Differential prognostic accuracy of right ventricular dysfunction, the Seattle heart failure model and the MAGGIC score in patients with severe mitral regurgitation undergoing the MitraClip® procedure.

BACKGROUND: MitraClip ® (MC) is an established procedure for severe mitral regurgitation (MR) in patients deemed unsuitable for surgery.Right ventricular dysfunction (RVD) is associated with a higher mortality risk. The prognostic accuracy of heart failure risk scores like the Seattle heart failure model (SHFM) and Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score in pts undergoing MC with or without RVD has not been investigated so far. METHODS: SHFM and MAGGIC score were calculated retrospectively. RVD was determined as tricuspid annular plane systolic excursion (TAPSE) ≤15 mm. Area under receiver operating curves (AUROC) of SHFM and MAGGIC were performed for one-year all-cause mortality after MC. RESULTS: N = 103 pts with MR III° (73 ± 11 years, LVEF 37 ± 17%) underwent MC with a reduction of at least I° MR. One-year mortality was 28.2%.In Kaplan-Meier analysis, one- year mortality was significantly higher in RVD-pts (34.8% vs 2.8%, p = 0.009).Area under the Receiver Operating Characteristic (AUROC) for SHFM and MAGGIC were comparable for both scores (SHFM: 0.704, MAGGIC: 0.692). In pts without RVD, SHFM displayed a higher AUROC and therefore better diagnostic accuracy (SHFM: 0.776; MAGGIC: 0.551, p < 0.05). In pts with RVD, MAGGIC and SHFM displayed comparable AUROCs. CONCLUSION: RVD is an important prognostic marker in pts undergoing MC. SHFM and MAGGIC displayed adequate over-all prognostic power in these pts. Accuracy differed in pts with and without RVD, indicating higher predictive power of the SHFM score in pts without RVD.

[Out-of-hospital airway management with a laryngeal tube or endotracheal intubation for out-of-hospital cardiac arrest : Influence on in-hospital mortality]. / Präklinisches Atemwegsmanagement mit Larynxtubus oder Endotrachealtubus bei präklinischem Herz-Kreislauf-Stillstand : Einfluss auf die Krankenhausmortalität.

BACKGROUND: Endotracheal (ET) intubation has been the gold standard in out-of-hospital airway management for a long time. Recent guidelines suggest an alternative airway management with supraglottic airway devices like the laryngeal tube (LT) especially for less experienced rescue personnel. However, scientific evidence on the prognostic impact of the laryngeal tube in the setting of cardiopulmonary resuscitation is limited. METHODS: We aimed to compare mortality outcomes in out-of-hospital cardiac arrest (OHCA) patients after preclinically initiated airway management with either ET or LT in a propensity score matched, single-center retrospective analysis. RESULTS: A total of 208 patients with OHCA were resuscitated and intubated with either ET (n = 160; 77%) or LT (n = 48; 23%) in the urban area of Frankfurt am Main, Germany, and treated thereafter on the intensive care unit of the University Hospital Frankfurt from 2006-2014. In-hospital mortality was 84% versus 85% in the ET and LT group (p = 0.86). No difference regarding in-hospital mortality has been observed between the two airway management techniques in univariate as well as in multivariate mortality analysis (HR = 0.98, 95% confidence interval [CI] 0.69-1.39; p = 0.92; adjusted HR = 1.01, 95% CI 0.76-1.56; p = 0.62). To adjust for potential confounders, propensity score matching was additionally performed resulting in a cohort of 120 matched patients in a 3:1 ratio (ET:LT). Again, survival to hospital discharge was comparable between the two patient groups (propensity-adjusted HR = 0.99, 95% CI 0.65-1.51, p = 0.97). Further, preclinical airway management with LT or ET showed no difference in mortality within first 24 h (propensity-adjusted HR = 1.02; 95% CI 0.44-2.36; p = 0.96). CONCLUSION: Preclinical airway management with LT shows similar mortality outcomes in direct comparison to intubation with ET in OHCA patients. Further randomized studies are warranted.

[Pulmonary artery pressure sensor for ambulatory assessment of ventricular filling pressure in advanced heart failure : What should be considered for the follow-up care?] / Pulmonalarterieller Drucksensor zur ambulanten Beurteilung des ventrikulären Füllungsdrucks bei fortgeschrittener Herzinsuffizienz : Was ist bei der Nachsorge zu beachten?

BACKGROUND: Patients with advanced heart failure suffer from frequent hospitalizations. Noninvasive hemodynamic telemonitoring for assessment of pulmonary filling pressure has been shown to reduce hospitalizations. In this article, our experience with possible control intervals and the standardization of the follow-up care of hemodynamic telemonitoring is reported. METHODS: A literature search and our own experience in the follow-up care concerning the implantable pulmonary artery pressure sensor for noninvasive hemodynamic telemonitoring in patients with advanced heart failure are presented. RESULTS: For standardized follow-up care of heart failure patients with hemodynamic monitoring a specialized team consisting of a heart failure nurse and heart failure physician is essential. These teams should ideally work based on a unique standard operating procedure (SOP) to ensure standardized control intervals and a standardized approach to classical hemodynamic changes. However, all therapeutic recommendations have to be prescribed by a physician and must be modified if individually appropriate. CONCLUSION: Optimized follow-up care for hemodynamically guided heart failure management requires the implementation of novel structures in the German health care system in order to transfer the clinical benefit from clinical trials into daily routine.

[Early onset pneumonia after successful resuscitation : Incidence after mild invasive hypothermia therapy]. / Early-onset-Pneumonien nach prähospitaler Reanimation : Inzidenz nach milder intravasaler Hypothermiebehandlung.

BACKGROUND: Targeted temperature management (TTM) represents an effective therapy to improve neurologic outcome in patients who survive an out-of-hospital cardiac arrest (OHCA). First publications about this therapy reported a higher incidence of infections in patients who underwent TTM induced by external cooling devices. Whether intravascular cooling devices are also associated with an increased infection rate has not been investigated so far. METHODS: In a single center retrospective study, the incidence of early onset pneumonia (EOP) in OHCA patients with or without intravascular TTM at 33 °C target temperature for 24 h who survived at least 24 h after admission was analyzed. RESULTS: A total of 68 OHCA survivors (mean age 65 ± 15 years) were included in this analysis. The most common causes of OHCA were myocardial infarction (35 %), primary ventricular fibrillation (24 %), asystole (15 %), and pulmonary embolism (7 %). Of those, 32 patients (48 %) received TTM. The overall incidence of EOP was 38 %. Incidence of EOP did not differ significantly between groups, was more frequent in the group without TTM (42 % vs. 34 %, p = 0.57) and had no impact on mortality (hazard ratio = 1.02; 95 % confidence interval 0.25-4.16; p = 0.97). CONCLUSION: Intravascular TTM at 33 °C with a cooling catheter is not associated with more infective complications in OHCA patients. This finding underscores the safety of TTM.

[Implantable sensors for outpatient assessment of ventricular filling pressure in advanced heart failure : Which telemonitoring design is optimal?] / Implantierbare Sensoren zur ambulanten Beurteilung des ventrikulären Füllungsdrucks bei fortgeschrittener Herzinsuffizienz : Welches Telemonitoring-Design ist optimal?

INTRODUCTION: Patients with advanced heart failure suffer from frequent hospitalizations. Non-invasive hemodynamic telemonitoring for assessment of ventricular filling pressure has been shown to reduce hospitalizations. We report on the right ventricular (RVP), the pulmonary artery (PAP) and the left atrial pressure (LAP) sensor for non-invasive assessment of the ventricular filling pressure. METHODS: A literature search concerning the available implantable pressure sensors for noninvasive haemodynamic telemonitoring in patients with advanced heart failure was performed. RESULTS: Until now, only implantation of the PAP-sensor was able to reduce hospitalizations for cardiac decompensation and to improve quality of life. The right ventricular pressure sensor missed the primary endpoint of a significant reduction of hospitalizations, clinical data using the left atrial pressure sensor are still pending. CONCLUSION: The implantation of a pressure sensor for assessment of pulmonary artery filling pressure is suitable for reducing hospitalizations for heart failure and for improving quality of life in patients with advanced heart failure.

[Aspiration and pneumonia risk after preclinical invasive resuscitation: Endotracheal intubation and supraglottic airway management with the laryngeal tube S]. / Aspirations- und Pneumonierisiko nach präklinischer invasiver Beatmung : Endotracheale Intubation und supraglottische Atemwegssicherung mittels Larynxtubus S.

BACKGROUND: Laryngeal tubes (LT) have substantially facilitated emergency airway management. However, it remains unclear whether LTs provide comparable protection against aspiration or even higher rates of aspiration and pneumonia compared to endotracheal intubation (ET) as the former gold standard. METHODS: The indices for aspiration and early onset pneumonia in patients after preclinical airway management by either LT or ET were retrospectively analyzed. Furthermore, in-hospital mortality was analyzed. RESULTS: A total of 90 patients with invasive ventilation by either ET (n = 69) or LT (n = 21) were analyzed. Patients were excluded if indication for ventilation was pneumonia, aspiration, drowning, or if they had preexisting tracheotomy. The ET and LT groups did not differ regarding age (ET: 62 ± 16 years, LT: 64 ± 8 years, p = 0.56), female gender (ET: 23.2%, LT: 33.3%, p = 0.25), or first paO2/FIO2 (ET: 300 ± 164, LT: 342 ± 178, p = 0.3). The majority of patients were survivors of out-of-hospital cardiac arrest (OHCA, 72.2%), with a significantly higher OHCA rate in the LT group (LT: 95.2% ET: 65.2%, p = 0.006). Analysis for radiological or endoscopic evidence of pulmonary aspiration revealed a higher aspiration rate in the ET group (43.5%, LT: 23.8%, p = 0.08), especially after OHCA (ET: 48.9%, LT: 20%, p = 0.025). In parallel, early onset pneumonia as a correlate for microaspiration in patients without evident aspiration was observed more frequently in ET patients (41% vs. 25%, p = 0.21). In OHCA patients without aspiration, rates of pneumonia were similar (ET: 26.1%, LT: 25%; p = 0.62). Analysis of in-hospital mortality showed significantly higher mortality in the LT group (57.1% vs 30.4%, p = 0.026). Also in OHCA patients, higher mortality was observed in the LT group (60 vs. 28.9%, p = 0.018). DISCUSSION AND CONCLUSION: Airway management by LT was not associated with higher risk of aspiration. In contrast, higher rates of aspiration and pneumonia were observed after ET, especially in OHCA patients. However, a possible prognostic impact of supraglottic airway devices remains to be elucidated.

[Characterization and economic impact of medical patients presenting at the emergency department of an university hospital]. / Internistische Patienten in einer universitären Notaufnahme: Charakterisierung und ökonomische Bedeutung für das Gesamtklinikum.

BACKGROUND: The number of patients in German emergency departments has been rising for years. This means additional need of staff and infrastructure for hospitals. METHODS: In this monocentric retrospective analysis the patient population of the central emergency department (ZNA) at the university hospital Frankfurt was investigated. Major symptoms, diagnoses with respect to diagnose-related groups and modes of admission to the emergency department have been analyzed. RESULTS: During 3 months, a total of 7376 patients presented to the ZNA. Analysis focused on 2186 patients referred to the department of internal medicine: most patients presented spontaneously (50.6%), 38.2% were admitted by ambulance services, only 9.7% were admitted by a primary physician. 44.9% of these patients were hospitalized, mainly with cardiological, pneumological and gastroenterological disorders. The predominant major symptoms were acute chest pain (15.4%), abdominal pain (7.1%) and syncope or collapse (6.1%). Patients hospitalized via ZNA contributed 31.9% of the total revenues of internal medicine departments. 31.7% of all hospitalized patients were admitted to the hospital by the ZNA. CONCLUSION: Emergency departments become more and more a regular part of ambulatory patients health care and contribute efficiently to the economic revenue of hospitals.

[Veno-arterial ECMO as bridge to recovery. Cardiogenic shock and suspected myocarditis in a 37-year-old patient]. / Venoarterielle ECMO als "bridge to recovery". Kardiogener Schock und Verdacht auf Myokarditis bei einer 37-Jährigen.

We report a case of a 37-year-old patient presenting with fulminant cardiogenic shock, almost noncontractile ventricles, followed by electromechanical dissociation. During performance of cardiopulmonary resuscitation, a veno-arterial extracorporeal membrane oxygenation device (VA ECMO) was implanted, which became necessary for 13 days. Subsequently, a total arrest of ventricular function was observed and prominent multiple organ failure emerged. A rapid test for respiratory syncytial virus was positive, supporting the suspected diagnosis of myocarditis. Despite numerous complications, complete recovery was achieved.

Multimarker risk model containing troponin-T, interleukin 10, myeloperoxidase and placental growth factor predicts long-term cardiovascular risk after non-ST-segment elevation acute coronary syndrome.

OBJECTIVE: To evaluate the predictive value of seven biomarkers, which individually have been shown to be independent predictors, for use in a combined multimarker model for long-term cardiovascular outcome after non-ST-segment elevation acute coronary syndrome (NSTEACS). DESIGN AND SETTING: Levels of high-sensitivity C-reactive protein (hsCRP), myeloperoxidase, pregnancy-associated plasma protein A, placental growth factor (PlGF), soluble CD40 ligand (sCD40L), interleukin 10 (IL-10) and troponin-T (TnT) were determined in patients enrolled in the CAPTURE trial. Cox proportional hazard regression analyses were applied to evaluate the relation between biomarkers and the occurrence of all-cause mortality or non-fatal myocardial infarction (MI). PATIENTS: 1090 patients with NSTEACS. MAIN OUTCOME MEASURE: All-cause mortality and non-fatal MI during a median follow-up of 4 years. RESULTS: The composite endpoint was reached by 15.3% of patients. Admission levels of TnT >0.01 µg/l (adjusted HR 1.8), IL-10 <3.5 ng/l (1.7), myeloperoxidase >350 µg/l (1.5) and PlGF >27 ng/l (1.9) remained significant predictors for the incidence of all-cause mortality or non-fatal MI after multivariable adjustment for other biomarkers and clinical characteristics, whereas hsCRP, pregnancy-associated plasma protein A and sCD40L were only associated with the endpoint in univariate analysis. A multimarker model consisting of TnT, IL-10, myeloperoxidase and PlGF predicted 4-year event rates that varied between 6.0% (all markers normal) and 35.8% (three or more biomarkers abnormal). CONCLUSION: In patients with NSTEACS, biomarkers characterising distinct aspects of the underlying atherosclerotic process and myocardial damage of the initial cardiac event can assist in predicting long-term adverse cardiac outcomes. The use of combinations of selected biomarkers adds incremental predictive value to further risk stratification in an otherwise seemingly homogeneous NSTEACS population.

Effective continuous systemic therapy of severe plaque-type psoriasis is accompanied by amelioration of biomarkers of cardiovascular risk: results of a prospective longitudinal observational study.

BACKGROUND: Severe psoriasis is associated with significant cardiovascular mortality. OBJECTIVES: We investigated the effects of continuous systemic therapy on the cardiovascular risk of patients with severe plaque-type psoriasis. METHODS: A total of 42 consecutive patients receiving systemic treatment for their severe plaque-type psoriasis were included. The clinical course was monitored over 24 weeks. Initially as well as after 12 and 24 weeks, oral glucose tolerance tests were performed along with comprehensive laboratory monitoring. RESULTS: Responding patients, defined as a Psoriasis Area and Severity Index (PASI)-50 response, showed correlations between the PASI and high-sensitive C-reactive protein (r = 0.45, P = 0.03) as well as with vascular endothelial growth factor (r = 0.76, P = 0.007). The adipokine resistin was positively and the potentially cardio-protective adiponectin was negatively correlated with the PASI (r = 0.50, P = 0.02 and r = -0.56, P = 0.007, respectively). Oral glucose tolerance tests yielded a correlation between the PASI and plasma levels for C-peptide (r = 0.73, P = 0.02) at t = 120 min in patients with a pathological Homeostasis Model Assessment (>2.5), indicating that the state of peripheral insulin resistance is driven at least in part by the severity of the psoriatic inflammation. Correlations between the change of adipokine levels and change in PASI were more pronounced among patients with better clinical improvement (PASI-75 vs. PASI-50). CONCLUSIONS: We document an amelioration of biomarkers of cardiovascular risk in patients with severe plaque-type psoriasis responding to continuous systemic therapy. The impact on the patients'metabolic state was found to be better if the psoriatic inflammation was controlled for longer. Future studies need to compare the cardioprotective effects of different treatment modalities, based on hard clinical endpoints.

Influence of the angiotensin converting enzyme inhibitor ramipril on high-sensitivity C-reactive protein (hs-CRP) in patients with documented atherosclerosis.

UNLABELLED: Some medications have been shown to produce reductions in hs-CRP levels after initiating therapy. Whereas the role of the renin-angiotensin system in the inflammatory process has been documented in more detail during the last few years, the impact of an ACE-inhibitor therapy on this process has not been fully understood so far. The aim of this study was to investigate the effect of a therapy with the angiotensin-converting enzyme (ACE) inhibitor ramipril on hs-CRP plasma concentrations in patients with atherosclerosis. METHODS AND RESULTS: A total of 24 patients were enrolled in this prospective, uncontrolled, open-label multicenter study. Inclusion criteria were documented atherosclerosis, baseline high-sensitivity C-reactive protein between 3 and 12 mg/l, LDL-Cholesterol < or =150 mg/dl and no previous treatment with ACE inhibitors or angiotensin receptor blockers. Ten patients, pretreated with statins, and 10 patients not previously treated with statins were eligible for statistical analysis. Baseline high-sensitivity C-reactive protein was significantly decreased from 3.99+/-1.61 mg/l (mean+/-SD) to 2.72+/-1.19 mg/l (-32%) after 3 months treatment with 10 mg ramipril daily (p=0.0002). The decrease was more pronounced in patients who had not been treated with statins previously (-1.50 mg/l+/-1.44 mg/l) compared to those who were pretreated (-0.90 mg/l+/-0.93 mg/l). CONCLUSIONS: The ACE inhibitor ramipril administered in a daily dose of 10 mg to patients with atherosclerosis reduces the high-sensitivity C-reactive protein concentration. This effect may contribute to cardiovascular risk reduction mediated by ramipril aside from the blood pressure lowering effect.

[Resuscitation after prehospital cardiovascular arrest]. / Reanimation nach prähospitalem Herz-Kreislauf-Stillstand.

Initiation of effective cardiopulmonary resuscitation (CPR) at the earliest possible moment is the most important determinant of prognosis for prehospital cardiac arrest. The prognosis is essentially defined by two parameters: survival to hospital admission and survival to discharge. In connection with prehospital cardiac arrest, early defibrillation is particularly important, including the widespread availability of (semi)automatic defibrillators. Further aspects of CPR have recently received increased attention: on the one hand, changed study status regarding the use of antiarrhythmic agents (especially amiodarone), on the other hand, administration of vasopressin during resuscitation, and finally, the efficacy of mild hypothermia following prehospital cardiac arrest. These aspects represent the main subject of the present overview, which also addresses the latest revision of the International Liaison Committee on Resuscitation (ILCOR) guidelines on CPR that resulted in corresponding changes in the European Resuscitation Council (ERC) guidelines.

[Coronary stent implantation in elderly patients: acute and long-term results]. / Koronare Stentimplantation bei alten Patienten. Akutergebnisse und Langzeitverlauf.

UNLABELLED: The number of elderly patients with coronary heart disease is rapidly growing. Morbidity, related with PTCA is increased in elderly patients, presumably because of the more complex adverse baseline characteristics. However, it has not been firmly elucidated whether routine use of coronary stents is associated with a more favourable outcome in this population. Therefore, we investigated the influence of age on acute procedural success, rate of restenosis (quantitative coronary angiography) and major cardiovascular events (death/myocardial infarction [MI]) 6 months after intra-coronary stent implantation in 1306 patients. Patients were categorised into < 65 years (n = 709),65-75 years (n = 443) and >75 years (n= 154). RESULTS: Older patients had a higher amount of multivessel disease (p < 0.001) and a lower left ventricular ejection fraction (p < 0.001). Nevertheless, the rate of acute success and restenosis were comparable between the different age groups. In contrast, older patients had significantly more adverse clinical events during long-term followup. (Death/MI < 65 years 3.0%, 65-75 years 3.9%, > 75 years 7.8%, p = 0.02). However, by multivariate analysis age was no longer an independent predictor of adverse clinical events (p = 0.26), which were predominantly determined by coexisting impaired left ventricular function (p < 0.001). CONCLUSION: After proper judgement of the clinical situation, coronary stent implantation should be considered in selected elderly patients. Thus, advanced age as a solely factor should not be regarded as a contraindication for coronary stent implantation.

Statin therapy, inflammation and recurrent coronary events in patients following coronary stent implantation.

OBJECTIVES: We sought to investigate whether statin therapy affects the association between preprocedural C-reactive protein (CRP) levels and the risk for recurrent coronary events in patients undergoing coronary stent implantation. BACKGROUND: Low-grade inflammation as detected by elevated CRP levels predicts the risk of recurrent coronary events. The effect of inflammation on coronary risk may be attenuated by statin therapy. METHODS: We investigated a potential interrelation among statin therapy, serum evidence of inflammation, and the risk for recurrent coronary events in 388 consecutive patients undergoing coronary stent implantation. Patients were grouped according to the median CRP level (0.6 mg/dl) and to the presence of statin therapy. RESULTS: A primary combined end point event occurred significantly more frequently in patients with elevated CRP levels without statin therapy (RR [relative risk] 2.37, 95% CI [confidence interval] [1.3 to 4.2]). Importantly, in the presence of statin therapy, the RR for recurrent events was significantly reduced in the patients with elevated CRP levels (RR 1.27 [0.7 to 2.1]) to about the same degree as in patients with CRP levels below 0.6 mg/dl and who did not receive statin therapy (RR 1.1 [0.8 to 1.3]). CONCLUSIONS: Statin therapy significantly attenuates the increased risk for major adverse cardiac events in patients with elevated CRP levels undergoing coronary stent implantation, suggesting that statin therapy interferes with the detrimental effects of inflammation on accelerated atherosclerotic disease progression following coronary stenting.

Tumor necrosis factor antagonism with etanercept improves systemic endothelial vasoreactivity in patients with advanced heart failure.

BACKGROUND: Anti-tumor necrosis factor (TNF)-alpha therapy with etanercept, a recombinant TNF receptor that binds to and functionally inactivates TNF-alpha, was shown to improve the functional status of patients with congestive heart failure (CHF). Because administration of TNF-alpha has been shown experimentally to depress endothelium-dependent relaxation, we hypothesized that TNF-alpha antagonism with etanercept might improve the depressed systemic endothelial vasodilator function, which importantly contributes to increased peripheral vascular resistance in patients with advanced CHF. METHODS AND RESULTS: Endothelium-dependent (acetylcholine, ACH; 10 to 50 microgram/min) and endothelium-independent (sodium nitroprusside, SNP; 2 to 8 microgram/min) forearm blood flow (FBF) responses were measured by venous occlusion plethysmography in 13 patients with documented CHF (New York Heart Association class III) before, 6 hours after, and 7 days after subcutaneous injection of a single dose of 25 mg etanercept. Maximum ACH-induced FBF increased significantly from 6.9+/-1.0 to 13.0+/-1.6 mL/min per 100 mL of forearm tissue (P<0.05) 6 hours after administration of etanercept and returned to 7.0+/-1.1 mL/min per 100 mL of forearm tissue after 7 days (P=NS), whereas SNP-induced FBF responses were not significantly affected. In contrast, FBF responses were not altered in control CHF patients, who did not receive etanercept (n=5). Etanercept-induced increases in ACH-mediated FBF were closely correlated with baseline TNF-alpha serum levels (r=0.66; P<0.02). CONCLUSIONS: The administration of etanercept profoundly improves systemic endothelial vasodilator capacity in patients with advanced heart failure, suggesting an important role of inflammatory mediators for impaired endothelial vasoreactivity in CHF. Improvement of systemic endothelial function might importantly contribute to the beneficial effects of etanercept on the functional status of patients with CHF.

Preprocedural C-reactive protein levels and cardiovascular events after coronary stent implantation.

OBJECTIVES: This study assessed the predictive value of preprocedural C-reactive protein (CRP) levels on six-month clinical and angiographic outcome in patients undergoing coronary stent implantation. BACKGROUND: Recent data indicate that low-grade inflammation as detected by elevated CRP serum levels predicts the risk of recurrent coronary events. METHODS: We prospectively investigated the predictive value of preprocedural CRP-levels on restenosis and six-month clinical outcome in 276 patients after coronary stent implantation. The primary combined end point was death due to cardiac causes, myocardial infarction related to the target vessel and repeat intervention of the stented vessel. RESULTS: Grouping patients into tertiles according to preprocedural CRP-levels revealed that, despite identical angiographic and clinical characteristics at baseline and after stent implantation, a primary end point event occurred in 24 (26%) patients of the lowest tertile, in 42 (45.6%) of the middle tertile and in 38 (41.3%) of the highest CRP tertile, p = 0.01. On multivariate analysis, tertiles of CRP levels were independently associated with a higher risk of adverse coronary events (relative risk = 2.0 [1.1 to 3.5], tertile I vs. II and III, p = 0.01) in addition to the minimal lumen diameter after stent (p = 0.04). In addition, restenosis rates were significantly higher in the two upper tertiles compared with CRP levels in the lowest tertile (45.5% vs. 38.3% vs. 18.5%, respectively, p = 0.002). CONCLUSIONS: Low-grade inflammation as evidenced by elevated preprocedural serum CRP-levels is an independent predictor of adverse outcome after coronary stent implantation, suggesting that a systemically detectable inflammatory activity is associated with proliferative responses within successfully implanted stents.

HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway.

HMG-CoA reductase inhibitors (statins) have been developed as lipid-lowering drugs and are well established to reduce morbidity and mortality from coronary artery disease. Here we demonstrate that statins potently augment endothelial progenitor cell differentiation in mononuclear cells and CD34-positive hematopoietic stem cells isolated from peripheral blood. Moreover, treatment of mice with statins increased c-kit(+)/Sca-1(+)--positive hematopoietic stem cells in the bone marrow and further elevated the number of differentiated endothelial progenitor cells (EPCs). Statins induce EPC differentiation via the PI 3-kinase/Akt (PI3K/Akt) pathway as demonstrated by the inhibitory effect of pharmacological PI3K blockers or overexpression of a dominant negative Akt construct. Similarly, the potent angiogenic growth factor VEGF requires Akt to augment EPC numbers, suggesting an essential role for Akt in regulating hematopoietic progenitor cell differentiation. Given that statins are at least as potent as VEGF in increasing EPC differentiation, augmentation of circulating EPC might importantly contribute to the well-established beneficial effects of statins in patients with coronary artery disease.

Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease.

Recent studies provide increasing evidence that postnatal neovascularization involves bone marrow-derived circulating endothelial progenitor cells (EPCs). The regulation of EPCs in patients with coronary artery disease (CAD) is unclear at present. Therefore, we determined the number and functional activity of EPCs in 45 patients with CAD and 15 healthy volunteers. The numbers of isolated EPCs and circulating CD34/kinase insert domain receptor (KDR)-positive precursor cells were significantly reduced in patients with CAD by approximately 40% and 48%, respectively. To determine the influence of atherosclerotic risk factors, a risk factor score including age, sex, hypertension, diabetes, smoking, positive family history of CAD, and LDL cholesterol levels was used. The number of risk factors was significantly correlated with a reduction of EPC levels (R=-0.394, P=0.002) and CD34-/KDR-positive cells (R=-0.537, P<0.001). Analysis of the individual risk factors demonstrated that smokers had significantly reduced levels of EPCs (P<0.001) and CD34-/KDR-positive cells (P=0.003). Moreover, a positive family history of CAD was associated with reduced CD34-/KDR-positive cells (P=0.011). Most importantly, EPCs isolated from patients with CAD also revealed an impaired migratory response, which was inversely correlated with the number of risk factors (R=-0.484, P=0.002). By multivariate analysis, hypertension was identified as a major independent predictor for impaired EPC migration (P=0.043). The present study demonstrates that patients with CAD revealed reduced levels and functional impairment of EPCs, which correlated with risk factors for CAD. Given the important role of EPCs for neovascularization of ischemic tissue, the decrease of EPC numbers and activity may contribute to impaired vascularization in patients with CAD. The full text of this article is available at http://www.circresaha.org.