Metabolic Syndrome and Cardiovascular Risk in Elderly Treated Hypertensive Patients.

BACKGROUND: The independent prognostic significance of the metabolic syndrome (MetS) in the elderly is not yet clear. We investigated the association between MetS and cardiovascular risk (composite endpoint of stroke and coronary events) in elderly treated hypertensive patients. METHODS: Cardiovascular outcome was evaluated in 1,191 elderly treated hypertensive patients (≥60 years). Among them, 578 (48.5%) had MetS according to a modified joint interim statement definition (body mass index in place of waist circumference). RESULTS: During the follow-up (9.1±4.9 years, range 0.4-20 years), 139 strokes and 120 coronary events occurred. In univariate analysis, patients with MetS had higher risk of the composite endpoint (hazard ratio (HR) 1.322, 95% confidence interval (CI) 1.035-1.688, P < 0.05). Among the single components of MetS, only blood pressure (BP) level and impaired fasting glucose/diabetes were significantly associated with increased cardiovascular risk. After adjustment for age, previous events, estimated glomerular filtration rate (eGFR), left ventricular (LV) hypertrophy and left atrial (LA) enlargement, the prognostic relevance of MetS was attenuated (HR 1.245, 95% CI 0.974-1.591, P = 0.08). After further adjustment for the above-mentioned variables and ambulatory BP parameters and impaired fasting glucose/diabetes, Cox regression analysis showed that MetS was not independently associated with increased cardiovascular risk (HR 1.090, 95% CI 0.805-1.475, P = 0.58). CONCLUSIONS: In elderly treated hypertensive patients, MetS is associated with increased cardiovascular risk, but not independently of BP and glucose levels and of organ damage.

Morning Blood Pressure Surge, Dipping, and Risk of Coronary Events in Elderly Treated Hypertensive Patients.

BACKGROUND: The independent prognostic significance of morning surge (MS) of blood pressure (BP) is not yet clear. We investigated the association between MS of systolic BP and risk of coronary events in elderly treated hypertensive patients. METHODS: The occurrence of coronary events was evaluated in 1,191 elderly treated hypertensive patients (age range 60-90 years). Subjects were divided according to tertiles of MS of systolic BP of the population as a whole, by dipping status and by group-specific tertiles of MS of systolic BP in dippers and nondippers. RESULTS: During the follow-up (9.1 ± 4.9 years, range 0.4-20 years), 120 coronary events occurred. In the population as a whole, coronary event risk was not significantly associated with tertiles of MS of systolic BP, whereas nondippers were at higher risk than dippers. When nondippers and dippers were analyzed separately, by group-specific tertiles of MS of systolic BP, coronary event risk was associated with MS of systolic BP in dippers but not in nondippers. After adjustment for various covariates, Cox regression analysis showed that dippers in the third tertile (>23 mm Hg) of MS of systolic BP (hazard ratio 1.912, 95% confidence interval 1.048-3.488, P = 0.03) and nondippers (hazard ratio 1.739, 95% confidence interval 1.074-2.815, P = 0.02) were at higher coronary event risk than dippers with MS of systolic BP <23 mm Hg . CONCLUSIONS: In elderly treated hypertensive patients, high MS of systolic BP predicts coronary events in dippers but not in nondippers. Nondippers, however, show higher risk of coronary events independently of MS in systolic BP.

Reactive aldehyde-scavenging enzyme activities in atherosclerotic plaques of cigarette smokers and nonsmokers.

OBJECTIVE: To investigate enzymatic reactive aldehyde-scavenging enzyme capacity together with lipid peroxidation as expression of oxidative stress in atherosclerotic plaques of cigarette smokers and nonsmokers. METHODS: We have assessed specific enzymatic activities of class 1, 2, and 3 aldehyde dehydrogenase (ALDH1, ALDH2, and ALDH3, respectively), glutathione S-transferase (isozyme A4-4, GSTA4-4), and aldose reductase (AR), namely the major reactive aldehyde-scavenging enzymes, together with lipid peroxidation, i.e., fluorescent damage products of lipid peroxidation (FDPL), in carotid atherosclerotic plaques surgically removed from 17 cigarette smokers and 17 nonsmokers. RESULTS: The enzymatic activities of ALDH1 plus ALDH2, ALDH3, GSTA4-4, and AR were significantly lower in the atherosclerotic plaques of smokers than in those of nonsmokers, while plaque FDPL levels were significantly higher in the smokers than in the nonsmokers. The amount of cigarette smoking was correlated inversely with the aforementioned plaque enzymatic activities and directly with plaque FDPL content. Plaque FDPL levels were inversely correlated with plaque enzymatic activities in smokers and nonsmokers. The degree of carotid atherosclerotic stenosis, as expression of atherosclerosis severity, was correlated inversely with plaque enzymatic activities and directly with plaque FDPL levels in smokers and nonsmokers; moreover, the degree of carotid stenosis was directly correlated with the amount of cigarette smoking. CONCLUSION: atherosclerotic lesions of cigarette smokers are endowed with a depressed enzymatic reactive aldehyde-scavenging capacity eventually favoring oxidative stress and the severity of atherosclerosis.

Assessment of EGFR mutations in circulating tumor cell preparations from NSCLC patients by next generation sequencing: toward a real-time liquid biopsy for treatment.

INTRODUCTION: Assessment of EGFR mutation in non-small cell lung cancer (NSCLC) patients is mandatory for optimization of pharmacologic treatment. In this respect, mutation analysis of circulating tumor cells (CTCs) may be desirable since they may provide real-time information on patient's disease status. EXPERIMENTAL DESIGN: Blood samples were collected from 37 patients enrolled in the TRIGGER study, a prospective phase II multi-center trial of erlotinib treatment in advanced NSCLC patients with activating EGFR mutations in tumor tissue. 10 CTC preparations from breast cancer patients without EGFR mutations in their primary tumors and 12 blood samples from healthy subjects were analyzed as negative controls. CTC preparations, obtained by the Veridex CellSearch System, were subjected to ultra-deep next generation sequencing (NGS) on the Roche 454 GS junior platform. RESULTS: CTCs fulfilling all Veridex criteria were present in 41% of the patients examined, ranging in number between 1 and 29. In addition to validated CTCs, potential neoplastic elements were seen in 33 cases. These included cells not fulfilling all Veridex criteria (also known as "suspicious objects") found in 5 (13%) of 37 cases, and isolated or clustered large naked nuclei with irregular shape observed in 33 (89%) cases. EGFR mutations were identified by NGS in CTC preparations of 31 (84%) patients, corresponding to those present in matching tumor tissue. Twenty-five (96%) of 26 deletions at exon 19 and 6 (55%) of 11 mutations at exon 21 were detectable (P = 0.005). In 4 (13%) cases, multiple EGFR mutations, suggesting CTC heterogeneity, were documented. No mutations were found in control samples. CONCLUSIONS: We report for the first time that the CellSearch System coupled with NGS is a very sensitive and specific diagnostic tool for EGFR mutation analysis in CTC preparations with potential clinical impact.

Left atrial enlargement and risk of ischemic stroke in elderly treated hypertensive patients.

BACKGROUND: The independent prognostic significance of left atrial enlargement is not yet completely clear. We investigated the association between left atrial enlargement and risk of ischemic stroke in elderly treated hypertensive patients. METHODS: The occurrence of ischemic stroke was evaluated in 1,191 elderly treated hypertensive patients (age range = 60-90 years). Left atrium diameter (cm) was indexed by body surface area (m(2)) and subjects were divided into those with normal or enlarged (≥2.4cm/m(2)) left atrium. RESULTS: During the follow-up (9.1±4.9 years; range = 0.4-20 years), 139 ischemic strokes occurred. The event rate per 100 patient-years was 1.28. There were 86 strokes in patients with normal (= 928) left atrium and 53 strokes in patients with enlarged (= 263) left atrium, respectively. Stroke-free survival curves were significantly different between the groups (P < 0.01). After adjustment for various covariables, including clinical variables, left ventricular hypertrophy, and ambulatory blood pressure parameters, Cox regression analysis showed that left atrial enlargement was significantly associated with increased risk of ischemic stroke (hazard ratio = 1.54; 95% confidence interval = 1.05-2.27; P = 0.03). CONCLUSIONS: In elderly treated hypertensive patients, left atrial enlargement is an independent predictor of ischemic stroke.

Myocardial glutathione metabolic status in fat-fed rabbits.

Short-term fat feeding could exert adverse cardiac effects by altering myocardial glutathione-related antioxidant defenses. We have here assessed total glutathione (TG), the activities of glutathione reductase (GSSG-Red), γ-glutamylcysteine synthetase (γ-GCS), γ-glutamyl transpeptidase (γ-GT) and glutathione peroxidase (GSH-Px), fluorescent damage products of lipid peroxidation (FDPL), thiobarbituric acid-reactive substances (TBARS), H2O2, and ATP in the aerobically perfused hearts of control rabbits and of rabbits fed a fat-enriched diet for 18 days. Such biochemical parameters, myocardial hemodynamics and infarct size were assessed in the perfused hearts of other control and fat-fed rabbits subjected to 60 min global ischemia plus 30 min reperfusion. Compared to controls, a reduced activity of GSSG-Red and γ-GT associated with decreased TG content was detected in the aerobically perfused hearts of fat-fed rabbits, which also showed insignificant γ-GCS activation, GSH-Px depressed activity, FDPL, TBARS and H2O2 burden, and unaltered ATP content. Ischemia-reperfusion decreased the myocardial levels of TG, ATP, and γ-GCS activity and augmented those of FDPL, TBARS, and H2O2 especially in the fat-fed rabbits, without significant changes in myocardial GSSG-Red, γ-GT, and GSH-Px activities. Ischemia-reperfusion induced greater hemodynamic dysfunction and infarct size in the hearts of fat-fed rabbits than in those of controls. Thus, short-term fat feeding and hyperlipidemia alter glutathione metabolic status of the rabbit myocardium, inducing a GSSG-Red- and γ-GT-related decrement of myocardial glutathione content, which, together with GSH-Px dysfunction, may favor tissue oxidative stress and render the myocardium more susceptible to ischemia-reperfusion injury.

Morning blood pressure surge, dipping, and risk of ischemic stroke in elderly patients treated for hypertension.

BACKGROUND: The independent prognostic significance of morning surge (MS) in blood pressure (BP) is not yet clear. We investigated the association between MS in systolic BP (SBP) and risk of ischemic stroke in elderly patients treated for hypertension. METHODS: Occurrence of ischemic stroke was evaluated in 1,191 elderly patients treated for hypertension (aged 60-90 years). Patients were divided according to tertiles of MS in SBP in the population as a whole, dipping status, and group-specific tertiles of MS in SBP in dippers and nondippers. RESULTS: During follow-up (9.1±4.9 years, range 0.4-20 years), 139 ischemic strokes occurred. The event rate per 100 patient-years was 1.28. After adjustment for various covariates, Cox regression analysis showed that stroke risk was not significantly associated with tertiles of MS in SBP in the population as a whole. When nondippers and dippers were analyzed separately by group-specific tertiles of MS in SBP, stroke risk was not associated with MS in nondippers. Conversely, in dippers, stroke risk was significantly higher in the third tertile (>23mm Hg) of MS in SBP (hazard ratio, 2.08; 95% confidence interval, 1.03-4.23; P = 0.04). Additional analysis showed that stroke risk was significantly and similarly higher in dippers with MS >23mm Hg and in nondippers than in dippers with MS <23mm Hg. CONCLUSIONS: In elderly patients treated for hypertension, high MS in SBP predicts stroke in dippers but not in nondippers. Nondippers are at high stroke risk with or without MS >23mm Hg.

Prediction of carotid plaques in hypertensive patients by risk factors, left ventricular hypertrophy, and epicardial adipose tissue thickness.

Hypertension and other risk factors (RFs) predispose to carotid plaques (CPs). An association between left ventricular hypertrophy (LVH) or epicardial adipose tissue (EAT) and CPs has also been reported. The aim of the study was to evaluate whether the assessment of LVH and EAT thickness, beyond RFs, would be of additive value in predicting CPs in hypertensive subjects. We studied 548 hypertensive patients aged ≥ 50 years without carotid bruit. LVH and CPs were evaluated and defined according to standard criteria. EAT was measured by echocardiography above the free wall of the right ventricle at end diastole. The presence of LVH and EAT thickness above the median value (3.9 mm) together significantly increased prevalence of CPs in subjects with 0-1 risk factor, but not in those with ≥ 2 RFs who showed high prevalence of CPs independently of LVH and/or EAT. Receiver operating characteristic curve analysis showed that the addition of LVH and higher EAT thickness together significantly improved prediction of CPs in patients with 0-1 risk factor. Indeed, the area under the curve improved from 0.63 (0.56-0.69) to 0.73 (0.67-0.79), which was significantly higher (p < 0.05). In patients with ≥ 2 RFs, the addition of LVH and EAT did not significantly improve prediction of CPs. This study shows that the presence of LVH and higher EAT thickness together improves prediction of CPs in hypertensive patients with 0-1 risk factor and that those with ≥ 2 RFs show high prevalence of CPs independently of LVH and/or EAT.

Meta-analysis of the relation of echocardiographic epicardial adipose tissue thickness and the metabolic syndrome.

Epicardial adipose tissue (EAT) is an emerging cardiometabolic risk factor, and its thickness can be measured using echocardiography. The relation of EAT to the metabolic syndrome (MS) is still unclear. A meta-analysis of published reports was performed to provide comprehensive insight on the association of EAT thickness as assessed by echocardiography and the MS. A systematic search was conducted for reports on echocardiographic EAT thickness in patients with and without the MS. Nine studies were identified. The pooled population consisted of 2,027 subjects, of whom 1,030 had the MS. EAT thickness was significantly higher in patients with the MS than in those without (standardized difference in means 1.15 mm, 95% confidence interval 0.78 to 1.53, p = 0.0001). Subgroup meta-analysis showed no difference between patients with and those without the MS by MS criteria used and echocardiographic cardiac cycle of measurement but did show a significant difference by ethnicity, with a greater difference in Caucasian subjects (standardized difference in means 1.75 mm, 95% confidence interval 1.43 to 2.07) than in other ethnic groups. In conclusion, echocardiographic EAT thickness is significantly higher in patients with the MS than in those without, but differences exist by ethnicity.

Effective assessment of egfr mutation status in bronchoalveolar lavage and pleural fluids by next-generation sequencing.

PURPOSE: The therapeutic choice for patients with lung adenocarcinoma depends on the presence of EGF receptor (EGFR) mutations. In many cases, only cytologic samples are available for molecular diagnosis. Bronchoalveolar lavage (BAL) and pleural fluid, which represent a considerable proportion of cytologic specimens, cannot always be used for molecular testing because of low rate of tumor cells. EXPERIMENTAL DESIGN: We tested the feasibility of EGFR mutation analysis on BAL and pleural fluid samples by next-generation sequencing (NGS), an innovative and extremely sensitive platform. The study was devised to extend the EGFR test to those patients who could not get it due to the paucity of biologic material. A series of 830 lung cytology specimens was used to select 48 samples (BAL and pleural fluid) from patients with EGFR mutations in resected tumors. These samples included 36 cases with 0.3% to 9% of neoplastic cells (series A) and 12 cases without evidence of tumor (series B). All samples were analyzed by Sanger sequencing and NGS on 454 Roche platform. A mean of 21,130 ± 2,370 sequences per sample were obtained by NGS. RESULTS: In series A, EGFR mutations were detected in 16% of cases by Sanger sequencing and in 81% of cases by NGS. Seventy-seven percent of cases found to be negative by Sanger sequencing showed mutations by NGS. In series B, all samples were negative for EGFR mutation by Sanger sequencing whereas 42% of them were positive by NGS. CONCLUSIONS: The very sensitive EGFR-NGS assay may open up to the possibility of specific treatments for patients otherwise doomed to re-biopsies or nontargeted therapies.

Bicarbonate-dependent, carbonate radical anion-driven tocopherol-mediated human LDL peroxidation: an in vitro and in vivo study.

We have here investigated possible occurrence of bicarbonate-dependent, carbonate radical anion (CO(3)(•-))-driven tocopherol-mediated human LDL peroxidation (TMP) in vitro and in vivo. CO(3)(•-), generated in vitro by the SOD1/H(2)O(2)/bicarbonate system, readily promoted TMP, which was dependent on α-tocopherol and bicarbonate concentrations, and was inhibited by the CO(3)(•-) scavenger ethanol; moreover, TMP induced in vitro by the SOD1/H(2)O(2)/bicarbonate system occurred in the presence of α-tocopherol that typically underwent slow oxidative consumption. In the in vivo clinical setting, we showed that, compared to controls, hypertensive patients with diuretic-induced metabolic alkalosis and heightened blood bicarbonate concentration had lipid hydroperoxide burden and decreased α-tocopherol content in the LDL fraction, with direct significant correlation between the LDL levels of α-tocopherol and those of lipid hydroperoxides; remarkably, after resolution of metabolic alkalosis, together with normalization of blood bicarbonate concentration, the LDL content of lipid hydroperoxides was decreased and that of α-tocopherol augmented significantly. These findings suggest bicarbonate-dependent, CO(3)(•-)-driven LDL TMP in vivo. In conclusion, the present study highlights the occurrence of bicarbonate-dependent, CO(3)(•-)-driven human LDL TMP, the role of which in pathological conditions such as atherosclerosis warrants, however, further investigation.

Cardiac events in hypertensive patients with renal artery stenosis treated with renal angioplasty or drug therapy: meta-analysis of randomized trials.

BACKGROUND: Cardiac outcome in patients with atherosclerotic renal artery stenosis (ARAS) undergoing percutaneous transluminal renal angioplasty (PTRA) or medical therapy is not yet completely clear. The aim of this study was to perform a meta-analysis of randomized controlled trials to compare the effect of PTRA and medical therapy on nonfatal myocardial infarction in patients with ARAS. METHODS: We searched for articles reporting cardiovascular outcome, including nonfatal myocardial infarction, in patients with renal artery stenosis randomized to PTRA with/without stenting or medical therapy. RESULTS: Five studies were identified. The pooled population consisted of 1,159 subjects who experienced 56 nonfatal myocardial infarctions. When compared with medical therapy, the overall relative risk (RR) was 0.85 (95% confidence interval (CI) 0.51-1.42), P = 0.55, for PTRA. There was no significant difference between PTRA and medical therapy according to procedural characteristics (with/without stent placement), mean serum creatinine at follow-up (higher or lower than 2.0 mg/dl), and maximum follow-up length (> or <2 years). CONCLUSIONS: In patients with ARAS and hypertension, there is a lack of evidence supporting the superiority of PTRA over medical therapy in prevention of nonfatal myocardial infarction. Awaiting for results of ongoing trials, our data and previous data suggest that PTRA and drug therapy have a similar impact on cardiovascular risk reduction in patients with renal artery stenosis and hypertension.

Complex mutations & subpopulations of deletions at exon 19 of EGFR in NSCLC revealed by next generation sequencing: potential clinical implications.

Microdeletions at exon 19 are the most frequent genetic alterations affecting the Epidermal Growth Factor Receptor (EGFR) gene in non-small cell lung cancer (NSCLC) and they are strongly associated with response to treatment with tyrosine kinase inhibitors. A series of 116 NSCLC DNA samples investigated by Sanger Sequencing (SS), including 106 samples carrying exon 19 EGFR deletions and 10 without deletions (control samples), were subjected to deep next generation sequencing (NGS). All samples with deletions at SS showed deletions with NGS. No deletions were seen in control cases. In 93 (88%) cases, deletions detected by NGS were exactly corresponding to those identified by SS. In 13 cases (12%) NGS resolved deletions not accurately characterized by SS. In 21 (20%) cases the NGS showed presence of complex (double/multiple) frameshift deletions producing a net in-frame change. In 5 of these cases the SS could not define the exact sequence of mutant alleles, in the other 16 cases the results obtained by SS were conventionally considered as deletions plus insertions. Different interpretative hypotheses for complex mutations are discussed. In 46 (43%) tumors deep NGS showed, for the first time to our knowledge, subpopulations of DNA molecules carrying EGFR deletions different from the main one. Each of these subpopulations accounted for 0.1% to 17% of the genomic DNA in the different tumors investigated. Our findings suggest that a region in exon 19 is highly unstable in a large proportion of patients carrying EGFR deletions. As a corollary to this study, NGS data were compared with those obtained by immunohistochemistry using the 6B6 anti-mutant EGFR antibody. The immunoreaction was E746-A750del specific. In conclusion, NGS analysis of EGFR exon 19 in NSCLCs allowed us to formulate a new interpretative hypothesis for complex mutations and revealed the presence of subpopulations of deletions with potential pathogenetic and clinical impact.

Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy.

BACKGROUND: Venous thromboembolism (VTE) often complicates the clinical course of cancer disease. The risk is further increased by chemotherapy but the safety and efficacy of primary thromboprophylaxis in cancer patients treated with chemotherapy is uncertain. OBJECTIVES: To assess the efficacy and safety of primary thromboprophylaxis in ambulatory cancer patients receiving chemotherapy. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched 3 May 2011) and CENTRAL (2011, Issue 2). The authors searched clinical trials registries and reference lists of relevant studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing unfractionated heparin (UFH), low molecular weight heparin (LMWH), vitamin K antagonists (VKA), direct thrombin inhibitors, direct factor Xa inhibitors or mechanical intervention to no intervention or placebo; or comparing two different anticoagulants. DATA COLLECTION AND ANALYSIS: Data were extracted on methodological quality, patients, interventions and outcomes including symptomatic VTE and major bleeding as the primary effectiveness and safety outcomes, respectively. MAIN RESULTS: Nine RCTs with a total of 3538 patients were considered. None of the RCTs tested UFH, fondaparinux, direct factor Xa inhibitors or mechanical interventions. Overall, the risk of bias was low in most of the studies. LMWH, when compared with inactive control, significantly reduced the incidence of symptomatic VTE (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.41 to 0.93) with no evidence of heterogeneity (I(2) = 0%). The number needed to treat to prevent a symptomatic VTE was 60. LMWH was associated with a 60% increase in major bleeding when compared with inactive control, although this was not statistically significant (RR 1.57, 95% CI 0.69 to 3.60; I(2) = 10%). There was a 45% reduction in overall VTE (RR 0.55, 95% CI 0.34 to 0.88; I(2) = 0%) while for symptomatic pulmonary embolism, asymptomatic VTE, minor bleeding and one-year mortality the differences between the LMWH and control groups were not statistically significant. The effect of the vitamin K antagonist warfarin on preventing symptomatic VTE, measured in only one study, was not statistically significant (RR 0.15, 95% CI 0.02 to 1.20). In one RCT of patients with myeloma, LMWH was associated with a 67% reduction in symptomatic VTE (RR 0.33, 95% CI 0.14 to 0.83) compared with warfarin, with no differences in major bleeding. Antithrombin, evaluated in one study on paediatric patients, had no significant effect on VTE nor major bleeding when compared with inactive control. AUTHORS' CONCLUSIONS: Primary thromboprophylaxis with LMWH significantly reduced the incidence of symptomatic VTE in ambulatory cancer patients treated with chemotherapy. However, the lack of power hampers definite conclusions on the effects on major safety outcomes, which mandates additional studies to determine the risk to benefit ratio of LMWH in this setting.

Epicardial adipose tissue and metabolic syndrome in hypertensive patients with normal body weight and waist circumference.

BACKGROUND: Metabolic syndrome (MetS) is a cluster of risk factors, related to visceral adiposity, which is frequently observed in overweight patients. However, it has also been reported in normal weight subjects. Epicardial adipose tissue (EAT) is a visceral fat. The aim of the study was to evaluate whether EAT is associated with MetS in hypertensive patients with normal weight and waist. METHODS: We studied 174 Caucasian hypertensive patients, aged ≥40 years, with body mass index (BMI) <25 kg/m(2) and waist circumference <102 cm in men and 88 cm in women. MetS was defined according to NCEP ATP III criteria, not including waist circumference. EAT was measured by echocardiography above the free wall of the right ventricle, at end diastole. RESULTS: MetS was present in 21 (12%) patients. EAT was significantly higher in patients with MetS than in those without MetS, 4.0 ± 0.8 vs 2.5 ± 0.9 mm, P < 0.01, respectively, but BMI and waist circumference were not. Multivariate analysis showed that EAT was independently associated with MetS. Receiver operating characteristic (ROC) curve analysis showed that EAT significantly improved prediction of MetS when added to BMI and waist circumference. Indeed, the area under the curve improved from 0.63 (0.50-0.76) to 0.91 (0.87-0.96), and resulted significantly higher (P < 0.01). ROC curve for EAT alone indicated that the cutoff value of 3.1 mm had the best performance in predicting MetS, that is, 100% sensitivity and 79% specificity. CONCLUSION: EAT thickness is associated with MetS in hypertensive patients with normal weight and waist.

Thrombophilia and outcomes of assisted reproduction technologies: a systematic review and meta-analysis.

Thrombophilia has been associated with pregnancy complications and recurrent miscarriage. The aim of this systematic review was to evaluate the controversial association between thrombophilia and failures of assisted reproduction technology (ART). A systematic search of the literature for studies reporting on thrombophilia in women undergoing ART up to April 2011 yielded 33 studies (23 evaluating anti-phospholipid antibodies, 5 inherited thrombophilia, and 5 both) involving 6092 patients. Overall, methodologic quality of the studies was poor. Combined results from case-control studies showed that factor V Leiden was significantly more prevalent among women with ART failure compared with fertile parous women or those achieving pregnancy after ART (odds ratio = 3.08; 95% confidence interval, 1.77-5.36). The prothrombin mutation, methylenetetrahydrofolate reductase mutation, deficiency of protein S, protein C, or anti-thrombin were all not associated with ART failure. Women with ART failure tested more frequently positive for anti-phospholipids antibodies (odds ratio = 3.33; 95% confidence interval, 1.77-6.26) with evidence of high degree of between-study heterogeneity (I(2) = 75%; P < .00001). Prospective cohort studies did not show significant associations between thrombophilia and ART outcomes. Although case-control studies suggest that women experiencing ART failures are more frequently positive for factor V Leiden and anti-phospholipid antibodies, the evidence is inconclusive and not supported by cohort studies.

A prospective evaluation of iron deficiency anemia in the GI endoscopy setting: role of standard endoscopy, videocapsule endoscopy, and CT-enteroclysis.

BACKGROUND: Iron deficiency anemia (IDA) is a frequently encountered condition in clinical practice. After conventional endoscopy, the cause of anemia remains unknown in up to 40% of patients. OBJECTIVE: To evaluate prospectively the diagnostic efficacy of a systematic endoscopic approach to IDA and to compare the diagnostic yield of videocapsule endoscopy (VCE) and CT-enteroclysis in endoscopy-negative patients. DESIGN: Consecutive patients with IDA were enrolled prospectively. SETTING: Open-access endoscopy within an academic hospital. PATIENTS: This study involved 189 patients with IDA, including 98 women and 91 men; mean (±standard deviation) age 68 years±16.6 years. INTERVENTION: Patients with IDA underwent gastroscopy and colonoscopy plus ileoscopy. Endoscopy-negative patients were further blindly evaluated by both CT-enteroclysis and VCE. MAIN OUTCOME MEASUREMENTS: Diagnostic yield of conventional endoscopy; diagnostic yield of VCE versus CT-enteroclysis. RESULTS: Endoscopy results were positive in 144 of 189 patients (76.2%). CT-enteroclysis and VCE allowed a diagnosis in 37 of 45 endoscopy-negative patients (82.2%). Overall, VCE was superior to CT-enteroclysis (77.8% vs 22.2%; P<.001), in particular when flat lesions were found. LIMITATIONS: Single-center study. CONCLUSION: A systematic approach to IDA, which includes standard endoscopy, VCE, and CT-enteroclysis allows an overall diagnostic rate of 95.7%; however, CT-enteroclysis should be limited to cases of nondiagnostic VCE.

Prognostic value of white-coat and masked hypertension diagnosed by ambulatory monitoring in initially untreated subjects: an updated meta analysis.

BACKGROUND: The prognostic relevance of white-coat hypertension (WCH) and masked hypertension (MH) is controversial. The aim of this study was to perform an updated meta-analysis on the prognostic value of WCH and MH diagnosed by ambulatory monitoring in initially untreated subjects. METHODS: We searched for articles evaluating cardiovascular outcome in WCH or MH or sustained hypertension (SH) in comparison with normotension, investigating untreated subjects at baseline or performing separate analysis for untreated or treated subjects, and reporting adjusted hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Eight studies were identified. Five whole studies and untreated groups of three others were included in the meta-analysis. The pooled population consisted of 7,961 subjects who experienced 696 events. When compared with normotension, the overall adjusted HR was 0.96 (95% CI 0.65-1.42) for WCH (P = 0.85), 2.09 (1.55-2.81) for MH (P = 0.0001), and 2.59 (2.0-3.35) for SH (P = 0.0001). There was no significant difference between WCH and normotension according to normotensive subjects source (same or different study population) and follow-up length. Where reported, prevalence of drug therapy was higher in subjects with WCH than in those with normotension at follow-up. CONCLUSIONS: Cardiovascular risk is not significantly different between WCH and normotension, regardless of normotensive population type and follow-up length. However, at follow-up drug therapy was more frequent in WCH than in normotension and its possible impact on outcome should be evaluated in future studies. MH shows significantly higher risk than normotension, although the best way for its detection and treatment remains to be established.

Obesity, poor muscle strength, and venous thromboembolism in older persons: the InCHIANTI study.

BACKGROUND: Both obesity and the decline in muscle strength, which often occur with aging, are accompanied by functional and metabolic changes that may affect the risk of thrombosis. This study evaluated whether obesity and poor muscle strength are associated with venous thromboembolism (VTE). METHODS: Objectively confirmed VTEs were assessed at baseline and more than a 6-year follow-up in 1,045 participants more than or equal to 60 years enrolled in the InCHIANTI study. RESULTS: At baseline, 97 participants had a positive history of VTE. Obese participants were almost twice more likely (odds ratio 1.76; 95% confidence interval 1.03-3.01) and obese with poor muscle strength were threefold more likely (odds ratio 2.99; 95% confidence interval 1.56-5.73) to have VTE compared with lean participants with normal strength. Fifty-five VTEs occurred during follow-up. History of VTE, obesity, and/or poor strength independently predicted new VTE events. In participants with previous VTE, the odds ratio (95% confidence interval) for thrombosis was 6.64 (1.92-22.95) with poor strength, 9.69 (3.13-30.01) in the obese, and 14.57 (5.16-41.15) in the obese with poor strength as compared with lean participants with normal strength. CONCLUSION: Obesity with or without poor muscle strength is a risk factor for VTE among older persons and significantly amplifies the risk of recurrent thrombosis.