Vazzana N, Guagnano MT, Aceto L, Innocenti P, Davì G. Thromboxane-Dependent Platelet Activation After Gastric Banding for Obesity. JAMA Surg. 2015;150(2):179-180. doi:10.1001/jamasurg.2014.1682
Laparoscopic adjustable gastric banding (LAGB) is associated with persistent weight reduction but variable health outcomes.1 The molecular heterogeneity of obesity may lead to substantial variability among its specific subtypes.2 In severe obesity, bariatric surgery is the only treatment that results in considerable, persistent weight loss. Compared with usual care, bariatric surgery reduced cardiovascular events among obese adults.3 We demonstrated in vivo platelet activation in obese women free from other cardiovascular risk factors.4 Moreover, visceral obesity was characterized by systemic inflammation and enhanced lipid peroxidation. A substantial reduction of this mechanistic chain of events was achieved with a successful weight loss program.4 Our study investigated whether platelet activation and oxidative stress were persistently modulated by LAGB in nondiabetic, normotensive obese participants.
Thirteen consecutive obese patients who were 18 years of age or older and scheduled to undergo LAGB were enrolled. Exclusion criteria were clinical evidence of cardiovascular disease, cancer, or altered liver or renal function, as well as treatment with lipid-lowering, antidiabetic, anti-inflammatory, antioxidant, or antithrombotic drugs. Patients were evaluated at baseline and after 3, 6, and 12 months. Overnight urine samples were obtained immediately before obtaining blood samples. Urinary 8-iso-prostaglandin F2α (PGF2α) and 11-dehydro-thromboxane B2 (TXB2) excretion rates were measured as previously described.4 The study protocol was approved by the local ethics committee, and patients provided written informed consent.
The effects of LAGB surgery were assessed using Friedman and Wilcoxon tests for paired samples. The Spearman rank correlation test and stepwise multiple linear regression analysis (using log-transformed data) were performed to assess variables associated with urinary 11-dehydro-TXB2 excretion rates. Two-sided P values of less than .05 were considered to be statistically significant.
The clinical and laboratory characteristics of the participants are shown in the Table. Lipid peroxidation (8-iso-PGF2α) and platelet activation (11-dehydro-TXB2), as well as C-reactive protein levels, progressively decrease at any time point following LAGB, with significant correlation among the 3 variables (P = .001). By pooling data from each time point after LAGB, we found that changes in urinary 8-iso-PGF2α and 11-dehydro-TXB2 excretion were significantly correlated (ρ = 0.67, P < .001). Moreover, both changes were significantly related to the amount of weight lost and to changes in body mass index, waist circumference, fasting plasma glucose level, and high-density lipoprotein cholesterol level. Changes in the homeostatic model assessment of insulin resistance (HOMA-IR) index correlated with changes in 11-dehydro-TXB2 (ρ = 0.466, P = .02).
A multiple regression analysis of pooled data from baseline and 6 and 12 months after LAGB indicates that only the 8-iso-PGF2α excretion rate (β = 0.611, t = 6.03, P < .001) and the HOMA-IR index (β = 0.385, t = 3.81, P = .001) can predict the rate of 11-dehydro-TXB2 excretion, independent of body mass index, waist circumference, serum lipid levels, fasting plasma glucose levels, postprandial plasma glucose levels, fat mass, and C-reactive protein levels (adjusted R2 = 0.665, P = .001).
We previously identified a novel mechanism through which obesity may affect cardiovascular morbidity and mortality (namely, thromboxane-dependent platelet activation).5 Moreover, we established that isoprostanes may be a link between obesity and platelet activation. Notably, a 10% reduction in body weight, obtained through a successful diet-induced weight loss program, was associated with more than a 50% reduction in thromboxane biosynthesis.4
In our study, the rates of 8-iso-PGF2α and 11-dehydro-TXB2 excretion were significantly reduced 12 months after LAGB (by approximately 45% and approximately 60%, respectively), correlated with an approximately 18% decrease in body weight and with a concomitant decrease (∼30%) in the level of C-reactive protein, a marker of systemic inflammation. However, because severe obesity is characterized by a very high rate of thromboxane biosynthesis, all but 4 values of thromboxane metabolite excretion did not return to the normal range 12 months after LAGB.
Moreover, weight loss following the surgical procedure significantly affected the fasting plasma glucose level, the postprandial plasma glucose level, and insulin sensitivity in our obese participants. Thus, the HOMA-IR index and the 8-iso-PGF2α excretion rate were the only predictors of the rate of thromboxane biosynthesis.
In conclusion, LAGB ameliorates the vicious cycle of inflammation, oxidative stress, and thromboxane-dependent platelet activation in obesity. However, the incomplete normalization of thromboxane biosynthesis in the majority of the obese participants may support the concept that different genotypic/phenotypic subtypes of obesity may exist.
Corresponding Author: Giovanni Davì, MD, Department of Internal Medicine, Center of Excellence on Aging, “G. d’Annunzio” University, Via Colle dell’Ara, 66013 Chieti, Italy (email@example.com).
Published Online: December 17, 2014. doi:10.1001/jamasurg.2014.1682.
Author Contributions: Drs Davì and Innocenti had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Guagnano, Innocenti, Davì.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Vazzana, Aceto, Innocenti, Davì.
Critical revision of the manuscript for important intellectual content: Guagnano.
Statistical analysis: Vazzana.
Obtained funding: Guagnano, Davì.
Administrative, technical, or material support: Guagnano, Aceto.
Study supervision: Innocenti, Davì.
Conflict of Interest Disclosures: None reported.