António J. Madureira

Adipokines, hormones related to body composition, and insulin resistance in HIV fat redistribution syndrome

BackgroundLipodystrophies are characterized by adipose tissue redistribution, insulin resistance (IR) and metabolic complications. Adipokines and hormones related to body composition may play an important role linking these alterations. Our aim was to evaluate adipocyte-derived hormones (adiponectin, leptin, resistin, TNF-α, PAI-1) and ghrelin plasma levels and their relationship with IR in HIV-infected patients according to the presence of lipodystrophy and fat redistribution.MethodsAnthropometric and metabolic parameters, HOMA-IR, body composition by DXA and CT, and adipokines were evaluated in 217 HIV-infected patients on cART and 74 controls. Fat mass ratio defined lipodystrophy (L-FMR) was defined as the ratio of the percentage of the trunk fat mass to the percentage of the lower limb fat mass by DXA. Patient’s fat redistribution was classified into 4 different groups according the presence or absence of either clinical lipoatrophy or abdominal prominence: no lipodystrophy, isolated central fat accumulation (ICFA), isolated lipoatrophy and mixed forms (MXF). The associations between adipokines levels and anthropometric, metabolic and body composition were estimated by Spearman correlation.ResultsLeptin levels were lower in patients with FMR-L and isolated lipoatrophy, and higher in those with ICFA and MXF. Positive correlations were found between leptin and body fat (total, trunk, leg, arm fat evaluated by DXA, and total, visceral (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT ratio evaluated by CT) regardless of FMR-L, and with HOMA-IR only in patients with FMR-L. Adiponectin correlated negatively with VAT, and its mean levels were lower in patients with ICFA and higher in those with no lipodystrophy. Resistin was not correlated with adipose tissue but positively correlated with HOMA-IR in FMR-L patients. PAI-1 levels were higher in MXF-patients and their levels were positively correlated with VAT in those with FMR-L. Ghrelin was higher in HIV-infected patients than controls despite BMI-matching.ConclusionThe overall body fat reduction in HIV lipoatrophy was associated with low leptin plasma levels, and visceral fat accumulation was mainly associated with decreased plasma levels of adiponectin.

Carotid intima media thickness is associated with body fat abnormalities in HIV-infected patients

BackgroundHIV-infected patients may be at increased risk of cardiovascular (CV) events, and lipodystrophy is generally associated with proatherogenic metabolic disturbances. Carotid intima-media thickness (cIMT) has been used as a surrogate marker for atherosclerosis and it has been shown to be an independent risk factor for CV disease. Our objective was to evaluate cIMT in HIV-infected patients on combined anti-retroviral therapy (cART) with and without lipodystrophy defined by fat mass ratio (L-FMR), and to determine the association of lipodystrophy and visceral obesity [(visceral (VAT), subcutaneous adipose tissue (SAT) volume and VAT/SAT ratio, objectively evaluated by CT scan] with cIMT.MethodsCross-sectional study of 199 HIV-infected patients. Body composition by DXA and abdominal CT, lipids, blood pressure, inflammatory markers, and cIMT by ultrasonography were performed. L-FMR was defined as the ratio of the percentage of trunk fat mass to the percentage of lower limb fat mass by DXA. Categorical variables were compared using the chi-square or Fisher’s exact test. Spearman correlation coefficients were estimated to study the association between cIMT and clinical and metabolic characteristics. Means of cIMT, adjusted for age, were calculated, using generalized linear models.ResultsL-FMR was present in 41.2% of patients and cIMT was higher in these patients [0.81 (0.24) vs. 0.76 (0.25); p = 0.037)]. Lipodystrophic patients had higher VAT and VAT/SAT ratio and lower SAT. cIMT was associated with lipodystrophy evaluated by FMR, trunk fat, total abdominal fat, VAT and VAT/SAT ratio. No association was observed between cIMT and leg fat mass. Using generalized linear models, cIMT means were adjusted for age and no significant differences remained after this adjustment. The adjusted mean of cIMT was 0.787 (95% CI: 0.751-0.823) in patients without lipodystrophy, and 0.775 (95% CI: 0.732-0.817) in those with lipodystrophy (p = 0.671).ConclusionsHIV-infected patients on cART with lipodystrophy defined by FMR, had a significantly higher cIMT. Carotid IMT was also associated with classical cardiovascular risk factors. In these patients, visceral adipose tissue had a significant impact on cIMT, although age was the strongest associated factor.

Prevalence of obesity and its relationship to clinical lipodystrophy in HIV-infected adults on anti-retroviral therapy.

Background: Combination antiretroviral therapy (cART) is associated with lipodystrophy (lipoatrophy and lipoaccumulation) and several metabolic abnormalities that together can contribute to an increased cardiovascular risk. The aim of this study was to evaluate the prevalence of obesity in patients on cART according to the presence of clinical lipodystrophy (CL) and to analyze factors associated with obesity. Methods: We evaluated 368 HIV-infected adults on cART. Results: CL was present in 59.0%. Independently of gender, patients with CL were more frequently underweight [5.7% (21/368)] and of normal weight [47.3% (174/368)], and less frequently overweight [33.2% (122/368)] or obese [13.9% (51/368)]. Mean body mass index was higher in patients with abdominal prominence regardless of the presence of clinical lipoatrophy. Patients with CL had lower waist circumference, higher waist/hip and fat mass ratio and lower total and subcutaneous fat, without significant difference in visceral fat but with a higher visceral/subcutaneous fat ratio, as evaluated by CT at abdominal level. CL was significantly less frequent in overweight [odds ratio (OR)=0.21, 95% confidence interval (CI): 0.05–0.92] and obese (OR=0.05, 95%CI: 0.01–0.26) patients, when compared to underweight ones, independent of age, gender, duration of infection, cART regimen, virological suppression, and HIV-infection risk factor. Conclusions: Being overweight or obese is highly prevalent in HIV-infected patients on cART. Patients with CL were more frequently under- or normal weight, and less frequently overweight or obese. Obesity is a condition that should be considered in HIV patients on cART.

Lipodystrophy defined by Fat Mass Ratio in HIV-infected patients is associated with a high prevalence of glucose disturbances and insulin resistance

IntroductionCombined antiretroviral therapy (cART) in the treatment of HIV-1 infection has been associated with complications, including lipodystrophy, hyperlipidaemia, insulin resistance (IR) and diabetes.AimsTo compare the prevalence of glucose homeostasis disturbances and IR in HIV patients on cART according to the presence of lipodystrophy (defined clinically and by Fat Mass Ratio) and different patterns of fat distribution and to establish their associations.DesignCross-sectional cohort study.MethodsWe evaluated body composition and IR and insulin sensitivity indexes in 345 HIV-infected adults.ResultsPatients with clinical lipodystrophy (CL) had higher plasma glucose levels than patients without CL, without significant differences in plasma insulin levels, A1c, HOMA-IR, HOMA-B, QUICKI, or MATSUDA index. Patients with lipodystrophy defined by FMR had higher plasma glucose and insulin levels, A1c, HOMA-IR, QUICKI and MATSUDA than patients without lipodystrophy, without differences in HOMA-B. Higher insulin resistance (HOMA-IR ≥ 4) was present in patients with FMR-defined lipodystrophy. Patients with FMR-defined lipodystrophy had a higher prevalence of IFG, IGT and DM than patients without lipodystrophy. Significant associations between HOMA-IR and total, central and central/peripheral fat evaluated by CT at abdominal level were found and no association between HOMA-IR and peripheral fat. Association between HOMA-IR and total and trunk fat but no association with leg and arm fat (evaluated by DXA) was found.ConclusionsIR and glucose disturbances were significantly increased in patients with FMR-defined lipodystrophy. FMR lipodystrophy definition seems to be a more sensitive determinant of insulin resistance and glucose disturbances than clinical definition.

Central⁄Peripheral Fat Mass Ratio Is Associated With Increased Risk of Hypertension in HIV-Infected Patients

J Clin Hypertens (Greenwich). 2012; 14:593–600.

Cardiac metastasis from epidermoid esophageal cancer mimicking anterior myocardial infarction

Cardiac metastases are more common than primary tumors. Several types of malignant tumors have been reported to metastasize to the heart, mainly lung cancer, but in the setting of esophageal cancer, myocardial metastasis is comparatively rare. We report a case of a cardiac metastasis from esophageal squamous cell carcinoma detected 9 months after surgically curative esophagectomy, which presented mimicking acute myocardial infarction. The use of different imaging modalities was fundamental to a correct diagnosis considering the challenging presentation.

Isolated papillary muscle hypertrophy: a variant of hypertrophic cardiomyopathy? Do not miss a hypertrophic cardiomyopathy

A 65-year-old Caucasian, hypertensive, and asymptomatic man was referred to cardiology consultation because of an abnormal electrocardiogram (ECG) with left ventricle (LV) hypertrophy and giant negative T waves ( Panel A ) (evolutive compared with ECG performed 10 years before). A transthoracic echocardiogram showed no significant abnormalities and the myocardial perfusion scintigraphy excluded ischaemia. Cardiac magnetic resonance confirmed …

IL-4 and IL-6 levels and adipose tissue distribution in HIV-1 patients under antiretroviral therapy

PurposeCombined antiretroviral therapy (cART) for the treatment of HIV-1 infection has been associated with complications, including lipodystrophy. Several interleukins have been implicated in the pathology and physiology of lipodystrophy. The present study aimed to compare the levels of IL-4 and IL-6 in HIV-1 patients under cART with and without, clinically and fat mass ratio defined, lipodystrophy and in four different groups of fat distribution: (1) no lipodystrophy; (2) isolated central fat accumulation; (3) isolated lipoatrophy and (4) mixed forms of lipodystrophy.MethodsIn the present cross-sectional study we evaluated IL-4 and IL-6 levels, insulin resistance and insulin sensitivity indexes in 86 HIV-infected adults under cART.ResultsNo significant differences in IL-4 and IL-6 levels between the four groups of body composition were observed. Patients with HOMA-IR >4 presented higher levels of IL-6 and lower levels of IL-4, although without statistical significance. No correlation between IL-6, or IL-4, HOMA-IR and quantitative body fat mass distribution was found.ConclusionAlthough there was a tendency for patients with isolated lipoatrophy and isolated fat accumulation to present higher IL-6 levels, these differences were not statistically significant. No differences were found relating IL-4 levels.

Spontaneous closure of a left ventricle pseudoaneurysm following apical venting

Cardiac surgery is the second most frequent aetiology of left ventricular pseudoaneurysm (LVP). Left ventricular apical venting is a recognized cause of LVP. Prompt surgical treatment is usually needed since there is a high risk of rupture and spontaneous closure is very rare. We describe a case of spontaneous closure of a left ventricle pseudoaneurysm following apical venting.

Visceral adipose tissue and carotid intima-media thickness in HIV-infected patients undergoing cART: a prospective cohort study

BackgroundCombined antiretroviral therapy (cART) in HIV-infected patients has been associated with lipodystrophy, metabolic abnormalities, and an increased risk of cardiovascular disease. Ultrasound measures of carotid artery intima-media thickness (cIMT) have been used as a valid measure of subclinical atherosclerosis and as a tool to predict the risk of cardiovascular events. Our aim was to evaluate the progression of cIMT in HIV-infected patients subjected to cART, with and without lipodystrophy, over a one-year period.MethodsWe performed a one-year prospective cohort study to compare changes in cIMT, metabolic and inflammation markers in HIV-infected patients undergoing cART. Body composition was assessed by dual-energy X-ray absorptiometry (DXA) and abdominal computed tomography (CT). Levels of blood pressure, lipids and inflammatory markers were evaluated, as well as ultrasound measures of cIMT. Lipodystrophy defined by Fat Mass Ratio (L-FMR) is measured as the ratio of the percentage of trunk fat mass to the percentage of lower limb fat mass by DXA. Categorical variables were compared, using the chi-square or Fisher’s exact test. Wilcoxon ranks tests and the McNemar chi-square tests were used to compare results of selected variables, from the first to the second year of evaluation. Means of cIMT, adjusted for age, glucose, triglycerides levels, systolic blood pressure (SBP), and waist to hip ratio were calculated, using generalised linear models for repeated measures.ResultsL-FMR was present in 44.3% of patients, and the mean of cIMT increased significantly in this group [0.82 (0.26) vs 0.92 (0.33); p = 0.037], as well as in patients without lipodystrophy [0.73 (0.20) vs 0.84 (0.30); p = 0.012]. In the overall sample, the progression of cIMT was statistically significant after the adjustment for age, glucose, triglycerides, and SBP, but the significance of the progression ceased after the adjustment for waist/hip ratio [0.770 (0.737–0.803) vs 0.874 (0.815–0.933); p = 0.514].ConclusionsCarotid IMT progressed significantly in both groups of this HIV-infected cohort, however no association between the progression of cIMT and the presence of lipodystrophy defined by FMR was found. Visceral adipose tissue had an impact on the increment of cIMT, both in patients with, and without lipodystrophy defined by FMR.