Contact activated kallikrein generation is reduced six months after gastric bypass

Abstract

Background: Prothrombotic and inflammatory variables decrease after obesity surgery. The contact activation system may be a common denominator of these changes.

Objective: To characterize the contact system before and 6 months after Roux-en-Y gastric bypass (RYGB) and to evaluate associations with changes (post-surgery minus pre-surgery) in metabolic variables.

Methods: Women (n = 42) and men (n = 18) with obesity underwent RYGB, and measures of kallikrein generation, factor XII (FXII), prekallikrein, high molecular weight kininogen (HK), and C1 esterase inhibitor (C1-inh) were determined before and 6 months after surgery. Associations were evaluated using correlation and multivariate regression analyses.

Results: After RYGB, the endogenous kallikrein potential (EKP), peak kallikrein generation, FXII, and prekallikrein were reduced, and kallikrein generation lag time was prolonged (all p < 0.0005). Before and after RYGB, absolute values of EKP, lag time, and peak kallikrein generation correlated consistently with contact system proteins (range of correlation coefficients (r_S): -0.43 to -0.28 and 0.24 to 0.45 (pre-surgery); -0.43 to -0.30 and 0.28 to 0.50 (post-surgery)). RYGB-associated changes in EKP correlated with C1-inh (r_S = -0.29, p = 0.025), but also with triglycerides (r_S = 0.34, p = 0.007) and cholesterol (r_S = 0.28, p = 0.029), and independently associated with changes in C1-inh (β = -0.40) and triglycerides (β = 0.39). Changes in C1-inh associated with reductions in body weight (β = -0.39) and HbA1c (β = 0.38).

Conclusion: The contact system was affected 6 months after RYGB. Absolute values of kallikrein generation before and after RYGB correlated with contact system proteins, whereas changes after RYGB associated with changes in C1-inh and metabolic variables.

Keywords: Bariatric surgery; Hemostasis; Inflammation; Metabolism; Obesity.