Decrease in microvesicle-associated tissue factor activity in morbidly obese patients after bariatric surgery.

BACKGROUND: Tissue factor (TF) is the main in vivo initiator of the blood coagulation cascade. Active circulating TF was detected on small, negatively charged membrane vesicles, the so-called microvesicles (MVs), which are released upon cell activation and apoptosis from a variety of cells. Increased coagulation activation was found in morbidly obese patients, and elevated levels of TF-bearing MVs may contribute to the prothrombotic state in these patients. AIM: To determine MV-associated TF activity levels in morbidly obese patients before and after weight loss due to bariatric surgery. METHODS: MV-TF activity was measured with a factor Xa generation assay in morbidly obese patients before and 2 years after bariatric surgery. In addition, clinical parameters were determined. RESULTS: Seventy-four morbidly obese patients (mean age: 42 (±11) years; 61 females) were included in this study. After bariatric surgery, the body mass index decreased from (median, 25-75th percentile) 45.5 (42.3-50.2) to 30.5 (28.0-34.4 kg m(-2); P<0.001), and a significant improvement in metabolic parameters was observed. Preoperative MV-TF activity correlated with C-reactive protein levels (r=0.3; P=0.02). Postoperatively, the mean MV-TF activity decreased significantly from 0.20 pg ml(-1) (0.18-0.47) to 0.02 (0.00-0.28; P<0.01). CONCLUSION: We could demonstrate a significant decrease in MV-TF activity after weight loss in morbidly obese patients. Decreased MV-TF activity might contribute to an improved coagulation profile in these patients after weight loss.

The association of incidentally detected heart valve calcification with future cardiovascular events.

OBJECTIVES: This study aims to investigate the prognostic value of incidental aortic valve calcification (AVC), mitral valve calcification (MVC) and mitral annular calcification (MAC) for cardiovascular events and non-rheumatic valve disease in particular on routine diagnostic chest CT. METHODS: The study followed a case-cohort design. 10410 patients undergoing chest CT were followed for a median period of 17 months. Patients referred for cardiovascular disease were excluded. A random sample of 1285 subjects and the subjects who experienced an endpoint were graded for valve calcification by three reviewers. Cox-proportional hazard analysis was performed to evaluate the prognostic value. RESULTS: 515 cardiovascular events were ascertained. Compared with patients with no valve calcification, patients with severe AVC, MVC or MAC had respectively 2.03 (1.48-2.78), 2.08 (1.04-4.19) and 1.53 (1.13-2.08) increased risks of experiencing an event during follow-up. For valve endpoints the hazard ratios were respectively 14.57 (5.19-40.53), 8.78 (2.33-33.13) and 2.43 (1.18-4.98). CONCLUSION: Incidental heart valve calcification, detected on routine chest CT is an independent predictor of future cardiovascular events. The study emphasises how incidental imaging findings can contribute to clinical care. It is a step in the process of composing an evidence-based approach in the reporting of incidental subclinical findings.

No association of obesity gene FTO with body composition at the age of 6 months. The Generation R Study.

BACKGROUND: Genome-wide association studies on body mass index (BMI) have identified an FTO polymorphism (rs9939609) as having the strongest effect. AIM: We examined the effect of FTO genotype on body composition at the age of 6 months using skinfold thickness measurements and dual energy X-ray absorptiometry (DXA). MATERIAL/SUBJECTS AND METHODS: This study was embedded in a population-based prospective cohort study from early fetal life onwards. FTO genotype was related to anthropometric measurements (weight and height), subcutaneous fat mass measured by skinfold thickness, and total, truncal, and peripheral fat mass and lean mass measured by DXA. Analyses for skinfold thickness and DXA were performed in 695 and 216 children, respectively. RESULTS: Genotype frequency was TT 40.3%, TA 45.5%, and AA 14.2%. No significant differences between FTO genotypes were found in weight, height or BMI. Furthermore, FTO genotype was not associated with any skinfold thickness. Finally, no associations between FTO genotype and body composition measures (fat and lean mass) assessed by DXA were found. CONCLUSIONS: We observed no association between this FTO polymorphism and body composition at the age of 6 months. Longer follow-up studies are necessary to examine at which age and by which mechanisms FTO genotype starts to influence fat mass and body composition.

Cardiovascular disease: prediction with ancillary aortic findings on chest CT scans in routine practice.

PURPOSE: To predict cardiovascular disease (CVD) in a clinical care population by using prevalent subclinical ancillary aortic findings detected on chest computed tomographic (CT) images. MATERIALS AND METHODS: The study was approved by the medical ethics committee of the primary participating facility and the institutional review boards of all other participating centers. From a total of 6975 patients who underwent diagnostic contrast material-enhanced chest CT for noncardiovascular indications, a representative sample population of 817 patients plus 347 patients who experienced a cardiovascular event during a mean follow-up period of 17 months were assigned visual scores for ancillary aortic abnormalities--on a scale of 0-8 for calcifications, a scale of 0-4 for plaques, a scale of 0-4 for irregularities, and a scale of 0-1 for elongation. Four Cox proportional hazard models incorporating different sum scores for the aortic abnormalities plus age, sex, and chest CT indication were compared for discrimination and calibration. The prediction model that performed best was chosen and externally validated. RESULTS: Each aortic abnormality was highly predictive, and all models performed well (c index range, 0.70-0.72; goodness-of-fit P value range, .45-.76). The prediction model incorporating the sum score for aortic calcifications was chosen owing to its good performance (c index, 0.72; goodness-of-fit P = .47) and its applicability to nonenhanced CT scanning. Validation of this model in an external data set also revealed good performance (c index, 0.71; goodness-of-fit P = .25; sensitivity, 46%; specificity, 76%). CONCLUSION: A derived prediction model incorporating ancillary aortic findings detected on routine diagnostic CT images complements established risk scores and may help to identify patients at high risk for CVD. Timely application of preventative measures may ultimately reduce the number or severity of CVD events.

Maternal anthropometrics are associated with fetal size in different periods of pregnancy and at birth. The Generation R Study.

OBJECTIVE: We aimed to examine the associations of maternal anthropometrics with fetal weight measured in different periods of pregnancy and with birth outcomes. DESIGN: Population-based birth cohort study. SETTING: Data of pregnant women and their children in Rotterdam, the Netherlands. POPULATION: In 8541 mothers, height, prepregnancy body mass index (BMI) and gestational weight gain were available. METHODS: Fetal growth was measured by ultrasound in mid- and late pregnancy. Regression analyses were used to assess the impact of maternal anthropometrics on fetal weight and birth outcomes. MAIN OUTCOME MEASURES: Fetal weight and birth outcomes: weight (grams) and the risks of small (<5th percentile) and large (>95th percentile) size for gestational age at birth. RESULTS: Maternal BMI in pregnancy was positively associated with estimated fetal weight during pregnancy. The effect estimates increased with advancing gestational age. All maternal anthropometrics were positively associated with fetal size (P-values for trend <0.01). Mothers with both their prepregnancy BMI and gestational weight gain quartile in the lowest and highest quartiles showed the highest risks of having a small and large size for gestational age child at birth, respectively. The effect of prepregnancy BMI was strongly modified by gestational weight gain. CONCLUSIONS: Fetal growth is positively affected by maternal BMI during pregnancy. Maternal height, prepregnancy BMI and gestational weight gain are all associated with increased risks of small and large size for gestational age at birth in the offspring, with an increased effect when combined.

Tracking and determinants of subcutaneous fat mass in early childhood: the Generation R Study.

OBJECTIVES: To examine the development and tracking of subcutaneous fat mass in the first 2 years of life and to examine which parental, fetal and postnatal characteristics are associated with subcutaneous fat mass. DESIGN: This study was embedded in the Generation R Study, a prospective cohort study from early fetal life onward. Subcutaneous fat mass was measured by skinfold thickness (biceps, triceps, suprailiacal, subscapular) at the ages of 1.5, 6 and 24 months in 1012 children. Information about parental, fetal and postnatal growth characteristics was collected by physical and fetal ultrasound examinations and questionnaires. RESULTS: Normal values of subcutaneous fat mass are presented. Total subcutaneous fat mass was higher in girls than in boys at the age of 24 months (P=0.01). Subjects in the lowest and highest quartiles at the age of 6 months tended to keep their position in the same quartile at the age of 24 months (odds ratios 1.86 (95% confidence interval (CI) 1.3, 2.7)) and 1.84 (95% CI: 1.3, 2.6), respectively). Maternal height and weight, paternal weight, fetal weight at 30 weeks, birth weight and weight at the age of 6 weeks were each inversely associated with subcutaneous fat mass at the age of 24 months after adjustment for current weight at 24 months. CONCLUSION: This study shows for the first time that subcutaneous fat mass tends to track in the first 2 years of life. Furthermore, the results suggest that an adverse fetal environment and growth are associated with increased subcutaneous fat mass at the age of 24 months. Further studies are needed to examine whether these associations persist in later life.

Influence of coronary anatomy and reimplantation on the long-term outcome of the arterial switch.

BACKGROUND: Abnormal coronary artery anatomy is reported to have a significant influence on the outcome of the arterial switch operation. This study examines the impact of coronary anatomy and the occurrence of late coronary obstruction on left ventricular (LV) function and long-term outcome. METHODS: Coronary artery anatomy, of 170 patients after arterial switch operation (1977-1999), was determined based on operative reports and pre-operative aortograms. Current status was evaluated using ECGs, echocardiograms, scintigraphy, and post-operative coronary angiograms. RESULTS: In 133/170 patients, coronary artery anatomy consisted of an anterior descending (LAD) and circumflex artery (Cx) from the left sinus and the right coronary artery (RCA) from the right or posterior sinus. The left coronary had an intramural initial course in two of these patients. Fifteen patients had the LAD from the left and Cx and RCA from the right sinus; eight had LAD and RCA from one sinus and Cx from the other; four had single ostium; and three had three separate ostia. Four patients had complex patterns and four patients had a supra commissural coronary. To date, follow-up angiography was performed in 59 patients. Surgical coronary sequellae were found in five patients. Two patients had an occluded left ostium. Initially, they were asymptomatic but showed polymorphic ventricular extrasystoles on ECG and moderate LV dysfunction with large irreversible perfusion defects on scintigraphy. Both patients developed ventricular fibrillation at the age of 14 years. One patient did not survive. The other patient required implantation of a defibrillator. One patient has an occluded RCA, one patient has stenosis of the right ostium and one patient has multiple tortuous collaterals without obstruction of a major branch. In the latter three patients, coronary sequellae were not suspected on ECG, echo, or scintigraphy and were only found on follow-up angiography. Retrograde collateral flow was noted in all three occluded coronaries. LV dysfunction, with normal coronaries, was noted in three patients. All, of these patients, had peri-operative ischaemia suggesting failure of myocardial protection. Two are now asymptomatic with mild LV dysfunction. One patient continues to have severe myocardial dysfunction and secondary aortic insufficiency. A Ross-like procedure was performed placing the original aortic valve in the neo-aortic root. Coronary artery anatomy did not influence early survival or late coronary sequellae. CONCLUSION: Abnormal coronary anatomy was not a determinant of outcome in our study. Surgical coronary obstruction is independent of original anatomy. It can be almost silent and is potentially fatal. Follow-up angiography must be considered in all patients after the arterial switch operation.

Parental anthropometrics, early growth and the risk of overweight in pre-school children: the Generation R Study.

BACKGROUND: There are limited data regarding the associations of both maternal and paternal anthropometrics with longitudinally measured post-natal growth measures in early childhood. OBJECTIVE: To assess the associations of maternal and paternal anthropometrics with growth characteristics and the risk of overweight in pre-school children. STUDY DESIGN: Population-based prospective cohort study from early foetal life onwards in the Netherlands. METHODS: Maternal pre-pregnancy anthropometrics and gestational weight gain, and paternal anthropometrics were related to foetal and post-natal growth measures and the risk of overweight until the age of 4 years. Analyses were based on 5674 mothers, fathers and their children. RESULTS: Both pre-pregnancy maternal and paternal height, weight and body mass index were associated with corresponding foetal and post-natal anthropometric measures. Maternal body mass index had a significantly stronger effect on childhood body mass index than paternal body mass index. As compared to children from parents with normal body mass index, children from two obese parents had an increased risk of overweight at the age of 4 years (odds ratio 6.52 (95% confidence interval 3.44, 12.38). Maternal gestational weight gain was only among mothers with normal body mass index associated with body mass index and the risk of overweight in the children. CONCLUSION: Maternal and paternal anthropometrics affect early growth in pre-school children differently. Gestational weight gain in mothers without overweight and obesity is related to the risk of overweight in early childhood.

Infant diet and subcutaneous fat mass in early childhood: the Generation R Study.

BACKGROUND/OBJECTIVES: Breastfeeding has a protective effect on childhood obesity, but the influences on body composition in early childhood are not known. The objective of this study is to assess whether the duration and exclusiveness of breastfeeding, and the timing of introduction of solid foods are associated with the subcutaneous fat mass in early childhood. SUBJECTS/METHODS: This study was embedded in a population-based prospective cohort study among 779 children. Peripheral (biceps, triceps) and central (suprailiacal and subscapular) subcutaneous fat mass was measured as skinfold thickness at the ages of 1.5, 6 and 24 months. RESULTS: Breastfeeding duration was not associated with subcutaneous fat mass at the age of 1.5 months. Shorter breastfeeding was associated with higher peripheral and total subcutaneous fat mass at the age of 6 months (P-value for trend <0.05), but not at the age of 24 months. As compared to children who were exclusively breast fed for 4 months, those who were non-exclusively breast fed had a higher central fat mass at the age of 24 months (P-value for trend <0.01). Timing of introduction of solid foods was not associated with subcutaneous fat mass. CONCLUSION: Our results suggest that a shorter duration and non-exclusive breastfeeding affect early body composition during the first 2 years of life. Follow-up studies at older ages are needed to explore the long-term consequences.

Thrombin generation in morbid obesity: significant reduction after weight loss.

BACKGROUND: Patients with morbid obesity (MO; body mass index > 40 kg m(-2)) suffer from an increased risk of cardiovascular disease, stroke, venous thromboembolism and all-cause mortality. OBJECTIVES: Because weight loss by bariatric surgery reduces cardiovascular and all-cause mortality, we hypothesized that the plasmatic clotting system might be involved in cardiovascular risk. PATIENTS/METHODS: Thirty-six MO patients [mean age 42 (+/-13) years; 29 female) were investigated before and 2 years after bariatric surgery. Thrombin generation was measured with a commercially available assay (Technothrombin-TGA,Technoclone). Metabolic parameters and parameters of the hemostatic system, such as tissue factor (TF), TF pathway inhibitor (TFPI), plasminogen activator inhibitor-1 (PAI-1) and prothrombinfragment 1.2 (F1.2), were determined. To investigate associations of changing parameters, deltas were calculated. RESULTS: Metabolic parameters improved with a mean weight loss of 41 (+/-19) kg. Postoperatively, the lag phase was significantly extended compared with preoperative values [median (25th-75th percentile), 7 (4-12) vs. 12 (7-19) min, P = 0.005]. Peak thrombin decreased after weight loss from 345 (232-455) to 282 (111-388) nm (P = 0.015) and the area under the curve from 3962 (3432-5023) to 3227 (2202-4030) nm thrombin (P < 0.001). TF, PAI-1 and F1.2 significantly decreased after weight loss. Analyses of the deltas showed a significant correlation between peak thrombin and total cholesterol (r = 0.50), triglycerides (r = 0.46) and HbA1c (r = 0.55). Moreover, an inverse correlation was found between insulin resistance and the lag phase (r = -0.46). CONCLUSION: Thrombin generation, a marker of the overall coagulation potential, decreased significantly with weight reduction. This might, at least in part, explain the decreased risk of cardiovascular disease after bariatric surgery.