Body fat and human cardiovascular ageing

Abstract

AbstractObjectiveCardiovascular ageing is a progressive loss of physiological reserve, modified by environmental and genetic risk factors, that contributes to multi-morbidity due to accumulated damage across diverse cell types, tissues and organs. Obesity is implicated in premature ageing but the effect of body fat distribution in humans is unknown. Here we assessed the association between image-derived adiposity phenotypes on cardiovascular age in men and women.MethodsWe analysed data from 21,241 participants in UK Biobank. Machine learning was used to predict cardiovascular age from 126 image-derived traits of vascular function, cardiac motion and myocardial fibrosis. An age-delta was calculated as the difference between predicted age and chronological age. The volume and distribution of body fat was assessed from whole body imaging. The association between adiposity phenotypes and cardiovascular age-delta was assessed using multivariable linear regression with age and sex as co-covariates, reporting β coefficients with 95% confidence intervals (CI). Two-sample Mendelian randomisation was used to assess causal associations.ResultsVisceral adipose tissue volume (β = 0.656, [95% CI, 0.537 - 0.755],P< 0.0001), muscle adipose tissue infiltration (β = 0.183, [95% CI, 0.122 - 0.244],P= 0.0003), and liver fat fraction (β = 1.066, [95% CI 0.835 - 1.298],P< 0.0001) were the strongest predictors of increased cardiovascular age-delta for both sexes. Abdominal subcutaneous adipose tissue volume (β = 0.688, [95% CI, 0.64 - 1.325],P< 0.0001) was associated with increased age-delta only in males. Genetically-predicted gluteo-femoral fat showed an association with decreased age-delta.ConclusionThis work demonstrates the contribution of sex-dependent patterns of visceral adipose tissue and subcutaneous fat distribution to biological cardiovascular ageing in middle aged adults. This highlights the potential for strategies to attenuate ageing through modifying adipose tissue function.