Longitudinal Changes in Adiposity Indices and Risk of Incident Cardiovascular Disease: A Prospective Cohort Study

Background: The cardiovascular implications of longitudinal changes in adiposity indices remain incompletely understood. Methods: This prospective cohort enrolled participants from UK Biobank with repeated measurements of adiposity indices. Participants were divided into five groups for change of body mass index (BMI), waist circumference (WC) and body fat percentage (BF%) based on different trajectory patterns. The primary outcome was major adverse cardiovascular events (MACE), a composite of coronary heart disease, artery diseases, heart failure, atrial fibrillation, nonrheumatic valve disorders and cardiovascular death. Cox proportional hazards models and restricted cubic splines were used. Joint associations of changes in different adiposity indices were visualized using heatmaps. Population impact fractions (PIFs) estimated preventable events under counterfactual trajectory-shift scenarios. Findings: Compared with stable group, an increase in BMI of 5-10% and >10% was associated with a higher risk of MACE (HR [95% CI]: 1.14 [1.02-1.27]; 1.37 [1.20-1.58], respectively), as were increases in WC of >10 cm (1.21 [1.06-1.39]) and BF% of >10% (1.11 [1.01-1.23]). A decrease in BMI of >10% or in BF% of 5-10% were also associated with higher MACE risk (HR [95% CI]: 1.16 [1.02-1.32]; 1.15 [1.01-1.32], respectively) compared with stable group. U-shaped association between adiposity indices and MACE was detected. Joint analyses showed that increased BMI with increased WC (1.20 [1.04-1.37]) or BF% (1.22 [1.07-1.40]), and decreased BMI with increased WC (1.29 [1.02-1.64]) had greater risks of MACE than stable BMI with stable WC or BF%. Under the counterfactual scenario of shifting extremely increase to the stable trajectory, estimated PIFs were 2.9% for BMI, 2.0% for WC and 3.4% for BF%. Interpretation: Substantial gains in adiposity were associated with an elevated risk of cardiovascular disease. Phenotypes characterized by concurrent increases in BMI and WC or BF%, as well as those with decreasing BMI but increasing WC, were identified as particularly high-risk groups.