Relation of levels of hemostatic factors and inflammatory markers to the ankle brachial index

Associations between hemostatic and inflammatory markers relative to the ankle brachial index (ABI), an indicator of the presence and severity of peripheral arterial disease (PAD), are not fully understood. We studied relations among selected hemostatic factors, inflammatory markers, and the ankle brachial index (ABI) in patients with and without peripheral arterial disease (PAD). Participants were 370 men and women with ABI <0.90 and 231 patients with ABI 0.90 to 1.50 identified from noninvasive vascular laboratories and general medicine practice. Blood factors were D-dimer, prothrombin 1.2, tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor-1 (PAI-1), and inflammatory markers (high-sensitivity C-reactive protein [CRP], fibrinogen, and serum amyloid A [SAA]). Among patients without a history of cardiac or cerebrovascular disease, the ABI was significantly inversely associated with log D-dimer (p <0.001), log prothrombin 1.2 (p = 0.001), log CRP (p <0.001), and log fibrinogen (p = 0.005) in unadjusted analyses. In multivariable regression analyses adjusting for all blood factors as well as potential confounders, D-dimer was associated independently with ABI in participants with a history of cardiac or cerebrovascular disease (p = 0.003) and in participants without a history of cardiac or cerebrovascular disease (p = 0.017). In these analyses, CRP was associated independently with ABI among participants with a history of cardiac or cerebrovascular disease (p = 0.026). CRP was not associated independently with ABI in participants without a history of cardiac or cerebrovascular disease. We conclude that D-dimer levels may be more sensitive than other blood markers for measuring the extent of atherosclerosis in lower extremity arteries.     

Ankle-brachial index and hemostatic markers in the Atherosclerosis Risk in Communities (ARIC) study cohort

To determine whether elevated levels of hemostatic and inflammatory markers [von Willebrand factor (vWF), fibrinogen, D-dimer, factor VII, factor VIII, PAI-1, tPA, beta-thromboglobulin (beta-TG), CRP, and WBC count] are associated with increased peripheral arterial disease (PAD) prevalence, measured by low ABI, we studied 13,778 participants from the ARIC study in a cross-sectional analysis after adjustment for major cardiovascular risk factors. PAD was positively associated with fibrinogen, vWF, factor VIII, WBC count, D-dimer, beta-TG, and CRP (p for trend <0.05) but not with the other markers. Adjusted odds ratios for the highest versus the lowest quartile of fibrinogen in men and women, respectively, were 3.49 (95% CI 1.68-7.26) and 2.44 (95% CI 1.58-3.77); for vWF 2.36 (95% CI 1.36-4.07) and 1.45 (95% CI 1.00-2.10); for factor VIII 2.31 (95% CI 1.36-3.94) and 1.68 (95% CI 1.14-2.48). In a smaller subset, the sex and risk factor adjusted odds ratio for the highest versus the lowest quartile of D-dimer was 2.70 (95% CI 1.56-4.65), for beta-TG was 1.80 (95% CI 1.12-2.88), and for CRP was 1.57 (95% CI 0.84-2.95). Plasma levels of hemostatic and inflammatory markers are elevated in PAD, suggesting these processes are involved in the pathophysiology of PAD.     

Elevated levels of inflammation, d-dimer, and homocysteine are associated with adverse calf muscle characteristics and reduced calf strength in peripheral arterial disease.

OBJECTIVES: This study determined whether increased levels of inflammatory blood markers, D-dimer, and homocysteine were associated with smaller calf skeletal muscle area, increased calf muscle percent fat, reduced calf muscle density, and poorer calf strength in persons with lower extremity peripheral arterial disease (PAD). BACKGROUND: Elevated levels of inflammatory markers and D-dimer are associated with greater functional impairment and functional decline in persons with PAD. Mechanisms of these associations are unknown. METHODS: Participants were 423 persons with PAD. Calf muscle area, percent fat, and density were measured with computed tomography. Physical activity levels were measured objectively over 7 days with the Caltrac (Muscle Dynamics Fitness Network, Inc., Rocklin, California) vertical accelerometer. Isometric plantarflexion strength was measured. Analyses were adjusted for age, gender, race, comorbidities, the ankle-brachial index, and other potential confounders. RESULTS: Higher levels of D-dimer (p = 0.014), C-reactive protein (CRP) (p = 0.002), interleukin (IL)-6 (p < 0.001), and soluble vascular cellular adhesion molecule (sVCAM)-1 (p = 0.008) were associated with smaller calf muscle area. Higher sVCAM-1 (p = 0.004) and IL-6 (p = 0.017) were associated with higher calf muscle percent fat. Higher D-dimer (p < 0.001), sVCAM-1 (p < 0.001), and homocysteine (p = 0.014) were associated with lower calf muscle density. These associations were generally unchanged after additional adjustment for physical activity. Higher sVCAM-1 (p = 0.013) was associated with lower calf strength. CONCLUSIONS: These data show, for the first time, that higher levels of inflammation, D-dimer, and homocysteine are associated with more adverse calf muscle characteristics in persons with PAD. These associations may contribute to previously established associations between elevated biomarkers and functional impairment and functional decline in PAD.     

Plasma fibrinogen, haemostatic factors and prediction of peripheral arterial disease in the Edinburgh Artery Study.

The role of fibrinogen and other haemostatic factors in prediction of peripheral arterial disease (PAD) has not been established. We examined the associations of plasma fibrinogen, von Willebrand Factor (vWF), tissue plasminogen activator (t-PA) antigen, fibrin D-dimer, and factor VII with the development and clinical progression of PAD. In the Edinburgh Artery Study, 1592 men and women, aged between 55 and 74 years, were followed prospectively over 5 years to detect the onset of PAD, and the deterioration of established PAD. At baseline, 418 individuals had evidence of PAD and 60 (14.4%) subsequently deteriorated. 1080 subjects had no baseline disease, but 59 (5.5%) developed PAD during follow-up. Median levels of fibrinogen and vWF were higher in the group developing disease compared with the group which did not (2.78 g/l versus 2.57 g/l, P< or =0.01; 116 IU/dl versus 104 IU/dl, P< or =0.05; respectively). After adjusting for age and sex, fibrinogen (P< or =0.01) and vWF (P< or =0.05) were significantly associated with the risk of developing PAD. The association between fibrinogen and development of disease remained after adjusting for cardiovascular risk factors and baseline ischaemic heart disease (relative risk, 1.35, 95% confidence interval, 1.05, 1.73; P< or =0.05). None of the haemostatic factors were significantly associated with progression of PAD. In conclusion, plasma fibrinogen levels are related to the future onset of PAD, providing further evidence of a possible role of elevated fibrinogen in the development of atherosclerotic disease.     

Relation of cardiorespiratory fitness to inflammatory markers, fibrinolytic factors, and lipoprotein(a) in patients with type 2 diabetes mellitus

Increased inflammation, fibrinolytic factors, and lipoprotein(a) (LP[a]) were associated with increased cardiovascular events in patients with type 2 diabetes, whereas higher levels of cardiorespiratory fitness (CRF) were associated with a lower incidence of cardiovascular mortality. Whether CRF is associated with inflammatory markers, fibrinolytic factors, and LP(a) in patients with type 2 diabetes was investigated. A total of 425 men with type 2 diabetes (mean age 55 +/- 8 years) who participated in a medical screening program were studied. CRF was measured using peak oxygen uptake with expired gas analysis during a symptom-limited exercise test. CRF inversely correlated with C-reactive protein (CRP; r = -0.27, p <0.05), white blood cell count (r = -0.13, p <0.05), fibrinogen (r = -0.28, p <0.05), LP(a) (r = -0.53, p <0.05), tissue plasminogen activator (t-PA) antigen (r = -0.65, p <0.05), and plasminogen activator inhibitor-1 activity (r = -0.17, p <0.05). Men in the highest tertile of CRF had significantly lower CRP, white blood cell count, fibrinogen, LP(a), and t-PA than men in the lowest tertile of CRF (all p <0.05). In separate multivariable linear regression models that adjusted for age, body mass index, smoking, lipid profiles, glucose, and systolic blood pressure, CRP (beta = -0.23, p <0.05), white blood cell count (beta = -0.16, p <0.05), fibrinogen (beta = -0.24, p <0.05), LP(a) (beta = -0.28, p <0.05), and t-PA (beta = -0.69, p <0.05) were each inversely associated with CRF. Each MET increment higher peak oxygen uptake was associated with a lower odds ratio of having abnormal LP(a) (odds ratio 0.43, 95% confidence interval 0.20 to 0.91) in a multivariate logistic regression model. In conclusion, CRF was inversely associated with inflammatory markers, fibrinolytic factors, and LP(a) in men with type 2 diabetes.     

Relation of depressive mood to plasminogen activator inhibitor, tissue plasminogen activator, and fibrinogen levels in patients with versus without coronary heart disease

The increased risk of coronary heart disease (CHD) associated with depression is well documented. We hypothesized that impaired fibrinolysis is involved in this link. To explore the association of depressive mood and/or vital exhaustion with various measurements of fibrinolysis activity, 231 men (40 to 65 years old; 123 without CHD and taking no medication and 108 with documented CHD), completed the Center of Epidemiologic Studies Depression Scale and the Maastricht Questionnaire for vital exhaustion. Using classic cut-off points (Center of Epidemiologic Studies Depression Scale score >or=17, Maastricht Questionnaire score >or=8), 6.5% and 9.8% of subjects without CHD and 38% and 48.1% of those with CHD were classified as depressed and exhausted, respectively. Patients with CHD were older, had a higher body mass index, and higher levels of total cholesterol, glucose, plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (t-PA) antigen, and fibrinogen; 47% were treated for hypertension. Depressed subjects had higher levels of PAI-1 activity (p = 0.006) and exhausted patients had higher levels of PAI-1 activity (p = 0.011) and fibrinogen (p = 0.009). After adjusting for clinical condition (with or without CHD), smoking, hypertension, triglyceride concentration, and body mass index, PAI-1 activity remained higher in depressed subjects (p = 0.03). This association persisted after further adjustment for vital exhaustion or for t-PA antigen and fibrinogen levels. t-PA antigen and fibrinogen levels were not associated with depressive mood in multivariate analyses. No fibrinolytic variable was associated with vital exhaustion in multivariate analyses. In conclusion, depressive mood, but not vital exhaustion, is associated with higher levels of PAI-1 activity, suggesting a possible impairment of fibrinolysis and indicating a potential additional mechanism by which depressive mood may act as a cardiovascular risk factor.     

丹红注射液对不稳定型心绞痛病人炎症反应物及纤溶活性的影响

目的探讨丹红注射液对不稳定型心绞痛(UA)病人血浆炎症反应物及纤溶活性的影响。方法140例UA病人随机分为常规治疗组(67例)和丹红治疗组(73例),另设正常对照组50名。丹红治疗组于常规治疗基础上加用丹红注射液20mL静脉输注,每日1次,疗程为3周。两组分别于治疗前及结束时测定血清C-反应蛋白(CRP)、白细胞介素-6(IL-6)、纤维蛋白原(FIB)、D-二聚体(DD)浓度和组织型纤溶酶原激活物(t-PA)、纤溶酶原激活物抑制物-1(PAI-1)活性。结果丹红注射液治疗3周后,CRP,IL-6,FIB,DD,PAI-1水平下降(P<0.05或P<0.01),t-PA活性升高(P<0.01)。治疗前UA病人的CRP与IL-6,PAI-1,DD呈正相关(P<0.05或P<0.01),与t-PA呈负相关(P<0.01)。丹红治疗组治疗后CRP与IL-6,PAI-1呈正相关(P<0.05或P<0.01),与t-PA呈负相关(P<0.05)。结论UA病人应用丹红注射液治疗,可能有利于抑制炎症反应,改善内皮功能,提高纤溶活性,稳定斑块。     

The metabolic syndrome and insulin resistance: relationship to haemostatic and inflammatory markers in older non-diabetic men

AIMS: We have examined the cross-sectional relationship between insulin resistance, the metabolic syndrome and haemostatic and inflammatory markers. METHODS AND RESULTS: We carried out the study in 2722 non-diabetic men aged 60-79 years with no history of coronary heart disease or stroke and who were not on warfarin treatment, drawn from general practices in 24 British towns. Insulin resistance (HOMA) was significantly associated with increased inflammatory markers (C-reactive protein (CRP), white cell count), coagulation factors VII-IX, von Willebrand factor (VWF) and tissue plasminogen activator (t-PA) antigens (markers of endothelial dysfunction) and blood viscosity after adjustment for age, smoking, physical activity, alcohol intake and waist circumference. Relationships with fibrinogen and fibrin D-dimer were weak. The relationship between HOMA and CRP was abolished after adjustment for t-PA. The prevalence of the metabolic syndrome was similar using World Health Organization (WHO) and National Cholesterol Education Program definitions (26.7% and 27.0%) but associations between the metabolic syndrome and increased haemostatic markers, particularly for raised factor VIII and VWF were stronger using WHO criteria. CONCLUSION: Insulin resistance and the metabolic syndrome showed significant associations with markers of haemostasis and inflammation, which may be relevant to their associations with cardiovascular disease.     

Effects of perindopril treatment on hemostatic function in patients with essential hypertension in relation to angiotensin converting enzyme (ACE) and plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms

BACKGROUND AND AIM: An imbalance in the hemostatic system is a frequent finding in untreated essential hypertension (HT), and it has been shown that treatment with angiotensin converting entyme (ACE) inhibitors improves hemostatic function. In order to elucidate the role of genetic factors, we studied hemostasis in patients with untreated and treated HT and correlated the results with ACE I/D and plasminogen activator enhibitor-1 (PAI-1) 4G/5G gene polymorphisms. METHODS AND RESULTS: Forty-three males with HT (mean age 31.7 +/- 6.8 years) were compared with 34 age and gender-matched controls. All of the patients were treated with perindopril (4 mg/day) and, after one and six months of therapy, their levels of plasma fibrinogen (Fb), t-PA antigen, PAI-1 antigen, von Willebrand factor (vWF), ACE activity and blood pressure were measured. ACE and PAI-1 genotypes were identified by means of the polymerase chain reaction on DNA isolated from peripheral blood lymphocytes. Untreated patients had significantly higher levels of Fb, PAI-1 (p < 0.01) and t-PA (p < 0.05) regardless of their ACE or PAI-1 genotypes. Perindopril reduced blood pressure regardless of ACE or PAI-1 genotype (p < 0.001). ACE II homozygotes showed the greatest decrease in ACE activity (p < 0.01) and a significant reduction in Fb levels (p < 0.05) after just one month of treatment. Analysis of the group as a whole revealed an increase in t-PA antigen levels after six months of treatment, regardless of ACE or PAI-1 genotype (p < 0.01). CONCLUSIONS: Our results show that essential hypertension predisposes to the procoagulant state characterized by hyperfibrinogenemia and hypofibrinolysis. Perindopril reduced fibrinogen levels in ACE II homozygotes due to its more potent inhibitory action on the renin-angiotensin system in such patients. It improved fibrinolysis by increasing t-PA levels regardless of ACE and PAI-1 genotype.     

A metabolic syndrome independent association between overweight, fibrinolysis impairment and low-grade inflammation in young women with venous thromboembolism.

It is known that overweight induces fibrinolysis impairment. Since this association has not been completely explored in patients with venous thromboembolism (VTE), we aimed to investigate its presence in young women with VTE and, if present, to determine its extent and the factors that influence it. Thirty women aged 23-49 years in the stable period after VTE were included [19 overweight (body mass index > or = 25) and 11 normal weight]; 52 healthy women (27 overweight and 25 normal weight) served as controls. The euglobulin clot lysis time (ECLT), plasminogen, D-dimer, tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) antigen and activity, lipids, fasting plasma glucose, insulin, fibrinogen, interleukin-6 and sedimentation rate were compared between the groups. Overweight patients had more impaired fibrinolysis (delayed ECLT, higher PAI-1 and t-PA antigen) than overweight controls (and normal weight patients). There was no difference in levels of insulin, glucose, fibrinogen and interleukin-6, whereas the sedimentation rate was significantly elevated in overweight patients compared with overweight controls [16 (8-31) versus 8 (5-12), P < 0.05]. The sedimentation rate in overweight patients significantly correlated with body mass index, ECLT, t-PA and PAI-1 antigen, but not with fibrinogen or interleukin-6. We found that overweight VTE patients have more prominent fibrinolysis impairment than predictable from parameters of metabolic syndrome and that is associated with an elevated sedimentation rate. This association could represent a new thrombotic risk profile in overweight women.     

Cross-sectional association of soluble thrombomodulin with mild peripheral artery disease; the ARIC study. Atherosclerosis Risk in Communities

Thrombomodulin, an endothelial membrane glycoprotein, is an essential part of the protein C anti-coagulant pathway. It may also have a role in the regulation of fibrinolysis. We carried out a cross-sectional study to assess the association of soluble thrombomodulin (sTM) with peripheral artery disease (PAD) in a stratified random sample (n=863) of otherwise healthy black and white participants of the Atherosclerosis Risk in Communities (ARIC) Study. PAD was more common in black than in white participants and associated with classical risk factors in an expected manner; positively with age, smoking, hypertension, diabetes (P=0.05), and LDL-cholesterol, and inversely with HDL-cholesterol. Significant positive associations were observed also with fibrinogen and white blood cell count. Overall, the sTM concentration was not a significant predictor of PAD. The association was, however, modified by the level of factor VIII:C in whites (P=0.002 for the interaction), but not in blacks. Protein C was inversely associated with PAD prevalence (odds ratio 0.33, 95% CI 0.18--0.61, P=0.0004). sTM was inversely associated with plasminogen, but no associations with t-PA, PAI-1, or D-dimer were seen. In conclusion, the present results provide some additional evidence on the role of thrombomodulin-protein C pathway in atherosclerotic disease and support our earlier observation on interaction between sTM and factor VIII:C.     

Imbalance of tissue-type plasminogen activator (t-PA) and its specific inhibitor (PAI-1) in patients with rheumatoid arthritis associated with disease activity

Summary The relationship between plasma fibrinogen, D-dimer (DD), t-PA and PAI-1 and their correlation with disease activity (DA) were studied in 45 patients with rheumatoid arthritis (RA) (group B) to further understand the implication of fibrinolysis in the pathophysiology of RA. The control group constituted 24 healthy subjects (group A). A Stoke index (SI) of DA was assigned to each patient. Patients were divided into two groups: C, minimal-mild DA (SI 1–7); D, moderate-severe DA (SI 8–17). Fibrinogen was elevated in RA correlating positively with SI and CRP. Hypercoagulability counteracted by reactive fibrinolysis was inferred from a 10-fold increase of DD in group B as compared to group A. The relatively lower levels of DD in group D compared to group C and their negative correlation with SI (r_s=–0.45, –0.49, p=0.0006) indicate the tendency of fibrinolysis to decrease with the increase of DA. Significant elevation of t-PA and PAI-1 were found in group B compared to group A. While t-PA progressively decreased with the increase of DA (r_s=–0.45, p=0.0019), a positive relation of PAI-1 to DA was observed (r_s=0.42, p=0.0042). A 2-fold increase of PAI-1/t-PA molar ratio in group D compared to groups A and C as well as its positive correlation with SI (r_s=0.63, p=0.0001) indicate the displacement of balance between t-PA and PAI-1 in favour of the inhibitor with the increase of DA in RA. The involvement of inflammatory mediators in PAI-1/t-PA imbalance was proposed from the relation of fibrinolytic abnormalities with the activity of systemic inflammatory process.     

Systemic inflammatory parameters in patients with atherosclerosis of the coronary and peripheral arteries.

Plasma concentration of markers of inflammation are increased in patients with atherosclerosis. However, it is unclear whether the pattern and magnitude of this increase vary with the site and extent of disease. In 147 patients undergoing semiquantitative coronary angiography, we measured the acute-phase reactants C-reactive protein (CRP) or serum amyloid A (SAA); the proinflammatory cytokine interleukin 6 (IL-6); the active and total fractions of the anti-inflammatory cytokine transforming growth factor-beta (TGF-beta); the macrophage activation marker neopterin; and the infection marker procalcitonin. Compared with 62 patients without either coronary artery disease (CAD) or peripheral artery disease (PAD), 57 patients with CAD but no PAD showed greater median CRP (0. 4 versus 0.2 mg/dL, P=0.004) and IL-6 (3.8 versus 1.6 pg/mL, P=0. 007) levels and a lower level of active-TGF-beta (57 versus 100 ng/mL, P=0.038). Moreover, CRP, IL-6, and neopterin levels showed a positive and the active TGF-beta level a negative correlation with the extent of coronary atherosclerosis. Compared with these 57 patients with CAD alone, 15 patients with PAD and CAD had higher median levels of SAA (17 versus 7 mg/mL, P=0.008), IL-6 (12 versus 4 pg/mL, P=0.002), neopterin (14 versus 11 mg/dL, P=0.006), and total TGF-beta (11834 versus 6417 ng/L, P=0.001). However, these strong univariate associations of markers of inflammation and atherosclerosis were lost in multivariate analysis once age, sex, and high density lipoprotein cholesterol or fibrinogen were taken into account. Increased plasma levels of CRP, SAA, IL-6, TGF-beta, neopterin, and procalcitonin constitute an inflammatory signature of advanced atherosclerosis and are correlated with the extent of disease but do not provide discriminatory diagnostic power over and above established risk factors.     

The role of haematological factors in diabetic peripheral arterial disease: the Edinburgh Artery Study

The relationship between haematological factors and peripheral arterial disease (PAD) among diabetics has not been widely examined. 1592 men and women aged 55-74 years were selected from the general population. They underwent an assessment for PAD and a glucose tolerance test. 288 subjects (18.7%) were identified as having diabetes or impaired glucose tolerance (IGT). Among the diabetes/IGT group, median levels of fibrinogen, von Willebrand factor (VWF), tissue plasminogen activator (t-PA), fibrin D-dimer and plasma viscosity were higher in subjects with PAD than those without PAD (P 相似文献   

Cardiovascular risk factors, including thrombotic variables, in a population with rheumatoid arthritis.

OBJECTIVE: To compare prevalent cardiovascular disease, conventional cardiovascular risk factors and thrombotic variables in a cohort with well-controlled rheumatoid arthritis (RA) and in population controls. METHODS: Seventy-six RA patients and 641 controls, randomly sampled from the local population in the North Glasgow MONICA study. Conventional cardiovascular risk factors (blood pressure, smoking, cholesterol) and thrombotic variables [fibrinogen, von Willebrand factor (vWF), tissue plasminogen activator antigen (t-PA), fibrin D-dimer, plasminogen activator inhibitor (PAI-1), plasma viscosity] were measured by standard procedures. RESULTS: RA patients had a significantly higher prevalence of angina pectoris (P=0.03). Stroke also tended to be more common in the RA group, but the difference did not reach statistical significance (P=0.08). Diastolic blood pressure was significantly higher and serum cholesterol significantly lower in the RA group than in controls. Current smoking habits and exercise history were similar in the two groups, although RA patients were more likely to have previously smoked. Significant elevations in several thrombotic predictors of cardiovascular disease (fibrinogen, vWF, t-PA antigen and fibrin D-dimer) were found in the RA group. CONCLUSIONS: In this RA patient population, diastolic blood pressure was higher than in controls and thrombotic variables were elevated compared with controls. These features are identified as potential additional cardiovascular risk factors in the RA patients studied. Prospective studies of risk modification may permit the identification of factors which could lead to a reduction in the known increased cardiovascular risk in RA.     

Intra- and postoperative fibrinolysis in patients undergoing cardiopulmonary bypass surgery

The influence of cardiopulmonary bypass (CPB) on fibrinolytic activity was assessed in 100 patients with valvular heart disease or atrial septal defects. Euglobulin fibrinolytic activity (EFA), tissue type plasminogen activator (t-PA) activity, plasminogen activator inhibitor 1 (PAI-1) activity, plasminogen, alpha 2-antiplasmin (alpha 2-AP), fibrinogen degradation products (FDP), and D-dimer were measured pre-, intra-, and postoperatively. There were significant increases in EFA and t-PA activity (p less than 0.002), and decreases in plasminogen and alpha 2-AP (p less than 0.0001) intraoperatively with respect to baseline values. t-PA activity decreased significantly after surgery (p less than 0.002), whereas PAI-1 activity showed a marked increase shortly after operation and on postoperative day 1 (p less than 0.0001). FDP and D-dimer levels were significantly increased both intra- and postoperatively, the latter showing higher values (p less than 0.01 and p less than 0.0001, respectively). This study shows that there is an activation of the fibrinolytic system, as a result of the increased activation of plasminogen and decreased levels of plasmin inhibitors, during CPB surgery followed by a postoperative fibrinolytic shutdown.     

Association between leisure time physical activity and markers of chronic inflammation related to coronary heart disease

BACKGROUND: Some markers of chronic inflammation have been recognized as predictors of cardiovascular risk in apparently healthy subjects and in patients with coronary heart disease (CHD). High sensitivity C-reactive protein (CRP) appears to be the most useful marker in clinical settings. Several studies reported associations between inflammatory markers and other cardiovascular risk factors, such as age, obesity, cholesterol levels, the presence of diabetes mellitus, physical activity, social level and smoking habits. We focussed on the association between C-reactive protein, serum amyloid A (SAA), fibrinogen and leisure time physical activity (LTPA). METHODS: This report deals with the results observed in a sub-sample of the BELSTRESS study. 892 male subjects, free from clinical CHD and major ECG abnormalities, working in the same environment, aged 35-59 years, were selected. A questionnaire was used to estimate the level of leisure time physical activity. Associations between CRP, SAA, fibrinogen and leisure time physical activity were evaluated through univariate and multivariate methods. Subjects taking statins or other lipid lowering medication were excluded from the study. RESULTS: Regular leisure time physical activity is associated with reductions of several cardiovascular risk factors, such as body mass index (BMI), waist hip ratio and the lipid profile. Smokers and low educated subjects had a lower physical activity status. Age adjustment did not alter the means of inflammatory parameters according to the levels of leisure time physical activity. After correction for personal characteristics (BMI, current smoking status, educational level, presence of diabetes and alcohol consumption) no significant relation was found between leisure time physical activity and levels of inflammatory markers. The differences of CRP and fibrinogen according to the level of physical activity, found in bivariate analysis, seem to be explained by linked differences in BMI, or related to current smoking habits. Leisure time physical activity, as reported in this study, is not significantly related to C-reactive protein, serum amyloid A or fibrinogen levels, after correction for other cardiovascular risk factors. CONCLUSION: These data indicate that leisure time physical activity, as reported in our study, is not an independent predictor of C-reactive protein, serum amyloid A or fibrinogen levels. Possible interactions of physical activity and other cardiovascular risk factors might explain the (indirect) relation we found in the bivariate analysis.     

Alterations in the fibrinolytic system components during acute myocardial infarction

The purpose of this study was to evaluate the changes in tissue-plasminogen activator (t-PA), plasminogen activator inhibitor - type 1 (PAI-1) and D-dimer (DD) antigen plasma levels in acute myocardial infarction (AMI) patients after thrombolytic therapy with two different thrombolytic agents, rt-PA or acetyl-streptokinase and to find out any correlation between the plasma t-PA, PAI-1 and DD levels with the infarct size as it is estimated from the peak of serum CPK levels. The plasma antigen levels of t-PA, PAI-1 and DD were measured by the enzyme immunoassay method (Stago), in 57 consecutive patients (M = 46, F = 11, mean age 55.6 +/- 8.8 years) and in 25 normal subjects (M = 18, F = 7, mean age 54.0 +/- 5.5 years). In 47 out of the 57 patients who were treated successfully with 100 mg of rt-PA (26 patients) or with 1.5 MU 21 of acetyl-streptokinase, as well as in 10 patients who were not treated, samples were obtained again 4 and 24 hours after the end of thrombolytic therapy or admission, respectively. During the acute phase of myocardial infarction the t-PA, PAI-1 and DD antigen plasma levels were significantly higher than in healthy people. There were no significant changes in the t-PA, PAI-1 and DD plasma levels of the patients who were not treated with a thrombolytic agent. We found a significant elevation of t-PA (p < 0.001), PAI-1 (p < 0.05) and DD (p < 0.001) after 4 hours in comparison with the baseline (at presentation, before therapy). After 24 hours the t-PA and DD plasma levels remained significantly higher (p < 0.001) while the PAI-1 plasma levels returned to the pre-therapy levels. There were no significantly different changes in the t-PA, PAI-1 and DD plasma levels of either group of patients, treated with rt-PA or acetyl-streptokinase while the t-PA and PAI-1 levels were positively correlated with infarct size as estimated from peak serum CPK levels.     

Alpha-1 microglobulin as a new inflammatory marker in newly diagnosed hypertensive patients

BACKGROUND: The alpha-1 microglobulin (A1M) is considered to be a marker of renal insufficiency, suggesting disturbed tubular function. In the present study we examined the ability of urinary A1M excretion to reflect the overall inflammatory status in patients with newly diagnosed essential hypertension and normal renal function. METHODS: The study population consisted of 1445 nondiabetic patients with newly diagnosed arterial hypertension and no evidence of renal insufficiency. Serum levels of C-reactive protein (CRP), serum amyloid alpha (SAA), and plasma fibrinogen, as well as urinary A1M excretion, were estimated. Multivariate analysis was performed to evaluate the associations between hypertension; A1M urinary excretion; and circulating levels of CRP, SAA, and fibrinogen. RESULTS: Patients with systolic hypertension had higher CRP, SAA, fibrinogen, and A1M compared with patients with isolated diastolic hypertension (P < .0001 for all). In multivariate analysis, systolic (but not diastolic) blood pressure (BP) was independently associated with A1M, CRP, and SAA (P < .0001 for all), whereas urinary A1M was also independently correlated with inflammatory markers such as CRP (P = .0001) and SAA (P = .0001). CONCLUSIONS: Urinary A1M is independently associated with circulating acute phase proteins in patients with newly diagnosed hypertension, whereas it is closely associated with systolic but not diastolic BP. Our findings suggest that urinary alpha-1 microglobulin may reflect the overall inflammatory status in patients with newly diagnosed essential hypertension, beyond its value as a marker of renal function.     

The methionine synthase reductase (MTRR) A66G polymorphism is a novel genetic determinant of plasma homocysteine concentrations

Recent data suggest that infections, inflammation and the immune system are involved in the process of atherosclerosis. The aim of the present study was to analyze the association of coronary heart disease (CHD) with three inflammation markers, C-reactive protein (CRP), serum amyloid-A (SAA) and plasma fibrinogen. The cross-sectional study included 1400 men aged 45-74 years, who participated in a cardiovascular risk factor survey in Finland in 1997. Participants with prevalent CHD had markedly higher CRP, SAA and fibrinogen levels than participants without CHD. In logistic regression models, the age, smoking, serum cholesterol and systolic blood pressure adjusted odds ratios (2nd, 3rd and 4th quartile as compared with the 1st quartile) of CHD increased gradually with increasing quartile of CRP (1.90, 2.27, 2.64), SAA (1.68, 1.83, 2.41), and fibrinogen (1.60, 1.95, 2.14). The associations weakened somewhat after further adjustment for indicators of obesity, particularly waist hip-ratio. CRP, SAA and fibrinogen levels were markedly lower among CHD patients using cholesterol-lowering medication as compared to non-users. In conclusion, CRP, SAA and fibrinogen, which are markers of inflammation, were positively and significantly associated with prevalent CHD. Central obesity needs to be considered as a confounding factor in the observed associations. These findings support the hypothesis that cholesterol-lowering drugs have an anti-inflammatory effect.