Relation between brown adipose tissue and measures of obesity and metabolic dysfunction in patients with cardiovascular disease.

PURPOSE: To evaluate whether brown adipose tissue (BAT) is present in middle-aged patients with cardiovascular comorbidities and to quantify how BAT presence associates with obesity and metabolic dysfunction. MATERIALS AND METHODS: Supraclavicular and subcutaneous adipose tissue fat-signal-fraction (FF) was determined with 1.5T water-fat magnetic resonance imaging (MRI) in 50 patients with coronary artery disease, cerebrovascular disease, or peripheral artery disease. The association between BAT presence, as measured by a higher FF difference between supraclavicular and subcutaneous adipose tissue, and obesity and metabolic dysfunction was quantified using multivariable linear regression. RESULTS: Supraclavicular adipose tissue displays a lower FF of 82.6% (interquartile range [IQR] 78.8-84.3) compared to 90.2% (IQR 87.3-91.9) in subcutaneous white adipose tissue (WAT, P < 0.0001). BAT presence was associated with less obesity and metabolic dysfunction. For example, 1 SD lower waist circumference (11.7 cm), 1 SD lower triglycerides (1.0 mmol/L), and absence of metabolic syndrome and type 2 diabetes were associated with 1.1% (95% confidence interval [CI] 0.1; 2.0), 1.1% (95% CI 0.1; 2.0), 2.1% (95% CI 0.1; 4.1), and 4.1% (95% CI 0.1; 7.1) higher FF difference between supraclavicular adipose tissue and subcutaneous WAT, respectively. CONCLUSION: Supraclavicular adipose tissue has BAT characteristics in adult patients with clinical manifest cardiovascular disease and BAT presence is associated with less obesity and a more favorable metabolic profile. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:497-504.

Reliability and agreement of adipose tissue fat fraction measurements with water-fat MRI in patients with manifest cardiovascular disease.

The supraclavicular fat depot is known for brown adipose tissue presence. To unravel adipose tissue physiology and metabolism, high quality and reproducible imaging is required. In this study we quantified the reliability and agreement of MRI fat fraction measurements in supraclavicular and subcutaneous adipose tissue of 25 adult patients with clinically manifest cardiovascular disease. MRI fat fraction measurements were made under ambient temperature conditions using a vendor supplied mDixon chemical-shift water-fat multi-echo pulse sequence at 1.5 T field strength. Supraclavicular fat fraction reliability (intraclass correlation coefficientagreement , ICCagreement ) was 0.97 for test-retest, 0.95 for intra-observer and 0.56 for inter-observer measurements, which increased to 0.88 when ICCconsistency was estimated. Supraclavicular fat fraction agreement displayed mean differences of 0.5% (limit of agreement (LoA) -1.7 to 2.6) for test-retest, -0.5% (LoA -2.9 to 2.0) for intra-observer and 5.6% (LoA 0.4 to 10.8) for inter-observer measurements. Median fat fraction in supraclavicular adipose tissue was 82.5% (interquartile range (IQR) 78.6-84.0) and 89.7% (IQR 87.2-91.5) in subcutaneous adipose tissue (p < 0.0001). In conclusion, water-fat MRI has good reliability and agreement to measure adipose tissue fat fraction in patients with manifest cardiovascular disease. These findings enable research on determinants of fat fraction and enable longitudinal monitoring of fat fraction within adipose tissue depots. Interestingly, even in adult patients with manifest cardiovascular disease, supraclavicular adipose tissue has a lower fat fraction compared with subcutaneous adipose tissue, suggestive of distinct morphologic characteristics, such as brown adipose tissue.

[A new definition of the I-category in the antibiogram: I-category antibiotics no longer an option to avoid]. / Nieuwe definitie van I-categorie in het antibiogram.

Currently, the meaning of the I-category of the antibiogram in culture results is changing in The Netherlands. Before, the I-category was called 'intermediate' and included combinations of antibiotics and micro-organisms in which the chance of therapeutic success was doubtful. Therefore, in clinical practice this category was mostly avoided and considered as 'in this case not clear'. From now on, the definition of I has changed to 'susceptible, increased exposure' and can be considered as a valid treatment option when adequate (higher) dosing is applied. Because of the large-scale implementation, not all microbiological laboratories may be able to implement the new I at the same moment and the way they may execute this may differ in detail. When considering treating a patient with 'susceptible, increased exposure' and you are in doubt whether your microbiological laboratory already has implemented the new definition of I or about the correct dosage, consult your clinical microbiologist or Antimicrobial Stewardship Team.

Reproducibility between two readout methods of a commercial broth microdilution assay for Pseudomonas aeruginosa isolates from patients with Cystic Fibrosis.

BACKGROUND: Pseudomonas aeruginosa isolates from Cystic fibrosis (CF) patients are growing slowly, and frequently rendering automated susceptibility testing unsuitable. Colistin is an important antibiotic for treatment of P. aeruginosa infections. Broth microdilution is the only EUCAST endorsed antimicrobial susceptibility test for colistin. The VIZION™ device aids in reading broth microdilution plates and allows safe data transfer to laboratory information systems. In this study, reproducibility between visual MIC readout and readout, employing the VIZION™ device was assessed in susceptibility testing of colistin and beta-lactam antibiotics in P. aeruginosa isolates from CF patients. METHODS: Fifty-six unique P. aeruginosa isolates were derived from respiratory secretions of CF patients. Susceptibility testing was performed using commercially available microdilution plates. MIC readout by VIZION™ was compared to visual readout aided by a mirror (reference test). RESULTS: Pseudomonas aeruginosa isolates displayed significantly slower growth rates compared to quality control isolates. Colistin exact MIC agreement between VIZION™ and visual readout after 24 and 48 h incubation, respectively, was 82% and 95%, essential MIC agreement was 98% and 100%, categorical agreement was 98% and 98% and reliability (weighted kappa) was 0.95 (95% CI = 0.91-0.99) and 0.99 (95% CI = 0.97-1.00). For all five antibiotics, the total number of errors (using VIZION™, in comparison with visual readout) decreased from 15 (5%) to 10 (4%) after 24 and 48 h incubation, respectively. CONCLUSIONS: VIZION™ readout reproducibly determines MIC values in comparison with visual readout after 24 h of incubation. Reproducibility between the VIZION™ and visual readout increases after prolonged incubation of 48 h.

Relation of Epicardial Adipose Tissue Radiodensity to Coronary Artery Calcium on Cardiac Computed Tomography in Patients at High Risk for Cardiovascular Disease.

Adipose tissue radiodensity detected by computed tomography (CT) is hypothesized to be associated with differences in adipose tissue composition which may contribute to the development of coronary atherosclerosis independent of epicardial adipose tissue volume. The aim of the present study is to quantify the relation between epicardial adipose tissue radiodensity and presence, distribution, and density of coronary artery calcium (CAC) in patients at high risk for cardiovascular disease. A total of 140 patients of the Secondary Manifestations of ARTerial disease (SMART) study underwent cardiac-CT angiography. Ordinal logistic and linear regression was used to quantify the relation between epicardial adipose tissue radiodensity (in Hounsfield Units, HU) and CAC. One SD lower attenuation (5 HU) was associated with a 1.90 (95% confidence interval [CI] 1.14 to 3.19) higher odds for men and a 1.07 (95% CI 0.41 to 2.75) higher odds for women of being in a higher CAC class (0, 1 to 100, 101 to 400, and >400), independent of age, coronary artery bypass graft history, epicardial adipose tissue volume, and body mass index. One SD lower attenuation was not associated with more diffuse distribution of CAC, but increased the odds of being in a higher tertile of CAC density per plaque (odds ratio 1.77, 95% CI 1.18 to 2.66). In conclusion, low epicardial adipose tissue CT attenuation is associated with higher CAC scores in men at high risk for cardiovascular disease, independent of epicardial depot volume and body mass index. Present results suggest a potential role for epicardial adipose tissue radiodensity as a measure of adipose tissue composition and may inform on the contribution of epicardial adipose tissue composition to coronary atherosclerosis.

Relation between cardiovascular disease risk factors and epicardial adipose tissue density on cardiac computed tomography in patients at high risk of cardiovascular events.

Background The radiodensity of epicardial adipose tissue may provide information on cardiovascular risk in addition to epicardial adipose tissue volume. The aim of this study was to quantify the relation between cardiovascular risk factors and the radiodensity of epicardial adipose tissue in patients at high risk of cardiovascular disease. Design This was a cross-sectional study in 140 patients at high risk of cardiovascular disease. Methods Patients from the Secondary Manifestations of ARTerial disease (SMART) cohort study were invited to undergo cardiac computed tomography angiography. The radiodensity (in Hounsfield units; HU) and volume (in cm3) of epicardial adipose tissue were quantified semi-automatically. Multivariable linear regression was used to quantify the relation between cardiovascular risk factors and the radiodensity of epicardial adipose tissue. Results The cardiovascular risk factors most strongly associated with epicardial adipose tissue density were sex, body mass index and visceral fat, with a lower adipose tissue attenuation of 3.5 HU (95% confidence interval (CI) 2.0-5.0 HU) for female sex, 1.6 HU (95%CI 0.2-2.9 HU) for body mass index >25 kg/m2 and 1.3 HU (95% CI 0.6-2.0 HU) for a one standard deviation higher quantity of visceral fat, adjusted for age, sex, coronary artery bypass graft history and epicardial adipose tissue volume. Conclusion Low epicardial adipose tissue computed tomography attenuation is associated with an adverse cardiovascular risk factor profile in patients at high risk of cardiovascular disease, independent of the volume of epicardial adipose tissue and waist circumference. These findings support the potential role for epicardial adipose tissue radiodensity as a valid biomarker of cardiovascular risk. Adipose tissue radiodensity may be a more sensitive marker than epicardial adipose tissue volume with which to study the contribution of epicardial adipose tissue to the coronary atheromatous disease process.

Metabolic consequences of adipose tissue dysfunction and not adiposity per se increase the risk of cardiovascular events and mortality in patients with type 2 diabetes.

OBJECTIVES: To quantify the risk of obesity and its associated metabolic dysfunction on the development of cardiovascular events and mortality in patients with type 2 diabetes. METHODS: In 1827 patients with type 2 diabetes enrolled in the Secondary Manifestations of ARTerial disease (SMART) cohort study, the risk of higher BMI, waist circumference and intra-abdominal fat on the development of cardiovascular events (composite of myocardial infarction, stroke, and vascular mortality) was quantified using Cox regression. Second, risk of cardiovascular events related to obesity associated metabolic dysfunction (≥3 adapted NCEP metabolic syndrome criteria) was quantified for tertiles of intra-abdominal fat. RESULTS: 217 patients died from cardiovascular causes and 338 patients developed the composite endpoint of cardiovascular events during a median follow-up of 7.0years (interquartile range 3.9 to 10.5years). No increased risk for cardiovascular events and mortality was observed per SD higher BMI, waist circumference and intra-abdominal fat (HR varying from 1.00, 95% CI 0.88-1.14 to 1.13, 95% CI 0.96-1.33). Compared to the first tertile of intra-abdominal fat without metabolic dysfunction, the presence of metabolic dysfunction increased the risk of cardiovascular events in all tertiles of intra-abdominal fat with the highest risk observed for metabolic dysfunction in the first tertile of intra-abdominal fat (HR 2.47, 95% CI 1.32-4.62). CONCLUSIONS: Body-mass index, waist circumference and intra-abdominal fat are not related to the risk of cardiovascular events and mortality in patients with type 2 diabetes. Instead, in these patients the metabolic consequences of adipose tissue dysfunction are more important than strict measures of adiposity when estimating cardiovascular risk.

Body weight, metabolic dysfunction, and risk of type 2 diabetes in patients at high risk for cardiovascular events or with manifest cardiovascular disease: a cohort study.

OBJECTIVE: To quantify the role of BMI and metabolic dysfunction in the risk of development of type 2 diabetes in patients at high risk or with manifest vascular disease. RESEARCH DESIGN AND METHODS: A total of 6,997 patients participating in the prospective Secondary Manifestations of ARTerial disease (SMART) cohort study were classified according to BMI and metabolic dysfunction, defined as three or more of the modified National Cholesterol Education Program (NCEP) metabolic syndrome criteria (waist circumference replaced by hs-CRP ≥2 mg/L). Risk of type 2 diabetes (assessed with biannually questionnaires) was estimated with Cox proportional hazards analysis. RESULTS: During a median follow-up of 6.0 years (interquartile range 3.1-9.1 years), 519 patients developed type 2 diabetes (incidence rate 12/1,000 person-years). In the absence of metabolic dysfunction (≤2 NCEP criteria), adiposity increased the risk of type 2 diabetes compared with normal-weight patients (HR 2.5 [95% CI 1.5-4.2] for overweight and HR 4.3 [95% CI 2.2-8.6] for obese patients). In the presence of metabolic dysfunction (≥3 NCEP criteria), an increased risk of type 2 diabetes was observed in patients with normal weight (HR 4.7 [95% CI 2.8-7.8]), overweight (HR 8.5 [95% CI 5.5-13.4]), and obesity (HR 16.3 [95% CI 10.4-25.6]) compared with normal-weight patients without metabolic dysfunction. CONCLUSIONS: Adiposity, even in the absence of metabolic dysfunction, is a risk factor for type 2 diabetes. Moreover, presence of metabolic dysfunction increases the risk of type 2 diabetes in all BMI categories. This supports the assessment of adiposity and metabolic dysfunction in patients with vascular disease or at high risk for cardiovascular events.