Neurotensin and Adverse Cardiovascular Outcomes in Patients Undergoing Percutaneous Coronary Intervention.

Background: Neurotensin is involved in fatty acid and glucose metabolism and promotes the development of obesity and diabetes. These associations appear to be more pronounced in women. We investigated the association of neurotensin with long-term major adverse cardiovascular events (MACE) in patients presenting with acute coronary syndrome (ACS) or chronic coronary syndrome (CCS) undergoing percutaneous coronary intervention (PCI). Methods: We included 452 consecutive patients [144 (31.9%) females] undergoing PCI for ACS or CCS. Plasma samples drawn after PCI were analyzed for neurotensin with an enzyme-linked immunoassay. As primary endpoint, a composite of MACE including all-cause death, non-fatal myocardial infarction and non-fatal stroke during 7 years of follow-up was investigated. As secondary endpoint, we investigated all-cause death. Results: Neurotensin levels did not differ between male and female patients (p = 0.560). MACE occurred in 150 (33.2%) patients. Restricted cubic splines demonstrated a U-shaped association of log-transformed neurotensin with the primary and secondary endpoint. Therefore, we dichotomized our cohort according to tertiles of log-transformed neurotensin. In Kaplan-Meier analysis including the total cohort and restricted to male patients log- neurotensin tertiles were not associated with MACE (both p > 0.05). Moreover, in the overall cohort and in male patients multivariable Cox regression analysis log-neurotensin tertiles were not associated with MACE or with all-cause death (all p > 0.05). However, in female patients log-neurotensin was associated with MACE in Kaplan-Meier analysis (log-rank p = 0.013). Also, after multivariable adjustment female patients in the first tertile had a significantly increased risk for MACE compared to female patients in the second tertile [HR 3.84 (95% CI 1.71-8.60), p = 0.001]. There was tendency for increased risk in female patients in the third tertile compared to the second tertile [HR 2.14 (95% CI 0.97-4.73), p = 0.058]. Moreover, in female patients the [first and the third tertile of log- neurotensin were associated with all-cause death 1s vs. 2nd tertile: HR 3.03 (95% CI 1.21-7.63), p = 0.018; 3rd vs. 2nd tertile: HR 3.01 (95% CI 1.22-7.44), p = 0.016]. Conclusion: In female patients with CAD undergoing PCI, neurotensin has a U-shaped relationship with adverse outcomes. These data suggest a sex specific association between neurotensin and long-term adverse events after PCI.

Re-appraisal of the obesity paradox in heart failure: a meta-analysis of individual data.

BACKGROUND: Higher body mass index (BMI) is associated with better outcome compared with normal weight in patients with HF and other chronic diseases. It remains uncertain whether the apparent protective role of obesity relates to the absence of comorbidities. Therefore, we investigated the effect of BMI on outcome in younger patients without co-morbidities as compared to older patients with co-morbidities in a large heart failure (HF) population. METHODS: In an individual patient data analysis from pooled cohorts, 5,819 patients with chronic HF and data available on BMI, co-morbidities and outcome were analysed. Patients were divided into four groups based on BMI (i.e. ≤ 18.5 kg/m2, 18.5-25.0 kg/m2; 25.0-30.0 kg/m2; 30.0 kg/m2). Primary endpoints included all-cause mortality and HF hospitalization-free survival. RESULTS: Mean age was 65 ± 12 years, with a majority of males (78%), ischaemic HF and HF with reduced ejection fraction. Frequency of all-cause mortality or HF hospitalization was significantly worse in the lowest two BMI groups as compared to the other two groups; however, this effect was only seen in patients older than 75 years or having at least one relevant co-morbidity, and not in younger patients with HF only. After including medications and N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin concentrations into the model, the prognostic impact of BMI was largely absent even in the elderly group with co-morbidity. CONCLUSIONS: The present study suggests that obesity is a marker of less advanced disease, but does not have an independent protective effect in patients with chronic HF. Categories of BMI are only predictive of poor outcome in patients aged > 75 years or with at least one co-morbidity (bottom), but not in those aged < 75 years without co-morbidities (top). The prognostic effect largely disappears in multivariable analyses even for the former group. These findings question the protective effect of obesity in chronic heart failure (HF).

Effect of marathon and ultra-marathon on inflammation and iron homeostasis.

The physiological response to high-level endurance exercise, such as running a marathon, poses several beneficial but also potentially harmful metabolic changes. The objective of this study was to determine the impact of marathon (M) and ultra-marathon (UM) on inflammation and iron homeostasis in paired samples. Fifteen well-trained, non-professional endurance athletes (14 males, 1 female) performed both a 130 km ultra-marathon and a traditional 42.195 km marathon. We determined markers of inflammation and iron homeostasis before, immediately after, and within 5 days after finishing each run, respectively. Biomarkers of inflammation (leucocytes, neutrophil granulocytes, monocytes, and c-reactive protein [CRP]) increased significantly after both marathon and ultra-marathon with higher levels of CRP after ultra-marathon compared with marathon both immediately after the race (18.15 ± 12.41 vs 5.58 ± 9.65 mg/L, P < .001) and at follow-up (15.67 ± 16.97 vs 7.19 ± 7.75 mg/L, P = .045) Concentrations of ferritin also increased significantly after both races and remained high at follow-up. Higher levels of ferritin immediately after the race (111.5 ± 103.2 vs 84.8 ± 86.3, P = .001) and at follow-up (102.7 ± 79.5 vs 74.6 ± 65.6, P = .001) were found in ultra-marathon finishers. The observed increase of serum iron and transferrin saturation (TSAT) after marathon and the decrease of serum iron and TSAT after ultra-marathon resulted in a significant absolute difference between the two races. The present data suggest a higher degree of inflammation after ultra-marathon compared with marathon. Markers of iron homeostasis also showed different response patterns with regard to running distance.

Von Willebrand Factor and ADAMTS13 and long-term outcomes in patients undergoing percutaneous coronary intervention.

BACKGROUND: Von Willebrand factor (VWF) and its cleaving protease a disintegrin-like and metalloprotease with thrombospondin type I repeats 13 (ADAMTS13) are pivotal mediators of thrombosis and are associated with the progression of atherosclerosis. We investigated the impact of VWF, ADAMTS13 and VWF/ADAMTS13 on long-term major adverse cardiovascular outcomes (MACE) in patients undergoing percutaneous coronary intervention (PCI). METHODS: We analysed 701 patients undergoing PCI between 2003 and 2006. VWF and ADAMTS13 antigen levels were measured before PCI. As primary endpoint, we investigated MACE, a composite of all-cause mortality, myocardial infarction or ischemic stroke during 8 years of follow-up. As secondary endpoint, we investigated all-cause mortality. RESULTS: Mean age was 63.8 years, 496 (70.8%) were male. Acute coronary syndrome (ACS) was diagnosed in 347 (49.5%) patients, stable coronary artery disease (SCAD) in 354 (50.5%). During follow-up 228 (32.5%) patients experienced MACE, and 161 (23.0%) died. In ACS patients, VWF was significantly associated with MACE (HR 1.402 (95%CI 1.003-1.959), p = 0.048), whereas ADAMTS13 and VWF/ADAMTS13 had no predictive value. In SCAD, neither VWF, ADAMTS13, nor VWF/ADAMTS13 correlated with MACE. VWF was significantly associated with all-cause death in ACS patients (HR 1.841 (95%CI 1.187-2.856), p = 0.006), but not in SCAD (1.394 (95%CI 0.856-2.269), p = 0.181). ADAMTS13 and VWF/ADAMTS13 were not correlated with ACS and SCAD, respectively. CONCLUSION: VWF but not ADAMTS13 and VWF/ADAMTS13 was associated with MACE and mortality in patients with ACS but not SCAD. This finding highlights the importance of VWF as an essential marker of risk in patients with ACS.

Impact of ultra-marathon and marathon on biomarkers of myocyte necrosis and cardiac congestion: a prospective observational study.

BACKGROUND: An elevation of cardiac biomarkers is observed after intense or long-lasting physical activity. However, a recent meta-analysis has suggested that there might be an inverse relationship between duration of exercise and degree of biomarker elevation. The objective of this observational study was to investigate the impact of ultra-marathon (UM) vs. marathon (M) on biomarkers of myocyte necrosis and hemodynamic stress/congestion. METHODS: Well-trained endurance athletes were recruited to participate in a 130-km UM and a M run. Troponin I (TnI), creatine kinase (CK), N-terminal pro-brain natriuretic peptide (NT-proBNP), mid-regional pro-adrenomedullin (MR-proADM), and copeptin were measured after both events, respectively. RESULTS: Fifteen athletes (14 males, one female) were included. There was no difference in exercise intensity according to the Borg scale (UM 16 [IQR 15-17], M 16 [IQR 14-17]; p = 0.424). Biomarkers of myocyte necrosis both differed significantly with higher levels of TnI (UM 0.056 ng/L [IQR 0.022-0.104), M 0.028 ng/L [IQR 0.022-0.049]; p = 0.016) and CK (UM 6992 U/l [IQR 2886-23038], M 425 U/l [IQR 327-681]; p = 0.001) after UM compared to M. Also, NT-proBNP (UM 723 ng/L [IQR 378-1152], M 132 ng/L [IQR 64-198]; p = 0.001) and MR-proADM (UM 1.012 nmol/L [IQR 0.753-0.975], M 0.877 nmol/L [IQR 0.550-0.985]; p = 0.023) as markers of myocardial congestion were significantly higher after UM. There was a tendency for elevated copeptin levels after M, but did not reach statistical significance (p = 0.078). CONCLUSION: Ultra-marathon is associated with higher levels of biomarkers of myocyte necrosis and cardiac congestion compared to marathon, highlighting the impact of exercise duration on the cardiovascular system.

Revisiting the obesity paradox in heart failure: Per cent body fat as predictor of biomarkers and outcome.

AIMS: Obesity defined by body mass index (BMI) is characterized by better prognosis and lower plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure. We assessed whether another anthropometric measure, per cent body fat (PBF), reveals different associations with outcome and heart failure biomarkers (NT-proBNP, high-sensitivity troponin T (hs-TnT), soluble suppression of tumorigenesis-2 (sST2)). METHODS: In an individual patient dataset, BMI was calculated as weight (kg)/height (m) 2 , and PBF through the Jackson-Pollock and Gallagher equations. RESULTS: Out of 6468 patients (median 68 years, 78% men, 76% ischaemic heart failure, 90% reduced ejection fraction), 24% died over 2.2 years (1.5-2.9), 17% from cardiovascular death. Median PBF was 26.9% (22.4-33.0%) with the Jackson-Pollock equation, and 28.0% (23.8-33.5%) with the Gallagher equation, with an extremely strong correlation (r = 0.996, p < 0.001). Patients in the first PBF tertile had the worst prognosis, while patients in the second and third tertile had similar survival. The risks of all-cause and cardiovascular death decreased by up to 36% and 27%, respectively, per each doubling of PBF. Furthermore, prognosis was better in the second or third PBF tertiles than in the first tertile regardless of model variables. Both BMI and PBF were inverse predictors of NT-proBNP, but not hs-TnT. In obese patients (BMI ≥ 30 kg/m2, third PBF tertile), hs-TnT and sST2, but not NT-proBNP, independently predicted outcome. CONCLUSION: In parallel with increasing BMI or PBF there is an improvement in patient prognosis and a decrease in NT-proBNP, but not hs-TnT or sST2. hs-TnT or sST2 are stronger predictors of outcome than NT-proBNP among obese patients.

A Sex-Specific Analysis of the Predictive Value of Troponin I and T in Patients With and Without Diabetes Mellitus After Successful Coronary Intervention.

Background: Elevated levels of troponin are associated with future major adverse cardiac events (MACE). Data on the prognostic value of high sensitive troponin T (hs-TnT) compared to high sensitive troponin I (hs-TnI) in diabetic and non-diabetic patients are sparse. Methods: We analyzed patients of a single-center registry undergoing coronary stenting between 2003 and 2006. As a primary endpoint we assessed MACE, a composite of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke according to sex and diabetes status using log-rank. As a second endpoint, we assessed the prognostic impact of hs-TnT and hs-TnI on MACE, adjusting for known confounders using Cox regression analysis. Results: Out of 818 investigated patients, 267 (32.6%) were female. Diabetes mellitus type 2 (T2DM) was diagnosed in 206 (25.2%) patients. After a mean follow-up of 6.6 ± 3.7 years, MACE occurred in 235 (28.7%) patients. The primary endpoint components of cardiovascular death occurred in 115 (14.1%) patients, MI in 75 (9.2%), and ischemic stroke in 45 (5.5%). Outcomes differed significantly according to sex and diabetes status (p = 0.003). In descending order, MACE rates were as follows: female diabetic patients (40.8%), female non-diabetic patients (32.7%), male diabetic patients (28.9%), and male non-diabetic patients (24.8%). Additionally, females with diabetes were at higher risk of cardiovascular death compared to diabetic men (28 vs. 15%). Hs-TnI (HR 1.477 [95% CI 1.100-1.985]; p = 0.010) and hs-TnT (HR 1.615 [95%CI 1.111-2.348]; p = 0.012) above the 99th percentile were significantly associated with MACE. Both assays showed tendency toward association with MACE in all subgroups. Conclusion: Diabetic patients, particularly females, with known coronary artery disease had a higher risk of subsequent MACE. Both, hs-TnI and hs-TnT significantly correlated with MACE.

High-sensitivity troponin T, NT-proBNP and glomerular filtration rate: A multimarker strategy for risk stratification in chronic heart failure.

BACKGROUND: In a recent individual patient data meta-analysis, high-sensitivity troponin T (hs-TnT) emerged as robust predictor of prognosis in stable chronic heart failure (HF). In the same population, we compared the relative predictive performances of hs-TnT, N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP), hs-C-reactive protein (hs-CRP), and estimated glomerular filtration rate (eGFR) for prognosis. METHODS AND RESULTS: 9289 patients (66 ±â€¯12 years, 77% men, 85% LVEF <40%, 60% ischemic HF) were evaluated over a 2.4-year median follow-up. Median eGFR was 58 mL/min/1.73 m2 (interquartile interval 46-70; n = 9220), hs-TnT 16 ng/L (8-20; n = 9289), NT-proBNP 1067 ng/L (433-2470; n = 8845), and hs-CRP 3.3 mg/L (1.4-7.8; n = 7083). In a model including all 3 biomarkers, only hs-TnT and NT-proBNP were independent predictors of all-cause and cardiovascular mortality and cardiovascular hospitalization. hs-TnT was a stronger predictor than NT-proBNP: for example, the risk for all-cause death increased by 54% per doubling of hs-TnT vs. 24% per doubling of NT-proBNP. eGFR showed independent prognostic value from both hs-TnT and NT-proBNP. The best hs-TnT and NT-proBNP cut-offs for the prediction of all-cause death increased progressively with declining renal function (eGFR ≥ 90: hs-TnT 13 ng/L and NT-proBNP 825 ng/L; eGFR < 30: hs-TnT 40 ng/L and NT-proBNP 4608 ng/L). Patient categorization according to these cut-offs effectively stratified patient prognosis across all eGFR classes. CONCLUSIONS: hs-TnT conveys independent prognostic information from NT-proBNP, while hs-CRP does not. Concomitant assessment of eGFR may further refine risk stratification. Patient classification according to hs-TnT and NT-proBNP cut-offs specific for the eGFR classes holds prognostic significance.

Prognostic Impact of Soluble P-Selectin on Long-Term Adverse Cardiovascular Outcomes in Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Soluble P-selectin (sP-selectin), a biomarker of inflammatory pathologies including cardiovascular disease, is known to have pro-atherosclerotic effects such as the ability to increase leukocyte recruitment and modulate thrombotic response. We aimed to assess the impact of sP-selectin on long-term major adverse cardiovascular events (MACE) in patients after coronary stenting for coronary artery disease. METHODS: We analysed 733 patients of a single-centre registry undergoing percutaneous coronary intervention (PCI) between 2003 and 2006. Plasma samples were analysed for sP-selectin antigen concentration with an enzyme-linked immunoassay. The study population was categorized according to sP-selectin quartiles. Endpoint of the study was long-term MACE, a composite of all-cause death, myocardial infarction (MI) and stroke. RESULTS: Of the total patient cohort, 361 (49.2%) patients were admitted for stable coronary artery disease and 372 (50.8%) for acute coronary syndrome. Median age was 64 years and 70.7% were male. After a mean follow-up period of 9.7 years, MACE occurred in 344 (46.9%) patients. The primary endpoint components of all-cause death occurred in 211 (28.8%), MI in 88 (12.0%) and ischaemic stroke in 45 (6.1%) patients. After adjustment for confounders, patients in the 2nd, 3rd and 4th quartile were at higher risk for MACE compared with the 1st quartile (hazard ration [HR], 1.234 [0.899-1.695], p = 0.193; HR, 1.480 [1.085-2.019], p = 0.013; and HR, 1.571 [1.115-2.152], p = 0.004). sP-selectin as continuous variable model was significantly associated with MACE after adjustment (HR per 1 ng/mL increase of 1.009 [95% confidence interval, 1.002-1.017]; p = 0.016). CONCLUSION: Elevated levels of sP-selectin were associated with increased risk for long-term MACE in patients undergoing PCI.

Prognostic Value of High-Sensitivity Troponin T in Chronic Heart Failure: An Individual Patient Data Meta-Analysis.

BACKGROUND: Most patients with chronic heart failure have detectable troponin concentrations when evaluated by high-sensitivity assays. The prognostic relevance of this finding has not been clearly established so far. We aimed to assess high-sensitivity troponin assay for risk stratification in chronic heart failure through a meta-analysis approach. METHODS: Medline, EMBASE, Cochrane Library, and Scopus were searched in April 2017 by 2 independent authors. The terms were "troponin" AND "heart failure" OR "cardiac failure" OR "cardiac dysfunction" OR "cardiac insufficiency" OR "left ventricular dysfunction." Inclusion criteria were English language, clinical stability, use of a high-sensitivity troponin assay, follow-up studies, and availability of individual patient data after request to authors. Data retrieved from articles and provided by authors were used in agreement with the PRISMA statement. The end points were all-cause death, cardiovascular death, and hospitalization for cardiovascular cause. RESULTS: Ten studies were included, reporting data on 11 cohorts and 9289 patients (age 66±12 years, 77% men, 60% ischemic heart failure, 85% with left ventricular ejection fraction <40%). High-sensitivity troponin T data were available for all patients, whereas only 209 patients also had high-sensitivity troponin I assayed. When added to a prognostic model including established risk markers (sex, age, ischemic versus nonischemic etiology, left ventricular ejection fraction, estimated glomerular filtration rate, and N-terminal fraction of pro-B-type natriuretic peptide), high-sensitivity troponin T remained independently associated with all-cause mortality (hazard ratio, 1.48; 95% confidence interval, 1.41-1.55), cardiovascular mortality (hazard ratio, 1.40; 95% confidence interval, 1.33-1.48), and cardiovascular hospitalization (hazard ratio, 1.42; 95% confidence interval, 1.36-1.49), over a median 2.4-year follow-up (all P<0.001). High-sensitivity troponin T significantly improved risk prediction when added to a prognostic model including the variables above. It also displayed an independent prognostic value for all outcomes in almost all population subgroups. The area under the curve-derived 18 ng/L cutoff yielded independent prognostic value for the 3 end points in both men and women, patients with either ischemic or nonischemic etiology, and across categories of renal dysfunction. CONCLUSIONS: In chronic heart failure, high-sensitivity troponin T is a strong and independent predictor of all-cause and cardiovascular mortality, and of hospitalization for cardiovascular causes, as well. This biomarker then represents an additional tool for prognostic stratification.

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.

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.

Determinants of growth differentiation factor 15 in patients with stable and acute coronary artery disease. A prospective observational study.

BACKGROUND: Growth differentiation factor 15 (GDF-15) is a member of the transforming growth factor ß family and has been associated with inflammation, cancer, aging, diabetes mellitus (DM) and atherosclerosis. Determinants of GDF-15 have been investigated in several conditions. We aimed to investigate determinants of GDF-15 plasma levels in patients with angiographically proven coronary artery disease (CAD). METHODS: Four hundred and seventy three consecutive patients with CAD were investigated between May 2009 and February 2011. Patients were separated into those with stable CAD (SCAD) and with ST-elevation and non-ST-elevation myocardial infarction (STEMI and NSTEMI). Blood samples for determination of GDF-15 were obtained before coronary angiography. Determinant of GDF-15 levels were analyzed by logistic regression analysis in unadjusted and adjusted models. Study endpoints were cardiovascular death (CV-death), myocardial infarction, unstable angina, unplanned revascularization, stent thrombosis and stroke assessed at a mean follow-up of 188 (177.2-243) days. RESULTS: Overall median and (25-27th percentile) GDF-15 level was 1212.8 pg/ml (833.2-1957 pg/ml). GDF-15 was significantly higher in STEMI compared to SCAD and NSTEMI groups (P < 0.0001). In a multivariate regression analysis advanced age, DM, acute hyperglycemia (AHG), CRP and chronic kidney disease (CKD) were independent predictors of elevated GDF-15 levels (P < 0.05). Receiver operating curve analysis of GDF-15 for prediction of CV-death showed an area under the curve of 0.852 with a confidence interval of 0.745-0.960, P < 0.0001. The estimated cut-off was 2094.6 pg/ml with a sensitivity of 76 % and specificity of 80 %. CONCLUSION: In patients with CAD undergoing PCI with stent implantation, GDF-15 is determined by advanced age, acute and chronic hyperglycemia, inflammation and CKD. GDF-15 is a valuable predictor of CV-death in a population of CAD patients after PCI.

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.

G-CSF Predicts Cardiovascular Events in Patients with Stable Coronary Artery Disease.

Granulocyte-colony-stimulating-factor (G-CSF) induces mobilization of progenitor cells but may also exert pro-inflammatory and pro-thrombotic effects. Treatment with recombinant G-CSF after acute myocardial infarction is currently under examination and has been associated with in-stent restenosis. However, it is not known whether plasma levels of endogenous G-CSF are also associated with an increased cardiovascular risk. Therefore we included 280 patients with angiographically proven stable coronary artery disease. G-CSF was measured by specific ELISA and patients were followed for a median of 30 months for the occurrence of major adverse cardiovascular events (MACE: death, myocardial infarction, re-hospitalization). Those with cardiac events during follow-up showed significant higher G-CSF levels (32.3 pg/mL IQR 21.4-40.5 pg/mL vs. 24.6 pg/mL IQR 16.4-34.9 pg/mL; p<0.05) at baseline. Patients with G-CSF plasma levels above the median had a 2-fold increased risk for MACE (p<0.05). This was independent from established cardiovascular risk factors. In addition, G-CSF above the median was a predictor of clinical in-stent restenosis after implantation of bare-metal stents (6.6% vs. 19.4%; p<0.05) but not of drug-eluting stents (7.7% vs. 7.6%; p = 0.98). This data suggests that endogenous plasma levels of G-CSF predict cardiovascular events independently from established cardiac risk factors and are associated with increased in-stent restenosis rates after implantation of bare metal stents.

Long-term mortality of patients with atrial fibrillation undergoing percutaneous coronary intervention with stent implantation for acute and stable coronary artery disease.

BACKGROUND: Patients with atrial fibrillation (AF) are of increased risk for ischemic and bleeding complications, particularly when requiring aggressive antithrombotic therapy after coronary stenting. However, data from unselected patients on long-term mortality are scarce. METHODS: We analyzed 2890 patients of a single-center registry undergoing coronary stenting between 2003 and 2012, of whom 1434 patients had stable coronary artery disease (CAD), while 1456 patients presented with acute coronary syndromes (ACS). As the primary endpoint, we compared long-term all-cause mortality between patients with AF and patients in sinus rhythm. RESULTS: History or presence of AF was found in 146 (10.2%) patients with stable CAD and 93 (6.4%) patients with ACS. The median CHA2DS2-VASc scores were similar between stable CAD and ACS patients (4[2; 5] vs. 3[2; 5], p=0.92). Patients with AF had a significantly higher atherothrombotic risk profile and more co-morbidities. Patients undergoing PCI before 2011 received triple therapy (aspirin, clopidogrel and a vitamin K antagonist) in 25% of cases, compared to 64% of cases thereafter. Patients undergoing elective or urgent revascularization and suffering from AF had a similar 2-fold increased adjusted relative risk of death after a mean follow-up of 4.8 years (HR 1.95, 95% CI 1.27; 2.99, p<0.01 for stable CAD and HR 1.95, 95% CI 1.23; 3.11, p<0.01 for ACS). CONCLUSION: In a general practice setting, patients with AF had significantly increased adjusted long-term mortality than patients without AF. After publication of the consensus document of different working groups of the European Society of Cardiology in 2010, triple therapy increased markedly.

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.

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.