The mobilization of endothelial progenitor cells (EPCs) into circulation from bone marrow is well known to be present in several clinical settings, including acute coronary syndrome, heart failure, diabetes and peripheral vascular disease. The aim of this review was to explore the current literature focusing on the great opportunity that EPCs can have in terms of regenerative medicine.

BackgroundMobilization of endothelial progenitor cells (EPCs) into circulation from bone marrow in patients with acute myocardial infarction has strong scientific evidence; less is known about EPC mobilization in patients with stable coronary artery disease (CAD). The aim of this study was to investigate the association of stable ischemic heart disease with EPC levels in tissue and blood.MethodsFifty-five consecutive patients admitted to a single treatment center for valve or coronary artery bypass grafting (CABG) surgeries were included in the study. Blood samples were collected in the morning before surgery and analyzed by flow-cytometry to determine peripheral EPC levels (EPC/ml). Tissue EPC (CD34+VEGFR2+) levels were assessed on a right atrial appendage segment.ResultsMean age was 76±5years, 48% were men, and 53% had CAD The number of CD34+ VEGFR2+ cells in the tissue of patients with CAD was significantly higher (p<0.005) and circulating EPC showed a tendency to be reduced by approximately 20% in peripheral blood of patients with CAD when compared to those without CAD.ConclusionPatients with stable CAD had higher EPC density values (EPC/mm2) and were more likely to have lower EPC blood levels when compare with normal controls.

Alexopoulou, Magdalinia; Violo, Caterinaa; Santini, Claudiaa; De Carlo, Marcob; Faggioni, Lorenzoc; Bortolotti, Ubertod; Balbarini, Albertoa Author Information

ObjectivesCirculating endothelial progenitor cells (EPCs) are related to endothelial function and progression of coronary artery disease. There is evidence of decreased numbers of circulating EPCs in patients with a current episode of major depression. We investigated the relationships between the level of circulating EPCs and depression and anxiety in patients with acute coronary syndrome (ACS).MethodsPatients with ACS admitted to three Cardiology Intensive Care Units were evaluated by the SCID‐I to determine the presence of lifetime and/or current mood and anxiety disorders according to DSM‐IV criteria. The EPCs were defined as CD133+CD34+ KDR+ and evaluated by flow cytometry. All patients underwent standardized cardiological and psychopathological evaluations. Parametric and nonparametric statistical tests were performed where appropriate.ResultsOut of 111 ACS patients, 57 were found to have a DSM‐IV lifetime or current mood or anxiety disorder at the time of the inclusion in the study. The ACS group with mood or anxiety disorders showed a significant decrease in circulating EPC number compared with ACS patients without affective disorders. In addition, EPC levels correlated negatively with severity of depression and anxiety at index ACS episode.ConclusionsThe current study indicates that EPCs circulate in decreased numbers in ACS patients with depression or anxiety and, therefore, contribute to explore new perspectives in the pathophysiology of the association between cardiovascular disorders and affective disorders. Copyright © 2015 John Wiley & Sons, Ltd.

Objective: The study aimed at exploring bereavement and complicated grief (CG) symptoms among subjects without a history of coronary heart disease (CHD) at the time of a first acute coronary syndrome (ACS) and to evaluate the relationship of CG symptoms and ACS.Method: Overall, 149 subjects with ACS (namely, acute myocardial infarct with or without ST-segment elevation or unstable angina), with no previous history of CHD, admitted to three cardiac intensive care units were included and evaluated by the Structured Clinical Interview for Complicated Grief (SCI-CG), Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, and the 36-item Short-Form Health Survey (MOS-SF-36).Results: Of the total sample of 149 subjects with ACS, 118 (79.2%) met criteria for DSM-5 persistent complex bereavement disorder. Among these, subjects who lost a partner, child, or sibling were older (P=0.008), less likely to be working (P=0.032), and more likely to be suffering from hypertension (P=0.021), returned higher scores on the SCI-CG (P=0.001) and developed the index ACS more frequently between 12 and 48 months after the death than those who lost a parent or another relative (P <= 0.0001). The occurrence of ACS 12-48 months (P=0.019) after the loss was positively correlated with SCI-CG scores. An inverse relationship with SCI-CG scores was observed for patients who experienced ACS more than 48 months after the loss (P=0.005). The SCI-CG scores significantly predicted lower scores on the "general health" domain of MOS-SF-36 (P=0.030), as well as lower scores on "emotional well-being" domain (P=0.010).Conclusion: A great proportion of subjects with ACS report the loss of a loved one. Among these, the loss of a close relative and the severity of CG symptoms are associated with poorer health status. Our data corroborate previous data indicating a strong relationship between CG symptoms and severe cardiac problems.

BACKGROUND:Carotid artery stenting (CAS) is a worldwide diffuse intervention, but may be associated with distal plaque component embolization, and sometimes major and minor stroke. Statin use has been demonstrated to reduce atherosclerotic plaque burden, but its effect in reducing distal embolization during carotid stenting has not yet been well validated. AIMS:With the Rosuvastatin Pretreatment to Reduce Embolization during Carotid Artery Stenting trial, we aim to discover if a pretreatement with high doses of rosuvastatin in dyslipidemic patients is able to reduce periprocedural cerebral ischemic complications following carotid stenting. METHODS:This is a phase III prospective, randomized controlled trial. All consecutive patients with asymptomatic carotid stenosis at least 80% will be randomized to a 6-week rosuvastatin treatment followed by carotid stenting, and to direct carotid stenting. Carotid stenting will be performed following common practice with distal or proximal embolic protection. The primary efficacy end point of the trial will be the prevalence of 'relevant' embolization during CAS, as a surrogate end point for cerebral ischemic complications. Other laboratory and clinical data will be registered and patients will be followed up to 1 year. In order to obtain the expected superiority of statin pretreatment on primary end point, a population of 130 patients will be enrolled into the study. CONCLUSION:In conclusion, with the Rosuvastatin Pretreatment to Reduce Embolization during Carotid Artery Stenting trial, we want to evaluate whether a high dose of rosuvastatin for 6 weeks before CAS in asymptomatic patients with severe carotid stenosis is able to reduce the rate of plaque embolization during the procedure, thus suggesting a possible reduction in cerebral ischemic complications.

AIMS:Depression has been identified as a risk factor for an adverse prognosis and reduced survival in patients with acute coronary syndrome (ACS). The number of endothelial progenitor cells (EPCs) is an independent predictor of clinical outcomes in patients with ACS. The aim of this study was to evaluate the impact of depression on EPC levels in patients with ACS. METHODS:Out of 74 ACS patients [23 non-ST-segment elevation myocardial infarction (NSTEMI), 48 STEMI], 36 had a diagnosis of major depressive episode (MDE) according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria at the time of the inclusion in the study. Control groups were as follows: 15 healthy individuals and 18 patients with current MDE without a history of cardiovascular diseases. EPCs were defined as CD34CD133KDR and evaluated by flow cytometry. All patients underwent standardized cardiological and psychopathological evaluations. Parametric and nonparametric statistical tests were performed wherever appropriate. RESULTS:ACS patients with MDE showed a significant decrease in circulating EPC number compared with ACS patients without MDE (P < 0.001). The ACS study population was then subdivided into STEMI and NSTEMI groups, and within each group patients with MDE again showed a significant decrease in circulating CD34CD133KDR EPCs compared with others (P <0.001). CONCLUSION:We showed that ACS patients with MDE have a reduced number of circulating CD34CD133KDR cells compared with ACS patients without MDE, suggesting that the presence of MDE reduces the response of bone marrow to acute ischemic events. Considering the reparative role of EPCs in ACS patients, we propose that patients with MDE might be protected less than patients without MDE.

The assessment of harm arising from the use of homeopathic medicine is much discussed, but there is little published data on the subject.To study prospectively adverse drug events related to homeopathic medicines.The data were gathered between 1 June 2003 and 30 June 2004 during follow-up visits consecutively carried out at the Homeopathic Clinic, Campo di Marte Hospital, Azienda USL 2, Lucca (Italy). They refer to effects following the administration of a homeopathic medicine, prescribed according to the classical homeopathic method.Reports collected by a homeopathic doctor (not the prescribing doctor) on the nature and intensity of the effect, dose and frequency of administration, time relationship between the drug use and the adverse events, challenge, unchallange possible concomitant factors, causality (improbable, unlikely, possible, probable, certain).Out of 335 homeopathic consecutive follow-up visits between 1 June 2003 and 30 June 2004, nine adverse reactions were reported (2.68%) including one case of allergy to lactose, excipient of the granules.Adverse events to homeopathic drugs exist and are distinguishable from homeopathic aggravations, but are rare and not severe.

Endothelialprogenitorcells(EPCs)aremobilizedfrombonemarrowinto peripheral blood, contributing to the revascularization of ischemicareas, to endothelial repair and to the physiological maintenance ofvascularization. EPC mobilization and homing have been primarilylinked to ischemia and inflammation presence [1]. EPCs are directlycorrelated with endothelial function and inversely correlated withcardiovascular risk factors and atherosclerosis progression [2].EPClevelshavealsobeencorrelatedtoprognosisevaluationincardiovascu-lar disease [3].Regarding EPC correlation with coronary artery disease (CAD)presence and severity, an inverse relationship with CAD severity, inde-pendent of traditional risk factors, was demonstrated by EPC colonycounting [4],whileahighnumberofEPCsassociatedwithCADandcorre-latedwithstenosisseveritywereshownby flowcytometry [5].Recentlyanew protocol, adapted from the standardized ISHAGE protocol for hema-topoieticstemcells,hasbeendevelopedforEPClevelevaluationtoenablecomparison of clinical and laboratory data [6].While thepresence of circulatingEPCshasbeenwidely evaluated indifferent diseases, few studies tried to evaluate the presence of EPCs inhuman vital myocardium.TheaimofourstudywastoinvestigateEPClevelsbothinperipheralbloodand inmyocardium in thesame patients atthesame time, evalu-atingthecorrelationwith CADpresence. In bothsampleswequantifiedCD34

AIMS:Distal embolisation during carotid artery stenting (CAS) is the main cause of cerebral complications; thus, the amount of embolisation occurring during CAS can be considered as a surrogate endpoint of cerebral complications. Our aim was to find patient characteristics which are associated with a higher risk of embolisation during CAS.METHODS AND RESULTS:From January to December 2010 all consecutive patients undergoing CAS with embolic protection at three medium- to high-volume Italian centres were prospectively enrolled in this multicentre study. After CAS, the embolic debris was classified by visual inspection into two groups: "scarce" (no debris or hardly visible debris), and "relevant" (visible embolic debris) embolisation. Two hundred and thirty-six consecutive patients (79% males, 32.7% symptomatic) were enrolled. Open cell stents were used in 52.7% of the patients, distal filters were employed in 85.5% and proximal protection in 14.5%. Procedural success was achieved in 100% of procedures. Relevant embolisation was observed in 16.1% of patients, including those who suffered all the periprocedural complications (4.2%). At multivariate statistical analysis, high circulating LDL cholesterol and C-reactive protein levels were the only factors associated with relevant embolisation.CONCLUSIONS:In this study, high circulating LDL cholesterol and C-reactive protein levels were associated with relevant embolisation after CAS, opening up the hypothesis that therapy with statins before elective CAS may reduce plaque embolisation and improve outcome. (EudraCT number: 016737-95).

We evaluated the effectiveness of intravenous iloprost (IVI) in outpatients with thromboangiitis obliterans (TAO) and lower limb noninvasive transcutaneous monitoring (TCM) at follow-up (FU). Ten consecutive patients with TAO underwent IVI therapy. Transcutaneous oxygen (TcPo 2 ) and carbon dioxide (TcPco 2 ) determination and laser Doppler flowmetry (LDF) were performed before and after IVI at 3, 6, and 12 months of FU. Clinical response was positive in 7 patients, whereas 3 nonresponders underwent a second IVI cycle with 1 showing a late positive clinical response. After 12 months of FU, all patients were alive without amputations. Supine and dependent TcP 2 levels significantly improved ( P < .005). Hallux LDF values showed significant change with the maximal hyperemic test at 44°C ( P < .005). Forefoot maximal hyperemic test at 44°C LDF ( P < .005) and improved venous arterial reflex ( P < .05) showed statistically significant time evolution. We demonstrated some degree of IVI effectiveness and evaluated TCM in patients with TAO.

Background: Depression and acute coronary syndrome (ACS) are both extremely prevalent diseases. Studies aimed at evaluating whether depression is an independent risk factor for cardiac events provided no definitive results. In most of these studies, depression has been broadly defined with no differentiation between unipolar (MDD) versus bipolar forms (BD). The aim of this study was to evaluate the frequency of DSM-IV BD (bipolar I and bipolar II subtypes, cyclothymia), as well as temperamental or isolated bipolar features in a sample of 171 patients hospitalized for ACS. We also explored whether these psychopathological conditions were associated with some clinical characteristics of ACS.Methods: Patients with ACS admitted to three neighboring Cardiac Intensive Care Units (CICUs) in a 12-month continuative period of time were eligible for inclusion if they met the criteria for either acute myocardial infarct with or without ST-segment elevation or unstable angina, verified by standard ACS criteria. All patients underwent standardized cardiological and psychopathological evaluations.Results: Of the 171 ACS patients enrolled, 37 patients (21.7%) were found to have a DSM-IV mood disorder. Of these, 20 (11.7%) had bipolar type I or type II or cyclothymia, while 17 (10%) were the cases of MDD. Rapid mood switches ranged from 11% of ACS patients with no mood disorders, to 47% of those with MDD to 55% of those with BD. Linear regression analysis showed that a diagnosis of BD (p = .023), but not that of MDD (p = .721), was associated with a significant younger age at the index episode of ACS. A history of previous coronary events was more frequent in ACS patients with BD than in those with MDD.Conclusions: Our data indicate that bipolar features and diagnosis are frequent in ACS patients. Bipolar disorder has a negative impact on cardiac symptomatology. Further research in this area is warranted. (C) 2013 Elsevier Masson SAS. All rights reserved.

No scientific evidence concerning the presence and role of endothelial progenitor cells (EPCs) in human vital myocardium exists. This study aimed to investigate the correlation between peripheral and myocardial EPC number and coronary artery disease (CAD) severity. 12 consecutive CAD patients, 5

Atherosclerosis and its complications are the most important causes of death all over the world, especially in Western countries. Diet habits, modern stress life, smoking, sedentary way of life and an involvement of genetic pattern of individuals lead to a sure degeneration of quality of life increasing the risk of atherosclerosis development. For this reason, the main purpose of actual medicine is to identify all the markers that could allow the physicians to evaluate the first moments of the development of this dangerous pathological process. The aim is to reduce the speed of its evolution, trying to delay indefinitely the risk coming from the morphological alterations of the vessels. 'Endothelium function' could allow physicians to detect the first moment of the natural history of atherosclerosis process. Its impairment is the first step in the degeneration of vascular structures. Many methods [flow-mediated vasodilatation (FMD); antero-posterior abdominal aorta diameter (APAO); intima-media thickness of the common carotid artery (CCA-IMT); arterial stiffness; and so on] try to evaluate its function, but many limitations come from general population characteristics. A standardization of the methods should take into account individuals' peculiarities. Two elements, not modifiable, should be taken into account for vascular evaluation: age and sex. The aim of this review is to outline the linkage among age, sex and instrumental evaluation of patients considered for a noninvasive assessment of their cardiovascular risk profile.

The human body's response to adverse environmental conditions and recovery is of great interest to understand mechanisms of physiologic adjustment in the cardiovascular system.