Original Article
Pregnancy-Associated Plasma Protein A as a Marker of Acute Coronary Syndromes
N Engl J Med 2001; 345:1022-1029October 4, 2001
- Abstract
Background
Circulating markers indicating the instability of atherosclerotic plaques could have diagnostic value in unstable angina or acute myocardial infarction. We evaluated pregnancy-associated plasma protein A (PAPP-A), a potentially proatherosclerotic metalloproteinase, as a marker of acute coronary syndromes.
Methods
We examined the level of expression of PAPP-A in eight culprit unstable coronary plaques and four stable plaques from eight patients who had died suddenly of cardiac causes. We also measured circulating levels of PAPP-A, C-reactive protein, and insulin-like growth factor I (IGF-I) in 17 patients with acute myocardial infarction, 20 with unstable angina, 19 with stable angina, and 13 controls without atherosclerosis.
Results
PAPP-A was abundantly expressed in plaque cells and extracellular matrix of ruptured and eroded unstable plaques, but not in stable plaques. Circulating PAPP-A levels were significantly higher in patients with unstable angina or acute myocardial infarction than in patients with stable angina and controls (P<0.001). A PAPP-A threshold value of 10 mIU per liter identified patients who had acute coronary syndromes with a sensitivity of 89.2 percent and a specificity of 81.3 percent. PAPP-A levels correlated with levels of C-reactive protein and free IGF-I, but not with markers of myocardial injury (troponin I and the MB isoform of creatine kinase).
Conclusions
PAPP-A is present in unstable plaques, and circulating levels are elevated in acute coronary syndromes; these increased levels may reflect the instability of atherosclerotic plaques. PAPP-A is a new candidate marker of unstable angina and acute myocardial infarction.
Media in This Article
Figure 3
Correlation between Pregnancy-Associated Plasma Protein A (PAPP-A) Levels and the Levels of the Cardiac Necrosis Markers Troponin I and Creatine Kinase MB in 17 Patients with Acute Myocardial Infarction.Figure 4
Receiver-Operating-Characteristic (ROC) Curves for the Levels of Pregnancy-Associated Plasma Protein A (PAPP-A) and C-Reactive Protein (CRP) in 17 Patients with Acute Myocardial Infarction and 20 Patients with Unstable Angina.Article Activity
- Article
Patients with acute coronary syndromes are at considerable risk for serious complications and death. Clinical outcomes might be improved by rapid and accurate diagnosis, followed by appropriate therapy. Diagnostic tests for myocardial injury include technetium-99m sestamibi scanning to identify defects in myocardial perfusion,1 echocardiography to identify abnormalities in left ventricular wall motion,2 and measurements of circulating levels of the MB isoform of creatine kinase,3 myoglobin,4 troponin I,5 and troponin T6 to identify myocardial necrosis. Each test reflects different steps of the pathway from coronary occlusion to myocardial ischemia: impairment of coronary-artery flow, ischemic myocardial dysfunction, and eventually, myocardial-tissue necrosis. The availability of a sensitive and specific early marker of the instability of plaques, whose levels become elevated before or in the absence of an elevation of other markers of myocardial-cell injury, might improve diagnostic and therapeutic decision making and, possibly, the value of traditional tests.7
We hypothesized that pregnancy-associated plasma protein A (PAPP-A), which is found in both men and women, might be such a marker and could identify patients with unstable atherosclerotic plaques. PAPP-A is a high-molecular-weight, zinc-binding metalloproteinase.8,9 It is thus a potentially proatherosclerotic molecule and has recently been shown to be a specific activator of insulin-like growth factor I (IGF-I),9 a mediator of atherosclerosis.10,11 PAPP-A antigen is typically measured during pregnancy (levels increase to about 100 IU per liter at term) with the use of routine assays with limited sensitivity.12-14
We examined the level of expression of PAPP-A in unstable plaques from patients who died suddenly of cardiac causes. We also assessed circulating PAPP-A levels in patients with acute coronary syndromes (unstable angina and acute myocardial infarction), using a highly sensitive immunoassay.
Methods
Collection and Analysis of Tissue
Atherosclerotic arteries were obtained at autopsy from eight patients within 24 hours after sudden death from cardiac causes, as defined previously.15 The characteristics of acute rupture of plaques, erosion of plaques, and stable plaques were also defined previously.15 Immunohistochemical staining was performed on 5-μm-thick paraffin sections with use of a peroxidase-labeled streptavidin–biotin method.16 Monoclonal human antibody against PAPP-A (234–5)13 was used at a concentration of 20 μg per milliliter. Sections were also stained with antibodies against macrophage CD68 (clone KP-1, Dako, Carpinteria, Calif.) at a dilution of 1:200 and with antibodies against smooth-muscle α-actin (clone 1A4, IgG2a, Dako) at a dilution of 1:500. The total area of plaque and the percentage of the area that stained for PAPP-A were evaluated. Quantitative immunohistochemical analysis was performed with use of a quantitative color-image analysis system (Diagnostic Instruments, Sterling Heights, Mich.).
Patient Population
The study groups consisted of 17 patients with acute myocardial infarction, 20 with unstable angina, 19 with stable angina, and 13 age-matched control patients without clinical or angiographic evidence of coronary atherosclerosis. All subjects were consecutively identified and approached for consent as they were scheduled to undergo coronary arteriography in the Mayo Clinic cardiac catheterization laboratory.
Acute myocardial infarction was defined as prolonged chest pain accompanied by ST-segment elevation or depression evolving into pathologic Q-wave or T-wave inversion and confirmed by a finding that the creatine kinase MB fraction was more than twice the upper limit of the normal range and by a troponin I level of more than 0.5 ng per milliliter. Unstable angina was defined as chest discomfort at rest with either ST-segment depression of at least 0.1 mV or T-wave inversion in two or more contiguous electrocardiographic leads, a creatine kinase MB fraction that was within normal limits, and angiographically confirmed coronary artery disease. Chronic, stable, effort-induced angina was diagnosed as chest pain of at least six months' duration accompanied by evidence of severe coronary artery disease on coronary angiography and by the absence of clinically evident ischemic episodes during the week preceding arteriography.
Exclusion criteria were advanced kidney or liver failure, overt heart failure, and a history of major surgery or trauma within the previous month. Patients with known or suspected systemic thrombotic disorders (other than those of coronary origin) or inflammatory diseases were excluded, as were those who were pregnant. Angiographically severe coronary artery disease was defined by the presence of one or more stenoses of at least 70 percent in any major coronary artery. To identify a possible association between PAPP-A levels and the extent and severity of coronary artery disease discovered at angiography, the Jenkins score was calculated for every patient.17 Scores can range from 0 to 32, with higher scores indicating more severe disease.
Blood samples were obtained at the time of coronary angiography, placed on ice, and centrifuged within 30 minutes at 1600×g for 5 minutes. All samples were analyzed by personnel who had no knowledge of the subjects' clinical data. The mean (±SD) time from the last ischemic episode to blood sampling was 8.4±3.0 hours in the group with myocardial infarction and 9.4±3.9 hours in the group with unstable angina.
The study was approved by the institutional review board of the Mayo Clinic and Foundation, and all patients gave oral informed consent.
Plasma Protein Assays
PAPP-A levels were determined by means of a biotin–tyramide–amplified enzyme immunoassay with a limit of detection of 0.03 mIU per liter and intraassay and interassay coefficients of variation of 10 percent and 15 percent, respectively. PAPP-A polyclonal antibodies were used for capture18 and a combination of monoclonal antibodies was used for detection.13 The assay was calibrated against the World Health Organization's international reference standard 78/610, which is the standard for pregnancy-associated proteins.
A highly sensitive latex-particle–enhanced immunoturbidimetric assay (Kamiya Biomedical, Seattle) was used to quantitate the level of C-reactive protein. Total IGF-I and free IGF-I were measured by commercially available immunoradiometric assays (Diagnostic Systems Laboratories, Webster, Tex.). We hypothesized that increased PAPP-A levels would lead to increased levels of free IGF-I as a result of proteolysis by IGF-binding protein 4.9 Creatine kinase MB and cardiac troponin I were measured with an immunochemiluminometric assay (Chiron, Emeryville, Calif.) in a standard fashion at the Mayo Clinic clinical laboratory.
Statistical Analysis
Results of analyses of histopathological data are presented as means ±SD. We used Student's t-test to compare eroded and ruptured plaques with stable plaques. We used analysis of variance or two-way cross-tabulation with the chi-square test, when appropriate, to compare differences between groups in demographic and angiographic characteristics. Data on PAPP-A, free IGF-I, total IGF-I, and C-reactive protein, which were not distributed normally, were summarized by medians and ranges and were compared among the groups with use of the Kruskal–Wallis test. When the results indicated that there were significant differences between groups, we made pairwise group comparisons using the Wilcoxon rank-sum statistic. Associations among circulating levels of these proteins were assessed by Spearman's rank-correlation coefficient. Associations of PAPP-A with risk factors and comparisons of PAPP-A levels in each group after adjustment for these risk factors were assessed with use of multiple linear regression, with the logarithm of PAPP-A as the dependent variable.
We used receiver-operating-characteristic (ROC) analysis on the levels of PAPP-A and C-reactive protein for myocardial infarction and unstable angina. The ROC curve is a common test to quantitate the diagnostic accuracy of medical tests. This strategy plots the true positive fraction, or sensitivity, against the false positive fraction (1 – specificity) by varying the threshold value for the test. The threshold is varied with increasingly stringent criteria for positivity. The ROC curve thus indicates the probability of a true positive result as a function of the probability of a false positive result for all possible threshold values. The area under the ROC curve assesses the relative accuracy of two diagnostic tests. An area of 0.5 indicates that the test results are no better than those obtained by chance, whereas an area of 1.0 indicates a perfectly sensitive and specific test. The areas under the curve for PAPP-A and C-reactive protein levels were compared according to the method of DeLong et al.19 P values less than 0.05 were considered to indicate statistical significance. All P values are two-sided.
Results
Expression of PAPP-A in Unstable Plaques
Four ruptured plaques and four eroded plaques were identified as culprit unstable lesions in the arteries obtained at autopsy from eight patients. Four stable plaques were also identified. There were no significant differences in the total area of the plaques among the ruptured plaques (mean, 7.1±1.4 mm2), eroded plaques (mean, 8.0±3.7 mm2), and stable plaques (mean, 5.7±2.1 mm2). In plaques with large lipid cores and cap rupture, staining for PAPP-A occurred mostly in the inflammatory shoulder region (Figure 1AFigure 1
Expression of Pregnancy-Associated Plasma Protein A (PAPP-A) in Unstable and Stable Coronary Atherosclerotic Plaques.), in areas surrounding the lipid core, and localized with CD68-positive cells (not shown). In fibrous plaques with superficial erosion, PAPP-A was identified within spindle-shaped smooth-muscle cells containing α-actin (not shown), in the extracellular matrix (Figure 1B), and in noneroded endothelial cells (Figure 1C). Quantitative image analysis showed that the level of expression of PAPP-A in fibrous eroded plaques exceeded that in ruptured plaques (28.3±16.8 percent vs. 18.5±8.0 percent), but the difference was not statistically significant (P=0.34). PAPP-A was absent or only minimally expressed in stable plaques (Figure 1D). Quantitative image analysis showed that the level of expression of PAPP-A was significantly lower in stable plaques (3.2±1.9 percent) than in ruptured plaques (P=0.01) or eroded plaques (P=0.02).Circulating Marker Proteins in Acute Coronary Syndromes
To determine whether the abundant expression of PAPP-A in unstable plaques might translate into elevated circulating levels, we measured PAPP-A levels in patients with acute coronary syndromes (myocardial infarction and unstable angina) and in those in stable condition (patients with stable angina and controls without atherosclerosis). Table 1Table 1
Characteristics of the Patients. shows the age, sex, risk factors, base-line therapy, and angiographic results in the four groups. Patients with stable angina had three-vessel disease significantly more frequently than did patients with myocardial infarction (P=0.004), but no significant differences were observed among the groups with stable angina, unstable angina, and myocardial infarction regarding the coronary atherosclerotic burden, as evaluated by the Jenkins score (P=0.88). The control subjects had lower levels of risk factors than the three other groups, but the levels were similar among these three groups.Circulating PAPP-A Levels
The data on PAPP-A levels are shown in Table 2Table 2
Median Levels of Pregnancy-Associated Plasma Protein A, C-Reactive Protein, and Free and Total Insulin-like Growth Factor I.. The Kruskal–Wallis test indicated that the differences among the groups were as follows. The median PAPP-A levels in control subjects (7.4 mIU per liter; range, 3.8 to 10.4) were not significantly different from those in patients with stable angina (8.4 mIU per liter; range, 4.4 to 22.5; P=0.07). In the group of patients with unstable angina, the median PAPP-A levels (14.9 mIU per liter; range, 6.3 to 63.4) were significantly higher than those in the control group (P<0.001) or the group with stable angina (P<0.001). In the group of patients with myocardial infarction, the median PAPP-A levels (20.6 mIU per liter; range, 9.2 to 46.6) were also significantly higher than those in the control group (P<0.001) or the group with stable angina (P<0.001). The PAPP-A levels did not differ significantly between the group with unstable angina and the group with myocardial infarction (P=0.75).Multiple-regression models showed that the PAPP-A level was not associated with age, sex, risk factors, or medications. Among the three groups with atherosclerosis, the PAPP-A level was significantly and inversely associated with the extent of atherosclerosis, expressed as the number of vessels with clinically significant luminal stenosis (one, two, or three vessels) (P=0.04), but it was not associated with the Jenkins score (P=0.27). This result probably reflects the coexistence of quiescent atherosclerotic plaques with active, vulnerable, or fissured plaques in the coronary tree.
Circulating Levels of C-Reactive Protein, IGF-I, and Markers of Myocardial Injury
The Kruskal–Wallis analysis of C-reactive protein levels indicated that there were significant differences among the groups. Levels of C-reactive protein were significantly higher in the patients who had had a myocardial infarction than in the patients with unstable and stable angina (P=0.02 and P=0.001, respectively), and the levels were slightly but significantly higher in the patients with unstable angina than in those with stable angina (P=0.045). In the control group the levels of C-reactive protein were significantly lower than those in the myocardial-infarction group (P=0.006). The level of C-reactive protein was significantly associated with the PAPP-A level in patients with acute coronary syndromes (Spearman's rho=0.61, P<0.001) (Figure 2Figure 2
Correlation between Levels of Pregnancy-Associated Plasma Protein A (PAPP-A) and Levels of C-Reactive Protein and Free Insulin-like Growth Factor I (IGF-I) in 17 Patients with Myocardial Infarction and 20 Patients with Unstable Angina.). The levels of C-reactive protein were not associated with age, sex, risk factors, medications, or the extent of coronary atherosclerosis.No significant differences in free IGF-I levels were found among the groups; however, a weak but significant correlation was observed between free IGF-I levels and PAPP-A levels in patients with acute coronary syndromes (Spearman's rho=0.39, P=0.02) (Figure 2). No significant differences were found in total IGF-I levels between patients with acute coronary syndromes and patients in stable condition (Table 2), and no correlation with PAPP-A levels was observed.
Creatine kinase MB levels were not elevated in blood samples from patients with unstable angina, and only 3 of 20 patients with unstable angina had troponin I levels above normal (mean, 1.6±0.7 ng per milliliter). In the group of patients with myocardial infarction, the peak levels of troponin I and creatine kinase MB were 60.9 ng per milliliter (range, 1.3 to 368) and 76.3 ng per milliliter (range, 4.4 to 341), respectively. In this group, there were no significant correlations between the level of PAPP-A and the level of either troponin I (Spearman's rho=0.33, P=0.18) or creatine kinase MB (Spearman's rho=0.23, P=0.36) (Figure 3Figure 3
Correlation between Pregnancy-Associated Plasma Protein A (PAPP-A) Levels and the Levels of the Cardiac Necrosis Markers Troponin I and Creatine Kinase MB in 17 Patients with Acute Myocardial Infarction.). Even when the patients with unstable angina and the patients with myocardial infarction were combined, there was no significant association between the level of PAPP-A and the level of either troponin I (Spearman's rho=0.07, P=0.69) or creatine kinase MB (Spearman's rho=0.10, P=0.57). Therefore, the elevated PAPP-A levels in these patients cannot be attributed to myocardial necrosis.PAPP-A as a Diagnostic Marker of Acute Coronary Syndromes
The mean (±SE) area under the ROC curve for PAPP-A was 0.94±0.03 among the patients with acute myocardial infarction and 0.88±0.05 among the patients with unstable angina, with control patients and patients with stable angina serving as the ROC control group. In a parallel analysis, C-reactive protein had a mean area under the curve of 0.81±0.07 among the patients with myocardial infarction and 0.67±0.08 among the patients with unstable angina. These differences between the two markers were significant both for the group with myocardial infarction (P=0.03) and for the group with unstable angina (P=0.01) (Figure 4Figure 4
Receiver-Operating-Characteristic (ROC) Curves for the Levels of Pregnancy-Associated Plasma Protein A (PAPP-A) and C-Reactive Protein (CRP) in 17 Patients with Acute Myocardial Infarction and 20 Patients with Unstable Angina.). These data suggest that PAPP-A is a valuable marker — better than C-reactive protein — for the identification of patients with acute coronary syndromes.A threshold level of 10 mIU of PAPP-A per liter had the highest combined sensitivity and specificity for the identification of acute coronary syndromes. The sensitivity and specificity of PAPP-A levels above 10 mIU per liter were 89.2 percent and 81.3 percent, respectively. The sensitivity of PAPP-A levels above 10 mIU per liter was 94.1 percent in the case of myocardial infarction and 85.0 percent in the case of unstable angina. In the case of the groups without atherosclerosis, only 1 of 13 control subjects (8 percent) and 5 of 19 patients with stable angina (26 percent) had PAPP-A levels of more than 10 mIU per liter.
Discussion
We found a relation between unstable coronary disease and the levels of PAPP-A. PAPP-A is a member of the metzincin superfamily of metalloproteinases9 originally identified in the serum of pregnant women.20 Circulating PAPP-A levels are used in the fetal diagnosis of Down's syndrome.14 Only recently has PAPP-A been identified outside pregnancy in nonplacental tissue.9,21
Histologic evidence of an association between PAPP-A and acute coronary syndromes comes from the evaluation of unstable plaques in patients who have died suddenly of cardiac causes. Using specific monoclonal antibodies, we found that PAPP-A was abundantly expressed in both eroded and ruptured plaques but was only minimally expressed in stable plaques. Our findings suggest that PAPP-A may be produced by activated cells in unstable plaques and released into the extracellular matrix. Whether PAPP-A can degrade extracellular matrix remains unclear. Other metalloproteinases have been associated with macrophage-rich shoulder regions of atherosclerotic lesions22 and circumstantially implicated in plaque rupture.23
The finding of a high level of expression of PAPP-A in unstable atherosclerotic plaques prompted us to assess circulating PAPP-A levels in patients with acute coronary syndromes. Circulating levels of PAPP-A were significantly elevated in patients with unstable angina and patients with myocardial infarction. We determined that a PAPP-A threshold of 10 mIU per liter accurately identified patients with acute coronary syndromes.
Several studies have assessed other serum markers in patients with unstable angina. Hamm and colleagues found that the diagnostic sensitivity of cardiac-specific troponins in unstable angina is low, since only 22 percent of patients had positive troponin T tests and 36 percent had positive troponin I tests.24 C-reactive protein is also a suboptimal diagnostic marker of unstable angina. Liuzzo et al. found that only 20 of 31 patients with unstable angina (65 percent) had elevated levels of C-reactive protein on admission.25 Both markers are nonetheless associated with unfavorable outcomes when they are elevated.6,25 In our study, troponin I levels were elevated in 3 patients with unstable angina (15 percent) and C-reactive protein levels were elevated in 10 (50 percent) of these patients. By comparison, PAPP-A levels of more than 10 mIU per liter were present in 17 of 20 patients with unstable angina (85 percent), and in 16 of 17 patients with myocardial infarction (94 percent). Thus, PAPP-A levels appear to be valuable for detecting unstable coronary disease even when the levels of troponins and C-reactive protein are not elevated, thus potentially identifying high-risk patients whose disease might otherwise remain undiagnosed.
In our study, the levels of troponin I and creatine kinase MB were not associated with PAPP-A levels in patients with acute coronary syndromes. This finding indicates that PAPP-A is not produced in response to myocardial necrosis, a potent stimulus for the synthesis of inflammatory cytokines and acute-phase reactants. The magnitude of injury may reflect the size of the infarction, which may not be related to the size or magnitude of the inflammatory response associated with an active plaque in the infarcted artery.
The significant association between PAPP-A levels and C-reactive protein levels in patients with acute coronary syndromes is consistent with growing evidence suggesting that inflammation has a pivotal role in these syndromes.26,27 The accumulation of macrophages in unstable atherosclerotic lesions stimulates the production of metalloproteinases28 and may be associated with increases in the plasma levels of C-reactive protein.29 We excluded patients with nonatherosclerotic inflammatory disorders in order to avoid potentially confounding results with respect to PAPP-A.
We also found an association between PAPP-A levels and free IGF-I levels. The recent identification of PAPP-A as the enzyme cleaving IGF-binding protein 4, an inhibitor of the action of IGF, suggests that PAPP-A increases the availability of IGF-I,9 thus contributing to the progression of both coronary atherosclerosis and restenosis.30 The free fraction of circulating and locally synthesized IGF-I induces the migration of vascular smooth-muscle cells31 and is important for monocyte chemotaxis and the activation and release of cytokines within the atherosclerotic lesion.32
Our study cannot answer questions such as whether PAPP-A is a primary or secondary component of acute coronary syndromes. Further studies are required to characterize the importance of PAPP-A within unstable coronary plaques and to elucidate the diagnostic and prognostic significance of elevated PAPP-A levels in patients with acute coronary syndromes. Our study was limited in terms of the number of patients examined, and it is important to confirm the findings with studies of more patients.
In conclusion, PAPP-A is a new candidate marker for the early diagnosis of acute coronary syndromes. Our results demonstrate that circulating PAPP-A levels can identify patients early in the process of plaque instability, when it might still be possible to avert myocardial injury. In addition to their practical clinical importance, our observations point out new avenues of investigation into the causes of unstable angina and myocardial infarction.
Supported in part by a grant from La Caixa Foundation (to Dr. Bayes-Genis).
Dr. Conover is a member of the scientific advisory board of Diagnostic Systems Laboratories, which provided the kit to measure IGF-I.
Source Information
From the Division of Cardiovascular Diseases (A.B.-G., D.R.H., R.S.S.), Endocrine Research Unit (C.A.C.), and Statistics Department (K.R.B.), Mayo Clinic and Foundation, Rochester, Minn.; the Department of Molecular and Structural Biology, University of Aarhus, Aarhus, Denmark (M.T.O., C.O.); the Department of Clinical Biochemistry, Statens Serum Institute, Copenhagen, Denmark (M.C.); and the Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, D.C. (R.V.).
Address reprint requests to Dr. Schwartz at the Division of Cardiovascular Diseases, Mayo Clinic, 200 First St., SW, Rochester, MN 55905.
- References
References
1
Kontos MC ,Jesse RL ,Schmidt KL ,Ornato JP ,Tatum JL . Value of acute rest sestamibi perfusion imaging for evaluation of patients admitted to the emergency department with chest pain. J Am Coll Cardiol 1997;30:976-982
CrossRef | Web of Science | Medline2
Sabia P ,Afrookteh A ,Touchstone DA ,Keller MW ,Esquivel L ,Kaul S . Value of regional wall motion abnormality in the emergency room diagnosis of acute myocardial infarction: a prospective study using two-dimensional echocardiography. Circulation 1991;84:Suppl:85-923
Puleo PR ,Meyer D ,Wathen C , et al. Use of a rapid assay of subforms of creatine kinase MB to diagnose or rule out acute myocardial infarction. N Engl J Med 1994;331:561-566
Full Text | Web of Science | Medline4
de Winter RJ ,Koster RW ,Sturk A ,Sanders GT . Value of myoglobin, troponin T, and CK-MBmass in ruling out an acute myocardial infarction in the emergency room. Circulation 1995;92:3401-3407
Web of Science | Medline5
Antman EM ,Tanasijevic MJ ,Thompson B , et al. Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med 1996;335:1342-1349
Full Text | Web of Science | Medline6
Ohman EM ,Armstrong PW ,Christenson RH , et al. Cardiac troponin T levels for risk stratification in acute myocardial ischemia. N Engl J Med 1996;335:1333-1341
Full Text | Web of Science | Medline7
Newby LK . Cardiac marker testing: where should we focus? Am Heart J 2000;140:351-353
CrossRef | Web of Science | Medline8
Oxvig C ,Sand O ,Kristensen T ,Kristensen L ,Sottrup-Jensen L . Isolation and characterization of circulating complex between human pregnancy-associated plasma protein-A and proform of eosinophil major basic protein. Biochim Biophys Acta 1994;1201:415-423
Web of Science | Medline9
Lawrence JB ,Oxvig C ,Overgaard MT , et al. The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A. Proc Natl Acad Sci U S A 1999;96:3149-3153
CrossRef | Web of Science | Medline10
Nichols TC ,du Laney T ,Zheng B , et al. Reduction in atherosclerotic lesion size in pigs by αVβ3 inhibitors is associated with inhibition of insulin-like growth factor-I-mediated signaling. Circ Res 1999;85:1040-1045
Web of Science | Medline11
Du J ,Delafontaine P . Inhibition of vascular smooth muscle cell growth through antisense transcription of a rat insulin-like growth factor I receptor cDNA. Circ Res 1995;76:963-972
Web of Science | Medline12
Oxvig C ,Haaning J ,Kristensen L , et al. Identification of angiotensinogen and complement C3dg as novel proteins binding the proform of eosinophil major basic protein in human pregnancy serum and plasma. J Biol Chem 1995;270:13645-13651
CrossRef | Web of Science | Medline13
Qin QP ,Christiansen M ,Oxvig C , et al. Double-monoclonal immunofluorometric assays for pregnancy-associated plasma protein A/proeosinophil major basic protein (PAPP-A/proMBP) complex in first-trimester maternal serum screening for Down syndrome. Clin Chem 1997;43:2323-2332
Web of Science | Medline14
Wald NJ ,Watt HC ,Hackshaw AK . Integrated screening for Down's syndrome on the basis of tests performed during the first and second trimesters. N Engl J Med 1999;341:461-467
Full Text | Web of Science | Medline15
Burke AP ,Farb A ,Malcolm GT ,Liang Y ,Smialek J ,Virmani R . Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N Engl J Med 1997;336:1276-1282
Full Text | Web of Science | Medline16
Bayes-Genis A ,Schwartz RS ,Lewis DA , et al. Insulin-like growth factor binding protein-4 protease produced by smooth muscle cells increases in the coronary artery after angioplasty. Arterioscler Thromb Vasc Biol 2001;21:335-341
CrossRef | Web of Science | Medline17
Jenkins PJ ,Harper RW ,Nestel PJ . Severity of coronary atherosclerosis related to lipoprotein concentration. BMJ 1978;2:388-391
CrossRef | Web of Science | Medline18
Christiansen M ,Jaliashvili I ,Overgaard MT ,Ensinger C ,Obrist P ,Oxvig C . Quantification and characterization of pregnancy-associated complexes of angiotensinogen and the proform of eosinophil major basic protein in serum and amniotic fluid. Clin Chem 2000;46:1099-1105
Web of Science | Medline19
DeLong ER ,DeLong DM ,Clarke-Pearson DL . Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988;44:837-845
CrossRef | Web of Science | Medline20
Lin TM ,Galbert SP ,Kiefer DJ ,Spellacy WN ,Gall S . Characterization of four human pregnancy-associated plasma proteins. Am J Obstet Gynecol 1974;118:223-236
Web of Science | Medline21
Overgaard MT ,Oxvig C ,Christiansen M , et al. Messenger ribonucleic acid levels of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein: expression in human reproductive and nonreproductive tissues. Biol Reprod 1999;61:1083-1089
CrossRef | Web of Science | Medline22
Nikkari ST ,O'Brien KD ,Ferguson M , et al. Interstitial collagenase (MMP-1) expression in human carotid atherosclerosis. Circulation 1995;92:1393-1398
Web of Science | Medline23
Galis ZS ,Sukhova GK ,Lark MW ,Libby P . Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest 1994;94:2493-2503
CrossRef | Web of Science | Medline24
Hamm CW ,Goldmann BU ,Heeschen C ,Kreymann G ,Berger J ,Meinertz T . Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin I. N Engl J Med 1997;337:1648-1653
Full Text | Web of Science | Medline25
Liuzzo G ,Biasucci LM ,Gallimore JR , et al. The prognostic value of C-reactive protein and serum amyloid A protein in severe unstable angina. N Engl J Med 1994;331:417-424
Full Text | Web of Science | Medline26
Lusis AJ . Atherosclerosis. Nature 2000;407:233-241
CrossRef | Web of Science | Medline27
Ross R . Atherosclerosis -- an inflammatory disease. N Engl J Med 1999;340:115-126
Full Text | Web of Science | Medline28
Galis ZS ,Sukhova GK ,Kranzhofer R ,Clark S ,Libby P . Macrophage foam cells from experimental atheroma constitutively produce matrix-degrading proteinases. Proc Natl Acad Sci U S A 1995;92:402-406
CrossRef | Web of Science | Medline29
Ridker PM ,Cushman M ,Stampfer MJ ,Tracy RP ,Hennekens CH . Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997;336:973-979
Full Text | Web of Science | Medline30
Bayes-Genis A ,Conover CA ,Schwartz RS . Insulin-like growth factor axis: a review of atherosclerosis and restenosis. Circ Res 2000;86:125-130
Web of Science | Medline31
Jones JI ,Prevette T ,Gockerman A ,Clemmons DR . Ligand occupancy of the αVβ3 integrin is necessary for smooth muscle cells to migrate in response to insulin-like growth factor. Proc Natl Acad Sci U S A 1996;93:2482-2487
CrossRef | Web of Science | Medline32
Renier G ,Clement I ,Desfaits AC ,Lambert A . Direct stimulatory effect of insulin-like growth factor-I on monocyte and macrophage tumor necrosis factor-α production. Endocrinology 1996;137:4611-4618
CrossRef | Web of Science | Medline
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Marta Kalousová, Hana Benáková, Aleš Antonín Kuběna, Sylvie Dusilová-Sulková, Vladimír Tesař, Tomáš Zima. (2012) Pregnancy-Associated Plasma Protein A as an Independent Mortality Predictor in Long-Term Hemodialysis Patients. Kidney and Blood Pressure Research 35:3, 192-201
CrossRef4
A.B. Postnikov, T.I. Smolyanova, A.V. Kharitonov, D.V. Serebryanaya, S.V. Kozlovsky, Y.A. Tryshina, R.V. Malanicev, A.G. Arutyunov, M.M. Murakami, F.S. Apple, A.G. Katrukha. (2012) N-terminal and C-terminal Fragments of IGFBP-4 as Novel Biomarkers for Short-Term Risk Assessment of Major Adverse Cardiac Events in Patients Presenting with Ischemia. Clinical Biochemistry
CrossRef5
Nabeel S. Bondagji. (2012) Ischemic heart disease in pregnancy. Journal of the Saudi Heart Association
CrossRef6
Ana M. Fernández-alonso, Carlos J. Valdera-simbrón, Gabriel Fiol-Ruiz, Firma Rodríguez-sánchez, Peter Chedraui, Faustino R. Pérez-lópez. (2011) First trimester serum levels of 25-hydroxyvitamin D, free β-human chorionic gonadotropin, and pregnancy-associated plasma protein A in Spanish women. Gynecological Endocrinology 27:12, 1061-1064
CrossRef7
M. Madjid, J. T. Willerson. (2011) Inflammatory markers in coronary heart disease. British Medical Bulletin 100:1, 23-38
CrossRef8
Julio A. Carbayo Herencia. (2011) Nuevos marcadores de riesgo cardiovascular. ¿Pueden influir en la clasificación del riesgo cardiovascular?. Clínica e Investigación en Arteriosclerosis
CrossRef9
Diego Sbardella, Giovanni Francesco Fasciglione, Magda Gioia, Chiara Ciaccio, Grazia Raffaella Tundo, Stefano Marini, Massimo Coletta. (2011) Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes. Molecular Aspects of Medicine
CrossRef10
J. Woelfle, C. L. Roth, R. Wunsch, T. Reinehr. (2011) Pregnancy-associated plasma protein A in obese children: relationship to markers and risk factors of atherosclerosis and members of the IGF system. European Journal of Endocrinology 165:4, 613-622
CrossRef11
Akira Funayama, Tetsuro Shishido, Shunsuke Netsu, Mitsunori Ishino, Toshiki Sasaki, Shigehiko Katoh, Hiroki Takahashi, Takanori Arimoto, Takuya Miyamoto, Joji Nitobe, Tetsu Watanabe, Isao Kubota. (2011) Serum Pregnancy-Associated Plasma Protein A in Patients With Heart Failure. Journal of Cardiac Failure 17:10, 819-826
CrossRef12
Alexandra Muravská, Anna Germanová, Marie Jáchymová, Zdeněk Hájek, Jana Švarcová, Tomáš Zima, Marta Kalousová. (2011) Association of pregnancy-associated plasma protein A polymorphism with preeclampsia — A pilot study. Clinical Biochemistry
CrossRef13
Eftihia Sbarouni, Panagiota Georgiadou, Vassilis Voudris. (2011) Gender-specific differences in biomarkers responses to acute coronary syndromes and revascularization procedures. Biomarkers 16:6, 457-465
CrossRef14
Konstantinos Mitsakakis, Electra Gizeli. (2011) Detection of multiple cardiac markers with an integrated acoustic platform for cardiovascular risk assessment. Analytica Chimica Acta 699:1, 1-5
CrossRef15
Jonathan W Waks, Benjamin M Scirica. (2011) Established and novel biomarkers in ST-elevation myocardial infarction. Future Cardiology 7:4, 523-546
CrossRef16
Peijing Liu, Jinchuan Yan, Jie Gong, Cuiping Wang, Guanghua Chen. (2011) Positive correlation between pregnancy-associated plasma protein-A level and OX40 ligand expression in patients with acute coronary syndromes. Biomedicine & Pharmacotherapy 65:3, 193-197
CrossRef17
Wei-Yi Mei, Zhi-Min Du, Qiang Zhao, Cheng-Heng Hu, Yi Li, Chu-Fan Luo, Gui-Fu Wu, Guo-Wei Chen, Le-Xin Wang. (2011) Pregnancy-associated plasma protein predicts outcomes of percutaneous coronary intervention in patients with non–ST-elevation acute coronary syndrome. Heart & Lung: The Journal of Acute and Critical Care 40:3, e78-e83
CrossRef18
Olaf Schulz, Markus Reinicke, Jochen Krämer, Gunnar Berghöfer, Ricarda Bensch, Ingolf Schimke, Allan Jaffe. (2011) Pregnancy-associated plasma protein A values in patients with stable cardiovascular disease: Use of a new monoclonal antibody-based assay. Clinica Chimica Acta 412:11-12, 880-886
CrossRef19
Giuseppe Sangiorgi, Alessandro Mauriello, Santi Trimarchi, Elena Bonanno, Luigi Giusto Spagnoli. 2011. Atherogenesis and Inflammation. , 10-29.
CrossRef20
Richard Body, Phil Pemberton, Fozia Ali, Garry McDowell, Simon Carley, Alexander Smith, Kevin Mackway-Jones. (2011) Low soluble P-selectin may facilitate early exclusion of acute myocardial infarction. Clinica Chimica Acta 412:7-8, 614-618
CrossRef21
Kasper Iversen, Ane Teisner, Soren Dalager, Karen Ege Olsen, Charlotte Floridon, Børge Teisner. (2011) Pregnancy associated plasma protein-A (PAPP-A) is not a marker of the vulnerable atherosclerotic plaque. Clinical Biochemistry 44:4, 312-318
CrossRef22
Kouji Kajinami, Yasuyuki Kawai. (2011) Beyond C-reactive protein; new evidence for another inflammatory biomarker predicting cardiovascular disease risk. Atherosclerosis 214:1, 39-40
CrossRef23
Kasper K. Iversen, Børge Teisner, Per Winkel, Christian Gluud, Erik Kjøller, Hans Jørn Kolmos, Per Rossen Hildebrandt, Jørgen Hilden, Jens Kastrup. (2011) Pregnancy associated plasma protein-A as a marker for myocardial infarction and death in patients with stable coronary artery disease: A prognostic study within the CLARICOR Trial. Atherosclerosis 214:1, 203-208
CrossRef24
Dilshad Ahmed Khan, Mariam S Sharif, Farooq Ahmad Khan. (2011) Diagnostic Performance of High-Sensitivity Troponin T, Myeloperoxidase, and Pregnancy-Associated Plasma Protein A Assays for Triage of Patients with Acute Myocardial Infarction. The Korean Journal of Laboratory Medicine 31:3, 172
CrossRef25
Saara Wittfooth, Risto Tertti, Mauri Lepäntalo, Pekka Porela, Qiu-Ping Qin, Joanna Tynjälä, Outi Inkinen, Juha Perttilä, K.E. Juhani Airaksinen, Kim Pettersson. (2011) Studies on the effects of heparin products on pregnancy-associated plasma protein A. Clinica Chimica Acta 412:3-4, 376-381
CrossRef26
Alkesh Jani. 2011. Biomarkers in Kidney Transplantation. , 233-290.
CrossRef27
Cheryl A. Conover. (2010) PAPP-A: a new anti-aging target?. Aging Cell 9:6, 942-946
CrossRef28
Linda Hermus, Joop D. Lefrandt, René A. Tio, Jan-Cees Breek, Clark J. Zeebregts. (2010) Carotid plaque formation and serum biomarkers. Atherosclerosis 213:1, 21-29
CrossRef29
Kasper K. Iversen, Morten Dalsgaard, Ane S. Teisner, Mikkel Schoos, Borge Teisner, Henrik Nielsen, Peer Grande, Peter Clemmensen. (2010) Pregnancy-associated plasma protein-a, a marker for outcome in patients suspected for acute coronary syndrome. Clinical Biochemistry 43:10-11, 851-857
CrossRef30
P. Heider, N. Pfäffle, J. Pelisek, M. Wildgruber, H. Poppert, M. Rudelius, H.-H. Eckstein. (2010) Is Serum Pregnancy-Associated Plasma Protein A Really a Potential Marker of Atherosclerotic Carotid Plaque Stability?. European Journal of Vascular and Endovascular Surgery 39:6, 668-675
CrossRef31
Gina Biasillo, Milena Leo, Roberta Della Bona, Luigi Marzio Biasucci. (2010) Inflammatory biomarkers and coronary heart disease: from bench to bedside and back. Internal and Emergency Medicine 5:3, 225-233
CrossRef32
C. A. Conover, L. K. Bale, J. R. Mader, M. A. Mason, K. P. Keenan, R. J. Marler. (2010) Longevity and Age-Related Pathology of Mice Deficient in Pregnancy-Associated Plasma Protein-A. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 65A:6, 590-599
CrossRef33
Vikas Singh, Pedro Martinezclark, Mario Pascual, Eric Scot Shaw, William W. OʼNeill. (2010) Cardiac biomarkers – the old and the new: a review. Coronary Artery Disease 21:4, 244-256
CrossRef34
JA Shand, IB Menown, DJ McEneaney. (2010) A timely diagnosis of myocardial infarction. Biomarkers in Medicine 4:3, 385-393
CrossRef35
Thomas Mueller, Benjamin Dieplinger, Thomas Forstner, Werner Poelz, Meinhard Haltmayer. (2010) Pregnancy-associated plasma protein-A as a marker for long-term mortality in patients with peripheral atherosclerosis: inconclusive findings from the Linz Peripheral Arterial Disease (LIPAD) study. Clinical Chemistry and Laboratory Medicine 48:4, 537-542
CrossRef36
C. Etter, Y. Straub, M. Hersberger, H. R. Raz, T. Kistler, D. Kiss, R. P. Wuthrich, H.-J. Gloor, D. Aerne, P. Wahl, R. Klaghofer, P. M. Ambuhl. (2010) Pregnancy-associated plasma protein-A is an independent short-time predictor of mortality in patients on maintenance haemodialysis. European Heart Journal 31:3, 354-359
CrossRef37
M. B. I. Lobbes, M. E. Kooi, E. Lutgens, A. W. Ruiters, V. Lima Passos, S. H. J. G. Braat, M. Rousch, H. Ten Cate, J. M. A. van Engelshoven, M. J. A. P. Daemen, S. Heeneman. (2010) Leukocyte Counts, Myeloperoxidase, and Pregnancy-Associated Plasma Protein A as Biomarkers for Cardiovascular Disease: Towards a Multi-Biomarker Approach. International Journal of Vascular Medicine 2010, 1-9
CrossRef38
Noriaki Kume, Hirokazu Mitsuoka, Kazutaka Hayashida, Masaru Tanaka, Toru Kita. (2010) Soluble Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Predicts Prognosis After Acute Coronary Syndrome. Circulation Journal 74:7, 1399-1404
CrossRef39
Katrin Brandt, Jing Wang, Kerstin Lundell, Marie Ståhlberg, Henrik von Horn, Ewa Ehrenborg, Kerstin Hall, Hans Jörnvall, Moira Lewitt. (2009) IGFBP-1 protease activity and IGFBP-1 fragments in a patient with multiple myeloma. Growth Hormone & IGF Research 19:6, 507-512
CrossRef40
Eline B. Furenes, Harald Arnesen, Svein Solheim, Haakon K. Grøgaard, Pavel Hoffmann, Ingebjørg Seljeflot. (2009) The profile of circulating metalloproteinases after PCI in patients with acute myocardial infarction or stable angina. Thrombosis Research 124:5, 560-564
CrossRef41
Peter A. Kavsak, Xuesong Wang, Matthew Henderson, Dennis T. Ko, Andrew R. MacRae, Allan S. Jaffe. (2009) PAPP-A as a marker of increased long-term risk in patients with chest pain. Clinical Biochemistry 42:10-11, 1012-1018
CrossRef42
Kasper K. Iversen, Ane S. Teisner, Borge Teisner, Anette Kliem, Pia Thanning, Henrik Nielsen, Peter Clemmensen, Peer Grande. (2009) Pregnancy associated plasma protein A, a potential marker for vulnerable plaque in patients with non-ST-segment elevation acute coronary syndrome. Clinical Biochemistry 42:9, 828-834
CrossRef43
Barry McDonnell, Stephen Hearty, Paul Leonard, Richard O'Kennedy. (2009) Cardiac biomarkers and the case for point-of-care testing. Clinical Biochemistry 42:7-8, 549-561
CrossRef44
Turgay Celik, Atila Iyisoy, Ejder Kardesoglu, Baris Bugan, Ersoy Isik. (2009) Matrix metalloproteinases in acute coronary syndromes: A new therapeutic target?. International Journal of Cardiology 134:3, 402-404
CrossRef45
Felicita Andreotti, Teresa Rio, Elena Conti. (2009) Role of PAPP-A in atherothrombosis: Messages to take home. Atherosclerosis 203:2, 353-354
CrossRef46
Luciano Consuegra-Sanchez, Salim Fredericks, Juan Carlos Kaski. (2009) Pregnancy-associated plasma protein-A (PAPP-A) and cardiovascular risk. Atherosclerosis 203:2, 346-352
CrossRef47
Ismet Bulut, Abdurrahman Coskun, Abdullah Ciftci, Erdogan Cetinkaya, Gundeniz Altiay, Tuncay Caglar, Erim Gulcan. (2009) Relationship Between Pregnancy-Associated Plasma Protein-A and Lung Cancer. The American Journal of the Medical Sciences 337:4, 241-244
CrossRef48
Christian J. Terkelsen, Claus Oxvig, Bjarne L. Nørgaard, Simon Glerup, Tina S. Poulsen, Jens F. Lassen, Holger J. Møller, Leif Thuesen, Erling Falk, Torsten T. Nielsen, Henning R. Andersen. (2009) Temporal Course of Pregnancy-Associated Plasma Protein-A in Angioplasty-Treated ST-Elevation Myocardial Infarction Patients and Potential Significance of Concomitant Heparin Administration. The American Journal of Cardiology 103:1, 29-35
CrossRef49
Olaf Boenisch, Anil Chandraker. (2008) Predictive biomarkers of renal allograft failure. Expert Opinion on Medical Diagnostics 2:11, 1279-1290
CrossRef50
Anand Prasad, Sotirios Tsimikas. (2008) Candidate biomarkers for the detection of coronary plaque destabilization and rupture. Current Atherosclerosis Reports 10:4, 309-317
CrossRef51
Cheryl A. Conover, Sean C. Harrington, Laurie K. Bale. (2008) Differential regulation of pregnancy associated plasma protein-A in human coronary artery endothelial cells and smooth muscle cells. Growth Hormone & IGF Research 18:3, 213-220
CrossRef52
Helen E. Gruber, Gretchen Hoelscher, Jane A. Ingram, Edward N. Hanley. (2008) Immunolocalization and Biochemical Evidence of Pregnancy-Associated Plasma Protein-A in the Intervertebral Disc. Spine 33:14, E447-E454
CrossRef53
C. Setacci, G. de Donato, E. Chisci, F. Setacci, A. Stella, G. Faggioli, B. Reimers, C. Cernetti, M.J. Lopera Quijada, B. Cappi, G. Sangiorgi. (2008) Deferred Urgency Carotid Artery Stenting in Symptomatic Patients: Clinical Lessons and Biomarker Patterns from a Prospective Registry. European Journal of Vascular and Endovascular Surgery 35:6, 644-651
CrossRef54
Kasper Karmark Iversen, Ane Sogaard Teisner, Borge Teisner, Anette Kliem, Morten Bay, Vibeke Kirk, Henrik Nielsen, Soren Boesgaard, Peer Grande, Peter Clemmensen. (2008) Pregnancy-associated plasma protein A in non-cardiac conditions. Clinical Biochemistry 41:7-8, 548-553
CrossRef55
Luciano Consuegra-Sanchez, Ivana Petrovic, Juan Cosin-Sales, David W. Holt, Michael Christiansen, Juan Carlos Kaski. (2008) Prognostic value of circulating pregnancy-associated plasma protein-A (PAPP-A) and proform of eosinophil major basic protein (pro-MBP) levels in patients with chronic stable angina pectoris. Clinica Chimica Acta 391:1-2, 18-23
CrossRef56
Trygve Brügger-Andersen, Hildegunn Aarsetøy, Heidi Grundt, Harry Staines, Dennis W.T. Nilsen. (2008) The long-term prognostic value of multiple biomarkers following a myocardial infarction. Thrombosis Research 123:1, 60-66
CrossRef57
Saara Wittfooth, Qiu-Ping Qin, Kim Pettersson. (2008) Performance of immunofluorometric point-of-care assays for free pregnancy-associated plasma protein A detection in whole blood samples. Clinical Chemistry and Laboratory Medicine 46:1, 18-20
CrossRef58
Xu-Ping Li, Sheng Hua Zhou, Jian Jun Tang, Qi Ming Liu, Zheng Fei Fang, Xing Qun Hu, Tao Zhou, Xiang Qian Sheng, Shui Ping Zhao. (2008) Association Between Plasma Pregnancy-Associated Plasma Protein A and Restenosis After Percutaneous Coronary Angioplasty. Circulation Journal 72:5, 729-733
CrossRef59
Michael D. Miedema, Cheryl A. Conover, Holly MacDonald, Sean C. Harrington, Dedra Oberg, Daniel Wilson, Timothy D. Henry, Robert S. Schwartz. (2008) Pregnancy-Associated Plasma Protein-A Elevation in Patients With Acute Coronary Syndrome and Subsequent Atorvastatin Therapy. The American Journal of Cardiology 101:1, 35-39
CrossRef60
Vidosava B. Đorđević, Tatjana Ristić, Vladan Ćosić, Predrag Vlahović, Lilika Zvezdanović, Gordana Đorđević. (2008) Inflammatory and Apoptotic Markers in Ischemic Heart Disease Patients. Journal of Medical Biochemistry 27:2, 154-160
CrossRef61
A. S. Astrup, L. Tarnow, M. Christiansen, P. R. Hansen, H.-H. Parving, P. Rossing. (2007) Pregnancy-associated plasma protein A in a large cohort of Type 1 diabetic patients with and without diabetic nephropathy—a prospective follow-up study. Diabetic Medicine 24:12, 1381-1385
CrossRef62
Cynthia Tallant, Raquel García-Castellanos, Aniebrys Marrero, Francesc Canals, Yongzheng Yang, Jean-Louis Reymond, Maria Solà, Ulrich Baumann, F. Xavier Gomis-Rüth. (2007) Activity of ulilysin, an archaeal PAPP-A-related gelatinase and IGFBP protease. Biological Chemistry 388:11, 1243-1253
CrossRef63
G. Onder, E. Capoluongo, M. Cesari, P. Lulli, R. Liperoti, B. Giardina, A. Russo, R. Bernabei, F. Landi. (2007) Association of Calcium Channel Blocker Use and Pregnancy-Associated Plasma Protein-A Among Older Adults With Hypertension: Results From the ilSIRENTE Study. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 62:11, 1274-1278
CrossRef64
Sungha Park, Jong-Chan Youn, Dong-Jik Shin, Chan-Mi Park, Jung-Sun Kim, Young-Guk Ko, Donghoon Choi, Jong-Won Ha, Yangsoo Jang, Namsik Chung. (2007) Genetic polymorphism in the pregnancy-associated plasma protein-A associated with acute myocardial infarction. Coronary Artery Disease 18:6, 417-422
CrossRef65
Sylvia Stracke, Klaus Konner, Isabella Köstlin, Markus Schneider, Rosa Herzog, Peter M. Jehle, Frieder Keller, Reinhard Friedl. (2007) Over-expression of IGF-related peptides in stenoses of native arteriovenous fistulas in hemodialysis patients. Growth Hormone & IGF Research 17:4, 297-306
CrossRef66
Amy K. Saenger, Allan S. Jaffe. (2007) The Use of Biomarkers for the Evaluation and Treatment of Patients with Acute Coronary Syndromes. Medical Clinics of North America 91:4, 657-681
CrossRef67
Xinkang Wang, J Lynn Rutkowsky, Giora Z Feuerstein. (2007) Imaging and molecular biomarkers of vulnerable atheromatous plaques. Biomarkers in Medicine 1:1, 23-35
CrossRef68
Eric M. Thorn, Ijaz A. Khan. (2007) Pregnancy-associated plasma protein-A: An emerging cardiac biomarker. International Journal of Cardiology 117:3, 370-372
CrossRef69
Qiu-Ping Qin, Saara Wittfooth, Kim Pettersson. (2007) Measurement and clinical significance of circulating PAPP-A in ACS patients. Clinica Chimica Acta 380:1-2, 59-67
CrossRef70
Allan S. Jaffe. (2007) Cardiovascular biomarkers: The state of the art in 2006. Clinica Chimica Acta 381:1, 9-13
CrossRef71
Ahmad A. Elesber, Amir Lerman, Ali E. Denktas, Zachary T. Resch, T. Jared Bunch, Robert S. Schwartz, Cheryl A. Conover. (2007) Pregnancy associated plasma protein-A and risk stratification of patients presenting with chest pain in the emergency department. International Journal of Cardiology 117:3, 365-369
CrossRef72
Marie Rossen, Kasper Iversen, Ane Teisner, Børge Teisner, Anette Kliem, Gedis Grudzinskas. (2007) Optimisation of sandwich ELISA based on monoclonal antibodies for the specific measurement of pregnancy-associated plasma protein (PAPP-A) in acute coronary syndrome. Clinical Biochemistry 40:7, 478-484
CrossRef73
Abdurrahman Coskun, Oner Balbay, Sadik Duran, Ali Nihat Annakkaya, Ismet Bulut, Ozlem Yavuz, Emel Kurt. (2007) Pregnancy-associated plasma protein-A and asthma. Advances in Therapy 24:2, 362-367
CrossRef74
Eliana Lucchinetti, Christoph Hofer, Lukas Bestmann, Martin Hersberger, Jianhua Feng, Min Zhu, Lukas Furrer, Marcus C. Schaub, Reza Tavakoli, Michele Genoni, Andreas Zollinger, Michael Zaugg. (2007) Gene Regulatory Control of Myocardial Energy Metabolism Predicts Postoperative Cardiac Function in Patients Undergoing Off-pump Coronary Artery Bypass Graft Surgery. Anesthesiology 106:3, 444-457
CrossRef75
B. Bayés, M.L. Granada, M.C. Pastor, R. Lauzurica, I. Salinas, A. Sanmartí, A. Espinal, A. Serra, M. Navarro, J. Bonal, R. Romero. (2007) Obesity, Adiponectin and Inflammation as Predictors of New-Onset Diabetes Mellitus After Kidney Transplantation. American Journal of Transplantation 7:2, 416-422
CrossRef76
Henning B. Boldt, Cheryl A. Conover. (2007) Pregnancy-associated plasma protein-A (PAPP-A): A local regulator of IGF bioavailability through cleavage of IGFBPs. Growth Hormone & IGF Research 17:1, 10-18
CrossRef77
Romana Ryšavá, Marta Kalousová, Tomáš Zima, Ctibor Dostál, Miroslav Merta, Vladimír Tesař. (2007) Does Renal Function Influence Plasma Levels of Advanced Glycation and Oxidation Protein Products in Patients with Chronic Rheumatic Diseases Complicated by Secondary Amyloidosis?. Kidney and Blood Pressure Research 30:1, 1-7
CrossRef78
Abdurrahman Coskun, Zerrin Bicik, Sadik Duran, Aytekin Alcelik, Zeki Soypacaci, Ozlem Yavuz, Sukru Oksuz. (2007) Pregnancy-associated plasma protein A in dialysis patients. Clinical Chemistry and Laboratory Medicine 45:1, 63-66
CrossRef79
Trygve Brügger-Andersen, Øyvind Hetland, Volker Pönitz, Heidi Grundt, Dennis W.T. Nilsen. (2007) The effect of primary percutaneous coronary intervention as compared to tenecteplase on myeloperoxidase, pregnancy-associated plasma protein A, soluble fibrin and D-dimer in acute myocardial infarction. Thrombosis Research 119:4, 415-421
CrossRef80
Saif Anwaruddin, Arman T. Askari, Eric J. Topol. (2007) Redefining Risk in Acute Coronary Syndromes Using Molecular Medicine. Journal of the American College of Cardiology 49:3, 279-289
CrossRef81
Evangelos Giannitsis, Kerstin Kurz, Hugo A Katus. (2007) Multimarker strategy in acute coronary syndrome—pro‐multimarker. Acute Cardiac Care 9:1, 6-9
CrossRef82
Leila Fernandes Araujo, Alexandre de Matos Soeiro, Juliano Lara Fernandes, Antônio Eduardo Pesaro, Carlos V Serrano. (2006) Coronary artery disease in women: a review on prevention, pathophysiology, diagnosis, and treatment. Vascular Health and Risk Management 2:4, 465-475
CrossRef83
E. T. H. YEH, B. V. KHAN. (2006) The potential role of antiplatelet agents in modulating inflammatory markers in atherothrombosis. Journal of Thrombosis and Haemostasis 4:11, 2308-2316
CrossRef84
James T. Willerson, Paul W Armstrong. 2006. Acute Myocardial Infarction. , 611-646.
CrossRef85
Zhen Yang, Dao Min Zhou. (2006) Cardiac markers and their point-of-care testing for diagnosis of acute myocardial infarction. Clinical Biochemistry 39:8, 771-780
CrossRef86
Raphael See, James A. Lemos. (2006) Current status of risk stratification methods in acute coronary syndromes. Current Cardiology Reports 8:4, 282-288
CrossRef87
Giuseppe Sangiorgi, Alessandro Mauriello, Elena Bonanno, Claus Oxvig, Cheryl A. Conover, Michael Christiansen, Santi Trimarchi, Vincenzo Rampoldi, David R. Holmes, Robert S. Schwartz, Luigi Giusto Spagnoli. (2006) Pregnancy-Associated Plasma Protein-A Is Markedly Expressed by Monocyte-Macrophage Cells in Vulnerable and Ruptured Carotid Atherosclerotic Plaques. Journal of the American College of Cardiology 47:11, 2201-2211
CrossRef88
Abelardo Martinez, James L. Januzzi. (2006) Novel Markers for the Evaluation of Patients With Suspected Ischemic Heart Disease. Point of Care: The Journal of Near-Patient Testing & Technology 5:1, 28-37
CrossRef89
Pablo Piñón, Juan Carlos Kaski. (2006) Inflamación, aterosclerosis y riesgo cardiovascular: PAPP-A, Lp-PLA2 y cistatina C. ¿Nuevas aportaciones o información redundante?. Revista Española de Cardiología 59:3, 247-258
CrossRef90
Marta Kalousová, Magdaléna Hodková, Sylvie Dusilová-Sulková, Jana Uhrová, Vladimír Tesař, Tomáš Zima. (2006) Effect of Hemodiafiltration on Pregnancy-Associated Plasma Protein A (PAPP-A) and Related Parameters. Renal Failure 28:8, 715-721
CrossRef91
Magdalena Hodkova, Sylvie Dusilova-Sulkova, Marta Kalousova, Jirina Soukupova, Tomas Zima, Dana Mikova, Ivan Matous Malbohan, Jirina Bartunkova. (2006) Influence of Oral Vitamin E Therapy on Micro-Inflammation and Cardiovascular Disease Markers in Chronic Hemodialysis Patients. Renal Failure 28:5, 395-399
CrossRef92
Marta Kalousová, Tomáš Zima, Vladimír Tesař, Sylvie Dusilová-Sulková, Jan Škrha. (2005) Advanced glycoxidation end products in chronic diseases—clinical chemistry and genetic background. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 579:1-2, 37-46
CrossRef93
Ricardo Lauzurica, Cruz Pastor, Beatriz Bay??s, Jose Maria Hern??ndez, Ramon Romero. (2005) Pretransplant Pregnancy-Associated Plasma Protein-A as a Predictor of Chronic Allograft Nephropathy and Posttransplant Cardiovascular Events. Transplantation 80:10, 1441-1446
CrossRef94
Jennifer M. Aviles, Ronnier J. Aviles. (2005) Advances in Cardiac Biomarkers. Emergency Medicine Clinics of North America 23:4, 959-975
CrossRef95
Christopher Heeschen, Stefanie Dimmeler, Stephan Fichtlscherer, Andreas M. Zeiher. (2005) Reply. Journal of the American College of Cardiology 46:8, 1584-1585
CrossRef96
R. Torres-Gárate, E. Álvarez-Rodríguez, E. Calvo Manuel. (2005) Historia natural de la arteriosclerosis. Expresividad clínica. Complicaciones agudas y crónicas. Medicine - Programa de Formación Médica Continuada Acreditado 9:38, 2525-2535
CrossRef97
Carlos A. G. Van. Mieghem, Nico Bruining, Johannes A. Schaar, Eugene McFadden, Nico Mollet, Filippo Cademartiri, Frits Mastik, Jurgen M. R. Ligthart, Gaston A. Rodriguez. Granillo, Marco Valgimigli, Georgios Sianos, Willem J. van der. Giessen, Bianca Backx, Marie-Angele M. Morel, Gerrit-Anne Van Es, Jonathon D. Sawyer, June Kaplow, Andrew Zalewski, Anton F. W. vander. Steen, Pim de Feyter, Patrick W. Serruys. (2005) Rationale and methods of the integrated biomarker and imaging study (IBIS): combining invasive and non-invasive imaging with biomarkers to detect subclinical atherosclerosis and assess coronary lesion biology. The International Journal of Cardiovascular Imaging 21:4, 425-441
CrossRef98
Ankie Amos, L. Kristin Newby. (2005) Using biomarkers to assess risk and consider treatment strategies in non-ST-segment elevation acute coronary syndromes. Current Cardiology Reports 7:4, 263-269
CrossRef99
R. De Caterina, M. Massaro. (2005) Omega-3 Fatty Acids and the Regulation of Expression of Endothelial Pro-Atherogenic and Pro-Inflammatory Genes. Journal of Membrane Biology 206:2, 103-116
CrossRef100
Omar F Laterza. (2005) PAPP-A: a marker of plaque instability. Is it ready for prime time?. Future Cardiology 1:4, 495-500
CrossRef101
James K McCord. (2005) Cardiac markers in acute coronary syndrome. Future Cardiology 1:4, 489-494
CrossRef102
Alessandro Mauriello, Giuseppe Sangiorgi, Stefano Fratoni, Giampiero Palmieri, Elena Bonanno, Lucia Anemona, Robert S. Schwartz, Luigi Giusto Spagnoli. (2005) Diffuse and Active Inflammation Occurs in Both Vulnerable and Stable Plaques of the Entire Coronary Tree. Journal of the American College of Cardiology 45:10, 1585-1593
CrossRef103
Alberto Dominguez-Rodriguez, Pedro Abreu-Gonzalez, Martín Garcia-Gonzalez, Julio Ferrer, Manuel Vargas. (2005) Circulating pregnancy-associated plasma protein A is not an early marker of acute myocardial infarction. Clinical Biochemistry 38:2, 180-182
CrossRef104
I. J. Kullo, C. M. Ballantyne. (2005) Conditional Risk Factors for Atherosclerosis. Mayo Clinic Proceedings 80:2, 219-230
CrossRef105
Magdalena Hodkova, Marta Kalousova, Sylvie Dusilova-Sulkova, Ivan Matous Malbohan, Tomas Zima. (2005) Intravenous Iron Gluconate Administration Increases Circulating PAPP-A in Hemodialysis Patients. Renal Failure 27:6, 707-711
CrossRef106
AJ Marian, Vijay Nambi. (2004) Biomarkers of cardiac disease. Expert Review of Molecular Diagnostics 4:6, 805-820
CrossRef107
Mohammad Madjid, Imran Awan, James T. Willerson, S. Ward Casscells. (2004) Leukocyte count and coronary heart disease. Journal of the American College of Cardiology 44:10, 1945-1956
CrossRef108
Omar F. Laterza, Scott J. Cameron, Derek Chappell, Lori J. Sokoll, Gary B. Green. (2004) Evaluation of pregnancy-associated plasma protein A as a prognostic indicator in acute coronary syndrome patients. Clinica Chimica Acta 348:1-2, 163-169
CrossRef109
James Kevin McCord. (2004) The Future of Cardiac Markers in the Emergency Department. Critical Pathways in Cardiology: A Journal of Evidence-Based Medicine 3:3, 107-109
CrossRef110
Kimberly R. Kalli, Bing-Kun Chen, Laurie K. Bale, Erica Gernand, Michael T. Overgaard, Claus Oxvig, William A. Cliby, Cheryl A. Conover. (2004) Pregnancy-associated plasma protein-A (PAPP-A) expression and insulin-like growth factor binding protein-4 protease activity in normal and malignant ovarian surface epithelial cells. International Journal of Cancer 110:5, 633-640
CrossRef111
Mehdi H. Shishehbor, Stanley L. Hazen. (2004) Inflammatory and oxidative markers in atherosclerosis: Relationship to outcome. Current Atherosclerosis Reports 6:3, 243-250
CrossRef112
Kathrin Weyer, Michael T. Overgaard, Lisbeth S. Laursen, Claus G. Nielsen, Alexander Schmitz, Michael Christiansen, Lars Sottrup-Jensen, Linda C. Giudice, Claus Oxvig. (2004) Cell surface adhesion of pregnancy-associated plasma protein-A is mediated by four clusters of basic residues located in its third and fourth CCP module. European Journal of Biochemistry 271:8, 1525-1535
CrossRef113
Kun-Tai Lee, Wen-Ter Lai, Chin-Sheng Chu, Li-Yu Tsai, Hsueh-Wei Yen, Wen-Choi Voon, Sheng-Hsiung Sheu. (2004) Effect of Withdrawal of Statin on C-Reactive Protein. Cardiology 102:3, 166-170
CrossRef114
Doron Aronson. (2004) Inflammatory markers: linking unstable plaques to coronary event, an interventional perspective. Acute Cardiac Care 6:3-4, 110-118
CrossRef115
Mauro Panteghini. (2004) Biochemical markers of cardiac diseases. Jugoslovenska medicinska biohemija 23:3, 201-211
CrossRef116
Harvey D White, John K French. (2003) Use of brain natriuretic peptide levels for risk assessment in non–ST-elevation acute coronary syndromes. Journal of the American College of Cardiology 42:11, 1917-1920
CrossRef117
M. Kalousova. (2003) Glycoxidation and inflammation in chronic haemodialysis patients. Nephrology Dialysis Transplantation 18:12, 2577-2581
CrossRef118
Gavin J. Blake. (2003) Inflammatory biomarkers of the patient with myocardial insufficiency. Current Opinion in Critical Care 9:5, 369-374
CrossRef119
S Doix, M Mahrousseh, M Jolak, Y Laurent, J.L Lorenzini, C Binquet, M Zeller, Y Cottin, J.E Wolf. (2003) Facteur V Leiden et infarctus du myocarde : à propos d'un cas, revue systématique de la littérature et méta-analyse. Annales de Cardiologie et d'Angéiologie 52:3, 143-149
CrossRef120
Hendrik Zimmet. (2003) The Twilight Zone of Troponins. Heart Lung <html_ent glyph="@amp;" ascii="&"/> Circulation 12:s2, S90-S94
CrossRef121
Marta Kalousova, Tomas Zima, Vladimir Tesar, Sylvie Sulkova, Lenka Fialova. (2003) Relationship between advanced glycoxidation end products, inflammatory markers/acute-phase reactants, and some autoantibodies in chronic hemodialysis patients. Kidney International 63:s84, 62-64
CrossRef122
R. Clay Bunn, John L. Fowlkes. (2003) Insulin-like growth factor binding protein proteolysis. Trends in Endocrinology & Metabolism 14:4, 176-181
CrossRef123
Gavin J Blake, Paul M Ridker. (2003) C-reactive protein and other inflammatory risk markers in acute coronary syndromes. Journal of the American College of Cardiology 41:4, S37-S42
CrossRef124
Eric J Topol. (2003) A guide to therapeutic decision-making in patients with non–ST-segment elevation acute coronary syndromes. Journal of the American College of Cardiology 41:4, S123-S129
CrossRef125
Richard Ceska, Tomas Stulc, Tomas Zima, Ivan Malbohan, Lenka Fialova. (2003) PAPP-A, a novel marker of unstable plaque, is not influenced by hypolipidemic treatment in contrast to CRP. Atherosclerosis 166:1, 195-196
CrossRef126
Javad Khosravi, Anastasia Diamandi, Radha G Krishna, Umesh Bodani, Jehangir Mistry, Najmuddin Khaja. (2002) Pregnancy associated plasma protein-A: ultrasensitive immunoassay and determination in coronary heart disease. Clinical Biochemistry 35:7, 531-538
CrossRef127
Stefan W. Suttner, Swen N. Piper, Joachim Boldt. (2002) The heart in the elderly critically ill patient. Current Opinion in Critical Care 8:5, 389-394
CrossRef128
James S. Zebrack, Jeffrey L. Anderson. (2002) Role of Inflammation in Cardiovascular Disease: How to Use C-Reactive Protein in Clinical Practice. Progress in Cardiovascular Nursing 17:4, 174-185
CrossRef129
Bret A. Rogers, L. Kristin Newby. (2002) New biomarkers in the risk stratification of patients with suspected acute myocardial infarction. Current Cardiology Reports 4:4, 341-347
CrossRef130
John L. Fowlkes, Margaret K. Winkler. (2002) Exploring the interface between metallo-proteinase activity and growth factor and cytokine bioavailability. Cytokine & Growth Factor Reviews 13:3, 277-287
CrossRef131
Chakib M. Ayoub, Maya I. Jalbout, Anis S. Baraka. (2002) The pregnant cardiac woman. Current Opinion in Anaesthesiology 15:3, 285-291
CrossRef132
Rikke Soe, Michael T. Overgaard, Anni R. Thomsen, Lisbeth S. Laursen, Inger M. Olsen, Lars Sottrup-Jensen, Jesper Haaning, Linda C. Giudice, Cheryl A. Conover, Claus Oxvig. (2002) Expression of recombinant murine pregnancy-associated plasma protein-A (PAPP-A) and a novel variant (PAPP-Ai) with differential proteolytic activity. European Journal of Biochemistry 269:8, 2247-2256
CrossRef133
Qiu-Ping Qin, Päivi Laitinen, Kirsi Majamaa-Voltti, Susann Eriksson, Eeva-Katri Kumpula, Kim Pettersson. (2002) Release Patterns of Pregnancy Associated Plasma Protein A (PAPP-A) in Patients with Acute Coronary Syndromes. Scandinavian Cardiovascular Journal 36:6, 358-361
CrossRef134
Rabbani, LeRoy E., . (2001) Acute Coronary Syndromes — Beyond Myocyte Necrosis. New England Journal of Medicine 345:14, 1057-1059
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&NA;. (2001) Promising new markers for acute coronary syndromes. Inpharma Weekly &NA;:1309, 4
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