OBJECTIVE

The aim of this study was assess serum ischemia modified albumin (IMA) in type 2 diabetes patients and determine its correlation with other risk factors for chronic complications such as inflammation and hyperglycemia.

METHODS

Fasting glucose, glycated albumin, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, creatinine, uric acid, albumin, lactic acid, high-sensitivity C-reactive protein (hs-CRP) and IMA were measured in 80 patients with type 2 diabetes and 26 controls.

RESULTS

Fasting glucose, glycated albumin, triglycerides, creatinine, IMA and hs-CRP were significantly higher in patients with type 2 diabetes. Correlations were weak but significant between IMA and fasting glucose, IMA and hs-CRP, hs-CRP and HDL cholesterol and hs-CRP and fasting glucose were observed.

CONCLUSIONS

We have shown higher levels of IMA and hs-CRP in type 2 diabetes. Hyperglycemia and inflammation reduces the capacity of albumin to bind cobalt, resulting in higher IMA levels.

Mitochondrial matrix cyclophilin D (CyPD) is known to promote development of the mitochondrial permeability transition (MPT). Kidney proximal tubule cells are especially prone to deleterious effects of mitochondrial damage because of their dependence on oxidative mitochondrial metabolism for ATP production. To clarify the role of CyPD and the MPT in proximal tubule injury during ischemia-reperfusion (I/R) and hypoxia-reoxygenation (H/R), we assessed freshly isolated tubules and in vivo injury in wild-type (WT) and Ppif(-/-) CyPD-null mice. Isolated mouse tubules developed a sustained, nonesterified fatty acid-mediated energetic deficit after H/R in vitro that could be substantially reversed by delipidated albumin and supplemental citric acid cycle substrates but was not modified by the absence of CyPD. Susceptibility of WT and Ppif(-/-) tubules to the MPT was increased by H/R but was less in normoxic and H/R Ppif(-/-) than WT tubules. Correction of the energetic deficit that developed during H/R strongly increased resistance to the MPT. Ppif(-/-) mice were resistant to I/R injury in vivo spanning a wide range of severity. The data clarify involvement of the MPT in oxygen deprivation-induced tubule cell injury by showing that the MPT does not contribute to the initial bioenergetic deficit produced by H/R but the deficit predisposes to subsequent development of the MPT, which contributes pathogenically to kidney I/R injury in vivo.

Objectives. Our aim was to determine the effect of chronic regular exercise on ischemia-modified albumin (IMA) levels and oxidative stress in type 2 diabetes mellitus (DM). Design and methods. Sixty patients with type 2 DM were randomly divided into two groups as exercise (17 M, 13 F) and non-exercise (12 M, 18 F) groups, each consisting of 30 patients. The exercise group underwent a 3-month aerobic regular exercise consisting of moderate-intensity power walking. The non-exercise subjects remained sedentary throughout the study period. Serum total antioxidant status (TAS), total oxidant status (TOS), and IMA levels of the groups were determined at baseline and 3 months later. Results. There was no significant change in TOS and IMA levels of exercise group but TAS levels were significantly increased (p < 0.05). Also, postexercise systolic (p < 0.001) and diastolic (p < 0.05) blood pressures of the exercise group were significantly lower than the baseline values. In addition, there was no significant change in TAS and TOS levels of the non-exercise group; however, IMA levels were significantly increased (p < 0.01). Conclusion. We have shown, for the first time, that exercise prevents increase in IMA levels in type 2 DM which might have resulted from increased levels of TAS and reduces the risk of ischemia in these patients. These findings show that chronic exercise is beneficial in the prevention of oxidative stress in patients with type 2 DM as documented by decreased IMA levels.

OBJECTIVE

The main goal of the present study was the evaluation of ischemia-modified albumin (IMA) in patients with type 2 diabetes mellitus and estimation of its connection with vascular complications, glycemic control, hypertension, dyslipidemia and obesity.

METHODS

In 76 diabetic patients and 25 control subjects, a plasma level of IMA by manually performed, spectrophotometric Co(II)-albumin binding assay was determined. Other parameters such as glucose, fructosamine, HbA_{1c}, total cholesterol and its fractions (HDL, LDL), triglicerydes were estimated by routine methods.

RESULTS

Diabetic patients had significantly higher level of IMA in comparison with control subjects. There were not significant differences between groups with various states of vascular complications although the lowest concentration of IMA was observed in patients with microangiopathy. Patients with poor glycemic control had higher IMA level in comparison with these with good glycemic control. Significant correlation was observed between IMA and HbA_{1c}. Among the risk factors, only blood pressure and LDL showed a weak relationship with IMA level.

CONCLUSIONS

Our results revealed, for the first time, higher level of IMA in diabetic patients which confirms that it may be of non-cardiac origin. We can suggest that the albumin molecule in plasma of diabetic patients is modified in the chronic hypoxia conditions provoked mainly by hyperglycemia and oxidative stress in diabetes.

BACKGROUND

Because of possible adverse outcomes, many of the >6 million annual emergency department (ED) patients with suspected acute coronary syndromes (ACS) undergo extensive evaluations. To minimize medical errors, chest pain evaluations are structured to identify accurately nearly 100% of patients with ACS. This is at a cost of negative evaluation rates that can exceed 90%. Ischemia-modified albumin (IMA), a serum biomarker with a high negative predictive value (NPV) at ED presentation, may exclude ACS. Our objective was to perform a meta-analysis of IMA use for ACS risk stratification.

METHODS

By computer literature search and communication with authors of unpublished information, all IMA data were considered. This analysis included studies if they reported IMA results from an ED presentation for suspected ACS. We defined a negative triple prediction test (TPT) as a nondiagnostic electrocardiogram, negative troponin, and negative IMA.

RESULTS

Eight studies of >1800 patients met the entry criteria. The TPT sensitivity and NPV for acute ACS were 94.4% and 97.1% and, for longer-term outcomes, were 89.2% and 94.5%, respectively.

CONCLUSIONS

A negative TPT of a nondiagnostic electrocardiogram, negative troponin, and negative IMA has a high NPV for excluding ACS in the ED.

BACKGROUND

Metabolic syndrome (MS) is described as a cluster of cardiometabolic risk factors. Studies suggest that ischemia-modified albumin (IMA) is a biomarker of cardiovascular diseases. IMA levels could be associated with cardiometabolic risks and represent a possible indication of microvascular dysfunction in MS patients.

OBJECTIVE

To confirm this possible association, we evaluated the association between IMA levels and MS.

METHODS

We performed a case-control study (32 healthy individuals and 74 subjects with MS) to evaluate the association between MS, IMA, and other biomarkers [high-sensitivity C-reactive protein (hs-CRP), oxidized low-density lipoprotein (OxLDL), oxidized low-density lipoprotein autoantibodies (anti-OxLDL), IL-6, lipid profile, and glucose].

RESULTS

The MS group showed higher levels of IMA (0.618 +/- 0.1355) as well as higher levels of hs-CRP, OxLDL, anti-OxLDL, and IL-6 than did control subjects (IMA = 0.338 +/- 0.0486) (P < 0.01). Multivariate analysis showed that IMA and MS association was independent of sex, age, diabetes mellitus 2, and hypercholesterolemia.

CONCLUSIONS

We found an association between IMA and MS. Additional studies including prospective genetic variation approaches need to be performed to help elucidate this association between IMA and MS and its potential clinical role.

Cerebral infarction (stroke) is a potentially disastrous complication of diabetes mellitus, principally because the extent of cortical loss is greater in diabetic patients than in nondiabetic patients. The etiology of this enhanced neurotoxicity is poorly understood. We hypothesized that advanced glycation endproducts (AGEs), which have previously been implicated in the development of other diabetic complications, might contribute to neurotoxicity and brain damage during ischemic stroke. Using a rat model of focal cerebral ischemia, we show that systemically administered AGE-modified bovine serum albumin (AGE-BSA) significantly increased cerebral infarct size. The neurotoxic effects of AGE-BSA administration were dose- and time-related and associated with a paradoxical increase in cerebral blood flow. Aminoguanidine, an inhibitor of AGE cross-linking, attenuated infarct volume in AGE-treated animals. We conclude that AGEs may contribute to the increased severity of stroke associated with diabetes and other conditions characterized by AGE accumulation.

OBJECTIVE

To evaluate the hypothesis of increased systemic oxidative stress in patients with endometriosis.

METHODS

Tertiary care university hospital.

METHODS

Cross-sectional study.

METHODS

Sixty-six women of reproductive age undergoing laparoscopy.

METHODS

All women were investigated for endometriotic foci during laparoscopy. Forty-five women had laparoscopically and histologically confirmed endometriosis, and 21 women did not have endometriosis.

METHODS

Four markers of oxidative stress were assessed in the serum of each patient: heat shock protein 70 (HSP70), HSP70b', thioredoxin (TRX), and ischemia-modified albumin (IMA).

RESULTS

Mean serum HSP 70b' level was higher in patients with endometriosis compared with controls (0.178 ng/mL, SD 0.103, and 0.135 ng/mL, SD 0.014, respectively). The disease stage did not affect HSP70b' levels. Heat shock protein 70, IMA, and TRX levels did not differ between patients with endometriosis and controls. Women with a history of arterial hypertension had higher mean IMA levels compared with women with normal blood pressure independently of the presence of endometriosis (106.7 [SD 25.4] U/mL and 85.0 [SD 11.5] U/mL, respectively).

CONCLUSIONS

Endometriosis is associated with increased systemic oxidative stress. The implication of increased systemic oxidative stress in disease progression or the association with other oxidative stress-related pathologic conditions needs to be addressed in further studies.

BACKGROUND

The primary study aim is to determine whether ischemia-modified albumin (IMA) levels predict mortality in patients with end-stage renal disease (ESRD). The secondary aim is to determine characteristics of patients with elevated IMA levels.

METHODS

A prospective observational study of 114 renal transplantation candidates was performed. All underwent coronary angiography and dobutamine stress echocardiography. The primary end point is total mortality.

RESULTS

During a follow-up period of 2.25 +/- 0.71 years, there were 18 deaths; 10 were cardiac related. Diabetes, severe coronary artery disease, positive dobutamine stress echocardiography result, cardiac troponin T (cTnT) level, IMA level, left ventricular (LV) end-systolic diameter, LV ejection fraction, left atrial size, and mitral peak velocity of early filling (E)/early diastolic velocity (Ea) ratio all predicted mortality. The receiver operating characteristic area under the curve for mortality prediction was similar for IMA and cTnT levels. An IMA level of 95 KU/L or greater (n = 46) predicted mortality with a sensitivity of 76% and specificity of 74%. cTnT level of 0.06 ng/mL or greater >> or = 0.06 microg/L; n = 51) predicted mortality with a sensitivity of 75% and specificity of 72%. Thirty-eight patients (33%) had both IMA and cTnT levels elevated. With multivariate analysis, a positive dobutamine stress echocardiography result (P = 0.003), combined elevated IMA and cTnT levels (P = 0.005), and E/Ea ratio (P = 0.009) were independent prognostic factors. IMA and cTnT levels alone were not independent predictors of mortality. Patients with an elevated IMA level had a significantly larger LV size, decreased LV systolic function, and greater E/Ea ratio compared with those without an increased level.

CONCLUSIONS

IMA level predicts mortality in patients with ESRD. Patients with elevated levels have larger LV size, decreased systolic function, and greater estimated LV filling pressures.

Ischemia-modified albumin (IMA) is a novel marker of tissue ischemia. Nowadays, IMA is accepted as a marker of oxidative stress. In this study, we aimed at establishing an association between IMA and hyperglycemia, blood pressure, lipid parameters, microvascular complications, hsCRP, and microalbuminuria in type 2 diabetes patients without overt macrovascular disease and acute ischemia. Fifty type 2 diabetes mellitus patients without a history of macrovascular disease or end-stage renal disease were enrolled into the study. Age-matched 30 healthy individuals were also included in the study as a control group. Plasma IMA (0.329 ± 0.046 and 0.265 ± 0.045 AbsU; P < 0.0001) and hsCRP levels (0.51 ± 0.36 and 0.32 ± 0.17 mg/dl; P < 0.0001) were significantly higher in the diabetic group compared to healthy controls. IMA level was significantly correlated with hsCRP (r = 0.76; P < 0.0001), HbA1c (r = 0.72; P < 0.0001), microalbuminuria (r = 0.40; P = 0.004), systolic blood pressure (r = 0.28; P = 0.049), diastolic blood pressure (r = 0.44; P = 0.005), and HOMA-IR (r = 0.42; P = 0.005) levels in the entire diabetic subjects. In the diabetic patients group, presence of microalbuminuria was associated with a higher plasma IMA level (0.355 ± 0.035 and 0.265 ± 0.0045 AbsU; P < 0.0001, patients with microalbuminuria and control subjects, respectively). In the type 2 diabetes patients with nephropathy, IMA level (0.355 ± 0.035 and 0.311 ± 0.046 AbsU; P = 0.002) was determined higher compared to the diabetes patients without nephropathy. Diabetic patients without an overt cardiovascular disease still have a higher serum IMA level compared to healthy controls. The correlation of high plasma IMA levels with high hsCRP and microalbuminuria levels in diabetic subjects indicates the presence of a chronic ischemic process. Therefore, elevated IMA levels may indicate an underlying subclinical vascular disease in type 2 diabetes mellitus patients.

OBJECTIVE

The objective was to determine the value of ischemia-modified albumin (IMA) in the diagnosis of mesenteric embolism. The authors investigated whether or not plasma IMA levels rose in the acute period in a rat model of mesenteric ischemia and the related time-dependent changes.

METHODS

In this randomized, controlled, nonblinded trial, 36 mature female Wistar rats were divided into six groups: three control (Groups I, III, and V) and three ischemia (Groups II, IV, and VI). In the control groups, blood was sampled at 30 minutes (Group I), 2 hours (Group III), and 6 hours (Group V) following a simple laparotomy. In the ischemia groups, following laparotomy, the superior mesenteric artery (SMA) was clamped using a bulldog clamp, and blood samples were taken at 30 minutes (Group II), 2 hours (Group IV), and 6 hours (Group VI).

RESULTS

Plasma IMA levels in the ischemia groups were significantly higher compared to those of the control groups (p < 0.004). In addition, levels were higher in the 6-hour blood samples of the ischemia group than in the 2-hour and 30-minute samples (p < 0.001). Serum IMA was also higher in the 2-hour blood samples of the ischemia group than in the 30-minute samples (p < 0.001).

CONCLUSIONS

These preliminary findings suggest that serum IMA levels may represent a significant parameter in the early diagnosis of acute mesenteric ischemia and that further studies are necessary.

CONCLUSIONS

The diagnosis of cardiac ischemia remains a challenge in contemporary emergency medicine. A blood-borne biomarker is an attractive alternative to cardiac imaging or stress testing as it would be cheaper and logistically faster to obtain. A number of candidate biomarkers have been proposed for the detection of cardiac ischemia; however, only Ischemia Modified Albumin (IMA) has been released for clinical use. IMA is a good discriminator between ischemic and non-ischemic patients. Changes in IMA concentration have shown to occur during coronary angioplasty-induced ischemia. Clinical studies indicate that IMA appears to offer on admission an early test which can be combined with electrocardiographic findings and cardiac troponin measurements for the early exclusion of acute coronary syndrome. IMA is an independent predictor of short and long term adverse outcomes in patients with acute chest pain. However, this test is relatively new and uncertainties remain. Elevations of IMA occur in conditions other than chest pain, thus questioning its specificity. The mechanism of IMA formation and the precise entity being measured are not fully known. Nevertheless, IMA measurement remains the only current clinical biomarker which may be used for the diagnosis of patients suspected of cardiac ischemia.

The advanced glycation end products (AGEs) are associated with increased cardiac endothelial injury. However, no causative link has been established between increased AGEs and enhanced endothelial injury after ischemia/reperfusion. More importantly, the molecular mechanisms by which AGEs may increase endothelial injury remain unknown. Adult rat cardiac microvascular endothelial cells (CMECs) were isolated and incubated with AGE-modified bovine serum albumin (BSA) or BSA. After AGE-BSA or BSA preculture, CMECs were subjected to simulated ischemia (SI)/reperfusion (R). AGE-BSA increased SI/R injury as evidenced by enhanced lactate dehydrogenase release and caspase-3 activity. Moreover, AGE-BSA significantly increased SI/R-induced oxidative/nitrative stress in CMECs (as measured by increased inducible nitric oxide synthase expression, total nitric oxide production, superoxide generation, and peroxynitrite formation) and increased SI/R-induced nitrative inactivation of thioredoxin-1 (Trx-1), an essential cytoprotective molecule. Supplementation of EUK134 (peroxynitrite decomposition catalyst), human Trx-1, or soluble receptor of advanced end product (sRAGE) (a RAGE decoy) in AGE-BSA precultured cells attenuated SI/R-induced oxidative/nitrative stress, reduced SI/R-induced Trx-1 nitration, preserved Trx-1 activity, and reduced SI/R injury. Our results demonstrated that AGEs may increase SI/R-induced endothelial injury by increasing oxidative/nitrative injury and subsequent nitrative inactivation of Trx-1. Interventions blocking RAGE signaling or restoring Trx activity may be novel therapies to mitigate endothelial ischemia/reperfusion injury in the diabetic population.

Pituitary adenylate cyclase activating polypeptide (PACAP) has neuroprotective effects against ischemia, even when given by intravenous (iv) administration 24 h after stroke. Transport of PACAP across the blood-brain barrier (BBB) by peptide transport system (PTS)-6 underlies its effectiveness after iv administration. However, PACAP transport is modified after central nervous system (CNS) injury, raising the question of whether cytokines or BBB disruption affects PTS-6 activity. Lipopolysaccharide (LPS) is derived from bacterial cell walls and affects the passage of other proteins across the BBB through its release of cytokines and disruption of the BBB. Here, we examined by several methods the transport of radioactively labeled PACAP (I-PACAP) across the BBB after intraperitoneal (ip) injection of LPS. After three doses of LPS, studies at a single time point found a differential effect of LPS on the brain/serum ratio for I-PACAP and radioactively labeled albumin (I-Albumin). Whereas LPS increased the ratio for I-Albumin, demonstrating BBB disruption, it decreased the ratio for I-PACAP. Multiple-time regression analysis, capillary depletion, and brain perfusion showed that this decrease was fully explained by a decrease in the initial, reversible binding of I-PACAP to brain endothelium, while the rate of transport of PACAP into the brain was not altered. These methods also showed that the LPS-treated mice were volume contracted. This volume contraction concentrated the amount of I-PACAP in the blood and so increased the amount of I-PACAP presented to the BBB. Lack of change in transport rate combined with volume contraction resulted in a net increase of about 30% of the iv dose of I-PACAP entering the brain. LPS did not alter the efflux of I-PACAP from the CNS. In conclusion, PTS-6 remains active and should be able to deliver therapeutic amounts of PACAP to the CNS in brain injuries involving cytokine release and BBB disruption.

BACKGROUND

Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality. Oxidative stress seems to play a pivotal role in this process, and purine metabolism may be involved in CKD-related oxidative stress. Xanthine oxidase (XO) is an enzyme involved in purine metabolism and is also responsible for the production of reactive oxygen species.

METHODS

This prospective study aimed to analyze the relation between plasma dosages of molecules involved in redox balance, purine metabolism and cardiovascular events in patients with non-diabetic CKD stages 3-5 or on chronic hemodialysis (HD). CKD (n = 51) and HD (n = 50) patients were compared to matched healthy controls (n = 38) and followed-up for 3 years.

RESULTS

Both CKD and HD patients had decreased plasma levels of antioxidants (selenium, zinc, vitamin C). HD patients had decreased levels of the antioxidant enzyme superoxide dismutase and increased levels of oxidation products (ischemia-modified albumin, malondialdehyde [MDA]). The following substrates and enzymes involved in purine metabolism were increased in the HD cohort: adenosine, adenosine deaminase and the pro-oxidant XO. XO activity was negatively correlated with super oxide dismutase and positively with MDA. Interestingly, XO activity was an independent predictor of cardiovascular events in CKD and HD patients, regardless of uric acid levels. Uric acid was not predictive of events.

CONCLUSIONS

This highlights a possible role of XO itself in CKD-related cardiovascular disease (CVD) and raises the hypothesis that beneficial effects observed with XO inhibitors on CVD in CKD may also be due to the reduction of oxidative stress.

Ischemia-modified albumin (IMA) is a sensitive marker of myocardial ischemia, skeletal muscle ischemia, pulmonary embolism, and stroke. However, there are no studies showing whether IMA increases in mesenteric ischemia. The aim of this study was to determine whether IMA was elevated in acute mesenteric ischemia. This case-controlled study was performed in an emergency department of a university hospital. The measurement of IMA levels in patient plasma yielded means of 0.264 +/- 0.057 absorbance units (ABSU) in the thromboembolic occlusion of the superior mesenteric artery (SMA) group and 0.163 +/- 0.025 ABSU in the control group. When plasma IMA levels in the thromboembolic occlusion SMA group were compared with those in the control group, statistically significant increases in IMA were observed in the occlusion group (P = .003). Findings indicating that IMA may have a place in the diagnosis of acute mesenteric embolism were obtained in this preliminary study. Further prospective studies are needed to see if IMA is clinically useful in the early detection of thromboembolic occlusion of the SMA.

BACKGROUND

Human serum albumin is the principal protein in human serum. It participates in regulation of plasma oncotic pressure and transports endogenous and exogenous ligands such as thyroxine, free fatty acids, bilirubin, and various drugs. Therefore, studying its ligand binding mechanism is important in understanding many functions of the protein.

METHODS

This review discusses the pleiotropic biochemical effects and their relevance to physiologic functions of albumin.

CONCLUSIONS

Although HSA is traditionally recognized for its ligand transport and oncotic effects in human circulation, our studies have revealed its participation in several other important physiological functions. In some instances, it may function as a catalyst. Pleiotropic properties of HSA have been exploited by development of recombinant HSA and its mutants, and the use of these recombinant proteins in studies with various biochemical and biophysical techniques. These studies allowed us to obtain new insights on the diverse roles of HSA in human physiology. The following aspects of HSA were discussed in this review: 1) HSA and its mutants' role in thyroxine transport, 2) structural details of the ligand binding functions of HSA to ligands such as warfarin, digoxin, halothane anesthetics, nitric oxide, bilirubin, free fatty acids, etc, and 3) the formation of modified albumin during myocardial ischemia, its diagnostic significance, and HSA's role in cardiovascular disease.

CONCLUSIONS

The appreciation and understanding of structural details and new physiological roles has provided a renewed interest in HSA research. Specific structural information gained on various mechanisms of HSA-ligand interaction can be used to develop a model to better understand protein-drug interactions, aid in the development of new drugs with improved pharmacokinetic effects, and ultimately be used to improve the quality of healthcare. This article is part of a Special Issue entitled Serum Albumin.

The aim of this study was to evaluate the inflammatory and oxidative biomarkers' levels in obese subjects and their associations with body mass index (BMI), in order to investigate the role of these biomarkers in obesity. Fasting glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, apolipoprotein A, apolipoprotein B, albumin, urinary albumin, creatinine, glomerular filtration rate, interleukin-6 (IL-6), nitrate/nitrite (NOx), and ischemia-modified albumin (IMA) were measured in 93 subjects divided according to different BMI. IL-6, urinary albumin, and IMA levels were significantly higher in obese subjects. However, the levels of NOx were significantly lower in this population. Significant correlations between BMI and IL-6 (r = 0.326, P = 0.002), NOx (r = -0.249, P = 0.021), urinary albumin (r = 0.270, P = 0.008), and IMA (r = 0.286, P = 0.005) were reported. We have shown an increase of IL-6, urinary albumin, and IMA combined with lower levels of NOx in obese patients and an association between of these biomarkers with BMI, suggesting a possible interplay of oxidative stress, inflammation, and endothelial dysfunction state in obesity.

BACKGROUND

Pulmonary embolism (PE) is a common condition, but the diagnostic strategy for the evaluation of suspected PE is somewhat controversial. Despite the use of various biochemical markers (such as D-dimer and C-reactive protein) and various probability calculation algorithms based on clinical findings for that purpose, there is still a need for more specific and practical markers in PE diagnosis. The aim of this study was to investigate the diagnostic value of ischemia-modified albumin (IMA) levels in the diagnosis of PE.

METHODS

This case-control study was performed in the emergency department between March and September 2006. The serum IMA levels of a total of 60 individuals, consisting of 30 PE patients who had been definitively diagnosed via spiral computed tomographic angiography and 30 healthy volunteers, were examined.

RESULTS

The measurement of IMA levels in patient plasma yielded mean values of 0.724 +/- 0.122 absorbance unit (ABSU) in the PE group and 0.360 +/- 0.090 ABSU in the control group. When plasma IMA levels in the PE group were compared with those in the control group, statistically significant increases in IMA were observed in the former (t = 13.19, df = 56, P < .0005). The value of 0.540 ABSU was calculated as the upper limit of reference interval. In the PE group, 97.7% (n = 29) had values exceeding 0.540 ABSU; none of the control subjects had values exceeding this cutoff value.

CONCLUSIONS

In conclusion, our data suggest that IMA levels may be useful as a discriminative marker to exclude pulmonary embolism.

The diagnostic approach to acute coronary syndromes (ACS) remains one of the most difficult and controversial challenges facing emergency physicians. In recent years, cardiac troponins have emerged as the biochemical "gold standard" for diagnosis of patients with acute chest pain, enhancing our ability to recognize ACS. Early diagnosis and treatment of myocardial ischemia improve patient outcomes, but conventional markers are often nondiagnostic at the time of arrival at the emergency department. Promising new biomarkers, which appear earlier after the onset of ischemia, are being studied and integrated into clinical practice. Some are markers of myocyte necrosis, but others, including ischemia-modified albumin and natriuretic peptides, detect myocardial ischemia and myocardial dysfunction. The aim of the present article is to review the diagnostic approach to ACS, focusing on recent literature describing novel biochemical markers. If ongoing and future studies confirm their role in probability-based models risk assessment, a new era in the diagnostic approach to ACS may be dawning.

BACKGROUND

Little is known about the capacity of ischemia-modified albumin (IMA) plasma concentration to predict long-term cardiac outcome in patients with established acute myocardial infarction (AMI). Because IMA is a marker of ischemia rather than myocardial cell damage, we hypothesized that IMA plasma levels could provide additional prognostic value to classic clinical and biological risk markers in patients with AMI. Therefore, we investigated the predictive value of plasma IMA in patients with AMI enrolled in the French Nationwide OPERA study.

METHODS

Plasma concentrations of IMA and other cardiac biomarkers (troponin, C-reactive protein, B-type natriuretic peptide) were measured within 24 hours of hospital admission in 471 patients hospitalized with an AMI (defined using European Society of Cardiology/American College of Cardiology criteria). Patients' characteristics, cardiovascular risk factors and treatments, and clinical outcomes were recorded. Univariate and multivariable predictors of cardiac outcome in-hospital and at 1 year were identified.

RESULTS

The primary composite end point (death, resuscitated cardiac arrest, recurrent myocardial infarction or ischemia, heart failure, stroke) occurred in 75 (15.6%) patients in-hospital and in 144 (30.6%) at 1 year: 40% of patients in the highest IMA quartile (>104 IU/mL) reached the end point compared with 20% in the lowest (<83 IU/mL) by 1 year. Multivariable logistic regression analysis identified 4 independent predictors of composite end point at 1 year: plasma concentrations of IMA (P = .01), brain natriuretic peptide (P = .001), heart failure (P = .005), and age (P = .003).

CONCLUSIONS

In patients with AMI, IMA measured within 24 hours is a strong and independent predictor of cardiac outcome at 1 year and may help identify those requiring more aggressive medical management.

BACKGROUND

Increased nitric oxide (NO) production may result in further brain damage via nitric oxide synthase uncoupling in patients with acute ischaemic stroke by increasing free radical formation and oxidative stress. In this connection, we measured nitrite and nitrate (NO metabolites), ischaemia-modified albumin (IMA) and thiobarbituric acid-reactive substances (TBARS) in patients with ischaemic stroke.

METHODS

We studied 41 patients with ischaemic stroke (22 men and 19 women, aged 65+/-13 years) and 37 age- and sex-matched controls (22 men and 15 women, aged 65+/-8 years). Blood samples were drawn within the first 24 h from the onset of symptoms in the patient group. Fasting morning samples were used in the control group. Concentrations of nitrite and nitrate were determined by Griess reagent; concentrations of IMA were determined by the albumin cobalt-binding test; and concentrations of TBARS were determined colorimetrically by thiobarbituric acid.

RESULTS

Nitrate, IMA and TBARS concentrations were significantly increased compared with controls (P<0.005, P<0.001, and P=0.01, respectively).

CONCLUSIONS

Patients with acute ischaemic stroke exhibit abnormalities in a range of markers of increased nitrosative and oxidative stress. These abnormalities may contribute to greater brain damage in patients with acute ischaemic stress.