Obesity is a rapidly growing epidemic that is associated with the development of cardiovascular disease (CVD). However, some individuals with obesity appear to be resistant to CVD, and other individuals demonstrate resilience to obesity and CVD risk factors. The investigator's overall objective is to understand factors contributing to the heterogeneity of CVD resistance and resilience among individuals with obesity at Duke.

The investigator aims to recruit participants with 4 phenotypes: 200 participants with obesity (BMI ≥ 30) and high 10-year ASCVD risk (≥20%), 200 participants with obesity (BMI ≥ 30) and low 10-year ASCVD risk (<7.5%), 100 participants with normal weight (BMI 18-25) and high 10-year ASCVD risk (≥20%), and 100 participants with normal weight (BMI 18-25) and low 10-year ASCVD risk (<7.5%). Clinical, behavioral, and molecular characteristics will be compared at baseline between the 4 groups to understand heterogeneity between obesity and risk for CVD, and participants with obesity will undergo a 6-month weight loss intervention. In individuals with obesity, clinical, behavioral, and molecular characteristics will be compared between baseline and 6 months to understand (a) predictors of response to the intervention and (b) how these factors change with weight loss. Differences in branched-chain amino acids will be compared between all groups, both at baseline and at 6 months (for those participants undergoing the digital-weight loss intervention). Other clinical, behavioral, metabolomic, genetic, and microbiome parameters will also be compared in an exploratory fashion. There may be possible risk of loss of confidentiality, but this risk is low and measures will be taken to minimize this risk.

Recruitment Sub-Study: We aim to determine optimal strategies to recruit participants into the study via electronic recruitment. We will identify potentially eligible participants within the Duke Electronic Health Record and reach out them via electronic means. Potentially eligible participants will be randomized in a 2x2 factorial fashion to receive personal email vs. MyChart message, and to different message content (1 of 4 types). We will analyze: a) which modality of introductory message delivery (MyChart vs personal email) will lead to greater engagement (as assessed by clicking on the study website page to get more information) b) which messages (altruism vs personal benefit vs scientific importance) will lead to greater engagement.

Consent Sub-Study: We aim to determine optimal strategies to consent participants into the study via e-consent portal. Potential participants who land on the study website will be randomized to consent via one of four methods, followed by a consent-comprehension quiz: a) video consent with study information provided by a representative patient, b) video consent with study information provided by the lead physician of the study, c) video consent with study information provided by animation/cartoon or d) text-based study information and consent (standard). We will analyze which type of consent form will lead to greater completion of consent forms and greater comprehension of the consent form.

Coronary Artery Calcium (CAC) Score Sub-Study: At baseline visit, a total of 300 participants (150 with obesity and 150 without obesity) will undergo CT testing to determine coronary artery calcium (CAC) score.

Basic Science Sub-Study: Thirty participants with obesity (15 high-risk for CV disease and 15 low-risk for CV disease) will participate in the basic science sub-study where additional blood will be drawn at baseline visit and at follow-up visit. This blood will be processed to isolate the endothelial colony forming cells and we will examine the effect of altered plasma branched chain amino acid (BCAA) levels on vascular function within these groups.

Inclusion Criteria:

• Adults 40-75 years old
• At least one clinic encounter at Duke with BMI record in the EHR within previous year
• Has a current primary care provider listed listed in EHR
• No prior history of ASCVD, as defined by ICD9, ICD10, and CPT codes for coronary artery disease, myocardial infarction, stroke, peripheral arterial disease, prior revascularization for coronary, cerebral, or peripheral arteries.
• Fall into 1 of 4 categories: 200 participants with obesity (BMI ≥ 30) and high 10-year ASCVD risk (≥20%), 200 participants with obesity (BMI ≥ 30) and low 10-year ASCVD risk (<7.5%), 100 participants with normal weight (BMI 18-25) and high 10-year ASCVD risk (≥20%), and 100 participants with normal weight (BMI 18-25) and low 10-year ASCVD risk (<7.5%).
• Have internet access
• Have an email address listed in the EHR
• Have access to MyChart
• Have a smartphone
• Be able to read and understand English

Exclusion Criteria:

• Participants "opted out" of being contacted for research in Maestro Care
• Pregnant at the time of enrollment or <12 months post-partum
• Prior bariatric surgery