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Background Sodium-induced microcirculatory changes, endothelial surface layer alterations in particular, may play an important role in sodium-mediated blood pressure elevation. However, effects of acute and chronic sodium loading on the endothelial surface layer and microcirculation in humans have not been established. The objective of this study was to assess sodium-induced changes in blood pressure and body weight as primary outcomes and also in microvascular permeability, sublingual microcirculatory dimensions, and urinary glycosaminoglycan excretion in healthy subjects. Methods Twelve normotensive males followed both a low-sodium diet (less than 50 mmol/day) and a high-sodium diet (more than 200 mmol/day) for eight days in randomized order, separated by a crossover period. After the low-sodium diet, hypertonic saline (5 mmol sodium/liter body water) was administered intravenously in 30 min. Results Both sodium interventions did not change blood pressure. Body weight increased with 2.5 (95% CI, 1.7 to 3.2) kg (P < 0.001) after dietary sodium loading. Acute intravenous sodium loading resulted in increased transcapillary escape rate of 125I-labeled albumin (2.7 [0.1 to 5.3] % cpm · g−1 · h–1; P = 0.04), whereas chronic dietary sodium loading did not affect transcapillary escape rate of 125I-labeled albumin (−0.03 [−3.3 to 3.2] % cpm · g−1 · h–1; P = 1.00), despite similar increases of plasma sodium and osmolality. Acute intravenous sodium loading coincided with significantly increased plasma volume, as assessed by the distribution volume of albumin, and significantly decreased urinary excretion of heparan sulfate and chondroitin sulfate. These changes were not observed after dietary sodium loading. Conclusions Our results suggest that intravenous sodium loading has direct adverse effects on the endothelial surface layer, independent of blood pressure.

Unfractionated heparin (UFH) plasma protein binding and elimination might be impaired in patients with chronic kidney disease (CKD—defined as creatinine clearance

Aims Galectin-3 (Gal-3) is an important mediator of cardiac fibrosis, particularly in heart failure. Increased Gal-3 concentration (Gal-3), associated with increased risk of developing atrial fibrillation (AF), may reflect atrial fibrotic remodelling underlying AF progression. We aimed to investigate whether the change in serum Gal-3 reflects alterations of the arrhythmogenic atrial substrate following thoracoscopic AF surgery, and predicts absence of AF. Methods and results Consecutive patients undergoing thoracoscopic AF surgery were included. Left atrial appendages (LAAs) and serum were collected during surgery and serum again 6 months thereafter. Gal-3 was determined in tissue and serum. Interstitial collagen in the LAA was quantified using Picrosirius red staining. Ninety-eight patients (76% male, mean age 60 ± 9 years) underwent thoracoscopic surgery for advanced AF. Patients with increased Gal-3 after ablation compared to baseline had a higher recurrence rate compared to patients with decreased or unchanged Gal-3 (HR 2.91, P = 0.014). These patients more frequently had persistent AF, longer AF duration and thick atrial collagen strands (P = 0.049). At baseline, Gal-3 was similar between patients with and without AF recurrence: 14.8 ± 3.9 µg/L vs. 13.7 ± 3.7 µg/L, respectively in serum (P = 0.16); 94.5 ± 19.4 µg/L vs. 93.3 ± 30.8µg/L, respectively in atrial myocardium (P = 0.83). There was no correlation between serum Gal-3 and left atrial Gal-3 (P = 0.20), nor between serum Gal-3 and the percentage of fibrosis in LAA (P = 0.18). Conclusion The change of circulating Gal-3, rather than its baseline value, predicts AF recurrence after thoracoscopic ablation. Patients in whom Gal-3 increases after ablation have a high recurrence rate reflecting ongoing profibrotic signalling, irrespective of arrhythmia continuation.

OBJECTIVES: Hypertension is a major burden among African migrants, but the extent of the differences in prevalence, treatment, and control among similar African migrants and nonmigrants living in different contexts in high-income countries and rural and urban Africa has not yet been assessed. We assessed differences in hypertension prevalence and its management among relatively homogenous African migrants (Ghanaians) living in three European cities (Amsterdam, London, and Berlin) and nonmigrants living in rural and urban Ghana. METHODS: A multicenter cross-sectional study was conducted among Ghanaian adults (n = 5659) aged 25-70 years. Comparisons between sites were made using prevalence ratios with adjustment for age, education, and BMI. RESULTS: The age-standardised prevalence of hypertension was 22 and 28% in rural Ghanaian men and women. The prevalence was higher in urban Ghana [men, 34%; adjusted prevalence ratio = 1.37, 95% confidence interval (CI), 1.10-1.70]; and much higher in migrants in Europe, especially in Berlin (men, 57%; prevalence ratio = 2.21, 1.78-2.73; women, 51%; prevalence ratio = 1.74, 1.45-2.09) than in rural Ghana. Hypertension awareness and treatment levels were higher in Ghanaian migrants than in nonmigrant Ghanaians. However, adequate hypertension control was lower in Ghanaian migrant men in Berlin (20%; prevalence ratio = 0.43 95%, 0.23-0.82), Amsterdam (29%; prevalence ratio = 0.59, 0.35-0.99), and London (36%; prevalence ratio = 0.86, 0.49-1.51) than rural Ghanaians (59%). Among women, no differences in hypertension control were observed. About 50% of migrants to 85% of rural Ghanaians with severe hypertension (Blood pressure > 180/110) were untreated. Antihypertensive medication prescription patterns varied considerably by site. CONCLUSION: Hypertension prevalence, awareness, and treatment levels were generally higher in African migrants, but blood pressure control level was lower in Ghanaian migrant men compared with their nonmigrant peers. Further work is needed to identify key underlying factors to support prevention and management efforts.Supplement Figure 1, http://links.lww.com/HJH/A831.

Sodium-induced microcirculatory changes, endothelial surface layer alterations in particular, may play an important role in sodium-mediated blood pressure elevation. However, effects of acute and chronic sodium loading on the endothelial surface layer and microcirculation in humans have not been established. The objective of this study was to assess sodium-induced changes in blood pressure and body weight as primary outcomes and also in microvascular permeability, sublingual microcirculatory dimensions, and urinary glycosaminoglycan excretion in healthy subjects.Twelve normotensive males followed both a low-sodium diet (less than 50 mmol/day) and a high-sodium diet (more than 200 mmol/day) for eight days in randomized order, separated by a crossover period. After the low-sodium diet, hypertonic saline (5 mmol sodium/liter body water) was administered intravenously in 30 min.Both sodium interventions did not change blood pressure. Body weight increased with 2.5 (95% CI, 1.7 to 3.2) kg (P0.001) after dietary sodium loading. Acute intravenous sodium loading resulted in increased transcapillary escape rate of I-labeled albumin (2.7 [0.1 to 5.3] % cpm · g · h; P = 0.04), whereas chronic dietary sodium loading did not affect transcapillary escape rate of I-labeled albumin (-0.03 [-3.3 to 3.2] % cpm · g · h; P = 1.00), despite similar increases of plasma sodium and osmolality. Acute intravenous sodium loading coincided with significantly increased plasma volume, as assessed by the distribution volume of albumin, and significantly decreased urinary excretion of heparan sulfate and chondroitin sulfate. These changes were not observed after dietary sodium loading.Our results suggest that intravenous sodium loading has direct adverse effects on the endothelial surface layer, independent of blood pressure.

No five-year long-term follow-up data is available regarding the prognostic value of GDF-15. Our aim is to evaluate the long-term prognostic value of admission growth-differentiation factor 15 (GDF-15) regarding death or myocardial infarction (MI) in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). This is a subanalysis from the ICTUS (Invasive versus Conservative Treatment in Unstable coronary Syndromes) trial, including troponin positive NSTE-ACS patients. The main outcome for the current analysis was 5-year death or spontaneous MI. GDF-15 samples were available in 1151 patients. The prognostic value of GDF-15, categorized into 1800 ng/L, was assessed in unadjusted and adjusted Cox regression models. Adjustments were made for identified univariable risk factors. The additional discriminative and reclassification value of GDF-15 beyond the independent risk factors was assessed by the category-free net reclassification improvement (1/2 NRI(>0)) and the integrated discrimination improvement (IDI) RESULTS: Compared to GDF-15 1800 ng/L was associated with an increased hazard ratio for death or spontaneous MI, mainly driven by mortality. GDF-15 levels were predictive after adjustments for other identified predictors. Additional discriminative value was shown with the IDI, not with the NRI. In patients presenting with NSTE-ACS and elevated troponin T, GDF-15 provides prognostic information in addition to identified predictors for mortality and spontaneous MI and can be used to identify patients at high risk during long-term follow-up

We have previously shown that older thrombus is associated with a 2-fold higher long-term mortality in ST-segment elevation myocardial infarction (STEMI) patients after primary percutaneous coronary intervention (pPCI). We evaluated whether the addition of the presence of older thrombus to a multimarker model would result in increased predictive power for 1-year mortality in STEMI patients. The study population (N = 1442) consists of STEMI patients treated with thrombus aspiration during pPCI. Patients were included if aspirated thrombus material could histopathologically be classified according to thrombus age (N=870) and laboratory measurements of biomarkers (cardiac troponin T, glucose, N-terminal pro-brain natriuretic peptide, estimated glomerular filtration rate, and C-reactive protein) were available. The additional prognostic value of the presence of older thrombus beyond multiple biomarkers and established clinical risk factors was evaluated using multivariate Cox regression models. Serum biomarker concentrations were similar between patients with fresh and older thrombus. Sixty patients (7%) died within 1 year. The presence of older thrombus remained strongly associated with mortality at 1-year after multivariable adjustment for multiple biomarkers and established clinical risk factors. Addition of older thrombus to either a model including clinical risk factors and biomarkers or a model including solely biomarkers resulted in significant increases in the discriminative value, evidenced by net reclassification improvement and integrated discriminative improvement. The presence of older thrombus provides independent complementary information to a multimarker model including established clinical risk factors and multiple biomarkers for predicting 1-year mortality in STEMI patients treated with pPCI and thrombus aspiration. This article is protected by copyright. All rights reserved.

Objective Pulmonary arterial hypertension due to congenital heart disease (CHD-PAH) has a poor prognosis. We sought to determine whether the biomarker high-sensitivity troponin T (hsTnT) measured on routine visit at the outpatient clinic is associated with prognosis. Patients Consecutive adult CHD-PAH (86% Eisenmenger syndrome) patients referred for advanced medical therapy between January 2005 and March 2007 in the Academic Medical Center in Amsterdam. Patients with severe renal impairment were excluded. Main Outcome Measure The primary outcome was mortality. Results Of all 31 patients (mean age 45 ± 12 years) with CHD-PAH, eight patients died during a median follow-up of 5.6 (range 1.6 to 6.8) years. A hsTnT level >0.014 μg/L was the 99th percentile cutoff of the normal distribution and therefore defined as elevated. At baseline, elevated levels of hsTnT were found in eight patients (26%). In univariate Cox regression, hsTnT elevated at baseline, NT-pro-BNP and right ventricular function were determinants of death (P

Objectives We investigated whether multiple biomarkers improve prognostication in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention. Background Few data exist on the prognostic value of combined biomarkers. Methods We used data from 1,034 STEMI patients undergoing primary percutaneous coronary intervention in a high-volume percutaneous coronary intervention center in the Netherlands and investigated whether combining N-terminal pro-brain natriuretic peptide, glucose, C-reactive protein, estimated glomerular filtration rate, and cardiac troponin T improved the prediction of mortality. A risk score was developed based on the strongest predicting biomarkers in multivariate Cox regression. The additional prognostic value of the strongest predicting biomarkers to the established prognostic factors (age, body weight, diabetes, hypertension, systolic blood pressure, heart rate, anterior myocardial infarction, and time to treatment) was assessed in multivariable Cox regression. Results During follow-up (median, 901 days), 120 of the 1,034 patients died. In Cox regression, glucose, estimated glomerular filtration rate, and N-terminal pro-brain natriuretic peptide were the strongest predictors for mortality (p l 0.05, for all). A risk score incorporating these biomarkers identified a high-risk STEMI subgroup with a significantly higher mortality when compared with an intermediate- or low-risk subgroup (p l 0.001). Addition of the 3 biomarkers to established prognostic factors significantly improved prediction for mortality, as shown by the net reclassification improvement (0.494, p l 0.001) and integrated discrimination improvement (0.0295, p l 0.01). Conclusions Our data suggest that addition of a multimarker to a model including established risk factors improves the prediction of mortality in STEMI patients undergoing primary percutaneous coronary intervention. Furthermore, the use of a simple risk score based on these biomarkers identifies a high-risk subgroup.

Data on the ability of serum biomarkers to predict microvascular obstruction by ST-segment recovery after primary percutaneous coronary intervention (PCI) is largely absent. Therefore, we determined the association between 5 serum biomarkers, obtained before emergency coronary angiography, and immediate ST-segment recovery in patients who had undergone primary PCI for ST-segment elevation myocardial infarction. We measured N-terminal pro-brain natriuretic peptide (NT-pro-BNP), cardiac troponin T, creatinine kinase-MB fraction, high-sensitivity C-reactive protein, and serum creatinine from blood samples obtained through the arterial sheath at the start of primary PCI. Serial 12-lead electrocardiograms were recorded in the catheterization laboratory before arterial puncture and at the end of the PCI. ST-segment recovery was defined as incomplete if = 608 ng/L) was the strongest predictor of incomplete ST-segment recovery (adjusted odds ratio 2.6, 95% confidence interval 1.6 to 4.1; p

Circulating levels of B-type natriuretic peptide (BNP) and the amino-terminal portion of the prohormone (NT-proBNP) have been reported to increase immediately after myocardial ischemia. The association between extent of exercise-induced myocardial ischemia measured using myocardial perfusion scintigraphy and the magnitude and time course of changes in NT-proBNP was studied. One hundred one patients underwent symptom-limited exercise myocardial perfusion scintigraphy. Myocardial ischemia was assessed semiquantitatively. Serum samples were obtained before the start of exercise (baseline), at maximal exercise, and every hour up to 6 hours after maximal exercise. Myocardial ischemia was present in 37 patients (37%). NT-proBNP rapidly increased during exercise (to 113%, interquartile range 104 to 144, and 118%, interquartile range 106 to 142, of baseline, respectively), with a second peak at 4 (141%, interquartile range 119 to 169) and 5 hours (136%, interquartile range 93 to 188), respectively. Absolute changes between NT-proBNP at baseline and at maximum exercise in patients with versus without ischemia were similar (median, 30 pg/ml, interquartile range 7 to 45 vs 15, interquartile range 4 to 46, respectively, p = 0.230), but absolute change between baseline and the secondary peak was higher in patients with ischemia than in patients without ischemia (median 64 pg/ml, interquartile range 32 to 172 vs 34, interquartile range 19 to 85, respectively, p = 0.024). In multivariate linear stepwise regression analysis of determinants of changes in NT-proBNP after exercise, baseline NT-proBNP was the only independent determinant of absolute changes at maximum exercise, whereas the presence of ischemia was not predictive. Baseline NT-proBNP, cystatin C, and end-systolic volume were independent determinants of the absolute increase to secondary peak levels. In conclusion, myocardial ischemia per se did not lead to additional increases in NT-proBNP within 6 hours after exercise. (C) 2009 Elsevier Inc. (Am J Cardiol 2009;103:604-610)

Contains fulltext : 53418.pdf (Publisher’s version ) (Closed access) BACKGROUND: New evidence has emerged that the assessment of multiple biomarkers such as cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with non-ST-elevation acute coronary syndrome (nSTE-ACS) provides unique prognostic information. The purpose of this study was to assess the association between baseline NT-proBNP levels and outcome in patients who have nSTE-ACS with an elevated cTnT and to determine whether patients with elevated NT-proBNP levels benefit from an early invasive treatment strategy. METHODS: Baseline samples for NT-proBNP measurements were available in 1141 patients who have nSTE-ACS with an elevated cTnT randomized to an early or a selective invasive strategy. Patients were followed-up for the occurrence of death, myocardial infarction (MI), and rehospitalization for angina. RESULTS: We showed that increased levels of NT-proBNP were associated with several indicators of risk and severe coronary artery disease. Mortality by 1 year was 7.3% in the highest quartile (> or = 1170 ng/L for men, > or = 2150 ng/L for women) compared with 1.1% of patients in the lower 3 quartiles (P < .0001). N-terminal pro-brain natriuretic peptide (highest quartile vs lower 3 quartiles) was a strong independent predictor of mortality (hazard ratio 5.0, 95% CI 2.1-11.6, P = .0002). However, NT-proBNP levels were not associated with the incidence of recurrent MI by 1 year. Furthermore, we could not demonstrate a benefit of an early invasive strategy compared with a selective invasive strategy in patients with an elevated NT-proBNP level. CONCLUSIONS: We confirmed that NT-proBNP is a strong independent predictor of mortality by 1 year but not of recurrent MI in patients who have nSTE-ACS with an elevated cTnT. We could not demonstrate a benefit of an early invasive strategy compared with a selective invasive strategy.

This study is the first that combines a serum marker of inflammation (C-reacitive protein) and intracoronary-derived fractional flow reserve. A low C-reactive protein level was strongly associated with uncomplicated follow-up in patients with hemodynamic nonsignificant coronary lesions. These results show that C-reactive protein provides additional information relevant for clinical decision-making in patients with intermediate (30% to 70%) coronary lesions. (C) 2003 by Excerpta Medica, Inc

To assess the critical difference in serial measurements of CK-MBmass and the ability of this critical difference to detect myocardial damage, we studied 110 patients in whom an acute myocardial infarction (AMI) had been ruled out. Blood samples were drawn at 3, 4, 5, 6, 7, 8, 12, 16, 20, and 24 h after onset of symptoms. With a critical difference of 72.6%, an increase of >2.0 μg/L between two CK-MBmass measurements was determined to be significant. Twenty-three of the non-AMI patients had an increase in CK-MBmass >2.0 μg/L, but five of these did not have an abnormal concentration of troponin T (i.e., not >0.1 μg/L). Also among the 110 non-AMI patients, 22 did have an abnormal troponin T value, 18 of whom (82%) also had CK-MBmassincreased by >2.0 μg/L. In 20 of the 23 patients with an increase in CK-MBmass >2.0 μg/L, this increase was detected from the values for two samples collected at 5 and 12 h after onset of symptoms. In conclusion, using the critical difference for CK-MBmassdefined as an increase >2.0 μg/L detected myocardial damage in patients without AMI.

Background Serum levels of N–terminal proB–type natriuretic peptide (NT–proBNP) are elevated in patients acute respiratory distress syndrome (ARDS). Recent studies showed a lower incidence of acute cor pulmonale in ARDS patients ventilated with lower tidal volumes. Consequently, serum levels of NT–proBNP may be lower in these patients. We investigated the relation between serum levels of NT–proBNP and tidal volumes in critically ill patients without ARDS at the onset of mechanical ventilation. Methods Secondary analysis of a randomized controlled trial of lower versus conventional tidal volumes in patients without ARDS. NT–pro BNP were measured in stored serum samples. Serial serum levels of NT–pro BNP were analyzed controlling for acute kidney injury, cumulative fluid balance and presence of brain injury. The primary outcome was the effect of tidal volume size on serum levels of NT–proBNP. Secondary outcome was the association with development of ARDS. Results Samples from 150 patients were analyzed. No relation was found between serum levels of NT–pro BNP and tidal volume size. However, NT-proBNP levels were increasing in patients who developed ARDS. In addition, higher levels were observed in patients with acute kidney injury, and in patients with a more positive cumulative fluid balance. Conclusion Serum levels of NT–proBNP are independent of tidal volume size, but are increasing in patients who develop ARDS.

The Boehringer Mannheim Hitachi 911 is a selective analyzer for 35 different methods including 3 ion-selective electrode (ISE) methods. We have evaluated this analyzer primarily to obtain objective information on its applicability for routine urine analyses in our laboratory. We also implemented appropriate assays for various special serum- and whole blood-tests, some for the first time on the Hitachi 911 and some with modified settings. Analytical evaluation involved NCCLS EP5-T2 (imprecision), NCCLS EP6-P (linearity), Krouwer 27 (multifactor) and Passing & Bablok (method comparison) evaluation protocols. With the exception of evidence of systematic erroneous sample predilution, overall results were favourable. Practicability of the Hitachi 911 was judged by simulating daily routine. During a period of two weeks, daily urine samples were rerun on the Hitachi 911, leading to a gain of about 50% in total processing time. It was concluded that the Hitachi 911 meets the requirements in terms of analytical performance, reliability, versatility and speed for an analyzer to be used in a routine (urine) setting, while having a distinct role in special (serum/whole blood) measurements.

Pulmonary arterial hypertension due to congenital heart disease (CHD-PAH) has a poor prognosis. We sought to determine whether the biomarker high-sensitivity troponin T (hsTnT) measured on routine visit at the outpatient clinic is associated with prognosis.Consecutive adult CHD-PAH (86% Eisenmenger syndrome) patients referred for advanced medical therapy between January 2005 and March 2007 in the Academic Medical Center in Amsterdam. Patients with severe renal impairment were excluded.The primary outcome was mortality.Of all 31 patients (mean age 45 ± 12 years) with CHD-PAH, eight patients died during a median follow-up of 5.6 (range 1.6 to 6.8) years. A hsTnT level0.014 μg/L was the 99th percentile cutoff of the normal distribution and therefore defined as elevated. At baseline, elevated levels of hsTnT were found in eight patients (26%). In univariate Cox regression, hsTnT elevated at baseline, NT-pro-BNP and right ventricular function were determinants of death (P.05 for all). Patients with elevated levels of hsTnT showed a significantly higher mortality rate as compared to patients with normal hsTnT levels (62% vs. 13%, P = .005).Levels of hsTnT were abnormal in a substantial proportion of CHD-PAH patients. A significant inverse relationship was found between hsTnT and survival.

Background The multimarker risk score, based on estimated glomerular filtration rate, glucose, and N-terminal probrain natriuretic peptide (NT-proBNP), has been shown to predict mortality in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). In this study, we investigated the relation between the multimarker risk score and cardiovascular mechanistic markers of outcomes in STEMI patients undergoing PPCI.Methods Complete biomarkers were available in 197 patients with STEMI. Angiographic Thrombolysis In Myocardial Infarction flow grade and myocardial blush grade at the end of the PPCI, electrocardiographic ST-segment resolution (STR) at the time of last contrast injection and 240 minutes after last contrast, and cardiac magnetic resonance (CMR) left ventricular ejection fraction (LVEF) and infarct size at 4 to 6 months after the index event were available.Results In linear regression models, higher multimarker scores were associated with worse angiographic (P Conlusions The multimarker risk score is associated with angiographic, electrocardiographic, and CMR mechanistic markers of outcomes. These data support the ability of the multimarker risk score to identify patients at high risk for suboptimal reperfusion and CMR outcomes and may aid in the early triage of patients who stand to benefit most of adjuvant treatments in STEMI. (Am Heart J 2012;163:783-9.)

Little is known about the long-term prognostic value of N-terminal pro B-type natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) in low-risk patients with chest pain. Between June 1997 and January 2000, a standard rule-out protocol was performed in patients presenting to the emergency department within 6 hours of onset of chest pain with a normal or nondiagnostic electrocardiogram (ECG) on admission at the Academic Medical Center Amsterdam, VU University Medical Center Amsterdam and Medical Center Alkmaar, The Netherlands. Patients with acute coronary syndrome were identified by troponin T, recurrent angina, and serial ECGs. CRP and NT-proBNP on admission were measured using standardized methods. A total of 524 patients were included (145 with acute coronary syndrome and 379 with rule-out acute coronary syndrome). Long-term follow-up was successfully carried out in 96% of the study population. Death occurred in 78 patients (15%), 43 (11%) in the rule-out acute coronary syndrome group and 35 (24%) in the acute coronary syndrome group (P 87 pg/mL, as derived from the receiver operating characteristic curve) were independent predictors of long-term cardiovascular mortality in the rule-out acute coronary syndrome group. In the acute coronary syndrome group, these predictors were age more than 65 years, documented coronary artery disease, and elevated NT-proBNP levels. Elevated levels of CRP were an independent predictor for cardiovascular mortality in patients with rule-out acute coronary syndrome at 3-year follow-up only. In patients with rule-out acute coronary syndrome with normal CRP and NT-proBNP levels, the cardiovascular mortality incidence rate was 4.7 per 1000 person-years, compared with a death rate of 20 in patients with both biomarkers elevated, which was comparable to the 17.9 per 1000 person-years incidence rate in patients with acute coronary syndrome. A positive biomarker panel discriminates patients with rule-out acute coronary syndrome chest pain with a normal or nondiagnostic ECG who have a high risk for long-term cardiovascular mortality

The purpose of the present study was to determine the prognostic value of N-terminal pro-brain natriuretic peptide (NT-pro-BNP), among other serum biomarkers, on cardiac magnetic resonance (CMR) imaging parameters of cardiac function and infarct size in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. We measured NT-pro-BNP, cardiac troponin T, creatinine kinase-MB fraction, high-sensitivity C-reactive protein, and creatinine on the patients' arrival at the catheterization laboratory in 206 patients with ST-segment elevation myocardial infarction. The NT-pro-BNP levels were divided into quartiles and correlated with left ventricular function and infarct size measured by CMR imaging at 4 to 6 months. Compared to the lower quartiles, patients with nonanterior wall myocardial infarction in the highest quartile of NT-pro-BNP (>= 260 pg/ml) more often had a greater left ventricular end-systolic volume (68 vs 39 ml/m(2), p = 260 pg/ml was the strongest independent predictor of left ventricular ejection fraction in patients with nonanterior wall myocardial infarction compared to the other serum biomarkers (beta = 5.8; p = 0.019). In conclusion, in patients with nonanterior wall myocardial infarction undergoing primary percutaneous coronary intervention, an admission NT-pro-BNP level of >= 260 pg/ml was a strong, independent predictor of left ventricular function assessed by CMR imaging at follow-up. Our findings suggest that NT-pro-BNP, a widely available biomarker, might be helpful in the early risk stratification of patients with nonanterior wall myocardial infarction. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;105:1065-1069)

Background: We assessed the value of cystatin C for improvement of risk stratification in patients with non–ST elevation acute coronary syndrome (nSTE-ACS) and increased cardiac troponin T (cTnT), and we compared the long-term effects of an early invasive treatment strategy (EIS) with a selective invasive treatment strategy (SIS) with regard to renal function. Methods: Patients (n = 1128) randomized to an EIS or an SIS in the ICTUS trial were stratified according to the tertiles of the cystatin C concentration at baseline. The end points were death within 4 years and spontaneous myocardial infarction (MI) within 3 years. Results: Mortality was 3.4%, 6.2%, and 13.5% in the first, second, and third tertiles, respectively, of cystatin C concentration (log-rank P < 0.001), and the respective rates of spontaneous MI were 5.5%, 7.5%, and 9.8% (log-rank P = 0.03). In a multivariate Cox regression analysis, the cystatin C concentration in the third quartile remained independently predictive of mortality [hazard ratio (HR), 2.04; 95% CI, 1.02–4.10; P = 0.04] and spontaneous MI (HR, 1.95; 95% CI, 1.05–3.63; P = 0.04). The mortality rate in the second tertile was lower with the EIS than with the SIS (3.8% vs 8.7%). In the third tertile, the mortality rates with the EIS and the SIS were, respectively, 15.0% and 12.2% (P for interaction = 0.04). Rates of spontaneous MI were similar for the EIS and the SIS within cystatin C tertiles (P for interaction = 0.22). Conclusions: In patients with nSTE-ACS and an increased cTnT concentration, mild to moderate renal dysfunction is associated with a higher risk of death and spontaneous MI. Use of cystatin C as a serum marker of renal function may improve risk stratification.

Background Quantitative proteomic analysis with mass spectrometry holds great promise for simultaneously quantifying proteins in various biosamples, such as human plasma. Thus far, studies addressing the reproducible measurement of endogenous protein concentrations in human plasma have focussed on targeted analyses employing isotopically labelled standards. Non-targeted proteomics, on the other hand, has been less employed to this end, even though it has been instrumental in discovery proteomics, generating large datasets in multiple fields of research. Results Using a non-targeted mass spectrometric assay (LCMSE), we quantified abundant plasma proteins (43 mg/mL—40 ug/mL range) in human blood plasma specimens from 30 healthy volunteers and one blood serum sample (ProteomeXchange: PXD000347). Quantitative results were obtained by label-free mass spectrometry using a single internal standard to estimate protein concentrations. This approach resulted in quantitative results for 59 proteins (cut off ≥11 samples quantified) of which 41 proteins were quantified in all 31 samples and 23 of these with an inter-assay variability of ≤ 20%. Results for 7 apolipoproteins were compared with those obtained using isotope-labelled standards, while 12 proteins were compared to routine immunoassays. Comparison of quantitative data obtained by LCMSE and immunoassays showed good to excellent correlations in relative protein abundance (r = 0.72–0.96) and comparable median concentrations for 8 out of 12 proteins tested. Plasma concentrations of 56 proteins determined by LCMSE were of similar accuracy as those reported by targeted studies and 7 apolipoproteins quantified by isotope-labelled standards, when compared to reference concentrations from literature. Conclusions This study shows that LCMSE offers good quantification of relative abundance as well as reasonable estimations of concentrations of abundant plasma proteins.

The albumin cobalt-binding test (Ischemia Technologies), which measures the concentration of ischemia-modified albumin (IMA), has been cleared by the US Food and Drug Administration for use as a rule-out marker for acute myocardial ischemia (1). The test is based on the reduced capacity of human albumin to bind cobalt as a result of structural changes in the NH2 terminus of the albumin molecule in conditions of myocardial ischemia (2)(3). Moreover, IMA concentrations correlated with disease severity in systemic sclerosis (4), and an exercise-induced decrease in IMA concentrations correlated with the ankle-brachial index in patients with peripheral artery sclerosis (5). Little is known, however, about the relationship between exercise-induced myocardial ischemia, albumin kinetics, and IMA kinetics. We therefore investigated this relationship in 38 patients with chest complaints and suspected coronary artery disease who were undergoing symptom-limited exercise myocardial perfusion scintigraphy. Myocardial perfusion scintigraphy was performed according to the guidelines of the American Society of Nuclear Cardiology (6), with a 2-day stress/rest protocol. A dose of 500 MBq of [99mTc]-Tetrofosmin was administered at rest and at peak exercise. Electrocardiogram-gated single photon emission tomography imaging was started 45 min to 1 h after the administration of radioactive-labeled tracer. All patients exercised on a bicycle ergometer with a starting workload of 50 W, increasing every 2 min by 25 W. Endpoints for exercise included achievement of at least 85% of the age-predicted heart …

B-type natriuretic peptide (BNP) and the N-terminus of pro-BNP (NT-pro-BNP) have prognostic value in patients with heart failure and patients with acute coronary syndromes. Little is known about the prognostic value of baseline NT-pro-BNP alone or in combination with C-reactive protein (CRP) for clinical outcome after percutaneous coronary intervention (PCI). Within a single center registry of contemporaneous PCI, we investigated the prognostic value of baseline plasma NT-pro-BNP and CRP concentrations for the prediction of death or nonfatal myocardial infarction (MI) during 12 to 14 months of follow-up. Among 1, 172 consecutive patients, the occurrence of death or MI increased significantly with baseline NT-pro-BNP before PCI (first quartile 0 of 294, second quartile. 6 of 291 [2.1%], third quartile 4 of 294 [1.4%], fourth quartile 22 of 293 [7.5%)]; p 65 years and NT-pro-BNP as independent significant predictors of death/Ml (age OR 3.18, 95% Cl 1.32 to 7.67, p = 0.01; NT-pro-BNP OR 4.57, 95% Cl 2.07 to 10.10, p = 0.0001). Baseline NT-pro-BNP before PCl provides important, independent prognostic information for the occurrence of death or nonfatal MI during long-term follow-up. (C) 2004 by Excerpta Medica Inc

Background: We assessed the predictive value of preprocedural plasma C-reactive protein (CRP) concentrations and statin therapy on 6 months angiographic and 1-year clinical outcome after nonurgent coronary stent placement. Methods and Results: Baseline plasma high-sensitivity CRP concentrations were prospectively measured in 345 patients undergoing elective stent placement in a native coronary artery. The binary angiographic in-stent restenosis (ISR; stenosis ≥50% of vessel diameter) rate was 19% in patients with CRP values within the reference interval (≤3 mg/L) and 22% in patients with CRP >3 mg/L [odds ratio (OR) = 1.2; 95% confidence interval (CI), 0.73–2.09]. Statin therapy in a univariate analysis significantly reduced both angiographic and clinical ISR rates. Multivariate logistic regression analysis identified unstable angina, smoking, and stent length, but neither CRP concentration nor statin therapy as independent predictors for angiographic ISR. Patients with an abnormal CRP value showed a trend toward a higher risk of nonfatal myocardial infarction (3.8% vs 0.5%; OR = 7.43; 95% CI, 0.87–61.65). Target lesion revascularization rates did not differ between the two groups (9.6% vs 10.6%; OR = 1.13; 95% CI, 0.56–2.28). In multivariate analysis, male sex (OR = 0.44, 95% CI, 0.19–0.97) and statin therapy (OR = 0.26; 95% CI, 0.09–0.68) were independent predictors for the occurrence of target lesion revascularization. Conclusions: This study demonstrated a lack of association between preprocedural plasma CRP concentrations and angiographic coronary ISR or clinically driven target lesion revascularization. Patients with an abnormal CRP concentration showed a trend toward higher risk of nonfatal myocardial infarction during 1 year of follow-up. Statin therapy was independently associated with decreased clinically driven target lesion revascularization, underlining the beneficial effects of statins on clinical outcome.

PURPOSE: To assess the prognostic value of markers of inflammation for rule-out purposes in patients admitted to the emergency department with troponin T-negative chest pain. METHODS: Patients presenting to the emergency department within 6 hours of symptom onset and who had a normal or nondiagnostic electrocardiogram were eligible. The standard rule-out protocol, which included serial creatine kinase and creatine kinase-MB measurements, was applied, and markers of inflammation (C-reactive protein, erythrocyte sedimentation rate, and total white blood cell count and differential count) were measured. The study group comprised patients with negative serial troponin T results ( 0.3 mg/dL) was associated with future clinical events (hazard risk [HR] = 4.5; 95% confidence interval [CI]: 1.2 to 17.0; P = 0.03), as was a positive test (>13 mm/h) for erythrocyte sedimentation rate (HR = 5.6; 95% CI: 1.5 to 22.2; P = 0.01). Patients with positive results for both tests were at highest risk of clinical events (9.3%) compared with patients with other combinations of test results (1.1% to 2.1%; HR 7.5; 95% CI: 2.2 to 25.5; P = 0.001). CONCLUSION: The combination of C-reactive protein and erythrocyte sedimentation rate had prognostic value in patients with troponin T-negative chest pain and a normal or nondiagnostic electrocardiogram in whom unstable coronary artery disease was ruled out. (C) 2003 by Excerpta Medica Inc

PURPOSE: We investigated the associations between baseline C-reactive protein levels in patients undergoing percutaneous coronary angioplasty and death, nonfatal myocardial infarction, and repeat revascularization during 14 months of follow-up. METHODS: In a single-center, prospective, cohort study, plasma levels of C-reactive protein were measured in 1458 consecutive patients undergoing elective or urgent coronary angioplasty. Patients were followed at 12 to 14 months for the occurrence of death, nonfatal myocardial infarction, and repeat revascularization. RESULTS: The incidence of death or myocardial infarction was 6.1% (44/716) in patients with an increased C-reactive protein level (>3 mg/L) and 1.5% (11/742) in patients with a normal level (relative risk [RR] = 4.4; 95% confidence interval (Cl]: 2.2 to 8.5; P

OBJECTIVES We prospectively studied the prognostic value of predischarge dobutamine stress echocardiography (I)SE) in low-risk chest pain patients with a normal or nondiagnostic electrocardiogram (ECG) and a negative serial troponin T. BACKGROUND Noninvasive stress testing is recommended before discharge or within 72 h in patients with low-risk chest pain. The prognostic value of immediate DSE has not been studied in a blinded, prospective fashion. METHODS Patients presenting at the emergency room within 6 h of symptom onset and a normal or nondiagnostic ECG were eligible. Dobutamine stress echocardiography was performed after unstable coronary artery disease was ruled out by a standard rule-out protocol and a negative serial troponin T; the occurrence of any new wall motion abnormality was considered positive. Results were kept blinded. End points were cardiac death, myocardial infarction, rehospitalization for unstable angina or revascularization. RESULTS In total, 377 patients were included. There were 2 deaths, 2 myocardial infarctions, 8 rehospitalization for unstable angina, and 10 revascularizations at six-month follow-up. The end points occurred in 8/26 (30.8%) patients with a positive versus 14/351 (4.0%) patients with a negative DSE (odds ratio, 10.7; 95% confidence interval, 4.0 to 28.8; p

Baseline levels of N-terminal fragment of the brain natriuretic peptide prohormone (NT-pro-BNP) are associated with myocardial ischemia in non-diabetic patients with stable angina pectoris. A total of 281 patients with diabetes mellitus type 2 and stable angina pectoris underwent myocardial perfusion scintigraphy (MPS). Myocardial ischemia on MPS was present in 140 (50%) patients. These ischemic patients had significantly higher NT-pro-BNP levels compared with patients without ischemia: 183 pg/ml (64-324 pg/ml) vs. 88 pg/ml (34-207 pg/ml), respectively (p

Objective To evaluate gender differences in the prognostic value of renal function for mortality in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). Design Prospective single-center cohort. Setting Single tertiary referral center in Amsterdam, The Netherlands. Patients consecutive STEMI patients undergoing PPCI (1412 men and 558 women). Main outcome measure The authors calculated adjusted HRs for 3-year all-cause mortality according to the presence of a reduced renal function (estimated glomerular filtration rate, Article summary Article focus To evaluate gender differences in the prognostic value of renal function in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention. Key message Renal dysfunction has prognostic significance for mortality in both male and female patients. Strengths and limitations of this study Renal function was routinely measured at admission in a large tertiary referral center. Single-center cohort and information on the cause of death was not available.

To the Editor: Unloading the left ventricle (LV) after ST-segment elevation myocardial infarction (STEMI) in addition to reperfusion therapy may reduce infarct size and may give the myocardium time to recuperate from ischemic stunning ([1][1]). This may be particularly true in STEMI patients with

Loss of enamel and a deep black stain of the teeth in a 40-year-old diabetic patient are strongly suggested to be caused by the daily consumption of a cheap white wine and, possibly, by the chewing of cayenne. The wine proved to be rather acid, thereby promoting abrasion as a result of gnashing, and to contain a high concentration of tannin. The exact role of the tannins is described.