Contact activated kallikrein generation is reduced six months after gastric bypass

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 (rS): −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 (rS = −0.29, p = 0.025), but also with triglycerides (rS = 0.34, p = 0.007) and cholesterol (rS = 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.