Jan P. van Straalen

Bone-alkaline phosphatase as indicator of bone formation

Bone-alkaline phosphatase was determined in patients at risk of osteoporosis due to treatment with oral corticosteroids, and in patients at risk of increased bone synthesis because of treatment with cyclosporin. Both a significant decrease of bone-alkaline phosphatase during corticosteroid treatment, and a significant increase of bone-alkaline phosphatase during cyclosporin treatment could be demonstrated. It is concluded that bone-alkaline phosphatase is a useful parameter for monitoring changes in bone formation.

Prognostic value of predischarge dobutamine stress echocardiography in chest pain patients with a negative cardiac troponin T

OBJECTIVES We prospectively studied the prognostic value of predischarge dobutamine stress echocardiography (DSE) 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 < 0.0001). By multivariate analysis, DSE remained a predictor of end points (p < 0.0001). CONCLUSIONS A predischarge DSE had important, independent prognostic value in low-risk, troponin negative, chest pain patients.

Left ventricular unloading in acute ST-segment elevation myocardial infarction patients is safe and feasible and provides acute and sustained left ventricular recovery

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

Multiple Biomarkers at Admission Significantly Improve the Prediction of Mortality in Patients Undergoing Primary Percutaneous Coronary Intervention for Acute ST-Segment Elevation Myocardial Infarction

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 < 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 < 0.001). Addition of the 3 biomarkers to established prognostic factors significantly improved prediction for mortality, as shown by the net reclassification improvement (0.481, p < 0.001) [corrected] and integrated discrimination improvement (0.0226, p = 0.03) [corrected]. 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.

C-reactive protein and coronary events following percutaneous coronary angioplasty

Abstract 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 [CI]: 2.2 to 8.5; P P = 0.0001). The incidence of repeat revascularization was similar in patients with or without an increased C-reactive protein level (23% [168/716] vs. 22% [163/742], P = 0.54). Statin therapy at the time of the procedure was associated with a lower mean (± SD) C-reactive protein level (5.8 ± 9.7 mg/L vs. 7.2 ± 12.1 mg/L, P = 0.02), but was not associated with the risk of death, nonfatal myocardial infarction, and repeat revascularization during follow-up. Conclusion An increased C-reactive protein level is an independent prognostic indicator for the occurrence of death or nonfatal myocardial infarction following coronary angioplasty, but is not associated with the need for repeat revascularization.

Predictive Value of Plasma Glucose Level on Admission for Short and Long Term Mortality in Patients With ST-Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention

Published reports describe a strong association between plasma glucose levels on admission and mortality in patients who undergo primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. The aim of this study was to assess the predictive value of admission glucose levels for early and late mortality. From 2005 to 2007, 1,646 patients underwent primary percutaneous coronary intervention for ST-segment elevation myocardial infarction and were stratified according to admission plasma glucose level in category 1 (<7.8 mmol/L; n = 747), category 2 (7.8 to 11.0 mmol/L; n = 620), or category 3 (>11 mmol/L; n = 279). Event rates were estimated using the Kaplan-Meier method. A landmark survival analysis to 3-year follow-up was performed, with a landmark set at 30 days. Time-extended Cox regression was used to assess the predictive value of admission glucose levels. Furthermore, a stratified analysis was performed for known diabetes mellitus status at admission. Thirty-day mortality was 2.4% in category 1, 6% in category 2, and 22% in category 3 (p <0.01). Three-year mortality in 30-day survivors was 5.9% in category 1, 8.2% in category 2, and 7.1% in category 3 (p = 0.27). Glucose level on admission was a strong predictor of 30-day mortality: for every 1 mmol/L increase, the hazard increased by 14% (hazard ratio 1.14, 95% confidence interval 1.09 to 1.19, p <0.01) in patients without diabetes, by 12% (hazard ratio 1.12, 95% confidence interval 1.05 to 1.19, p <0.01) in those with diabetes, and by 13% (hazard ratio 1.13, 95% confidence interval 1.09 to 1.17, p <0.01) in the total cohort. After 30 days, glucose level at admission lost its predictive value. In conclusion, in patients with and those without diabetes, glucose level at admission is an independent predictor of early but not late mortality.

Cystatin C for Enhancement of Risk Stratification in Non–ST Elevation Acute Coronary Syndrome Patients with an Increased Troponin T

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.

Rationale and cross-sectional study design of the Research on Obesity and type 2 Diabetes among African Migrants: the RODAM study.

Introduction Obesity and type 2 diabetes (T2D) are highly prevalent among African migrants compared with European descent populations. The underlying reasons still remain a puzzle. Gene–environmental interaction is now seen as a potential plausible factor contributing to the high prevalence of obesity and T2D, but has not yet been investigated. The overall aim of the Research on Obesity and Diabetes among African Migrants (RODAM) project is to understand the reasons for the high prevalence of obesity and T2D among sub-Saharan Africans in diaspora by (1) studying the complex interplay between environment (eg, lifestyle), healthcare, biochemical and (epi)genetic factors, and their relative contributions to the high prevalence of obesity and T2D; (2) to identify specific risk factors within these broad categories to guide intervention programmes and (3) to provide a basic knowledge for improving diagnosis and treatment. Methods and analysis RODAM is a multicentre cross-sectional study among homogenous sub-Saharan African participants (ie, Ghanaians) aged >25 years living in rural and urban Ghana, the Netherlands, Germany and the UK (http://rod-am.eu/). Standardised data on the main outcomes, genetic and non-genetic factors are collected in all locations. The aim is to recruit 6250 individuals comprising five subgroups of 1250 individuals from each site. In Ghana, Kumasi and Obuasi (urban stratum) and villages in the Ashanti region (rural stratum) are served as recruitment sites. In Europe, Ghanaian migrants are selected through the municipality or Ghanaian organisations registers. Ethics and dissemination Ethical approval has been obtained in all sites. This paper gives an overview of the rationale, conceptual framework and methods of the study. The differences across locations will allow us to gain insight into genetic and non-genetic factors contributing to the occurrence of obesity and T2D and will inform targeted intervention and prevention programmes, and provide the basis for improving diagnosis and treatment in these populations and beyond.

High-sensitivity troponin T is associated with poor outcome in adults with pulmonary arterial hypertension due to congenital heart disease.

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 < .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). CONCLUSION Levels of hsTnT were abnormal in a substantial proportion of CHD-PAH patients. A significant inverse relationship was found between hsTnT and survival.

Growth-differentiation factor 15 for long-term prognostication in patients with non-ST-elevation acute coronary syndrome: An Invasive versus Conservative Treatment in Unstable coronary Syndromes (ICTUS) substudy

BACKGROUND 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). METHODS 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 <1200 ng/L, 1200-1800 ng/L and >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<1200 ng/L, a 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. CONCLUSION 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.