Impact of a Physical Activity Intervention on Cardiometabolic Health, Mental Health, and Lifestyle Factors.

The first objective of this study is to compare cardiometabolic and mental health across the four interregion Meuse-rhine (IMR). The second objective is to compare six key lifestyle pillars, as defined by the American College of Lifestyle Medicine: physical activity, diet, stress management, sleep quality, social connection, and substance use. Physical activity will be objectively and continuously monitored using a wearable device, while the other five lifestyle factors will be assessed through validated questionnaires at pre- and postintervention. Finally, we will evaluate the effects of a physical activity intervention on cardiometabolic health, mental health, and the six lifestyle pillars. By addressing these objectives, this study aims to generate valuable insights to inform policymakers and support region-specific interventions for improving health and lifestyle across the IMR.

Study design This multicentric interventional study will be conducted at four sites: Hasselt University, Liège University, Maastricht University, and Aachen University. The study includes a pre- and post-intervention visit, with a three-month intervention period followed by a three-month follow-up.

Participants will be recruited via a subscription link, where they will provide demographic information after giving informed consent. Based on the inclusion criteria, 1000 participants will be included in total (250 participants per site).

Eligible participants will be invited for the first study visit, during which they will receive a wearable device. They will then follow a three-month intervention, after which they will return for a second study visit. This will be followed by a three-month follow-up period, during which there will be no direct contact with the research team. At the end of this period, participants will receive questionnaires via email. To ensure participants have not had an infection before their scheduled testing day, an automated email will be sent via Castor EDC two weeks in advance. This email will remind them of their study visit and ask whether they have experienced a viral or bacterial infection in the past week. If so, they will be instructed to contact the research team to reschedule their appointment.

Ethical approval documents for the two sites in Belgium will be submitted simultaneously. Documents for Maastricht University and Aachen University will be submitted afterward, and the ethical approvals will be sent to the Belgian ethical committees.

Participants A quota for educational level will be implemented, limiting highly educated participants to a maximum of 25% per region to reflect the educational distribution of the IMR population. This ensures a more representative sample, as highly educated individuals are often overrepresented in research.

To minimise seasonal effects on physical activity, participant inclusion will be divided into four groups and spread throughout the year. At each site, approximately 65 participants will start in September 2025, another group in December '25/January '26, a third group in March/April '26, and a final group in June/July '26.

Participants will be recruited through online and paper advertisements, including a subscription link to the screening questionnaire. Selected participants will receive detailed study information via phone or email, based on their indicated preference. Data from unselected participants will be deleted after recruitment is completed. Those who agree to participate will be invited for a first study visit, where they will provide written informed consent. Selected participants may withdraw at any time for any reason. In such cases, previously collected research data will be retained, but contact details will be deleted, and their name will be removed from the subject identification list.

Participants will be included if they meet the following eligibility criteria:

Aged between 40 and 65 years Resident of Belgian Limburg, Liège, Netherlands Limburg or Aachen, with the intention to remain there for at least one year Able to wear a wrist-worn wearable for at least 10 hours per day during waking hours Own a smartphone and have a valid email address Adequate proficiency in Dutch or English, defined as the ability to read, understand, and ask questions Not pregnant and no plans to become pregnant within the next year

Study visits During the first study visit, all study procedures and outcome measures will be explained, and participants will provide written informed consent. Next, they will complete questionnaires on their sociodemographic factors, mental health and lifestyle factors using an iPad or computer. These questionnaires will be accessed via a secured link sent by the EDC Castor system to a fictitious email address created in advance for each participant. A member of the research team will prepare the questionnaires for each participant and verify their correct submission afterward.

Following this, blood pressure and anthropometric measurements will be taken, and a venous blood sample will be drawn by a certified nurse or doctor. Participants will then receive their wearable along with assistance for installation and connection to their smartphone.

Additionally, a subsample of participants (n = 75 per site) will be asked to install M-Path on their smartphone for ecological momentary assessment of mental health. Technical support will be provided as needed.

The same measurements will be repeated during the post-intervention study visit. For sociodemographic factors, participants will be asked if any changes have occurred and, if so, to specify them. In addition, participants will have to answer four questions on intervention adherence and possible barriers they experienced.

Intervention (3 months) The intervention will be based on the physical literacy model for older adults as described by Jones et al.(2018) to promote long-term physical activity participation. This model takes an ecological approach, with a primary focus on the intrapersonal level by enhancing physical competence, motivation, confidence, and knowledge. Additionally, it incorporates interpersonal, organisational, and community factors to create a supportive environment for sustained physical activity.

Participants will receive a wearable (model to be determined based on the public procurement procedure) to track their physical activity levels. Step goals will be provided before the intervention begins and again in weeks 4, 7, and 10 via email. These personalised goals will be based on each participant's actual step count from the previous week.

The initial goal will encourage participants to increase their baseline step count by 500 steps per day. If they meet this target, their next goal (week 4) will be to increase by 1,000 steps per day from baseline. If they do not meet the first goal, they will again be encouraged to increase by 500 steps per day. Participants who significantly exceed their goal (\>500 steps/day above their goal) will be encouraged to maintain their activity level, with reassessment at each goal-setting point. Participants who meet all targets will achieve a total increase of 2,000 steps per day. This is based on the findings of Stens et al., which indicate that every additional 1,000 steps per day reduces the risk of incident cardiovascular disease (CVD), regardless of baseline activity levels. Furthermore, an umbrella review by Mair et al. shows that comparable digital interventions typically lead to an average increase of 1,000 to 2,000 steps per day.

The mailing system is designed based on the findings of Mair et al., who identified key behaviour change techniques in digital health interventions\[15\]. These include 'graded goal setting' (progressively increasing goals), 'prompts and cues' (multiple reminder emails), 'feedback on behaviour' (motivating participants based on their previous activity), and personalised content (adapting goals based on prior achievements), all of which are shown to be effective in promoting behavioural change.

In addition, educational videos will be made available via a YouTube channel to enhance knowledge and engage participants at organisational and community levels by highlighting local initiatives at each site, such as organised walks and existing walking routes. Each email will include a link to a new video.

The webinars will focus on increasing daily step count, as this is central to the intervention goals. The following themes will be covered:

Promotion of walking and its benefits. Incorporating non-exercise physical activities into daily life, such as gardening, household chores, parking further from a building entrance, and opting for cycling or walking instead of using a car or public transport.

Engaging in structured physical activities that can be performed at home, such as walking, running, cycling, and seated gymnastics.

Practical strategies for increasing step count, incorporating behaviour change techniques such as 'action planning' and 'implementation intentions'.

Follow-up (3 months) During the follow-up period, participants will no longer receive new step goals via email. However, they are required to continue wearing the wearable and synchronising it weekly. The educational videos will remain accessible on the YouTube channel.

Outcome measures Health Cardiometabolic health : 10-year cardiovascular disease (CVD) risk

A venous blood sample will be collected in two tubes: one 9ml lithium-heparin (Li-hep) tube and 6ml ethylenediaminetetraacetic acid (EDTA) tube. These samples will be used to assess the following parameters:

Cholesterol (total cholesterol \[CHOL\]; high-density lipoprotein cholesterol \[HDL-CHOL\], low-density lipoprotein cholesterol \[LDL-CHOL\]), Inflammation (high-sensitivity C-reactive protein (\[hs-CRP\]) Kidney function (creatinine to estimate the glomerular filtration rate) Glucose metabolism (glycated haemoglobin \[HbA1c\]) CHOL, HDL-CHOL, LDL-CHOL, hs-CRP and creatinine will be analysed from the Li-hep tube, which will be centrifuged immediately after collection (room temperature, 1,290 × g, 15 minutes, brake setting 9). HbA1c will be analysed from whole blood collected in the EDTA tube. Plasma from the Li-hep tube and whole blood from the EDTA tube will be aliquoted immediately and stored at -80°C until analysis.

Before participants begin completing the questionnaires on an iPad, an electronic sphygmomanometer (Omron®, Omron Healthcare, IL, USA) will be placed on the dominant arm. While they complete the questionnaire in a seated position, the cuff remains in place. After they finish, systolic and diastolic blood pressure as well as resting heart rate will be measured four times and documented as the mean value of the final 3 measurements. Mean arterial pressure (MAP) is calculated as MAP = systolic BP + (2 x diastolic BP) / 3.

The 10-year risk of cardiovascular disease (CVD), including non-fatal stroke, non-fatal myocardial infarction, or death due to CVD, will be calculated using different risk models based on participants' health status. SCORE2 will be used for apparently healthy individuals (without a history of CVD or diabetes mellitus), SMART2 for those with a history of CVD (including coronary artery disease, cerebrovascular disease, peripheral arterial disease, abdominal aneurysms, and polyvascular disease), and SCORE2-Diabetes for individuals with type 2 diabetes.

All risk calculations incorporate the blood lipid profile, systolic blood pressure, sex, age, and smoking behaviour, while also accounting for regional risk variations. Additionally, the SMART2 model includes kidney function, diabetes status, body mass index, medication use, and duration of previous CVD. The SCORE2-Diabetes model also includes HbA1c and diabetes duration.

Anthropometrics and body fat distribution To measure anthropometrics and body fat distribution, participants will be in light clothing. Body height will be measured to th

• Sociodemograpgics variables [Срок оценки: T0 = baseline]