Depression and cardiovascular risk-association among Beck Depression Inventory, PCSK9 levels and insulin resistance.

BACKGROUND: Depression and cardiovascular disease (CVD) are among the most common causes of disability in high-income countries, depression being associated with a 30% increased risk of future CV events. Depression is twice as common in people with diabetes and is associated with a 60% rise in the incidence of type 2 diabetes, an independent CVD risk factor. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of low-density lipoprotein cholesterol, has been related to a large number of CV risk factors, including insulin resistance. Aim of this study was to investigate whether the presence of depression could affect PCSK9 levels in a population of obese subjects susceptible to depressive symptoms and how these changes may mediate a pre-diabetic risk. RESULTS: In 389 obese individuals, the Beck Depression Inventory (BDI-II) was significantly associated with PCSK9 levels. For every one-unit increment in BDI-II score, PCSK9 rose by 1.85 ng/mL. Depression was associated also with the HOMA-IR (homeostatic model assessment index of insulin resistance), 11% of this effect operating indirectly via PCSK9. CONCLUSIONS: This study indicates a possible mechanism linking depression and insulin resistance, a well-known CV risk factor, providing evidence for a significant role of PCSK9.

Urinary chromium is associated with changes in leukocyte miRNA expression in obese subjects.

BACKGROUND/OBJECTIVES: Epidemiological studies suggest a link between chromium (Cr) status and cardiovascular disease. Increased urinary excretion of Cr was reported in subjects with diabetes compared with non-diabetic controls and those with non-diabetic insulin resistance. Epigenetic alterations have been linked to the presence of Cr, and microRNA (miRNA) expression has been implicated in the pathogenesis of metabolic diseases and cardiovascular diseases (CVDs). We investigated the association between Cr excretion and miRNA expression in leukocytes from obese subjects. We also examined the relationship between altered miRNA expression and selected clinical parameters to further investigate mechanisms linking Cr to metabolic diseases and CVDs. SUBJECTS/METHODS: We analyzed urinary Cr in 90 Italian subjects using inductively coupled plasma-mass spectrometry. Peripheral blood miRNA levels were screened with TaqMan Low-Density Array Human MicroRNA A. Cr level-associated expression of miRNAs was detected with multivariate regression analyses, and the top 10 candidate miRNAs were selected for validation. We also used multivariate regression analyses to assess possible associations between validated miRNAs and glycated hemoglobin (A1c) and blood pressure (BP). The validated miRNAs were further investigated by functional analysis with Ingenuity Pathway Analysis software. RESULTS: Urinary Cr levels (mean: 0.35 µg/l; s.d.=0.24) ranged from 0.05 to 1.27 µg/l. In the screening phase, 43 miRNAs were negatively associated with Cr. Of the top 10 miRNAs selected for validation, nine (miR-451, miR-301, miR-15b, miR-21, miR-26a, miR-362-3p, miR-182, miR-183 and miR-486-3p) were downregulated in association with Cr (P-false discovery rate (FDR)<0.10). miR-451 expression was associated with A1c (ß=-0.06; P=0.0416), whereas miR-486-3p expression was associated both with diastolic (ß=2.1; P=0.004) and systolic BP (ß=3.3; P=0.003). CONCLUSIONS: These results indicate that miR-451 and miR-486-3p are involved in the link between Cr levels and metabolic diseases and CVDs.

Circulating cardiovascular biomarkers in recurrent atrial fibrillation: data from the GISSI-atrial fibrillation trial.

OBJECTIVE: we evaluated the prognostic role of circulating cardiovascular biomarkers in patients with a history of recent atrial fibrillation (AF). BACKGROUND: predicting long-term maintenance of sinus rhythm in patients with AF is difficult. METHODS: plasma concentrations of three specific cardiac markers [high-sensitivity troponin T (hsTnT), N-terminal probrain natriuretic peptide (NT-proBNP) and mid-regional proatrial natriuretic peptide (MR-proANP)] and three stable fragments of vasoactive peptides [mid-regional proadrenomedullin (MR-proADM), copeptin (CT-proAVP) and CT-proendothelin-1 (CT-proET-1)] were measured at baseline and after 6 and 12 months in 382 patients enrolled in the GISSI-AF study, a prospective randomized trial to determine the effect of valsartan to reduce the recurrence of AF. The association between these markers, clinical characteristics and recurrence of AF was tested by univariate and multivariate Cox models. RESULTS: mean patient age was 68 ± 9 years (37.2% females). A total of 84.8% of patients had a history of hypertension. In total, 59.7% qualified for history of AF because of successful cardioversion, 11.8% because of two or more episodes of AF in the 6 months preceding randomization and 28.5% because of both. Patients in AF at 6 or 12 months (203 (53.1%) with first recurrence) had significantly higher concentrations of most biomarkers. Despite low baseline levels, higher concentrations of hsTnT {adjusted hazard ratio (HR) [95% confidence intervals (CIs) for 1 SD increment] (1.15 [1.04-1.28], P = 0.007), MR-proANP (1.15 [1.01-1.30], P = 0.04), NT-proBNP (1.24 [1.11-1.39], P = 0.0001) and CT-proET-1 (1.16 [1.01-1.33], P = 0.03) independently predicted higher risk of a first recurrence of AF. Changes over time of MR-proANP tended to predict subsequent recurrence (adjusted HR [95%CI]) (1.53 [0.98-2.37], P = 0.06). CONCLUSION: circulating markers of cardiomyocyte injury/strain and endothelin are related to recurrence of AF in patients in sinus rhythm with a history of recent AF.

"CADEAT": considerations on the use of CAD (computer-aided diagnosis) in mammography.

Computer-aided diagnosis (CAD) has been extensively reported to increase sensitivity by about 10% when added to a single reading while increasing recall rate by 12%, and its current use can be safely recommended in clinical practice. CAD has been suggested as a possible alternative to conventional double reading in screening. Uncontrolled comparison is consistent and suggests that CAD is comparable to double reading in incremental cancer detection rate (CAD +10.6%, double reading +9.1%) and possibly better in recall rate (CAD +12.5%, double reading +28.8%). However, controlled studies comparing single reading + CAD to conventional double reading are not consistent and on average suggest a lower cancer detection rate (-5.1%) and a lower recall rate (-9.8%) for CAD. Scientific evidence is not sufficient for a safe recommendation of single reading + CAD as a current alternative to conventional double reading.

Virtual colonoscopy.

Computed axial colonography, usually called virtual colonoscopy, is a new diagnostic method potentially useful for investigating polyps and tumors of the colon and rectum. It uses spiral axial tomography data to build up images similar to those given by conventional colonoscopy, offering advantages in that it causes no adverse reactions, and is accepted well by patients, who do not need to be sedated. Reports to date show its sensitivity and specificity vary in identifying polyps in the colon, and there are still many problems with the new method, such as its cost, its learning curve, the identification of flat lesions, and detection of extracolonic abnormalities. There is a pressing need to establish the accuracy and cost-effectiveness of virtual colonoscopy as a screening method for colorectal tumors, and for post-polypectomy surveillance.

[Pulse inversion ultrasonography with ultrasonography contrast media (levovist) in the evaluation of hepatic metastasis]. / Ecografia con tecnica di inversione di impulso e mezzo di contrasto ecografico (Levovist) nella valutazione delle metastasi epatiche.

PURPOSE: To evaluate if Pulse Inversion Harmonic Imaging with contrast agent injection (Levovist) is able to determine an increase of echogenicity in normal hepatic parenchyma, and to compare its capability to detect metastatic focal lesions with that of standard US and spiral CT. To define and standardize the technical and methodological aspects of this new technique. MATERIAL AND METHODS: A selected group of 72 patients (42 males and 30 females) with clinical and instrumental suspect of hepatic metastatic lesions was included in the prospective study. Each patient was examined by conventional ultrasound (US), Pulse Inversion Harmonic Imaging (PI) and spiral-CT (spCT). US examination was performed using an HDI 5000 (ATL, Bothell, USA) equipped with a broadband probe (5.0-2.0 MHz). 2.5 g Levovist (Schering AG-Berlin) was administered intravenously, at concentration of 300 mg/ml and a flow rate of 7 ml/min. Video clips obtained with the acquired images before and after contrast medium administration were transferred to a magnet optic disk unit. Examinations were evaluated by an experienced radiologist blindly on a workstation that allowed a qualitative-quantitative analysis. SpCT images were evaluated separately by another experienced radiologist. US images were evaluated qualitatively (number of lesions, site of lesion, diameter of the smallest lesion detectable) and quantitatively (increase in parenchymal echogenicity 20", 40", 60" and 5' after the injection of contrast agent). RESULTS: In all cases examined, the echogenicity of normal hepatic parenchyma increased after contrast agent administration, reaching a peak of about 250% (1DS) at 60 s and a decreasing gradually in 5 minutes. Conventional US detected 195 focal lesions, CT 231, and US with pulse inversion technique and contrast agent (US-PI) 287. Mean differences among the number of lesions detected by the different techniques per each patient were also calculated. Wilcoxon Signed Rank Test showed a statistically significant difference between US-PI and US (p < .0001), CT and US (p = .0052) and US-PI and CT (p = .0121). US-PI detected the smallest lesions, which went undetected by the CT and conventional US examinations. DISCUSSION AND CONCLUSIONS: In 10 cases (14.3%) contrast enhanced US-PI demonstrated the presence of a number of lesions greater than 5 (diffuse metastatization and inoperability) in comparison to that detected by spCT). The greater echogenicity of normal hepatic parenchyma using pulse inversion technique after Levovist infusion allowed to better demonstrate hepatic metastases. This technique showed a higher identification rate of small lesions in comparison to basal examination and to spiral CT. Contrast enhanced US-PI demonstrated a remarkable increase in echogenicity of hepatic parenchyma in portal phase. The technique significantly improves the detection of focal lesions allowing visualization of smaller lesions compared to CT and US. These results indicate that the technique could be used in the staging of liver metastasis. However, large multicentric trials are required to validate US-PI and better define its role in the work-up of patients with neoplastic disorder.

Computed tomographic colonography and conventional colonoscopy for colon diseases: a prospective, blinded study.

OBJECTIVES: Computed tomographic (CT) colonography or virtual colonoscopy is a new diagnostic method for the colon and rectum, developed on the basis of spiral computed axial tomography and employing virtual reality technology. The aim of this study was to determine the sensitivity, specificity, and diagnostic accuracy of CT colonography compared with colonoscopy in a prospective, blinded study in one single institution in Italy. METHODS: Ninety-nine patients randomly selected among those attending the open-access endoscopy unit for diagnostic colonoscopy underwent colonoscopy and spiral CT. The images obtained were transmitted to generate the virtual colonoscopy pictures. A supervisor compared the results with the findings of conventional colonoscopy. RESULTS: CT colonography diagnosed seven of eight tumors, one being missed because the patient had been inadequately prepared. In 28 patients, CT colonography identified 26 polyps of 45 (57.8% sensitivity, 92.6% specificity, 86.7% positive predictive value), regardless of their size. The sensitivity in detecting colonic polyps was 31.8% (7/22) in the first 25 cases and 91.6% (11/12) in the last 20 patients. CT colonography missed one flat adenoma, some angioectasias and colonic lesions because of portal hypertension in one patient, Crohn's disease ulcers in two patients, and ulcerative colitis lesions in three. CONCLUSIONS: CT colonography shows poor sensitivity for identifying colonic polyps and does not always detect neoplastic lesions. Flat lesions are impossible to see by this method.

A new Doppler signal enhancing agent for flow assessment in breast lesions.

OBJECTIVE: To determine the diagnostic performance of SonoVue (Bracco) in the enhancement of Doppler signals in breast lesions and in the improvement of diagnostic accuracy. METHODS: This multicenter study included 220 patients undergoing investigations of parenchymal lesions, 40 of which had breast tumors. After a baseline Doppler examination, intravenous doses of 0.3, 0.6, 1.2 and 2.4 ml SonoVue were injected. Doppler signal quality before and after injection was compared. Off-site assessment of the global quality of Doppler signal and duration of clinical useful enhancement, as well as off-site and on-site evaluation of quality of color and spectral Doppler, were performed. On-site evaluation of diagnostic accuracy was also carried out. Safety assessments included monitoring of adverse events up to 24 h following the last injection of SonoVue. RESULTS: On-site evaluations: baseline Doppler was conclusive in only 4/21 carcinomas and in 2/17 benign lesions. Enhanced Doppler improved differential diagnosis in 20/21 carcinomas and in 9/12 benign lesions. Time to color enhancement was 0.55 min for the lowest and 0.35 min for the highest dose. The total duration of enhancement was 3.47 min for the lowest and 5.62 min for the highest dose, respectively. Off-site assessment: SonoVue improved the quality of Doppler blood flow information both in parenchymal and focal lesions. Statistically significant changes from baseline in global quality of Doppler investigations were observed at all four SonoVue doses (P<0.05). The duration of clinically useful signal enhancement increased with doses and a significant dose relationship was obtained (P<0.001). Mild adverse events were observed in two patients only. CONCLUSION: The results obtained from this study, following both off-site and on-site assessment, demonstrate that the administration of SonoVue to patients with focal breast lesions provides significant improvement over the baseline of Doppler signal quality and a clinically useful duration of signal enhancement, related to the dose. SonoVue was shown to be a safe and well-tolerated compound.

[Mammography changes associated with hormone replacement therapy in post-menopausal patients]. / Le modificazioni mammografiche nella terapia ormonale sostitutiva nelle pazienti dopo la menopausa.

Hormone replacement therapy (HRT) in post-menopausal or ovariectomized women reduces mortality due to cardiovascular diseases, lowers morbidity due to osteoporosis and improves vasovagal symptoms. Long-term therapy, however, increase the risk of side-effects. HRT may decrease mammographic sensitivity, markedly increasing glandular density. Enlargement of pre-existing cysts and fibroadenomas has also been reported after HRT. The correlation between HRT and breast cancer is highly controversial. We examined 650 women: 550 of them (84.6%) received HRT (157 estrogens and 393 estrogens-progestins) and 100 (15.4%) refused treatment and were thus considered as a control group. All patients underwent mammography and DEXA before HRT and, during treatment, were followed-up yearly with mammography, often combined with US, and DEXA. Fisher's test was used for data analysis (confidence interval: 95%). The statistical analysis showed a significant difference between the HRT group and the control group only for the lumbar spine. Mammographic changes (Tab. II) were shown in 150 of 550 HRT patients. Increased breast density was the most frequent finding. Benign lesions arising de novo or increasing in size and/or number were observed in 41 of 150 patients (27.3%) in the HRT group, where 3 breast carcinomas were detected, versus 1 breast cancer only in the control group. HRT had a marked positive effect on bone mineral content (BMC) at 2 years' follow-up, but it remains debated if it reduces breast cancer risk. In conclusion, our results indicate that a yearly mammography is mandatory in long-term HRT subjects and US may be also needed in particularly dense breasts.