Sex and age interaction with genetic association of atherogenic uric acid concentrations

BackgroundHigh serum uric acid levels are associated with gout, atherosclerosis and cardiovascular disease. Three genes (SLC2A9, ABCG2, and SLC17A3) were reported to be involved in the regulation of uric acid levels.ResearchDesign and Methods: SNPs rs2231142 (ABCG2) and rs1165205 (SLC17A3) were genotyped in three cohorts (n = 4492) and combined with previously genotyped SNPs within SLC2A9 (rs6855911, rs7442295, rs6449213, rs12510549).ResultsEach copy of the minor allele decreased uric acid levels by 0.30–0.38 mg/dL for SLC2A9 (p values: 10^?20–10^?36) and increased levels by 0.34 mg/dL for ABCG2 (p = 1.1 × 10^?16). SLC17A3 influenced uric acid levels only modestly. Together the SNPs showed graded associations with uric acid levels of 0.111 mg/dL per risk allele (p = 3.8 × 10^?42). In addition, we observed a sex-specific interaction of age with the association of SLC2A9 SNPs with uric acid levels, where increasing age strengthened the association of SNPs in women and decreased the association in men.ConclusionsGenetic variants within SLC2A9, ABCG2 and SLC17A3 show highly significant associations with uric acid levels, and for SNPs within SLC2A9 this association is strongly modified by age and sex.     

Combination therapy with an immunomodulator and anti-TNFα agent improves bone mineral density in IBD patients

ObjectiveThere is a high prevalence of low bone mineral density (BMD) among patients with inflammatory bowel disease (IBD) although there is a lack of clinical data on the impact of IBD specific medications and recommended vitamin D (VD) and calcium (Ca) supplements on it.DesignThe cohort consisted of 150 IBD patients. The average change in BMD at the lumbar spine per year (∆BMDL/year) was calculated and the impact of clinical characteristics, medications and VD and Ca supplements was analysed.ResultsThe prevalence of osteopenia was 69/150 (46%) and osteoporosis was identified in 15/150 (10%) patients at baseline. The presence of osteoporosis was associated with the disease duration OR = 1.07 per year of disease duration (95% CI = 1.01–1.14), p = 0.03. The average ∆BMDL/year was 0.010 g/cm²/year. Among patients with no IS the ∆BMDL/year was − 0.001 ± 0.010 g/cm²/year, with AZA − 0.001 ± 0.013 g/cm²/year, with anti-TNFα 0.003 ± 0.006 g/cm²/year and with COMBO 0.027 ± 0.004 g/cm²/year; p < 0.05 COMBO vs any other subgroup. ∆BMDL/year among patients treated with CS was − 0.031 ± 0.012 g/cm²/year versus CS free patients 0.013 ± 0.004 g/cm²/year; p < 0.001. There was no effect of VD/Ca supplementation on BMDL.ConclusionsThe prevalence of low BMD was 55%. Duration of disease was the only independent predictor of low BMD. The BMDL was reduced by high cumulative dose of CS and improved by combined anti-TNFα/AZA therapy. The supplementation with recommended doses of VD and Ca had no effect on BMDL.     

Relationship between circulating endothelial progenitor cells and insulin resistance in non-diabetic patients with ischemic chronic heart failure

AimThe objective of this study was to assess a relationship between insulin resistance (IR) and counts of CD45⁻CD34⁺, CD14⁺CD309⁺, and CD14⁺CD309⁺Tie2⁺ phenotyped circulating endothelial progenitor cells (EPCs) in patients with ischemic chronic heart failure (CHF).MethodsThe study involved 300 CHF patients (186 males) aged 48–62 years with angiografically proven coronary artery disease and/or previously defined myocardial infarction. Insulin resistance was assessed by the homeostasis model assessment for insulin resistance (HOMA-IR). EPC populations were phenotyped by flow cytofluorimetry.ResultsCirculating EPCs counts were statistically significantly lower in CHF patients with IR than in patients without IR. We found that the most valuable multivariable predictors of the depletion of the CD45⁺CD34⁺ EPCs were NT-pro-brain natriuretic peptide (BNP) (1.32; 95% CI = 1.19–2.77; P = 0.001), left ventricular ejection fraction (OR = 1.30; 95% CI = 1.09–1.60; P = 0.002), NYHA class (OR = 1.12; 95% CI = 1.02–1.19; P = 0.001). NT-pro-BNP (OR = 1.45; 95% CI = 1.15–2.90; P = 0.003), left ventricular ejection fraction (OR = 1.32; 95% CI = 1.11–1.65; P = 0.001) were found as powerful predictors for depletion in CD45⁻CD34⁺ EPCs. We also identified six independent variables with high predictive value for depletion of CD14⁺CD309⁺ EPCs: NT-pro-BNP (OR = 1.41; 95% CI = 1.15–2.90; P = 0.003), left ventricular ejection fraction (OR = 1.18; 95% CI = 1.10–1.76; P = 0.036), NYHA class (OR = 1.15; 95% CI = 1.07–1.22; P = 0.001), hs-C reactive protein (OR = 1.02; 95% CI = 1.01–1.05; P = 0.012). As independent multivariable predictors for depletion in CD14⁺CD309⁺Tie2⁺ EPCs were selected five variables: NT-pro-BNP (OR = 1.65; 95% CI = 1.44–4.70; P = 0.006), left ventricular ejection fraction (OR = 1.07; 95% CI = 1.02–1.12; P = 0.018), NYHA class (OR = 1.13; 95% CI = 1.06–1.21; P = 0.001), hs-C-reactive protein (OR = 1.08; 95% CI = 1.03–1.16; P = 0.002).ConclusionIR may be an additional factor contributing decreased circulating level of proangiogenic EPCs in non-diabetic CHF patients.     

Non-invasive and invasive evaluation of aortic valve area in 100 patients with severe aortic valve stenosis: Comparison of cardiac computed tomography with ECHO (transesophageal/transthoracic) and catheter examination

BackgroundCurrent guidelines place emphasis on the determination of aortic valve area (AVA) for defining an appropriate treatment strategy. Invasive and non-invasive modalities are used to perform planimetric [transesophageal echocardiography (TEE) and cardiac multidetector computed tomography (MDCT)] and calculated [catheter examination (CE), transthoracic echocardiography (TTE)] AVA measurements.Purpose and methodsWe investigated 100 patients admitted to evaluate the AVA using cardiac MDCT (CT), TEE/TTE as well as invasive CE.ResultsIn all 100 patients we calculated a mean AVA of 0.79 ± 0.29 cm² (female 50/100, 0.70 ± 0.19 cm², male 0.9 ± 0.21 cm²) determined by all investigated examinations (mean ± SEM). AVA measurements determined by CT were significantly greater (0.86 ± 0.25 cm²) than those determined by CE: 0.75 ± 0.18 cm², p = 0.01. Echocardiographically determined AVA was comparable to CE (statistically not significant). Similar results were seen in all patients regardless of gender, presence of atrial fibrillation, and heart rate. We calculated a mean AVA for each patient and evaluated the variance of the AVA determined through investigated specific examinations as the bias. Overall, we found for CT 0.13 ± 0.1 cm², CE 0.13 ± 0.11 cm², TEE 0.16 ± 0.09 cm², and for TTE 0.16 ± 0.08 cm² a specific statistical non-significant variance. On subgroups: sinus rhythm, atrial fibrillation, females, males or combination, we found no further significant relevance for the specific variance.ConclusionOur data suggest the feasibility of cardiac MDCT to evaluate the correct AVA regardless of rhythm, heart rate, and sex. The planimetric concept to determine the AVA with CT displaces the “gold-standard” CE with respect to elucidating the potencies for complications, i.e. cerebral stroke. Regardless of CT's accessing of AVA measurement the TTE examination should remain the primary method of screening for aortic valve pathologies.     

Slow Ca2 + sparks de-synchronize Ca2 + release in failing cardiomyocytes: Evidence for altered configuration of Ca2 + release units?

In heart failure, cardiomyocytes exhibit slowing of the rising phase of the Ca^2 + transient which contributes to the impaired contractility observed in this condition. We investigated whether alterations in ryanodine receptor function promote slowing of Ca^2 + release in a murine model of congestive heart failure (CHF). Myocardial infarction was induced by left coronary artery ligation. When chronic CHF had developed (10 weeks post-infarction), cardiomyocytes were isolated from viable regions of the septum. Septal myocytes from SHAM-operated mice served as controls. Ca^2 + transients rose markedly slower in CHF than SHAM myocytes with longer time to peak (CHF = 152 ± 12% of SHAM, P < 0.05). The rise time of Ca^2 + sparks was also increased in CHF (SHAM = 9.6 ± 0.6 ms, CHF = 13.2 ± 0.7 ms, P < 0.05), due to a sub-population of sparks (≈ 20%) with markedly slowed kinetics. Regions of the cell associated with these slow spontaneous sparks also exhibited slowed Ca^2 + release during the action potential. Thus, greater variability in spark kinetics in CHF promoted less uniform Ca^2 + release across the cell. Dyssynchronous Ca^2 + transients in CHF additionally resulted from T-tubule disorganization, as indicated by fast Fourier transforms, but slow sparks were not associated with orphaned ryanodine receptors. Rather, mathematical modeling suggested that slow sparks could result from an altered composition of Ca^2 + release units, including a reduction in ryanodine receptor density and/or distribution of ryanodine receptors into sub-clusters. In conclusion, our findings indicate that slowed, dyssynchronous Ca^2 + transients in CHF result from alterations in Ca^2 + sparks, consistent with rearrangement of ryanodine receptors within Ca^2 + release units. This article is part of a Special Issue entitled “Calcium Signaling in Heart”.     

Circulating endothelial and platelet derived microparticles reflect the size of myocardium at risk in patients with ST-elevation myocardial infarction

ObjectivesMicroparticles (MP) are small membrane vesicles, released from activated, damaged and apoptotic endothelial cells (EMP) or platelets (PMP) that may actively modulate inflammation, coagulation and vascular function. We tested the hypothesis that the number of circulating EMP or PMP in acute myocardial infarction correlates with the myocardium at risk (MaR) and infarct size (IS).MethodsEMP were quantified in plasma samples of 36 patients (age: 63 ± 10 years) with first time ST-elevation myocardial infarction (STEMI) using flow cytometry. EMP were defined as CD31⁺/CD42^? MP and CD144⁺ MP and PMP as CD31⁺/CD42⁺ MP. MaR and IS was determined by cardiovascular magnetic resonance imaging one week after the index event.ResultsPlasma levels of CD31⁺/CD42^? EMP were 251.0 ± 178.8/μl and CD144⁺ 106.3 ± 33.7/μl. PMP levels were 579.2 ± 631.8/μl. MaR was 31.0 ± 11.2% of the left ventricle and IS was 11.4 ± 7.1% of the left ventricle. Patients with STEMI in the left anterior descending artery had higher levels of CD31⁺/CD42^? EMP and PMP than those with other infarct-related arteries (p < 0.05). The numbers of CD31⁺/CD42^? EMP and PMP correlated to MaR, but not to IS.ConclusionsCirculating EMP and PMP correlate to the size of MaR in patients with STEMI suggesting that they reflect the severity of the endothelial injury and platelet activation during myocardial ischemia.     

Early HHV-6 replication is associated with morbidity non-related to CMV infection after kidney transplantation

Human herpesvirus type 6-(HHV-6) has been associated with morbidity after liver transplantation.ObjectiveThe aim of this study was to determine the HHV-6 seroprevalence among donorrecipient pairs, analyze the incidence of early active infection, its clinical manifestation, interaction with CMV, and the related morbidity in the first year after kidney transplantation.Methods46 donor-recipient pairs had IgG evaluated by ELISA before transplantation: HHV-6-(Pambio – USA) and CMV-(Roche – USA). A frozen whole blood sample collected weekly (from the 1^st to the 6^th week) was retrospectively tested for HHV-6 viral load (VL) determination by real time quantitative PCR (qPCR, Nanogen – Italy). Patients were preemptively surveyed for CMV by pp65 antigenemia (Ag, APAAP, immunohistochemistry, Biotest – Germany) from the 4^th to the 12^th week after transplantation. Active infection was defined as qPCR-HHV6+ (viral-load/mL-VL) and Ag+ (+cells/100.000 granulocytes), for HHV-6 and CMV, respectively. DCMV was defined as simultaneous positive antigenemia and suggestive signs/symptoms. Concerning +qPCR-HHV6, associated factors, clinical manifestation, interaction with CMV and morbidity were searched.ResultsPre-transplant HHV-6 seroprevalence was significantly higher among kidney recipients compared to their donors (82.6×54.8%; p = 0.005 [3.9 (1.4–10.4)]). Active infection by this virus occurred in 26.1% (12/46), with no association with previous IgG (p = 0.412). Median VL was 125 copies/mL (53–11.264), and the median Ag was 21 +cells (2–740). There was no association between HHV-6 and CMV activation after transplantation (p = 0.441), neither concerning DCMV (p = 0.596). Median highest Ag+ and days of ganciclovir treatment were similar between qPCR-HHV6 + or ? (p = 0.206 and p = 0.124, respectively). qPCR-HHV6+ was associated with higher incidence of bacterial (p = 0.009) and fungal (p = 0.001) infections, and higher number (p = 0.001) of hospital admission and longer duration of hospitalization over the first 6 and 12 months post-transplantation (p = 0.033 and p = 0.001).ConclusionLatent HHV-6 infection is more common among recipients than donors before transplantation. Early active infection by this pathogen after transplantation does not increase DCMV incidence or severity during the first 3 months of follow-up. However, early HHV-6 replication is associated with other infections and hospitalizations in the first year.     

Acute caloric restriction improves glomerular filtration rate in patients with morbid obesity and type 2 diabetes

AimThe role of caloric restriction in the improvement of renal function following bariatric surgery is still unclear; with some evidence showing that calorie restriction can reduce proteinuria. However, data on the impact of caloric restriction on renal function are still lacking.MethodsRenal function, as measured by glomerular filtration rate (GFR), was evaluated in 14 patients with type 2 diabetes mellitus, morbid obesity and stage 2 chronic kidney disease before and after a 7-day very low-calory diet (VLCD).ResultsAfter the VLCD, both GFR and overall glucose disposal (M value) significantly increased from 72.6 ± 3.8 mL/min/1.73 m⁻² BSA to 86.9 ± 6.1 mL/min/1.73 m⁻² BSA (P = 0.026) and from 979 ± 107 μmol/min¹/m² BSA to 1205 ± 94 μmol/min¹/m² BSA (P = 0.008), respectively. A significant correlation was observed between the increase in GFR and the rise in M value (r = 0.625, P = 0.017).ConclusionOur observation of improved renal function following acute caloric restriction before weight loss became relevant suggesting that calory restriction per se is able to affect renal function.     

Renal plasma flow: glomerular filtration rate relationships in man during direct renin inhibition with aliskiren

We examined the relation between change in renal plasma flow (RPF) and change in glomerular filtration rate (GFR) in healthy humans on a low-salt diet during direct renin inhibition with aliskiren. We measured the renal hemodynamic response to acute dosing of 300 mg aliskiren by mouth to 19 healthy normotensive subjects (age, 33 ± 3 years; baseline RPF, 575 ± 23; GFR, 138 ± 14 mL/min/1.73 m²) on a low-sodium diet (10 mmol/day). GFR and RPF were measured by the clearance of inulin and para-aminohippurate. There was a marked increase in average RPF (169 ± 24 mL/min/1.73 m²) and a small rise in average GFR (1.4 ± 5 mL/min/1.73 m²) from baseline in response to aliskiren. There was a clear correlation between the change in RPF and the change in GFR between subjects (r = 0.65; P < .003). A substantial increase in RPF was accompanied by a rise in GFR. Dependence of GFR on RPF was identified in healthy humans after RPF rose significantly with aliskiren. The responsible mechanism likely involves intravascular oncotic pressure along the glomerular capillary resulting in greater surface area available for filtration.     

Contrast-induced thrombocytopenia following percutaneous coronary intervention

Contrast-induced thrombocytopenia is a rare complication distinguished by acute and severe platelet consumption, with spontaneous recovery within days. We describe a case of acute thrombocytopenia 6 hours after coronary angioplasty in a patient with a negative antiplatelet factor 4 test. The count reached 1 × 10³/µL, but improved spontaneously to 210 × 10³/µL after 8 days. In conclusion, physicians should be aware of this complication, particularly when dual antiplatelet therapy is being considered.     

Fumigant toxicity of Citrus sinensis essential oil on Musca domestica L. adults in the absence and presence of a P450 inhibitor

Essential oils (EOs) are potential tools for controlling Musca domestica L. In a fumigant assay, M. domestica adults treated with Citrus sinensis EO (LC₅₀ = 3.9 mg/dm³), with (4R)(+)-limonene (95.1%) being its main component, died within 15 min or less. The terpenes absorbed by the flies and their metabolites, analyzed using SPME fiber, were (4R)(+)-limonene (LC₅₀ = 6.2 mg/dm³), α-pinene (LC₅₀ = 11.5 mg/dm³), β-pinene (LC₅₀ = 6.4 mg/dm³), and two new components, carveol (LC₅₀ = 1122 mg/dm³) and carvone (LC₅₀ = 19 mg/dm³), in a proportion of 50, 6.2, 12.5, 6.3 and 25%, respectively. Carveol and carvone were formed by oxidation of (4R)(+)-limonene mediated by cytochrome P450, as was suggested by a fumigation assay on flies previously treated with piperonyl butoxide, a P450 inhibitor. In this experiment, an increase in the toxicity of the EO and (4R)(+)-limonene was observed, as well as a lower production of carveol and carvone.     

Switch from metformin monotherapy to bitherapy with metformin and repaglinide to achieve glycated haemoglobin target in type 2 diabetes (REPAMET Study)

AimTo evaluate glycaemic control, including HbA_1c, following the addition of repaglinide to monotherapy with metformin as part of routine follow-up of adult type 2 diabetes patients no longer controlled with metformin (i.e. in secondary monotherapy failure).Subjects and methodsProspective, open-label, observational study in primary care setting, consisting of 2 visits (metformin/repaglinide bitherapy initiation and follow-up within 10–20 weeks), with analysis of HbA_1c levels, fasting glycaemia, body mass index and hypoglycaemic episodes within past month.Results2171 patients were included, with average diabetes duration (mean ± 1 SD) 7 ± 6 years, BMI 30.2 ± 5.5 kg/m², and fasting glucose at entry 179 ± 50 mg/dl. Mean decrements in fasting glycaemia and HbA_1c between visits rose with increasing HbA_1c at Visit 1. The proportion of patients with controlled fasting glycaemia increased by an absolute 40% for therapeutic goal set at 90–130 mg/dl. Treatment goal (HbA_1c < 7.0%) was achieved by 38% of patients at Visit 2, with number of patients with HbA_1c ≥ 8.0% decreasing by an absolute 34%. The percentage of patients experiencing ≥1 hypoglycaemic episode(s) within the previous month marginally rose from 5.0 to 5.6%.ConclusionCombining metformin with repaglinide appears a safe and effective therapeutic option once monotherapy with metformin is no longer adequate in adult patients with type 2 diabetes followed in a primary care setting.     

Different prognostic value of white blood cell subtypes in patients with acute cerebral infarction

ObjectiveWe aimed to investigate the relationship of each white blood cells (WBC) subtype with neurologic severity and outcome in acute stroke.MethodsWe included 779 patients with first-ever acute cerebral infarction within 72 h after symptom onset. We investigated the association between counts for WBC subtypes in peripheral blood at admission and (1) initial stroke severity; (2) early change in stroke severity within one week; and (3) functional outcome at three months.ResultsHigher total WBC and neutrophil counts were associated with more severe stroke at admission (p < 0.001). In contrast, lower lymphocyte counts were associated with a lesser improvement during the first week after admission (p < 0.05) and with poor functional outcome at three months (OR = 0.706 per 1000 lymphocyte counts/mm³, p = 0.020).ConclusionsOur study merits further investigation on the role of each WBC subtype in ischemic injury and different prognostic value of WBC subtypes measured at admission in acute stroke.     

Comparative performance of FAS equation and Asian modified CKD-EPI in the determination of GFR in Chinese patients with CKD with the 99mTc-DTPA plasma clearance as the reference method

BackgroundGlomerular filtration rate (GFR) is a useful index in many clinical conditions. However, very few studies have assessed the performance of full age spectrum (FAS) equation and the Asian modified Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation in the approximation of GFR in Chinese patients with chronic kidney disease.ObjectiveThis study aimed to compare the diagnostic performance of the above two creatinine-based equations.MethodsA well designed single-center cross-sectional study was performed and the GFR was determined by 3 methods separately in the same day: technetium-99m-diethylene triamine pentaacetic acid (^99mTc-DTPA) dual plasma sample clearance method (mGFR); FAS equation method; Asian modified CKD-EPI equation method. The gold standard method was the mGFR. Equations performance criteria considered correlation coefficient, bias, precision, accuracy and the ability to detect the mGFR less than 60 ml/min/1.73 m².ResultsA total of 160 patients were enrolled. The diagnostic performance of FAS showed no significant difference in the correlation coefficient (0.89 vs 0.89), precision (15.9 vs 16.1 ml/min/1.73 m²), accuracy (75.0% vs 76.3%) and the ability to detect the mGFR less than 60 ml/min/1.73 m² (0.94 vs 0.94) compared with the Asian modified CKD-EPI equation in all participants. The FAS showed a negative bias, while the new CKD-EPI equation showed a positive bias (?1.20 vs 1.30 ml/min/1.73 m², P < 0.001). However, they were all near to zero. In the mGFR < 60 ml/min/1.73 m² subgroup and mGFR > 60 ml/min/1.73 m² subgroup were consistent with that in the whole cohort. The precision and accuracy decreased when GFR > 60 ml/min/1.73 m² in both equations.ConclusionsThe FAS equation and the Asian modified CKD-EPI equation had similar performance in determining the glomerular filtration rate in the Chinese patients with chronic kidney disease. Both the FAS equation and Asian modified CKD-EPI can be a satisfactory method and may be the most suitable creatinine-based equation.     

Corneal endothelial cell density and morphology in patients with acromegaly

ObjectiveAcromegaly has various impacts on many organs. The ophthalmologic effects of acromegaly have not yet been investigated in detail. The aim of the current study was to evaluate qualitative and quantitative changes in corneal endothelial cells and central corneal thickness (CCT) of the patients with acromegaly.DesignIn this prospective, cross-sectional study, 128 eyes of 64 patients with acromegaly (female/male = 40/24) and 208 eyes of 104 age and gender-matched healthy volunteers (female/male = 69/35) were included. Endothelial cell density (ECD), cellular area (CA), coefficient of variation (CV) in cell size, percentage of hexagonal cells, and CCT were measured in patients with acromegaly and in healthy volunteers using the noncontact specular microscopy (SP-3000P: Topcon Corporation, Tokyo, Japan).ResultsECD and CA were lower in cases with acromegaly than in controls (ECD in acromegaly: 2615.65 cell/mm² and in controls: 2700.35 cell/mm²; p = 0.002. CA in acromegaly: 382.30 μm² and in controls: 400.30 μm²; p = 0.02). In the entire group with acromegaly, the time elapsed since diagnosis was positively correlated with CA and was negatively correlated with ECD (r = + 0.39, p = 0.001 and r = − 0.42, p = 0.001).ConclusionsThe endothelial layer of the cornea may be under risk of impairment with prolonged disease duration in acromegaly. Consistency of the corneal endothelium should be also sought during long-term follow-up of the cases with acromegaly.     

Vascular reactivity in patients with undifferentiated connective tissue diseases

Assessment of changes in plaque volume is increasingly used as a surrogate-endpoint in clinical trials testing the efficacy of anti-atherosclerotic interventions. Multi-detector computed tomography (MDCT) can detect and quantify non-calcified atherosclerotic plaques, but its ability to monitor changes in plaque volume has not yet been tested.We sought to test the ability of MDCT to detect and quantify serial changes in atheroma burden in comparison with magnetic resonance imaging (MRI).MethodsRabbits (n = 12) with experimentally induced abdominal atherosclerosis were randomized to receive a plaque-regressing agent (recombinant apoA-I_Milano, n = 8) or placebo (n = 4). All animals underwent two 64-slice MDCT angiography and MRI studies (pre- and post-treatment). The primary endpoint was the change in plaque burden (defined as vessel wall volume in the 5 cm distal to the left renal artery) between pre- and post-treatment MDCT in comparison with MRI.ResultsMDCT detected a significant decrease in plaque burden caused by recombinant apoA-I_Milano (464 [423–535] to 405 [363–435] mm³, p = 0.03) that was confirmed by MRI (324 [286–412] to 298 [282–399] mm³, p = 0.03). No significant effect was noted in the placebo group either by MDCT or MRI. There were strong correlations between both modalities for the quantification of plaque burden (r = 0.750, p < 0.001) and change in plaque burden (r = 0.657, p = 0.020). MDCT overestimated plaque burden compared to MRI.On MDCT, the mean interobserver variability for plaque burden was 2.5 ± 0.4%.ConclusionsIn an animal model of atherosclerosis, MDCT accurately documented serial changes in aortic plaque burden, demonstrating good correlation and agreement with MRI-derived measurements and low interobserver variability.     

Proinflammatory cytokines and cardiac abnormalities in uncomplicated obesity: relationship with abdominal fat deposition

Background and aimObesity can be considered a state of chronic, low-grade inflammation. Particularly, visceral adipose tissue (VAT) seems to be an active compartment in pro-inflammatory molecule secretion. The possible existence of a correlation between circulating cytokines, their soluble receptors, abdominal fat accumulation and echocardiographic abnormalities in uncomplicated obesity was investigated.Methods and resultsEchocardiographic parameters, C-reactive protein (CRP), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6-R), tumor necrosis factor-α (TNF-α) and soluble TNF receptor I (TNFR-I) were assessed in 27 normotensive obese women (age 33.3 ± 8.3 years; BMI 43.5 ± 4.8 kg/m²) and 15 normal-weight controls (age 36.8 ± 8.2 years; BMI 22.6 ± 1.7 kg/m²). VAT was assessed by CT. The obese patients had higher serum IL-6 (p < 0.01), sIL-6-R (p < 0.0001), sIL-6-R/IL-6 complex (p < 0.05), TNF-α (p < 0.02), sTNF-α-RI (p < 0.03) and CRP (p < 0.0001) levels than normal women. Moreover, end-diastolic septum thickness (SW), end-diastolic posterior wall thickness (PW), absolute and indexed left ventricular mass, deceleration time (DT), myocardial performance index (MPI) and isovolumetric relaxation time (IVRT) were correlated with sIL-6-R, sIL-6-R/IL-6 complex and CRP levels. Interestingly, sIL-6-R, sIL-6-R/IL-6 complex, CRP, SW, PW, DT and MPI were higher in patients with a VAT area >130 cm² than those with <130 cm².ConclusionIn normotensive obese women several pro-inflammatory molecules correlate with both echocardiographic abnormalities and the amount of intra-abdominal fat; these results may support a role for visceral fat in predisposing to cardiac dysfunction, possibly through a low-grade state of inflammation.     

Randomization to a low-carbohydrate diet advice improves health related quality of life compared with a low-fat diet at similar weight-loss in Type 2 diabetes mellitus

AimsTo compare the effects on health-related quality of life (HRQoL) of a 2-year intervention with a low-fat diet (LFD) or a low-carbohydrate diet (LCD) based on four group-meetings to achieve compliance. To describe different aspects of taking part in the intervention following the LFD or LCD.MethodsProspective, randomized trial of 61 adults with Type 2 diabetes mellitus. The SF-36 questionnaire was used at baseline, 6, 12 and 24 months. Patients on LFD aimed for 55–60 energy percent (E%) and those on LCD for 20 E% from carbohydrates. The patients were interviewed about their experiences of the intervention.ResultsMean body-mass-index was 32.7 ± 5.4 kg/m² at baseline. Weight-loss did not differ between groups and was maximal at 6 months, LFD: −3.99 ± 4.1 kg, LCD: −4.31 ± 3.6 kg (p < 0.001 within groups). There was an increase in the physical component score of SF-36 from 44.1 (10.0) to 46.7 (10.5) at 12 months in the LCD group (p < 0.009) while no change occurred in the LFD group (p < 0.03 between groups). At 12 months the physical function, bodily pain and general health scores improved within the LCD group (p values 0.042–0.009) while there was no change within the LFD group.ConclusionsWeight-changes did not differ between the diet groups while improvements in HRQoL only occurred after one year during treatment with LCD. No changes of HRQoL occurred in the LFD group in spite of a similar reduction in body weight.     

Coffee consumption is not associated with prevalent subclinical cardiovascular disease (CVD) or the risk of CVD events,in nonalcoholic fatty liver disease: results from the multi-ethnic study of atherosclerosis

BackgroundAtherosclerosis and its clinical sequelae represent the leading cause of mortality among patients with nonalcoholic fatty liver disease (NAFLD). While epidemiologic data support the hepatoprotective benefits of coffee in NAFLD, whether coffee improves NAFLD-associated CVD risk is unknown.MethodsWe examined 3710 ethnically-diverse participants from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, without history of known liver disease, and with available coffee data from a validated 120-item food frequency questionnaire. All participants underwent baseline non-contrast cardiac CT from which NAFLD was defined by liver:spleen ratio (L:S < 1.0), and subclinical CVD was defined by coronary artery calcium (CAC) > 0. Major CVD events were defined by the first occurrence of myocardial infarction, cardiac arrest, angina, stroke, or CVD death. We used log-binomial regression to calculate the adjusted prevalence ratio (PR) for CAC > 0 by coffee intake and NAFLD status, and events were compared between groups using frequency of events within adjusted Cox proportional hazard regression models.ResultsSeventeen percent (N = 637) of participants met criteria for NAFLD. NAFLD participants were more likely to have elevated BMI (mean 31.1 ± 5.5 kg/m² vs. 28.0 ± 5.2 kg/m², p < 0.0001), and diabetes (22% vs. 11%, p < 0.0001), but did not differ in daily coffee consumption (p = 0.97). Among NAFLD participants, coffee consumption was not associated with prevalent, baseline CAC > 0 (PR = 1.02 [0.98–1.07]). Over 12.8 years of follow-up, 93 NAFLD and 415 non-NAFLD participants experienced a CV event. However, coffee intake was not associated with incident CVD events, in either NAFLD (HR = 1.05 [0.91–1.21]) or non-NAFLD participants (HR = 1.03 [0.97–1.11]).ConclusionIn a large, population-based cohort, coffee consumption was not associated with the prevalence of subclinical CVD, nor did coffee impact the future risk of major CVD events, regardless of underlying NAFLD status.     

Predictors of sarcopenia in young hospitalized patients living with HIV

The prevalence of sarcopenia in hospitalized people living with HIV is underdiagnosed, as assessment instruments are not always available. This study aimed to identify factors related to sarcopenia, correlating their anthropometric and clinical markers in hospitalized people living with HIV. This was an observational cross-sectional clinical study, carried out from September 2018 through October 2019. Handgrip strength, muscle mass index, calf circumference and gait speed test were evaluated in recruited patients within three days of hospital admission. The sample consisted in 44 patients, mostly men (66%), black (68%), young adults (41.65 ± 12.18 years) and immunodeficient (CD4 cell count 165 cells/mm³ [34.25–295.5]). Sarcopenia was present in 25% of the sample. Calf circumference showed a significant correlation with CD4 cell count and viral load (p < 0.05) while handgrip strength and gait speed test did not. Calf circumference > 31 cm and gait speed test > 0.8 m/s reduced the chance of sarcopenia by 60% (OR = 0.396 [−1.67 to −0.18]; p < 0.05) and 98% (OR = 0.02 [−8.16 to 0.13]; p < 0.05) respectively. Calf circumference > 31 cm and gait speed test > 0.8 m/s are associated with a reduced chance of sarcopenia in hospitalized HIV patients.