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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.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 associated with a range of adverse metabolic consequences, including endothelial dysfunction, systemic inflammation, and insulin resistance. Therefore, to provide effective protection against the development of atherosclerosis and heart disease, obese patients require combination drug regimens that target several cardiometabolic risk factors.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EObesity\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiometabolic Disorder\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHypertensive Disease\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EObesity is associated with a range of adverse metabolic consequences, including endothelial dysfunction, systemic inflammation, and insulin resistance. Therefore, to provide effective protection against the development of atherosclerosis and heart disease, obese patients require combination drug regimens that target several cardiometabolic risk factors.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EKwang Kon Koh, MD, Gachon University Gil Hospital, Incheon, Korea, described the rationale for multiple targeted therapy in patients with abdominal obesity.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EAdipose tissue acts as a complex endocrine organ that secretes both atherogenic cytokines, such as leptin and high-sensitivity C-reactive protein (hsCRP), and anti-atherogenic hormones, such as adiponectin. As individuals gain weight, the accumulation of visceral adipocytes leads to macrophage infiltration, increased release of atherogenic cytokines, and decreased secretion of adiponectin. Together, these pathologic mechanisms promote the development of atherosclerosis.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EModerate weight loss, defined as a loss of 5% to 10% of total body weight and 15% to 30% of visceral adipose tissue, improves cardiometabolic risk profile by lowering low-density lipoprotein (LDL) and triglyceride levels and improving glycemic control [Roberts CK et al. \u003Cem\u003EJ Appl Physiol\u003C\/em\u003E 2006]. However, weight loss goals are difficult to achieve. In a study of obese patients following 1 of 4 popular weight loss programs, the drop-out rate ranged from 35% to 50% after 12 months [Dansinger ML et al. \u003Cem\u003EJAMA\u003C\/em\u003E 2005]. Among patients who remained in the program, the mean weight loss ranged from 4.7 to 7.1 lbs. Therefore, although moderate weight loss is an effective tool for reducing cardiometabolic risk, many obese patients will require additional interventions.\u003C\/p\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EStatin-based Combination Therapy\u003C\/h2\u003E\n         \u003Cp id=\u0022p-6\u0022\u003ECombination drug therapy can be tailored to address the related mechanisms that underlie obesity, diabetes, dyslipidemia, hypertension, atherosclerosis, and coronary heart disease (CHD). Statins and renin-angiotensin-aldosterone system blockers, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), have beneficial vascular and metabolic effects in patients with multiple risk factors. For instance, in a randomized, double-blind, placebo-controlled study of 47 patients with hypertension and hypercholesterolemia, combination therapy with simvastatin 20 mg\/day and losartan 100 mg\/day improved vasomotor function and reduced inflammatory markers to a greater extent than statin or ARB monotherapy [Koh KK et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2004]. In another randomized, double-blind, placebo-controlled study of 50 patients with type 2 diabetes, combination treatment with simvastatin 20 mg\/day and ramipril 10 mg\/day provided a greater reduction in hsCRP levels and a greater improvement in endothelium-dependent dilation than either statin or ACE inhibitor therapy alone [Koh KK et al. \u003Cem\u003EHypertension\u003C\/em\u003E 2005].\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003ENot all statin therapies have similar metabolic effects in patients with elevated LDL levels. Prof. Koh and colleagues showed that despite providing similar reductions and LDL levels and similar improvements in endothelium-dependent dilation, simvastatin and pravastatin had different effects on adipocytokine levels and glucose metabolism. In a study of 43 patients with hypercholesterolemia, treatment with pravastatin 40 mg\/day significantly increased plasma adiponectin levels by 10% (p=0.012) and insulin sensitivity by 6% (p=0.008) compared with baseline. In contrast, treatment with simvastatin 20 mg\/day significantly decreased plasma adiponectin levels by 10% (p=0.012) and insulin sensitivity by 6% (p=0.007) compared with baseline [Koh KK. \u003Cem\u003EAtherosclerosis\u003C\/em\u003E 2009].\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003ETreatment with atorvastatin also appears to adversely effect glucose metabolism. In a study of 213 patients with hypercholesterolemia, treatment with atorvastatin 10 to 80 mg\/day significantly reduced LDL and apolipoprotein B levels compared with placebo after 2 months (p\u0026lt;0.001) [Koh KK et al. \u003Cem\u003EJ Am Coll Cardiol\u003C\/em\u003E 2010]. All doses of atorvastatin also significantly increased glycated hemoglobin levels (p=0.008) and significantly decreased insulin sensitivity (p=0.033) compared with placebo (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). These findings support the hypothesis that lipophilic statins, including atorvastatin, simvastatin, and rosuvastatin, might increase the onset of new diabetes in patients with hypercholesterolemia. Prof. Koh suggests a weak hydrophilic, but strong HMGCoA enzyme inhibiting statin, following rosuvastatin because rosuvastatin is not lipophilic.\u003C\/p\u003E\n         \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\/11\/2\/16\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Atorvastatin (10, 20, 40, or 80 mg\/day) Significantly Increases HbA1C Levels and Insulin Resistance In Hypercholesterolemic Patients.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1304552680\u0022 data-figure-caption=\u0022Atorvastatin (10, 20, 40, or 80 mg\/day) Significantly Increases HbA1C Levels and Insulin Resistance In Hypercholesterolemic Patients.\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\/11\/2\/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\/11\/2\/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\/11\/2\/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\/12248\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-9\u0022 class=\u0022first-child\u0022\u003EAtorvastatin (10, 20, 40, or 80 mg\/day) Significantly Increases HbA1C Levels and Insulin Resistance In Hypercholesterolemic Patients.\u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EA10=atorvastatin 10 mg\/day; A20=atorvastatin 20 mg\/day; A40=atorvastatin 40 mg\/day; A80=atorvastatin 80 mg\/day; ANOVA=analysis of variance; Pl=placebo; QUICKI=Quantitative Insulin-Sensitivity Check Index.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EFibrate-Based Combination Therapy\u003C\/h2\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EElevated triglyceride levels are another important target for combination therapy. According to a meta-analysis of 262,525 participants in 29 studies, there is a significant correlation between triglyceride values and CHD risk. Indeed, patients in the top tertile of triglyceride values have a 72% higher risk of CHD than those in the bottom tertile (OR, 1.72; 95% CI, 1.56 to 1.90) [Sarwar N et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2007].\u003C\/p\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EFibrates are emerging as an important therapeutic option for patients with elevated triglyceride levels. In addition to lowering triglyceride levels, fibrate therapy improves endothelium-dependent vasodilation, exerts anti-inflammatory effects, stabilizes atherosclerotic plaques, and inhibits platelet thrombus formation. In a meta-analysis of 18 trials, fibrates significantly reduced the risk of major cardiovascular events in patients with combined dyslipidemia (RR, 0.90; p=0.048), primarily by preventing coronary events (RR, 0.87; p\u0026lt;0.0001) [Jun M et al. \u003Cem\u003ELancet\u003C\/em\u003E 2010].\u003C\/p\u003E\n         \u003Cp id=\u0022p-12\u0022\u003EFibrates also enhance the cardioprotective effects of other drug classes. In a randomized, double-blind, placebo-controlled study of 44 patients with hypertension and hypertriglyceridemia, combination therapy with fenofibrate and candesartan provided greater improvement in endothelial function and greater reduction in hsCRP level compared with fibrate or ARB monotherapy. All treatment options, including combination therapy, fenofibrate monotherapy, and candesartan monotherapy, also significantly increased adiponectin levels and insulin sensitivity compared with baseline [Koh KK et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E 2006].\u003C\/p\u003E\n         \u003Cp id=\u0022p-13\u0022\u003EIn summary, there are multiple etiologies for atherosclerosis and cardiovascular disease. Thus, combination therapy with drugs that have distinct and separate mechanisms of action appear to provide greater protection against cardiovascular events than individual monotherapies. Clinicians should select specific combination regimens that have been shown to provide comprehensive protection against the adverse consequences of abdominal obesity and increased cardiometabolic risk, Prof. Koh said.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2011 MD Conference Express\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\/11\/2\/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?nzn43e\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?nzn43e\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}