Midregional pro-A-type natriuretic peptide as part of a dual biomarker strategy for the early rule out of non-ST segment elevation acute coronary syndrome - The WilCop study.

BACKGROUND: Mr-proANP is a biomarker produced in atrial and left ventricular myocardium. We investigated the effect of combined measurement of mr-proANP and high-sensitive cardiac Troponin I assay of the penultimate generation (s-cTnI) for an early type-1 and type-2 NSTE-ACS rule-out with emphasis on the very early presenters' subgroup with symptom onset time (SOT) ≤ 2 h. METHODS: This was a prospective cohort study of 311 consecutive patients admitted to ER with symptoms suggestive of an acute coronary syndrome (ACS). All patients had baseline mr-proANP and s-cTnI measurements. RESULTS: Of the total cohort, 17.6% (n = 55) had final diagnosis of NSTE-ACS: 9.6% (n = 30) had an angiographically-confirmed type-1 infarction and 8.0% (n = 25) had type-2 infarction. In the subgroup of very early presenters (SOT ≤ 2 h) the negative predictive value (NPV) of s-cTnI for type-1 NSTE-ACS was 96.7% (95%-CI: 87.5-99.4) and the NPV of mr-proANP was 100% (95%-CI: 87.1-100). The dual biomarker strategy yielded an NPV of 100% (95%-CI: 86.7-100). In the same time-related subgroup, the NPV of s-cTnI alone for type-2 was 98.3% (95%-CI: 89.8-99.9) and the NPV of mr-proANP was 97.0% (95%-CI: 82.5-100). The combination of biomarker increased the NPV to 100% (95%-CI: 86.7-100). CONCLUSIONS: Our study demonstrated an immediate release pattern of mr-proANP in NSTE-ACS that may bridge the silent troponin time phenomenon when highest-sensitivity cardiac troponin assays are not used. This concept performed best in the very early presenters' subgroup with an excellent NPV of 100% and might result in an early rule-out of NSTE-ACS thus accelerating the diagnostic work-up.

Usefulness of Elevated Levels of Growth Differentiation Factor-15 to Classify Patients With Acute Coronary Syndrome Having Percutaneous Coronary Intervention Who Would Benefit from High-Dose Statin Therapy.

The aim of this study was to evaluate whether growth differentiation factor-15 (GDF-15) plasma concentration at the time of percutaneous coronary intervention (PCI) might help identify those patients with acute coronary syndrome (ACS), who benefit most from high-dose statin treatment. Two hundred eighty-four consecutive patients, who underwent percutaneous coronary intervention (PCI) for ACS, were included in a prospective registry. The combined end point at 3 months after PCI consisted of cardiovascular death, nonfatal myocardial infarction, and unstable angina. Patients were divided into those with elevated levels of GDF-15 and those with lower levels in relation to the median plasma concentration. Results were compared between patients receiving high-dose, highly efficient statins and patients receiving low-dose statins or no statins. The median GDF-15 plasma concentration was 3.31 ng/ml. One hundred six patients (74.6%) of the high GDF-15 group and 122 patients (85.9%) of the low GDF-15 group received high-dose statins. The combined end point was statistically lower in patients with high levels of GDF-15 treated with high-dose statins compared with patients treated with low-dose statins or without statin treatment (3.8% vs 22.2%, hazard ratio [HR] = 0.156; 95% confidence interval [CI], 0.047 to 0.519; p = 0.002). After propensity score adjustment, the results remained significant (adjusted HR for high-dose statins = 0.148; 95% CI, 0.045 to 0.494; p = 0.002). In contrast, in patients with lower levels of GDF-15, there was no significant reduction in combined end point rates associated with high-dose statin treatment (1.6% vs 5.0%, HR = 0.320; 95% CI 0.029 to 3.534; p = 0.353). In conclusion, increased GDF-15 plasma concentrations at the time of PCI and stent implantation might classify high-risk patients with ACS who benefit from high-dose, highly efficient statins.

Fasting glucose, NT-proBNP, treatment with eptifibatide, and outcomes in non-ST-segment elevation acute coronary syndromes: An analysis from EARLY ACS.

BACKGROUND: Higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels have been linked to a more favorable glucometabolic profile. Little is known about the interaction of NT-proBNP and fasting glucose in non-ST-segment elevation acute coronary syndrome (NSTE ACS). METHODS: Fasting glucose and NT-proBNP were measured in 2240 patients enrolled in the EARLY ACS trial. Multivariable Cox models were used to assess associations between fasting glucose and NT-proBNP and a 96-hour composite of death, myocardial infarction (MI), recurrent ischemia, or thrombotic bailout; 30-day death or MI; and 1-year mortality. RESULTS: In adjusted Cox models, neither NT-proBNP nor fasting glucose was associated with the 96-hour endpoint (p=0.95 and p=0.87). NT-proBNP was associated with 30-day death or MI (hazard ratio [HR] 1.11, 95% confidence interval [CI] 1.02-1.22, p=0.02) and 1-year mortality (HR 1.63, 95% CI 1.42-1.89, p<0.0001), but fasting glucose was associated only with 1-year death (HR 1.53, 95% CI 1.08-2.16, p=0.02). NT-proBNP×glucose interaction terms were non-significant in all models. As fasting glucose levels increased, the risk of 96-hour and 30-day endpoints increased among patients who received early eptifibatide but not delayed, provisional use (pint=0.035 and pint=0.029). Higher NT-proBNP levels were associated with greater 30-day death or MI among patients who received early eptifibatide but not delayed, provisional use (pint=0.045). CONCLUSION: NT-proBNP and fasting glucose concentrations were associated with intermediate-term ischemic outcomes and may identify differential response to treatment with eptifibatide. CLINICALTRIALS. GOV IDENTIFIER: NCT00089895.

Activated protein C levels and outcome in patients with cardiogenic shock complicating acute myocardial infarction.

INTRODUCTION: In patients with severe sepsis, low levels of activated protein C are associated with high morbidity and mortality. In an observational study we investigated whether patients with cardiogenic shock have decreased circulatory levels of activated protein C, and if these are associated with increased mortality. METHODS: We measured serum activated protein C and interleukin-6 levels in 43 patients with cardiogenic shock following acute myocardial infarction and in 15 control patients with uncomplicated myocardial infarction at days 0-5 and 7 after the onset of shock/myocardial infarction. RESULTS: Activated protein C levels were significantly lower in patients with cardiogenic shock compared to controls. In cardiogenic shock patients, there was no difference in activated protein C levels at baseline, whereas activated protein C levels significantly declined in 28-day non-survivors at day 2, compared with 28-day survivors. Lower levels of activated protein C were associated with a higher degree of vasopressor need, whereas there was no significant association with multiple organ failure in the first days. Regarding the inflammatory response, a strong inverse correlation was observed between interleukin-6 and activated protein C levels. CONCLUSION: Patients with cardiogenic shock who did not survive up to 28 days showed a decline in activated protein C levels during the course of the disease, which was inversely correlated with interleukin-6. This study underlines sustained inflammatory mechanisms in the development and persistence of cardiogenic shock, highlighting a potential effect of anti-inflammatory interventions early during cardiogenic shock.

Impact of bivalirudin on mortality and bleeding complications in acute coronary syndrome patients undergoing invasive revascularization : A real world experience.

BACKGROUND: In a retrospective analysis of a prospective single center registry we compared the use of bivalirudin, unfractionated heparin (UFH) monotherapy, UFH + abciximab in 1240 consecutive patients with acute coronary syndrome (ACS) undergoing stent implantation. RESULTS: Bivalirudin was associated with tendentially reduced in-hospital minor or major bleeding rates compared to UFH monotherapy (5.9 % vs. 9.4 % adjusted odds ratio (OR) 0.82, 95 % confidence interval CI 0.45-1.51, p = 0.53) and compared to the pooled UFH group (5.9 % vs. 11.9 %, adjusted OR 0.62, 95 % CI 0.36-1.08, p = 0.09) but with significantly lower bleeding hazards compared to UFH + abciximab (5.9 % vs. 16 %, adjusted OR 0.41, 95 % CI 0.22-0.78, p < 0.01). After 3 years of follow-up, adjusted cardiovascular mortality rates were similar between all groups, particularly between bivalirudin vs. UFH monotherapy (hazard ratio HR 1.12, 95 % CI 0.58-2.16, p = 0.73) and vs. UFH + abciximab (HR 0.91, 95 % CI 0.40-2.10, p = 0.83). Acute or subacute stent thrombosis occurred at a rate of 0.8 % with no significant differences between the groups. CONCLUSIONS: This retrospective analysis in a real world situation of medium to high-risk ACS patients undergoing invasive revascularization confirmed the results of most large-scale randomized trials by demonstrating reduced bleeding rates in favor of bivalirudin vs. UFH + GPI but with no significant differences between treatment strategies for long-term all-cause and cardiovascular mortality.

Contrast induced acute kidney injury in acute coronary syndrome patients: A single centre experience.

BACKGROUND: The aim of the study was to investigate predictors of contrast induced acute kidney injury, in-hospital and long-term mortality in patients with acute coronary syndrome treated by percutaneous coronary intervention. METHODS: We investigated 536 consecutive patients with acute coronary syndrome who underwent percutaneous coronary intervention. Contrast induced acute kidney injury was classified according to risk, injury, failure, loss of kidney function and end-stage kidney disease/acute kidney injury network (RIFLE/AKIN) criteria into those with normal kidney function, risk, RIFLE stage I and those with stage ⩾ II. We investigated in-hospital, all-cause mortality during index hospitalization and long-term all-cause mortality during the follow-up period of 94 months (interquartile 81.6-108.9 months) in adjustment with parameters of the Global Risk of Acute Coronary Events score. RESULTS: Patients with contrast induced acute kidney injury had worse baseline clinical characteristics and displayed more co-morbidities than patients with normal kidney function. In multivariate logistic regression analysis intra-aortic balloon pump use, congestive heart failure, age >75 years and admission serum creatinine >1.5mg/dl were independent predictors of contrast induced acute kidney injury development. contrast induced acute kidney injury RIFLE stage ⩾ II was an independent predictor of in-hospital mortality (odds ratio 33.16, confidence interval 1.426-770.79, p=0.029) and long-term mortality (hazard ratio 4.713, confidence interval 1.53-14.51, p=0.007) even after adjustment for confounders (variables of Global Risk of Acute Coronary Events score). CONCLUSION: Contrast induced acute kidney injury is a common complication of acute coronary syndrome patients treated by percutaneous coronary intervention. Advanced deterioration in renal function after percutaneous coronary intervention is an independent predictor for in-hospital and long-term mortality.

Sex-related differences in baseline characteristics, management and outcome in patients with acute coronary syndrome without ST-segment elevation.

AIM: To detect sex-related differences in baseline characteristics, management and outcome in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). METHODS: Data from 812 consecutive patients admitted to our cardiology department for NSTE-ACS between 2001 and 2004 were obtained. Early invasive therapy was defined as revascularization during first hospital stay. A seven-year follow-up for the clinical endpoint of all-cause mortality could be obtained in 342 women and 440 men, respectively. RESULTS: Compared with men, women were significantly older and more likely to suffer from renal insufficiency. The proportion treated with clopidogrel at admission was 43.6% for women and 52.7% for men, respectively (p=0.011). Significantly fewer women underwent an early invasive therapy compared with men (27.5% vs. 35.2%; p=0.021). Age and renal insufficiency were the strongest predictors for a conservative approach in both female and male patients. After adjustment for baseline characteristics there was no significant difference in treatment between women and men (odds ratio 0.89; 95% confidence interval 0.59-1.35; p=0.588). While in-hospital mortality was similar between the sexes, long-term mortality was significantly higher in women compared with men (8.2% vs. 7.0%; p=0.549 for in-hospital mortality and 54.8% vs. 39.3%; p<0.001 for seven-year mortality). However, after adjustment for baseline characteristics and treatment there was no significant difference in long-term mortality between women and men (hazard ratio 1.14; 95% confidence interval 0.89-1.47; p=0.307). CONCLUSION: In these patients with NSTE-ACS women were less likely to undergo an early invasive therapy compared with men due to their higher age and the higher rate of renal insufficiency. After adjustment for age, comorbidities and treatment female sex was not associated with worse long-term outcome.

Soluble ST2 and interleukin-33 levels in coronary artery disease: relation to disease activity and adverse outcome.

OBJECTIVES: ST2 is a receptor for interleukin (IL)-33. We investigated an association of soluble ST2 (sST2) and IL-33 serum levels with different clinical stages of coronary artery disease. We assessed the predictive value of sST2 and IL-33 in patients with stable angina, non-ST elevation myocardial infarction (NSTEMI) and ST elevation myocardial infarction (STEMI). METHODS: We included 373 patients of whom 178 had stable angina, 97 had NSTEMI, and 98 had STEMI. Patients were followed for a mean of 43 months. The control group consisted of 65 individuals without significant stenosis on coronary angiography. Serum levels of sST2 and IL-33 were measured by ELISAs. RESULTS: sST2 levels were significantly increased in patients with STEMI as compared to patients with NSTEMI and stable angina as well as with controls. IL-33 levels did not differ between the four groups. During follow-up, 37 (10%) patients died and the combined endpoint (all cause death, MI and rehospitalisation for cardiac causes) occurred in 66 (17.6%) patients. sST2 serum levels significantly predicted mortality in the total cohort. When patients were stratified according to their clinical presentation, the highest quintile of sST2 significantly predicted mortality in patients with STEMI, but not with NSTEMI or stable coronary artery disease. sST2 was a significant predictor for the combined endpoint in STEMI patients and in patients with stable angina. Serum levels of IL-33 were not associated with clinical outcome in the total cohort, but the highest quintile of IL-33 predicted mortality in patients with STEMI. CONCLUSIONS: Serum levels of sST2 are increased in patients with acute coronary syndromes as compared to levels in patients with stable coronary artery disease and in individuals without coronary artery disease. sST2 and IL-33 were associated with mortality in patients with STEMI but not in patients with NSTEMI or stable angina.

An increase of interleukin-33 serum levels after coronary stent implantation is associated with coronary in-stent restenosis.

The study aim was to determine the predictive value of interleukin (IL)-33, a recently described member of the IL-1 family of cytokines, for the development of in-stent restenosis (ISR). IL-33 serum levels were measured in 387 consecutive patients undergoing percutaneous coronary intervention (PCI) of whom 193 had stable angina, 93 non-ST elevation myocardial infarction (NSTEMI), and 101 ST-elevation MI (STEMI), respectively. Blood was taken directly before and 24h after stent implantation. The presence of ISR was initially evaluated by clinical means after six to eight months. When presence of myocardial ischemia was suspected, coronary angiography was performed to confirm the suspected diagnosis of ISR. Clinical ISR was present in total in 34 patients (8.8%). IL-33 was detectable in 185 patients and was below detection limit in 202 patients. In patients with decreased IL-33 (n=95), unchanged or non-detectable levels (n=210) or increased levels of IL-33 after PCI (n=82), ISR-rate was 2.1%, 9.5% and 14.6%, respectively (p<0.05). Accordingly, patients with ISR showed a significant increase of IL-33 upon PCI (p<0.05). This association was independent from clinical presentation and risk factors as well as numbers and type of stents. In patients with both stable and unstable coronary artery disease, an increase of IL-33 serum levels after stent implantation is associated with a higher rate of in-stent restenosis.

Effects of AV-delay optimization on hemodynamic parameters in patients with VDD pacemakers.

AIM: Atrioventricular (AV) delay optimization improves hemodynamics and clinical parameters in patients treated with cardiac resynchronization therapy and dual-chamber-pacemakers (PM). However, data on optimizing AV delay in patients treated with VDD-PMs are scarce. We, therefore, investigated the acute and chronic effects of AV delay optimization on hemodynamics in patients treated with VDD-PMs due to AV-conduction disturbances. METHODS: In this prospective, single-center interventional trial, we included 64 patients (38 men, 26 women, median age: 77 (70-82) years) with implanted VDD-PM. AV-delay optimization was performed using a formula based on the surface electrocardiogram (ECG). Hemodynamic parameters (stroke volume (SV), cardiac output (CO), heart rate (HR), and blood pressure (BP)) were measured at baseline and follow-up after 3 months using impedance cardiography. RESULTS: Using an ECG formula for AV-delay optimization, the AV interval was decreased from 180 (180-180) to 75 (75-100) ms. At baseline, AV-delay optimization led to a significant increase of both SV (71.3 ± 15.8 vs. 55.3 ± 12.7 ml, p < 0.001, for optimized AV delay vs. nominal AV interval, respectively) and CO (5.1 ± 1.4 vs. 3.9 ± 1.0 l/min, p < 0.001), while HR and BP remained unchanged. At follow-up, the improvement in CO remained stable (4.9 ± 1.3 l/min, p = 0.09), while SV slightly, but significantly, decreased (to 65.1 ± 17.6, p < 0.01). CONCLUSION: AV-delay optimization in patients treated with VDD-PMs exhibits immediate beneficial effects on hemodynamic parameters that are sustained for 3 months.

Influence of high-dose highly efficient statins on short-term mortality in patients undergoing percutaneous coronary intervention with stenting for acute coronary syndromes.

Statins are recommended for prevention of progression of cardiovascular disease after percutaneous coronary intervention (PCI). Although high-dose highly efficient statins are recommended, especially in high-risk patients, clinical data are scarce and further investigation in "real-world" settings is needed. One thousand five hundred twenty-eight consecutive patients, who underwent PCI for acute coronary syndrome, were included in a prospective registry from January 2003 to January 2011. In post hoc analysis, cardiovascular risk factors, co-morbidities, and circulating lipid parameters at the time of intervention were evaluated. As a primary end point, all-cause mortality after a follow-up period of 3 months was investigated. Results were compared between patients receiving high-dose highly effective statins (atorvastatin 80 mg or rosuvastatin 20 mg) versus patients receiving low-dose statins or who were without lipid-lowering therapy at the time of discharge. Nine hundred twenty-six patients (60.6%) received high-dose atorvastatin or rosuvastatin and 602 patients (39.4%) received low-dose statin therapy or were not on statins at discharge. Eight patients (0.9%) receiving high-dose statin therapy and 21 patients (3.5%) taking low-dose statins or no statins at discharge died during the 3-month follow-up (hazard ratio 0.244, 95% confidence interval 0.108 to 0.551, p=0.001). After propensity score adjustment the results remained significant (adjusted hazard ratio for high-dose statins 0.405, 95% confidence interval 0.176 to 0.931, p=0.033). In conclusion, in this single-center series of 1,528 real-world patients undergoing PCI for acute coronary syndrome, a significant reduction in short-term all-cause mortality could be demonstrated in patients receiving high-dose highly efficient statins compared with patients receiving low-dose statins or no lipid-lowering therapy.

Variability of on-treatment platelet reactivity in patients on clopidogrel.

Response to clopidogrel therapy is subject to inter-individual variability. However, data with regard to on-treatment platelet reactivity over time in patients undergoing coronary stenting are scarce. For this prospective observational study, 102 consecutive patients on dual antiplatelet therapy undergoing coronary stenting due to stable coronary artery disease (CAD; n = 29), non ST-elevation acute coronary syndrome (NSTE-ACS; n = 45) and ST-elevation myocardial infarction (STEMI; n = 28) were enrolled. Vasodilator-stimulated phosphoprotein-phosphorylation assay was performed at baseline, as well as 1, 3 and 6 months thereafter. Platelet reactivity index (PRI) measured after 1, 3 and 6 months was lower compared to baseline values (p < 0.001). Variables responsible for reduced response to clopidogrel at baseline (reticulated platelet fraction, simvastatin therapy) and during steady-state phase (body mass index, blood glucose concentrations, cholesterol/HDL-ratio and quality of life score) were different. High on-treatment platelet reactivity (HTPR)-phenotype (cut-off = 50% PRI) within the first month changed in 31% of stable CAD, 33% of NSTE-ACS and 39% of STEMI patients, respectively. HTPR-phenotype in the steady-state phase (month 1 to 6) changed in 45% of stable CAD, 33% of NSTE-ACS and 25% of STEMI patients. Response to clopidogrel and accordingly platelet function might vary over time, especially when a cut-off based approach, is used. There was a significant reduction of on-treatment platelet reactivity within the first month after percutaneous coronary intervention with stenting which was maintained for up to 6 months. Variables associated with reduced response to clopidogrel at baseline and during steady-state phase were different, as the latter mainly reflected an unfavorable metabolic profile, comprising elevated BMI, blood glucose levels as well as cholesterol/HDL-ratio.

B-type natriuretic peptide and risk of contrast-induced acute kidney injury in acute ST-segment-elevation myocardial infarction: a substudy from the HORIZONS-AMI trial.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) after percutaneous coronary intervention is associated with adverse short- and long-term outcomes. However, identification of patients at risk for CI-AKI is challenging. Using a large contemporary randomized trial database of patients with ST-segment-elevation myocardial infarction, we therefore sought to examine whether admission B-type natriuretic peptide (BNP) levels predict the development of CI-AKI. METHODS AND RESULTS: A total of 979 ST-segment-elevation myocardial infarction patients enrolled in the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial had BNP levels measured in the emergency room prior to primary percutaneous coronary intervention as part of the study protocol. CI-AKI was defined as a relative increase in serum creatinine of ≥25%, or an absolute increase of ≥0.5 mg/dL, occurring within 48 hours after contrast administration. Logistic regression analysis was used to estimate the association of admission BNP with development of CI-AKI. CI-AKI occurred in 131 patients (13.3%). Baseline BNP was a significant univariable correlate of CI-AKI (odds ratio 1.31, 95% confidence interval, 1.14-1.51; P=0.0001). After multivariable adjustment for clinical, laboratory, and angiographic variables, BNP remained a significant independent predictor of CI-AKI (1.29 [1.10, 1.51]; P<0.001). Significant net reclassification improvement was achieved by addition of BNP to the current clinical risk prediction model (net reclassification improvement=0.177; P<0.001) and to the Mehran Risk Score (net reclassification improvement=0.100; P=0.015). CONCLUSIONS: Measurement of serum BNP at hospital admission may help identify patients who are at risk for developing CI-AKI after primary percutaneous coronary intervention in ST-segment-elevation myocardial infarction. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00433966.

Fetuin-A Characteristics during and after Pregnancy: Result from a Case Control Pilot Study.

Objective. Fetuin-A has been associated with gestational diabetes mellitus (GDM). We investigated fetuin-A levels during and after pregnancy in women with GDM. Fetuin-A measurements were performed in 10 women with GDM and 10 age and body mass index (BMI) matched healthy pregnant women. All women underwent an oral glucose tolerance test (OGTT) in and 3 months after gestation. Results. Fasting fetuin-A correlated with BMI in women with former GDM (r = 0.90, P < 0.0001) but showed no association with parameters of glucose tolerance in women with GDM or post-GDM. GDM featured significantly lower insulin sensitivity and higher insulin and C-peptide secretion profiles compared to NGT during pregnancy (P < 0.05). Fasting and postprandial fetuin-A did not differ between groups, neither during nor after pregnancy. Conclusion. Fetuin-A is not influenced by glucose tolerance during or after pregnancy or acute glucose elevations following glucose ingestion in young women, but closely relates to BMI early postpartum.

Comparison of HbA1c and oral glucose tolerance test for diagnosis of diabetes in patients with coronary artery disease.

BACKGROUND: Measurement of glycated hemoglobin A1c (HbA1c) to diagnose diabetes mellitus (DM-2) is recommended by several expert groups. DM-2 occurs very frequently among patients with coronary artery disease (CAD). Therefore, we aimed to investigate the diagnostic strengths of HbA1c and oral glucose tolerance test (OGTT) in detecting latent glucometabolic disturbances among patients with CAD. MATERIALS AND METHODS: One hundred ninety-nine consecutive patients admitted with CAD were included in this observational study. Fasting plasma glucose as well as HbA1c measurement was performed in all study participants and those without preexisting DM-2 underwent an OGTT. RESULTS: Patients were subdivided according to their medical history into those with previous DM-2 (n = 37). The remaining 162 patients underwent OGTT, which revealed 39 patients with diabetes (DM-(OGTT)), 35 with impaired glucose tolerance (IGT), 20 with impaired fasting glucose (IFG) and 68 with normal glucose tolerance (NGT). Using HbA1c resulted in 6.8% DM and 45.6% at risk (HbA1c 5.7-6.4%) diagnosis. OGTT identified 24.1% DM (p = 0.002 compared with HbA1c) and 21.6% IGT patients. Among those with intermediate HbA1c (5.7-6.4%) 26.5% patients were NGT and only 30.9% displayed DM-2 by use of OGTT. Among patients with HbA1c of <5.7%, 44% (n = 31) of patients had disturbed glucose metabolism. Using receiver-operating curve HbA1c cutoff with the highest sensitivity and specificity was found to be 5.8%. DISCUSSION: There is a large discordance between OGTT and HbA1c in terms of detecting latent DM-2 in patients with CAD. Measurement of HbA1c could result in lower propensity of DM-2 diagnosis.

The role of ST-segment elevation in lead aVR in the risk assessment of patients with acute pulmonary embolism.

UNLABELLED: BACKGROUD AND AIM: Patients with acute pulmonary embolism (APE) present with highly variable symptoms and ECG abnormalities. As ST-elevation in lead aVR has recently been described to predict right ventricular dysfunction (RVD), we aimed to correlate this sign to the severity of APE. METHODS: Three-hundred ninety-six consecutive patients (in centers a and b) with proven APE were retrospectively analysed with respect to 12-lead-ECG, symptoms, thrombus location, echocardiograpy, troponin T, initial therapy and outcome. Data were then compared between patients with and without aVR-ST-elevation. RESULTS: On admission aVR-ST-elevation was present in 34.3% (n = 136). Presence of aVR-ST-elevation was assossiated with more severe clinical presentation (dyspnoea at rest 44.9 vs. 29.2%; p = 0.002, hypotension 17.0 vs. 6.5%; p = 0.001, syncope 16.2 vs. 6.5%; p = 0.002), higher median troponin T levels (0.035 [0.01-0.2] versus 0.01 [0.01-0.02]; p < 0.001), more frequent RVD (74.5 vs. 46.6%; p < 0.001) and central located thrombi (50.8 vs. 29.2; p < 0.001). Thrombolysis was used more frequently (29.1 vs. 7.5%; p < 0.001) and in-hospital-mortality was increased (10.3 vs. 5.4%; p = 0.07) when compared to patients without that sign. Mortality in intermediate-risk APE patients with aVR-ST-elevation was 8.9% compared to 0% in those without (p = 0.04). In contrast, the presence of other classical ECG pattern of APE did not further increase mortality in intermediate-risk patients. CONCLUSIONS: ST-elevation in lead aVR is associated with a more severe course of APE, especially in patients with intermediate-risk. Therefore, aVR-ST-elevation might be useful in risk stratification of APE.

Usefulness of pre-operative copeptin concentrations to predict post-operative outcome after major vascular surgery.

The aim of this study was to investigate whether preoperative determination of plasma copeptin levels in addition to plasma N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) could help improve risk stratification in patients who undergo major vascular surgery. One hundred ninety-eight consecutive patients who underwent major vascular surgery (58.6% infrainguinal aortic reconstruction, 23.7% abdominal aortic aneurysm surgery, 17.7% carotid endarterectomy) were included in this study. Patients were monitored for in-hospital and long-term (2-years) major adverse cardiac events, consisting of cardiac death, nonfatal myocardial infarction, and emergent coronary revascularization. Overall, 40 patients (20.2%) reached the primary end point, and most of these events occurred during the index hospital stay (n = 18 [45%]). In univariate Cox regression analysis, increasing concentrations of copeptin were significant determinants of outcome as a continuous variable (hazard ratio [HR] 1.012, p = 0.005) and as a dichotomized variable according to the recommended cutoff of 14.0 pmol/L (HR 4.116, p <0.001). Subgroup analyses revealed that especially patients at low estimated risk according to plasma NT-pro-BNP levels were at significantly higher risk for worse outcomes with higher copeptin levels (HR 5.983, p = 0.002). In multivariate Cox regression analysis, copeptin concentrations >14 pmol/L were significant independent predictors of outcome (HR 2.842, p = 0.002) in addition to type of surgery, history of myocardial infarction, elevated levels of cardiac troponin T, and NT-pro-BNP levels. In conclusion, the results of this study suggest that preoperative determination of this new biomarker could substantially improve prediction of perioperative and postoperative outcomes in vascular surgery patients.

Admission proinsulin is associated with mortality in patients with admission hyperglycemia during acute coronary syndrome: results from a pilot observational study.

BACKGROUND: Acute hyperglycemia (AHG) is associated with mortality in patients with acute coronary syndrome (ACS). The extent to which hyperproinsulinemia contributes to worse clinical outcomes for this specific patient population is unknown. METHODS: We included 308 consecutive ACS patients who underwent coronary angioplasty in this pilot observational study. Patients were separated into 3 groups: patients with proven diabetes mellitus (DM group) (n =55), nondiabetic patients with a normal glucose concentration at admission (NAG group) (n =175), and nondiabetic patients with AHG at presentation (AHG group) (n =78). Blood samples for glucose, insulin, and proinsulin measurements were obtained at admission. The primary end point of the study was all-cause mortality, which was assessed at a mean follow-up of 19 months (interquartile range, 12-28 months). RESULTS: Patients in the AHG and DM groups had significantly (P =0.048) higher all-cause mortality compared with the NAG group. A univariate Cox regression analysis revealed that the proinsulin concentration was significantly associated with all-cause mortality for all study participants (hazard ratio, 1.013; 95% CI, 1.002-1.024; P =0.023). AHG patients with increased proinsulin concentrations showed a mortality rate similar to that of DM patients but had a significantly higher mortality rate than patients with AHG and a low proinsulin concentration (χ² =7.57; P =0.006) and patients with NAG (with or without increased proinsulin) [χ² =7.66 (P =0.006) and 13.98 (P < 0.001), respectively]. A multivariate regression analysis revealed that the concentrations of glucose and proinsulin at admission were significant (P =0.002) predictors of all-cause mortality. CONCLUSIONS: An increased proinsulin concentration may be a marker for mortality in ACS patients with hyperglycemia at admission and without known diabetes. Further studies are needed to evaluate the role of metabolic parameters such as proinsulin.

Complementary role of copeptin and high-sensitivity troponin in predicting outcome in patients with stable chronic heart failure.

AIMS: Copeptin, the C-terminal part of the vasopressin pro-hormone, is elevated after myocardial infarction and predicts adverse outcome. In the present study we investigated whether the complementary role of copeptin and cardiac troponin T (cTnT) could be used for identification of high-risk patients with chronic stable heart failure. METHODS AND RESULTS: We measured copeptin and high-sensitivity cTnT (hs-cTnT) levels in 172 consecutive patients with stable chronic heart failure. Patients were followed for all-cause mortality and hospitalization due to heart failure for a median of 1301 days (interquartile range: 707-1636). In univariate analysis, plasma copeptin showed a moderate but significant correlation with hs-cTnT (r= 0.40 P< 0.001), age (r= 0.36 P< 0.001), creatinine (r= 0.52 P< 0.001), and amino-terminal pro-B type natriuretic peptide (NT-proBNP; r= 0.42 P< 0.001). Both copeptin (P= 0.002) and hs-cTnT (P= 0.005) concentrations were significantly increased in patients with higher New York Heart Association classes. While 109 (58%) patients had hs-cTnT concentrations above normal (>14 pg/mL) 104 patients (55%) had copeptin concentrations above normal (16.4 pmol/L). In survival analysis, both elevated copeptin and hs-cTnT concentrations were significant predictors of outcome (P< 0.001 for both). The combination of both markers showed a graded and highly significant association with impaired clinical outcome, which was independent of plasma NT-proBNP levels (adjusted hazard ratios 1.40, 95% CI, 1.20-1.70; P< 0.001). Adding copeptin concentrations to a prediction model with NT-proBNP and hs-cTnT resulted in significant improvement in model performance (net reclassification improvement 0.208; P< 0.05). CONCLUSION: Our data suggest that the combined use of hs-cTnT and copeptin might predict clinical outcome of patients with chronic stable heart failure.

Platelet function variability and non-genetic causes.

Dual antiplatelet therapy (DAPT) has been established for the treatment of coronary artery disease, especially in and after acute coronary syndromes, and after coronary interventions. Data suggest that a significant percentage of individuals treated with clopidogrel do not receive the expected therapeutic benefit because of a decreased responsiveness of their platelets, which is caused by several extrinsic and intrinsic mechanisms. The clinical consequence of clopidogrel non-responsiveness is severe cardiovascular complications. Besides genetic variability in response to antiplatelet therapy, non-genetic causes such as drug interactions (proton-pump inhibitors, statins, calcium-channel blockers, coumarin derivates, antibiotics, antimycotics) and co-morbidities (diabetes mellitus, renal failure, obesity) are responsible for this phenomenon. Large clinical trials with standardised laboratory methods and hard clinical endpoints are needed to identify these interactions with clopidogrel and predictors for its non-responsiveness.