Abstract
Arterial stiffness, measured by pulse wave velocity (PWV), is linked to obesity, cardiovascular disease, and all-cause mortality. Short-term weight loss improves PWV, but the long-term effects are unknown. We investigated the effect of pronounced long-term weight loss on PWV and whether anthropometric/metabolic parameters and/or white adipose tissue (WAT) phenotype could predict this change in PWV. Eighty-two obese subjects were examined before and 2 years after Roux-en-Y gastric bypass. Analyses included anthropometrics, routine clinical chemistry, and hyperinsulinemic-euglycemic clamp. Arterial stiffness was measured as aortic PWV (aPWV) using the Arteriograph device. WAT mass and distribution were assessed by dual-X-ray absorptiometry. Baseline visceral and subcutaneous WAT samples were obtained to measure adipocyte cell size. Transcriptomic profiling of subcutaneous WAT was performed in a subset of subjects (n = 30). At the 2-year follow-up, there were significant decreases in body mass index (39.4 ± 3.5 kg/m2 vs. 26.6 ± 3.4 kg/m2; P < 0.0001) and aPWV (7.8 ± 1.5 m/s vs. 7.2 ± 1.4 m/s; P = 0.006). Multiple regression analyses showed that baseline subcutaneous adipocyte volume was associated with a reduction in aPWV (P = 0.014), after adjusting for confounders. Expression analyses of 52 genes implicated in arterial stiffness showed that only one, COL4A1, independently predicted improvements in aPWV after adjusting for confounders (P = 0.006). Bariatric surgery leads to long-term reduction in aPWV. This improvement can be independently predicted by subcutaneous adipocyte volume and WAT COL4A1 expression, which suggests that subcutaneous WAT has a role in regulating aPWV. Trial Number NCT01727245 (clinicaltrials.gov).
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