Association of Parental Obesity and Diabetes Mellitus With Circulating Adipokines in Nonobese Nondiabetic Offspring.

BACKGROUND: Adipokines are implicated in the development of obesity-related traits. We hypothesized that nonobese participants without diabetes mellitus (DM) whose parents were obese or had DM would have altered circulating adipokines compared with those without parental history of these conditions. METHODS AND RESULTS: Participants in the community-based Framingham Third Generation cohort who were not obese (body mass index <30) and not diabetic with both parents in the Framingham Offspring cohort were included in this analysis (n=2034, mean age 40 years, 54% women). Circulating concentrations of fetuin A, RBP4 (retinol binding protein 4), FABP4 (fatty acid binding protein 4), leptin, LEP-R (leptin receptor), and adiponectin were assayed. Parental DM was defined as occurring before age 60 years, and obesity was defined as body mass index ≥30 before age 60 years. General estimating equations were used to compare concentrations of adipokines among participants with 0, 1, or 2 parents affected by obesity or DM (separate analyses for each), adjusting for known correlates of adipokines. Overall, 44% had at least 1 parent who was obese and 15% had parents with DM. Parental obesity was associated with higher serum levels of FABP4 and LEP-R in their offspring (P=0.02 for both). Parental DM was associated with lower adiponectin but higher RBP4 concentrations in offspring (P≤0.02 for both). CONCLUSIONS: In our community-based sample, a parental history of DM or obesity was associated with an altered adipokine profile in nonobese nondiabetic offspring. Additional studies are warranted to evaluate whether such preclinical biomarker alterations presage future risk of disease.

Prospective Relation of Circulating Adipokines to Incident Metabolic Syndrome: The Framingham Heart Study.

BACKGROUND: Adipokines are elaborated by adipose tissue and are associated with glycemic, lipid, and vascular traits. We hypothesized that in a cross-sectional analysis circulating adipokines are altered among subsets of obesity stratified by presence versus absence of metabolic syndrome (MetS) and prospectively predict the incidence of MetS. METHODS AND RESULTS: Participants in the community-based Framingham Third Generation Cohort who attended examination cycle 1 were included in the study (2002-2005; N=3777, mean age, 40 years; 59% women). Circulating adiponectin, leptin, leptin receptor, fetuin-A, fatty acid-binding protein 4, and retinol binding protein 4 were assayed and related to incident MetS in follow-up (mean 6 years). The adipokines were compared among individuals with excess body weight (body mass index ≥25 kg/m2) and prevalent MetS, excess body weight without MetS (metabolically healthy obese), and normal-weight with MetS (metabolically obese, normal-weight) with normal-weight participants without MetS as a referent. Metabolically healthy obese individuals (n=1467) had higher circulating levels of fetuin-A and fatty acid-binding protein 4 but lower levels of leptin, leptin receptor, and adiponectin (P<0.001 for all). The adipokine panel was associated with incident MetS (263 new-onset cases; P=0.002). Higher circulating concentrations of retinol-binding protein 4 and fetuin-A were associated with incidence of MetS (odds ratio per 1-SD increment log marker, 1.21; 95% CI, 1.03-1.41 [P=0.02] and 1.17; 95% CI, 1.01-1.34 [P=0.03], respectively). CONCLUSIONS: In our community-based sample of young to middle-aged adults, metabolically healthy obese individuals demonstrated an adverse adipokine profile. Higher circulating levels of retinol-binding protein 4 and fetuin-A marked future cardiometabolic risk.

Safety and immunogenicity of an intramuscular quadrivalent influenza vaccine in children 3 to 8 y of age: A phase III randomized controlled study.

A quadrivalent, inactivated, split-virion influenza vaccine containing a strain from both B lineages (IIV4) has been developed, but its safety and immunogenicity in young children has not been described. This was a phase III, randomized, double-blind, active-controlled, multi-center study to examine the immunogenicity and safety of IIV4 in children 3-8 y of age (EudraCT no. 2011-005374-33). Participants were randomized 5:1:1 to receive the 2013/2014 Northern Hemisphere formulation of IIV4, an investigational trivalent comparator (IIV3) containing the B/Victoria lineage strain, or the licensed Northern Hemisphere IIV3 containing the B/Yamagata lineage strain. Participants who had not previously received a full influenza vaccination schedule received 2 doses of vaccine 28 d apart; all others received a single dose. 1242 children were included. For all 4 strains, IIV4 induced geometric mean haemagglutination inhibition titres non-inferior to those induced by the IIV3 comparators. For both B strains, geometric mean antibody titres induced by IIV4 were superior to those induced by the IIV3 with the alternative lineage strain. Similar proportions of participants vaccinated with IIV4 and IIV3 reported solicited injection-site reactions, solicited systemic reactions, and vaccine-related adverse events. A single vaccine-related serious adverse event, thrombocytopenia, was reported 9 d after vaccination with IIV4 and resolved without sequelae. In conclusion, in children aged 3-8 y who received one dose or 2 doses 28 d apart, IIV4 had an acceptable safety profile, was as immunogenic as IIV3 for the shared strains, and had superior immunogenicity for the additional B strain.

Association of Parental Hypertension With Arterial Stiffness in Nonhypertensive Offspring: The Framingham Heart Study.

High arterial stiffness seems to be causally involved in the pathogenesis of hypertension. We tested the hypothesis that offspring of parents with hypertension may display higher arterial stiffness before clinically manifest hypertension, given that hypertension is a heritable condition. We compared arterial tonometry measures in a sample of 1564 nonhypertensive Framingham Heart Study third-generation cohort participants (mean age: 38 years; 55% women) whose parents were enrolled in the Framingham Offspring Study. A total of 468, 715, and 381 participants had 0 (referent), 1, and 2 parents with hypertension. Parental hypertension was associated with greater offspring mean arterial pressure (multivariable-adjusted estimate=2.9 mm Hg; 95% confidence interval, 1.9-3.9, and 4.2 mm Hg; 95% confidence interval, 2.9-5.5, for 1 and 2 parents with hypertension, respectively; P<0.001 for both) and with greater forward pressure wave amplitude (1.6 mm Hg; 95% confidence interval, 0.6-2.7, and 1.9 mm Hg; 95% confidence interval, 0.6-3.2, for 1 and 2 parents with hypertension, respectively; P=0.003 for both). Carotid-femoral pulse wave velocity and augmentation index displayed similar dose-dependent relations with parental hypertension in sex-, age-, and height-adjusted models, but associations were attenuated on further adjustment. Offspring with at least 1 parent in the upper quartile of augmentation index and carotid-femoral pulse wave velocity had significantly higher values themselves (P≤0.02). In conclusion, in this community-based sample of young, nonhypertensive adults, we observed greater arterial stiffness in offspring of parents with hypertension. These observations are consistent with higher vascular stiffness at an early stage in the pathogenesis of hypertension.

Comparison of characteristics and outcomes of patients with heart failure preserved ejection fraction versus reduced left ventricular ejection fraction in an urban cohort.

Despite significant advances in therapies for patients with heart failure with reduced ejection fraction (HFrEF), there are no evidence-based therapies for heart failure with preserved ejection fraction (HFpEF), also known as diastolic heart failure (HF). Differences in pathophysiologic mechanisms are touted as to why patients with HFpEF purportedly do not derive similar therapeutic benefits compared with HFrEF. Similarly, the relative frequencies of HFpEF and HFrEF may differ between hospitalized and ambulatory settings. There are limited data on the prevalence, characteristics, treatment, and short-term outcomes of patients hospitalized with HFpEF. We sought to investigate these in patients hospitalized with HFpEF in an urban, hospitalized setting using the Get With The Guidelines registry. We retrospectively reviewed all consecutive discharges (n = 1,701) with a diagnosis of acute decompensated HF from December 1, 2006 to September 30, 2008. Patients with HFpEF (n = 499) were older, overweight, predominantly women, and had underlying hypertension and dyslipidemia. Presenting blood pressure and levels of creatinine were higher, with lower brain natriuretic peptide levels compared with patients with HFrEF (n = 598). Length of stay and 30-day mortality were comparable between patients with HFpEF and HFrEF. Thirty-day readmission was initially lower in patients with HFpEF. However 30-day mortality from any cause after the index HF hospitalization and survival curve at 1-year was no different between patients with HFpEF and HFrEF. In conclusion, lower 30-day readmissions do not translate into improved long-term outcome in patients with HFpEF.

Frecuencia de virus respiratorios y características clínicas de niños que acuden a un hospital en México / Frequency of respiratory viruses and clinical characteristics in children attending a care center in Mexico City

OBJETIVO. Describir la frecuencia de virus respiratorios y características clínicas en niños con cuadros respiratorios de un hospital de tercer nivel en México. MATERIAL Y MÉTODOS. Se incluyeron niños con diagnóstico de infección respiratoria y un resultado positivo por inmunofluorescencia de enero 2004 a octubre 2006. RESULTADOS. De 986 muestras nasofaríngeas, 138 (14 por ciento) fueron positivas. La frecuencia fue: 80 por ciento virus sincicial respiratorio (VSR), 8 por ciento parainfluenza 1, 5 por ciento parainfluenza3, 2 por ciento adenovirus, 2 por ciento influenza A, 1 por ciento parainfluenza 2 y 1 por ciento influenza B. CONCLUSIONES. La frecuencia de virus respiratorios fue de 14 por ciento. El VSR se identificó asociado con más frecuencia, a neumonía y bronquiolitis en menores de 3 años.

OBJECTIVE. To describe the frequency of respiratory viruses and clinical characteristics in children with respiratory signs and symptoms in a tertiary care center in Mexico. MATERIAL AND METHODS. Patients with a clinical diagnosis of respiratory infection and a positive immunofluorescence result (Light Diagnostics) from January 2004 to October 2006 were included. RESULTS. From the 986 nashopharyngeal samples, 138 (14 percent) were positive by immunofluorescence. The frequency was: 80 percent RSV, 8 percent parainfluenza 1, 5 percent parainfluenza 3, 2 percent adenovirus, 2 percent influenza A, 1 percent parainfluenza 2 and 1 percent influenza B. CONCLUSIONS. Respiratory viruses were detected in 14 percent of samples tested. RSV was the most frequently identified virus and was associated with pneumonia and bronchiolitis in children younger than 3 years old.

[Frequency of respiratory viruses and clinical characteristics in children attending a care center in Mexico City]. / Frecuencia de virus respiratorios y características clínicas de niños que acuden a un hospital en México.

OBJECTIVE: To describe the frequency of respiratory viruses and clinical characteristics in children with respiratory signs and symptoms in a tertiary care center in Mexico. MATERIAL AND METHODS: Patients with a clinical diagnosis of respiratory infection and a positive immunofluorescence result (Light Diagnostics) from January 2004 to October 2006 were included. RESULTS: From the 986 nashopharyngeal samples, 138 (14%) were positive by immunofluorescence. The frequency was: 80% RSV, 8% parainfluenza 1, 5% parainfluenza 3, 2% adenovirus, 2% influenza A, 1% parainfluenza 2 and 1% influenza B. CONCLUSIONS: Respiratory viruses were detected in 14% of samples tested. RSV was the most frequently identified virus and was associated with pneumonia and bronchiolitis in children younger than 3 years old.

Prospective, comprehensive assessment of cardiac troponin T testing after coronary artery bypass graft surgery.

BACKGROUND: The significance and clinical role of cardiac troponin testing after coronary artery bypass grafting remain unclear. METHODS AND RESULTS: Cardiac troponin T (cTnT) was measured during the first 24 hours after coronary artery bypass graft surgery in 847 consecutive patients. Only 17 patients (2.0%) had new Q waves or left bundle-branch block after surgery; however, cTnT elevation was observed in nearly all subjects, with a median cTnT concentration of 1.08 ng/mL overall. Direct predictors of postoperative cTnT values included preoperative myocardial infarction (P<0.001), preoperative intraaortic balloon pump (P<0.001), intraoperative/postoperative intraaortic balloon pump (P<0.001), number of distal anastomoses (P=0.005), bypass time (P<0.001), and number of intraoperative defibrillations (P=0.009), whereas glomerular filtration rate (P<0.001), off-pump coronary artery bypass grafting (P=0.003), and use of warm cardioplegia (P=0.02) were inversely associated with cTnT values. A linear association was seen between cTnT levels and length of stay and ventilator hours, and in an analysis adjusted for the Society for Thoracic Surgery Risk Model, cTnT remained independently prognostic for death (odds ratio, 3.20; P=0.003), death or heart failure (odds ratio, 2.04; P=0.008), death or need for vasopressors (odds ratio, 2.70; P<0.001), and the composite of all 3 (odds ratio, 2.57; P<0.001). In contrast to consensus-endorsed cTnT cut points for postoperative evaluation, a cTnT <1.60 ng/mL had a negative predictive value of 93% to 99% for excluding various post-coronary artery bypass graft surgery complications. CONCLUSIONS: cTnT concentrations after coronary artery bypass graft surgery are nearly universally elevated, are determined by numerous factors, and are independently prognostic for impending postoperative complications when used at appropriate cut points.

Interval increase in right-left ventricular diameter ratios at CT as a predictor of 30-day mortality after acute pulmonary embolism: initial experience.

PURPOSE: To retrospectively determine if the interval increase of right ventricular-left ventricular (RV/LV) diameter ratio from negative prior to positive current computed tomographic (CT) examination findings for pulmonary embolism (PE) is more accurate for predicting 30-day mortality than positive CT ratio alone, by using patient 30-day mortality as reference standard. MATERIALS AND METHODS: This IRB-approved, HIPAA-compliant study had waiver of informed consent and retrospectively reviewed 50 patients (19 men, 31 women; mean age, 60 years) with negative prior and positive current CT findings for acute PE (median interval, 63 days). Interval increase was defined as percentage change in RV/LV diameter ratio by using reformatted four-chamber views. Receiver operating characteristic (ROC) analysis compared the interval increase with the RV/LV diameter ratio from the positive findings alone for PE-related and all-cause mortality. RESULTS: Twelve (24%) patients died in 30 days; nine were PE-related. The interval increase was significantly more accurate overall than the ratio from the positive study alone for PE-related (area under the ROC curve [AUC] = 0.95 vs 0.73, P = .003) and all-cause (AUC = 0.81 vs 0.66, P = .05) mortality. The respective sensitivity, specificity, positive predictive value, and negative predictive value were 0.78 (seven of nine; 95% confidence interval [CI]: 0.43, 1.00), 0.93 (38 of 41; 95% CI: 0.83, 1.00), 0.70 (seven of 10; 95% CI: 0.38, 1.00), and 0.95 (38 of 40; 95% CI: 0.87, 1.00) for PE-related mortality (interval increase, >18%) and 0.75 (nine of 12; 95% CI: 0.49, 1.00), 0.89 (34 of 38; 95% CI: 0.80, 0.99), 0.69 (nine of 13; 95% CI: 0.44, 0.95), and 0.92 (34 of 37; 95% CI: 0.83, 1.00) for all-cause mortality (interval increase, >15%). At target sensitivity (0.75), specificity of interval increase was significantly higher than from positive scans alone for both PE-related (0.93 vs 0.59, P = .001) and all-cause (0.89 vs 0.58, P = .05) mortality. CONCLUSION: The interval increase in four-chamber RV/LV diameter ratio is more accurate than the diameter ratio of the CT examination with with positive findings for PE alone for mortality prediction after acute PE.

Comparison of a single end point to determine optimal initial warfarin dosing (5 mg versus 10 mg) for venous thromboembolism.

There remains considerable controversy regarding optimal initial warfarin dosing in patients with acute venous thromboembolism. Therefore, an open-label, randomized trial comparing 2 warfarin initiation nomograms (5 vs 10 mg) was conducted in patients with acute venous thromboembolism. All participants received fondaparinux for > or = 5 days as a "bridge" to warfarin. The primary end point was defined as the number of days necessary to achieve 2 consecutive international normalized ratio laboratory test values > 1.9. A total of 50 patients were enrolled and randomly assigned to each of the treatment arms. The median time to 2 consecutive international normalized ratios was 5 days in the 2 groups. There was no statistical difference in achieving the primary end point using either the 5- or the 10-mg nomogram (p = 0.69). These results should provide clinicians with increased warfarin dosing options in patients presenting with acute venous thromboembolism.

Chest CT assessment following thrombolysis or surgical embolectomy for acute pulmonary embolism.

Right ventricular (RV) enlargement, assessed by two-dimensional reconstructed 4-chamber views on contrast-enhanced multirow detector computed tomography (MDCT), is emerging as an important marker for predicting adverse clinical events in patients with acute pulmonary embolism (PE). It is unclear whether dynamic changes occur on chest computed tomography (CT) in response to thrombolysis or embolectomy to treat acute PE. We retrospectively investigated 23 consecutive patients who met the criteria of (1) a positive MDCT PE protocol; (2) RV dysfunction on echocardiography; (3) reperfusion therapy by systemic thrombolysis (n=17) or surgical embolectomy (n=6); and (4) follow-up MDCT study after completion of therapy. Two blinded observers reconstructed 4-chamber views on a Leonardo (Siemens, Munich, Germany) workstation using multiplanar reformats of axial CT data and then measured right and left ventricular dimensions (RV(D), LV(D)). RV enlargement was defined as RV(D)/LV(D) > 0.9. Mean age was 52 years, and there were 10 (43%) women. The median time to MDCT follow-up was 21 (range 2-231) days. Seventeen (74%) patients had their chest MDCT follow-up within 30 days. All 23 patients had RV enlargement (mean RV(D)/LV(D) 1.28, range 0.94 to 1.74) prior to initiation of reperfusion therapy. Although right ventricular enlargement was found in 43% of patients at follow-up, the mean RV(D)/LV(D) decreased from 1.28 +/- 0.21 cm to 0.94 +/- 0.16 cm (p < 0.001). The mean change in RV(D)/LV(D) was 0.31 +/- 0.42 in thrombolysis patients and 0.42 +/- 0.09 in embolectomy patients (p = 0.33). Reconstructed 4-chamber views on chest CT provide noninvasive imaging of right ventricular enlargement and permit dynamic assessment of the right ventricular response to thrombolysis and embolectomy in patients with acute PE.

Clinical validity of a negative computed tomography scan in patients with suspected pulmonary embolism: a systematic review.

CONTEXT: The clinical validity of using computed tomography (CT) to diagnose peripheral pulmonary embolism is uncertain. Insufficient sensitivity for peripheral pulmonary embolism is considered the principal limitation of CT. OBJECTIVE: To review studies that used a CT-based approach to rule out a diagnosis of pulmonary embolism. DATA SOURCES: The medical literature databases of PubMed, MEDLINE, EMBASE, CRISP, metaRegister of Controlled Trials, and Cochrane were searched for articles published in the English language from January 1990 to May 2004. STUDY SELECTION: We included studies that used contrast-enhanced chest CT to rule out the diagnosis of acute pulmonary embolism, had a minimum follow-up of 3 months, and had study populations of more than 30 patients. DATA EXTRACTION: Two reviewers independently abstracted patient demographics, frequency of venous thromboembolic events (VTEs), CT modality (single-slice CT, multidetector-row CT, or electron-beam CT), false-negative results, and deaths attributable to pulmonary embolism. To calculate the overall negative likelihood ratio (NLR) of a VTE after a negative or inconclusive chest CT scan for pulmonary embolism, we included VTEs that were objectively confirmed by an additional imaging test despite a negative or inconclusive CT scan and objectively confirmed VTEs that occurred during clinical follow-up of at least 3 months. DATA SYNTHESIS: Fifteen studies met the inclusion criteria and contained a total of 3500 patients who were evaluated from October 1994 through April 2002. The overall NLR of a VTE after a negative chest CT scan for pulmonary embolism was 0.07 (95% confidence interval [CI], 0.05-0.11); and the negative predictive value (NPV) was 99.1% (95% CI, 98.7%-99.5%). The NLR of a VTE after a negative single-slice spiral CT scan for pulmonary embolism was 0.08 (95% CI, 0.05-0.13); and after a negative multidetector-row CT scan, 0.15 (95% CI, 0.05-0.43). There was no difference in risk of VTEs based on CT modality used (relative risk, 1.66; 95% CI, 0.47-5.94; P = .50). The overall NLR of mortality attributable to pulmonary embolism was 0.01 (95% CI, 0.01-0.02) and the overall NPV was 99.4% (95% CI, 98.7%-99.9%). CONCLUSION: The clinical validity of using a CT scan to rule out pulmonary embolism is similar to that reported for conventional pulmonary angiography.

CT pulmonary angiography for acute pulmonary embolism: cost-effectiveness analysis and review of the literature.

Pulmonary embolism (PE) continues to be a diagnostic challenge. Clinical assessment tools, D-dimer testing, ventilation perfusion (V/Q) scanning, ultrasound of the lower limbs, computed tomography (CT), and pulmonary angiography are all adequate methods used in the diagnosis of acute PE. With several options available to physicians, variation in regional costs and practices, and conflicting views on imaging modality performance data, there is considerable uncertainty regarding the most cost-effective strategy. Cost-effectiveness analysis is a helpful tool for determining the most effective diagnostic strategy when several viable options exist. Although limited by a number of necessary assumptions, cost-effective analyses offer a feasible solution to a diagnostic process by using an evidence-based approach. Current evidence shows that CT is a cost-effective alternative to V/Q scanning, particularly when sensitivity is sufficiently high. The purpose of this article is to review the cost-effective role of CT in the diagnosis of acute PE.