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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EObesity is an inflammatory process, and as visceral adipose tissue (VAT) increases, inflammation increases. As the components of metabolic syndrome increase, inflammation increases, as shown by increases in C-reactive protein (CRP) in the Women\u0027s Health Study [Ridker PM et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2003]. Additionally, this article discusses the role of epicardial and intrathoracic fat with cardiovascular (CV) risk factors, and the association between low levels of high-density lipoprotein cholesterol (HDL-C; \u0026lt;60 mg\/dL) and increased hazard of coronary heart disease, stroke, and CV events.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EPrevention \u0026amp; Screening\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiometabolic Disorder\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EObesity\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ELipid Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EPrevention \u0026amp; Screening\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiometabolic Disorder\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EEndocrinology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Metabolic Syndrome\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EObesity\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ELipid Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EObesity is an inflammatory process, and as visceral adipose tissue (VAT) increases, inflammation increases, stated Peter Libby, MD, Brigham and Women\u0027s Hospital, Boston, Massachusetts, USA. As the components of metabolic syndrome increase, inflammation increases, as shown by increases in C-reactive protein (CRP) in the Women\u0027s Health Study [Ridker PM et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2003]. Evidence from the prospective observational Women\u0027s Health Study showed that inflammation precedes diabetes, with women in higher quartiles of CRP having a higher (nearly 4-fold) adjusted risk for incident diabetes [Pradhan AD et \u003Cem\u003Eal. JAMA\u003C\/em\u003E 2001].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EAdipose tissue is teaming with metabolic activity and inflammatory cytokines, an \u201calphabet soup of mediators,\u201d said Dr. Libby, most of which are proinflammatory. However, the anti-inflammatory adiponectin, which has protective effects on thrombosis, [Okamoto Y et al. \u003Cem\u003EAtherosclerosis\u003C\/em\u003E 2013] is underproduced by VAT.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EPET imaging has shown that glucose uptake is higher from VAT than from subcutaneous adipose tissue in lean and obese persons [Christen T et al. \u003Cem\u003EJACC Cardiovasc Imaging\u003C\/em\u003E 2010]. A hint of important metabolic differences between VAT and subcutaneous adipose tissue which supported the imaging findings came from a mouse model in this study that showed hexokinase-1 activity was higher in VAT-derived, compared with subcutaneous adipose tissue-derived, stromal vascular cells during glucose uptake.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EInnate immunity and specific cell populations in adaptive immunity may be important in visceral, versus lean, adipose tissue, and may be regulators of some inflammatory responses in VAT. TH1 cells produce interferon gamma (IFN-\u03b3), which regulates inflammatory activation in VAT. IFN-\u03b3 is increased in high-fat, versus low-fat, fed mice [Rocha V et al. \u003Cem\u003ECire Res\u003C\/em\u003E 2008]. Obese adipose tissue contains regulatory T cells that affect metabolic parameters [Feuerer M. \u003Cem\u003ENat Med\u003C\/em\u003E 2009], and T-lymphocyte infiltration into VAT has been shown, which may contribute to local inflammatory cell activation [Kintscher U. \u003Cem\u003EArterioscler Thromb Vase Biol\u003C\/em\u003E 2008]. CD8+ effector T cells are activated in obese adipose tissue, which promotes recruitment and activation of macrophages into the tissue [Nishimura S et al. \u003Cem\u003ENat Med\u003C\/em\u003E 2009].\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EObesity drives inflammation that underlies atherosclerosis initiation, progression, and complications, and diabetes. The vicious cycle between inflammation and thrombosis is illustrated in \u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E. Plasminogen activator inhibitor 1 (PAI-1), the most important endogenous inhibitor of the fibrinolytic system, is a direct link between inflammation and thrombosis. Furthermore, PAI-1 is increased in diabetes and adipose tissue is thought to be one source of PAI-1.\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/16\/16\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Inflammation and Thrombosis Drive the Other in a Ongoing Cycle\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-873920365\u0022 data-figure-caption=\u0022Inflammation and Thrombosis Drive the Other in a Ongoing Cycle\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/16\/16\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/16\/16\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/16\/16\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13618\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003EInflammation and Thrombosis Drive the Other in a Ongoing Cycle\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EAdapted from Croce K, Libby P. \u003Cem\u003ECurr Opin Hem\u003C\/em\u003E 2007.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EROLE OF EPICARDIAL AND INTRATHORACIC FAT\u003C\/h2\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EIn the setting of obesity, epicardial adiposity and VAT mass increase in concert, and an increase in either has a significant independent association with established cardiovascular (CV) risk factors, according to work reviewed by Amalia Gastaldelli, PhD, Institute of Clinical Physiology, CNR, Pisa, Italy, and University of Texas Health Science Center, San Antonio, Texas, USA.\u003C\/p\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EOn imaging, epicardial adiposity can be visualized as perivascular adipose tissue, surrounding coronary vessels, and, as with adipose tissue in other depots, it releases fatty acids and cytokines. Fat deposition also occurs in the intrathoracic region and inside cardiomyocytes. All of the cardiac fat depots have been shown to be markers of cardiac lipotoxicity, mitochondrial dysfunction, inflammation, local and systemic insulin resistance, atherosclerosis, and cardiac dysfunction, she stated.\u003C\/p\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EAlthough cardiac fat is associated with impairment in heart metabolism and cardiac dysfunction, Prof. Gastaldelli stated that the interplay between cardiac fat accumulation, insulin resistance, and cardiac dysfunction remains to be fully established. Men accumulated more fat around their heart, with more intrathoracic and epicardial fat deposition, than women in a CT study [Rosito GA et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2008]. A study of men with untreated hypertension showed that increased levels of epicardial and visceral adipose tissue were independent from subcutaneous fat accumulation [Sironi AM et al. \u003Cem\u003EHypertension\u003C\/em\u003E 2004].\u003C\/p\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EIn the Framingham Heart Study women with higher levels of both epicardial adiposity and visceral fat had a higher prevalence of impaired fasting glucose and hypertension while in men the association was with metabolic syndrome [Rosito GA et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2008]. In general visceral fat was a stronger predictor than epicardial adiposity of cardiometabolic risk factors, probably because of its size.\u003C\/p\u003E\n         \u003Cp id=\u0022p-12\u0022\u003EAn association was shown between cardiac fat accumulation and fatty liver, and between increased epicardial adiposity and reduced myocardial energy [Perseghin G. \u003Cem\u003EHepatology\u003C\/em\u003E 2008]. Epicardial adiposity thickness was correlated with endothelial dysfunction, as measured by reduced flow mediated vasodilation in patients with metabolic syndrome [Aydin H et al. \u003Cem\u003EMetab Syndr Relat Disord\u003C\/em\u003E 2010]. Pericardial fat was an independent risk factor for coronary artery stenosis in the Korean Atherosclerosis Study 2 although the odd ratio was small when adjusted for age, gender, and body mass index (BMI; OR, 1.01; p\u0026lt;0.03) [Kim TH et al. \u003Cem\u003EObesity (Silver Spring)\u003C\/em\u003E 2011]. \u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E details the relation between fat depots and CV disease burden in the Framingham Heart Study [Mahabadi AA et al. \u003Cem\u003EEur Heart J\u003C\/em\u003E 2009].\u003C\/p\u003E\n         \u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/13620\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/13620\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13620\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-13\u0022 class=\u0022first-child\u0022\u003ECVD Burden in Relation to Fat Deposition in the FHS\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-15\u0022\u003EEpicardial adiposity increases in parallel to intrathoracic fat and BMI [Rosito G et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2008; Sironi et al. \u003Cem\u003EDiabet Med\u003C\/em\u003E 2011; Yerramasu A et al. \u003Cem\u003EAtherosclerosis\u003C\/em\u003E 2012]. Both epicardial adiposity and intrathoracic fat were shown to be associated with glucose metabolism and type 2 diabetes, decreased left ventricular diastolic function [Sironi AM et al. \u003Cem\u003EHypertension\u003C\/em\u003E 2008], and increased blood pressure in men with newly detected, untreated essential hypertension [Sironi AM et al. \u003Cem\u003EHypertension\u003C\/em\u003E 2004] and in the Framingham Heart Study [Rosito G et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2008].\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003ERAISING HDL-C TO REDUCE CV RISK\u003C\/h2\u003E\n         \u003Cp id=\u0022p-16\u0022\u003EEpidemiologic data have shown a robust association between low levels of high-density lipoprotein cholesterol (HDL-C; \u0026lt;60 mg\/dL) and increased hazard of coronary heart disease, stroke, and CV events, according to Philip Barter, MD, PhD, University of New South Wales, Sydney, Australia. Low HDL-C (\u0026lt;42 mg\/dL) remains associated with CV events even in patients with low-density lipoprotein cholesterol (LDL-C) levels, as shown by the TNT study [Barter P et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2007]. Furthermore, HDL-C has several properties with the potential to inhibit development of atherosclerosis.\u003C\/p\u003E\n         \u003Cp id=\u0022p-17\u0022\u003EHowever, to date, interventions that raise HDL-C have not shown CV benefits in statin-treated patients. The AIM-HIGH and HPS2-THRIVE trials tested the benefit of raising HDL-C with niacin and failed to show a benefit. Prof. Barter stated AIM-HIGH was not powered to detect the 8% between-group difference in CV event rate expected from population-studies [Boden WE et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2011], and the negative result in HPS2-THRIVE, presented at ACC. 13 in March 2013, was consistent with what would be predicted from modest changes in the lipid profile observed in the trial. Further, he stated the absence of a positive result in HPS2-THRIVE does not refute the hypothesis of significant beneficial effects with greater reductions in LDL-C or greater increases in HDL-C.\u003C\/p\u003E\n         \u003Cp id=\u0022p-18\u0022\u003ETrials with cholesteryl ester transfer protein (CETP) inhibitors that have been reported to date have also not shown a benefit. Torcetrapib was associated with adverse off-target pharmacology unrelated to CETP that likely was responsible for the negative result of ILLUMINATE, said Prof. Barter [Barter PJ et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2007]. The dal-OUTCOMES trial with dalcetrapib, which increases HDL-C by about 30% with minimal effects on LDL-C levels, was terminated early for futility [Schwartz GG et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2012]. Prof. Barter stated CETP inhibition may not be effective in patients treated soon after an acute coronary syndrome (ACS), which is supported by the observation that HDL-C isolated from patients after an ACS has impaired function, and by the unexpected observation in dal-OUTCOMES that the level of HDL-C in the placebo group did not predict CV risk.\u003C\/p\u003E\n         \u003Cp id=\u0022p-19\u0022\u003EThe future of CETP inhibitors depends on the results of ongoing, clinical outcome trials with more potent agents without off-target effects. REVEAL HPS-3 TIMI 55 trial is testing anacetrapib in 30,000 patients with stable coronary artery disease and the ACCELERATE trial is testing evacetrapib in 11,000 patients with high-risk vascular disease.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2013 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/13\/16\/16.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nznmdp\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nznmdp\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nznmdp\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}