Longitudinal Associations of Changes in Body Mass Index and Waist‐to‐Height Ratio With Cardiometabolic Risk Factors: Sex‐Specific Analyses in UK Biobank

ABSTRACT Aims To examine associations of within‐person changes in body mass index (BMI) and waist‐to‐height ratio (WHtR) with cardiometabolic outcomes, characterise dose–response non‐linearity and investigate effect modification by sex. Materials and Methods In this observational UK Biobank cohort, participants had repeated anthropometric and biochemical measurements approximately 4 years apart. Those with baseline cardiovascular disease, renal failure or cancer were excluded. Associations of BMI and WHtR change with cardiometabolic outcomes were examined using multivariable analysis of covariance and restricted cubic splines, with multiple imputation for missing data. Results Among 16 911 participants with a mean baseline BMI 26.8 kg/m 2 (SD: 4.5), 679 experienced ≥ 10% BMI loss and 705 ≥ 10% gain over median 4.4 years. Compared with stable BMI (±5%), ≥ 10% loss was associated with lower systolic blood pressure (−6.11 mmHg; 95% CI: −7.14 to −5.07), triglycerides (−23.4%; −25.7 to −21.0) and C‐reactive protein (−39.5%; −43.7 to −35.1), with lower DBP, total and LDL cholesterol, HbA1c and SCORE2 and higher HDL cholesterol. Conversely, ≥ 10% gain was associated with higher SBP (+4.23 mmHg; 3.22–5.23), triglycerides (+16.9%; 13.4–20.5) and C‐reactive protein (+45.7%; 36.0–56.1), with adverse differences across most outcomes. Associations were broadly similar for BMI and WHtR, with non‐linearity for selected outcomes. Sex modified associations with DBP, lipids and SCORE2, with larger triglyceride reductions accompanying BMI loss in men. Conclusions Adiposity reduction was associated with favourable cardiometabolic profiles, whereas gain was associated with adverse profiles. BMI and WHtR showed broadly similar directions and patterns of association, with some variation by outcome and sex. These observational associations support prevention of excess adiposity gain and sustained adiposity reduction where clinically appropriate.