Future Biomarkers for Detection of Ischemia and Risk Stratification in Acute Coronary Syndrome

Apple, Fred S.; Wu, Alan H.B.; Mair, Johannes; Ravkilde, Jan; Panteghini, Mauro; Tate, Jillian R.; Pagani, F.; Christenson, Robert H.; Möckel, Martin; Danne, O.; Jaffe, Allan S.

doi:10.1373/clinchem.2004.046292

Cited by 387 publications

(307 citation statements)

References 108 publications

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“…However, we think the index may be efficient only for the monitoring of patients with known baseline IMA and albumin concentrations. Lippi et al 11,14 IMA values may be affected by albumin concentrations also within reference limits. In the present study, IMA elevation after PCI reflects, at least in part, decreased albumin concentrations in patients with mild ischaemia during PCI.…”

Section: Discussionmentioning

confidence: 97%

Ischaemia-modified albumin elevation after percutaneous coronary intervention reflects albumin concentration rather than ischaemia

et al. 2009

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Background: Percutaneous coronary intervention (PCI) is accepted as a model of myocardial ischaemia in studies of ischaemia markers, especially of ischaemia-modified albumin (IMA). However, there is concern that IMA levels may reflect changes in albumin concentrations rather than myocardial ischaemia also during PCI. Methods: Twenty-one consecutive patients (17 men and 4 women) undergoing single-vessel percutaneous coronary angioplasty were enrolled in the study. IMA and albumin levels were measured together with myoglobin, creatine kinase 2 and cardiac troponin I, before (Group 1), immediately after (Group 2) and 6 h after (Group 3) the procedure of PCI. Results: The IMA levels of Group 2 were significantly higher than those of Group 1 and Group 3 (P , 0.05 for both). However, correction of IMA by multiplying with the (individual albumin concentration of the patient/median albumin concentration of Group 1) ratio gave no statistical differences between the groups (P . 0.05). There were strong negative correlations between IMA levels and albumin concentrations within individual groups (r ¼ 20.757, P , 0.001; r ¼ 20.712, P , 0.001; and r ¼ 20.705, P , 0.001 for Group 1, Group 2 and Group 3, respectively). Conclusion:The results confirm the close dependency of IMA results on albumin concentrations. Therefore, IMA results reflect albumin concentrations rather than myocardial ischaemia also in PCI. This situation and lack of standard reference materials for the albumin cobalt binding assay can lessen the diagnostic performance of IMA.

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Section: Discussionmentioning

confidence: 97%

Ischaemia-modified albumin elevation after percutaneous coronary intervention reflects albumin concentration rather than ischaemia

et al. 2009

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“…18 The significance of this assay in determining periods of ischemia is evident in that it has recently been licensed by the U.S. Food and Drug Administration as a rule-out test for cardiac ischemia. 25 Though the presence of IMA is not diagnostic of a cardiac infarct, as any regional ischemia has the potential to generate IMA, its absence indicates that it is most unlikely and patients with a low IMA score can be discharged. The loss of metal chelation function, as evidenced by increasing IMA, would contribute to an environment of continued oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Alterations in the functional capacity of albumin in patients with decompensated cirrhosis is associated with increased mortality†‡§

Schnurr²,

et al. 2009

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Albumin concentration is diminished in patients with liver failure. Albumin infusion improves survival of cirrhotic patients with spontaneous bacterial peritonitis, and it is hypothesized that this may be due in part to its detoxifying capabilities. The aim of this study was to perform detailed quantitative and qualitative assessment of albumin function in patients with cirrhosis. Healthy controls and patients with acute deterioration of cirrhosis requiring hospital admission (n ‫؍‬ 34) were included. Albumin function was assessed using affinity of the fatty acid binding sites using a spin label (16 doxyl-stearate) titration and electron paramagnetic resonance spectroscopy and ischemia-modified albumin (IMA) was measured. Twenty-two patients developed acute-on-chronic liver failure. Twelve were treated with the Molecular Adsorbents Recirculating System (MARS) and 10 with standard medical therapy. For each parameter measured, the patients' albumin had reduced functional ability, which worsened with disease severity. Fifteen patients died, and IMA, expressed as an albumin ratio (IMAR), was significantly higher in nonsurvivors compared with survivors (P < 0.001; area under the receiver operating curve ‫؍‬ A lbumin is the major plasma protein and constitutes around 50% of the cell free protein in healthy individuals. It is produced exclusively in the liver, and therefore its concentration is reduced during hepatic dysfunction. 1 Following the Cochrane meta-analysis describing potential harmfully effect of albumin infusion in critically ill patients, there has been a reexamination of the use of albumin infusions for volume replacement. However, the results of the recently published SAFE study have provided new data confirming the safety of albumin infusion in critically ill patients. 2,3 Liver failure results in multiple organ dysfunction, and mortality rates without liver transplantation remain unacceptably high. 4 However, recovery is associated with complete reversal of multiorgan dysfunction. At present, in patients with cirrhosis, albumin is used mainly to replenish the circulating volume. With increasing severity of cirrhosis, there is a progressive increase in cardiac output, which is associated with a progressive reduction in individual organ blood flow. This peculiar circulatory disturbance is thought to occur as a result of splanchnic

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“…12 In support of this idea, recent studies have shown that the circulating levels of MMP-9 may be used as a bloodborne biochemical marker for cardiovascular diseases. 12,[14][15][16] Furthermore, MMP-9 plasma levels predicted mortality in patients with coronary artery disease. 12 Together, these findings suggest that plasma MMP-9 and MMP-2 may have diagnostic and prognostic value.…”

Section: Introductionmentioning

confidence: 99%

A genetic polymorphism of matrix metalloproteinase 9 (MMP-9) affects the changes in circulating MMP-9 levels induced by highly active antiretroviral therapy in HIV patients

et al. 2009

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We examined whether two functional polymorphisms (g.À1562C4T and g.À90(CA)14-24) in the matrix metalloproteinase (MMP)-9 gene or MMP-9 haplotypes affect the circulating levels of pro-MMP-9 and pro-MMP-9/TIMP-1 (tissue inhibitor of metalloproteinase-1) ratios in AIDS patients, and modulate alterations in these biomarkers after highly active antiretroviral therapy (HAART). We studied 82 patients commencing HAART. Higher pro-MMP-9 concentrations and pro-MMP-9/TIMP-1 ratios were found in CT/TT patients compared with CC patients. HAART decreased pro-MMP-9 levels and pro-MMP-9/TIMP-1 ratios in CT/TT patients, it did not modify pro-MMP-9 levels and it increased pro-MMP-9/TIMP-1 ratios in CC patients. The g.À90(CA)14-24 polymorphism, however, produced no significant effects. Moreover, we found no significant differences in HAARTinduced changes in plasma pro-MMP-9, TIMP-1 and pro-MMP-9/TIMP-1 ratios when different MMP-9 haplotypes were compared. These findings suggest that the g.À1562C4T polymorphism affects pro-MMP-9 levels in patients with AIDS and modulates the alterations in pro-MMP-9 levels caused by HAART, thus possibly affecting the risk of cardiovascular complications.

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Future Biomarkers for Detection of Ischemia and Risk Stratification in Acute Coronary Syndrome

Cited by 387 publications

References 108 publications

Ischaemia-modified albumin elevation after percutaneous coronary intervention reflects albumin concentration rather than ischaemia

Ischaemia-modified albumin elevation after percutaneous coronary intervention reflects albumin concentration rather than ischaemia

Alterations in the functional capacity of albumin in patients with decompensated cirrhosis is associated with increased mortality†‡§

A genetic polymorphism of matrix metalloproteinase 9 (MMP-9) affects the changes in circulating MMP-9 levels induced by highly active antiretroviral therapy in HIV patients

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