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.

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.

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.

Plasma N-terminal fragment of the prohormone B-type natriuretic peptide concentrations in relation to time to treatment and Thrombolysis in Myocardial Infarction (TIMI) flow: a substudy of the Assessment of the Safety and Efficacy of a New Treatment Strategy with Percutaneous Coronary Intervention (ASSENT IV-PCI) trial.

BACKGROUND: We investigated the prognostic significance of plasma N-terminal fragment of the prohormone B-type natriuretic peptide (Nt-proBNP) concentrations in addition to time to reperfusion and Thrombolysis in Myocardial Infarction (TIMI) flow before and after coronary intervention in patients with ST elevation myocardial infarction (STEMI) from the database of the Assessment of the Safety and Efficacy of a New Treatment Strategy with Percutaneous Coronary Intervention (ASSENT IV-PCI) trial. METHODS: Plasma Nt-proBNP was available in 1,037 patients with STEMI. Patients were randomized either to primary (p-PCI) or to full-dose tenecteplase before PCI (f-PCI).The study end point was the composite of death, cardiogenic shock, or congestive heart failure at 90 days. RESULTS: According to classification tree analysis, patients with Nt-proBNP levels >694 pg/mL had the highest primary end point rates (33.8% vs 11%, P < .001). In Cox regression analysis, Nt-proBNP >694 pg/mL strongly predicted 90-day survival even among patients with short treatment delay (f-PCI < or =3 hours: hazard ratio [HR] 2.63, P = .002 and p-PCI < or =3 hours: HR 4.87, P < .001, respectively). Patients with TIMI 3 flow after coronary intervention were at significantly higher risk of the primary end point if admission Nt-proBNP exceeded 694 pg/mL (f-PCI: HR 2.88, P < .001 and p-PCI: HR 3.84, P < .001, respectively). In multivariable analysis, Nt-proBNP >694 pg/mL significantly (P = .001) predicted 90-day survival in addition to age (P < .001), TIMI flow after PCI (P < .001), body mass index (P = .026), anterior wall infarction (P = .035), and systolic blood pressure at randomization (P = .036), respectively. CONCLUSION: Elevated plasma concentrations of Nt-proBNP in the early phase of STEMI determine in-hospital and 90-day outcome after infarction irrespective of time to treatment and pre- or postinterventional TIMI flow.

Prediction of cardiogenic shock using plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone [corrected] concentrations in ST elevation myocardial infarction: an analysis from the ASSENT-4 Percutaneous Coronary Intervention Trial.

OBJECTIVE: Cardiogenic shock is a major cause of death in ST elevation myocardial infarction. We investigated whether determination of plasma [corrected] B-type natriuretic peptide and the N-terminal fragment of its pro-hormone in the acute phase of ST elevation myocardial infarction could identify patients prone to development of cardiogenic shock. DESIGN: Retrospective analysis of a multicenter, randomized open-label trial (ASSENT-4 PCI; ClinicalTrials.gov Identifier: NCT00168792). METHODS: Plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone were determined in available stored samples of 1016 ST elevation myocardial infarction patients without signs of cardiogenic shock at randomization to primary percutaneous coronary intervention or to full-dose tenecteplase before percutaneous coronary intervention. The end point of the present analysis was in-hospital cardiogenic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 57 (5.6%) patients had cardiogenic shock during index hospitalization. In-hospital cardiogenic shock increased precipitously with higher baseline concentrations of plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone (B-type natriuretic peptide and the N-terminal fragment of its pro-hormone < or =67 pg/mL: 1.9%; 68-1482 pg/mL: 5.9%; >1482 pg/mL: 14.9%; p < .001). Higher plasma [corrected] B-type natriuretic peptide and the N-terminal fragment of its pro-hormone concentrations were predictors of in-hospital shock, especially among those patients with relatively low clinical risk (no requirement of inotropic support before angiography, systolic blood pressure >100 mm Hg, heart rate <100 bpm, Global Utilization of Streptikonase and Tissue-Plasminogen Activator for Occluded Coronary Arteries score of <122). In multivariate Cox regression analysis, higher plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone concentrations remained significant predictors of shock, in addition to age, systolic blood pressure, heart rate, and randomization to facilitated percutaneous coronary intervention and Killip classification. Furthermore, plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone significantly predicted in-hospital shock independently of the validated Global Utilization of Streptikonase and Tissue-Plasminogen Activator for Occluded Coronary Arteries score (p = .014). CONCLUSION: Plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone concentrations measured early in the acute phase of ST elevation myocardial infarction are useful in predicting the development of in-hospital cardiogenic shock.

Reperfusion before percutaneous coronary intervention in ST-elevation myocardial infarction patients is associated with lower N-terminal pro-brain natriuretic peptide levels during follow-up, irrespective of pre-treatment with full-dose fibrinolysis.

AIMS: N-terminal pro-brain natriuretic peptide (NT-proBNP) levels predict outcomes in ST-elevation myocardial infarction patients treated with fibrinolysis or primary percutaneous coronary intervention (PCI). However, its role in facilitated PCI has not yet been assessed; it may be a tool to evaluate the lower event rates with primary PCI in ASSENT-4. METHODS AND RESULTS: In ASSENT-4, 1667 patients were randomized to tenecteplase (TNK) followed by PCI or primary PCI alone. Baseline, discharge/Day 7, and 90-day NT-proBNP levels were available for 1008, 971, and 813 patients. Increasing quartiles of baseline NT-proBNP levels were associated with a higher risk of the combined endpoint of death, heart failure, and shock at 90 days and 1-year mortality (P < 0.001). Events were more common with TNK + PCI, regardless of baseline NT-proBNP quartile. When analysing baseline NT-proBNP as a continuous variable, no treatment interaction was observed for the primary endpoint (P = 0.17) or 1-year mortality (P = 0.08). Overall, NT-proBNP levels at Day 7 or 90 were not different between the two treatments. In patients with TIMI 2-3 flow before PCI, NT-proBNP at Day 90 was lower in PCI-only patients (P = 0.01), although no interaction was observed (P = 0.14). In TNK-pre-treated patients without reperfusion (TIMI 0-1) after PCI, NT-proBNP levels at Day 7 or 90 were not significantly higher than in PCI patients. CONCLUSION: Baseline NT-proBNP predicts outcome at 90 days and 1 year in patients undergoing PCI with or without facilitation with TNK. A higher rate of reperfusion in lytic-pre-treated patients did not result in lower NT-proBNP during follow-up. Thus, baseline and subsequent NT-proBNP levels do not explain the lower mortality rate with PCI alone seen in this trial.

Human cardiac fibroblasts express B-type natriuretic peptide: fluvastatin ameliorates its up-regulation by interleukin-1alpha, tumour necrosis factor-alpha and transforming growth factor-beta.

B-type natriuretic peptide (BNP) is a cardiac hormone, which plays a major role in body fluid and cardiovascular homeostasis. Produced by cardiac ventricles, its expression is highly regulated by various mediators. Canine cardiac fibroblasts have been identified as a source of BNP. Cardiac fibroblasts are key regulators of myocardial structure and function. We treated cultured human adult cardiac fibroblasts (HACF) with 2000 U/ml tumour necrosis factor-alpha (TNF-alpha), 200 U/ml interleukin-1alpha (IL-1alpha) or 50 ng/ml transforming growth factor-beta (TGF-beta) in the presence or absence of 500 nM fluvastatin. N-terminal pro-BNP (Nt-proBNP) concentration was determined by a competitive enzyme immunoassay. RealTime polymerase chain reaction (real-time PCR) was performed to investigate changes in BNP mRNA expression. Nt-proBNP peptide was present in the conditioned media of HACF and incubation with fluvastatin significantly reduced Nt-proBNP peptide levels. Treatment of HACF with TNF-alpha, IL-1alpha or TGF-beta significantly increased Nt-proBNP levels compared with untreated cells. This effect was completely abolished in the presence of fluvastatin. Real-time PCR analysis confirmed these changes at the level of mRNA expression. Our data suggest that cardiac fibroblasts are a potential source of BNP in the human heart. Pro-inflammatory cytokines, associated with ventricular dysfunction and cardiac fibrosis, seem to be major inducers of BNP production in cardiac fibroblasts. This effect can be reverted by a statin. Based on our data, we speculate that elevated plasma BNP levels might not only reflect increased myocardial stretch but also inflammatory and remodelling processes. A possible benefit of statin-induced reduction in BNP production requires further studies.

Early assessment of outcome in cardiogenic shock: relevance of plasma N-terminal pro-B-type natriuretic peptide and interleukin-6 levels.

OBJECTIVE: Plasma N-terminal pro-B-type natriuretic peptide (Nt-pro-BNP) levels are frequently elevated in critically ill patients and are associated with an increased mortality. In this study, we determined Nt-pro-BNP levels in patients with cardiogenic shock (CS) and evaluated its association with clinical and hemodynamic parameters and 30-day mortality. DESIGN: Retrospective study. SETTING: Two, eight-bed intensive care units at a university and a community hospital. PATIENTS: Retrospective study on stored plasma samples of 58 patients with CS, obtained at admission to the intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Massively elevated Nt-pro-BNP concentrations showed no significant association with duration of shock, total Sequential Organ Failure Assessment score, or invasive hemodynamic parameters at the time of blood sampling but a significant association with estimated glomerular filtration rate (p < 0.001), C-reactive protein (p = 0.03), age (p = 0.005), and body weight (p = 0.03). Both in univariate and multivariate survival analyses, Nt-pro-BNP levels above the median (>12,782 pg/mL) were significant predictors of 30-day mortality (p < 0.001) and showed a complementary role with interleukin (IL)-6 in predicting outcome. Patients with IL-6 >195 pg/mL and Nt-pro-BNP above the median value had the highest 30-day mortality (93.7%), whereas patients with lower IL-6 levels together with lower Nt-pro-BNP levels had significantly better survival (mortality rate 26.3%). Among patients who had acute myocardial infarction, those with Nt-pro-BNP concentrations above the median level showed a highly impaired clinical course even if coronary revascularization was successful (30-day mortality 90.9% vs. 29.4%, p = 0.001), whereas survival of patients with unsuccessful revascularization did not differ significantly with respect to the median of Nt-pro-BNP (30-day survival rate 81.8% vs. 75.0%, p = 0.71). CONCLUSION: The massive elevations of Nt-pro-BNP observed in the early phase of CS seem to be independent of ventricular performance. Nt-pro-BNP levels are nevertheless predictive of 30-day survival in patients with CS especially in those with successful revascularization and might be used in combination with IL-6 for estimation of outcome early on.

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.

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.

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.

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.

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.

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.

Circulating B-type natriuretic peptides in patients with acute coronary syndromes. Pathophysiological, prognostical and therapeutical considerations.

Fifty percent of patients who experience death or develop heart failure after acute coronary syndromes (ACS) have extremely elevated concentrations of plasma B-type natriuretic peptides. These elevations, however, seem not to reflect permanent ventricular dysfunction or heart failure and are assumed to exist already at the onset of ischemic symptoms. The underlying mechanisms of BNP/Nt-proBNP elevations in patients with ACS are still not known at present. Furthermore, the relationship of elevated BNP/Nt-proBNP with mortality but not with atherothrombotic complications of underlying disease makes it difficult to choose optimal therapeutic strategies based on plasma levels of these peptides. The remarkably high short- and long-term mortality rate associated with increases of BNP/Nt-proBNP elevations clearly show the need of further investigation to focus on this high-risk group of patients in order to clarify underlying pathomechanisms and to find optimal therapeutic approaches.

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.

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.

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.