Thoracic Periaortic Adipose Tissue Research Articles

Role of thoracic periaortic adipose tissue in major adverse cardiovascular events in heart failure

Abstract Objecitve: Adipose tissue is defined as a complex endocrine organ that exerts various regulatory functions and has effects on the cardiovascular system. Previous studies have shown that epicardial adipose tissue is associated with heart failure (HF) and cardiovascular outcome. The effect of thoracic periaortic fat tissue (PFT) on this issue is unknown. We aimed to investigate the relationship between PFT and long-term clinical outcomes in patients with HF. Materials and Methods: This retrospective cohort study included 71 patients with HF and 45 patients without HF. We calculated their PFT volumes by examining multi-detector computed tomography images with special software. Adverse cardiac events occurring within one year were recorded. Results: Adverse cardiac events were seen in 23 of the patients during follow-up. Only one of the events was in the healthy group. In the HF group, there was a statistically significant PFT volume compared to the healthy group (54.5 (41.2-66.5) vs. 42.1 (29.9-52.7), p= 0.014). Logistic regression analysis showed that PFT was an independent predictor of MACE (hazard ratio [HR]: 0.96; 95% CI: 0.94-0.99; p = 0.027). Conclusion: The study has shown for the first time in the literature that PFT volume can be a useful parameter in predicting adverse cardiac events in the follow-up of patients with HF.

The association of pericardial fat and peri-aortic fat with severity of nonalcoholic fatty liver disease

Visceral adipose tissue (VAT) is associated with central obesity, insulin resistance and metabolic syndrome. However, the association of body-site specific adiposity and non-alcoholic fatty liver disease (NAFLD) has not been well characterized. We studies 704 consecutive subjects who underwent annual health survey in Taiwan. All subjects have been divided into three groups including normal (341), mild (227) and moderate and severe (136) NAFLD according to ultrasound finding. Pericardial (PCF) and thoracic peri-aortic adipose tissue (TAT) burden was assessed using a non-contrast 16-slice multi-detector computed tomography (MDCT) dataset with off-line measurement (Aquarius 3DWorkstation, TeraRecon, SanMateo, CA, USA). We explored the relationship between PCF/TAT, NAFLD and cardiometabolic risk profiles. Patients with moderate and mild NAFLD have greater volume of PCF (100.7 ± 26.3vs. 77.1 ± 21.3 vs. 61.7 ± 21.6 ml, P < 0.001) and TAT (11.2 ± 4.1 vs. 7.6 ± 2.6 vs. 5.5 ± 2.6 ml, P < 0.001) when compared to the normal groups. Both PCF and TAT remained independently associated with NAFLD after counting for age, sex, triglyceride, cholesterol and other cardiometabolic risk factors. In addition, both PCF and TAT provided incremental prediction value for NAFLD diagnosis. (AUROC: 0.85 and 0.87, 95%, confidence interval: 0.82–0.89 and 0.84–0.90). Both visceral adipose tissues strongly correlated with the severity of NAFLD. Compared to PCF, TAT is more tightly associated with NAFLD diagnosis in a large Asian population.

Pericardial fat, thoracic peri-aortic adipose tissue, and systemic inflammatory marker in nonalcoholic fatty liver and abdominal obesity phenotype

Researchers have conducted many studies about the relationships between peri-cardiovascular fat, nonalcoholic fatty liver disease (NAFLD), waist circumference, and cardiovascular disease (CVD). Nevertheless, the relationship between NAFLD and pericardial fat (PCF)/thoracic peri-aortic adipose tissue (TAT) phenotypes was still unknown. This study aimed to explore whether PCF/TAT was associated with NAFLD/abdominal obesity (AO) phenotypes in different high-sensitivity C-reactive protein (hs-CRP) levels. We consecutively studied 1655 individuals (mean age, 49.44 ± 9.76 years) who underwent a health-screening program. We showed a significant association between PCF/TAT and NAFLD/AO phenotypes in the cross-sectional study. We observed that the highest risk occurred in both abnormalities’ groups, and the second highest risk occurred in the AO-only group. Subjects with AO had a significantly increased risk of PCF or TAT compared to those with NAFLD. Notably, the magnitude of the associations between PCF/TAT and NAFLD/AO varied by the level of systemic inflammatory marker (hs-CRP level). We suggested that people with AO and NAFLD must be more careful about changes in PCF and TAT. Regular measurement of waist circumference (or AO) can be a more accessible way to monitor peri-cardiovascular fat (PCF and TAT), which may serve as a novel and rapid way to screen CVD in the future.

Subclinical Hypothyroidism Represents Visceral Adipose Indices, Especially in Women With Cardiovascular Risk.

Context From previous studies, decreased thermogenesis and metabolic rate in the patients with overt and subclinical hypothyroidism lead to an increase in visceral adipose tissue (VAT) incidence, and which was associated with cardiovascular diseases. In this paper, we want to explore the relationship between various forms of VAT [pericardial (PCF), and thoracic periaortic adipose tissue (TAT)] and obesity indices [body shape index (ABSI), and body roundness index (BRI), Chinese visceral adiposity index (CVAI)] with subclinical hypothyroidism by gender.Objective This study aims to evaluate region-specific cardiovascular (CV) fat tissue (pericardial fat [PCF] and thoracic periaortic fat [TAT) and noninvasive visceral adipose indices (a body shape index [ABSI], body roundness index [BRI]), and Chinese visceral adiposity index [CVAI]) in patients with subclinical hypothyroidism (SCH) as compared to a control population and relative to variations in CV risk.MethodsA total of 125 Taiwanese patients recently diagnosed with SCH (age: 52.9 ± 10.16 years, 41.6% female) and 1519 healthy volunteers (age: 49.54 ± 9.77 years, 29.0% female) were evaluated for this study. All participants underwent PCF and TAT assessment using a multidetector computed tomography scanner, ABSI, BRI, and CVAI evaluation using a mathematical formula. CV risk was classified by Framingham risk score (FRS).ResultsMultivariable logistic regression models showed that the independent association of TAT and BRI with SCH were stronger in women than men. The adjusted model associations (odds ratio [OR]; 95% CI) with SCH for TAT and BRI in women were 2.61 (95% CI, 1.03-6.97) and 2.04 (95% CI, 1.07-3.92). The incidences of TAT and BRI third tertile were also higher in women with SCH (SCH vs euthyroid, TAT third tertile, 9 [17.3%] vs 35 [7.9%], P = .04; BRI third tertile, 22 [42.3%] vs 111 [25.2%], P = .01). In addition to BRI and TAT, there were higher risks of CVAI in SCH with intermediate/high FRS, especially in women (OR; 95% CI, TAT: 4.01; 95% CI, 1.01-6.640; BRI: 6.91; 95% CI, 1.03-10.23; CVAI: 7.81 95% CI, 1.01-12.03).ConclusionOur findings show that patients with SCH have significantly greater TAT, BRI, and CVAI values than control groups, especially in women (with different FRS).

Associations of region‐specific visceral adiposity with subclinical atrial dysfunction and outcomes of heart failure

AimsExcessive visceral adiposity (VAT) plays an essential role in metabolic derangements with those close to heart further mediates myocardial homeostasis. The disparate biological links between region‐specific VAT and cardiometabolic profiles as mediators influencing atrial kinetics remain unexplored.Methods and resultsAmong 1326 asymptomatic individuals, region‐specific VAT including peri‐aortic root fat (PARF) and total pericardial fat (PCF) of cardiac region, together with thoracic peri‐aortic adipose tissue (TAT), was assessed using multiple‐detector computed tomography. VAT measures were related to functional left atrial (LA) metrics assessed by speckle‐tracking algorithm and clinical outcomes of atrial fibrillation (AF) and heart failure (HF). Multivariate linear regression models incorporating body fat, metabolic syndrome, and E/TDI‐e' consistently demonstrated independent associations of larger PARF/PCF with peak atrial longitudinal systolic strain (PALS) reduction, higher LA stiffness, and worsened strain rate components; instead, TAT was independently associated with cardiometabolic profiles. PARF rather than PCF or TAT conferred independent prognostic values for incident AF/HF by multivariate Cox regression (adjusted hazard ratio: 1.56, 95% confidence interval: 1.17–2.08, P = 0.002) during a median of 1790 days (interquartile range: 25th to 75th: 1440–1927 days) of follow‐up, with subjects categorized into worst PALS and largest VAT tertiles demonstrating highest events (all log‐rank P < 0.001). Mediation analysis showed that higher triglyceride and lower high‐density lipoproteins may serve as intermediary factors for effects between VAT and LA functional metrics, with lesser role by glucose level.ConclusionsVisceral adiposity surrounding atrial region was tightly associated with subclinical atrial dysfunction and incident AF or HF beyond metabolic factors. Instead, peri‐aortic adiposity may mediate their toxic effects mainly through circulating cardiometabolic profiles.

Sex Differences in the Association of Fat and Inflammation Among People with Treated HIV Infection.

Introduction:Ectopic fat deposition may contribute to chronic inflammation in people with HIV (PWH). To provide information for future mechanistic studies of metabolic risk in this population, we sought to determine which fat measures relate more strongly to inflammation and whether the fat-inflammation relationship is modified by sex or HIV status.Methods:We conducted a cross-sectional study of 105 PWH and 20 age- and sex-matched HIV-negative controls. Interleukin-6 (IL-6) and high-sensitivity C reactive protein (hs-CRP) levels were measured from plasma. Pericardial fat (PCF) and thoracic periaortic adipose tissue (TAT) volumes and peri-right coronary artery (RCA), left atrium (LA) roof, and liver densities were measured from cardiac CT scans. Unadjusted and multivariate adjusted linear regression models were used to determine the relationship between ectopic fat measures and inflammation biomarkers.Results:Forty participants had BMI < 25, 33 had BMI 25 to 30, and 52 had BMI > 30. Systolic blood pressure and insulin resistance increased with BMI. Participants with higher BMI had a higher CD4+ count. In models adjusted for demographics, HIV status, and metabolic risk factors, BMI was positively associated with IL-6 and hs-CRP. Ectopic PCF and TAT volumes were positively associated with IL-6 and hs-CRP; however, these relationships were somewhat attenuated in adjusted models. LA roof (but not peri-RCA) fat radiodensity was inversely associated with hs-CRP in fully adjusted models, and the association with IL-6 was borderline statistically signifi-cant (P = 0.054). IL-6 was more strongly associated with BMI and LA roof density in women than in men (P for interaction = 0.05).Conclusions:Among PWH receiving antiretroviral therapy, higher BMI and excessive ectopic fat burden were associated with circulating markers of systemic inflammation. Because these measures appear to be more strongly related to inflammation among women than men, future clinical studies of metabolic risk and inflammation among PWH should include sex-stratified analyses.

Associations between CT-determined visceral fat burden, hepatic steatosis, circulating white blood cell counts and neutrophil-to-lymphocyte ratio.

Visceral adiposity is associated with cardiovascular disease, an association that may be mediated in part by inflammation. We hypothesized that regional measures of visceral adiposity would associate with commonly obtained clinical measures of immune status. We consecutively studied 3,291 subjects (mean age, 49.8±9.8 years) who underwent an annual cardiovascular risk survey. Peri-cardial (PCF) and thoracic peri-aortic adipose tissue (TAT) volumes were determined by dedicated computed tomography (CT) software (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). Hepatic steatosis was assessed by abdominal ultrasonography. We explored cross-sectional associations between visceral fat measures and high-sensitivity C-reactive protein (hs-CRP), leukocyte counts, and the neutrophil-to-lymphocyte ration (NLR). Among 3,291 study participants, we observed positive linear associations between PCF and TAT, higher degree of hepatic steatosis and hs-CRP, various leukocyte counts, either total and its differential counts, and NLR (all trend p<0.001). Multi-variate linear and logistic regression models showed independent associations between PCF/TAT (ß-Coef: 0.14/0.16, both p<0.05) and total WBC counts, with only TAT further demonstrated significant relations with neutrophil counts and NLR (both p<0.05) and independently identified abnormally high WBC and NLR (Odds ratio: 1.18 & 1.21, both p<0.05). C-statistics showed significant incremental model prediction for abnormally high WBC and NLR (both ΔAUROC<0.05) when TAT was superimposed on traditional cardiovascular risks and biochemical information. Greater visceral adiposity burden and hepatic steatosis may be associated with higher circulating leukocyte counts and markers for atherosclerosis, with more pronounced influences for peri-aortic adiposity. Our data suggested the differential biological impacts for region-specific visceral adiposity.

Transplantation of periaortic adipose tissue inhibits atherosclerosis in apoE−/− mice by evoking TGF-β1-mediated anti-inflammatory response in transplanted graft

Perivascular adipose tissue (PAT) is associated with vascular homeostasis; however, its causal effect on atherosclerosis currently remains undefined. Here, we investigated the effect of experimental PAT transplantation on atherosclerosis. The thoracic periaortic adipose tissue (tPAT) was dissected from 16-week-old wild-type mice and transplanted over the infrarenal aorta of 20-week-old apoE deficient (apoE−/−) mice fed high-cholesterol diet for 3 months. Oil-red O staining after 4 weeks showed a significant 20% decrease in the atherosclerotic lesion of suprarenal aorta compared with that of sham control mice, while that of infrarenal aorta showed no difference between the two groups. TGF-β1 mRNA expression was significantly higher in grafted tPAT than donor tPAT, accompanied by a significant increase in serum TGF-β1 concentration, which was inversely correlated with the suprarenal lesion area (r = −0.63, P = 0.012). Treatment with neutralizing TGF-β antibody abrogated the anti-atherogenic effect of tPAT transplantation. Immunofluorescent analysis of grafted tPAT showed that TGF-β-positive cells were co-localized with Mac-2-positive cells and this number was significantly increased compared with donor tPAT. There was also marked increase in mRNA expression of alternatively activated macrophages-related genes. Furthermore, the percentage of eosinophils in stromal vascular fraction of donor tPAT was much higher than that in epididymal white adipose tissue, concomitant with the significantly higher protein level of IL-4. IL-4 mRNA expression levels in grafted tPAT were increased in a time-dependent manner after tPAT transplantation. Our findings show that tPAT transplantation inhibits atherosclerosis development by exerting TGF-β1-mediated anti-inflammatory response, which may involve alternatively activated macrophages.

Obstrüktif Uyku Apnesi ve Artmış Göğüs Periaortik Yağ Dokusu Arasındaki İlişki

Obstrüktif Uyku Apnesi ve Artmış Göğüs Periaortik Yağ Dokusu Arasındaki İlişki

Thoracic periaortic adipose tissue is increased in patients with subclinical hypothyroidism.

To evaluate thoracic periaortic adipose tissue (TAT) volume in patients with subclinical hypothyroidism (SH) in comparison with controls and in relation to cardiovascular risk factors. The study population consisted of 28 newly diagnosed SH patients (mean (s.d.) age: 37.3 (±11.4) years, 85.7% were females) and 37 healthy volunteers (mean (s.d.) age: 35.3 (±10.7) years, 81.5% were females). Comparisons between patient and control groups used demographic characteristics, anthropometrics, and laboratory findings. All participants underwent thoracic radiographic assessment in the supine position, using an eight-slice multidetector computed tomography scanner and TAT volume was measured. The TAT volume was determined to be 27.2 (±12.7) cm(3) in the SH group and 16.3 (±8.1) cm(3) in the control group, and the difference was statistically significant (P<0.001). In addition, TSH levels were significantly higher in the patient group compared with the control group (P<0.001). A significant correlation was also found between TSH levels and TAT volume (r=0.572; P<0.001). In SH patients, no significant difference was noted in TAT levels with respect to sex (P=0.383) or concomitant smoking status (P=0.426). Our findings indicate that SH patients have significantly higher TAT values than controls and that increased TAT levels correlate with increased TSH levels.

Maternal high-fat diet exaggerates atherosclerosis in adult offspring by augmenting periaortic adipose tissue-specific proinflammatory response.

Maternal obesity elicits offspring's metabolic disorders via developmental modifications of visceral adipose tissue; however, its effect on atherogenesis remains undefined. Perivascular adipose tissue has recently been implicated in vascular remodeling and vasoreactivity. We hypothesize that developmental modifications of perivascular adipose tissue by maternal high-fat diet (HFD) exposure promotes atherosclerosis in adult offspring. Eight-week-old female apolipoprotein E-deficient mice were fed an HFD or normal diet (ND) during gestation and lactation. Offspring were fed a high-cholesterol diet from 8 weeks of age. Twenty-week-old male offspring of HFD-fed dams (O-HFD) showed a 2.1-fold increase in atherosclerotic lesion of the entire aorta compared with those of ND-fed dams (O-ND). Although mRNA expressions of interleukin-6, tumor necrosis factor, and monocyte chemotactic protein-1 and accumulation of macrophages in epididymal white adipose tissue were less in O-HFD than in O-ND, thoracic periaortic adipose tissue (tPAT) showed an exaggerated inflammatory response in O-HFD. Intra-abdominal transplantation of tPAT from 8-week-old O-HFD alongside the distal abdominal aorta exaggerated atherosclerosis development of the infrarenal aorta in recipient apolipoprotein E-deficient mice compared with tPAT from O-ND (210%, P<0.01). Although macrophage accumulation was rarely detected in tPAT of 8-week-old offspring, mRNA expression and protein levels of macrophage colony-stimulating factor were markedly elevated in O-HFD (2.3-fold, 3.3-fold, respectively, P<0.05), suggesting that increased macrophage colony-stimulating factor expression contributes to the augmented accumulation of macrophages, followed by the enhanced proinflammatory response. Our findings demonstrate that maternal HFD exaggerates atherosclerosis development in offspring by augmenting tPAT-specific inflammatory response proceeded by an increased expression of macrophage colony-stimulating factor.

Thoracic periaortic adipose tissue in relation to cardiovascular risk in type 2 diabetes mellitus.

To evaluate thoracic periaortic adipose tissue (TAT) burden in patients with type 2 diabetes mellitus (DM) in comparison with controls and in relation to cardiovascular risk factors. A total of 93 patients with type 2 DM (mean (standard deviation; SD) age: 56.7 (11.2) years, 71.0 % were men) and 85 nondiabetic control subjects (mean (SD) age: 54.6 (10.9) years, 58.8 % were men) who were admitted to Mevlana University hospital between January 2011 and June 2013 and underwent multidetector computed tomography for any reason were included in this retrospective cohort study. Patient and control groups were compared in terms of demographic characteristics, anthropometrics, and laboratory findings. TAT volume was evaluated in both groups, while correlates of TAT were determined via linear regression analysis among patients. In patients with type 2 DM, TAT volume (40.1 (23.9) versus 16.9 (7.7) cm(3), p < 0.001), fasting blood glucose (p < 0.001), total cholesterol (p < 0.001), triglyceride (p = 0.017), and low-density lipoprotein (LDL) cholesterol (p = 0.034) levels were significantly higher compared with the control group. Strong positive correlation of TAT was noted with body mass index (r = 0.339, p = 0.001) and serum levels for fasting blood glucose (r = 0.343, p < 0.001), hemoglobin A1c (HbA1c; r = 0.615, p < 0.001), total cholesterol (r = 0.269, p = 0.009), and LDL cholesterol (r = 0.258, p = 0.013). In stepwise regression analysis, Hba1c emerged as a significant predictor of TAT (b = 0.610, p < 0.001), contributing to 19 % of its variability. In conclusion, our findings indicate significantly higher values for TAT in diabetics than controls, being associated positively with body weight, poor glycemic control, and dyslipidemia and strongly predicted by HbA1c levels in diabetic patients, while not differing with respect to gender, smoking status, and concomitant hypertension.

Transplantation of periaortic adipose tissue from angiotensin receptor blocker-treated mice markedly ameliorates atherosclerosis development in apoE-/- mice.

Perivascular adipose tissue is implicated in vasoreactivity; however, its effect on atherosclerosis remains undefined. We examined the effect of a high-cholesterol diet (HCD) on phenotypic alterations of the thoracic periaortic adipose tissue (tPAT) in apoE-deficient (apoE(-/-)) mice. Gene expression of the components of the renin angiotensin system and that of macrophage markers were significantly higher in apoE(-/-) mice fed an HCD than in those fed a chow diet (CD). These changes were absent both in angiotensin II (AngII) receptor blocker (ARB)-treated apoE(-/-) mice and in Ang II type 1 (AT1) receptor-deficient apoE(-/-) (Agtr1(-/-)/apoE(-/-)) mice. To evaluate their effect on atherosclerosis, we transplanted tPAT into apoE(-/-) mice alongside the distal abdominal aorta. Transplanted tPAT was harvested from apoE(-/-) and Agtr1(-/-)/apoE(-/-) mice fed a CD (tPAT-CD/apoE(-/-), tPAT-CD/Agtr1(-/-)/apoE(-/-)), HCD (tPAT-HCD/apoE(-/-), tPAT-HCD/Agtr1(-/-)/apoE(-/-)), or HCD in combination with ARB treatment (tPAT-HCD/ARB/apoE(-/-)). Four weeks after transplantation, a significantly increased oil red O-positive area was observed in the aorta of tPAT-HCD/apoE(-/-) mice than in tPAT-CD/apoE(-/-) mice. Such a change was absent in tPAT-HCD/ARB/apoE(-/-) and tPAT-HCD/Agtr1(-/-)/apoE(-/-) mice. Our findings demonstrated that AT1 receptor plays a crucial role in HCD-induced phenotypic alterations of tPAT, modulation of which could exert beneficial effects on atherosclerosis.

High pericardial and peri-aortic adipose tissue burden in pre-diabetic and diabetic subjects

BackgroundCentral obesity in relation to insulin resistance is strongly linked to the development of type 2 diabetes. However, data regarding the association between pericardial and peri-aortic adiposity, a potential estimate of visceral adipose tissue burden, and pre-diabetes status remains unclear.The aim of this study was to examine whether the degree of pericardial and thoracic peri-aortic adipose tissue, when quantified by multi-detector computed tomography (MDCT), differs significantly in a normal, pre-diabetic, and overtly diabetic population.MethodsWe studied 562 consecutive subjects including 357 healthy, 155 pre-diabetic, and 50 diabetic patients selected from participants who underwent annual health surveys in Taiwan. Pre-diabetes status was defined by impaired fasting glucose or impaired glucose intolerance according to American Diabetes Association guidelines. Pericardial (PCF) and thoracic peri-aortic (TAT) adipose tissue burden was assessed using a non-contrast 16-slice multi-detector computed tomography (MDCT) dataset with off-line measurement (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). Body fat composition, serum high-sensitivity C-reactive protein (hs-CRP) level and insulin resistance (HOMA-IR) were also assessed.ResultsPatients with diabetes and pre-diabetes had greater volume of PCF (89 ± 24.6, 85.3 ± 28.7 & 67.6 ± 26.7 ml, p < 0.001) as well as larger TAT (9.6 ± 3.1 ml vs 8.8 ± 4.2 & 6.6 ± 3.5 ml, respectively, p < 0.001) when compared to the normal group, although there were no significant differences in adiposity between the diabetic and pre-diabetic groups. For those without established diabetes in our study, increasing TAT burden, but not PCF, appear to correlate with insulin resistance (HOMA-IR) and hs-CRP in the multivariable models.ConclusionsPre-diabetic and diabetic subjects, compared to normoglycemia, were associated with significantly higher pericardial and peri-aortic adipose tissue burden. In addition, visceral fat accumulation adjacent to the thoracic aorta seemed to exert a significant impact on insulin resistance and systemic inflammation.

Periaortic adipose tissue-specific activation of the renin-angiotensin system contributes to atherosclerosis development in uninephrectomized apoE−/− mice

Chronic kidney disease (CKD) is an independent risk factor for the development of cardiovascular disease. The perivascular adipose tissue is closely implicated in the development of atherosclerosis; however, the contribution to CKD-associated atherogenesis remains undefined. Eight-week-old apoE-deficient mice were uninephrectomized and fed a high-cholesterol diet starting at 12 wk of age. The atherosclerotic lesion area in the thoracic aorta was comparable in 16-wk-old uninephrectomized (UNX) mice and sham control mice; however, the lesion area was markedly exaggerated in 20-wk-old UNX mice compared with the control (54%, P < 0.05). While the accumulation of monocytes/macrophages and the mRNA expression levels of inflammatory cytokines/chemokines in the thoracic periaortic adipose tissue (PAT) did not differ between the two groups, angiotensinogen (AGT) mRNA expression and the angiotensin II (ANG II) concentration in the PAT were significantly higher in 16-wk-old UNX mice than in the control (1.9- and 1.5-fold increases vs. control, respectively; P < 0.05). ANG II concentrations in both the plasma and epididymal white adipose tissue (WAT) were comparable between the two groups, suggesting that PAT-specific activation of the renin-angiotensin system (RAS) is primarily involved in CKD-associated atherogenesis. The homeostasis model assessment-insulin resistance (HOMA-IR) index and plasma insulin level after glucose loading were significantly elevated in 16-wk-old UNX mice. In vitro stimulation of preadipocytes with insulin exaggerated the AGT mRNA expression along with increased mRNA expression of PPARγ. These findings suggest that PAT-specific RAS activation probably primarily contributes in accelerating atherosclerotic development in UNX mice and could thus represent a therapeutic target for preventing CKD-associated atherogenesis.

Thoracic periaortic and visceral adipose tissue and their cross‐sectional associations with measures of vascular function

ObjectivePerivascular fat may have a local adverse effect on the vasculature. We evaluated whether thoracic periaortic adipose tissue (TAT), a type of perivascular fat, and visceral adipose tissue (VAT) are associated with vascular function.Design and MethodsTAT and VAT were quantified in Framingham Heart Study participants using multidetector computed tomography; vascular function was assessed using brachial artery vasodilator function, peripheral arterial tone and arterial tonometry (n= 2735, 48% women, mean age 50 years, mean BMI 27.7 kg/m2). Using multiple linear regression, we examined relations between TAT, VAT, and vascular measures while adjusting for cardiovascular risk factors.ResultsMean TAT and VAT volumes were 13.2 and 1763 cm3. TAT and VAT were associated with multiple vascular function measures after multivariable adjustment. After BMI adjustment, TAT and VAT remained negatively associated with peripheral arterial tone and inverse carotid femoral pulse wave velocity (p<0.02); TAT was negatively associated with hyperemic mean flow velocity (p=0.03). Associations of TAT with vascular function were attenuated after VAT adjustment (all p>0.06).ConclusionThoracic periaortic and visceral fat are associated with microvascular function and large artery stiffness after BMI adjustment. These findings support the growing recognition of associations between ectopic fat and vascular function.

Abstract 025: Multidetector Computed Tomography Adipose Tissue Depots and Incident Cardiovascular Disease

Introduction: Ectopic fat depots may play a role in obesity-mediated cardiovascular disease (CVD). We tested the association of several distinct fat depots and incident CVD in an asymptomatic community-based sample. Methods: Participants from the Framingham Heart Study (n=3086, 49% women, mean age 50.2 years, free of CVD at baseline) underwent volumetric assessment of multiple fat depots using multidetector computed tomography from 2002–2005, and were followed longitudinally for CVD events. Fat depots included subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), pericardial adipose tissue, intra-thoracic adipose tissue and thoracic periaortic adipose tissue (TAT). Adipose volumes were standardized within sex to a mean of 0 and a standard deviation of 1. Cardiovascular events included coronary heart disease (myocardial infarction, coronary insufficiency or angina), cerebrovascular disease (stroke or transient ischemic attack), intermittent claudication, heart failure or CVD death. Using Cox proportional hazards regression models, we examined the association of each fat depot with the risk of CVD after adjustment for age, sex, systolic blood pressure, hypertension treatment, diabetes, total cholesterol, high-density lipoprotein cholesterol, smoking, and then additionally for BMI. We additionally examined the association of pericardial fat and incident coronary heart disease. Results: During a mean follow-up of 4.7 years, 90 CVD events occurred. After multivariable adjustment, VAT, VAT/SAT ratio, intra-thoracic fat and TAT were significantly associated with incident CVD events. The hazard ratios (95% confidence intervals) per each standard deviation higher were 1.37 (1.10–1.71, p=0.006 [VAT]), 1.30 (1.05–1.60, p=0.02 [VAT/SAT ratio]), 1.28 (1.03–1.59, p=0.03 [intra-thoracic fat]), and 1.30 (1.03–1.67, p=0.03 [TAT]), respectively. We observed no association between BMI (HR 1.15, 0.92–1.43, p=0.21), SAT (HR 1.13, 0.90–1.42, p=0.28) or pericardial fat (HR 1.14, 0.95–1.37, p=0.15) and incident CVD. After additional adjustment for BMI, VAT, VAT/SAT ratio and TAT remained significantly associated with incident CVD events [HR 1.44 (1.08–1.92, p=0.01 [VAT]), 1.34 (1.08–1.65, p=0.007 [VAT/SAT ratio]), and 1.31 (1.03–1.67, p=0.03 [TAT])], respectively. Pericardial fat was also not associated with incident coronary heart disease, even when limiting our events to myocardial infarction or coronary heart disease death (HR 0.97, p=0.81). Conclusion: Several distinct ectopic fat depots, including VAT, VAT/SAT ratio, intra-thoracic fat, and TAT, but not generalized obesity, are significantly associated with CVD events after adjustment for risk factors in our community-based sample. These findings support the growing recognition of several potentially pathogenic ectopic fat depots.

Abstract 9913: Different Impacts of Body Fat Composition and Computed-Tomography-Determined Visceral Fat on Left Ventricular Mass, Geometry and Left Atrial Structural Alteration

Background The adverse effects of body fat distribution on left ventricular (LV) mass and geometry has recently been recognized. Excessive visceral fat deposition, specifically those surrounding the heart and central aorta, was associated with adverse cardiovascular events. We sought to examine the impact of body fat composition and visceral adipose tissue on cardiac structure and geometry. Methods We studied 1,063 subjects (age: 49.5±10.5, 39.4% female) without angina or heart failure symptoms. Cardiac structures and LV geometry parameters including LV mass index (LVMI), relative wall thickness (RWT) and mass-to-volume ratio were all determined by echocardiography. Body fat composition (both fat and fat-free mass) was assessed by Tanita foot-to-foot bioimpedance analysis. A subgroup of 361 subjects further underwent multidetector computed tomography (MDCT) for three-dimensional, volume-based epicardial adipose tissue (EAT) and thoracic peri-aortic adipose tissue (TAT) quantification. Results Both fat and fat-free mass were positively related to LV mass (β coef: 0.42 &amp; 0.31, both p&lt;0.001) after multivariate adjustment for age, gender, blood pressure and medical histories. However, only fat mass (β coef: 0.15, p&lt;0.001) contributed independently to concentric remodeling (RWT&gt;0.42). For each standard-deviation increase of EAT and TAT volume, there was an observed increase of LVMI (β coef: 0.14 &amp; 0.15, both p&lt;0.05) after multivariate adjustment. In addition, left atrial dimension was also positively related to both EAT and TAT even after adjusting for severity of mitral regurgitation (β coef: 0.16 &amp; 0.12, both p&lt;0.05). Conclusions While both fat and fat-free mass exert their independent effect on ventricular mass increase, only fat mass had independent impact on ventricular geometry. Our data also suggested that epicardial adipose tissue may further impact LA dimension, possibly mediated by impeding ventricular diastolic filling.

Obesity Promotes Inflammation in Periaortic Adipose Tissue and Angiotensin II-Induced Abdominal Aortic Aneurysm Formation

Obesity promotes macrophage infiltration into adipose tissue and is associated with increases in several cardiovascular diseases. Infusion of angiotensin II (AngII) to mice induces formation of abdominal aortic aneurysms (AAAs) with profound medial and adventitial macrophage infiltration. We sought to determine whether obesity promotes macrophage infiltration and proinflammatory cytokines in periaortic adipose tissue surrounding abdominal aortas and increases AngII-induced AAAs. Hypertrophied white adipocytes surrounded abdominal aortas, whereas brown adipocytes surrounded thoracic aortas of obese mice. mRNA abundance of macrophage proinflammatory chemokines and their receptors were elevated with obesity to a greater extent in abdominal compared to thoracic periaortic adipose tissue. Periaortic adipose tissue explants surrounding abdominal aortas of obese mice released greater concentrations of MCP-1 and promoted more macrophage migration than explants from thoracic aortas. Male C57BL/6 mice were fed a high-fat (HF) diet for 1, 2, or 4 months and then infused with AngII (1000 ng/kg/min) for 28 days. AAA incidence increased progressively with the duration of HF feeding (18%, 36%,and 60%, respectively). Similarly, AngII-infused ob/ob mice exhibited increased AAAs compared to lean controls (76% compared to 32%, respectively, P<0.05). Infusion of AngII to obese mice promoted further macrophage infiltration into periaortic and visceral adipose tissue, and obese mice exhibiting AAAs had greater macrophage content in visceral adipose tissue than mice not developing AAAs. Increased macrophage accumulation in periaortic adipose tissue surrounding abdominal aortas of AngII-infused obese mice is associated with enhanced AAA formation.

Novel measurements of periaortic adipose tissue in comparison to anthropometric measures of obesity, and abdominal adipose tissue

Perivascular adipose tissue may be associated with the amount of local atherosclerosis. We developed a novel and reproducible method to standardize volumetric quantification of periaortic adipose tissue by computed tomography (CT) and determined the association with anthropometric measures of obesity, and abdominal adipose tissue. Measurements of adipose tissue were performed in a random subset of participants from the Framingham Heart Study (n=100) who underwent multidetector CT of the thorax (ECG triggering, 2.5 mm slice thickness) and the abdomen (helical CT acquisition, 2.5 mm slice thickness). Abdominal periaortic adipose tissue (AAT) was defined by a 5 mm cylindrical region of interest around the aortic wall; thoracic periaortic adipose tissue (TAT) was defined by anatomic landmarks. TAT and AAT were defined as any voxel between -195 and -45 HU and volumes were measured using dedicated semiautomatic software. Measurement reproducibility and association with anthropometric measures of obesity, and abdominal adipose tissue were determined. The intra- and inter-observer reproducibility for both AAT and TAT was excellent (ICC: 0.97 and 0.97; 0.99 and 0.98, respectively). Similarly, the relative intra- and inter-observer difference was small for both AAT (-1.85+/-1.28% and 7.85+/-6.08%; respectively) and TAT (3.56+/-0.83% and -4.56+/-0.85%, respectively). Both AAT and TAT were highly correlated with visceral abdominal fat (r=0.65 and 0.77, P<0.0001 for both) and moderately correlated with subcutaneous abdominal fat (r=0.39 and 0.42, P<0.0001 and P=0.009), waist circumference (r=0.49 and 0.57, P<0.0001 for both) and body mass index (r=0.47 and 0.58, P<0.0001 for both). Standardized semiautomatic CT-based volumetric quantification of periaortic adipose tissue is feasible and highly reproducible. Further investigation is warranted regarding associations of periaortic adipose tissue with other body fat deposits, cardiovascular risk factors and clinical outcomes.