Survival and quality of life after early discharge in low-risk pulmonary embolism.

INTRODUCTION: Early discharge of patients with acute low-risk pulmonary embolism requires validation by prospective trials with clinical and quality-of-life outcomes. METHODS: The multinational Home Treatment of Patients with Low-Risk Pulmonary Embolism with the Oral Factor Xa Inhibitor Rivaroxaban (HoT-PE) single-arm management trial investigated early discharge followed by ambulatory treatment with rivaroxaban. The study was stopped for efficacy after the positive results of the predefined interim analysis at 50% of the planned population. The present analysis includes the entire trial population (576 patients). In addition to 3-month recurrence (primary outcome) and 1-year overall mortality, we analysed self-reported disease-specific (Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire) and generic (five-level five-dimension EuroQoL (EQ-5D-5L) scale) quality of life as well as treatment satisfaction (Anti-Clot Treatment Scale (ACTS)) after pulmonary embolism. RESULTS: The primary efficacy outcome occurred in three (0.5%, one-sided upper 95% CI 1.3%) patients. The 1-year mortality was 2.4%. The mean±sd PEmb-QoL decreased from 28.9±20.6% at 3 weeks to 19.9±15.4% at 3 months, a mean change (improvement) of -9.1% (p<0.0001). Improvement was consistent across all PEmb-QoL dimensions. The EQ-5D-5L was 0.89±0.12 at 3 weeks after enrolment and improved to 0.91±0.12 at 3 months (p<0.0001). Female sex and cardiopulmonary disease were associated with poorer disease-specific and generic quality of life; older age was associated with faster worsening of generic quality of life. The ACTS burden score improved from 40.5±6.6 points at 3 weeks to 42.5±5.9 points at 3 months (p<0.0001). CONCLUSIONS: Our results further support early discharge and ambulatory oral anticoagulation for selected patients with low-risk pulmonary embolism. Targeted strategies may be necessary to further improve quality of life in specific patient subgroups.

Early discharge and home treatment of patients with low-risk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban: an international multicentre single-arm clinical trial.

AIMS: To investigate the efficacy and safety of early transition from hospital to ambulatory treatment in low-risk acute PE, using the oral factor Xa inhibitor rivaroxaban. METHODS AND RESULTS: We conducted a prospective multicentre single-arm investigator initiated and academically sponsored management trial in patients with acute low-risk PE (EudraCT Identifier 2013-001657-28). Eligibility criteria included absence of (i) haemodynamic instability, (ii) right ventricular dysfunction or intracardiac thrombi, and (iii) serious comorbidities. Up to two nights of hospital stay were permitted. Rivaroxaban was given at the approved dose for PE for ≥3 months. The primary outcome was symptomatic recurrent venous thromboembolism (VTE) or PE-related death within 3 months of enrolment. An interim analysis was planned after the first 525 patients, with prespecified early termination of the study if the null hypothesis could be rejected at the level of α = 0.004 (<6 primary outcome events). From May 2014 through June 2018, consecutive patients were enrolled in seven countries. Of the 525 patients included in the interim analysis, three (0.6%; one-sided upper 99.6% confidence interval 2.1%) suffered symptomatic non-fatal VTE recurrence, a number sufficiently low to fulfil the condition for early termination of the trial. Major bleeding occurred in 6 (1.2%) of the 519 patients comprising the safety population. There were two cancer-related deaths (0.4%). CONCLUSION: Early discharge and home treatment with rivaroxaban is effective and safe in carefully selected patients with acute low-risk PE. The results of the present trial support the selection of appropriate patients for ambulatory treatment of PE.

Gender-specific diagnostic performance of a new high-sensitivity cardiac troponin I assay for detection of acute myocardial infarction.

BACKGROUND: The determination of cardiac troponin is essential for diagnosing myocardial infarction. A troponin I assay has recently been developed that provides the highest analytical sensitivity to date. METHODS: The analysis included 1560 patients with chest pain, of whom 1098 were diagnosed with non-coronary chest pain, 189 with unstable angina pectoris and 273 with non-ST-segment elevation myocardial infarction. The troponin I concentration was determined on admission (0 hours) and 3 hours later. The diagnostic algorithm incorporated troponin I elevation above the gender-specific 99th percentile as well as predefined relative or absolute 3-hour changes in the troponin I concentration (delta). RESULTS: The diagnostic criterion of troponin I above the 99th percentile resulted in a negative predictive value of 98.0% and 98.2% in men and women, respectively. For rule-in of non-ST-segment elevation myocardial infarction, the use of absolute deltas yielded higher positive predictive values and sensitivities compared to relative deltas. With detection rates of about 85% and 82% in men and women, respectively, non-ST-segment elevation myocardial infarction was diagnosed with a positive predictive value close to 84% in men and 80% in women. CONCLUSIONS: The investigational troponin I assay provides an excellent non-ST-segment elevation myocardial infarction rule out. With gender-specific differences, the application of absolute changes in troponin concentration was superior to relative changes to rule in patients with non-ST-segment elevation myocardial infarction.

Lipopolysaccharide responsiveness is an independent predictor of death in patients with chronic heart failure.

BACKGROUND: The origin of pro-inflammatory activation in chronic heart failure (HF) remains a matter of debate. Lipopolysaccharide (LPS) may enter the blood stream through the morphologically altered and leaky gut barrier. We hypothesized that lower LPS reactivity would be associated with worse survival as compared to normal or higher LPS reactivity. METHODS: LPS responsiveness was studied in 122 patients with chronic HF (mean±SD: age 67.3±10.3 years, 24 female, New York Heart Association class [NYHA] class: 2.5±0.8, left ventricular ejection fraction [LVEF]: 33.5±12.5%) and 27 control subjects of similar age (63.7±7.7 years, p>0.05). Reference LPS was added at increasing doses to ex vivo whole blood samples and necrosis factor-α (TNFα) was measured. Patients were subgrouped into good- and poor-responder status according to their potential to react to increasing doses of LPS (delta TNFα secretion). The optimal cut-off value was calculated by receiver-operator characteristic curve (ROC) analysis. RESULTS: A total of 56 patients with chronic HF died from any cause during follow-up. At 24 months, cumulative mortality was 16.4% (95% confidence interval 16.0-16.7%). The delta TNFα value representing the optimal cut-off for the prediction of mortality was 1522 pg/mL (24 months) with a sensitivity of 49.3% (95% confidence interval 37.2-61.4%) and specificity of 81.5% (95% confidence interval 61.9-93.6%). LPS responder status remained an independent predictor of death after multivariable adjustment (hazard ratio 0.09 for good- vs. poor-responders, 95% confidence interval 0.01-0.67, p<0.05). CONCLUSIONS: LPS responsiveness in patients with chronic HF is an independent predictor of death.

Prognostic information of glycogen phosphorylase isoenzyme BB in patients with suspected acute coronary syndrome.

Early and adequate risk stratification is essential in patients with suspected acute coronary syndrome (ACS). The aim of the present study was to investigate whether glycogen phosphorylase BB (GPBB) could add prognostic information in the context of contemporary sensitive troponin I determination and B-type natriuretic peptide (BNP). Patients with suspected ACS were consecutively enrolled at 3 German study centers from January 2007 through December 2008. Troponin I, GPBB, and BNP were determined at admission. Follow-up information on the combined end point of death, myocardial infarction, revascularization, and hospitalization owing to a cardiovascular cause was obtained 6 months after enrollment. In total 1,818 patients (66% men) were enrolled of whom 413 (23%) were diagnosed as having acute myocardial infarction and 240 (13%) as having unstable angina pectoris, whereas in 1,165 patients (64%) an ACS could be excluded. Follow-up information was available in 98% of patients; 203 events were registered. GPBB measured on admission predicted an unfavorable outcome with a hazard ratio of 1.24 (p <0.05) in an unadjusted Cox regression model and showed a tendency with a hazard ratio of 1.13 (p = 0.07) in a fully adjusted model. Kaplan-Meier analysis revealed a poorer outcome in patients with increased GPBB levels amendatory to the information provided by troponin I or BNP. In conclusion, GPBB measurement provides predictive information on midterm prognosis in patients with chest pain in addition to BNP and troponin I.

Serial changes in highly sensitive troponin I assay and early diagnosis of myocardial infarction.

CONTEXT: Introduction of highly sensitive troponin assays into clinical practice has substantially improved the evaluation of patients with chest pain. OBJECTIVE: To evaluate the diagnostic performance of a highly sensitive troponin I (hsTnI) assay compared with a contemporary troponin I (cTnI) assay and their serial changes in the diagnosis of acute myocardial infarction (AMI). DESIGN, SETTING, AND PATIENTS: A total of 1818 patients with suspected acute coronary syndrome were consecutively enrolled at the chest pain units of the University Heart Center Hamburg, the University Medical Center Mainz, and the Federal Armed Forces Hospital Koblenz, all in Germany, from 2007 to 2008. Twelve biomarkers including hsTnI (level of detection, 3.4 pg/mL) and cTnI (level of detection, 10 pg/mL) were measured on admission and after 3 and 6 hours. MAIN OUTCOME MEASURES: Diagnostic performance for AMI of baseline and serial changes in hsTnI and cTnI results at 3 hours after admission to the emergency department. RESULTS: Of the 1818 patients, 413 (22.7%) were diagnosed as having AMI. For discrimination of AMI, the area under the receiver operating characteristic (ROC) curve was 0.96 (95% CI, 0.95-0.97) for hsTnI on admission and 0.92 (95% CI, 0.90-0.94) for cTnI on admission. Both were superior to the other evaluated diagnostic biomarkers. The use of hsTnI at admission (with the diagnostic cutoff value at the 99th percentile of 30 pg/mL) had a sensitivity of 82.3% and a negative predictive value (for ruling out AMI) of 94.7%. The use of cTnI (with the diagnostic cutoff value at the 99th percentile of 32 pg/mL) at admission had a sensitivity of 79.4% and a negative predictive value of 94.0%. Using levels obtained at 3 hours after admission, the sensitivity was 98.2% and the negative predictive value was 99.4% for both hsTnI and cTnI assays. Combining the 99th percentile cutoff at admission with the serial change in troponin concentration within 3 hours, the positive predictive value (for ruling in AMI) for hsTnI increased from 75.1% at admission to 95.8% after 3 hours, and for cTnI increased from 80.9% at admission to 96.1% after 3 hours. CONCLUSIONS: Among patients with suspected acute coronary syndrome, hsTnI or cTnI determination 3 hours after admission may facilitate early rule-out of AMI. A serial change in hsTnI or cTnI levels from admission (using the 99th percentile diagnostic cutoff value) to 3 hours after admission may facilitate an early diagnosis of AMI.

Copeptin improves early diagnosis of acute myocardial infarction.

OBJECTIVES: Early identification of myocardial infarction in chest pain patients is crucial to identify patients at risk and to maintain a fast treatment initiation. BACKGROUND: The aim of the current investigation is to test whether determination of copeptin, an indirect marker for arginin-vasopressin, adds diagnostic information to cardiac troponin in early evaluation of patients with suspected myocardial infarction. METHODS: Between January 2007 and July 2008, patients with suspected acute coronary syndrome were consecutively enrolled in this multicenter study. Copeptin, troponin T (TnT), myoglobin, and creatine kinase-myocardial band were determined at admission and after 3 and 6 h. RESULTS: Of 1,386 (66.4% male) enrolled patients, 299 (21.6%) had the discharge diagnosis of acute myocardial infarction, 184 (13.3%) presented with unstable angina, and in 903 (65.2%) an acute coronary syndrome could be excluded. Combined measurement of copeptin and TnT on admission improved the c-statistic from 0.84 for TnT alone to 0.93 in the overall population and from 0.77 to 0.9 in patients presenting within 3 h after chest pain onset (CPO) (p < 0.001). In this group the combination of copeptin with a conventional TnT provided a negative predictive value of 92.4%. CONCLUSIONS: In triage of chest pain patients, determination of copeptin in addition to troponin improves diagnostic performance, especially early after CPO. Combined determination of troponin and copeptin provides a remarkable negative predictive value virtually independent of CPO time and therefore aids in early and safe rule-out of myocardial infarction.

Thrombosis, fracture, and percutaneous removal of a patent foramen ovale closure device 1 month after successful deployment.

Several different devices have been developed for the percutaneous closure of interatrial defects and patent foramen ovale. Although the implantation of these devices is both safe and effective, a number of complications, both in the early and the late follow-up, may occur. We describe a case of device fracture manifested early (1 month after implantation) with the formation of massive thrombosis on the right atrial disc. The patient was treated with anticoagulants and the device was percutaneously retrieved. Our images allowed early noninvasive therapy and emphasize the need for echocardiographic follow-up early after implantation.

Improved outcome in acute coronary syndrome by establishing a chest pain unit.

AIMS: Chest pain units (CPUs) have been established to optimize treatment of patients with acute coronary syndrome (ACS) and to early and accurately discharge patients with non-coronary chest pain. The aim of this analysis was to elucidate whether treatment of ACS patients in the CPU versus emergency department (ED) has prognostic implications. METHODS AND RESULTS: Patients presenting with suspected ACS to either the ED between August 2004 and June 2005 or the CPU between July 2005 and May 2006 were retrospectively analyzed. Of 1,796 included patients, 483 had the discharge diagnosis ACS. When compared to patients with exclusion of ACS they had more cardiovascular risk factors and higher troponin, creatinine and C-reactive protein levels (P < 0.001) at admission. Within 1 year, 37 patients of the ACS group suffered an event. Treatment in the ED compared with the CPU showed a significant increase in hazard ratio of 2.1 (P = 0.034) for the combined endpoint death, myocardial infarction and stroke, remaining unchanged after adjusting for confounders. Event-free 1-year survival was higher in CPU patients for the combined endpoint (P (logrank) = 0.02). CONCLUSION: These results demonstrate a better 1-year prognosis for ACS patients treated in the CPU instead of the ED, therefore, supporting the idea to establish CPUs in Europe.

Inflammation in right ventricular dysfunction due to thromboembolic pulmonary hypertension.

OBJECTIVES AND BACKGROUND: Activation of the immune system is well established in patients with chronic heart failure (CHF) and impaired left ventricular function. High levels of pro-inflammatory cytokines are associated with a poor prognosis. Chronic thromboembolic pulmonary hypertension (CTEPH) frequently leads to impaired right ventricular function. It is not known whether such patients display chronic immune activation as well. METHODS AND RESULTS: We studied 49 patients with CTEPH (50±2 years, right ventricular ejection fraction [RVEF] 29±2%, left ventricular ejection fraction [LVEF] 51±3%, mean±SEM) and compared their results with 17 patients with CHF (71±2 years, LVEF 23±1%) and 34 age-matched control subjects (age 57±2 years). We studied serum levels of tumor necrosis factor-α (TNFα), its soluble receptors 1 and 2 (sTNFR1 and 2), interleukin-10 (IL-10) and plasma N-terminal-pro-B-type natriuretic peptide (NT-proBNP). Serum TNFα was not different in CTEPH compared with CHF patients (p=0.67) but both their levels were significantly higher than in controls (both p<0.001). Similar results were obtained for sTNFR1, sTNFR2, and IL-10. Levels of NT-proBNP were not different in patients with CTEPH or CHF (p=0.54), but significantly higher than in control subjects (both p<0.001). There were significant correlations between RVEF as assessed by magnetic resonance imaging and sTNFR1, sTNFR2, IL-6, high sensitivity C-reactive protein, and NT-proBNP (all p<0.05) in patients with CTEPH. CONCLUSION: Similar levels of immune activation as reflected by high levels of pro-inflammatory cytokines are present in patients with isolated right ventricular dysfunction due to CTEPH and patients with CHF and left ventricular dysfunction.

Sensitive troponin I assay in early diagnosis of acute myocardial infarction.

BACKGROUND: Cardiac troponin testing is central to the diagnosis of acute myocardial infarction. We evaluated a sensitive troponin I assay for the early diagnosis and risk stratification of myocardial infarction. METHODS: In a multicenter study, we determined levels of troponin I as assessed by a sensitive assay, troponin T, and traditional myocardial necrosis markers in 1818 consecutive patients with suspected acute myocardial infarction, on admission and 3 hours and 6 hours after admission. RESULTS: For samples obtained on admission, the diagnostic accuracy was highest with the sensitive troponin I assay (area under the receiver-operating-characteristic curve [AUC], 0.96), as compared with the troponin T assay (AUC, 0.85) and traditional myocardial necrosis markers. With the use of the sensitive troponin I assay (cutoff value, 0.04 ng per milliliter) on admission, the clinical sensitivity was 90.7%, and the specificity was 90.2%. The diagnostic accuracy was virtually identical in baseline and serial samples, regardless of the time of chest-pain onset. In patients presenting within 3 hours after chest-pain onset, a single sensitive troponin I assay had a negative predictive value of 84.1% and a positive predictive value of 86.7%; these findings predicted a 30% rise in the troponin I level within 6 hours. A troponin I level of more than 0.04 ng per milliliter was independently associated with an increased risk of an adverse outcome at 30 days (hazard ratio, 1.96; 95% confidence interval, 1.27 to 3.05; P=0.003). CONCLUSIONS: The use of a sensitive assay for troponin I improves early diagnosis of acute myocardial infarction and risk stratification, regardless of the time of chest-pain onset.

Leukocyte redistribution: effects of beta blockers in patients with chronic heart failure.

BACKGROUND: Overproduction of pro-inflammatory cytokines is a well established factor in the progression of chronic heart failure (CHF). Changes in cellular immunity have not been widely studied, and the impact of standard medication is uncertain. Here we investigate whether a leukocyte redistribution occurs in CHF and whether this effect is influenced by beta-blocker therapy. METHODOLOGY: We prospectively studied 75 patients with systolic CHF (age: 68+/-11 years, left ventricular ejection fraction 32+/-11%, New York Heart Association class 2.5+/-0.7) and 20 age-matched healthy control subjects (age: 63+/-10 years). We measured the response of cells to endotoxin exposure in vitro, analysed subsets of lymphocytes using flow cytometry, and assessed plasma levels of the pro-inflammatory markers interleukin 1, 6, tumor necrosis factor-alpha, and soluble tumor necrosis factor receptors 1 and 2. PRINCIPAL FINDINGS: While no differences in the number of leukocytes were noted between patients with CHF and healthy controls, we detected relative lymphopenia in patients with CHF (p<0.001 vs. control), mostly driven by reductions in T helper cells and B cells (both p<0.05). The number of neutrophils was increased (p<0.01). These effects were pronounced in patients who were beta-blocker naïve (32% of all patients with CHF). Increased plasma levels of soluble tumor necrosis receptor-1 correlated with the relative number of lymphocyte subsets. CONCLUSIONS: In patients with CHF, we detected a redistribution of leukocyte subsets, i.e. an increase in neutrophils with relative lymphopenia. These effects were pronounced in patients who were beta-blocker naïve. The underlying mechanism remains to be elucidated.

Elevated TNFalpha production in whole blood in patients with severe COPD: the potential link to disease severity.

OBJECTIVE: The relationship between tumour necrosis factor-alpha (TNFalpha), severity of pulmonary disease and nutritional depletion in chronic obstructive pulmonary disease (COPD) remains unclear. We aimed to clarify the role of lipopolysaccharide (LPS) as a potential stimulus of cytokine production and the role of these cytokines in the alteration of body composition in patients with different degrees of COPD. PATIENTS AND METHODS: We studied 29 weight-stable out-patients with different severites of COPD who had no evidence of recent infection or significant co-morbidity. Baseline serum TNFalpha levels and TNFalpha response to LPS in whole blood were measured in patients and 20 aged matched controls. RESULTS: Serum TNFalpha was significantly elevated in patients versus controls (2.1 +/- 0.3 vs. 1.1 +/- 0.1 pg/ml, mean +/- SEM, P = 0.007). In patients with COPD, we found a significant correlation between serum TNFalpha levels and disease severity, assessed as FEV(1) %predicted (r = 0.49, P = 0.02). Response to lipopolysaccharide did not differ significantly between patients and controls. However, within the patient group those with more severe disease (FEV(1) < or = 30% predicted, n = 12) had an enhanced response compared to patients with mild-to-moderate disease (all P < 0.05 for LPS > 1 ng/ml). Spontaneous TNFalpha production was 5.0 times higher in patients with severe COPD compared to mild-to-moderate COPD (P = 0.02). There was no relation between body composition and serum TNFalpha or TNFalpha response to LPS. CONCLUSION: Increasing airflow obstruction and hypercapnia are associated with an enhanced TNFalpha response in COPD.

Association between chronic dental infection and acute myocardial infarction.

INTRODUCTION: In patients with cardiovascular diseases several risk factors such as high blood pressure, diabetes, smoking and drinking habits, genetic disposition, and chronic inflammation must be considered. The aim of this study was to investigate whether there is a correlation between dental origin infections and the presence of an acute myocardial infarction (AMI). METHODS: A total of 125 patients who had experienced a myocardial infarction and 125 healthy individuals were included in this study. The oral examination was carried out following the consent of the ethics committee and the National Board for Radiation Protection and included the number of teeth, endodontically treated teeth, periodontal screening index (PSI), clinical attachment level, and radiographic apical lesions (radiograph examination). The medical examination included, among others, blood glucose level, C-reactive protein (CRP) serum levels, and leukocyte number. RESULTS: The study demonstrated that patients with AMI exhibited an unfavorable dental state of health. After statistical adjustment for age, gender, and smoking, they exhibited a significantly higher number of missing teeth (P = .001), less teeth with root canal fillings (P = .0015), a higher number of radiologic apical lesions (P = .001), and a higher PSI value (P = .001) compared with individuals without myocardial infarction. The medical data showed a nonsignificant correlation between CRP and the number of radiologic apical lesions. CONCLUSIONS: This study presents evidence that patients who have experienced myocardial infarction also exhibit an unfavorable dental state of health in comparison to healthy patients and suggests an association between chronic oral infections and myocardial infarction.

Impact of inflammatory markers on cardiovascular mortality in patients with metabolic syndrome.

BACKGROUND: Recent investigations suggest the inclusion of inflammatory markers in the definition of the metabolic syndrome (MS). The aim of this study was to address the role of C-reactive protein, fibrinogen, interleukin-6 (IL-6) and IL-18 (IL-18) on cardiovascular prognosis in accordance to MS. METHODS: A total of 1263 patients with documented coronary artery disease were prospectively included. We defined MS (MS yes: N=533, 42.2%) as the presence of at least three of the following criteria: triglycerides>or=150 mg/dl; low high-density lipoprotein cholesterol (men: <40 mg/dl women: <50 mg/dl); body mass index greater than 30 kg/m; blood pressure>or=130/85 mmHg; fasting glucose>or=100 mg/dl. In addition, we determined C-reactive protein, fibrinogen, IL-6 and IL-18 levels. RESULTS: Follow-up data (median 6.1 years) were available for 1257 patients (99.5%). 139 patients (11.1%) died from cardiovascular causes. Cardiovascular mortality was related to MS (MS yes: 15.1% versus MS no: 8.1%, P<0.0001) and was further increased by elevation of each inflammatory marker. To address whether elevation of inflammatory markers provides additional prognostic information, a subgroup analysis was performed including patients with MS. In a multivariate-adjusted model including all four inflammatory markers, only IL-18 could be identified as an independent predictor of cardiovascular mortality. CONCLUSION: The measurement of inflammatory markers, especially IL-18, adds important prognostic information with regard to the long-term prognosis of patients with MS.

Association of adiponectin with adverse outcome in coronary artery disease patients: results from the AtheroGene study.

AIMS: In primary prevention, the adipocytokine adiponectin seems to be protective against diabetes mellitus and cardiovascular disease. Data in patients with manifest coronary artery disease (CAD) are scant stimulating the investigation of the association of adiponectin concentrations and cardiovascular outcome in a prospective CAD cohort. METHODS AND RESULTS: In 1890 consecutive patients with documented CAD [1130 with stable angina (SAP) and 760 with acute coronary syndrome (ACS)] baseline concentrations of adiponectin were measured by enzyme-linked immuno assay. During a median follow-up of 2.5 years cardiovascular events were registered (cardiovascular deaths 70; non-fatal myocardial infarction 46). Baseline adiponectin concentrations were similar in patients presenting with SAP [9.03 microg/mL (6.7, 13.45)] or ACS [9.19 microg/mL (6.72, 13.15)], P = 0.779. Kaplan-Meier survival analysis showed a stepwise decrease in event-free survival across quartiles of adiponectin baseline concentration (P log rank = 0.0188). A similar pattern was observed in both subgroups of patients (SAP P = 0.075 and ACS P = 0.254). In univariate analyses, continuous adiponectin concentration was related to event-free survival in all patients [HR 1.02 (95% confidence interval 1.0-1.04), P = 0.012] as well as in the subgroup of SAP subjects [1.03 (1.01-1.05), P = 0.012]. The relation was less strong in the subgroup presenting with ACS [1.014 (0.99-1.04), P = 0.280]. A correlation of adiponectin with high density cholesterol (r = 0.39) and a negative relation to triglyceride levels (r = -0.22) could be described. An increase of one interquartile distance in adiponectin concentration was associated with a 1.17-fold risk for future cardiovascular events (P = 0.013), in B-type natriuretic peptide (BNP) it meant a 1.13-fold risk (P < 0.001). In the overall patient group, this risk association remained robust after the adjustment for classical risk factors, clinical presentation and cardiac medication. Only after adjustment for BNP adiponectin lost its independent predictive value. CONCLUSION: In contrast to studies including initially healthy individuals, the current prospective study demonstrates that adiponectin is associated with adverse cardiovascular outcome in patients with manifest CAD.

Inflammatory pathways in patients with heart failure and preserved ejection fraction.

UNLABELLED: Immune activation is well established in patients with chronic heart failure and reduced ejection fraction (HF and reduced EF) and is associated with an impaired prognosis. Patients with heart failure and preserved ejection fraction (HF and preserved EF) have an impaired prognosis as well. It is not known whether they have signs of immune activation. METHODS: We studied patients with HF and preserved EF (n=17, NYHA II [n=7]/III [n=10]) and patients with HF and reduced EF (n=17 NYHA II [n=1]/III [n=16]) and 20 controls. Echocardiography demonstrated preserved ejection fraction (LVEF 59+/-9%), but LV hypertrophy in patients with preserved EF as compared with patients with reduced EF (LVEF 23+/-5%). We evaluated levels of TNFalpha, its receptors (sTNFR-1 and 2), IL-6, IL-10 and NT-proBNP. RESULTS: TNFalpha, was highest in HF with reduced EF (2.87+/-0.65 vs 1.67+/-0.58 pg/mL, p<0.001) compared to preserved EF and similar between HF with preserved EF and controls. However, sTNFR1 (1618+/-384 vs 1017+/-302 pg/mL, p<0.001) and sTNFR2 levels (3554+/-916 vs 2041+/-586 pg/mL, p<0.001) in HF with preserved EF were significantly higher compared with controls. The same was true for IL-6, IL-10 and NT-proBNP. The highest cytokine and NT-proBNP levels were present in HF with reduced EF. There was a negative correlation between TNFalpha, and LVEF (r=- 0.700; p<0.0001) and positive correlations between sTNFR1 and 2 with NT-proBNP. CONCLUSION: Patients with HF and preserved EF already show signs of systemic-immune activation which may contribute to the impaired prognosis and the progression to HF with reduced EF.

Impact of metabolic syndrome on atherosclerotic burden and cardiovascular prognosis.

Patients with metabolic syndrome (MS) are at increased risk of cardiovascular atherosclerosis. The aim of this study was to evaluate the impact of MS on cardiovascular prognosis in context with atherosclerotic burden. A total of 811 patients with coronary heart disease (CHD) were included and carotid and leg arteries were examined using sonographic methods. Patients with low (CHD only, n = 428, 52.8%) or high atherosclerotic burden (CHD and peripheral atherosclerosis, n=383, 47.2%) were compared. Patients with >or=3 of the following criteria: triglycerides>or=150 mg/dl, high-density lipoprotein cholesterol<40 mg/dl (men) and <50 mg/dl (women), body mass index>30 kg/m2, blood pressure>or=130/85 mm Hg, and fasting glucose>or=100 mg/dl were defined as having MS (n=349, 43.0%). Follow-up data (median 6.7 years) were available for 807 patients (99.5%), and 175 patients (21.7%) experienced cardiovascular events (myocardial infarction, death, and stroke). The presence of MS significantly increased cardiovascular events in patients with low and high atherosclerotic burden (low: MS yes 21.2%, MS no 12.9%, p=0.02; high: MS yes 34.3%, MS no 26.5%, p=0.01). MS could be identified as an independent predictor for cardiovascular events in all patients (hazard ratio 1.7, 95% confidence interval 1.3 to 2.3, p<0.0001, adjusted) and patients with high atherosclerotic burden in particular (hazard ratio 1.8, 95% confidence interval 1.2 to 2.6, p=0.005, adjusted). In conclusion, MS markedly worsens the long-term prognosis of patients with both low and high atherosclerotic burden. Moreover, patients with high atherosclerotic burden and MS should be considered a high-risk population and treated accordingly.

Glutathione peroxidase-1 activity, atherosclerotic burden, and cardiovascular prognosis.

Recent findings suggest that erythrocyte intracellular glutathione peroxidase-1 (GPX-1) activity is related inversely to future cardiovascular events. The aim of this study is to evaluate the association of GPX-1 activity to extent of atherosclerosis, as well as its long-term prognosis in context with atherosclerotic burden. In a prospective study, we included 508 patients before coronary angiography. Atherosclerosis of carotid and leg arteries was documented using sonographic methods. Blood samples were drawn after an overnight fasting period, and GPX-1 activity was determined in washed erythrocytes. GPX-1 activity tended to decrease with increasing numbers of atherosclerotic vascular beds, so that patients without clinically relevant atherosclerosis had GPX-1 activity of 49.3 U/g hemoglobin compared with 46.0 U/g hemoglobin in patients with prevalent atherosclerosis in all 3 vascular beds (p = NS). Follow-up data (median 6.5 years) were available for 504 patients (99.2%), and 96 patients (19.0%) experienced cardiovascular events (cardiovascular death, infarction, and stroke). The event rate was inversely associated with level of GPX-1 activity divided into tertiles (hazard ratio 2.3, 95% confidence interval 1.4 to 4.0 for lowest vs highest tertile of GPX-1 activity, p = 0.002, adjusted). The highest event rate was found in persons with low GPX-1 activity and multivascular atherosclerosis (event rate 36.9%, p <0.0001). In conclusion, decreased red blood cell GPX-1 activity is associated with increased cardiovascular risk according to the extent of atherosclerosis.