Early effects of gastric bypass on endothelial function, inflammation, and cardiovascular risk in obese patients

Background: Obesity is associated with a chronic low-grade inflammatory state, insulin resistance, and endothelial dysfunction, all of which contribute to increased risk of cardiovascular disease. We hypothesized that gastric bypass would produce rapid improvements in endothelial function, reduce inflammation, and lead to a decrease in cardiovascular risk. Methods: We performed a prospective study of morbidly obese patients who underwent laparoscopic Roux-en-Y gastric bypass (RYGB). Clinical data, biochemical markers of inflammation, and parameters indicative of cardiovascular risk were collected preoperatively and at 3 and 6 months postoperatively. Metabolic and inflammatory mediators that were quantified included C-reactive protein, fibrinogen, PAI-1, IL-6, IL-10, IL-1Ra, adiponectin, leptin, triglycerides, total cholesterol, HDL, LDL, glucose, insulin, and HbA1c. Brachial artery reactivity testing (BART) was performed to assess peripheral arterial endothelial function, and Framingham cardiovascular risk score (FRS) was calculated on all study participants pre- and postoperatively. Results: Fifteen patients (11 female) were enrolled (age = 49.2 ± 10.4 years; BMI = 48.1 ± 5.3 kg/m²). Six months post RYGB, mean BMI decreased to 35.4 ± 4.5, corresponding to 51.7% excess weight loss (P < 0.001). Mean waist circumference decreased significantly from 132 cm at baseline to 110 cm at 3 months (P = 0.003) and 107 cm at 6 months (P < 0.001). Six months after RYGB, weight loss led to significant improvements in clinical parameters indicative of cardiovascular disease or risk, including brachial artery diameter, endothelial independent vasodilation, and FRS. Favorable improvements in the proinflammatory markers CRP (P = 0.01) and leptin (P = 0.005), the anti-inflammatory mediator adiponectin (P = 0.002), and insulin sensitivity (HOMA-IR, P = 0.007) were evident at 3 months. At 6 months, improvements in CRP, leptin, and fasting insulin were maintained and fibrinogen levels also decreased (P = 0.047). Adiponectin continued to increase at 6 months (P = 0.004). Conclusion: Gastric bypass is associated with early reversal of endothelial dysfunction, a more favorable inflammatory milieu, and, most importantly, a reduction in cardiovascular risk.