Matthias Lidin

Background: Physical inactivity negatively affects health and is associated with type 2 diabetes, cardiovascular disease, cognitive dysfunction and shorter life span. Despite the growing body of evidence for detrimental effects, the population is increasingly sedentary and currently sitting nine to ten hours per day

the pattern is seen across all age groups. This harmful development must be mitigated to combat the increasing epidemic of lifestyle-related diseases in society. Stair walking has the potential to incentivize people to be more physically active seamlessly integrated into everyday life. Objectives: To investigate whether six months of daily stair walking (200 stair steps daily) in addition to walking on level ground (75 minutes per week) versus only walking on level ground (150 minutes per week) - in a time-effective manner - confers greater blood pressure reduction as well as greater improvement in aerobic fitness, strength, cardiovascular risk factor control and self-assessed health parameters. Work plan: Study subjects will be screened for inclusion through an online screening tool. Participants are both men and women 40-70 years old with increased cardiometabolic risk defined by hypertension, abdominal obesity and sedentary lifestyle (less than 4000 steps per day). Study subjects (n=400) will be randomized into two groups: 1) daily stair walking plus half the weekly recommended walking on level ground and 2) recommended weekly walking on level ground alone. Activity levels will be monitored regularly. Subjects will be followed for six months. Measured outcomes are blood pressure, aerobic fitness, strength, cardiovascular risk factor control and self-assessed health parameters. Significance: If stair walking is a feasible and time-effective physical activity it could improve individual health through a simplistic training alternative that can be seamlessly integrated into everyday life. It could inform infrastructure planning by ensuring that stairs are readily available and promoted for pedestrians. Healthcare costs could be decreased by keeping vulnerable groups more physically active thus reducing the growing burden of lifestyle-related diseases. Positive findings have population-level scalability and could corroborate the European Society of Cardiology s guidelines on both individual prevention and strong policy suggestions on physical activity when planning/building new landscaping.

Background: Cardiovascular diseases (CVD) are responsible for almost one third of the deaths worldwide. Individuals with mental disorders have shown to be a group particularly vulnerable to suffer from CVD. For example, using data from the Swedish registers, our team has established that individuals with obsessive-compulsive disorder (OCD), an impairing disorder affecting about 2% of the population, have an increased risk of obesity, type 2 diabetes, circulatory system diseases, and specific CVDs, with the subtypes venous thrombo-embolism and heart failure being the most relevant. We have also established that these risks in OCD are likely to be a consequence of the disorder itself, rather than attributable to familial factors or medication. Given this, it is crucial to consider lifestyle habits (e.g., physical activity, diet) which may be responsible for the observed CVD risks and are known to be amenable to modification. Objectives: This project is a collaboration between Karolinska Institutet, the Department of Cardiology at Karolinska Universitetssjukhuset, and the specialist OCD and related disorders clinic at Psykiatri Sydväst, Region Stockholm. With the help and support of the Swedish OCD association (Svenska OCD-förbundet), we have developed a lifestyle intervention to reduce metabolic and cardiovascular risk factors in individuals with OCD, which we aim to evaluate in this project. Workplan: We will follow a two-step approach. First, we will conduct a pilot study to test whether our lifestyle intervention, including physical exercise, modification of dietary habits, and other behavioural changes is feasible, safe, and acceptable for the participants. Second, we will conduct a fully powered randomized controlled trial to establish the efficacy of this intervention, compared to medical advice and treatment as usual. We will also evaluate whether this intervention is cost-effective from a societal perspective. Meaning: Our results have the potential to prevent and reduce the cardiometabolic outcomes observed in individuals with OCD. If the lifestyle intervention program proves to be successful in reducing this risk and does so in a cost-effective manner, we will aim to implement the intervention in routine clinical care. Additionally, the intervention could be expanded to individuals with other common mental disorders, such as anxiety and depression, as well as other groups at risk.

Obsessive-compulsive disorder (OCD) is a prevalent and impairing mental disorder associated with an increased risk of metabolic and cardiovascular diseases (CVD) and death due to cardiovascular causes. However, the mechanisms underlying this association are unknown. Moreover, it is unknown if lifestyle modification interventions can reduce cardiometabolic risk factors in individuals with OCD. The objectives of this research project are two-fold. First, we will investigate the causal associations between OCD and CVD using genetic correlations and bi-directional Mendelian randomization. Second, we will evaluate a lifestyle intervention to reduce cardiometabolic risk factors in individuals with OCD. We will do this in two steps. Step 1 is a pilot study to evaluate trial procedures and test the feasibility of the intervention. Step 2 will consist of a randomized controlled trial examining efficacy and cost-effectiveness of the lifestyle intervention for OCD, compared to medical advice and treatment as usual. The results of this project will inform prevention and intervention strategies and clinical guidelines. Additionally, if our lifestyle intervention program proves to be successful in reducing cardiometabolic risk and does so in a cost-effective manner, we will aim to implement the intervention in routine clinical care, which would contribute to reducing morbidity and mortality rates in this population.