Major bleeding risk prediction using Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease equations in acute coronary syndrome.

BACKGROUND: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular filtration rate more accurately than the Modification of Diet in Renal Disease (MDRD) Study equation. Our aim was to evaluate whether CKD-EPI equations based on serum creatinine and/or cystatin C (CysC) predict risk for major bleeding (MB) more accurately than the MDRD Study equation in patients with non-ST-segment elevation acute coronary syndromes (ACS). MATERIALS AND METHODS: Three hundred and fifty consecutive subjects with non-ST-segment elevation ACS (68 ± 12 years, 70% male) were studied. Glomerular filtration rate was estimated using the CKD-EPI and MDRD Study equations. The primary endpoint was the occurrence of MB during the follow-up, which was defined according to the Bleeding Academic Research Consortium Definition criteria as bleeding types 3-5. RESULTS: During the median follow-up of 589 days (interquartile range, 390-986), 27 patients had MB (0.04% events per person year). Patients with MB had worse kidney function parameters, regardless of the estimating equation used (P < 0.001). After multivariate Cox regression adjustment, both CysC-based CKD-EPI equations were independent predictors of MB (CKD-EPI(creatinine-cystatin) C per mL/min/1.73 m(2), HR = 0.973 (95%CI 0.955-0.991; P = 0.003) and CKD-EPI(cystatin) C per mL/min/1.73 m(2), HR = 0.976 (95%CI 0.976-0.992; P = 0.003), while the CKD-EPI(creatinine) and MDRD equations did not achieve statistical significance. Both CKD-EPI(creatine-cystatin) C and CKD-EPI(cystatin) C were associated with a significant improvement in MB risk reclassification. CONCLUSIONS: In this cohort of non-ST-segment elevation ACS patients with relatively preserved renal function, both CysC-based CKD-EPI equations improved ability to predict risk for MB and were superior to other equations for this application.

Beta-trace protein and cystatin c as predictors of major bleeding in non-ST-segment elevation acute coronary syndrome.

BACKGROUND: Beta-trace protein (BTP) and cystatin C (CysC) are novel biomarkers of renal function. We assessed the ability of both to predict major bleeding (MB) in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS), compared to other renal function parameters and clinical risk scores. METHODS AND RESULTS: We included 273 patients. Blood samples were obtained within 24h of admission. The endpoint was MB. During a follow-up of 760 days (411-1,098 days), 25 patients (9.2%) had MB. Patients with MB had higher concentrations of BTP (0.98 mg/L; 0.71-1.16 mg/L vs. 0.72 mg/L, 0.60-0.91 mg/L, P=0.002), CysC (1.05 mg/L; 0.91-1.30 mg/L vs. 0.90 mg/L, 0.75-1.08 mg/L, P=0.003), higher CRUSADE score (39 ± 16 points vs. 29 ± 15 points, P=0.002) and lower estimated glomerular filtration rate (eGFR; 66 ± 27 vs. 80 ± 30 ml·min(-1)·1.73 m(-2), P=0.02) than patients without MB; there was no difference in creatinine level between the groups (P=0.14). After multivariable adjustment, both were predictors of MB, while eGFR and creatinine did not achieve statistical significance. Among subjects with eGFR >60 ml·min(-1)·1.73 m(-2), those with elevated concentrations of both biomarkers had a significantly higher risk for MB. Net reclassification indexes from the addition of BTP and CysC to CRUSADE risk score were 38% and 21% respectively, while the relative integrated discrimination indexes were 12.5% and 3.8%. CONCLUSIONS: Among NSTE-ACS patients, BTP and CysC were superior to conventional renal parameters for predicting MB, and improved clinical stratification for hemorrhagic risk.

High-sensitivity troponin T and copeptin in non-ST acute coronary syndromes: implications for prognosis and role of hsTnT and copeptin in non-STEACS.

UNLABELLED: High-sensitivity TnT (hsTnT) has been proposed to improve the diagnosis and stratification in acute coronary syndromes. Copeptin has been proposed for a rapid and accurate rule out of acute myocardial infarction, but some doubts exist about its use out of the first hours from admission. Abnormalities of serum hsTnT and copeptin levels in non-STEACS and negative TnT, could have prognostic implications. METHODS: We included 122 non-STEACS patients without raised TnT, 33 disease controls and 43 healthy controls. We measured hsTnT and copeptin levels. Clinical follow-up at 12 months was performed for adverse endpoints. RESULTS: Non-STEACS patients had raised hsTnT compared with both control groups (P = 0.036 and P < 0.001). Copeptin levels were higher in non-STEACS patients than healthy controls (P = 0.021), without differences with disease controls. Raised levels of hs-TnT presented prognostic implications [HR 3.29 (95%CI: 1.33-7.49), P = 0.010]. hs-TnT could be used for invasive approach decision, as it shows prognostic relevance in conservative approach-patients whereas remains unrelevant for catheterized-patients. Copeptin levels were not associated with adverse events. CONCLUSION: hsTnT levels increased in non-STEACS, were predictive of adverse events and could be important for recommending an invasive management. We cannot confirm a predictive role of copeptin out of the first hours from admission.

P2Y12 inhibitors in acute coronary syndrome patients with renal dysfunction: an analysis from the RENAMI and BleeMACS projects.

AIMS: The aim of the present study was to establish the safety and efficacy profile of prasugrel and ticagrelor in real-life acute coronary syndrome (ACS) patients with renal dysfunction. METHODS AND RESULTS: All consecutive patients from RENAMI (REgistry of New Antiplatelets in patients with Myocardial Infarction) and BLEEMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registries were stratified according to estimated glomerular filtration rate (eGFR) lower or greater than 60 mL/min/1.73 m2. Death and myocardial infarction (MI) were the primary efficacy endpoints. Major bleedings (MBs), defined as Bleeding Academic Research Consortium bleeding types 3 to 5, constituted the safety endpoint. A total of 19 255 patients were enrolled. Mean age was 63 ± 12; 14 892 (77.3%) were males. A total of 2490 (12.9%) patients had chronic kidney disease (CKD), defined as eGFR <60 mL/min/1.73 m2. Mean follow-up was 13 ± 5 months. Mortality was significantly higher in CKD patients (9.4% vs. 2.6%, P < 0.0001), as well as the incidence of reinfarction (5.8% vs. 2.9%, P < 0.0001) and MB (5.7% vs. 3%, P < 0.0001). At Cox multivariable analysis, potent P2Y12 inhibitors significantly reduced the mortality rate [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.54-0.96; P = 0.006] and the risk of reinfarction (HR 0.53, 95% CI 0.30-0.95; P = 0.033) in CKD patients as compared to clopidogrel. The reduction of risk of reinfarction was confirmed in patients with preserved renal function. Potent P2Y12 inhibitors did not increase the risk of MB in CKD patients (HR 1.00, 95% CI 0.59-1.68; P = 0.985). CONCLUSION: In ACS patients with CKD, prasugrel and ticagrelor are associated with lower risk of death and recurrent MI without increasing the risk of MB.

Efficacy and Safety of Clopidogrel, Prasugrel and Ticagrelor in ACS Patients Treated with PCI: A Propensity Score Analysis of the RENAMI and BleeMACS Registries.

INTRODUCTION: Real-life data comparing clopidogrel, prasugrel, and ticagrelor for unselected patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) are lacking, as are data for the temporal distribution of ischemic and bleeding risks. METHODS: A total of 19,825 patients were enrolled from the RENAMI and BleeMACS registries. Both were multicenter, retrospective, observational registries including the data and outcomes of consecutive patients with ACS who underwent primary PCI and were discharged with dual antiplatelet therapy (DAPT). We evaluated the long-term outcome stratified by the different antiplatelet agents. RESULTS: A total of 14,105 patients (71.2%) were treated with clopidogrel, 2364 patients (11.9%) with prasugrel and 3356 patients (16.9%) with ticagrelor. After propensity score matching, at 1 year, prasugrel reduced the incidence of net adverse clinical events (NACE; a composite endpoint of all-cause death, myocardial infarction [MI] and Bleeding Academic Research Consortium [BARC] 3-5 bleeding) (4.2% vs.7.6%, p = 0.002) and of major adverse cardiovascular events (MACE; a composite endpoint of death and MI) compared with clopidogrel (2.6% vs. 5.2%, p = 0.007). Ticagrelor decreased rates of MACE compared with clopidogrel (2.7% vs. 6.2%, p < 0.001), but not of NACE (6.6% vs. 8.7%, p = 0.07). Ticagrelor presented similar performance in terms of MACE compared with prasugrel (2.8% vs. 2.4%, p = 0.56), with a trend towards a reduction in MI (0.2% vs. 0.4%, p = 0.56), but with higher risk of BARC 3-5 bleedings (3.8% vs. 1.7%, p = 0.04). In the daily risk analysis, clopidogrel presented a binomial distribution with a peak of ischemic risk at 3 months, which decreased towards bleedings; prasugrel had a constant equivalence between opposite risks; and ticagrelor constantly reduced recurrent MIs despite higher risk of BARC 3-5 events. CONCLUSION: In real life, ticagrelor is more effective in reducing ischemic events during the first year after ACS, despite an increased risk of major bleedings, while prasugrel assures a better balance between ischemic and bleeding recurrent events.

Comparative external validation of the PRECISE-DAPT and PARIS risk scores in 4424 acute coronary syndrome patients treated with prasugrel or ticagrelor.

BACKGROUND: The PRECISE-DAPT and PARIS risk scores (RSs) were recently developed to help clinicians at individualizing the optimal dual antiplatelet therapy duration (DAPT) after percutaneous coronary intervention (PCI). Nevertheless, external validation of these RSs it has not yet been performed in ACS (acute coronary syndrome) patients treated with prasugrel or ticagrelor in a real- world scenario. METHODS: 4424 ACS patients who underwent PCI and survived to hospital discharge, from January 2012 to December 2016 at 12 European centers, were included. PRECISE-DAPT and PARIS bleeding RS, as well as PARIS ischemic RS, were computed, and their performance at predicting major bleeding (MB; BARC type 3 or 5) and ischemic events (MI and stent thrombosis) during follow up was compared. RESULTS: After a median follow-up of 14 (interquartile range 12-20.9) months, 83 (1.88%) patients developed MB and 133 (3.0%) suffered an ischemic episode. PRECISE-DAPT performed better than PARIS bleeding RS (c-statistic = 0.653 vs. 0.593; p = .01 for comparison) in predicting MB. The RSs performance for MB prediction remained consistent in STEMI patients (c-statistic = 0.632 vs 0.575) or in those treated with prasugrel (c-statistic = 0.623 vs 0.586). PARIS ischemic RS exhibited superior discrimination in predicting ischemic complications compared to PRECISE-DAPT (c-statistic = 0.604 vs 0.568 p = .05 for comparison). CONCLUSION: Our data provide support to the use of PRECISE-DAPT in MB risk stratification for patients receiving DAPT in form of aspirin and prasugrel or ticagrelor whereas the PARIS ischemic RS has potential to complement the risk prediction with respect to ischemic events.

Renin-Angiotensin System Blockade and Risk of Heart Failure After Myocardial Infarction Based on Left Ventricular Ejection Fraction: A Retrospective Cohort Study.

INTRODUCTION: The goal of this study was to determine the association between the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) and follow-up heart failure (HF) according to left ventricular ejection fraction (LVEF) in patients with acute myocardial infarction (AMI). METHODS: This cohort study used a retrospective registry of 8169 consecutive patients discharged with a diagnosis of AMI from two university hospitals in Spain between 2010 and 2016. We used a multivariable competing risk analysis, survival-time inverse probability weighting (IPW) propensity score adjusting, and propensity score matching (PSM) to investigate the association between ACEI/ARB treatment and follow-up HF. RESULTS: During the follow-up (3.3 ± 2.2 years), 1296 patients were admitted for HF (5.2 per 100 person-years). ACEI/ARB use was not associated with fewer follow-up HF admissions in patients with LVEF > 40% (univariate analysis: sub-hazard ratio [sHR] 1.10; 95% confidence interval [CI] 0.95-1.27; p = 0.197; IPW adjusting analysis: sHR 1.11; 95% CI 0.95-1.29; p = 0.192; PSM analysis: sHR 1.12; 95% CI 0.92-1.36; p = 0.248). However, ACEI/ARB use was associated with a significant reduction in HF admission rates in patients with LVEF ≤ 40% (univariate analysis: HR 0.70; 95% CI 0.56-0.88; p = 0.003; IPW adjusting analysis: HR 0.64; 95% CI 0.50-0.83; p = 0.001; PSM analysis: HR 0.65; 95% CI 0.46-0.92; p = 0.014). CONCLUSION: Among hospitalized survivors of AMI, the use of ACEIs/ARBs was associated with a lower risk of follow-up HF in patients with LVEF ≤ 40% but not in those with LVEF > 40%. Further prospective studies are needed to confirm our results.

Differential Prognostic Impact on Mortality of Myocardial Infarction Compared With Bleeding Severity in Contemporary Acute Coronary Syndrome Patients.

INTRODUCTION AND OBJECTIVES: The impact on mortality of myocardial infarction (MI) compared with the specific degree of bleeding severity occurring after discharge in acute coronary syndrome is poorly characterized. Defining this relationship may help to achieve a favorable therapeutic risk-benefit balance. METHODS: Using Cox-based shared frailty models, we assessed the relationship between mortality and postdischarge MI and bleeding severity-graded according to Bleeding Academic Research Consortium (BARC)-in 4229 acute coronary syndrome patients undergoing in-hospital coronary arteriography between January 2012 and December 2015. RESULTS: Both MI (HR, 5.8; 95%CI, 3.7-9.8) and bleeding (HR, 5.1; 95%CI, 3.6-7.7) were associated with mortality. Myocardial infarction had a stronger impact on mortality than BARC type 2 and 3a bleedings: (RRr, 3.8 and 1.9; P < .05), respectively, but was equivalent to BARC type 3b (RRr, 0.9; P = .88). Mortality risk after MI was significantly lower than after BARC type 3c bleeding (RRr, 0.25; P < .001). Mortality was higher after an MI in patients on dual antiplatelet therapy (DAPT) at the time of the event (HR, 2.9; 95%CI, 1.8-4.5) than in those off-DAPT (HR, 1.5; 95%CI, 0.7-3.4). In contrast, mortality was lower after a bleeding event in patients on-DAPT (HR, 1.6; 95%CI, 1.1-2.6) than in those off-DAPT (HR, 3.2; 95%CI, 1.7-5.8). CONCLUSIONS: The differential effect on mortality of a postdischarge MI vs bleeding largely depends on bleeding severity. The DAPT status at the time of MI or bleeding is a modifier of subsequent mortality risk.

Large saphenous graft aneurysm that compresses the right heart.

We present an illustrative case of a very rare complication of saphenous bypass: a huge aneurysm that severely compresses the right-heart cavities.

Evaluation of the CRUSADE Risk Score for Predicting Major Bleeding in Patients with Concomitant Kidney Dysfunction and Acute Coronary Syndromes.

BACKGROUND: Kidney dysfunction (KD) has been associated with increased risk for major bleeding (MB) in patients with acute coronary syndromes (ACS) and may be in part related to an underuse of evidence-based therapies. Our aim was to assess the predictive ability of the Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE) risk score in patients with concomitant ACS and chronic kidney disease. METHODS: We conducted a retrospective analysis of a prospective registry including 1,587 ACS patients. In-hospital MB was prospectively recorded according to the CRUSADE and Bleeding Academic Research Consortium (BARC) criteria. KD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2. RESULTS: The predictive ability of the CRUSADE risk score was assessed by discrimination and calibration analyses. A total of 465 (29%) subjects had KD. In multivariate logistic regression analyses, we found high CRUSADE risk score values to be associated with a higher rate of in-hospital MB; however, among patients with KD, it was not associated with BARC MB. Regardless of the MB definition, the predictive ability of the CRUSADE score in patients with KD was lower: area under the curve (AUC) 0.71 versus 0.79, p = 0.03 for CRUSADE MB and AUC 0.65 versus 0.75, p = 0.02 for BARC MB. Hosmer-Lemeshow analyses showed a good calibration in all renal function subgroups for both MB definitions (all p values >0.3). CONCLUSIONS: The CRUSADE risk score shows a lower accuracy for predicting in-hospital MB in KD patients compared to those without KD.

Comparison of Risk Prediction With the CKD-EPI and MDRD Equations in Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular filtration rate (GFR) more accurately than the Modification of Diet in Renal Disease (MDRD) equation. HYPOTHESIS: New CKD-EPI equations improve risk stratification in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and provide complementary information to the Global Registry of Acute Coronary Events (GRACE) risk score. METHODS: We studied 350 subjects (mean age, 68 ± 12 years; 70% male) with NSTE-ACS. Estimated GFR was calculated using the MDRD and new CKD-EPI equations based on serum creatinine (SCr) and/or cystatin C (CysC) concentrations obtained within 48 hours of hospital admission. The primary endpoint was all-cause death during follow-up. RESULTS: Over the study period (median, 648 days [interquartile range, 236-1042 days]), 31 patients died (0.05% events per person-year). Decedents had poorer renal-function parameters (P < 0.001). Both CysC-based CKD-EPI equations had the highest areas under the receiver operating characteristic curve for the prediction of all-cause mortality. After multivariate adjustment, only CysC-based CKD-EPI equations were independent predictors of all-cause mortality (CKD-EPISCr - CysC , per mL/min/1.73 m(2) : hazard ratio: 0.975, 95% confidence interval: 0.956-0.994, P = 0.009; CKD-EPICysC , per mL/min/1.73 m(2) : hazard ratio: 0.976, 95% confidence interval: 0.959-0.993, P = 0.005). Reclassification analyses showed that only CysC-based CKD-EPI equations improved predictive accuracy of the GRACE risk score. CONCLUSIONS: In patients with NSTE-ACS, CysC-based CKD-EPI equations improved clinical risk stratification for mortality and added complementary prognostic information to the GRACE risk score.

Comparison between type-2 and type-1 myocardial infarction: clinical features, treatment strategies and outcomes.

OBJECTIVE: To assess the differences in incidence, clinical features, current treatment strategies and outcome in patients with type-2 vs. type-1 acute myocardial infarction (AMI). METHODS: We included 824 consecutive patients with a diagnosis of type-1 or type-2 AMI. During index hospitalization, clinical features and treatment strategies were collected in detail. At 1-year follow-up, mortality, stroke, non-fatal myocardial infarction and major bleeding were recorded. RESULTS: Type-1 AMI was present in 707 (86%) of the cases while 117 (14%) were classified as type-2. Patients with type-2 AMI were more frequently female and had higher co-morbidities such as diabetes, previous non-ST segment elevation acute coronary syndromes, impaired renal function, anaemia, atrial fibrillation and malignancy. However, preserved left ventricular ejection fraction and normal coronary arteries were more frequently seen, an invasive treatment was less common, and anti-platelet medications, statins and beta-blockers were less prescribed in patients with type-2 AMI. At 1-year follow-up, type-2 AMI was associated with a higher crude mortality risk (HR: 1.75, 95% CI: 1.14-2.68; P = 0.001), but this association did not remain significant after multivariable adjustment (P = 0.785). Furthermore, we did not find type-2 AMI to be associated with other clinical outcomes. CONCLUSIONS: In this real-life population, compared with type-1, type-2 AMI were predominantly women and had more co-morbidities. Invasive treatment strategies and cardioprotective medications were less used in type-2, while the 1-year clinical outcomes were similar.

Comparison of the Global Registry of Acute Coronary Events Risk Score Versus the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse outcomes With Early Implementation of the ACC/AHA Guidelines Risk Score to Predict In-Hospital Mortality and Major Bleeding in Acute Coronary Syndromes.

Risk assessment plays a major role in the management of acute coronary syndrome. The aim was to compare the performance of the Global Registry of Acute Coronary Events (GRACE) and the Can Rapid risk stratification of Unstable angina patients Suppress Adverse outcomes with Early implementation of the American College of Cardiology/American Heart Asociation guidelines (CRUSADE) risk scores to predict in-hospital mortality and major bleeding (MB) in 1,587 consecutive patients with acute coronary syndrome. In-hospital deaths and bleeding complications were prospectively collected. Bleeding complications were defined according to CRUSADE and Bleeding Academic Research Consortium (BARC) criteria. During the hospitalization, 71 patients (4.5%) died, 37 patients (2.3%) had BARC MB and 34 patients (2.1%) had CRUSADE MB. Receiver operating characteristic curves analyses showed GRACE risk score has better discrimination capacity than CRUSADE risk score for both, mortality (0.86 vs 0.79; p = 0.018) and BARC MB (0.80 vs 0.73; p = 0.028), but similar for CRUSADE MB (0.79 vs 0.79; p = 0.921). Both scores had low discrimination for predicting MB in the elderly (>75 years) and patients with atrial fibrillation, whereas CRUSADE risk score was especially poor for predicting MB in patients with <60 ml/min/1.73 m(2) or those treated with new antiplatelets. Reclassification analyses showed GRACE risk score was associated with a significant improvement in the predictive accuracy of CRUSADE risk score for predicting mortality (net reclassification improvement: 22.5%; p <0.001) and MB (net reclassification improvement: 17.6%; p = 0.033) but not for CRUSADE MB. In conclusion, GRACE risk score has a better predictive performance for predicting both in-hospital mortality and BARC MB. In light of these findings, we propose the GRACE score as a single score to predict these in-hospital complications.

Red cell distribution width and additive risk prediction for major bleeding in non-ST-segment elevation acute coronary syndrome.

INTRODUCTION AND OBJECTIVES: Red cell distribution width has been linked to an increased risk for in-hospital bleeding in patients with non-ST-segment elevation acute coronary syndrome. However, its usefulness for predicting bleeding complications beyond the hospitalization period remains unknown. Our aim was to evaluate the complementary value of red cell distribution width and the CRUSADE scale to predict long-term bleeding risk in these patients. METHODS: Red cell distribution width was measured at admission in 293 patients with non-ST-segment elevation acute coronary syndrome. All patients were clinically followed up and major bleeding events were recorded (defined according to Bleeding Academic Research Consortium Definition criteria). RESULTS: During a follow-up of 782 days [interquartile range, 510-1112 days], events occurred in 30 (10.2%) patients. Quartile analyses showed an abrupt increase in major bleedings at the fourth red cell distribution width quartile (> 14.9%; P=.001). After multivariate adjustment, red cell distribution width >14.9% was associated with higher risk of events (hazard ratio=2.67; 95% confidence interval, 1.17-6.10; P=.02). Patients with values ≤ 14.9% and a CRUSADE score ≤ 40 had the lowest events rate, while patients with values >14.9% and a CRUSADE score >40 points (high and very high risk) had the highest rate of bleeding (log rank test, P<.001). Further, the addition of red cell distribution width to the CRUSADE score for the prediction of major bleeding had a significant integrated discrimination improvement of 5.2% (P<.001) and a net reclassification improvement of 10% (P=.001). CONCLUSIONS: In non-ST-segment elevation acute coronary syndrome patients, elevated red cell distribution width is predictive of increased major bleeding risk and provides additional information to the CRUSADE scale.

ß-Trace protein: from GFR marker to cardiovascular risk predictor.

ß-Trace protein, also known as Lipocalin type prostaglandin D synthase, is a low-molecular mass glycoprotein (between 23,000 and 29,000 Da depending on the degree of glycosylation) that converts prostaglandin H2 into prostaglandin D2. ß-Trace protein was initially isolated from cerebrospinal fluid and served as a marker of cerebrospinal fluid leakage; however, its cDNA and gene have been isolated in numerous human body tissues, including central nervous system, retina, melanocytes, heart, and male genital organs. In recent years, ß-trace protein has emerged as a promising novel endogenous marker of GFR, representing a more sensitive marker for mild kidney dysfunction than serum creatinine. In this regard, ß-trace protein has been proposed as an alternative marker to Cystatin C for measuring kidney function. Beyond its role for estimating renal function, ß-trace protein is also emerging as a novel biomarker in cardiovascular risk. It has been associated with several cardiovascular disorders, playing a potential role for prognostic stratification in patients with acutely decompensated heart failure and acute coronary syndromes and being advocated as a novel marker for cardiovascular risk prediction.

Small-size circulating microparticles in acute coronary syndromes: relevance to fibrinolytic status, reparative markers and outcomes.

BACKGROUND: Recent evidence suggests that circulating microparticles (MPs) contribute to inflammation, coagulation and vascular injury. Majority of MPs have usually not been included into prior analyses due their small size and limited resolution of conventional equipment. Our aim was to assess levels of MPs of different cellular origin sized below 0.5 µm polystyrene beads, denoted as small-size microparticles (sMP), their relation to markers of cardiovascular repair and their impact on prognosis in patients with acute coronary syndromes (ACS). METHODS: In a cross-sectional study, we initially compared levels of sMP between patients with ST-segment elevation myocardial infarction (STEMI, n = 50), non-STEMI (n = 47), stable coronary artery disease (CAD, n = 40) and healthy individuals (HC, n = 40). In a separate study, the prognostic value of sMP was assessed in patients with non-STEMI (n = 160). Annexin V-binding sMP (sAMP), platelet CD42b(+) sMPs (sPMP), endothelial CD144(+) sMP (sEMP) and monocyte CD14(+) sMP (sMMP) were quantified using high resolution flow cytometry. Endothelial progenitor cells (EPCs) and monocyte expression of scavenger receptors was quantified by flow cytometry. Fibrinolytic factors were measured by ELISA. RESULTS: Counts of sAMP and sEMP were lower in STEMI after PCI (p < 0.001 and p = 0.025, respectively) but not in non-STEMI vs. CAD. sAMP was positively correlated with EPCs in non-STEMI (p < 0.001). Likewise, plasminogen activators negatively correlated with sAMP in non-STEMI and STEMI (p = 0.02 and p = 0.002, respectively). In non-STEMI patients, sEMP and sMMP were independently predictive for future admissions related to heart failure (p = 0.034 and 0.013, respectively) and sPMP for major bleedings (p = 0.002). The sAMP/EPCs ratio was higher in patients (before PCI) compared to STEMI patients. CONCLUSIONS: Small-size MPs could be potentially implicated in the modulation of the post-ACS reparative response to injury, with prognostic implications. Besides, the sAMP/EPCs ratio could reflect a change in the apoptotic/reparative potential, being a putative indicator for vascular repair.

Exercise eco-Doppler in hypertrophic cardiomyopathy patients. Determinant factors of exercise intolerance.

INTRODUCTION AND OBJECTIVES: At-rest echocardiography is a poor predictor of exercise capacity in patients with hypertrophic cardiomyopathy. We aimed to test the performance of treadmill exercise Doppler echocardiography in the prediction of functional limitations in these patients. METHODS: Eighty-seven consecutive patients with hypertrophic cardiomyopathy underwent treadmill exercise echocardiography with direct measurement of oxygen consumption. Both at rest and at peak exercise, the mitral inflow, mitral regurgitation, left ventricular outflow tract obstruction and mitral annulus velocities were assessed. RESULTS: Forty-three patients developed left ventricular outflow tract obstruction during exercise, which significantly decreased oxygen consumption (21.3 [5.7] mL/kg/min vs 24.6 [6.1] mL/kg/min; P=.012), and had greater left atrial volume (42.1 [14.5] mL/m(2) vs 31.1 [11.6] mL/m(2); P<.001) and a higher degree of mitral regurgitation and E/E' ratio during exercise. Exercise variables improved the predictive value of functional capacity (adjusted R(2) rose from 0.38 to 0.49). Independent predictors of oxygen consumption were age, left atrial volume, E/E' ratio and the presence of left ventricular outflow tract obstruction. In a subset of patients without left ventricular outflow obstruction, only left ventricular and atrial volume indexes were independent predictors of exercise capacity. CONCLUSIONS: In patients with hypertrophic cardiomyopathy, left ventricular outflow tract obstruction and left atrial volume are the main predictors of exercise capacity. Exercise echocardiography is a better predictor of functional performance than at-rest echocardiography, although its predictive power is under 50%. In nonobstructed patients, left atrial and ventricular volumes were the independent factors.

Interleukin-6 and high-sensitivity C-reactive protein for the prediction of outcomes in non-ST-segment elevation acute coronary syndromes.

INTRODUCTION AND OBJECTIVES: High baseline levels of interleukin-6 and C-reactive protein confer an increased risk of mortality in non-ST-segment elevation acute coronary syndrome. The aim of the study was to determine whether serial measurements of interleukin-6 and high-sensitivity C-reactive protein provide additional information to baseline measurements for risk stratification of non-ST-segment elevation acute coronary syndrome. METHODS: Two hundred and sixteen consecutive patients with non-ST-segment elevation acute coronary syndrome were prospectively included. Blood samples were obtained within 24 h of hospital admission and at 30 days of follow-up. The endpoint was a composite of all-cause death, nonfatal myocardial infarction, or acute decompensated heart failure. RESULTS: Both interleukin-6 and high-sensitivity C-reactive protein levels decreased from day 1 to day 30, regardless of adverse events (both P<.001). Interleukin-6 levels at 2 time points (interleukin-6 day 1, per pg/mL; hazard ratio=1.006, 95% confidence interval, 1.002-1.010; P=.002 and interleukin-6 day 30, per pg/mL, hazard ratio=1.047, 95% confidence interval, 1.021-1.075, P<.001) were independent predictors of adverse events, whereas high-sensitivity C-reactive protein day 1 and high-sensitivity C-reactive protein day 30 levels were not. Patients with interleukin-6 day 1≤8.24 pg/mL and interleukin-6 day 30≤4.45 pg/mL had the lowest event rates (4.7%), whereas those with both above the median values had the highest event rates (35%). After addition of interleukin-6 day 30 to the multivariate model, C-index increased from 0.71 (95% confidence interval, 0.63-0.78) to 0.80 (95% confidence interval, 0.72-0.86), P=.042, and net reclassification improvement was 0.39 (95% confidence interval, 0.14-0.64; P=.002). CONCLUSIONS: In this population, both interleukin-6 and high-sensitivity C-reactive protein concentrations decreased after the acute phase. Serial samples of interleukin-6 concentrations improved the prognostic risk stratification of these patients.

Severe aortic valve stenosis with low-gradient and preserved ejection fraction: a misclassification issue?

INTRODUCTION AND OBJECTIVES: Low-gradient severe aortic stenosis with preserved ejection fraction is a controversial entity. Misclassification of valvulopathy severity could explain the inconsistencies reported in the prognosis of these patients. Planimetry of the aortic area using three-dimensional transesophageal echocardiography could clear up these doubts. The objectives were to assess the agreement between measurements of the valvular aortic area by continuity equation in transthoracic echocardiography and that obtained through planimetry with three-dimensional transesophageal echocardiography in low-gradient severe aortic stenosis patients. METHODS: Cross-sectional descriptive study of consecutive patients referred due to severe aortic stenosis. Patients underwent transthoracic echocardiography and three-dimensional transesophageal echocardiography. Paradoxical low-gradient severe aortic stenosis was defined by the presence in the transthoracic echocardiography of aortic valve area<1 cm(2), mean ventricular gradient<40 mmHg, and ejection fraction ≥ 50%. Concordance between the two techniques was evaluated. RESULTS: Of 212 consecutive severe aortic stenosis patients evaluated, 63 cases (29.7%) fulfilled the paradoxical low-gradient inclusion criteria. We obtained three-dimensional aortic valve planimetry in 61 (96.8%) of those patients. In 52 patients (85.2%), aortic valve area by transesophageal echocardiography was <1 cm(2). The intraclass correlation coefficient between the two methods was 0.505 (95% confidence interval, 0.290-0.671; P<.001). CONCLUSIONS: Paradoxical low-gradient severe aortic stenosis is an actual entity, confirmed in 85% of cases evaluated by three-dimensional transesophageal echocardiography.

Prognostic value of mean platelet volume in patients with non-ST-elevation acute coronary syndrome.

The aim of this study is to determine mean platelet volume (MPV) in a population with non-ST-elevation acute coronary syndrome (nSTEACS) and explore its relation with prognosis. Patients (n = 329) with a diagnosis of nSTEACS at admission were recruited, with a determination of MPV in the first 12 hours at admission. We also collected blood from 87 healthy controls. A composite end point of cardiovascular death and new ACS was assessed at 6-month follow-up. Patients with nSTEACS showed larger platelets (MPV: 11.0 [10.3-11.8] vs 9.2 [8.6-10.0] fL; P < .001.). In Cox regression analysis, MPV at admission was a significant predictor of cardiovascular adverse events in univariate analysis, hazard ratio (HR) 1.4 95% confidence interval (CI) 1.1-1.8; P = .018; but after adjustment with clinical variables, MPV lost its statistical significance. In conclusion, patients with nSTEACS present with larger platelets than healthy controls, however this parameter did not show an independent prognostic significance at 6-month follow-up.