N-terminal pro-B-type natriuretic peptide and echocardiographic abnormalities in severely obese patients: correlation with visceral fat

To gain further information on the utility of NT-proBNP as an indicator of possible preclin. cardiac disease in normotensive, severely obese individuals, we measured NT-proBNP concns. in 27 severely obese women with no complications and 15 normal-wt. patients. Serum NT-proBNP concns. were measured by the proBNP (Roche) assay. Obese patients showed impairment of several echocardiog. characteristics compared with lean individuals, and some of these differences correlated significantly with the s.c. adipose tissue (VAT) area. The most novel finding in our study is the significant correlation between NT-proBNP and echocar-diqgraphic characteristics (left ventricular mass indexed for height, left ventricular mass, end-diastolic posterior wall, end-diastolic septum thickness, myocardial performance index, early diastolic filling wave velocity) in a homogeneous population. This may indicate that NT-proBNP itself could serve as an indicator of left ventricular morpho-functional changes. NT-proBNP appears to offer possibilities for identifying preclin. cardiac disease, particularly in obese women with large amts. of visceral fat. [on SciFinder (R)

The “Lipid Accumulation Product” Is Associated with 2-Hour Postload Glucose Outcomes in Overweight/Obese Subjects with Nondiabetic Fasting Glucose

“Lipid accumulation product” (LAP) is a continuous variable based on waist circumference and triglyceride concentration previously associated with insulin resistance. We investigated the accuracy of LAP in identifying oral glucose tolerance test (OGTT) abnormalities and compared it to the homeostasis model assessment of insulin resistance (HOMA-IR) in a population of overweight/obese outpatients presenting with nondiabetic fasting glucose. We studied 381 (male: 23%) adult (age: 18–70 years) overweight/obese Caucasians (body mass index: 36.9 ± 5.4 Kg/m2) having fasting plasma glucose < 7.0 mmol/L. OGTT was used to diagnose unknown glucose tolerance abnormalities: impaired glucose tolerance (IGT) and type-2 diabetes mellitus (T2-DM). According to OGTT 92, subjects had an IGT and 33 were diagnosed T2-DM. Logistic regression analysis detected a significant association for both LAP and HOMA-IR with single (IGT and T2-DM) and composite (IGT + T2-DM) abnormal glucose tolerance conditions. However, while the association with diabetes was similar between LAP and HOMA-IR, the relationship with IGT and composite outcomes by models including LAP was significantly superior to those including HOMA-IR (P=0.006 and P=0.007, resp.). LAP seems to be an accurate index, performing better than HOMA-IR, for identifying 2-hour postload OGTT outcomes in overweight/obese patients with nondiabetic fasting glucose

The density of crown-like structures in epicardial adipose tissue could play a role in cardiovascular diseases

The visceral fat of patients affected by abdominal obesity is inflamed, and the main histopathologic feature is the high density of crown-like structures (CLS). Epicardial adipose tissue (EAT) is a visceral fat of paramount importance for its relationships with coronary vessels and myocardium. Its inflammation in patients with abdominal obesity could be of clinical relevance, but histopathological studies on CLS density in EAT are lacking. This study aimed to assess the histopathology of EAT biopsies obtained from patients undergoing open-heart surgery. We collected EAT biopsies from 10 patients undergoing open-heart surgery for elective coronary artery bypass grafting (CABG) (n = 5) or valvular replacement (VR) (n = 5). Biopsies were treated for light microscopy and immunohistochemistry. We quantify the CLS density in each EAT sample. Despite all patients having abdominal obesity, in EAT samples, no CLS were detected in the VR group; in contrast, CLS were detected in the CABG group (about 17 CLS/10 adipocytes vs. 0.0 CLS/10 adipocytes, CABG vs. VR group, respectively). An impressive density of CLS (100 times that of other patients) was found in one patient (LS) in the CABG group that had a relevant anamnestic aspect: relatively rapid increase of weight gain, especially in abdominal adipose tissue, coincident with myocardial infarction. CLS density could be an important predictive tool for cardiovascular diseases. Furthermore, the LS case implies a role for timing in weight gain. No level of evidence; this is a basic science study

Epicardial fat inflammation response to COVID‐19 therapies

OBJECTIVE: Adipose tissue plays a role in the novel coronavirus disease 2019 (COVID‐19). Epicardial adipose tissue (EAT), a unique visceral fat, presents with high degree of inflammation in severe COVID‐19 disease. Whether and how adipose tissue may respond to the COVID‐19 therapies is unknown. METHODS: We retrospectively analyzed the difference in computed tomography (CT) measured EAT and subcutaneous (SAT) attenuation, defined as mean attenuation expressed in Hounsfield units (HU), in 72 patients [mean±SD age was 59.6±12.4 years, 50 (69%) were men] at the hospital admission for COVID‐19 and 99 days [IQR (71‐129)] after discharge. RESULTS: At the admission, EAT HU was significantly correlated with blood glucose levels, interleukin 6 , troponin T levels and waist circumference. EAT HU decreased from ‐87.21±16.18 to ‐100.0±11 (p<0.001) whereas SAT HU did not change (‐110.21±12.1 to ‐111.11±27.82, p=0.78) after therapy. Changes in EAT HU (expressed as ∆) significantly correlated with dexamethasone therapy (r= ‐ 0.46, p= 0.006), and when dexamethasone was combined with tocilizumab (r= ‐0.24, p=0.04). CONCLUSIONS: Dexamethasone therapy was associated with significant reduction of EAT inflammation in COVID‐19 patients, whereas SAT showed no changes. Anti‐inflammatory therapies targeting visceral fat may be helpful in COVID‐19 diseases

Abdominal obesity phenotype is associated with COVID-19 chest X-ray severity score better than BMI-based obesity

Chest X-ray (CXR) severity score and BMI-based obesity are predictive risk factors for COVID-19 hospital admission. However, the relationship between abdominal obesity and CXR severity score has not yet been fully explored. This retrospective cohort study analyzed the association of different adiposity indexes, including waist circumference and body mass index (BMI), with CXR severity score in 215 hospitalized patients with COVID-19. Patients with abdominal obesity showed significantly higher CXR severity scores and had higher rates of CXR severity scores ≥ 8 compared to those without abdominal obesity (P < 0.001; P = 0.001, respectively). By contrast, patients with normal weight, with overweight and those with BMI-based obesity showed no significant differences in either CXR severity scores or in the rates of CXR severity scores ≥ 8 (P = 0.104; P = 0.271, respectively). Waist circumference and waist-to-height ratio (WHtR) correlated more closely with CXR severity scores than BMI (r = 0.43, P < 0.001; r = 0.41, P < 0.001; r = 0.17, P = 0.012, respectively). The area under the curves (AUCs) for waist circumference and WHtR were significantly higher than that for BMI in identifying a high CXR severity score (≥ 8) (0.68 [0.60-0.75] and 0.67 [0.60-0.74] vs 0.58 [0.51-0.66], P = 0.001). A multivariate analysis indicated abdominal obesity (risk ratio: 1.75, 95% CI: 1.25-2.45, P < 0.001), bronchial asthma (risk ratio: 1.73, 95% CI: 1.07-2.81, P = 0.026) and oxygen saturation at admission (risk ratio: 0.96, 95% CI: 0.94-0.97, P < 0.001) as the only independent factors associated with high CXR severity scores. Abdominal obesity phenotype is associated with a high CXR severity score better than BMI-based obesity in hospitalized patients with COVID-19. Therefore, when visiting the patient in a hospital setting, waist circumference should be measured, and patients with abdominal obesity should be monitored closely. Level of evidence Cross-sectional descriptive study, Level V

Human Epicardial Adipose Tissue Expresses Glucose-dependent Insulinotropic Polypeptide, Glucagon and Glucagon-Like Peptide 1 Receptors as Potential Targets of Pleiotropic Therapies

Human Epicardial Adipose Tissue (EAT) plays a crucial role in the development and progression of coronary artery disease, atrial fibrillation and heart failure. Microscopically, EAT is composed of adipocytes, nerve tissues, inflammatory, stromovascular and immune cells. EAT is a white adipose tissue, albeit it also has brown-fat like or beige fat features. No muscle fascia divides EAT and myocardium; this allows a direct interaction and cross talk between the epicardial fat and the myocardium. Thus, it might be a therapeutic target for pharmaceutical compounds acting on G-Protein-Coupled Receptors, such as those for Glucose-dependent Insulinotropic Polypeptide (GIP), Glucagon (GCG) and Glucagon-Like Peptide-1 (GLP-1), whose selective stimulation with innovative drugs has demonstrated beneficial cardiovascular effects. The precise mechanism of these novel drugs and their tissue and cellular target(s) need to be better understood. We evaluate whether human EAT expresses GIP, GCG and GLP-1 receptors and whether their presence is related to EAT transcriptome. We also investigated protein expression and cell type localization specifically for GIPR and GCGR. EAT samples were collected from 33 patients affected by cardiovascular diseases undergoing open heart surgery (90.9% males, age 67.2±10.5 years mean ± SD). Microarray and immunohistochemistry analysis were performed. Microarray analysis showed that GIPR and GCGR messenger Ribonucleic Acids (mRNAs) are expressed in EAT, beyond confirming the previously found GLP-1(3776±1377 arbitrary unit (A.U.), 17.77±14.91 A.U., and 3.41±2.27 A.U., respectively). The immunohistochemical analysis consistently indicates that GIPR and GCGR are expressed in EAT, mainly in macrophages, isolated and in crown-like structures. In contrast, only some mature adipocytes of different sizes showed cytoplasmic immunostaining, similar to endothelial cells and pericytes in the capillaries and pre-capillary vascular structures. Notably, EAT GIPR is statistically associated with the low expression of genes involved in Free Fatty Acid (FFA) oxidation and transport and those promoting FFA biosynthesis and adipogenesis (p<0.01). EAT GCGR, in turn, is related to genes involved in FFA transport, mitochondrial fatty acid oxidation, and white-to-brown adipocyte differentiation, in addition to genes involved in the reduction of fatty acid biosynthesis and adipogenesis (p<0.01). Having reported the expression of the GLP-1 receptor previously, here, we showed that GIPR and GCGR similarly present at mRNA and protein levels in human EAT, particularly in macrophages and partially adipocytes, suggesting these G-protein-coupled receptors as pharmacological targets on the ongoing innovative drugs, which seem cardiometabolically healthy well beyond their effects on glucose and body weight.