Depression and inflammation in patients with coronary heart disease: findings from the Heart and Soul Study.

BACKGROUND: Depression and inflammation independently predict adverse cardiovascular outcomes in patients with coronary heart disease (CHD). Depression has been associated with elevated levels of inflammation in otherwise healthy patients without known CHD. However, studies investigating the link between depression and inflammation in patients with established CHD have produced inconclusive results. METHODS: We sought to examine the association of major depression with inflammation in 984 outpatients with established CHD from the Heart and Soul Study. We assessed current major depression with the Computerized Diagnostic Interview Schedule and collected venous blood samples for measurement of five inflammatory biomarkers (white blood cell count, CD40 ligand, C-reactive protein [CRP], fibrinogen, and interleukin-6 [IL-6]). We used multivariate analysis of variance to examine the association of current depression with inflammatory markers, adjusted for potential confounding variables. RESULTS: Of the 984 participants, 217 (22%) had current major depression. Depression was not associated with increased levels of any inflammatory marker. Contrary to our hypothesis, depression was associated with lower levels of CRP (p = .09), fibrinogen (p = .006), and IL-6 (p = .007) in both unadjusted and adjusted models. CONCLUSIONS: We found no evidence that current depression is associated with greater inflammation in outpatients with CHD. Inflammation is unlikely to explain the adverse cardiovascular outcomes associated with depression in patients with established CHD.     

Are admission plasma fibrinogen levels useful in the characterization of risk groups after myocardial infarction treated with fibrinolysis?

The aim of our study was to prove or disprove the independent prognostic importance of fibrinogen after myocardial infarction. Plasma fibrinogen levels were determined on admission in 135 patients with an acute myocardial infarction and symptoms up to 4 h (mean: 1.8 h) immediately before starting fibrinolytic treatment with 1.5 mio U. streptokinase i.v. All patients were free from other diseases which are known to cause elevated fibrinogen levels. Coronary angiography was carried out in 87%. During a mean follow-up period of 26.2 months 31 coronary events could be observed in 26 patients: 18 reinfarctions, 6 cases of sudden death, and 7 coronary artery bypass graft surgeries because of new symptoms. While plasma fibrinogen levels were higher in smokers than in non-smokers (3.30 vs 2.94 g/l p = 0.011) and correlated with the number of involved coronary arteries (p = 0.08), values were similar in patients with and without coronary events during follow-up (3.07 vs 3.16 g/l, p = 0.70). This applied as well to univariate analysis as to multivariate Cox's regression model. We conclude that plasma fibrinogen levels determined very early in patients with acute myocardial infarction do correlate with other important prognostic variables, but have no independent prognostic importance.     

Variability of fibrinogen measurements in post-myocardial infarction patients. Results from the AIRGENE study center Augsburg

Elevated fibrinogen levels are strongly and consistently associated with incident coronary heart disease (CHD). A possible causal contribution of fibrinogen in the pathway leading to atherothrombotic cardiovascular disease complications has been suggested. However, for implementation in clinical practice, data on validity and reliability, which are still scarce, are needed that are still scarce, especially in subjects with a history of CHD. For the present study, levels of plasma fibrinogen were measured in 200 post-myocardial infarction (post-MI) patients aged 39-76 years, with approximately six blood samples collected at monthly intervals between May 2003 and March 2004, giving a total of 1,144 samples. Inter-individual variability (between-subject variance component, VCb and coefficient of variation, CVb), intra-individual and analytical variability (VCw+a and CVw+a), intraclass correlation coefficient (ICC) and the number of measurements required for an ICC of 0.75 were estimated to assess the reliability of serial fibrinogen measurements. Mean fibrinogen concentration of all subjects over all samples was 3.34 g/l (standard deviation 0.67). Between-subject variation for fibrinogen was VCb = 0.34 (CVb'=17.5%) whereas within-subject and analytical variation was estimated as VCw+a = 0.14 (CVw+a=11.0%). The variation was mainly explained by between-subject variability, shown by the proportion of total variance of 71.3%. Two different measurements were required to reach sufficient reliability, if subjects with extreme values were not excluded. The present study indicates a fairly good reproducibility of serial individual fibrinogen measurements in post-MI subjects.     

Heart rate variability and markers of inflammation and coagulation in depressed patients with coronary heart disease

BACKGROUND: Depression is associated with an increased risk for cardiac morbidity and mortality in patients with coronary heart disease (CHD). Cardiac autonomic nervous system (ANS) dysregulation, proinflammatory processes, and procoagulant processes have been suggested as possible explanations. METHODS: Heart rate variability (HRV), an indicator of cardiac autonomic regulation, and markers of inflammation [C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha)] and coagulation (fibrinogen) were assessed in 44 depressed patients with CHD. RESULTS: Moderate, negative correlations were found between fibrinogen and four measures of HRV. IL-6 also negatively correlated with one measure of HRV (total power) and was marginally related to two others (very low frequency and low frequency power). Neither CRP nor TNF-alpha was significantly related to any measure of HRV. CONCLUSIONS: The finding that fibrinogen and IL-6 are moderately related to HRV suggests a link between these factors in depressed CHD patients. The relationship between ANS function and inflammatory and coagulant processes should be investigated in larger mechanistic studies of depression and cardiac morbidity and mortality.     

The factor II G20210A and factor V G1691A gene transitions and coronary heart disease

BACKGROUND: G to A transitions at nucleotide position 20210 of the factor II (Fll) gene and at 1691 of the factor V (FV) gene have been shown to be associated with an increased risk of venous thrombosis. Since it is still unclear whether both gene variations are also related to an increased risk of coronary heart disease (CHD), we studied the relation of both gene variations to coronary artery disease (CAD) and myocardial infarction (MI) in a sample of 2210 male individuals whose coronary anatomy were defined by coronary angiography. RESULTS: In the total sample, the FII G20210A gene variation was not associated with the presence or the extent of CAD, the latter defined either by the degree of vessel disease or by a CHD score according to Gensini. However, individuals with unfavourable lipid profiles showed pronounced differences in CHD scores between GA heterozygotes and GG homozygotes: this observation applied in particular to younger patients (<62 years; mean age of total sample) who simultaneously had low apoAI/apoB ratios (< 1.19, mean value) and high Lp(a) plasma levels (>28 mg/dl; mean value). In addition, in subjects without acetylsalicylic acid treatment GA heterozygotes had clearly higher CHD scores than AA genotypes. Further restriction to smokers, to subjects with high fibrinogen plasma levels (>3.47 g/l; mean value) or to patients with high glucose concentrations (>112 mg/dl; mean value) tended to increase the difference in CHD score between FII G20210A genotypes. An association of the FII G20210A gene variation with non-fatal MI was not observed. In the total sample and in high and low risk subpopulations, an association of the FV G1691A gene variation was not detected neither with presence and extent of CAD or with nonfatal MI. CONCLUSION: The importance of the factor II G20210A gene variation for CHD may be restricted to individuals with major cardiovascular risk factors. In addition, the present study did not strengthen the hypothesis of the factor V G 1691 A transition as a risk factor of coronary heart disease neither in the total sample nor in subgroups of individuals who were at high or low risk of CHD.     

Comparison of plasma concentrations of fibrinogen in patients with ischemic stroke due to large vessel disease and small vessel disease

BACKGROUND AND PURPOSE: Hyperfibrinogenemia is a known cardiovascular risk factor, but its role as a risk factor for ischemic stroke remains controversial. Most studies on this topic did not consider the different etiologies of ischemic stroke. We designed this study to compare plasma fibrinogen concentrations in patients with acute ischemic stroke due to large vessel disease (LVD) or small vessel disease (SVD). MATERIAL AND METHODS: We studied 203 patients with acute ischemic stroke, including 107 patients with SVD and 96 subjects with LVD. Etiology of stroke was established according to the TOAST criteria, using computed tomography, ultrasonography of the carotid and vertebral arteries as well as echocardiography. The plasma concentration of fibrinogen was measured in venous blood samples drawn within 48 hours from the onset of stroke. RESULTS: Patients with LVD were more likely to be men and more likely to have ischemic heart disease. The median plasma concentration of fibrinogen was higher in patients with LVD [3.7 g/l (2.9-4.9 g/l)] than in patients with SVD [3.2 g/l (2.6-3.8 g/l); p=0.0001]. Hyperfibrinogenemia (i.e. plasma fibrinogen concentration >3.5 g/l) occurred more frequently in patients with LVD (54.2%) than in patients with SVD (35.5%; p=0.008). CONCLUSIONS: Patients with ischemic stroke due to LVD have a higher concentration of plasma fibrinogen than patients with SVD, they also present more frequently with hyperfibrinogenemia. Further studies of risk factors for stroke should take into account various etiologies of ischemic stroke.     

Haemostatic, endothelial and lipoprotein parameters and blood pressure levels in women with a history of preeclampsia

To determine whether perturbations of haemostatic function and lipoprotein metabolism prevail long after preeclampsia and increase the risk of future coronary heart disease (CHD), we conducted a follow-up study in women with (cases, n = 25) or without (controls, n = 24) a history of preeclampsia. Blood samples were taken in the follicular and in the luteal phases of a menstrual cycle. Levels of blood pressure (BP) and proteinuria measured during the index pregnancy were included in the evaluation. Compared to control women who had undergone a normal pregnancy, the formerly preeclamptic patients had higher systolic (p <0.01) and diastolic (p <0.05) BPs and increased plasma levels of von Willebrand factor (vWF), fibrinogen, cholesterol, triglycerides and very low density lipoprotein (VLDL) (all p <0.05). The lipid, vWF, and fibrinogen levels were positively related to the degree of BP elevation but not to the degree of proteinuria during the index pregnancy. Except for the increase in vWF level, all biochemical perturbations were only present in the luteal but not in the follicular phase samples. In conclusion, persistent endothelial dysfunction with ensuing dysregulation of blood pressure, haemostatic perturbation and dyslipoproteinemia after preeclampsia may indicate a proneness to future CHD.     

Increased tumor necrosis factor-alpha concentrations with interleukin-4 concentrations in exacerbations of schizophrenia

Several studies have indicated that cytokines may be involved in the pathophysiology of schizophrenia. Previous studies, however, have yielded contradictory results; in this study we assess the plasma levels of both T-helper-1 (Th1) and T-helper-2 (Th2) cytokines in patients with acute exacerbations of schizophrenia. Plasma concentrations of interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha) and soluble receptor of interleukin-6 (sIL-6R) were measured with high sensitivity, enzyme-linked immunosorbent assays (ELISA) in patients with acute exacerbations of schizophrenia as compared with healthy controls. Patients with an acute exacerbation of schizophrenia had significantly increased production of TNF-alpha and significantly reduced production of IL-4 as compared with healthy subjects. No significant difference was observed in IL-6, sIL-6R, IL-8 and IL-10. Acute exacerbations of schizophrenia are associated with increased TNF-alpha concentrations (Th1) with concomitantly reduced concentrations of IL-4 (Th2) and a resulting increased TNF-alpha/IL-4 ratio.     

Fibrinogen and the amount of leukoaraiosis in patients with symptomatic small-vessel disease

We investigated whether there is a direct correlation between plasma fibrinogen levels and the amount of leukoaraiosis (LA) in patients with symptomatic small-vessel disease. The study included 28 patients: 12 with a first-ever lacunar infarction (LI) and 16 with Binswanger's disease (BD). The mean age was 71 years (SD 8.6), and 21 were men. For each patient, we recorded demographic data, vascular risk factors and the results of blood chemistry analysis including fibrinogen (g/l), hematocrit (decimal fraction) and total serum proteins (g/l). A cerebral MR scan was performed in each patient and an LA score was obtained by an investigator blind to clinical data, using a semiquantified scale in six areas of each cerebral hemisphere (0-4 points in each area, total scoring range 0-48 points). RESULTS: The mean (SD) for the LA score was 18.9 (10.7) and for plasma fibrinogen 3.97 (1.1). Pearson's and Spearman's correlation coefficients between fibrinogen and LA score were 0.43 (p = 0.02) and 0.49 (p = 0.007), respectively. Multiple-regression analysis between groups (LI or BD) and fibrinogen versus LA score showed the strongest association for the BD group (p = 0.014) and a direct relation with fibrinogen (p = 0.018). No statistically significant association was found between LA score and age, sex, any vascular risk factor, hematocrit or total serum protein. CONCLUSION: There is a significant correlation between plasma fibrinogen levels and the amount of LA in patients with symptomatic cerebral small-vessel disease. This result suggests that fibrinogen may be involved in the pathophysiology of LA in these patients.     

Relationship Between Fibrinogen Protein and Fibrinogen Function in Postmyocardial Infarction Patients

The present study investigates the association between increases in the concentration and function of plasma fibrinogen in two groups of patients with chronic ischemic heart disease (11 with recurrent ischemic events and 19 free of these episodes) and in 34 healthy controls. The fibrinogen function index (fibrinogen function per unit of fibrinogen protein) (FgFI) was used as a measure of the fibrinogen clotting potential. The prothrombin fragment 1+2 (F1+2) and thrombin–antithrombin (TAT) were used as procoagulant markers. Plasma sialic acid (SA) was also evaluated as an inflammatory marker. No differences were found between FgFI (1.06±0.13 vs. 1.02±0.13), F1+2 (1.2±0.5 vs. 1.1±0.4 nmol/l) and TAT (2.5±1.3 vs. 2.5±0.7 μg/ml) in postinfarction patients without recurrent coronary ischemic events and the control group. However, postinfarction patients who suffered recurrent coronary ischemic events had significantly higher FgFI than patients without these symptoms (1.19±0.09 vs. 1.06±0.13), P<.01) and than the control group (1.19±0.09 vs. 1.02±0.13, P<.001). Moreover, the F1+2 (1.4±0.5 vs. 1.1±0.4 nmol/l, P<.05) and TAT (3.6±3.3 vs. 2.5±0.7 μg/ml, P<.05) were significantly higher in patients who suffered recurrent coronary ischemic events than in the control group. However, F1+2 and TAT were not different between patients with and without these symptoms. The fibrinogen protein (Fg-protein) concentration and high molecular weight fibrinogen (HMW-Fg) levels were significantly higher in both postinfarction patient groups than in the control group and in postinfarction patients with recurrent coronary ischemic events than in postinfarction patients without these symptoms. The plasma SA levels were significantly increased in postinfarction patients with and without recurrent coronary ischemia as compared with the control group. A positive correlation was found between fibrinogen and SA levels (r=.5, P<.01). In conclusion, our study indicates that the procoagulant factors, among which we include fibrinogen, F1+2 and TAT play a very active role in recurrent ischemic events in postmyocardial infarction patients. High plasma concentrations of both fibrinogen and SA suggests that fibrinogen becomes elevated as a consequence of inflammatory processes. The FgFI as an indicator of clotting potential of fibrinogen appears to be associated with ischemic events in chronic coronary artery disease.     

Self-rated health and vital exhaustion, but not depression, is related to inflammation in women with coronary heart disease

Poor subjective well-being has been associated with increased coronary heart disease (CHD) morbidity and mortality in population-based studies and with adverse outcomes in existing CHD. Little is known about the mechanisms responsible for this association, but immune activity appears to be a potential pathway. Despite the growing evidence linking immune activity to subjective feelings, very few studies have examined patients with CHD, and the results are conflicting. We examined consecutive women patients hospitalized for acute myocardial infarction, and/or underwent percutaneous transluminal coronary angioplasty or coronary artery bypass grafting. We assessed depression, vital exhaustion, and self-rated health by questionnaires. Circulating levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and interleukin-1 receptor antagonist (IL-1ra) concentrations were determined. After controlling for potential confounding factors there was a significant positive correlation between IL-6 levels and vital exhaustion and poor self-rated health. The association between hsCRP and vital exhaustion and self-rated health was borderline significant. In contrast, the correlations between psychological factors and IL-1ra levels were weak and non-significant, as were the correlations between inflammatory markers and depression. Similar relationships between the inflammatory markers and the measures of psychological well-being were obtained when the latter ones were categorized into tertiles. In conclusion, inflammatory activity, assessed by IL-6 and hsCRP levels, was associated with vital exhaustion and self-rated health in CHD women. These findings may provide further evidence for a possible psychoneuroimmune link between subjective well-being and CHD. Our observations also raise the possibility that a cytokine-induced sickness response in CHD may be better represented by constructs of vital exhaustion and self-rated health than of depression.     

Effects of omega-3 polyunsaturated fatty acids on plasma indices of thrombogenesis and inflammation in patients post-myocardial infarction

OBJECTIVE: To determine the effects of n-3 PUFAs supplementation on plasma indices of coagulation (fibrinogen), fibrin D-Dimer (an index of thrombogenesis and fibrin turnover), endothelial damage/dysfunction (von Willebrand factor (vWf)), platelet activation (soluble P-selectin (sP-sel)) and inflammation (interleukin-6, IL-6) in patients following acute myocardial infarction. METHODS: Open-labelled randomised controlled trial. Seventy-seven post-myocardial infarction (MI) patients stabilized on standard secondary prevention therapy were randomised either to 3 months' treatment with Omacor 1 g/day (n=37) or 'usual care' control (n=40). Plasma levels of fibrinogen, D-Dimer, vWf, sP-sel, IL-6 and plasma viscosity at baseline and after 3 months were determined. RESULTS: At baseline, there were no significant differences between the groups in all research indices, except vWf levels were higher in patients allocated to Omacor supplementation. After 3 months, there were no significant changes in the levels of any research indices in either the Omacor supplemented or the 'usual care' control patients when compared to baseline. Patients who received Omacor experienced a fall in total cholesterol (p=0.019), total/HDL-cholesterol ratio (p=0.009) and LDL-cholesterol (p=0.023). However, the relative changes in plasma lipids and lipoproteins did not differ between the two groups. CONCLUSIONS: Three-month supplementation of Omacor at 1 g per day in post-MI patients is not associated with an improvement in the levels of peripheral indices of coagulation potential, endothelial function, platelet reactivity and inflammation.     

Blood rheology, cardiovascular risk factors, and cardiovascular disease: the West of Scotland Coronary Prevention Study

The West of Scotland Coronary Prevention Study (WOSCOPS) showed that pravastatin reduced the risk of coronary heart disease (CHD) events in 6,595 middle-aged hypercholesterolaemic men aged 45-64 years without prior myocardial infarction followed for an average of 4.9 years. We hypothesised prospectively (a) that baseline levels of haemorheological variables were related to baseline and incident CHD and to mortality; and (b) that reduction in lipoproteins by pravastatin would lower plasma and blood viscosity, a potential contributory mechanism to CHD events. We therefore studied plasma and blood viscosity, fibrinogen, haematocrit, and blood cell counts at baseline and 1 year. At baseline, plasma and blood viscosity were related to risk factors, CHD measures, and claudication. On univariate analysis, baseline levels of all rheological variables (except platelet count) were related to incident CHD; CHD mortality; and total mortality. On multivariate analysis including baseline CHD and risk factors, plasma and blood viscosity, haematocrit and white cell count each remained significantly associated with incident CHD; while fibrinogen remained an independent predictor of mortality (all p < 0.03). After one year, lipoprotein reduction by pravastatin was associated with significant reductions (about one quarter of a standard deviation) in plasma viscosity (mean difference 0.02 mPa.s, p <0.001) and in blood viscosity (mean difference 0.06 mPa.s, p<0.001), but was not associated with significant changes in other rheological variables. We therefore suggest that pravastatin therapy, which reduces elevated lipoproteins in hypercholesterolaemic men, may lower risks of CHD and mortality partly by lowering plasma and blood viscosity. Further studies are required to test this hypothesis.     

The 4G4G genotype of the plasminogen activator inhibitor 4G/5G gene polymorphism is associated with coronary atherosclerosis in patients at high risk for this disease.

BACKGROUND: Disturbances in fibrinolytic activity, such as increase in plasminogen activator inhibitor (PAI) activity, have been linked with an increased risk for coronary artery disease (CAD) and myocardial infarction (MI). Since 4G4G homozygotes of an insertion/deletion (4G/5G) gene variation in the promoter of PAI-I have been shown to have increased levels of PAI-I, we analysed the relation of this gene polymorphism to CAD and MI in a population of 2565 participants who underwent coronary angiography for diagnostic purposes. RESULTS: In the total sample, the PAI-I 4G/4G genotype was associated with the presence, but not with the extent of CAD. However, in a subgroup of former and present smokers (n = 1782) or of individuals with a BMI above the mean value of 26.9 kg x m(-2) (n = 1269), the PAI-I 4G4G genotype was not only associated with the presence, but also with the extent of CAD, defined either by the number of diseased vessels or by the CHD score according to Gensini. This observation also applied to other high-risk groups of individuals with high BMI and hypertension (n = 869), of subjects with high fibrinogen plasma levels (>3.53 g x l(-1), mean value) and hypertension (n = 599) and of former and present smokers with high fibrinogen and hypertension (n = 452). An association of the gene variation with MI was not detected. CONCLUSIONS: The present data indicate that the 4G/4G genotype of the PAI-I gene polymorphism is an independent risk factor for coronary artery disease and that the additional presence of major cardiovascular risk factors accelerates the risk for this disease.     

A comparison of ten-year cardiac risk estimates in schizophrenia patients from the CATIE study and matched controls

OBJECTIVE: Standardized mortality rates are elevated in schizophrenia compared to the general population. The incidence of coronary heart disease (CHD) and the relative contribution of CHD to increased mortality in schizophrenia patients are not clear, despite recent concerns about metabolic complications of certain atypical antipsychotics. METHOD: Ten-year risk for CHD was calculated for 689 subjects who participated in the Clinical Trials of Antipsychotic Treatment Effectiveness (CATIE) Schizophrenia Trial at baseline using the Framingham CHD risk function and were compared with age-, race- and gender-matched controls from the National Health and Nutrition Examination Survey (NHANES) III. RESULTS: Ten-year CHD risk was significantly elevated in male (9.4% vs. 7.0%) and female (6.3% vs. 4.2%) schizophrenia patients compared to controls (p = 0.0001). Schizophrenia patients had significantly higher rates of smoking (68% vs. 35%), diabetes (13% vs. 3%), and hypertension (27% vs. 17%) and lower HDL cholesterol levels (43.7 vs. 49.3 mg/dl) compared to controls (p < 0.001). Only total cholesterol levels did not differ between groups. Ten-year CHD risk remained significantly elevated in schizophrenia patients after controlling for body mass index (p = 0.0001). CONCLUSIONS: These results are consistent with recent evidence of increased cardiac mortality in schizophrenia patients. While the impact of cigarette smoking is clear, the relative contributions to cardiac risk of specific antipsychotic agents, diet, exercise, and quality of medical care remain to be clarified.     

血清C-反应蛋白、白细胞介素-6水平与老年冠心病患者焦虑情绪的关系

目的:探讨血清炎性因子C-反应蛋白(CRP)、白细胞介素(IL-6)水平与老年冠心病患者伴焦虑情绪的相关性。方法:收集老年冠心病患者64例,进行焦虑自评量表(SAS)评分,根据评分结果将其分为冠心病不伴焦虑情绪组、冠心病伴焦虑情绪组,测定所有研究对象的血清CRP、IL-6水平。结果:64例患者中男性36例(56.25%),女性28例(43.75%),伴有焦虑情绪35例(47.45%),其中男性有15例(42.9%),女性20例(57.1%),男女冠心病患者伴焦虑情绪差异有统计学意义(P<0.05)。伴有焦虑情绪的血清CRP、IL-6水平与不伴有焦虑情绪的差异有统计学意义(P<0.05)。血清炎症因子水平CRP、IL-6与焦虑程度呈正相关。结论:伴有焦虑情绪的老年冠心病患者血清CRP、IL-6水平升高,且与焦虑程度呈正相关。     

Interleukin 6 plasma levels predict with high sensitivity and specificity coronary stenosis detected by coronary angiography

In recent years new biomarkers able to measure the coronary atherosclerotic burden have been investigated. The aim of the present study was: i) to measure plasma levels of four biomarkers: C reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin 6 (IL-6), 8-isosprostane (8-ISO), in a series of patients undergoing coronary angiography; ii) to assess the power of the biomarkers to predict critical coronary stenosis detected by angiography. The study population consisted of a group of 438 subjects undergoing coronary angiography; 160 patients with 0, 1, 2, or 3 critical vessels were selected, and biomarkers plasma levels were measured in plasma samples obtained before the procedure. The most predictive biomarker was then assayed in 120 patients with critical stenosis and 120 unmatched patients without stenosis. CRP, sICAM-1, IL-6 and 8-ISO plasma levels increased with the number of diseased vessels. All biomarkers were good predictors of critical stenosis (receiver-operator-curve [ROC] areas; CRP = 0.880, IL-6 = 0.936, sICAM-1 = 0.907, 8-ISO = 0.873). IL-6 was confirmed in an expanded sample of 240 subjects to be the best predictor with a ROC area = 0.959. With a threshold of 3.6 ng/l, a 100% sensitivity (120/120) and a 90% specificity (108/120) was observed. In conclusion, IL-6, sICAM-1, CRP and 8-ISO are predictive of CAD. IL-6 predicts critical coronary stenosis with the highest sensitivity and specificity.     

Complement C3 and C-reactive protein levels in patients with stable coronary artery disease

The aim of this study was to determine whether complement C3 is an indicator of coronary artery disease (CAD). We measured plasma C3 and CRP levels in 278 patients undergoing coronary angiography for typical symptoms of CAD and 269 healthy age and sex matched controls. C3 levels were significantly higher in patients compared with controls (1.15 g/l and 0.92 g/l respectively; p<0.001). In the patient group, C3 levels correlated with BMI, fasting glucose, HbA1c, fibrinogen, CRP and HDL in both men and women. CRP levels were also higher in patients compared with controls (1.14 mg/l and 0.86 mg/l respectively; p=0.005) and correlated with markers of the metabolic syndrome. In a logistic regression model including C3, smoking, hypertension, cholesterol and diabetes, C3 was independently associated with CAD with an odds ratio of 3.20 for a 1 SD increase in C3 levels. In contrast, CRP was not independently associated with CAD in a similar regression analysis. In conclusion, both C3 and CRP plasma levels are elevated in patients with symptoms of CAD. However, C3 seems to be a better indicator of CAD than CRP in this study, suggesting that C3 could be an additional marker for risk stratification in atherosclerosis.     

Coagulation factor VII in middle-aged women with and without coronary heart disease

Epidemiological studies of coagulation factor VII as a risk factor for coronary heart disease (CHD), mainly conducted in men, have shown discrepant results. We examined the associations of coagulation factor VII antigen (VIIag) and activated factor VII (VIIa) with manifest CHD in a community-based case-control study of women aged < or =65 years. Mean plasma concentrations of VIIag and VIIa in patients and controls were 443 +/- 10(8) and 418 +/- 89 ng/L (p <0.01) and 5.26 +/- 2.21 and 4.90 +/- 1.65 ng/L (NS), respectively. The odds ratio (OR) for CHD for the highest versus the lowest quartile of VIIag was 1.75 (95% CI, 1.05 to 2.92). The adjusted OR was 0.76 (95% CI, 0.28-1.98) after controlling for other cardiovascular risk factors. The corresponding ORs for VIIa were non-significant. In conclusion, the plasma concentration of VIIa was not significantly increased in a large group of women with precocious CHD, and VIIag levels, although elevated, were not independently associated with manifest disease.     

Major depression, heart rate, and plasma norepinephrine in patients with coronary heart disease.

BACKGROUND: Although it is now well established that psychiatric depression is associated with adverse outcomes in patients with coronary heart disease (CHD), the mechanism underlying this association is unclear. Elevated heart rate (HR) and plasma norepinephrine (NE), possibly reflecting altered autonomic nervous system activity, have been documented in medically well depressed psychiatric patients, and this pattern is associated with increased risk for cardiac events in patients with CHD. The purpose of this study was to determine whether autonomic nervous system activity is altered in depressed CHD patients. METHODS: HR, plasma NE, and blood pressure (BP) were measured in 50 depressed and 39 medically comparable nondepressed CHD patients at rest and during orthostatic challenge. RESULTS: Resting HR (p = .005), and the change from resting HR at 2, 5, and 10 min after standing (p = .02, .004, and .02, respectively), were significantly higher in the depressed than in the nondepressed patients. There were no differences between the groups in NE or in BP at rest, or in standing minus resting change scores at any time during orthostatic challenge (p < .05). CONCLUSIONS: Depression is associated with altered autonomic activity in patients with CHD, as reflected by elevated resting HR and an exaggerated HR response to orthostatic challenge. Previously reported differences in NE levels between depressed and nondepressed patients were not replicated.