Comment on Immunoassays Developed for Pregnancy-Associated Plasma Protein-A (PAPP-A) in Pregnancy May Not Recognize PAPP-A in Acute Coronary Syndromes

Fredericks, Salim; Bertomeu‐González, Vicente; Petrović, Ivana; Holt, David W.; Kaski, Juan Carlos

doi:10.1373/clinchem.2006.074138

Cited by 9 publications

(5 citation statements)

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“…We found no previous reports on the relationship between plasma PAPP-A levels and the hemostatic parameters evaluated that were selected to globally identify coagulation or fibrinolysis activation in diabetic patients. The absolute PAPP-A serum concentrations found in our study could not be compared with those reported in other studies (2,10,11,15) owing to the different methods used for PAPP-A measurement (16 …”

contrasting

confidence: 95%

Pregnancy-Associated Plasma Protein-A Levels Are Related to Glycemic Control but Not to Lipid Profile or Hemostatic Parameters in Type 2 Diabetes

Pellitero¹,

Reverter²,

Pizarro³

et al. 2007

Diabetes Care

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Pregnancy-associated plasma protein-A (PAPP-A) is a zinc-binding matrix metalloproteinase that regulates extracellular matrix remodeling. PAPP-A degrades IGFBP-4, increasing levels of local IGF-1 in response to injury, and could be involved in the pathogenesis of atherosclerosis (1-6). Inflammatory cytokines tumor necrosis factor (TNF)-␣ and interleukin (IL)-1␤, implicated in insulin resistance (7), are potent stimulators of 9). The association between PAPP-A levels and metabolic parameters such as cholesterol and high-sensitivity C-reactive protein (hsCRP) is controversial (2,10,11). We aimed to study the relationship between PAPP-A, glycemic control and other metabolic and hemostatic parameters, inflammatory cytokines, and ankle-brachial pressure index (ABI) in diabetic patients.RESEARCH DESIGN AND METHODS -Type 2 diabetic patients (n ϭ 175, 65 of whom were women) with stable glycemic control (variation in A1C Ͻ10% in the last 5 years) and without diagnosis of clinical macrovascular disease, inflammatory disease, malignancies, or pregnancy were studied. Fifty-three (20 of whom were women) nondiabetic subjects without previous clinical macrovascular disease and normal ABI (Ն0.9) were recruited as control subjects.Demographic, anthropometric, and clinical data and ABI were recorded in all subjects. Laboratory data were measured by commercially available assays, hsCRP by nephelometry, ultrasensitive PAPP-A using an enzyme-linked immunosorbent assay, and TNF-␣ and IL-6 concentrations using an enzyme chemiluminescence immumometric assay.Continuous variables were expressed as means Ϯ SD or median (interquartile range). Differences between groups were examined by Student's t test or MannWhitney and correlation between variables by Pearson's or Spearman's tests as required. Multiple logistic regression analysis was performed.RESULTS -Clinical and biochemical characteristics of all study subjects are shown in Table 1. PAPP-A levels were significantly higher in male than in female subjects in both groups ( No differences in PAPP-A levels were observed when subjects with normocholesterolemia were compared with those with hypercholesterolemia (median [interquartile range] 0.6 [0.45-1.14] vs. 0.8 mUI/l [0.48 -1.38], respectively) and with diabetic patients (0.6 [0.45-1.14] vs. 0.8 mUI/l [0.48 -1.38]). On the other hand, when control subjects and diabetic patients with normocholesterolemia were compared, PAPP-A levels remained significantly higher in control subjects than in diabetic patients (0.6 [0.45-1.14] vs. 0.33 mUI/l [0.13-0.83], respectively, P ϭ 0.04). We obtained the same results when control subjects and diabetic patients with hypercholesterolemia were compared (0.8 [0.48 -1.38] vs. 0.44 mUI/l [0.22-0.78], P Ͻ 0.0001). Moreover, PAPP-A levels were similar in subjects treated with statins compared with those in untreated subjects in both groups.No differences were observed in PAPP-A levels between diabetic patients with or without a history of diabetic vasculopathy (n ϭ 25), abnormal ABI (n ϭ 54), nephropathy (n ϭ...

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contrasting

confidence: 95%

Pregnancy-Associated Plasma Protein-A Levels Are Related to Glycemic Control but Not to Lipid Profile or Hemostatic Parameters in Type 2 Diabetes

Pellitero¹,

Reverter²,

Pizarro³

et al. 2007

Diabetes Care

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“…[215][216][217] Different assays may therefore perform differently. 218 It has been shown that free PAPP-A is a better predictor than total PAPP-A. 219 Finally, it has been demonstrated that administration of intravenous heparin causes a rise in PAPP-A due to release from the arterial wall.…”

Section: Pregnancy-associated Plasma Protein Amentioning

confidence: 99%

Randomised Assessment of Treatment using Panel Assay of Cardiac markers – Contemporary Biomarker Evaluation (RATPAC CBE)

Collinson

Gaze²,

Thokala³

et al. 2013

Health Technol Assess

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Reports are published in Health Technology Assessment (HTA) if (1) they have resulted from work for the HTA programme, and (2) they are of a sufficiently high scientific quality as assessed by the reviewers and editors.Reviews in Health Technology Assessment are termed 'systematic' when the account of the search appraisal and synthesis methods (to minimise biases and random errors) would, in theory, permit the replication of the review by others. HTA programmeThe HTA programme, part of the National Institute for Health Research (NIHR), was set up in 1993. It produces high-quality research information on the effectiveness, costs and broader impact of health technologies for those who use, manage and provide care in the NHS. 'Health technologies' are broadly defined as all interventions used to promote health, prevent and treat disease, and improve rehabilitation and long-term care.The journal is indexed in NHS Evidence via its abstracts included in MEDLINE and its Technology Assessment Reports inform National Institute for Health and Care Excellence (NICE) guidance. HTA research is also an important source of evidence for National Screening Committee (NSC) policy decisions.For more information about the HTA programme please visit the website: http://www.hta.ac.uk/ This reportThe research reported in this issue of the journal was funded by the HTA programme as project number 09/22/16. The contractual start date was in August 2010. The draft report began editorial review in February 2012 and was accepted for publication in June 2012. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors' report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.This report presents independent research funded by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, NETSCC, the HTA programme or the Department of Health. Published by the NIHR Journals Library, produced by Prepress Projects Ltd, Perth, Scotland (www.prepress-projects.co.uk). Objectives: To test the diagnostic accuracy for detecting an acute myocardial infarction (AMI) using highly sensitive troponin assays and a range of new cardiac biomarkers of plaque destabilisation, myocardial ischaemia and necrosis; to test the prognostic accuracy for detecting adverse cardiac events using highly sensitive troponin assays and this range of new cardiac biomarkers; and to estimate the cost-effectiveness of using highly sensitive troponin assays or this range of new cardiac biomarkers instead of an admission and 10-to 12-hour troponin measurement. NIHR Journals LibraryDesign: Substudy of the point-of-care arm of the RATPAC (Randomised Assessment ...

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“…Prior studies involving these markers in ACS have shown that circulating levels vary with culprit lesion morphology [ 15 ], severity of clinical presentation (highest in STEMI) [ 18 ; 19 ; 21 ] and time from symptom onset [ 21 ], with decreasing sensitivity and specificity as the time increases [ 20 ]; the latter may explain the low concentrations observed in the NSTEMI-L group. Additionally, commercially available assays vary in their cut-off values and diagnostic sensitivities and specificities [ 30 ]. Naturally, since the release of these markers is not exclusive for ACS, differences in sensitivities and specificities are expected to vary according to the studied populations.…”

Section: Discussionmentioning

confidence: 99%

A Plaque Disruption Index Identifies Patients with Non-STE-Type 1 Myocardial Infarction within 24 Hours of Troponin Positivity

et al. 2016

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BackgroundMarkers of plaque destabilization and disruption may have a role in identifying non-STE- type 1 Myocardial Infarction in patients presenting with troponin elevation. We hypothesized that a plaque disruption index (PDI) derived from multiple biomarkers and measured within 24 hours from the first detectable troponin in patients with acute non-STE- type 1 MI (NSTEMI-A) will confirm the diagnosis and identify these patients with higher specificity when compared to individual markers and coronary angiography.MethodsWe examined 4 biomarkers of plaque destabilization and disruption: myeloperoxidase (MPO), high-sensitivity interleukin-6, myeloid-related protein 8/14 (MRP8/14) and pregnancy-associated plasma protein-A (PAPP-A) in 83 consecutive patients in 4 groups: stable non-obstructive coronary artery disease (CAD), stable obstructive CAD, NSTEMI-A (enrolled within 24 hours of troponin positivity), and NSTEMI-L (Late presentation NSTEMI, enrolled beyond the 24 hour limit). The PDI was calculated and the patients’ coronary angiograms were reviewed for evidence of plaque disruption. The diagnostic performance of the PDI and angiography were compared.ResultsCompared to other biomarkers, MPO had the highest specificity (83%) for NSTEMI-A diagnosis (P<0.05). The PDI computed from PAPP-A, MRP8/14 and MPO was higher in NSTEMI-A patients compared to the other three groups (p<0.001) and had the highest diagnostic specificity (87%) with 79% sensitivity and 86% accuracy, which were higher compared to those obtained with MPO, but did not reach statistical significance (P>0.05 for all comparisons). The PDI had higher specificity and accuracy for NSTEMI-A diagnosis compared to coronary angiography (P<0.05).ConclusionsA PDI measured within 24 hour of troponin positivity has potential to identify subjects with acute Non-ST-elevation type 1 MI. Additional evidence using other marker combinations and investigation in a sufficiently large non-selected cohort is warranted to establish the diagnostic accuracy of the PDI and its potential role in differentiating type 1 and type 2 MI in patients presenting with troponin elevation of uncertain etiology.

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Comment on Immunoassays Developed for Pregnancy-Associated Plasma Protein-A (PAPP-A) in Pregnancy May Not Recognize PAPP-A in Acute Coronary Syndromes

Cited by 9 publications

References 10 publications

Pregnancy-Associated Plasma Protein-A Levels Are Related to Glycemic Control but Not to Lipid Profile or Hemostatic Parameters in Type 2 Diabetes

Pregnancy-Associated Plasma Protein-A Levels Are Related to Glycemic Control but Not to Lipid Profile or Hemostatic Parameters in Type 2 Diabetes

Randomised Assessment of Treatment using Panel Assay of Cardiac markers – Contemporary Biomarker Evaluation (RATPAC CBE)

A Plaque Disruption Index Identifies Patients with Non-STE-Type 1 Myocardial Infarction within 24 Hours of Troponin Positivity

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