European Journal of Clinical Investigation (Eur J Clin Investig )

Publisher: European Society for Clinical Investigation, Blackwell Publishing

Description

The Journal of the European Society for Clinical Investigation. The European Journal of Clinical Investigation publishes papers in the field of clinical investigation, provided they contribute to the advancement of knowledge in this field. The term 'clinical investigation' is interpreted widely and includes studies relevant to humans in health or disease, including such studies that may have taken place with animals.

  • Impact factor
    3.37
  • 5-year impact
    3.05
  • Cited half-life
    8.00
  • Immediacy index
    0.70
  • Eigenfactor
    0.01
  • Article influence
    0.90
  • Website
    European Journal of Clinical Investigation website
  • Other titles
    European journal of clinical investigation (Online)
  • ISSN
    1365-2362
  • OCLC
    46653881
  • Material type
    Document, Periodical, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Blackwell Publishing

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Restrictions
    • Some journals impose embargoes typically of 6 or 12 months, occasionally of 24 months
    • no listing of affected journals available as yet
  • Conditions
    • See Wiley-Blackwell entry for articles after February 2007
    • Publisher version cannot be used
    • On author or institutional or subject-based server
    • Server must be non-commercial
    • Publisher copyright and source must be acknowledged with set statement ("The definitive version is available at www.blackwell-synergy.com ")
    • Articles in some journals can be made Open Access on payment of additional charge
    • 'Blackwell Publishing' is an imprint of 'Wiley-Blackwell'
  • Classification
    ​ yellow

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Although generic and earlier brand-name counterparts are bioequivalent, their equivalence in preventing relevant clinical outcomes is of concern.Objective To compare effectiveness of generic and brand-name antihypertensive drugs for preventing the onset of cardiovascular (CV) outcomes.Design and subjectsA population-based, nested case-control study was carried out by including the cohort of 78,520 patients from Lombardy (Italy) aged 18 years or older who were newly treated with antihypertensive drugs during 2005. Cases were the 2,206 patients who experienced a hospitalization for CV disease from initial prescription until 2011. One control for each case was randomly selected from the same cohort that generated cases. Logistic regression was used to model the CV risk associated with starting on and/or continuing with generic or brand-name agents.ResultsThere was no evidence that patients who started on generics experienced different CV risk than those on brand-name product (OR 0.86; 95% CI 0.63 to 1.17). Patients at whom generics were main dispensed had not significantly difference in CV outcomes than those mainly on brand-name agents (OR 1.19; 95% CI 0.86 to 1.63). Compared with patients who kept initial brand-name therapy, those who experienced brand-to-generic or generic-to-brand switches, and those always on generics, did not show differential CV risks, being the corresponding ORs (and 95% CIs), 1.18 (0.96 to 1.47), 0.87 (0.63 to 1.21), and 1.08 (0.80 to 1.46).Conclusions Our findings do not support the notion that brand-name antihypertensive agents are superior to generics for preventing CV outcomes in the real world clinical practice.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 08/2014;
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    ABSTRACT: Background Serum cholesterol has been demonstrated to correlate with blood pressure values, therefore abnormal levels of serum cholesterol might contribute to the development of hypertension. The aim of the present study was to assess the new-onset of hypertension over a period of 8 years in a pharmacologically untreated population sample in normo- and hypercholesterolemic individuals.Design1864 Caucasian subjects with baseline blood pressure values <140/90 mmHg were subdivided into two different groups, according to LDL-Cholesterol changes observed over a period of 8 years. Group 1 included subjects whose LDL-Cholesterol levels remained or decreased within the normal range, while Group 2 included those whose LDL-Cholesterol levels were persistently increased above the normal range. The 8-year incidence of new-onset hypertension was 7.1% in group 1 and 13.8% in group 2 (p=0.02), after adjustment for the main confounding risk factors. The difference between group 1 and 2 was confirmed in men (8.2 vs. 13.1%, p=0.04) and women (6.1. vs. 14.5%, p=006), as well as in subjects younger than 65 years (5.7 vs. 10.9%; p=0.011), but not in older ones.Conclusions Baseline serum LDL-Cholesterol levels are related to the rate of new-onset hypertension in patients with normal or marginally elevated blood pressure values.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 08/2014;
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    ABSTRACT: BackgroundA new 4-classification of left ventricular hypertrophy (LVH) based on LV concentricity and dilation has been proposed, however, the association between the new categorization of LV geometry and outcomes in patients with coronary artery disease (CAD) is still unknown.Methods All the 2297 CAD patients included underwent echocardiographic examination prior to discharge. Left ventricular mass (LVM) was calculated and left ventricular end-diastolic volume (EDV) was indexed by body surface area (BSA). Study cohort were divided into 5 groups according to LV geometry: 1) eccentric non-dilated LVH (normal LVM/EDV(2/3) and EDV/BSA) (n=129); 2) eccentric dilated LVH (normal LVM/EDV(2/3) with increased EDV/BSA) (n=222); 3) concentric non-dilated LVH (increased LVM/EDV(2/3) with normal EDV/BSA) (n=441); 4) concentric dilated LVH (increased LVM/EDV(2/3) and EDV/BSA) (n=118); 5) normal LV mass (n=1387).ResultsDilated LVH was associated with a higher event rates of all-cause death (eccentric 13.1% vs. 3.1%; concentric: 13.6% vs. 8.4%) and composite events (eccentric: 17.6% vs. 5.4%; concentric: 18.6% vs. 12.7%) compared with non-dilated LVH. While eccentric non-dilated LVH had comparable risk for adverse outcomes compared with normal LV mass (all-cause death: relative risk (RR) 0.68, 95% confidential interval (CI) 0.25-1.85; composite events: RR 0.75, 95% CI 0.36-1.58). Cox regression analyses showed that eccentric dilated LVH had the highest propensity to all-cause death (adjusted hazard ratio [aHR] 2.752 [95% CI 1.749-4.328], P<0.001) and composite events (aHR 2.462 [95% CI 1.688-3.592], P<0.001).Conclusion In patients with CAD, dilated and non-dilated LVH provide distinct prognostic information. Eccentric non-dilated LVH does not predict adverse outcomes.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 08/2014;
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    ABSTRACT: Background Periodontitis is the most common oral infection seen in humans worldwide. It is characterized by gradual destruction of tooth supporting tissues, eventually leading to loss of tooth. The periodontal biofilm associated with periodontitis comprises of gram-positive and gram-negative bacteria, instrumental for the initiation and progression of periodontitis. Evidence based literature has identified the nature of periodontal infection as a possible causative condition in the inducement of “low grade systemic inflammation and infection.” The periodontal pathogens exert systemic effects via the hematogenous route.AimThe present review provides an insight into the pathophysiology of the endothelial dysfunction with reference to periodontal infectionand highlights the association between periodontitis and endothelial dysfunction. Various studies addressing the implication of periodontitis on endothelial dysfunction will be described, with a focus of periodontal treatment on improvement of endothelial function.Materials and methodsStudies examining the effects of periodontitis on vascular endothelial function were segregated. Studies conducted on both animal and human models were identified using MEDLINE data base search with key search terms such as ‘‘Periodontitis’’, ‘‘vascular endothelium’’, “endothelial dysfunction”, “periodontal bacteria”, ‘‘periodontal therapy”. Systematic reviews, meta-analysis were also screened. Only studies published in English language were considered. The review has been prepared by screening MEDLINE database from 1989 to 2012.Results and conclusionsChronic periodontitis results in altered vascular response, increased expression of pro-inflammatory cytokines and adhesion molecules inducing vascular endothelial dysfunction. Periodontal therapy may ameliorate the perturbed vascular endothelial function.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 08/2014;
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    ABSTRACT: PurposeTo evaluate whether diabetes is a risk factor for breast cancer considering confounders and potential detection examinations.Methods National Health Insurance data on 501,747 women without breast cancer were retrieved. Three-year cumulative incidence (2003–2005) and risk ratios (RRs) between diabetic and non-diabetic women were calculated. Potential detection examinations were compared between diabetic and non-diabetic women by Chi square test. Odds ratios (ORs) were estimated by logistic regression for diabetes status/duration with and without adjustment for potential detection examinations and confounders.ResultsThe crude RR (95% confidence interval [CI]) for all ages, and age groups <50, 50–64 and ≥65 years, was 2.62 (2.31–2.91), 2.69 (2.11–3.44), 1.39 (1.15–1.68) and 1.37 (1.03–1.84), respectively. Diabetes patients more frequently received potential detection examinations than non-diabetes (17.5% versus 7.4%, P-value <0.001). The unadjusted OR (95% CI) for breast cancer for diabetes status (yes versus no) was 2.63 (2.31-2.98), and was significant for any diabetes duration. The OR for diabetes status was 1.81 (95% CI: 1.59-2.06) after adjustment for potential detection examinations. In models adjusted for potential detection examinations, age, living region, occupation, comorbidities and used medications, OR for diabetes status attenuated to 1.13 (95% CI 0.96-1.32, P-value=0.14); and none was significant for any diabetes duration. Potential detection examinations were associated with a 5-fold to 7-fold higher risk in various models, indicating a strong impact of detection bias.Conclusions An association between diabetes and breast cancer is observed, but this can be due to potential detection bias and confounders.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 08/2014;
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    ABSTRACT: IntroductionIrisin activates the thermogenic function in adipose tissues. However, little is known on the association between human irisin and different cardiometabolic risk factors. We analyze the influence of morbid obesity on irisin levels and its relation with leptin and different cardiovascular risk factors.Material and Methods We measured the serum irisin level and the fibronectin type III domain containing 5 (FNDC5) expression in adipose tissue from 33 morbidly obese subjects and 12 non-obese subjects. We also studied the effect of leptin on FNDC5 expression.ResultsSerum irisin was higher in the non-obese subjects than in morbidly obese subjects, both before (p=0.043) and after bariatric surgery (p=0.042). The variable that best explained the serum irisin levels in a multiple linear regression model was the waist-to-hip ratio (WHR) (R2=0.201) (Beta=-0.357, p=0.046). Those morbidly obese subjects with android-type obesity had lower serum irisin levels than those with gynecoid-type obesity, both before (p=0.027) and after bariatric surgery (p=0.006). Only the percentage change in WHR was associated with serum irisin levels after bariatric surgery (r=-0.529, p=0.005). FNDC5 expression levels in subcutaneous adipose tissue (SAT) were higher in the non-obese than in the morbidly obese subjects (p=0.042). In SAT explants from non-obese subjects, leptin (20 and 150 ng/ml) produced a decrease in FNDC5 expression (p=0.009 and p=0.037, respectively).Conclusions We showed decreased serum irisin levels in morbidly obese subjects, related mainly to WHR. FNDC5 expression could be regulated by leptin.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 08/2014;
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    ABSTRACT: Background In animal models and clinical trials, statins are reported as effective in reducing cholesterol levels and lowering the risk of cardiovascular diseases. We have aggregated the findings in animal models - mice, rats and rabbits - using the technique of systematic review and meta-analysis to highlight differences in the efficacy of statins.Materials and Methods We searched Medline and Embase. After examining all eligible articles, we extracted results about total cholesterol and other blood parameters, blood pressure, myocardial infarction and survival. Weighted and standard mean difference random effects meta-analysis was used to measure overall efficacy in pre-specified species, strains and subgroups.ResultsWe included in systematic review 161 animal studies and we analyzed 120 studies, accounting for 2432 animals. Statins lowered the total cholesterol across all species, although with large differences in the effect size: -30% in rabbits, -20% in mice and -10% in rats. The reduction was larger in animals fed on a high-cholesterol diet. Statins reduced infarct volume, but did not consistently reduce the blood pressure or effect the overall survival. Few studies considered strains at high risk of cardiovascular diseases or hard outcomes.Conclusions Although statins showed substantial efficacy in animal models, few preclinical data considered conditions mimicking human pathologies for which the drugs are clinically indicated and utilized. The empirical finding that statins are more effective in lowering cholesterol derived from an external source (i.e. diet) conflicts with statin's supposed primary mechanism of action.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 07/2014;
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    ABSTRACT: Atrial fibrillation is a sustained arrhythmia commonly encountered in clinical practice. It has a high prevalence among the elderly, and contributes significantly to the global social-economic burden. Among many risk factors predisposing to atrial fibrillation is left atrial remodeling and wall fibrosis. Frequently, pathological left atrial wall remodeling and fibrosis results in low atrial compliance and elastance significantly increase the risk of developing permanent atrial fibrillation. Current imaging tools may play a role in the detection of atrial fibrosis hence providing valuable information for risk stratification and management of patients with atrial fibrillation.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 07/2014;
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    ABSTRACT: Background Uremia and cardiovascular disease appear to be associated with an increased oxidative burden. One of the key players in the genesis of reactive oxygen species (ROS) is nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.Based on initial experiments demonstrating a decreased inhibitory effect on NADPH oxidase activity in the presence of plasma from CKD-5D patients after dialysis compared to before dialysis, we investigated the effect of forty-eight known and commercially available uremic retention solutes on the enzymatic activity of NADPH oxidase.Methods Mononuclear leukocytes isolated from buffy coats of healthy volunteers were isolated, lysed and incubated with NADH in the presence of plasma from healthy controls and CKD-5D patients. Furthermore, the leukocytes were lysed and incubated in the presence of uremic retention solute of interest and diphenyleneiodonium chloride (DPI), an inhibitor of NADPH oxidase. The effect on enzymatic activity of NADPH oxidase was quantified within an incubation time of 120 minutes.ResultsThirty-nine of the forty-eight uremic retention solutes tested had a significant decreasing effect on NADPH oxidase activity. Oxalate has been characterized as the strongest inhibitor of NADPH oxidase (90% of DPI inhibition). Surprisingly, none of the uremic retention solutes we investigated was found to increase NADPH oxidase activity. Furthermore, plasma from CKD-5D patients before dialysis caused significantly higher inhibitory effect on NADPH oxidase activity compared to plasma from healthy subjects. However, this effect was significantly decreased in plasma from CKD-5D patients after dialysis.Conclusions The results of this study show that uremic retention solutes modulated the activity of the NADPH oxidase. The results of this study might be the basis for development of inhibitors applicable as drug in the situation of increased oxidative stressThis article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 07/2014;
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    ABSTRACT: Background The goal of the study was to evaluate angiogenesis and lymphangiogenesis in differentiated thyroid cancer and recurrences.Methods Twenty-seven patients with recurrent differentiated thyroid cancer (20 papillary and 7 follicular thyroid carcinomas) and 24 non-recurrent thyroid cancers were included in this study. Additionally, 24 thyroid adenomas were included as benign controls. All thyroid cancer recurrences were operatively managed, and local recurrences in cervical lymph nodes or cervical soft tissue were histologically confirmed. Altogether, a total of 108 samples were evaluated using CD31 and D2-40 immunohistochemical staining and microscopy.ResultsAs measured in primary tumours, the median density of CD31 positive vascular structures was 327 vessels (v)/mm2 for recurrent cancers, 362 v/mm2 for non-recurrent cancers and 484 v/mm2 for thyroid adenomas (p=0.017). Among the subgroups, the lowest median vascular density of 316 v/mm2 was found in recurrent papillary cancers and the highest vascular density of 604 v/mm2 was observed in non-recurrent follicular cancers (p=0.018). The median density of D2-40 positive peritumoural lymphatic vessels was 101/mm2 in recurrent cancers, 56.1/mm2 in non-recurrent cancers and 53.9/mm2 for adenomas (p=0.015). In the subgroups, peritumoural lymphatic vascular density was 102 v/mm2 in recurrent papillary cancers and 56.0 v/mm2 in non-recurrent papillary cancers (p=0.044).Conclusions Recurrent thyroid cancers expressed less intratumoural microvessels than thyroid adenomas. A high density of peritumoural lymphatic vessels was found in recurrent papillary cancers. High blood vessel density may be a marker for less aggressive tumours, while high peritumoural lymphatic vasculature is a marker for more aggressive and recurrence-prone tumours.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 07/2014;
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    ABSTRACT: Background The burden of chronic disease is projected to assume crisis proportions in most parts of the world by the middle of the century, focusing attention on the need for preventive interventions. We identify and review published research on primary prevention individual-level interventions in current practice, and describe and discuss the limitations of the current evidence. The report facilitates prioritizing a research agenda for potential interventions that might be investigated within cohort studies.Method(s)This study is a rapid review. Computerized database searches (PubMed and EMBASE) were performed in October 2012 to identify articles on primary prevention interventions that are directed at the individual level. Potentially relevant International Agency of Research on Cancer handbooks and monographs were also reviewed. The review includes articles reported in English on the efficacy or effectiveness of a preventive intervention in an adult population. It excludes articles on alcohol or tobacco smoking.ResultsMany chronic disease interventions directed at individuals report a protective effect in the short-term and some evidence for the efficacy of chemoprevention in chronic disease prevention exists. Evidence these effects persist in the longer-term is inconsistent.Conclusion There are currently only limited evidence-based preventions for most chronic diseases, for which a summary is available in table 1 (see appendix B). Most individual-level intervention research studies have been conducted using case-control designs and some small, randomized studies. There are fewer impediments to lifestyle modifications when compared to prevention using chemoprevention and vaccination or other methods of prevention of persistent infectionThis article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 07/2014;
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    ABSTRACT: Background In the general population, poor self-rated health (SRH) is associated with malnutrition; however, these associations have not been studied in hospitalized patients. We aimed to evaluate SRH, indicators of nutrition, nutritional status, and their association with in-hospital mortality.Materials and methodsThe study is based on data from the nutritionDay, a multinational, multicenter European-wide standardized one-day cross-sectional survey of nutritional factors, food intake, and in-hospital mortality in hospitalized patients. A dataset of surveys on SRH in 2010 and 2011 was used in the analysis.ResultsComplete sets of data were available for 28,106 patients (64±18 years, 50% men, 7% terminally ill). In relation to body mass index, 7% were undernourished and 16% were obese. Fair/poor SRH was reported by 59% of patients and was associated with low food intake during the previous week or on survey day (p<0.005). Thirty-day in-hospital mortality was 3%; in adjusted multivariate survival analysis, fair/poor SRH (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.14-2.05) and reduced food intake (nothing eaten [HR 2.13, 95% CI 1.46-3.11] or not allowed to eat on nutritionDay [HR 2.01, 95% CI 1.30-3.11]) predicted fatal outcome. At particularly high risk were patients who rated their health poor and had reduced food intake on the survey day or within the previous week with relative risks of 7.37 and 8.80, respectively.Conclusions We demonstrated high prevalence of poor SRH and insufficient food intake in hospitalized patients. This was associated, particularly in combination, with increased risk of in-hospital mortality.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 07/2014;
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    ABSTRACT: In primary hyperparathyroidism (PHPT) high levels of parathyroid hormone (PTH) are associated with significant mobilisation of bone marrow-derived cells (BMCs) into peripheral blood. To address the fate of BMCs we analyzed in the present study cells with typical surface markers of BMCs within parathyroid adenomas (PA) of patients with PHPT. We therefore investigated PA and normal parathyroid glands (NPG) of 15 patients with PHPT by immunohistochemistry and PCR. mRNA levels of CD31, CD34 and CD45 were significantly increased in PA compared to NPG. Immunohistochemical staining for CD31 and CD34 revealed a significantly higher vessel density in PA compared to NPG. Furthermore, scattered single cells expressing CD31, CD34 or CD45 were significantly augmented compared to NPG and directly correlated with vessel density. mRNA expression of SDF-1 in PA was increased whereas its major inhibitor dipeptidylpeptidase IV (DPP IV) was decreased compared to normal tissue suggesting a important role of the SDF-1 axis in migration of BMCs into PA. In summary, these data indicate a possible role of BMCs in the pathophysiology of PA of patients with PHPT.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 07/2014;
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    ABSTRACT: AimsThe appropriate timing for surgery in severe asymptomatic primary mitral regurgitation (MR) remains controversial. It has been shown that late gadolinium enhancement on cardiovascular magnetic resonance (LGE CMR), which may identify myocardial fibrosis, is associated with a worse outcome in various cardiomyopathies. We sought to investigate the prevalence and significance of delayed enhancement in primary MR.Methods We prospectively included 41 patients with at least moderate primary MR and without overt signs of left ventricular (LV) dysfunction. Patients with evidence of coronary artery disease, arrhythmias or significant concomitant valvular disease were excluded. All patients were scheduled for transthoracic echocardiography and LGE CMR.Results39 patients had interpretable LGE CMR images. Among them, 12 (31%) had late contrast uptake of the LV wall. LGE CMR showed an infarct pattern in 3 patients, a pattern of mid-wall fibrosis in 7 patients and 2 patients had a combined pattern. Patients with delayed enhancement on CMR had significant higher LV diameters (LV end-systolic diameter 39±4 vs. 34±5mm, p=0.002; LV end-diastolic diameter 57±5 vs. 50±5mm, p=0.001). There was a trend towards a higher indexed left atrial volume (55±21 vs. 44±13ml/m², p=0.06). By contrast, there was no significant association between myocardial contrast uptake and age, LV ejection fraction and MR severity.ConclusionLV remodeling seems to be associated with the presence of delayed enhancement on CMR in primary MR. Further data are needed to determine whether LGE CMR can predict a less favourable outcome or could improve risk stratification in asymptomatic primary MR.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 07/2014;
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    ABSTRACT: Microcirculatory function can be assessed by post occlusive reactive hyperemia (PORH) using laser Doppler fluxmetry. Previous studies have shown that PORH reveals microvascular damage at an early stage. Especially at younger ages PORH might depend on age and gender. To implement PORH into a larger scale of clinical studies one has to be aware of the influence of age and gender on microcirculation. The aim of this study was to assess the impact of age and gender on microcirculatory function during adolescence.
    European Journal of Clinical Investigation 06/2014;
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    ABSTRACT: The majority of sera from patients with primary membranous nephropathy have autoantibodies against the M-type phosholipase A2 receptor (PLA2R) which is expressed on human podocytes. The rabbit variant of PLA2R attaches to collagen type IV via the fibronectin type II domain, which is also present in the human variant of PLA2R.
    European Journal of Clinical Investigation 06/2014;
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    ABSTRACT: Fibroblast growth factor (FGF)-23 is a key regulator of phosphate homeostasis. Higher FGF-23 levels are correlated with poor outcomes in cardiovascular diseases. FGF-23 can produce cardiac hypertrophy and increase intracellular calcium, which can change cardiac electrical activity. However, it is not clear whether FGF-23 possesses arrhythmogenic potential through calcium dysregulation. Therefore, the purposes of this study were to evaluate the electrophysiological effects of FGF-23 and identify the underlying mechanisms.
    European Journal of Clinical Investigation 06/2014;
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    ABSTRACT: Vitamin D (25-OH D3) deficiency represents a rising social and economic problem in Western countries. Vitamin D has been recently reported to modulate inflammatory processes, endothelium and smooth muscle cell proliferation and even platelet function, thus potentially modulating atherothrombosis. Great interest has been addressed on its impact on cardiovascular outcome, with contrasting results. The aim of current study was to evaluate the relationship between 25-OH D3 and the extent of coronary artery disease in a consecutive cohort of patients undergoing coronary angiography. Patients undergoing elective coronary angiography were included in a cross-sectional study. Fasting samples were collected for 25-OH D3 levels assessment. Significant CAD was defined as at least 1 vessel stenosis > 50%, while severe CAD as left main and/or trivessel disease, as evaluated by Quantitative Coronary Angiography. Hypovitaminosis D was observed in 70.4% out of 1484 patients. Patients were divided according to vitamin D tertiles (<9.6; 9.6-18.4; >18.4). Lower vitamin D levels were associated with age, female gender (p<0.001, respectively), renal failure (p=0.05), active smoking (p=0.001), acute coronary syndrome at presentation (p<0.001), therapy with calcium-antagonists (p=0.02) and diuretics (p<0.001), less beta-blockers (p=0.02) and statins (p=0.001) use. Vitamin D directly related to haemoglobin (p<0.001) and inversely with platelet count (p=0.002), total and LDL cholesterol (p=0.002 and p<0.001) and triglycerides (p=0.01). Vitamin D did not influence angiographic features of coronary lesions, but was associated with higher prevalence of left main or right coronary artery disease (p=0.03). Vitamin D deficiency was significantly associated with higher prevalence of CAD (adjusted OR[95%CI]=1.32[1.1-1.6],p=0.004) and severe CAD (adjusted OR[95%CI]= 1.18[1-1.39], p=0.05). In patients undergoing coronary angiography hypovitaminosis D was observed in the vast majority of patients. Vitamin D deficiency is significantly associated with the prevalence and extent of CAD, especially for patients with values < 10 ng/ml. Therefore, future large studies are needed to evaluate whether vitamin D supplementation may prevent CAD and its progression. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 05/2014;
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    ABSTRACT: This review was commissioned to generate broad discussion about how to select intervention delivery modes when designing a complex, preventive intervention aimed at chronic disease through the promotion of physical activity, healthy diet, and/or medication adherence. In this context, we asked, what are the delivery modes? What are the important design considerations? And how do these compare (e.g., strengths, limitations)? This review ulitized the methods of rapid review, an emerging methodology arising from health technology assessment. The search strategy was applied in Embase and Medline. A qualitative, narrative synthesis was performed on included articles. After screening, 21 articles remained for synthesis (10 systematic reviews, including 1 review of reviews; 4 trials or studies; 3 commentaries or conference proceedings; and 2 were scoping projects). Our synthesis determined that major categories of design considerations when selecting intervention delivery modes include attention to the (i) candidate mode types, (ii) settings and social environment, (iii) intensity and timing, (iv) provider, (v) study population and participants; (vi) cost; (vii) behavior change technique; and (viii) theoretical basis. An array of modes of delivery are available for each of the intervention strategies under consideration (i.e., physical activity, dietary change, and medication adherence). No single delivery mode was clearly more appropriate or more effective than another, each having unique strengths and limitations. Delivery mode decisions that take the above factors (i-viii) into account will be more fit-for-purpose than those that do not. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 05/2014;
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    ABSTRACT: Background & AimsFetuin-A is a liver derived peptide associated with insulin resistance. Aim of this cross sectional study was to evaluate whether Fetuin-A is increased in patients with nonalcoholic fatty liver disease (NAFLD) vs. healthy subjects without metabolic abnormalities, and the association with insulin resistance and liver damage. To investigate the causal relationship between fatty liver and Fetuin-A, we also analyzed whether the inherited I148M PNPLA3 variant modulates Fetuin-A.Methods In 137 patients with histological NAFLD, complete metabolic characterization, PNPLA3 genotype, and in 260 healthy subjects without metabolic alterations Fetuin-A was measured by enzyme-linked immunoabsorbent assay.ResultsSerum Fetuin-A was higher in NAFLD patients than in controls (p<0.0001), independently of age, sex, BMI, insulin resistance, dyslipidemia, adiponectin, PNPLA3 I148M, and ALT levels (OR 1.006 95% CI 1.003-1.11; p=0.003). In NAFLD patients, Fetuin-A was associated with steatosis severity (p=0.03) and metabolic syndrome features, but not with hepatic inflammation. At multivariate analysis, Fetuin-A levels were associated with BMI, triglycerides, hyperglycemia, and PNPLA3 I148M (p=0.034) independently also of age, sex, and ALT levels. Since PNPLA3 I148M is a strong and inherited determinant of liver fat without affecting insulin resistance and lipid levels, these data suggest that steatosis has a causal role in determining serum Fetuin-A levels.Conclusions Liver fat accumulation and the I148M variant of PNPLA3 are associated with serum Fetuin-A levels independently of insulin resistance. Fetuin-A may be implicated in the pathogenesis of metabolic complications associated with NAFLD.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 05/2014;

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