Biomedical subjects

A Siegbahn

Publications and source records attributed to A Siegbahn.

At least 37 records · Page 2Linked to original sources

PubMed2000

The role of RAR and RXR activation in retinoid-induced tissue factor suppression.

Excessive expression of tissue factor (TF) is a common finding in leukaemic cells and may contribute to thrombotic complications in patients. Retinoic acid has been shown to induce differentiation and reduce TF expression in acute promyelocytic leukaemia (APL) cells in vitro, and to induce remission in APL patients. Treatment of the APL cell line NB4 with the specific retinoic acid receptor-alpha (RARalpha) agonists Ro4-6055 or TTNPB resulted in down-regulation of TF expression and in induction of differentiation. The activation of RARbeta, RARgamma or retinoid X receptor (RXR) did not suppress the constitutive TF expression in NB4 cells. Moreover, the RARalpha antagonist Ro41-5253 blocked the retinoid-induced down-regulation of TF. In contrast, in the monoblastic U-937 cell line only a partial suppression of TF antigen expression and activity was observed by treatment with the RAR agonist TTNPB or the RXR agonist SR11237 alone. However, the combination of TTNPB and SR11237 resulted in a pronounced down-regulation of TF expression and induction of differentiation in U-937 cells. We show for the first time that the activation of both subunits of the RARalpha-RXR transcriptional complex is needed for TF suppression in U-937 cells, whereas in NB4 cells RARalpha activation alone is sufficient. Thus, distinct molecular mechanisms for TF suppression seem to be operating in leukaemic cell lines of different origin.

Base Sequence↗

PubMed2000

Markers of hypercoagulation and von Willebrand factor in postmenopausal women with unstable coronary artery disease. Discriminatory ability regarding unstable coronary artery disease and coronary atherosclerosis using receiver operating characteristics.

OBJECTIVES: Many women with typical anginal chest pain have normal coronary angiograms. The pathogenetic mechanisms behind the chest pain in these patients are unknown but may be due to increased thrombogenicity. We evaluated markers of hypercoagulation and thrombosis in women with clinical signs of unstable coronary artery disease (CAD). METHODS AND RESULTS: A total of 158 patients with unstable CAD and 101 controls were examined: 16% of the patients had normal vessels and 84% had coronary atherosclerosis at coronary angiography. Mean plasma concentrations of von Willebrand factor antigen, soluble fibrin (SF), thrombin-antithrombin complex and D-dimer were significantly higher, whereas there was no difference regarding prothrombin fragment 1+2 between patients and controls. Patients with coronary atherosclerosis had higher mean plasma levels for most variables compared with those with normal coronary vessels, although only significantly higher for SF. D-Dimer was significantly higher in patients with normal coronary vessels compared with the control group. Although multivariate analyses showed strong significant correlations of the haemostatic variables to the diagnosis of unstable CAD, receiver operating characteristics (ROC) revealed that none of the variables represented high diagnostic accuracy in separating patients with unstable CAD. Likewise, none of the variables was particularly good at identifying coronary atherosclerosis. CONCLUSION: Our results are in favour of a hypercoagulable state in postmenopausal women with unstable CAD and coronary atherosclerosis, whereas this does not seem to be the case in patients with normal vessels. ROC revealed no variable to be particularly clinically useful in separating patients from controls or patients from those without coronary atherosclerosis.

Aged↗

PubMed2000

Haemostasis in patients with Behçet's disease.

AIM: to determine whether Behçet's disease affects haemostatic function. SETTING: University Hospital, Turkey. PATIENTS: one hundred and twenty-seven consecutive patients with Behçet's disease, 34 of whom with a history of vascular involvement. METHODS: prothrombin fragment 1+2 tissue plasminogen activator, protein S and C, antithrombin, fibrinogen, von Willebrand factor, thrombomodulin and prothrombin time (PT) were measured in patient plasma. RESULTS: soluble thrombomodulin was significantly lower and von Willebrand factor (vWF) and tissue plasminogen activator (tPA) significantly higher in Behçet's patients. Patients with vascular involvement showed the highest levels of vWF and tPA. There was no activation of coagulation, not even in patients with an active disease at the time of sampling. CONCLUSION: there were indirect signs of endothelial activity or damage, particularly in patients with vascular involvement. Coagulation was not activated.

Adult↗

PubMed2000

Heparin-coated cardiopulmonary bypass circuits reduce circulating complement factors and interleukin-6 in paediatric heart surgery.

Children are sensitive to the inflammatory side effects of cardiopulmonary bypass (CPB). Our intention was to investigate if the biocompatibility benefits of heparin-coated CPB circuits apply to children. In 20 operations, 19 children were randomized to heparin-coated (group HC, n = 10) or standard (group C, n = 10) bypass circuits. Plasma levels of acute phase reactants, interleukins, granulocytic proteins and complement factors were measured. All were significantly elevated after CPB. Levels of complement factor C3a (851 (791-959)ng/ml [median with quartiles] in group C, 497 (476-573)ng/ml in group HC, p < 0.001), Terminal Complement Complex (114 (71-130) AU/ml in group C, 35.5 (28.9-51.4) AU/ml in group HC, p < 0.001), and interleukin-6 (570 (203-743) pg/ml in group C, 168 (111-206)pg/ml in group HC, p = 0.005), were significantly reduced in group HC. Heparin-coated CPB circuits improve the biocompatibility of CPB during heart surgery in the paediatric patient population, as reflected by significantly reduced levels of circulating complement factors and interleukin-6.

Anticoagulants↗

PubMed2000

Cellular consequences upon factor VIIa binding to tissue factor.

Tissue factor (TF) is a cell-surface-bound glycoprotein that binds the zymogen, factor (F) VII, and the active serine protease, FVIIa. The FVIIa/TF complex is the major activator of coagulation in vivo. Under normal physiological conditions, TF is expressed only on extravascular sites and perivascularly in the adventitial layer of blood vessels. Although not normally expressed by cells within the circulation, TF can be induced in monocytes and endothelial cells. Also, several malignant cells express high levels of TF. Recent reports have shown that FVIIa binding to TF can influence a number of biological functions, such as angiogenesis and cancer metastasis. TF also seems to play an important role in cell adhesion and migration. The intracellular signalling is independent of downstream activation of the blood coagulation cascade. FVIIa/TF seems to transduce signalling by two distinct mechanisms: one independent of the cytoplasmatic domain but dependent on the proteolytic activity of FVIIa, and one dependent on the cytoplasmatic domain of TF.

Animals↗

PubMed2000

Role of platelet P-selectin and CD40 ligand in the induction of monocytic tissue factor expression.

Activated platelets can express CD40 ligand (CD40L) and trigger inflammatory response and tissue factor (TF) expression in endothelial cells through interaction with CD40. This pathway is also important for T cell-induced monocyte and endothelial cell procoagulant activity. We have studied the potential role of the CD40-CD40L pathway in platelet-induced TF expression in a monocytic cell line and in whole-blood monocytes. In vitamin D(3)-differentiated U-937 cells, thrombin-stimulated platelets increased TF expression as measured by mRNA quantification, flow cytometry, and procoagulant activity. Maximum antigen expression occurred after 2 hours. Neutralizing anti-P-selectin antibody yielded a 50% suppression of procoagulant activity, whereas antibody to CD40L had no effect. In thrombin receptor activator-stimulated citrated blood, monocytes were up to 77% TF-positive, with peak expression after only 15 minutes. However, no TF mRNA was detectable at that time. Anti-P-selectin antibody reduced TF by 50%, whereas antibody to CD40L gave a 17% reduction. Thus, we conclude that P-selectin exposed on activated platelets induces the expression of TF in both U-937 cells and whole-blood monocytes but by different mechanisms. Platelet CD40L does not display any significant effect on U-937 cells but may be of some importance on whole-blood monocytes. This suggests a possible functional difference between U-937 and monocyte CD40. Another important finding in this study is the rapid appearance of surface TF on monocytes without detectable mRNA formation. This indicates that TF may be stored intracellularly in these cells and can be exposed on the surface independent of de novo protein synthesis.

Antibodies↗

PubMed1999

Coagulation and fibrinolysis after open infrarenal abdominal aortic aneurysm repair in a long-term perspective.

In patients with abdominal aortic aneurysms (AAA) the coagulation and fibrinolytic systems have been found to be activated preoperatively. Does the increased activity of the coagulation and fibrinolytic systems persist after AAA surgery in a long-term perspective? Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), tissue plasminogen activator (tPA), human plasminogen activator inhibitor type 1, and human cross-linked fibrin degradation product (D-dimer) were analysed in 18 patients after open AAA surgery (postop-AAA). The median time between surgery and blood sampling was 19 months (range, 5-37 months). Comparisons were made with both preoperative values of 23 patients with AAA (preop-AAA) as well as 20 age-matched healthy controls (AMC). F1+2, TAT, and D-dimer in preop-AAA were significantly higher compared to AMC (p<0.001). In post-op AAA patients these parameters were significantly lower compared to preop-AAA (p<0.05 for F1+2 and TAT, p<0.001 for D-dimer). However, TAT and D-dimer levels were still higher in postop-AAA than in AMC (p<0.01 for both). The activity of the coagulation and fibrinolytic systems seems to decrease after AAA surgery. However, the activity is still higher than in healthy AMC. A possible explanation may be that the thrombogenicity is lower in a vascular graft than in an aneurysmal sac but still higher than in a nonaneurysmal aorta.

Aged↗

PubMed1999

Overactivation of phospholipase C-gamma1 renders platelet-derived growth factor beta-receptor-expressing cells independent of the phosphatidylinositol 3-kinase pathway for chemotaxis.

We have previously shown that porcine aortic endothelial cells expressing the Y934F platelet-derived growth factor (PDGF) beta-receptor mutant respond to PDGF-BB in a chemotaxis assay at about 100-fold lower concentration than do wild-type PDGF beta-receptor-expressing cells (Hansen, K., Johnell, M., Siegbahn, A. , Rorsman, C., Engström, U., Wernstedt, C., Heldin, C.-H., and Rönnstrand, L. (1996) EMBO J. 15, 5299-5313). Here we show that the increased chemotaxis correlates with increased activation of phospholipase C-gamma1 (PLC-gamma1), measured as inositol-1,4, 5-trisphosphate release. By two-dimensional phosphopeptide mapping, the increase in phosphorylation of PLC-gamma1 was shown not to be selective for any site, rather a general increase in phosphorylation of PLC-gamma1 was seen. Specific inhibitors of protein kinase C, bisindolylmaleimide (GF109203X), and phosphatidylinositol 3-kinase (PI3-kinase), LY294002, did not affect the activation of PLC-gamma1. To assess whether increased activation of PLC-gamma1 is the cause of the hyperchemotactic behavior of the Y934F mutant cell line, we constructed cell lines expressing either wild-type or a catalytically compromised version of PLC-gamma1 under a tetracycline-inducible promoter. Overexpression and concomitant increased activation of wild-type PLC-gamma1 in response to PDGF-BB led to a hyperchemotactic behavior of the cells, while the catalytically compromised PLC-gamma1 mutant had no effect on PDGF-BB-induced chemotaxis. Furthermore, in cells expressing normal levels of PLC-gamma1, chemotaxis was inhibited by LY294002. In contrast, the increase in chemotactic response seen upon overexpression of PLC-gamma1 was not inhibited by the PI3-kinase inhibitor LY294002. These observations suggest the existence of two different pathways which mediate PDGF-induced chemotaxis; depending on the cellular context, the PI3-kinase pathway or the PLC-gamma1 pathway may dominate.

Amino Acid Substitution↗

PubMed1999

Serum amyloid A induces chemotaxis of human mast cells by activating a pertussis toxin-sensitive signal transduction pathway.

Serum amyloid A (SAA) is an acute-phase protein and its concentration increases in the blood up to 1000 times during an inflammatory response. Mast cells are known to accumulate in various inflammatory processes, some of which are associated with increased levels of acute-phase reactants such as SAA. We report here that SAA can act as a mast cell chemoattractant. Recombinant SAA at concentrations corresponding to those found during the acute phase induced directional migration of human mast cells. No chemokinetic effect was observed. Preincubation of the cells with pertussis toxin inhibited SAA chemotaxis, suggesting that the effect is mediated by G proteins of the Gi class. Furthermore, chemotaxis was diminished after pretreatment with genistein, a tyrosine kinase inhibitor, or bisindolylmaleimide I, a protein kinase C inhibitor. We suggest that SAA may participate in the migration of mast cells to inflamed tissues during an acute-phase response, acting through a pertussis toxin-sensitive signaling pathway.

Cell Line↗

PubMed1999

Influences of sex and smoking habits on anticoagulant activity in low-molecular-weight heparin treatment of unstable coronary artery disease.

BACKGROUND: In the FRISC trial, dalteparin 120 IU/kg body weight twice daily for unstable coronary artery disease was safe and reduced the risk of new coronary events. This risk reduction was maintained during the following extended treatment with a fixed dose of 7500 IU dalteparin once daily. METHODS AND RESULTS: Minor bleeding was more frequent in women compared with men: relative risk (CI) 2.88 (1.78 to 4.67) during the weight-adjusted and 2.36 (1.37 to 2.63) during the fixed dose treatment. The anti-Xa activity determined in samples (n = 175) obtained during the acute phase treatment was higher in women compared with men (P <.001) and in nonsmokers compared with smokers (<.001) in multiple regression analysis. Also, during the fixed-dose treatment (n = 131) an independent relation between anti-Xa activity and sex (P <.001), but not smoking habits, persisted. CONCLUSION: To improve future low-molecular-weight heparin dose regimens for the treatment of acute coronary syndromes, it might be important to consider the influence of sex and smoking habits.

Adult↗

PubMed1999

Low molecular weight heparin (dalteparin) as adjuvant treatment of thrombolysis in acute myocardial infarction--a pilot study: biochemical markers in acute coronary syndromes (BIOMACS II).

OBJECTIVES: This randomized, double blind, placebo-controlled pilot trial evaluated the effect of dalteparin as an adjuvant to thrombolysis in patients with acute myocardial infarction regarding early reperfusion, recurrent ischemia and patency at 24 h. BACKGROUND: Low-molecular-weight heparin, given subcutaneously twice daily without monitoring, might be an attractive alternative to conventional intravenous heparin in the treatment of acute myocardial infarction. METHODS: In 101 patients dalteparin/placebo 100 IU/kg was given just before streptokinase and a second injection 120 IU/kg after 12 h. Monitoring with continuous vector-ECG was done to obtain signs of early reperfusion and later ischemic episodes. Blood samples for myoglobin were obtained at start and after 90 min to evaluate signs of reperfusion. Coronary angiography was performed after 20-28 h to evaluate TIMI-flow in the infarct-related artery. RESULTS: Dalteparin added to streptokinase tended to provide a higher rate of TIMI grade 3 flow in infarct-related artery compared to placebo, 68% versus 51% (p = 0.10). Dalteparin had no effects on noninvasive signs of early reperfusion. In patients with signs of early reperfusion, there seemed to be a higher rate of TIMI grade 3 flow, 74% versus 46% (myoglobin) (p = 0.04) and 73% versus 52% (vector-ECG) (p = 0.11). Ischemic episodes 6-24 h. after start of treatment were fewer in the dalteparin group, 16% versus 38% (p = 0.04). CONCLUSIONS: When dalteparin was added as an adjuvant to streptokinase and aspirin, there were tendencies for less ECG monitoring evidence of recurrent ischemia and better patency at 24 h, warranting further study.

Adult↗

PubMed1999

Cytokine and fibrinogen response in patients undergoing open abdominal aortic aneurysm surgery.

OBJECTIVES: To assess whether open abdominal aortic aneurysm (AAA) surgery influences cytokines and fibrinogen. METHODS: Twenty-three consecutive patients operated on for AAA were compared to 11 operated controls and 20 age-matched controls. Cubital blood was sampled pre-, intra- and postoperatively and femoral blood also sampled intraoperatively. RESULTS: Preoperatively, interleukin (Il)-6 was elevated in AAA patients. During aortic clamping, Il-6, Il-10 and monocyte chemoattractant protein-1 (MCP-1) increased significantly (p < 0.001, p < 0.01 and p < 0.05 respectively) while soluble interleukin-2 receptor (sIl-2R) and fibrinogen decreased significantly (p < 0.001 for both). After aortic declamping, Il-6, Il-10 and MCP-1 had further significant increases compared with levels during aortic clamping while sIl-2R had a further non-significant and fibrinogen a significant decrease (p < 0.05 in cubital and p < 0.001 in femoral blood). One week postoperatively Il-6, Il-10 and MCP-1 had all decreased but were still significantly elevated compared with baseline values while sIl-2R and fibrinogen showed an increase in comparison with baseline (p < 0.001 for both). Intraoperative levels of Il-6 and Il-10 showed a significant co-variation with the magnitude of operative trauma. CONCLUSIONS: These data indicate that open AAA surgery induces a profound inflammatory and coagulative response which persists at one week postoperatively.

Aged↗

PubMed1999

Ischaemia and reperfusion during open abdominal aortic aneurysm surgery induce extensive thrombin generation and activity.

OBJECTIVES: does open surgery for abdominal aortic aneurysm (AAA) influence coagulation? METHODS: in 23 patients operated on for AAA, cubital blood was sampled pre-, intra- and postoperatively. Femoral blood was also sampled intraoperatively. RESULTS: preoperatively, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT) and soluble fibrin (SF) were elevated in AAA patients. During aortic clamping all parameters increased significantly in cubital blood (p<0.01) as well as in femoral blood (p<0.001) and after aortic declamping F1+2 and TAT increased further. F1+2, TAT and SF were significantly higher in femoral than cubital blood. Postoperatively F1+2 and TAT returned to preoperative values, while SF still had a significantly higher level than preoperatively (p<0.001). Blood loss showed co-variation with F1+2 increase in femoral blood after aortic declamping (p<0.05). CONCLUSIONS: these data indicate that the coagulation system was strongly activated by the occurrence of an AAA. During AAA surgery a further extensive activation was seen. The activity was still high, but on decline, one week postoperatively. Ischaemia and reperfusion of the lower part of the body were the major stimuli for thrombin generation and activity.

Adult↗

PubMed1999

The effect of a low molecular mass thrombin inhibitor, inogatran, and heparin on thrombin generation and fibrin turnover in patients with unstable coronary artery disease.

AIM: This study evaluated a novel specific thrombin inhibitor, inogatran, in comparison with unfractionated heparin, with regard to markers for coagulation activity in patients with unstable coronary artery disease. METHODS AND RESULTS: In the Thrombin Inhibition In Myocardial Ischaemia (TRIM) study patients were randomized to one of three different doses of inogatran or to unfractionated heparin, given intravenously over 72 h. In a subpopulation of 320 patients, markers for coagulation activity were measured at baseline, during and after the study infusion. Prothrombin fragment 1 + 2, indicating thrombin generation, decreased in the low, medium and high dose inogatran groups and in the heparin group during the first 6 h of treatment by 12%, 15%, 21% and 26%, respectively. From 6 h to 72 h after the start of infusion the levels changed by -7%, -6%, -4% and +34%, respectively. The increase in the heparin group continued after the infusion was stopped. Thrombin-antithrombin complex, also indicating thrombin generation, decreased by 0%, 2%, 18% and 22%, respectively, during the first 6 h of treatment. During the same period soluble fibrin, an intermediate in fibrin formation, increased both in the low and medium inogatran group by 9%, while a decrease by 4% and 18%, respectively, was seen in the high dose inogatran group and in the heparin group. Fibrin dissolution, as measured by fibrin D-dimer, decreased during the first 24 h of treatment by 20%, 18%, 18% and 20%, respectively. The first 24 h after discontinuation of infusion, fibrin D-dimer increased by 6%, 23%, 25% and 44%, respectively. After 72 h, at the end of infusion, patients treated with inogatran, to a larger extent than those given heparin, had suffered from death, myocardial infarction or refractory angina pectoris. After 7 days this trend was less marked. CONCLUSION: The more pronounced decrease in thrombin generation and fibrin turnover during the first 6 h of infusion, and the later increase in thrombin generation and fibrin turnover, in the heparin group, as compared to the inogatran groups, may be related to the lower clinical event rate during infusion with heparin compared with inogatran and the recurrence of ischaemic events, early after cessation of heparin infusion.

Aged↗

PubMed1999

Activated partial thromboplastin time and clinical outcome after thrombin inhibition in unstable coronary artery disease.

UNLABELLED: Aims Direct thrombin inhibitors have failed to prove superiority over unfractionated heparin in several clinical trials of unstable coronary artery disease. We have investigated the relationship between activated partial thromboplastin time levels and adverse clinical events, i.e. death, myocardial (re-)infarction or refractory angina. Methods and Results One thousand two hundred and nine patients with unstable coronary artery disease were randomized to 72 h infusion with inogatran, a low molecular mass direct thrombin inhibitor, or unfractionated heparin. During 30 days follow-up there was no significant difference between inogatran and unfractionated heparin treatment as regards clinical outcome. 11.6% of the 464 inogatran treated patients with activated partial thromboplastin time above the median at 6 h (44 s) had a clinical event in 7 days, and 6.6% of the 423 patients with activated partial thromboplastin time below the median (P=0.01). After 30 days the event rate was still 41% higher in the inogatran patients with activated partial thromboplastin time above the median (P=0.06). Activated partial thromboplastin time in quartiles indicated a direct relationship between higher activated partial thromboplastin time and worse outcome. In contrast, during heparin infusion there was a trend for improved clinical outcome with activated partial thromboplastin time above the median, but this benefit was lost after cessation of treatment. CONCLUSIONS: Higher activated partial thromboplastin time levels during inogatran treatment are related to increased risk of death, myocardial infarction or refractory angina. This might, at least in part, be explained by differences in anticoagulant mechanisms between direct thrombin inhibitors and heparin, and further emphasizes the poorly defined optimal activated partial thromboplastin time range during treatment with direct thrombin inhibitors in unstable coronary artery disease.

Adult↗

PubMed1999

Induction of differentiation in U-937 and NB4 cells is associated with inhibition of tissue factor production.

Tissue factor (TF) production is under strict control in mature monocytic cells. However, constitutive expression of TF can be found in myelomonocytic cells and in haematopoietic cells arrested at an early stage of differentiation. In this paper we show that TF expression is down-regulated during the monocyte/granulocyte differentiation process, using the human monoblastic U-937 and the acute promyelocytic leukaemia NB4 cell lines as models. Expression of TF mRNA, protein and procoagulant activity (PCA) was constitutively high in untreated cells. Exposure of U-937 cells to 1alpha,25-dihydroxycholecalciferol (VitD3) and all-trans retinoic acid (ATRA) resulted in down-regulation of TF expression and PCA. In NB4 cells induction by ATRA, but not VitD3, resulted in the down-regulation of TF expression and PCA. Consistent with this, induction of terminal differentiation, as confirmed by the expression of differentiation associated antigens and cell cycle arrest, was inversely correlated to TF expression in U-937 and NB4 cells. Moreover, terminally differentiated U-937 cells retained the capacity to respond to inflammatory mediators, i.e. lipopolysaccharide and interferon-gamma, by a rapid increase in TF expression. In conclusion, we show that not only ATRA but also VitD3 is a potent suppressor of monocytic TF expression and thus might have potential clinical use for the treatment of coagulopathies.

Cell Cycle↗

PubMed1998

IL-10 inhibits LPS-induced human monocyte tissue factor expression in whole blood.

Interleukin 4 (IL-4), IL-10 and IL-13 are all known to modulate several proinflammatory functions in human monocytes. They have also previously been shown to down-regulate lipopolysaccharide (LPS)-induced tissue factor (TF) expression in isolated cultured monocytes. In this study we investigated the effect of these three cytokines on the induction of monocytic TF in a whole blood environment at three levels: mRNA quantitation, surface antigen expression and procoagulant activity. We showed that IL-10 attenuated LPS-induced monocyte TF expression and activity in whole blood in a concentration-dependent manner, both when added to the blood prior to LPS and, although to a lesser extent, when added up to 1 h subsequent to LPS challenge. Maximum inhibition occurred at 5 ng/ml of IL-10 when the cytokine was added before LPS. IL-4 and IL-13, however, did not exhibit any inhibitory effect in the whole blood environment, contrary to the reported findings in cell culture experiments. Our results confirm the potential of IL-10 as an anti-inflammatory, TF-preventing drug, whereas the effects of IL-4 and IL-13 on monocytes in whole blood seem more complex, and require further investigation.

Down-Regulation↗

PubMed1998

Increased fibrinogen levels are associated with persistent Chlamydia pneumoniae infection in unstable coronary artery disease.

AIM: Increased levels of acute phase proteins, e.g., fibrinogen, are related to a poor outcome in unstable coronary artery disease, but the cause of inflammation is unknown. We therefore investigated the prevalence of persistent Chlamydia pneumoniae infection, and its relationship to inflammation in this condition. METHODS AND RESULTS: In 256 patients participating in the FRISC trial, evaluating the effects of dalteparin (a low molecular weight heparin) in unstable angina or non-Q wave myocardial infarction, Chlamydia pneumoniae IgA antibody titres and levels of fibrinogen, C-reactive protein and troponin T were determined at inclusion. Increased C. pneumoniae IgA antibody titres were significantly more common in the patients (36%) than in a reference population of similar age (19%); P < 0.001. Raised titres were associated with male gender, increasing age, smoking, and elevated concentrations of fibrinogen, C-reactive protein and troponin T. The association between persistent C. pneumoniae infection and increased fibrinogen levels was independent of other risk factors evaluated in multivariate analysis (P = 0.009). CONCLUSION: Persistent C. pneumoniae infection is common in unstable coronary artery disease. The independent association between increased C. pneumoniae IgA antibody titres and fibrinogen levels indicates that chronic infection could be of importance for disease activity.

Angina, Unstable↗