Izabela Tuleta

Antiplatelet effects of antidepressant treatment: a randomized comparison between escitalopram and nortriptyline.

INTRODUCTION Depressive disorders have been identified as independent risk factors for coronary heart disease. The present study (i) compared platelet function of depressed patients with that of healthy controls, (ii) analysed possible aggregability changes during 3 months of treatment with antidepressants, and (iii) sought to assess different effects of escitalopram and nortriptyline on platelet aggregation. METHODS Blood samples of 91 major depressed patients and 91 healthy controls were analysed with whole blood aggregometry in a case-control setting. Depressed patients were randomized to two groups treated either with escitalopram (n=47) or nortriptyline (n=44). Platelet aggregation was studied on days 0, 1, 3, 7, 14, 21, 84 of continuing medication and was determined in response to adenosine diphosphate (ADP) and collagen. RESULTS Platelet aggregation induced by ADP was increased among depressive patients compared with that of healthy controls (26%, p=0.006). With antidepressant treatment, changes in platelet aggregation remained comparable in both groups at early time points (d1 to 21). In contrast, at day 84, patients with antidepressive response revealed significant differences in both medication groups: Patients receiving escitalopram showed a 23% decrease of ADP induced aggregation (p=0.03) and a 15% decrease of collagen induced aggregation (p=0.03). With nortriptyline the increase in impedance was reduced by 29% after ADP induction (p=0.046). CONCLUSION Depressed patients have higher ex vivo platelet aggregation that may contribute to increased cardiovascular morbidity. After three months of antidepressant treatment with either escitalopram or nortriptyline, platelet aggregation was significantly reduced in antidepressant responders, irrespective of the antidepressant medication type.

Improvement of quality of life in patients with concomitant allergic asthma and atopic dermatitis: one year follow-up of omalizumab therapy

ObjectiveAnti IgE treatment with omalizumab is efficacious in the treatment of patients suffering from allergic asthma, improving asthma control and improving quality of life. Furthermore, this approach could be beneficial for patients with concomitant atopic dermatitis. We assessed quality of life and asthma control in atopic patients with allergic asthma and concomitant atopic dermatitis versus those with asthma and without atopic dermatitis treated with omalizumab.MethodsA total of 22 patients with severe allergic asthma were treated with omalizumab for 12 months. 13 patients with allergic asthma without concomitant atopic dermatitis (IgE 212 ± 224 IU/ml) and 9 patients with concomitant allergic asthma and atopic dermatitis (IgE 3,528 ± 2,723 IU/ml) were included. Asthma-related quality of life (AQLQ), atopic dermatitis related quality of life (DLQI), and asthma-related treatment were compared between both groups at baseline and after initiating omalizumab treatment.ResultsDLQI was significantly in favor of omalizumab after 2 months in the atopic dermatitis/asthma group (P = 0.01); AQLQ was improved after 6 months in the asthma group (P = 0.01), while no change was seen in AQLQ in the atopic dermatitis/asthma group (P = 0.12). Omalizumab controlled oral corticosteroid use more effective (P < 0.01) in patients with asthma and atopic dermatitis (in 9/9 cases) compared to patients with asthma alone (9/13). Baseline IgE as well as other factors do not predict response to omalizumab.ConclusionsOmalizumab is effective in improving atopic dermatitis-related quality of life scores and modulates oral corticosteroid use in patients with concomitant asthma and atopic dermatitis in a positive fashion.

Monocyte subtypes and the CCR2 chemokine receptor in cardiovascular disease

Monocytes circulate in the blood and migrate to inflammatory tissues, but their functions can be either detrimental or beneficial, depending on their phenotypes. In humans, classical monocytes are inflammatory cluster of differentiation (CD)14++CD16-CCR2++ cells originated from the bone marrow or spleen reservoirs and comprise ≥92% of monocytes. Intermediate monocytes (CD14++CD16+CCR2+) are involved in the production of anti-inflammatory cytokines [such as interleukin (IL)-10], reactive oxygen species (ROS), and proinflammatory mediators [such as tumor necrosis factor-α (TNF-α) and IL-1β). Nonclassical monocytes (CD14+CD16++CCR2-) are patrolling cells involved in tissue repair and debris removal from the vasculature. Many studies in both humans and animals have shown the importance of monocyte chemoattractant protein-1 (MCP-1) and its receptor [chemokine receptor of MCP-1 (CCR2)] in pathologies, such as atherosclerosis and myocardial infarction (MI). This review presents the importance of these monocyte subsets in cardiovascular diseases (CVDs), and sheds light on new strategies for the blocking of the MCP-1/CCR2 axis as a therapeutic goal for treating vascular disorders.

Intermittent Hypoxia Impairs Endothelial Function in Early Preatherosclerosis

Intermittent hypoxia seems to be a major pathomechanism of obstructive sleep apnea-associated progression of atherosclerosis. The goal of the present study was to assess the influence of hypoxia on endothelial function depending on the initial stage of vasculopathy. We used 16 ApoE-/- mice were exposed to a 6-week-intermittent hypoxia either immediately (early preatherosclerosis) or after 5 weeks of high-cholesterol diet (advanced preatherosclerosis). Another 16 ApoE-/- mice under normoxia served as corresponding controls. Endothelial function was measured by an organ bath technique. Blood plasma CD31+/annexin V+ endothelial microparticles as well as sca1/flk1+ endothelial progenitor cells in blood and bone marrow were analyzed by flow cytometry. The findings were that intermittent hypoxia impaired endothelial function (56.6±6.2% of maximal phenylephrine-induced vasoconstriction vs. 35.2±4.1% in control) and integrity (increased percentage of endothelial microparticles: 0.28±0.05% vs. 0.15±0.02% in control) in early preatherosclerosis. Peripheral repair capacity expressed as the number of endothelial progenitor cells in blood was attenuated under hypoxia (2.0±0.5% vs. 5.3±1.9% in control), despite the elevated number of these cells in the bone marrow (2.0±0.4% vs. 1.1±0.2% in control). In contrast, endothelial function, as well as microparticle and endothelial progenitor cell levels were similar under hypoxia vs. control in advanced preatherosclerosis. We conclude that hypoxia aggravates endothelial dysfunction and destruction in early preatherosclerosis.

Angiotensin-converting enzyme I/D polymorphism in chronic obstructive pulmonary disease

Study objectiveThe etiology of chronic obstructive lung disease (COPD) is unclear. It is supposed to be the product of an exogenous antigenic stimulus, such as tobacco smoke, and an endogenous genetic susceptibility. The angiotensin-converting enzyme (ACE) gene contains a polymorphism based on the presence (insertion [I]) or absence (deletion [D]) of a 287-bp nonsense domain, resulting in three different genotypes (II, ID and DD). The aim of the study was to find out whether the ACE gene polymorphism can determine the course of COPD.Patients and designWe genotyped 152 Caucasian patients with COPD and 158 healthy controls for the ACE (I/D) polymorphism. We divided the COPD group into one group of 64 patients with a stable course of disease, defined as less than three hospitalizations over the last three years due to COPD, and another group of 88 patients with an instable course with more than three hospitalizations.ResultsThe I-allele was significantly associated with an increased risk for COPD in a dominant model (OR 1.67 (95% CI 1.00 to 2.78), p = 0.048), but not in a recessive or co-dominant model. Moreover, the I-allele of ACE (I/D) was significantly increased in patients with a stable course of COPD (p = 0.012) compared with controls. In a dominant model (II/ID v DD) we found an even stronger association between the I-allele and a stable course of COPD (OR 3.24 (95% CI 1.44 to 7.31), p = 0.003).ConclusionThese data suggest that the presence of an ACE I-allele determines a stable course of COPD.

Underdiagnosis of Obstructive Sleep Apnoea in Peripheral Arterial Disease

Background: Obstructive sleep apnoea (OSA) has interdependently been related to the onset and progression of a large portion of atherosclerotic cardiovascular disorders. In due consideration of OSA-mediated endothelial dysfunction, its impact on peripheral artery disease is conceivable, but undefined. Objectives: The aim of this study was to identify the prevalence of OSA in a lower extremity artery disease (LEAD) study population. Methods: A total of 91 patients receiving in- and outpatient treatment for LEAD were included in this prospectively conducted trial. In addition to an angiological examination, all patients underwent nocturnal screening for sleep-disordered breathing by use of SOMNOcheck micro® (SC micro) and - depending on the results obtained - polysomnography. Results: Patients were principally late middle-aged (69.3 ± 10.8 years), male (71.4%) and slightly overweight (BMI 26.8 ± 3.9). Overnight screening determined a sleep apnoea prevalence of 78.0%, of which 90.1% exhibited a predominantly obstructive genesis. The mean apnoea-hypopnoea index (AHI; events/h) and oxygen desaturation index (events/h) averaged 11.8 ± 13.4 and 8.9 ± 14.2, respectively. The individual AHI categories of non-pathological (<5), mild (5 to <15), moderate (15 to <30) and severe sleep apnoea (≥30) accounted for 22.0, 59.3, 13.2 and 5.5%, respectively. A distributive examination of AHI within LEAD severity groups evinced a significant association (p = 0.047). In cases of at least moderate sleep apnoea (AHI ≥15) polysomnography was performed (n = 17, 18.7% of the whole collective). Correlative analysis revealed a significant correlation between values obtained by SC micro recording and polysomnography, establishing the diagnostic accuracy of the screening results. Conclusions: OSA exhibits an important prevalence of 70.3% in LEAD patients with prior undiagnosed sleep-disordered breathing, indicating major OSA unawareness in this cardiovascular cohort. However, the impact of OSA treatment on LEAD propagation remains to be determined.

Risk and fate of residual interatrial shunting after transcatheter closure of patent foramen ovale: a long term follow up study

BackgroundPercutaneous transcatheter closure of patent foramen ovale (PFO) in cryptogenic stroke is an alternative to medical therapy. There is still debate on different outcome for each currently available device. The impact of residual shunting after PFO-clo- sure on recurrent arterial embolism is unknown.Aims(i) To evaluate the prevalence of residual interatrial shunting after device- closure of PFO, (ii) to identify risk factors predicting residual interatrial shunting after device implantation, and (iii) to investigate the outcome of patients after PFO-closure during long- term follow- up (FU).Methods and resultsBetween 2000- 2005 PFO-closure was performed in 124 patients using four different devices: Amplatzer PFO-(n = 52), CardioSeal (n = 33), Helex (n = 23) and Premere (n = 16) occluder. All patients underwent serial contrast-enhanced transesophageal echocardiography (TEE) for 24 months after PFO- closure; clinical FU was at minimum 5 years up to 9.75 years (mean 6.67 ± 1.31 years). Overall-closure rate was 87% at 2 years, device-specific closure time curves differed significantly (p-logrank = 0.003). Independent risk factors for residual-shunting were implantation of a Helex occluder (hazard ratio [HR] 12.6, 95% confidence interval [CI] 2.6- 57.4, p = 0.002), PFO- canal- lengths (HR 1.2, 95%CI 1.1- 1.3, p = 0.004) and extend of atrial-septal-aneurysm (HR 1.1, 95%CI 0.9- 1.3; p = 0.05). 4 (3.2%) arterial embolic events occurred during a FU-period of 817.2 patient-years, actuarial annual thromboembolic-risk was 0.49%. All ischemic events were not related to residual PFO-shunting or device-related thrombus- formation.ConclusionSuccess rates of PFO- closure are mainly dependent on occluder-type, extend of concomitant atrial-septum-aneurysm and PFO-canal- length. Importantly, residual shunting after PFO-closure was not associated with recurrence of arterial embolism during long-term follow-up.

Cells of Primarily Extravascular Origin in Neointima Formation following Stent Implantation

Objectives: In-stent restenosis due to neointima formation is a major limitation following stent implantation. Recently, several studies reported mobilization of primarily extravascular cells to the arterial sites after balloon angioplasty. Therefore, the goal of the present study was to assess the coordinated neointimal expression of endothelial progenitor, dendritic and neural crest-derived cells after stent implantation. Methods: Male minipigs underwent stent implantation in abdominal aortic segments. Animals were sacrificed at 1, 7, 14, 30, 60 or 90 days. Cross sections of the injured vessels were obtained for immunohistochemistry using specific antibodies for the detection of endothelial progenitor (CD133), dendritic (S100) and neural crest-derived cells (GFAP), as well as monocytes/macrophages (CD14) and T lymphocytes (CD3). Results: As a key finding, frequency of CD133, S100, GFAP, CD14 and CD3 (18.5 ± 3.6, 14.9 ± 1.8, 10.6 ± 1.1, 40.2 ± 8.3 and 5.0 ± 0.6%, respectively) in neointima was maximal at day 7. With ongoing neointima enlargement, expression of these cells decreased. In advanced neointima, labeled cells were predominantly localized at luminal and stented sites. Media showed almost no immunoreactivity of the markers studied, whereas adventitial zones of neovascularization revealed some signals. Conclusions: Endothelial progenitor, dendritic, neural crest-derived and inflammatory cells are consistently recruited into arterial neointima, mostly at early time points after stent implantation.

Obstructive sleep apnoea as a risk factor for atherosclerosis – implication for preventive and personalised treatment

Atherosclerosis with its manifestations and associated diseases is a main cause of morbidity and mortality in industrial countries. The pathomechanisms underlying atherosclerosis are complex and comprise exogenous factors as well as genetic predisposition. Beyond the well-defined risk factors for the development of atherosclerosis, obstructive sleep apnoea (OSA) merits more and more attention. A growing body of evidence has associated OSA with vascular pathologies. Although the exact mechanisms involved are not known, the occurrence of intermittent hypoxia typical for OSA may lead to oxidative stress, inflammation, metabolic and neural changes which in turn are responsible for vessel dysfunction underlying atherosclerosis. It has been demonstrated that therapy with continuous positive airway pressure (CPAP) plays a vasoprotective role. This review summarises data resulting from epidemiological and clinical studies with emphasis on the possible mechanisms linking OSA with atherosclerosis, predictive biomarkers helping identify OSA patients at high cardiovascular risk and personalised treatment approaches.

Impact of intimal pathogen burden in acute coronary syndromes—correlation with inflammation, thrombosis, and autoimmunity

BACKGROUND Increasing evidence supports a link between serological evidence of pathogen burden (PB) and the risk for future cardiovascular events. Our study evaluates the intimal presence of 4 pathogens in atheroma, clinically associated with acute coronary syndromes (ACS) and stable angina (SA), and the effect on the expression of intimal C-reactive protein (CRP), tissue factor (TF) and human heat-shock protein 60 (hHSP60). METHODS Coronary atherectomy specimens retrieved from 60 primary lesions of patients with ACS (n=35) or SA (n=25) were assessed immunohistochemically for the presence of Chlamydia pneumoniae (Cpn), Helicobacter pylori (HP), Cytomegalovirus (CMV) and Epstein–Barr Virus (EBV) and for the expression of CRP, TF, and hHSP60. RESULTS Analysis revealed eight lesions without, 22 lesions with one, 19 lesions with two, seven lesions with three, and four lesions with four pathogens. Cpn was present in 73%, HP in 31%, CMV in 16%, and EBV in 40%. Mean value of PB in ACS-lesions was significantly increased. Expressions of CRP, TF, and hHSP60 were significantly higher in ACS lesions. The number of infectious pathogens correlated significant with the expressions of CRP, TF, and hHSP60. CONCLUSIONS Our data demonstrate the impact of PB in plaque instability and suggest local proinflammatory, prothrombotic, and proimmunogenic effects.