and 802-15/2023-5, acronym [ACT-ON]), with assist. Prof. Armin Paravlic as the principal investigator.

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Author: Assist. Prof. Armin Paravlić,  PhD