Design and Rationale of the pERSonalized cardIovascuLar dIsease prEvention, treatmeNt, and CarE (RESILIENCE) study.

BACKGROUND

Obesity is a growing epidemic associated with cardiovascular disease (CVD). The RESILIENCE study aimed to understand the factors underlying heterogeneity in CVD development among individuals with obesity as well as the variability in response to weight loss interventions in this population, with a focus on branched-chain amino acids (BCAA).

METHODS

Four cohorts were recruited: individuals with obesity (BMI ≥ 30 kg/m2) and either high (≥20%) or low (<7.5%) 10-year atherosclerotic CVD (ASCVD) risk (calculated by the Pooled Cohorts Equation), and individuals with normal weight (BMI 18-25 kg/m2) and either high or low ASCVD risk. Clinical, behavioral, and molecular characteristics were collected at baseline between the four groups to assess heterogeneity between obesity and risk for CVD. Participants with obesity then participated in a 6-month remote weight loss intervention to evaluating predictors of response to the weight loss intervention. Our primary hypothesis was that BCAA are associated with CVD risk and obesity and that similarly, BCAA will predict response to weight loss interventions.

RESULTS

598 participants were recruited between 2019 and 2022 within the Duke University Health System. 100 had normal weight and low ASCVD risk, 103 had normal weight and high ASCVD risk, 196 patients had obesity and low ASCVD risk, and 199 patients had obesity and high ASCVD risk.

CONCLUSIONS

This two-stage design (stratified baseline cohort with nested intervention) enables independent evaluation of the mechanisms linking obesity, CVD risk, and BCAA, among other variables. This approach will clarify how these factors influence cardiovascular disease variability and weight loss outcomes.

TRIAL REGISTRATION: ClinicalTrials.gov (https://clinicaltrials.gov), NCT04551872.