Effect of Plasma Fibrinogen Levels on the Risk of Stroke in Patients with Type 2 Diabetes: A Systematic Review.

Aims In this systematic review, we assessed the literature on the association between fibrinogen levels and stroke in patients with type 2 diabetes (T2D). Methods MEDLINE and Ovid searches of English reports were performed on the relation between fibrinogen, stroke, and T2D in humans. The search was completed on May 4, 2023. Studies were eligible when T2D patients ≥18 years had stroke confirmed by computed tomography or magnetic resonance imaging, plasma fibrinogen was measured, and a relation between fibrinogen and stroke in T2D patients was reported. Screening of reports and extraction of data were done independently by two authors, and study quality was assessed by predefined issues. Results Five studies of different designs were included. Three studies reported on significantly increased fibrinogen levels in T2D patients with stroke compared with T2D patients without stroke. Two studies did not observe a significant association between fibrinogen levels and stroke risk. Conclusion No consistent association was observed between fibrinogen levels and risk of stroke in T2D patients. Due to differences in study design, low sample size, and poorly defined study participants, larger and better-defined studies are needed to elucidate the role of fibrinogen as a stroke risk marker in T2D patients.

Validation of a fibrinogen γ' enzyme-linked immunosorbent assay using a new monoclonal antibody: effects of bariatric surgery.

Background: Fibrinogen γ' is a naturally occurring 20-amino-acid splice variant of the fibrinogen γ chain. Animal studies link variations in fibrinogen to obesity, but it is unknown how fibrinogen γ' is associated with obesity in humans. Objectives: To develop and validate an enzyme-linked immunosorbent assay (ELISA) for fibrinogen γ' quantification in human plasma and analyze fibrinogen γ' before and after bariatric surgery. Methods: We generated C-terminal fibrinogen γ' specific mouse monoclonal antibodies and developed a γ' ELISA. Validation included measures of accuracy, sensitivity, and precision. Fibrinogen γ' and total fibrinogen were measured in 60 individuals before and 6 months after bariatric surgery and in 19 normal-weight controls and 120 blood donors. Results: Highly specific fibrinogen γ' monoclonal antibodies were produced and successfully used in the ELISA. Recovery was 88%, and limits of detection and quantification were 0.003 mg/mL and 0.014 mg/mL, respectively. Coefficients of variation were 3% for repeatability and 7% for within-laboratory variation. The fibrinogen γ' reference interval was 0.25 to 0.80 mg/mL. Fibrinogen γ' concentrations were reduced after bariatric surgery and were higher in individuals with obesity than in those with normal weight. The fibrinogen γ'/total fibrinogen ratio was unchanged after surgery but was higher than the ratio in normal-weight individuals. Conclusion: We developed a precise and sensitive ELISA for fibrinogen γ'. Levels of fibrinogen γ', but not the fibrinogen γ'/fibrinogen ratio, were reduced 6 months after bariatric surgery. Absolute and relative levels of fibrinogen γ' were increased in individuals with obesity compared to normal-weight individuals.

No Detectable Coagulation Activation After Vitamin K (MK-7) Supplementation in Patients on Dialysis With Functional Vitamin K Deficiency: A One-Year Randomized, Placebo-Controlled Study.

OBJECTIVE: Patients on dialysis treatment have poor functional vitamin K status, and this may increase the risk of vascular calcification. Vitamin K supplementation may therefore be relevant in patients on dialysis, but the procoagulant effects have not been studied. We evaluated effects of menaquinone-7 (MK-7) supplementation on biomarkers of coagulation in patients on dialysis. METHODS: Double-blinded, placebo-controlled study in 123 patients on dialysis randomized to 52 weeks of vitamin K (MK-7, 360 µg/daily, n = 61) or placebo (n = 62). Measurements at baseline and after 52 weeks of intervention included thrombin generation (endogenous thrombin potential, peak thrombin concentration, time to peak, and lag time); clot activities of vitamin K-dependent coagulation factors (F) II, VII, IX, and X; prothrombin fragment 1 + 2 (F1+2); and proteins induced by vitamin K absence II (PIVKA-II). Between-group differences (vitamin K vs. placebo) at 52 weeks were determined with an analysis of covariance. Within-group changes in vitamin K and placebo groups were analyzed with a paired t-test. Vascular adverse events and serious adverse events were registered based on hospital records, laboratory data, and participant interviews and compared between groups using Fisher's exact test or Pearson's Chi-Squared test. RESULTS: A between-group difference at 52 weeks was observed for PIVKA-II (P < .001). PIVKA-II decreased significantly from baseline to 52 weeks in the vitamin K group, but not in the placebo group. We observed no between-group differences or within-group changes for biomarkers of coagulation, except for FVII clot activity which was reduced in the placebo group (P = .04), and no between-group differences in adverse events and serious adverse events. CONCLUSION: One year of vitamin K supplementation in patients on dialysis has no detectable effects on biomarkers of coagulation activation, clot activities of vitamin K-dependent coagulation factors, and vascular events or death, indicating no procoagulant effects of this treatment.

Testosterone therapy increases the anticoagulant potential in men with opioid-induced hypogonadism: a randomized, placebo-controlled study.

Introduction: Hypogonadism is prevalent during opioid treatment, and low testosterone concentrations are associated with cardiovascular disease. The effect of testosterone replacement therapy (TRT) on the coagulation system in men with hypogonadism is not clarified. We investigate the effects of TRT on the tissue factor (TF) and contact activation pathways of coagulation in opioid-treated men. Materials and methods: This was a double-blinded, placebo-controlled study in 37 men with total testosterone < 12 nmol/L randomized to 24 weeks of testosterone injections (n = 17) or placebo (n = 20). Variables of the coagulation system were analysed at baseline and after 24 weeks. Measurements included the TF pathway (endogenous thrombin potential (ETP) and peak thrombin), the contact activation pathway (endogenous kallikrein potential (EKP) and peak kallikrein), coagulation factors (FVII, FX, prothrombin, and FXII), and inhibitors (tissue factor pathway inhibitor (TFPI), protein C, protein S, antithrombin, and C1 esterase inhibitor (C1inh)). Between-group differences at 24 weeks were determined with analysis of covariance. Within-group changes in TRT and placebo were analysed with paired t-test. Results: Between-group differences at 24 weeks were observed for ETP (P = 0.036), FVII (P = 0.044), FX (P = 0.015), prothrombin (P = 0.003), protein C (P = 0.004), and protein S (P = 0.038). Within the TRT group, ETP, peak thrombin, FVII, FX, prothrombin, TFPI, protein C, FXII, and C1inh decreased and protein S increased (all P < 0.05). Within the placebo group, coagulation outcomes were unchanged. Conclusion: TRT affects the coagulation system in an anticoagulant direction through suppressed TF pathway in men with opioid-induced hypogonadism.

Respiratory Effects of Treatment with a Glucagon-Like Peptide-1 Receptor Agonist in Patients Suffering from Obesity and Chronic Obstructive Pulmonary Disease.

PURPOSE: Chronic obstructive pulmonary disease (COPD) affects millions of people worldwide. Obesity is commonly seen concomitantly with COPD. People with COPD have reduced quality of life, reduced physical activity, chronic respiratory symptoms, and may suffer from frequent clinical exacerbations. Liraglutide is a glucagon-like peptide-1 receptor agonist (GLP-1RA) approved for weight loss and treatment of type-2 diabetes mellitus. In addition, liraglutide exerts anti-inflammatory actions by reducing IL-6 and MCP-1 levels. We investigated the effect of liraglutide on pulmonary function in people suffering from obesity and COPD. PATIENTS AND METHODS: In this controlled, double-blind trial, 40 people with obesity and COPD from two outpatient clinics were allocated randomly to receive liraglutide (3.0 mg, s.c.) or placebo (s.c.) for 40 weeks. At baseline and after 4, 20, 40, and 44 weeks, participants underwent pulmonary-function tests, 6-min walking test, and replied to a questionnaire regarding the clinical impact of COPD (COPD assessment test (CAT)-score). RESULTS: Compared with placebo, liraglutide use resulted in significant weight loss, increased forced vital capacity (FVC) and carbon monoxide diffusion capacity, and improved CAT-score. We found no significant changes in forced expiratory volume in one second (FEV1), FEV1/FVC, or 6-min walking distance. CONCLUSION: In patients suffering from obesity and COPD, 40 weeks of treatment with liraglutide improved some measures of pulmonary function. Our study suggests that liraglutide at 3.0 mg may be appropriate treatment in patients with obesity and COPD.

High-fat meals do not affect thrombin formation and fibrin clot lysis in individuals with obesity during intentional weight loss.

Repeated weight loss cycles are associated with increased cardiovascular morbidity. Meal-induced thrombin formation, measured as prothrombin fragment 1+2 (F1+2), is observed in individuals with overweight after weight loss, and postprandial effects can be one of the mechanisms underlying harmful effects during intentional weight loss. We hypothesize that consumption of high-fat meals during intentional weight loss triggers a prothrombotic state by increasing postprandial F1+2 or decreasing fibrin clot lysis in individuals with obesity, and that the response associates with the gut bacteria composition. A cross-over meal study was conducted in patients admitted to bariatric surgery during dietary weight loss (N = 20) and surgical weight loss (N = 16) (weight loss groups). High-fat (67 E%) and low-fat (16 E%) meals were served at 08:15 and 10:00 on 2 study days. Blood samples collected at 08:00 (fasting), 12:00, and 14:00 were analyzed for triglycerides, activated factor VII (FVIIa), F1+2, D-dimer, fibrinogen, tissue factor , and fibrin clot lysis. The proportion of Gram-negative bacteria and bacterial diversity were analyzed in fecal samples obtained less than 24 hours before the meal test. Triglyceride and FVIIa increased after high-fat meals in both weight loss groups, whereas D-dimer (dietary group) and F1+2 decreased and tissue factor and fibrin clot lysis did not change. There was a negative association between the proportion of Gram-negative bacteria and changes in FVIIa in the surgery group. Postprandial FVII activation after high-fat meals is not accompanied by increased F1+2, irrespective of the weight loss intervention, but might be associated with the proportion of Gram-negative gut bacteria.

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 (ß = -0.40) and triglycerides (ß = 0.39). Changes in C1-inh associated with reductions in body weight (ß = -0.39) and HbA1c (ß = 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.

Postprandial factor VII activation does not increase plasma concentrations of prothrombin fragment 1 + 2 in patients with morbid obesity.

INTRODUCTION: Increased postprandial factor VII activation is observed after high-fat meals, but is not accompanied by thrombin formation in normal weight individuals. Obesity is associated with a higher circulating concentration of tissue factor (TF) and postprandial uptake of lipopolysaccharide (LPS), and this may increase thrombin formation after high-fat meals. We therefore compared postprandial effects of high-fat meals and low-fat meals on biomarkers of coagulation activation in patients with morbid obesity and investigated whether the response was associated with the gut bacteria composition. MATERIALS AND METHODS: A controlled cross-over study was conducted in obese patients (15 women, 5 men, mean BMI = 44.1 kg/m2), where high-fat meals (67 E% fat) and low-fat meals (16 E% fat) were served at 8:15 and 10:00 in a random order on two study days within one week. Blood samples were collected at 08:00 (fasting), 12:00, and 14:00 and analysed for triglycerides, activated FVII (FVIIa), TF, FVIIa-antithrombin (FVIIa-AT), prothrombin fragment 1 + 2 (F1+2), and TF pathway inhibitor (TFPI). The gut bacteria composition, measured as gram-negative bacteria and diversity, was analysed in faecal samples. RESULTS: Triglycerides, FVIIa, and FVIIa-AT increased significantly after high-fat meals, whereas F1 + 2 decreased equally and significantly over time after both meals. There were no significant changes in TF and TFPI over time. The postprandial changes in F1 + 2 and TFPI after high-fat meals were negatively correlated with diversity. CONCLUSIONS: Increased postprandial FVIIa is not accompanied by thrombin formation four hours after high-fat meals in patients with morbid obesity, possibly due to FVIIa-inhibition by AT.

Reductions in plasmin inhibitor and fibrinogen predict the improved fibrin clot lysis 6 months after obesity surgery.

Prothrombotic and metabolic variables are decreased after obesity surgery, and fibrin clot lysis is increased. It is unknown how fibrinolytic variables are affected, and whether fibrinolytic and metabolic changes predict the enhanced clot lysis. Study aims were to determine fibrinolytic biomarkers before and 6 months after Roux-en-Y gastric bypass (RYGB) and to identify predictors of the RYGB-induced increase in clot lysis. Women (n = 42) and men (n = 18) with obesity underwent RYGB, and factor XIII (FXIII), thrombin activatable fibrinolysis inhibitor (TAFI), plasminogen and plasmin inhibitor (PI) were measured before and 6 months after surgery. Regression analyses identified determinants of the RYGB-induced increase in clot lysis among changes in fibrinogen and in fibrinolytic and metabolic variables. Results showed that after RYGB, FXIII, TAFI, plasminogen and PI were reduced (P < .0005). Reductions in PI (ß = -0.59) and fibrinogen (ß = -0.35), together with age (ß = -0.22) and male sex (ß = 0.22), predicted the enhanced clot lysis with the model explaining 56% (P < .0005). Predictors of the reduction in PI were reductions in cholesterol (ß = 0.37) and glucose (ß = 0.29), together with male sex (ß = -0.28), whereas reductions in fibrinogen were predicted by lowering of interleukin-6 (IL-6) (ß = 0.32). In conclusion, fibrinolytic variables were reduced 6 months after RYGB. Targeting PI and fibrinogen, by reducing metabolic variables such as glucose, cholesterol and IL-6, has a profibrinolytic effect in obesity.

Effects of Obesity Surgery on Blood Coagulation and Fibrinolysis: A Literature Review.

OBJECTIVE: Obesity is characterized by a disturbed hemostatic balance with increased coagulation and impaired fibrinolysis. This increases the risk of thrombosis, and the risk is lowered after obesity surgery. Over the past 25 years, several studies have contributed to understand the mechanisms behind the antithrombotic effect of obesity surgery, and this literature review summarizes the results of these studies. METHODS: A detailed literature search on the effects of obesity surgery on the hemostatic balance was conducted. RESULTS: The 25 relevant studies reviewed demonstrated that obesity surgery has favorable effects on many biomarkers of coagulation and fibrinolysis. The evidence is substantial for fibrinogen and plasminogen activator inhibitor type 1 with average reductions from 1 to 24 months after obesity surgery of 17 and 48%, respectively. For most other biomarkers, the evidence is moderate or weak with average effect sizes varying from 2% for fiber mass length ratio to 70% for prothrombin fragment 1 + 2 and with a large variation between studies. Many studies are small and of short duration, and the surgical techniques differ. Also, studies are confounded by changes in medication, comorbidity, diet, and exercise. It is unknown whether the hemostatic changes are mediated by weight loss alone or by the accompanying metabolic improvements. CONCLUSION: Despite issues of confounding, this review suggests that obesity surgery shifts the hemostatic balance in the antithrombotic direction, thereby reducing the thrombotic potential of people with obesity, but more studies are needed for most of the biomarkers.

Venous thromboembolism in anorexia nervosa: four cases from a specialized unit. Indication for thromboprophylaxis?

BACKGROUND: Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is a major cause of mortality and morbidity. VTE may occur asymptomatic or subclinical. Fluid retention during intensive re-nutrition or rapid weight changes are well-known phenomena in anorexia nervosa (AN) and may represent a significant risk factor for VTE. OBJECTIVE: The incidence of VTE in patients with AN is unknown, and the conditions may be overlooked in a complex clinical picture. METHOD: This study report four cases of VTE in women with severe AN (age range 19-41 years, BMI range 10.6-13.1) admitted to a specialized unit for medical stabilization. RESULTS: DVT or PE was diagnosed in all four patients. The patients were admitted for intensive re-nutrition according to conventional conservative guidelines with slow increase in energy supply (start low and advance slow). Due to suspected VTE, thromboprophylaxis was given during hospitalization, three of whom were undergoing re-nutrition. CONCLUSION: The four presented cases suggest that VTE during re-nutrition in AN may be an overlooked risk which may not be sufficiently addressed in the literature. General recommendations should not be issued on the basis of case reports; however, we want to raise awareness and call for studies to identify the VTE risk and appropriate thromboprophylaxis in AN patients.

The effects of sampling from a peripheral venous catheter compared to repeated venepunctures on markers of coagulation, inflammation, and endothelial function.

Peripheral venous (PV) catheters are often used for serial blood sampling, but studies suggest that PV catheters increase markers of coagulation activation and inflammation. Whether the increase is caused by irritation of the vessel wall or diurnal variation is unknown. We therefore compared the effects of a PV catheter and repeated venepunctures on markers of coagulation, inflammation, and endothelial function.A PV catheter was inserted at 07:45 in a hand vein in 10 healthy subjects, and blood samples were collected at 8:00, 10:00, 12:00, and 14:00. In the contralateral arm, blood was simultaneously obtained by venepunctures. Measures of coagulation, i.e., activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen, prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin (TAT), inflammation, i.e., interleukin 6 (IL-6) and C-reactive protein (CRP), and endothelial function, i.e., plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA), von Willebrand factor (vWF), and tissue factor (TF) were measured in plasma.The concentrations of TAT and F1 + 2 were significantly increased (10:00; p < .01, 12:00; p < .05, and 14:00; p < .01) in PV catheter samples compared with venepuncture samples. There was a minor increase in PT and INR and no increase in APTT, fibrinogen, CRP, PAI-1, tPA, vWF, and TF, with no differences between sampling methods. IL-6 concentrations increased in many PV catheter samples and venepuncture samples, but the response varied between the subjects.Blood collection through a PV catheter induces coagulation activation, whereas endothelial function is not affected. More studies are needed to disclose the effect of blood sampling on IL-6.

Physical training following gastric bypass: effects on physical activity and quality of life-a randomized controlled trial.

BACKGROUND: Obesity is associated with physical inactivity and impaired health-related quality of life (HRQoL). We aim to test the hypothesis that Roux-en-Y gastric bypass (RYGB) followed by supervised physical training improves physical activity (PA) levels and HRQoL. METHODS: Sixty patients, qualified for RYGB, were at 6 months post-surgery randomized to 26 weeks of a supervised physical training intervention (INT) or to a control (CON) group. PA was assessed by accelerometry and using the questionnaire RPAQ. HRQoL was measured by the SF-36 questionnaire. All assessments were performed pre-surgery and 6, 12, and 24 months post-surgery. RESULTS: RYGB did not improve objectively or self-reported PA, but improved all domains of SF-36 (all p < 0.01). Objectively measured light PA, moderate to vigorous PA, and step counts tended to increase in INT compared to CON 12 months after RYGB (0.05 < p < 0.09), but the effects failed to persist. The SF-36 domain "general health" increased in INT compared to CON 24 months after RYGB (p = 0.041). CONCLUSION: RYGB improves HRQoL, but does not increase PA. Supervised physical training intervention improves general health 24 months after RYGB and tends to improve certain domains of PA right after the intervention period, but fails to increase the patients' overall PA level over time. Clinical Trial Registration Registered at ClinicalTrials.gov-no. NCT01690728.

Effects of 6 Months of Active Commuting and Leisure-Time Exercise on Fibrin Turnover in Sedentary Individuals with Overweight and Obesity: A Randomised Controlled Trial.

Obesity and exercise constitute important factors for cardiovascular disease risk, but the long-term effects of different exercise modalities on haemostatic biomarkers are not well elucidated. We investigated the effects of 6 months of active commuting or leisure-time exercise on measures of fibrin turnover in individuals who are overweight and obese. Ninety younger (20-40 years), sedentary, healthy women and men who are overweight and obese (BMI: 25-35 kg/m2) were randomised to 6 months of habitual lifestyle (CON, n=16), active commuting (BIKE, n=19), or leisure-time exercise of moderate (MOD, ∼50% VO2peak reserve, n=31) or vigorous intensity (VIG, ∼70% VO2peak reserve, n=24). Fasting blood samples (baseline and 3 and 6 months) were analysed for cholesterols and triglycerides, thrombin generation, prothrombin fragment 1 + 2, D-dimer, fibrin clot properties, and fibrinolytic activity. We observed no differences between CON, BIKE, MOD, and VIG during the intervention and no time effects for any of the variables measured despite increased VO2peak in all exercise groups. We found no difference between CON and all exercise groups combined and no gender-specific effects of exercise. Our findings suggest that thrombin generation capacity, coagulation activation, fibrin clot structure, and lysability are unaffected by long-term active commuting and leisure-time exercise in women and men who are overweight and obese.

Effects of gastric bypass followed by a randomized study of physical training on markers of coagulation activation, fibrin clot properties, and fibrinolysis.

BACKGROUND: The risk of cardiovascular disease is reduced by bariatric surgery, but it is unknown if exercise after bariatric surgery reduces this risk even further. OBJECTIVE: To investigate if Roux-en-Y-gastric bypass (RYGB) and supervised physical training after RYGB improve cardiovascular disease risk markers within coagulation activation, fibrin clot properties, and fibrinolysis. SETTING: Bariatric center, Hospital of Southwest Jutland, Denmark. METHODS: Sixty obese patients underwent RYGB and 6 months after RYGB were randomized to 26 weeks of physical training or a control group. Biomarkers within coagulation activation, fibrin clot properties, and fibrinolysis were measured presurgery, and 6, 12, and 24 months postsurgery. RESULTS: Six months after RYGB, the endogenous thrombin potential decreased from 1744 (1603-2003) to 1416 (1276-1582) nM × min (P<.001). Alterations in fibrin clot properties resulted in an increased clot lysis from 23.8% (16.1%-38.9%) to 40.3% (28.5%-59.35; P<.0001). Furthermore, fibrinogen was reduced from 12.6 (11.1-14.7) to 11.5 (9.90-13.3) µM (P<.001), and plasminogen activator inhibitor antigen was reduced from 40.5 (28.4-49.4) to 24.4 (15.4-32.7) ng/mL (P<.0001). Physical training after RYGB increased fibrinolytic activity from 58.0 (36.0-75.5) to 88.0 (66.0-132.0) IU/mL compared with 52.5 (30.0-80.0) to 64.0 (49.0-100.0) IU/mL in controls (P<.01) and reduced plasminogen activator inhibitor antigen from 23.5 (16.7-35.4) to 18.1 (14.3-25.4) ng/mL compared with 24.4 (13.9-28.7) to 24.2 (14.1-29.6) ng/mL in controls (P<.05). No effects of physical training were observed on markers of coagulation activation and fibrin clot properties. CONCLUSION: We observed favorable long-term reductions in markers of thrombin generation, improved fibrin clot properties, and increases in fibrinolysis after RYGB. Supervised physical training after RYGB further increased fibrinolysis.

Effects of gastric bypass surgery followed by supervised physical training on inflammation and endothelial function: A randomized controlled trial.

BACKGROUND AND AIMS: Obesity and physical inactivity are both associated with low-grade inflammation and endothelial dysfunction. Bariatric surgery improves markers of inflammation and endothelial function, but it is unknown if physical training after bariatric surgery can improve these markers even further. Therefore, we aimed to investigate the effects of Roux-en-Y gastric bypass (RYGB) followed by physical training on markers of low-grade inflammation and endothelial function. METHODS: Sixty patients approved for RYGB underwent examinations pre-surgery, 6, 12, and 24 months post-surgery. Six months post-surgery, they were randomized 1:1 to an intervention group or a control group. The interventions consisted of two weekly sessions of supervised moderate intensity physical training for a period of 26 weeks. Fasting blood samples were analyzed for concentrations of interleukin 6 (IL-6), C-reactive protein (CRP), intercellular adhesion molecule 1 (ICAM-1), tissue-type plasminogen activator antigen (t-PA:Ag) and von Willebrand factor (vWF). RESULTS: RYGB markedly improved markers of inflammation (IL-6, CRP) (p < 0.001) and endothelial function (ICAM-1, t-PA:Ag, vWF) (p < 0.05), and the improvements were sustained 24 months post-surgery (p < 0.01), except for the effects on vWF. We found no correlations between the changes in weight or BMI and the changes in markers of inflammation and endothelial function, except that the change in vWF was found to be inversely correlated with the changes in weight and BMI. We observed no effects of supervised physical training on markers on inflammation or endothelial function (p>0.1 for all). CONCLUSIONS: RYGB causes substantial and sustained favorable effects on markers of inflammation and endothelial function. Supervised physical training after RYGB did not cause additional improvements.

Supervised Physical Training Improves Weight Loss After Roux-en-Y Gastric Bypass Surgery: A Randomized Controlled Trial.

OBJECTIVE: Bariatric surgery results in significant weight loss and reduces cardiovascular morbidity. However, a large variation in postsurgery weight loss is seen. Physical activity promotes weight loss in nonsurgically treated subjects with obesity. The aim of this study was to investigate the effects of 6 months of supervised physical training following Roux-en-Y gastric bypass surgery (RYGB) on body weight and cardiovascular risk markers. METHODS: Sixty participants eligible for RYGB were included. Six months post surgery, the participants were randomly assigned to either twice-weekly supervised physical training sessions in a fitness center (INT) or a control group (CON) for 26 weeks. Before surgery and 6, 12, and 24 months after surgery, the participants underwent an examination program that included anthropometric measurements, blood pressure, heart rate, blood samples, and an abdominal computed tomography scan. RESULTS: RYGB significantly reduced body weight and improved cardiovascular risk markers (all P < 0.01). The supervised physical training intervention resulted in a 4.2-kg (CI: -0.2 to -8.3 kg) lower body weight in INT compared with CON at the study end (P = 0.042). The high-density lipoprotein concentration was significantly higher in INT than in CON at the termination of the intervention, but this was not maintained at the 24-months examination. CONCLUSIONS: Physical training following RYGB improves weight loss and cardiovascular health.

Anti-inflammatory effects of active commuting and leisure time exercise in overweight and obese women and men: A randomized controlled trial.

BACKGROUND AND AIMS: Physical inactivity is linked to low-grade inflammation, endothelial dysfunction and cardiovascular disease. We aimed to determine effects of active commuting and leisure time exercise on markers of low-grade inflammation and endothelial function in overweight and obese women and men. METHODS: We randomized 130 younger (20-45 years), physically inactive, healthy, overweight and obese (BMI: 25-35 kg/m2) women and men recruited from the Copenhagen area, Denmark, to either 6 months of habitual lifestyle (CON, n = 18), active commuting (BIKE, n = 35), or leisure time exercise of moderate (MOD, ∼50% VO2peak, n = 39) or vigorous intensity (VIG, ∼70% VO2peak, n = 38). Fasting blood samples were collected at baseline, 3, and 6 months and analyzed for concentrations of C-reactive protein (CRP), fibrinogen, von Willebrand factor (vWF), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor type 1 (PAI-1), and 90 participants (CON, n = 16; BIKE, n = 19; MOD, n = 31, VIG, n = 24) were included in a per-protocol analysis. RESULTS: We observed lower concentrations of CRP in MOD compared with CON at 6 months (p = 0.013) and within-group decreases in CRP in BIKE (3 months: p = 0.045) and MOD (3 months: p = 0.061; 6 months: p = 0.038) corresponding to a 30% decrease in BIKE and 19% in MOD from baseline till 6 months. No effects of exercise were observed on fibrinogen, vWF, t-PA, PAI-1 or the t-PA/PAI-1 ratio within or between groups. CONCLUSIONS: Our findings suggest an anti-inflammatory effect of active commuting and moderate, but not vigorous, intensity leisure time exercise, but no alterations in endothelial function during 6 months of intervention.

Endurance exercise per se reduces the cardiovascular risk marker t-PA antigen in healthy, younger, overweight men.

INTRODUCTION: The cardiovascular risk marker tissue plasminogen activator antigen (t-PA:Ag) can be reduced by long-term exercise interventions, but it is unknown, whether this is due to the weight loss induced by physical activity or due to the physical activity per se. MATERIALS AND METHODS: This was tested in 60 healthy, younger (20-40years), overweight (BMI: 25-30kg/m2) men randomly assigned to 12weeks of intervention in one of four groups: training (T); energy-reduced diet (D); training and increased diet (T-iD); sedentary lifestyle and unchanged diet (controls, C). Fasting blood samples were obtained before and after 12weeks of intervention and analyzed for plasma t-PA:Ag. RESULTS: Body weight was reduced in groups T and D. We observed a decrease in t-PA:Ag from baseline to 12weeks in all three exercise and diet intervention groups, and no change in the control group. A between-group difference in t-PA:Ag was observed at 12weeks (p=0.001), and this was due to lower values in T (p=0.0005), D (p=0.005) and T-iD (p=0.009) compared with the control group. Total body fat mass was reduced in all three exercise groups, and we observed a positive correlation between changes in t-PA:Ag and changes in intra-abdominal and subcutaneous adipose tissue volume. CONCLUSIONS: Our results demonstrate that t-PA:Ag was reduced in all three intervention groups. This suggests that 12weeks of endurance training per se, irrespective of concomitant weight loss, beneficially affects cardiovascular risk in healthy, younger, overweight men.