OBJECTIVE -Obesity is an important risk factor for heart failure in both women and men. Dyssynchrony between right and left ventricular contraction and relaxation has been identified as an independent predictor of heart failure. We examined the relationship of ventricular synchronization abnormalities with the concentration of proinflammatory cytokines in obese women at baseline and after sustained weight loss.RESEARCH DESIGN AND METHODS -Echocardiographic parameters of ventricular dyssynchrony, circulating levels of tumor necrosis factor (TNF)-␣, interleukin (IL)-6, IL-18, and C-reactive protein (CRP) were investigated in 67 healthy, premenopausal obese women and 40 age-matched normal-weight women.RESULTS -Compared with nonobese women, obese women had increased concentrations of CRP (P Ͻ 0.01), TNF-␣ (P Ͻ 0.01), IL-6 (P Ͻ 0.01), and IL-18 (P Ͻ 0.01). Moreover, obese women had a higher myocardial performance index (P Ͻ 0.02) and lower transmitral Doppler flow (P Ͻ 0.05), pulmonary venous flow analysis (P Ͻ 0.02), and ejection fraction (P Ͻ 0.05), indicating ventricular dyssynchrony. Concentrations of CRP, TNF-␣, and IL-6 were related to anthropometric indexes of obesity and to echocardiographic parameters of ventricular dyssynchrony. After 1 year of a multidisciplinary program of weight reduction, obese women lost at least 10% of their original weight. This was associated with reduction of cytokine (P Ͻ 0.01) and CRP (P Ͻ 0.02) concentrations and with improvement of echocardiographic parameters of ventricular dyssynchrony, which correlated with changes in adiposity, particularly visceral adiposity.CONCLUSIONS -In obese women, ventricular dyssynchrony correlates with body fat, possibly through inappropriate secretion of cytokines. Weight loss represents a safe method for downregulating the inflammatory state and ameliorating cardiac function in obese women. Diabetes Care 27:47-52, 2004D yssynchrony between right and left ventricular contraction and relaxation has been identified as an independent predictor of cardiac mortality in patients with heart failure (1,2). Moreover, cardiac resynchronization reduces mortality from progressive heart failure in patients with symptomatic left ventricular dysfunction and ventricular dyssynchrony (3). Because approximately onehalf of all deaths among patients with heart failure occur because of progressive cardiac dysfunction, it may be important to evaluate heart function among people at risk of heart failure.Obesity is an important risk factor for heart failure in both women and men. Approximately 11 and 14% of heart failure cases among men and women in the community, respectively, are attributable to increased BMI (4). This is associated with altered left ventricular remodeling, possibly owing to increased hemodynamic load, neurohormonal activation, and increased cytokine production (5). Adipocytes synthesize and secrete several cytokines, including tumor necrosis factor (TNF)-␣ (6) and interleukin (IL)-6 (7). Elevated levels of IL-6, TNF-␣, and IL-18 as well as the sensiti...

This article is available online at http://www.jlr.org tural basis of the progression from well-compensated hypertrophy to HF is still largely unknown in MS patients. Emerging evidence suggests that inherited and acquired cardiomyopathies, such as impaired glucose tolerance and diabetes, are associated with marked intracellular lipid accumulation in the heart ( 2, 3 ). In the normal body, most triglyceride is stored in adipocytes; the amount of triglyceride stored in nonadipocyte tissues (liver, and myocardium) is minimal and very tightly regulated. However, several-fold increased cardiomyocyte triglyceride stores are observed in animal models of obesity and diabetes ( 4 ). This lipid accumulation may contribute to cardiomyocyte death by nonoxidative and oxidative ( 5 ) metabolic pathways and to HF. Even in humans, myocardial lipid content was recently reported to increase with the degree of adiposity and contribute to cardiac dysfunction ( 6 ), suggesting that myocardial lipid content may be a biomarker and putative therapeutic target for cardiac disease in patients with MS.Genes involved in lipid metabolism are nutritionally regulated at the transcriptional level in a coordinated fashion ( 7 ). Sterol-regulatory element binding protein (SREBP)-1c is a transcription factor that controls lipogenesis and is induced during overnutrition to facilitate the conversion of glucose to fatty acids and triglycerides for the storage of excess energy ( 8 ). Uncontrolled activation of nuclear SREBP-1c in the liver can cause hepatosteatosis Metabolic syndrome (MS) is strongly associated with left ventricular (LV) hypertrophy and cardiac function derangements that lead to heart failure (HF) ( 1 ). The struc-

OBJECTIVE -Stress hyperglycemia has been associated with increased mortality in patients with myocardial infarction (MI). We examined the association between plasma glucose levels, circulating inflammatory markers, T-cell activation, and functional cardiac outcome in patients with first MI. RESEARCH DESIGN AND METHODS -Echocardiographic parameters, circulating levels of interleukin-18 (IL-18), C-reactive protein (CPR), and the percent of CD16-CD56, CD4/CD8, CD152, and HLA-DR expression were investigated in 108 patients with acute MI on admission to the emergency ward.RESULTS -Our review found that 31 new hyperglycemic patients (glycemia Ն7 mmol/l) had higher infarct segment length (P Ͻ 0.05) and myocardial performance index (P Ͻ 0.02) and reduced transmitral Doppler flow (P Ͻ 0.05), pulmonary flow analysis (P Ͻ 0.02), and ejection fraction (P Ͻ 0.05) compared with 36 hyperglycemic diabetic patients and 41 normoglycemic patients. Plasma IL-18 and CRP were higher in the hyperglycemic than in the normoglycemic patients (P Ͻ 0.005), with the highest values in patients with new hyperglycemia (P Ͻ 0.05). Hyperglycemic patients had a higher percent of CD16ϩ/CD56ϩ cells and CD4/CD8 ratio (P Ͻ 0.01), whereas they had lower CD152 expression (which has a negative regulatory function in T-cell activation) compared with normoglycemic patients (P Ͻ 0.001).CONCLUSIONS -During MI, hyperglycemia is associated with increased levels of inflammatory markers, enhanced expression of cytotoxic T-cells, and reduced expression of T-cells, which are implicated in limiting the immune process. An increased inflammatory immune process seems a likely mechanism linking acute hyperglycemia to poor cardiac outcome in MI patients. Diabetes Care 26:3129 -3135, 2003A n unusually high prevalence of glycosuria in nondiabetic patients who have acute myocardial infarction (MI) was noted as early as 1931 (1). Stress hyperglycemia after MI is associated with an increased risk of in-hospital mortality in patients with and without diabetes (2). Moreover, a positive association between hyperglycemia at the time of the event and subsequent mortality from MI has been reported (3). Although the mechanisms underlying this association are not fully understood, evidence that the use of insulin to lower glucose concentrations decreases mortality in diabetic patients who have MI (4) suggests that hyperglycemia is not simply an epiphenomenon of a stress response. Consequently, hyperglycemia at the time of MI may be an important and potentially modifiable risk factor for poor outcome.A growing body of evidence suggests that MI is associated with local and systemic inflammation (5). Cell activation, which is mediated to some extent by immune mechanisms, is an important component of inflammatory reaction (6). Atherosclerotic plaques contain large numbers of activated T-cells, suggesting that immune mechanisms are important factors in the pathogenesis of the atherosclerotic background (6). Indeed, inflammatory cells infiltrate nearly all plaques, and culprit lesions of...