Adiposity and coronary heart disease in the UK Biobank: a prospective cohort study of 500 000 adults

Thesis

Background Excess adiposity is a known risk factor for coronary heart disease (CHD). However, the underlying mechanisms have not been fully elucidated, and the relevance of different adiposity phenotypes remains unclear.

Methods The UK Biobank is a prospective study of 500 000 adults enrolled between 2006 and 2010 across the UK. Correlates of adiposity at baseline were explored for established and emerging cardiovascular risk factors. Cox regression analyses were used to obtain adjusted hazard ratios (HRs) for the associations of usual levels of body-mass index (BMI), body fat %, trunk fat % , waist circumference (WC), waist-to-height ratio (WHTR) and waist-to-hip ratio (WHR), or with genetically elevated BMI-adjusted WHR (WHRadjBMI) and BMI with incident CHD.

Results Among 455 148 participants without prior cardiovascular disease, 13 114 first-ever CHD events occurred over a mean follow-up period of 8 years. Measurement error and within-person variability was less extreme for BMI (regression dilution ratio: 0.92) than other measures, particularly WHR (0.66). Adiposity measures were closely correlated with each other at baseline, as well as with a number of socio-demographic, lifestyle and biological characteristics. In analyses adjusted for age, sex, socio-economic status, smoking and alcohol consumption, increasing usual levels of adiposity (i.e. corrected for regression dilution) were positively and log-linearly associated with CHD risk across all measures. Associations were notably stronger for central adiposity, particularly WHR (HR per usual SD 1.34, 95% CI 1.31-1.38) compared with BMI (1.24, 1.22-1.26). The relevance of usual WHR to CHD was particularly strong among women (1.41, 1.35-1.48), and remained strongly associated with CHD after adjustment for BMI. The observed prospective associations were partially mediated by blood pressure, lipids and insulin resistance, which explained at least half of the observed excess risk. Additional adjustment for glomerular filtration rate, liver enzymes and inflammatory markers completely attenuated associations with all measures except WHTR and WHR, which remained independently associated with CHD risk. Genetically elevated adiposity measures were associated with CHD risk (HR per SD higher WHRadjBMI: 1.31, 1.11 – 1.55; BMI: 1.22, 1.06 - 1.41), and with cardiometabolic traits.

Conclusion Adiposity measures demonstrated strong, positive and approximately log-linear associations with CHD risk, with no evidence of threshold effects within the ranges studied in this UK population. Central body fat distribution was associated with higher CHD risk compared with BMI and likely involves distinct and independent mechanisms.

Authors: Malden, DE

• DOI: 10.5287/ora-9onx004no
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford