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Mechanisms Driving the Effect of Weight Loss on Arterial Stiffness

Abstract

Aims Arterial stiffness decreases with weight loss in overweight and obese adults, but the mechanisms by which this occurs are poorly understood. We aimed to elucidate these mechanisms. Methods We evaluated carotid-femoral pulse wave velocity (cfPWV), a measure of aortic stiffness, and brachial-ankle pulse wave velocity (baPWV), a mixed measure of central and peripheral arterial stiffness, in 344 young adults (mean age 38 yrs, mean body mass index (BMI) 32.9 kg/m2, 23% male) at baseline, 6 and 12 months in a behavioral weight loss intervention. Linear mixed effects models were used to evaluate associations between weight loss and arterial stiffness and to examine the degree to which improvements in obesity-related factors explained these associations. Pattern-mixture models using indicator variables for dropout pattern and Markov Chain Monte Carlo multiple imputation were used to evaluate the influence of different missing data assumptions. Results At 6 months (7% mean weight loss from baseline), there was a statistically significant median decrease of 47.5 cm/s (interquartile range (IQR) -44.5, 148) in cfPWV (p<0.0001) and a mean decrease of 11.7 cm/s (standard deviation (SD) 91.4) in baPWV (p=0.049). At 12 months (6% mean weight loss from baseline) only cfPWV remained statistically significantly reduced from baseline (p=0.02). Change in BMI (p=0.01) was statistically significantly positively associated with change in cfPWV after adjustment for changes in mean arterial pressure (MAP) or any other measured obesity-related factor. Common carotid artery diameter (p=0.003) was associated and heart rate (p=0.08) and MAP (p=0.07) marginally associated longitudinally with cfPWV. Reductions in heart rate (p<0.0001) and C-reactive protein (p=0.02) were associated with reduced baPWV, and each removed the statistical significance of the effect of weight loss on baPWV. Pattern-mixture modeling revealed several differences between completers and non-completers in the models for cfPWV, but marginal parameter estimates changed little from the original models for either PWV measure. Conclusions The public health importance of this thesis is that firstly, weight loss improves arterial stiffness in overweight and obese young adults. Secondly, its effect on baPWV may be explained by concurrent reductions in heart rate and inflammation. Missing data did not appear to bias these results

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