Epicardial fat: the role of testosterone and lipid metabolism in a cohort of patients with Klinefelter syndrome.

CONTEXT: Klinefelter syndrome (KS), in which subjects have additional copies of X chromosomes, is the most common male sex chromosome abnormality, with a prevalence of 1 in 660 and an incidence of about 1 in 500-700 newborns. Its sign and symptoms include infertility, generally low testosterone levels, and an increased prevalence of obesity and metabolic syndrome. Epicardial fat thickness (EFT) reflects visceral adiposity rather than general obesity. OBJECTIVE: The aim of this study was to analyze echocardiographic EFT in a cohort of patients with KS in comparison with non-obese and obese euploid controls, and to evaluate its correlation with biochemical parameters. DESIGN, SETTING AND PARTICIPANTS: Two hundred and twenty-one KS patients referred to our Rare Endocrine Diseases clinic and 77 age-matched controls underwent Doppler echocardiography and a full investigation of anthropometric and body composition, Serum levels of total testosterone (T), estradiol (E2), sex hormone binding globulin (SHBG), fasting plasma glucose, insulin, cholesterol and triglycerides were obtained. All participants underwent dual energy X-ray absorptiometry (DEXA) scan to assess truncal body fat (TrBF). MAIN OUTCOME MEASURE: EFT, body composition and metabolic parameters in KS patients and how they are affected by genotype. RESULTS: EFT was greater in KS patients than in healthy non-obese (NOb) controls, but lower than in obese (OB) controls. When KS patients were divided into groups (hypogonadal; eugonadal; receiving testosterone replacement therapy [TRT]), EFT was greater in hypogonadal patients than in NOb controls and eugonadal patients, but showed no difference from the OB controls or TRT patients. Hypogonadal patients showed increased TrBF in comparison with NOb controls and eugonadal and TRT patients, and similar TrBF to OB controls. As expected, there was a strong correlation between BMI and EFT in both KS patients and controls (P < 0.0001). In contrast, there was a strong inverse correlation between testosterone and EFT in the control group, but not in KS patients. EFT was significantly correlated with TrBF in both populations (P < 0.0001). Multivariate analyses showed that the major determinants of both EFT and TrBF were BMI and the presence of KS itself. Testosterone and triglycerides were not included as variables in the models. CONCLUSION: EFT in hypogonadal KS subjects was similar to that of the obese eugonadal controls. Even though there was a direct correlation between BMI and EFT in both populations, the influence of TrBF on EFT was stronger. The presence of the supernumerary X chromosome appeared to be one of the strongest determinants of EFT and TrBF, independent of testosterone levels.

Circulating SIRT1 inversely correlates with epicardial fat thickness in patients with obesity.

BACKGROUND AND AIM: Obesity is increasing worldwide and is related to undesirable cardiovascular outcomes. Epicardial fat (EF), the heart visceral fat depot, increases with obesity and correlates with cardiovascular risk. SIRT1, an enzyme regulating metabolic circuits linked with obesity, has a cardioprotective effect and is a predictor of cardiovascular events. We aimed to assess the relationship of EF thickness (EFT) with circulating SIRT1 in patients with obesity. METHODS AND RESULTS: Sixty-two patients affected by obesity and 23 lean controls were studied. Plasma SIRT1 concentration was determined by enzyme-linked immunosorbent assay (ELISA). EFT was measured by echocardiography. Body mass index (BMI), waist circumference, heart rate (HR), blood pressure, and laboratory findings (fasting glucose, insulin, HbA1c, cholesterol, and triglycerides) were assessed. SIRT1 was significantly lower (P = 0.002) and EFT was higher (P < 0.0001) in patients with obesity compared with lean controls. SIRT1 showed a negative correlation with EFT and HR in the obesity group (ρ = -0.350, P = 0.005; ρ = -0.303, P = 0.008, respectively). After adjustment for obesity-correlated variables, multiple linear regression analysis showed that EFT remained the best correlate of SIRT1 (ß = -0.352, P = 0.016). CONCLUSIONS: Circulating SIRT1 correlates with the visceral fat content of the heart. Serum SIRT1 levels might provide additional information for risk assessment of coronary artery disease in patients with obesity.

Effects of testosterone undecanoate replacement and withdrawal on cardio-metabolic, hormonal and body composition outcomes in severely obese hypogonadal men: a pilot study.

PURPOSE: Modifications of cardiovascular and metabolic parameters during testosterone (T) replacement and withdrawal have never been investigated in severely obese hypogonadal men. METHODS: Twenty-four severely obese (mean BMI 42; mean age 54.5) hypogonadal men (mean T = 245 ± 52 ng/dL) were enrolled in an observational, parallel-arm, open-label, 54-week study of hypocaloric diet plus physical activity (DPE; n = 12) or DPE plus T injections (DPE + T; n = 12), followed by 24 weeks of DPE alone. Primary endpoints were variations from baseline of cardiovascular (cardiac performance, blood pressure, endothelial function, carotid intima-media thickness, CIMT; epicardial fat thickness, EF) and body composition (fat/lean mass) parameters. Secondary endpoints were variations from baseline of hormonal (T and GH) and metabolic (oral glucose tolerance test, lipids, fibrinogen) parameters. RESULTS: At 54 weeks, DPE + T showed improvements in EF, ejection fraction, diastolic function, CIMT and endothelial function (p < 0.01 vs. controls). Also, hormonal (T, p < 0.0001; GH, p < 0.01), metabolic (HOMA, p < 0.01; microalbuminuria, p < 0.01), lipid (total cholesterol, p < 0.05) and inflammatory (fibrinogen, p < 0.05) parameters improved. After 24 weeks from T withdrawal, all cardiac and hormonal parameters returned to baseline, while fat but not lean mass and blood pressure ameliorations were maintained. An inverse relationship either between EF vs. endothelial function and EF vs. T levels was found (r (2) = -0.46, p < 0.001 and r (2) = -0.56, p < 0.0005, respectively) while direct relationship between T vs. endothelial function occurred (r (2) = 0.43, p < 0.005) in DPE + T. A 33 % dropout rate was reported in DPE without serious adverse events. CONCLUSIONS: In middle-aged hypogonadal obese men, 1-year T treatment was safe and improved cardio-metabolic and hormonal parameters. We firstly demonstrated that T withdrawal determines a return back to hypogonadism within 6 months, with loss of cardiovascular and some body composition improvements attained.

Metabolic or bariatric surgery? Long-term effects of malabsorptive vs restrictive bariatric techniques on body composition and cardiometabolic risk factors.

BACKGROUND: Obesity is an increasing health problem and surgery seems to be the only treatment effective in achieving weight loss without relapse. Among bariatric techniques, many differences exist in terms of weight loss and resolution of comorbidities. Up to now, there are no prospective studies comparing long-term effects of malabsorptive vs restrictive techniques. OBJECTIVE: In this study, cardiometabolic risk factors and body composition changes after malabsorptive biliointestinal bypass (BIBP) and restrictive laparoscopic adjustable gastric banding (LAGB) were compared during a 4-year follow-up. DESIGN: Prospective, case-control and cohort study. PATIENTS: In all, 80 obese subjects, matched for weight and age. Altogether, 40 patients underwent BIBP and 40 underwent LAGB. MEASUREMENTS: Weight, body composition, fasting and post-loading plasma glucose and insulin, homeostatic model assessment index (HOMA-I), lipid profile, blood pressure (BP), erythrocyte sedimentation rate and fibrinogen were monitored at baseline, 12 and 48 months. RESULTS: At 12 months after surgery, a significant reduction in body mass index, total fat mass (FM), trunk FM (trFM), trFM/legs FM (lFM) ratio (trFM/lFM), triglycerides, BP and inflammation markers was observed in both groups. BIBP patients showed a significant reduction in total cholesterol (Tot-C), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), whereas the LAGB group showed a significant increase of HDL-C. A further improvement of all the parameters evaluated was seen in the BIBP group at 48 months after surgery. CONCLUSIONS: Both bariatric procedures exerted positive effects on cardiometabolic risk factors and on weight loss in the population studied, but on the long-term period, HOMA-I, Tot-C/HDL-C ratio and body composition improvements were more evident after BIBP. We conclude that malabsorptive BIBP seems to be more effective than LAGB in treating visceral obesity and its metabolic complications.

Vascular injury, hypertension and coronary artery disease in human immunodeficiency virus infection.

The atherogenic effects of some highly active antiretroviral therapy (HAART) regimens, especially those including protease inhibitors (PI), may synergistically promote the acceleration of cardiovascular disease and increase the risk of death from cardiovascular events even in young HIV-infected people. Along with the endothelial dysfunction associated with visceral fat accumulation and related metabolic alterations of HIV-lipodystrophy syndrome (eg, insulin resistance), vascular injury has been associated with HIV-1 infection itself, with an autoimmune reaction to viral infection (vasculitis) and with a direct action of drugs included in HAART regimens. Clinical studies suggest that HIV-infected patients under PI-including HAART and with preexisting cardiovascular risk factors, should be considered at risk for developing coronary artery disease, and that this risk increases with the time of exposure to HAART. A careful cardiovascular screening and monitoring of HIV-infected patients receiving HAART is needed according to the most recent clinical guidelines.

Management of chronic hepatitis in drug addicts: a systematic review.

Injection drug users constitute the largest group of person at high risk for acquiring chronic hepatitis C, B and Delta. In particular viral, host and environmental factors all seem to favour rapid spread of these infections among drugs addicts. Host factors include behaviours that expose individuals to hepatitis virus such as the shared use of drug preparation, injection equipment and not protected sexual relationship with other drugs users. While in some clinical studies adherence to treatment regimens was often poor and to treat chronic hepatitis in injection drug users was stated as futile, in other controlled clinical studies adherence and sustained biological response to antiviral treatment was slightly lower or similar to that reported in other groups of patients. In this review we describe the epidemiology, diagnosis and treatment of chronic hepatitis C, B and Delta in intravenous drug users.

The double role of epicardial adipose tissue as pro- and anti-inflammatory organ.

Obesity is associated with low grade inflammation. Whether this is just an adaptive response to excess adiposity to maintain a normal oxygen supply or a chronic activation of the innate immune system is still unknown. Recent research has focused on the origin of the inflammatory markers in obesity and the extent to which adipose tissue has a direct effect. The production of adipokines by visceral adipose tissue is of particular interest since their local secretion by visceral fat depots may provide a novel mechanistic link between obesity and the associated vascular complications. Growing evidences suggest that the epicardial adipose tissue, the visceral fat depot located around the heart, may locally interact with myocardium and coronary arteries. Epicardial fat is a source of adiponectin and adrenomedullin, adipokines with anti-inflammatory properties, and several proinflammatory cytokines as well as Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin 1 (IL1), IL-1 h, Interleukin (IL6), Monocyte Chemoattractive Protein-1 (MCP-1), Nerve Growth Factor (NGF), resistin, Plasminogen Activator Inhibitor-1 (PAI-1), and free fatty acids. Epicardial adipose tissue could locally modulate the heart and vasculature, through paracrine secretion of pro- and anti-inflammatory cytokines, thereby playing a possible role in the adiposity-related inflammation and atherosclerosis. On the other hand, epicardial fat could exert a protective effect through adiponectin and adrenomedullin secretion as response to local or systemic metabolic or mechanical insults. Future studies will continue to provide new and fascinating insights into the double role of epicardial adipose tissue in the development of cardiovascular pathology and/or in protecting the heart and arteries.

Coronary artery bypass graft in HIV-infected patients: a multicenter case control study.

Coronary artery disease (CAD) is an emerging complication in HIV-infected patients treated with highly active antiretroviral therapy. Immediate results and long-term outcome after coronary artery bypass graft (CABG) have not been yet evaluated in this population. Between January 1997 and December 2005, we compared baseline characteristics, immediate results and clinical outcome [Major Adverse Cardiac Events (MACE): death for cardiac cause, myocardial infarction (MI), coronary revascularization] at 41 months in 27 consecutive HIV-infected (HIV+) patients and 54 HIV-uninfected (HIV-) controls matched for age and gender (mean age of the cohort, 49+/-8 years; 96% male) who underwent CABG. Cardiovascular risk factors were well-balanced and nearly identical in both groups. In HIV+ group, mean preoperative CD4 was 502+/-192/mm(3) compared with 426.2+/-152.6/mm(3) postoperatively (p=0.004) without clinical manifestations at follow-up. At 30-day, the rate of post-operative death, MI, stroke, mediastinitis, re-intervention was identical in both groups. At follow-up [median: 41-months (range: 34-60)], rate of occurrence of 1(st) MACE was higher in HIV+ group compared with HIV- group (11, 42% versus 13, 25%, p=0.03), mostly due to the need of repeated revascularization using percutaneous coronary intervention of the native coronary arteries but not of the grafts in the HIV+ group [9 (35%) versus 6 (11%), p=0.02]. CABG is a feasible and safe revascularization procedure in HIV+ patients with multivessel CAD. Immediate postoperative outcome was similar compared to controls. However, long-term follow-up was significantly different, due to an increased rate of repeated revascularization procedure in the native coronary arteries of HIV+ patients.

Cardiac autonomic imbalance in patients with reversible ventricular dysfunction takotsubo cardiomyopathy.

BACKGROUND: Although in reversible takotsubo cardiomyopathy (TC), wall motion generally recovers dramatically within a few weeks, there are few data on changes in autonomic function in this condition. AIM: To investigate cardiac autonomic function in the acute and chronic phases of TC. METHODS: Ten patients with TC (mean age 70.1 +/- 13.7 years) underwent cardiac catheterization on the first hospital day, when left ventricular (LV) ejection fraction (EF) was calculated. A Holter electrocardiographic study was performed within 3 days after the onset of symptoms (0 months) and 3 months after discharge (3 months). The standard deviation of the mean cycle length of normal-normal R-R (NN) intervals over 24 h (SDNN), and the 24-h standard deviation of the mean value of the difference between the NN intervals for each 5-min segment (SDANN), were calculated according to time-area analysis of heart rate variability over 24 h. Frequency domain analysis was also done. RESULTS: Coronary angiography in the acute and chronic phases revealed no significant stenosis in any TC patient. LV wall motion returned to normal in 17.6 +/- 6.4 days. LVEF was 45.7 +/- 8.8% in the acute phase and 69.8 +/- 6.8% after the improvement of wall motion (p < 0.001). Between 0 months and 3 months, SDNN and SDANN improved significantly, from 88.8 +/- 35.5 to 109.5 +/- 33.4 ms (p = 0.01) and from 79.9 +/- 34.7 to 99.3 +/- 40.3 ms (p = 0.03), respectively. No significant changes were observed in frequency domain parameters. DISCUSSION: These results support our previous hypothesis that TC might be caused by neurogenic stunning of the myocardium, due to acute autonomic dysfunction.

Reviewing the cardiovascular complications of HIV infection after the introduction of highly active antiretroviral therapy.

Studies published before the introduction of highly active antiretroviral therapy (HAART) have tracked the incidence and course of human immunodeficiency virus (HIV) infection in relation to cardiac disease.The introduction of HAART regimens, by preventing opportunistic infections and reducing the incidence of myocarditis, has reduced the prevalence of HIV-associated cardiomyopathy of about 30% and the prevalence of cardiac involvement of AIDS-associated malignancies of about 50%. However, HAART regimens, especially those including protease inhibitors have been shown to cause, in a high proportion of HIV-infected patients, a metabolic syndrome (lipodystrophy/lipoatrophy, dyslipidemia, type 2 diabetes mellitus, insulin resistance) that may be associated with an increased risk of cardiovascular disease (approximately 1.4 cardiac events per 1000 years of therapy according to the Framingham score). A careful stratification of the cardiovascular risk and cardiovascular monitoring of patients under HAART according to the most recent clinical guidelines is needed.

Intermittent left anterior hemiblock. A rare case report.

The Authors report a rare case of intermittent left anterior hemiblock in a 86-year-old man admitted to Department of Emergency Medicine for progressive impoverishment of intellectual functions and episodes of chest pain. They present this rare case of intermittent left anterior hemiblock where the intermittence was not linked to heart rate variations preceding the beginning of the hemiblock being present on the same ECG two different QRS complexes with no modification in frequency or A-V conduction: this finding suggesting a vascular origin of the disturbance. They also stress the importance of a prompt diagnosis in a Department of Emergency Medicine.

HIV-associated cardiovascular complications: a new challenge for emergency physicians.

Cardiac complications associated with the AIDS may present to emergency physicians and are often secondary to opportunistic infections or malignancy, but may also be associated with other aspects of the human immunodeficiency virus (HIV) or its treatment. In this review article, we will discuss HIV-associated cardiac disease which may be encountered in the ED, emphasizing the prevalence, pathogenesis, and treatment of related disorders.

Long-term efficacy of interferon alpha-2b and lamivudine in combination compared to lamivudine monotherapy in patients with chronic hepatitis B. An Italian multicenter, randomized trial.

BACKGROUND/AIMS: To evaluate the therapeutic efficacy of interferon alpha-2b and lamivudine in combination compared to lamivudine monotherapy in patients with chronic hepatitis B. METHODS: One hundred and fifty-one patients were randomly assigned to receive either recombinant interferon alpha-2b (nine million units three times per week) and lamivudine (100 mg/daily per os) for 24 weeks or lamivudine alone (100 mg/daily per os) for 52 weeks. Patients were followed up for a further 48 weeks. RESULTS: Sustained HBeAg seroconversion with undetectable serum levels of HBV DNA was observed in 25 of 76 patients (33%) treated with the combination therapy and in 11 of 75 patients (15%) treated with monotherapy (P=0.014). Histological improvement defined as a reduction of at least two points in the inflammation score as compared with pretreatment score was observed in 35 of 76 patients (46%) treated with combination therapy and in 20 of 75 patients (27%) treated with monotherapy (P=0.021). Both therapeutic regimens were well tolerated. CONCLUSIONS: Six-month treatment with interferon alpha-2b and lamivudine in combination appeared to increase the rate of sustained HBeAg seroconversion compared to 1-year lamivudine monotherapy. However, the potential benefit of combining lamivudine and interferon should be investigated further in studies with different regimens of combination therapy.