Surgical banding for refractory hemodialysis access-induced distal ischemia (HAIDI).

Hemodialysis patients may develop distal ischemia in an extremity harboring a functioning arteriovenous access (AVA). Surgery is indicated if conservative treatment including catheter-based therapies fails. The role of surgical banding for refractory hemodialysis access-induced distal ischemia (HAIDI) is systematically reviewed (n=39 articles). If banding is executed without an intraoperative monitoring tool ("blind"), or guided by finger pressures only, clinical success and access patency rates are low (<50%). In contrast, banding is clinically successful when access flow is monitored during the operative procedure, with excellent long-term patency of banded AVA's (97%, 17 +/- 3 months). Banding is the method of choice in HAIDI patients with a normal or high access flow (>1.2 l/min) provided that flow and distal perfusion are closely monitored intraoperatively.

Perioperative hyperinsulinaemic normoglycaemic clamp causes hypolipidaemia after coronary artery surgery.

BACKGROUND: Glucose-insulin-potassium (GIK) administration is advocated on the premise of preventing hyperglycaemia and hyperlipidaemia during reperfusion after cardiac interventions. Current research has focused on hyperglycaemia, largely ignoring lipids, or other substrates. The present study examines lipids and other substrates during and after on-pump coronary artery bypass grafting and how they are affected by a hyperinsulinaemic normoglycaemic clamp. METHODS: Forty-four patients were randomized to a control group (n=21) or to a GIK group (n=23) receiving a hyperinsulinaemic normoglycaemic clamp during 26 h. Plasma levels of free fatty acid (FFA), total and lipoprotein (VLDL, HDL, and LDL)-triglycerides (TG), ketone bodies, and lactate were determined. RESULTS: In the control group, mean FFA peaked at 0.76 (sem 0.05) mmol litre(-1) at early reperfusion and decreased to 0.3-0.5 mmol litre(-1) during the remaining part of the study. GIK decreased FFA levels to 0.38 (0.05) mmol litre(-1) at early reperfusion, and to low concentrations of 0.10 (0.01) mmol litre(-1) during the hyperinsulinaemic clamp. GIK reduced the area under the curve (AUC) for FFA by 75% and for TG by 53%. The reduction in total TG was reflected by a reduction in the VLDL (-54% AUC) and HDL (-42% AUC) fraction, but not in the LDL fraction. GIK prevented the increase in ketone bodies after reperfusion (-44 to -47% AUC), but was without effect on lactate levels. CONCLUSIONS: Mild hyperlipidaemia was only observed during early reperfusion (before heparin reversal) and the hyperinsulinaemic normoglycaemic clamp actually resulted in hypolipidaemia during the largest part of reperfusion after cardiac surgery.

Phospholipid composition of in vitro endothelial microparticles and their in vivo thrombogenic properties.

INTRODUCTION: Microparticles from activated endothelial cells (EMP) are well known to expose tissue factor (TF) and initiate coagulation in vitro. TF coagulant activity is critically dependent on the presence of aminophospholipids, such as phosphatidylserine (PS) and phosphatidylethanolamine (PE), but it is unknown whether or not TF-exposing EMP are enriched in such aminophospholipids. Furthermore, despite the fact that EMP have been reported in several pathological conditions, direct evidence for their (putative) coagulant properties in vivo is still lacking. We investigated the phospholipid composition of endothelial MP (EMP) and their thrombogenic properties in vivo. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVEC; n=3) were incubated with or without interleukin (IL)-1alpha (5 ng/mL; 0-72 h). Phospholipid composition of EMP was determined by high-performance thin layer chromatography. The association between EMP, TF antigen and activity was confirmed in vitro (ELISA, Western blot and thrombin generation). Thrombogenic activity of EMP in vivo was determined in a rat venous stasis model. RESULTS: Levels of TF antigen increased 3-fold in culture medium of IL-1alpha-treated cells (P<0.0001). This TF antigen was associated with EMP and appeared as a 45-47 kDa protein on Western blot. In addition, EMP from activated cells were enriched in both PS (P<0.0001) and PE (P<0.0001), and triggered TF-dependent thrombin formation in vitro and thrombus formation in vivo. In contrast, EMP from control cells neither initiated coagulation in vitro nor thrombus formation in vivo. CONCLUSIONS: EMP from activated endothelial cells expose coagulant tissue factor and are enriched in its cofactors PS and PE.

Periodontitis is characterized by elevated PAI-1 activity.

OBJECTIVES: Periodontitis is a chronic infectious disease and has been associated with cardiovascular diseases (CVD). We investigated whether plasma levels of markers of a prothrombotic state were elevated in patients with periodontitis in comparison with healthy controls. MATERIALS AND METHODS: Untreated patients with moderate (n=53) and severe periodontitis (n=38) and healthy controls (n=39) were recruited. Levels of von Willebrand factor (vWF), prothrombin fragment 1+2 (F1+2), plasminogen activator inhibitor-1 (PAI-1) activity and D-dimer were measured as markers of a prothrombotic state. RESULTS: The erythrocyte sedimentation rate (ESR), plasma C-reactive protein (CRP) and leucocyte counts (WBC) were significantly higher in patients with periodontitis. No statistically significant difference was found among the three groups for vWF (p=0.264), F1+2 (p=0.295) and D-dimer (p=0.572). However, PAI-1 was clearly elevated in the severe periodontitis group (p=0.001), even after adjusting for potential confounding factors (p(adj)=0.004). Moreover, more patients than controls were having vWF and PAI-1 levels above the respective population medians. CONCLUSIONS: In periodontitis, elevated levels of PAI-1 activity are observed compared with healthy controls. This may increase the potential for impaired fibrinolysis, a condition that results in a prothrombotic state. We suggest that this state, if left untreated, may contribute to an increased risk for CVD.

Steal in hemodialysis patients depends on type of vascular access.

OBJECTIVES: To study incidence and severity of steal phenomena in hemodialysis patients and to investigate possible methods for its detection. METHODS: A questionnaire was composed based on a literature search. A subgroup of patients having steal as identified by the questionnaire was studied using physical examination, arterial blood pressure, skin temperature, digital oxygenation, grip strength and plethysmography. Contralateral arms served as controls. RESULTS: A cold hand was present in 50% of the patients with a brachiocephalic (BC) arteriovenous fistula (AVF, n = 28) compared to 25% of prosthetic forearm loops (loop, n = 27) and 12% of the radiocephalic (RC, n = 65, p < 0.05) fistulas. Diabetics were at risk for steal (p < 0.001). Intensity of steal was not related to magnitude of access flow. Digital skin temperatures and grip strength were lower in steal hands (p < 0.02). Manual compression of the AVF normalised low digital pressures in steal hands (106 +/- 33 vs 154 +/- 25 mmHg, p < 0.001, contralateral side 155 +/- 21 mmHg). CONCLUSIONS: Mild to moderate steal symptoms are common in a hemodialysis patient. Individuals with a BC are at a higher risk for developing complaints associated with reduced hand circulation compared to patients with a RC or loop. Low finger pressures in the presence of steal symptoms are usually reversible.

The phospholipid composition and cholesterol content of platelet-derived microparticles: a comparison with platelet membrane fractions.

BACKGROUND: The processes that govern the distribution of molecules between platelets and the microparticles (MP) they release are unknown. Certain proteins are sorted selectively into MP, but lipid sorting has not been studied. OBJECTIVES: To compare the phospholipid composition and cholesterol content of platelet-derived MP obtained with various stimuli with that of isolated platelet membrane fractions. METHODS: Washed platelets from venous blood of healthy individuals (n = 6) were stimulated with collagen, thrombin, collagen plus thrombin, or A23187. Platelet activation, MP release and antigen exposure were assessed by flow cytometry. MPs were isolated by differential centrifugation. Platelet plasma-, granule- and intracellular membranes were isolated from platelet concentrates (n = 3; 10 donors each) by pressure homogenization and Percoll density gradient fractionation. The phospholipid composition and cholesterol content of MPs and membrane fractions were analyzed by high performance thin layer chromatography. RESULTS: The phospholipid composition of MPs was intermediate compared with that of platelet plasma- and granule membranes, and differed significantly from that of intracellular membranes. There were small but significant differences in phospholipid composition between the MPs produced by the various agonists, which paralleled differences in P-selectin exposure in case of the physiological agonists collagen, thrombin, or collagen plus thrombin. The cholesterol content of MPs tended to be higher than that of the three-platelet membrane fractions. CONCLUSIONS: Regarding its phospholipid content, the MP membrane is a composite of the platelet plasma- and granule membranes, showing subtle differences depending on the platelet agonist. The higher cholesterol content of MPs suggests their enrichment in lipid rafts.

Glucose, insulin and potassium applied as perioperative hyperinsulinaemic normoglycaemic clamp: effects on inflammatory response during coronary artery surgery.

BACKGROUND: The clinical benefits of glucose-insulin-potassium (GIK) and tight glycaemic control in patients undergoing coronary artery bypass grafting (CABG) may be partly explained by an anti-inflammatory effect. We applied GIK as a hyperinsulinaemic normoglycaemic clamp for >25 h and quantified its effect on systemic inflammation in patients undergoing CABG. METHODS: Data obtained in 21 non-diabetic patients with normal left ventricular function scheduled for elective coronary artery surgery, who were randomly allocated to a control or GIK group, were analysed. In GIK patients, regular insulin was infused at a fixed rate of 0.1 IU kg(-1) h(-1). The infusion rate of glucose (30%) was adjusted to maintain blood glucose levels within a target range of 4.0-5.5 mmol litre(-1). Plasma concentrations of interleukins 6, 8 and 10, C-reactive protein (CRP) and serum amyloid A (SAA) were measured on the day of surgery and on the first and second postoperative days (POD1 and POD2). RESULTS: In the GIK group hypoglycaemia (glucose <2.2 mmol litre(-1)) did not occur, whereas hyperglycemia (glucose >6.1 mmol litre(-1)) developed in 15% of all measurements. In control patients, hyperglycaemia developed in >80% of all measurements in the presence of low endogenous insulin levels. CRP and SAA levels increased in both groups, with maximum levels measured on POD2. GIK treatment significantly reduced CRP and SAA levels. Interleukin levels increased significantly in both groups following cardiopulmonary bypass, but no differences were found between the groups. CONCLUSION: Hyperinsulinaemic normoglycaemic clamp is an effective method of maintaining tight glycaemic control in patients undergoing CABG and it attenuates the systemic inflammatory response in these patients. This effect may partly contribute to the reported beneficial effect of glycaemic control in patients undergoing CABG.

Plasma antibody levels in periodontitis patients and controls.

BACKGROUND: A major aspect of the adaptive host response in periodontitis is the production of antibodies. Several risk and susceptibility factors for periodontitis, including smoking, age and composition of the subgingival microflora, have also been suggested to influence antibody production. AIM: The present study was conducted to investigate plasma levels of immunoglobulin (Ig) G, A and M antibodies in periodontitis patients of Caucasian European heritage in relation to disease severity, smoking, diagnosis and prevalence of periodontopathogens. METHODS: In this study, 29 patients with severe periodontitis, 51 with moderate periodontitis and 55 controls without periodontal destruction were enrolled. From the total of 80 patients, 18 were diagnosed with aggressive periodontitis and 62 with chronic periodontitis. Total IgG, IgA and IgM as well as IgG isotypes were analyzed in plasma samples. RESULTS: Levels of total IgG, IgA and IgM were not different between patients and controls; however, in periodontitis, higher levels of IgG1 and IgG2 were observed. Smoking appeared to be significantly and inversely related to antibody levels in periodontitis, in particular for total IgG and IgG2. The absence of an elevated total IgG and IgG2 in smoking patients was irrespective of severity, prevalence of periodontal pathogens and diagnosis. The elevation of total IgG and IgG1 and IgG2 in non-smoker periodontitis patients was observed in patients with moderate periodontitis and even greater in patients with severe periodontitis, but was independent whether patients were infected with Actinobacillus actinomycetemcomitans or Porphyromonas gingivalis and independent of diagnosis. Clinically, it was observed that patients who smoked had more periodontal bone loss; the current findings on antibody levels may be one of several mechanisms related to more extensive periodontal breakdown in smoker patients. CONCLUSION: The current study shows that non-smoker periodontitis patients have higher levels of total IgG and IgG2 than smoker periodontitis patients.

Lower numbers of erythrocytes and lower levels of hemoglobin in periodontitis patients compared to control subjects.

BACKGROUND: Anemia of chronic disease (ACD) is defined as the anemia occurring in chronic infections and inflammatory conditions, that is not due to marrow deficiencies or other diseases and in the presence of adequate iron stores and vitamins. The purpose of the present study was to investigate whether periodontitis patients show signs of anemia. METHOD: 39 patients with severe periodontitis, 71 patients with moderate periodontitis and 42 controls, all with good general health, participated in this study. The mean age of all groups was 42 years. Several red blood cell parameters were determined from peripheral blood samples. RESULTS: Overall data analysis indicated that periodontitis patients have a lower hematocrit, lower numbers of erythrocytes, lower hemoglobin levels and higher erythrocyte sedimentation rates. These results were adjusted for the following possible confounders: gender, age, smoking, ethnicity and level of education. Further, more periodontitis patients (23%) than controls (7%), had hemoglobin levels below the normal reference range. CONCLUSIONS: The present study provides further evidence that periodontitis has systemic effects and that periodontitis may tend towards anemia. This phenomenon may be explained by a depressed erythropoiesis.

IC14, an anti-CD14 antibody, inhibits endotoxin-mediated symptoms and inflammatory responses in humans.

CD14 is a receptor for cell wall components of Gram-negative and Gram-positive bacteria that has been implicated in the initiation of the inflammatory response to sepsis. To determine the role of CD14 in LPS-induced effects in humans, 16 healthy subjects received an i.v. injection of LPS (4 ng/kg) preceded (-2 h) by i.v. IC14, a recombinant chimeric mAb against human CD14, at a dose of 1 mg/kg over 1 h, or placebo. In subjects receiving IC14, saturation of CD14 on circulating monocytes and granulocytes was >90% at the time of LPS injection. IC14 attenuated LPS-induced clinical symptoms and strongly inhibited LPS-induced proinflammatory cytokine release, while only delaying the release of the anti-inflammatory cytokines soluble TNF receptor type I and IL-1 receptor antagonist. IC14 also inhibited leukocyte activation, but more modestly reduced endothelial cell activation and the acute phase protein response. The capacity of circulating monocytes and granulocytes to phagocytose Escherichia coli was only marginally reduced after infusion of IC14. These data provide the first proof of principle that blockade of CD14 is associated with reduced LPS responsiveness in humans in vivo.

Effect of rectal distension on gallbladder emptying and circulating gut hormones.

BACKGROUND: Abnormalities of upper gut motility, including a delay of gastric emptying and small bowel transit, found in patients with constipation may be secondary to factors originating in the colon or rectum as a result of faecal stasis. The aim was to determine if stimulation of mechanosensory function by rectal distension affects postprandial gallbladder emptying and release of gastrointestinal peptides participating in control of upper gut motility. MATERIALS AND METHODS: Eight healthy volunteers were studied with an electronic barostat and a plastic bag positioned in the rectum. Intrabag pressure was maintained at minimal distension pressure + 2 mmHg on one occasion and on a pressure that induced a sensation of urge on the other. Gallbladder volume and plasma concentrations of cholecystokinin (CCK), pancreatic polypeptide (PP) and peptide YY (PYY) were measured before and after ingestion of a 450-kcal mixed liquid meal. RESULTS: Rectal distension enhanced maximum gallbladder emptying from 66 +/- 7% to 78 +/- 5% (P < 0.05). Distension tended to increase integrated plasma PYY from 77 +/- 30 pM min to 128 +/- 40 pM min in the first hour after the meal (P = 0.08) and it suppressed integrated plasma PP from 1133 +/- 248 pM min to 269 +/- 284 pM min in the second hour (P < 0.05). Integrated plasma CCK concentrations were not significantly affected. CONCLUSION: Mechanosensory stimulation of the rectum enhances postprandial gallbladder emptying and influences postprandial release of gut hormones involved in the regulation of gastrointestinal motility in healthy subjects. These mechanisms may play a role in the pathogenesis of the upper gastrointestinal motor abnormalities observed in constipated patients.

Elevation of systemic markers related to cardiovascular diseases in the peripheral blood of periodontitis patients.

BACKGROUND: Periodontitis is a common, often undiagnosed, chronic infection of the supporting tissues of the teeth, epidemiologically associated with cardiovascular diseases. Since C-reactive protein (CRP) and other systemic markers of inflammation have been identified as risk factors for cardiovascular diseases, we investigated whether these factors were elevated in periodontitis. METHODS: Consecutive adult patients with periodontitis (localized n = 53; generalized n = 54), and healthy controls (n = 43), all without any other medical disorder, were recruited and peripheral blood samples were taken. RESULTS: Patients with generalized periodontitis and localized periodontitis had higher median CRP levels than controls (1.45 and 1.30 versus 0.90 mg/L, respectively, P = 0.030); 52% of generalized periodontitis patients and 36% of the localized periodontitis patients were sero-positive for interleukin-6 (IL-6), compared to 26% of controls (P= 0.008). Plasma IL-6 levels were higher in periodontitis patients than in controls (P = 0.015). Leukocytes were also elevated in generalized periodontitis (7.0 x 10(9)/L) compared to localized periodontitis and controls (6.0 and 5.8 x 10(9)/L, respectively, P= 0.002); this finding was primarily explained by higher numbers of neutrophils in periodontitis (P= 0.001). IL-6 and CRP correlated with each other, and both CRP and IL-6 levels correlated with neutrophils. The current findings for periodontitis were controlled for other known factors associated with cardiovascular diseases, including age, education, body mass index, smoking, hypertension, cholesterol, and sero-positivity for CMV, Chlamydia pneumoniae, and Helicobacter pylori. CONCLUSIONS: Periodontitis results in higher systemic levels of CRP, IL-6, and neutrophils. These elevated inflammatory factors may increase inflammatory activity in atherosclerotic lesions, potentially increasing the risk for cardiac or cerebrovascular events.

Postulating a dermal pathway for exposure to anti-neoplastic drugs among hospital workers. Applying a conceptual model to the results of three workplace surveys.

Dermal exposure to anti-neoplastic drugs has been suggested as a potentially important route of exposure of hospital workers. Three small-scale workplace surveys were carried out in several hospitals focusing on contamination by leakage from IV infusion systems; contamination by spilled urine of patients treated with anti-neoplastic drugs and particulate phase anti-neoplastic drugs in the air of outpatient and nursing clinics. A new visual scoring technique using a fluorescent tracer was developed. The method showed a very low limit of detection (0.02 microl of contamination) and a very high inter-observer agreement (ICC=0.99). Evaluation of IV systems and connectors showed distinct differences between the systems. It was estimated that 0.5-250 microg of a drug can become available for contamination during each infusion. Differences in average contamination between nurses were negligible in the experimental set-up. Widespread and frequent contamination due to spillage of contaminated urine was revealed and appeared not to be restricted to the patient's room. Airborne particulate concentrations went undetected for 80% of the measurements. However, in a few cases concentrations up to 2 ng/m(3) of cyclophosphamide were measured predominantly in a room of a patient treated with this anti-neoplastic drug. Based on these results and a recently proposed conceptual model for dermal exposure a most likely exposure scenario was postulated both for nurses involved in administering drugs and nurses caring for treated patients. Estimation of all relevant mass transport rates will be a challenge for the near future.

Effects of rectal mobilization and lateral ligaments division on colonic and anorectal function.

PURPOSE: Colonic and anorectal function are altered after posterior rectopexy. The aim of this randomized, prospective study was to evaluate the effects of rectal mobilization and division of the lateral ligaments on colonic and anorectal function. METHODS: Posterior rectopexy was performed in 18 patients with complete rectal prolapse. Anal manometry and measurement of rectal compliance, total and segmental colonic transit time, constipation score, and defecation frequency were performed preoperatively and three months postoperatively. Ligaments were divided in ten patients. RESULTS: Mean preoperative total transit time was similar between the two patient groups and doubled postoperatively (P = 0.03). Mean postoperative segmental transit time increased by a factor of 1.7 in segments I (ascending colon) and II (descending colon) and by a factor of 2.3 in segment III (rectosigmoid). The same pattern was found in both groups. Mean resting pressure decreased after division of the lateral ligaments and increased after preservation. Mean rectal compliance decreased after division of the ligaments and increased when they were preserved. Mean postoperative constipation score differed little from the preoperative score. Mean defecation frequency was decreased in the group with the ligaments preserved and increased in the group with the ligaments divided. None of the effects of rectal mobilization or division of the lateral ligaments on anorectal function reached statistical significance. CONCLUSION: Rectal mobilization had a statistically significant effect on colonic function. Total and segmental colonic transit times doubled. The effects on anorectal function were not significant. Division of the lateral ligaments did not significantly influence postoperative functional outcome.

Diagnostic accuracy of myoglobin concentration for the early diagnosis of acute myocardial infarction.

STUDY OBJECTIVE: We evaluated the diagnostic accuracy of myoglobin determination for the early diagnosis of acute myocardial infarction (AMI). METHODS: Consecutive patients with chest pain were included in the study. Receiver operating characteristic (ROC) analysis was used to assess optimal timing of blood sampling and cutoff values. RESULTS: A total of 309 patients were included, of whom 162 patients had a diagnosis of AMI. ROC analysis revealed that the diagnostic accuracy of myoglobin concentration as indicated by the area under the ROC curve (AUC) increased significantly from 3 (0.89+/-0.026) and 4 hours (0.93+/-0.019) to 5 hours after onset of symptoms (0. 96+/-0.014; P=.0040 and.035, respectively). At 5 hours (the earliest time point with maximal AUC), sensitivity was 87% and specificity was 97% using a myoglobin cutoff value of 90 microg/L. With a myoglobin cutoff value of 50 microg/L, sensitivity was 95% (95% confidence interval 90% to 98%), but specificity was 86% (95% confidence interval 80% to 93%). CONCLUSION: Myoglobin has maximal diagnostic accuracy for the diagnosis of AMI at 5 hours after the onset of symptoms, using a cutoff value of 50 microg/L. In combination with the measurement of other biochemical markers, myoglobin determination could be particularly useful for triage of patients with AMI at an early stage.

Possible role of nitric oxide in postoperative ileus: a comparative study.

In the present study, the possible involvement of nitric oxide (NO) in the pathogenesis of postoperative ileus was investigated indirectly by measuring nitrate, a stabile metabolite of NO. Plasma levels and 24-h urinary excretion of nitrate and nitrite were determined in the peri-operative period in three different groups of patients undergoing surgery: group 1 (LT, n=11) underwent a laparotomy, group 2 (LS, n=12) underwent a laparoscopic procedure, whereas group 3 underwent an extra-abdominal procedure (EA, n=9). Duration of postoperative ileus was assessed clinically using first occurrence of flatus and defaecation as the end of the period of ileus. Postoperative ileus lasted significantly longer in the LT group (first flatus after 3.0 [3.0-4.0] days) compared with the LS (1.0 [1.0-2.0] days) and EA (1.0 [1.0-3.0] days) groups. Urinary nitrate excretion increased significantly in the LT and EA groups during the first 24 h after surgery (from 797.0 [214.0-810.0] and 551.5 [438.3-1215.8] to 2079.0 [889.0-4644.0] and 1102.5 [315.3-1238. 0] micromol/24 h, median [IQR]), but normalized before the end of postoperative ileus. Plasma levels of nitrate were unchanged after surgery, whereas CRP levels were significantly increased in all groups (LT > LS=EA). In the first 24 h following surgery, urinary nitrate excretion is increased, suggesting increased endogenous synthesis of NO postoperatively. As no correlation was found between urinary nitrate excretion and duration of postoperative ileus, we conclude that assessment of nitrate has no value in predicting clinical outcome after surgery.

Independent prognostic value of C-reactive protein and troponin I in patients with unstable angina or non-Q-wave myocardial infarction.

OBJECTIVES: Elevated concentrations of C-reactive protein (CRP), a non-specific acute phase reactant, and troponin I (TnI), a cardiac-specific marker of myocardial damage, have been found to be associated with a higher risk for cardiac events in patients with an acute coronary syndrome. We evaluated CRP alone and in combination with TnI for predicting the incidence of major cardiac complications within 6 months in patients with unstable angina or non-Q-wave infarction (NQMI). METHODS: CRP and TnI was measured on admission in patients with unstable angina or NQMI, but results were kept blinded. Patients were treated according to a conservative management strategy, and the incidence of major cardiac events within 6 months was assessed. RESULTS: An abnormal CRP (> 5 mg/l) and an abnormal TnI (> 0.4 microgram/l) were more frequent in patients that suffered a major cardiac event (CRP: 93 vs. 35%, P < 0.0001; TnI: 73 vs. 26%, P < 0.001). The incidence of major cardiac events was higher in patients with an abnormal CRP than in patients with a normal CRP, both when TnI was abnormal (42 vs. 4.5%, P = 0.003) and when TnI was normal (11 vs. 0%, P = 0.014). Mean event-free survival was excellent in patients with both a normal CRP and TnI, whereas survival was poorest in patients with both an abnormal CRP and TnI (121 +/- 16 vs. 180 days, P < 0.0001). CONCLUSIONS: An abnormal CRP on admission in patients with unstable angina or NQMI is associated with increased incidence of major cardiac events within 6 months, both in patients with normal and abnormal TnI. CRP and TnI have independent and additive prognostic value in this patient group, and the combination may be useful for early risk stratification.