Effect of Revascularization on Exercise-Induced Changes in Cardiac and Prothrombotic Biomarkers in Patients with Coronary Artery Disease.

We examined whether resting levels and exercise-induced changes during exercise ECG stress test (EST) of cardiac Troponin T (cTnT), NT-proBNP and prothrombotic markers were affected by revascularization in patients with coronary artery disease (CAD).EST1 was performed before coronary angiography and revascularization, and patients (n = 20) with confirmed CAD, performed another EST (EST2) 9 weeks later. Blood samples were drawn at rest and within five min after termination of ESTs.cTnT and NT-proBNP increased during exercise at both ESTs (p < 0.001, all). Resting cTnT levels at EST2 versus EST1 were significantly higher (p = 0.02) whereas NT-proBNP did not differ. At both visits, increased D-dimer (p = 0.008 and <0.001), pro-thrombin fragment 1 + 2 (p = 0.009 and 0.001) and tissue factor pathway inhibitor (TFPI) (p < 0.001 and 0.001) during exercise were demonstrated. Resting levels of endogenous thrombin potential (ETP) and TFPI were reduced at EST2 versus EST1 (p < 0.01).Revascularization did not affect exercise-induced release of cardiac and prothrombotic biomarkers and did not reduce resting levels of cTnT or NT-proBNP, suggesting revascularization per se not to prevent secretion of biomarkers. The lower resting levels of ETP and TFPI after revascularization may however, be indicative of reduced thrombin generation and endothelial activation.Clinicaltrials.gov, CADENCE, NCT01495091 https://clinicaltrials.gov/ct2/show/NCT01495091?term = 01495091&draw = 2&rank = 1.

Galectin-3, a marker of cardiac remodeling, is inversely related to serum levels of marine omega-3 fatty acids. A cross-sectional study.

OBJECTIVE: Marine polyunsaturated n-3 fatty acids (n-3 PUFA) may have cardioprotective effects and beneficial influence on the fibrotic process. We evaluated the associations between serum marine n-3 PUFA and selected biomarkers of fibrosis and cardiac remodeling in elderly patients with acute myocardial infarction. SETTING: From the ongoing OMega-3 fatty acids in Elderly patients with Myocardial Infarction (OMEMI) trial, 299 patients were investigated. Soluble ST2 (sST2), Galectin-3 (Gal-3) and the serum content of major marine n-3 and n-6 PUFA were analyzed 2-8 weeks after the index acute myocardial infarction. RESULTS: Gal-3 was inversely correlated to eicosapentaenoic acid (r = -.120, p = .039) and docosahexaenoic acid (r = -.125, p = .031) and positively correlated to the n-6/n-3 ratio (r = .131, p = .023). Gal-3 levels were significantly higher in diabetics vs non-diabetics (12.00 vs 9.61 ng/mL, p = .007) and in patients with NYHA class ≥III for dyspnea at inclusion (11.33 vs 9.75 ng/mL, p = .006). CONCLUSIONS: The associations between the marine n-3 PUFA and levels of Gal-3 indicate beneficial effects of n-3 PUFA on cardiac remodeling in an elderly population with acute myocardial infarction.

Cigarette smoking represses expression of cytokine IL-12 and its regulator miR-21-An observational study in patients with coronary artery disease.

RATIONALE: The heterodimer IL-12 is an inducer of Th1 responses and stimulates INFÆ´ production. Micro-RNA-21 (miR-21) is described as a key regulator of the pro-inflammatory response and has IL-12p35 mRNA as one of its main targets. The IL-12p40 1188A/C genetic variant located in 3'untranslated region (UTR), thus environmentally exposed, has further been reported to modify IL-12 levels. We have previously reported on the lowering effect of cigarette smoke on circulating IL-12 in patients with coronary artery disease (CAD). OBJECTIVES: To explore if cigarette smoking affects IL-12p35, IL-12p40, INFÆ´ and miR-21 gene-expression and further modulates any effect of the IL-12p40 polymorphism on circulating IL-12 levels. METHODS AND RESULTS: The IL-12p40 1188A/C polymorphism was analyzed in 1001 stable CAD patients, of which 330 subjects were included for IL-12p35, IL-12p40 and INFÆ´ gene-expression analyses in circulating leukocytes and 200 were further selected for plasma miR-21 analysis. Smoking associated with lower expression of miR-21 and its target IL-12p35 mRNA (adjusted p<0.05, both) whereas the influence on INFÆ´ expression tended to be high-dose reliant (p = 0.057). The IL-12p40 CC genotype associated with elevated circulating IL-12 levels, however, when stratified according to smoking, only in the non-smoking group (adjusted p < 0.05). Although the markers were mainly downregulated in current smokers, their inter-correlations were potentiated. CONCLUSION: Smoking associated with reduced miR-21 gene-repression and the results can therefore not explain the previously observed reduction in circulating IL-12. Smoking attenuated the IL-12 pro-inflammatory axis in which the investigated IL-12p40 genetic variant may have different clinical impact in smokers vs non-smokers.

Markers of thrombin generation are associated with myocardial necrosis and left ventricular impairment in patients with ST-elevation myocardial infarction.

INTRODUCTION: Platelet activation, thrombin generation and fibrin formation play important roles in intracoronary thrombus formation, which may lead to acute myocardial infarction. We investigated whether the prothrombotic markers D-dimer, pro-thrombin fragment 1 + 2 (F1 + 2) and endogenous thrombin potential (ETP) are associated with myocardial necrosis assessed by Troponin T (TnT), and left ventricular impairment assessed by left ventricular ejection fraction (LVEF) and N-terminal pro b-type natriuretic peptide (NT-proBNP). MATERIALS/METHODS: Patients (n = 987) with ST-elevation mycardial infarction (STEMI) were included. Blood samples were drawn at a median time of 24 h after onset of symptoms. RESULTS: Statistically significant correlations were found between both peak TnT and D-dimer (p < 0.001) and F1 + 2 (p < 0.001), and between NT-proBNP and D-dimer (p = 0.001) and F1 + 2 (p < 0.001). When dividing TnT and NT-proBNP levels into quartiles there were significant trends for increased levels of both markers across quartiles (all p < 0.001) D-dimer remained significantly associated with NT-proBNP after adjustments for covariates (p = 0.001) whereas the association between NTproBNP and F1 + 2 was no longer statistically significant (p = 0.324). A significant inverse correlation was found between LVEF and D-dimer (p < 0.001) and F1 + 2 (p = 0.013). When dichotomizing LVEF levels at 40 %, we observed significantly higher levels of both D-dimer (p < 0.001) and F1 + 2 (p = 0.016) in the group with low EF (n = 147). SUMMARY/CONCLUSION: In our cohort of STEMI patients we demonstrated that levels of D-dimer and F1 + 2 were significantly associated with myocardial necrosis as assessed by peak TnT. High levels of these coagulation markers in patients with low LVEF and high NTproBNP may indicate a hypercoagulable state in patients with impaired myocardial function.

A brief review on high on-aspirin residual platelet reactivity.

Although aspirin is effective in secondary prevention in coronary heart disease, new thromboembolic events in patients on aspirin are frequently seen. In trials on aspirin-treated patients, platelet function tests have revealed large variability in platelet aggregation. This phenomenon has been named aspirin resistance, aspirin non-responsiveness or high-on-aspirin residual platelet reactivity. The mechanism of aspirin antiplatelet effect is due to the inhibition of cyclooxygenase-1 enzyme in platelets. In some trials, almost all patients on aspirin have a very low level of serum thromboxane B2, indicating that the measured platelet reactivity in aspirin-treated patients might be due to platelet activation via other pathways, such as ADP or thrombin. The prevalence of real aspirin resistance seems to be very low, and probably the term "high-on-aspirin residual platelet reactivity" should be preferred to describe this phenomenon.

Biomarkers of inflammation in major vascular surgery: a prospective randomised trial.

BACKGROUND: Surgery induces inflammation and pro-inflammatory cytokines are associated with post-operative complications. In cardiac surgery, it has been shown that volatile anaesthetics have cardioprotective properties. We explored whether sevoflurane affects the pro-inflammatory response favourably compared with total intravenous anaesthesia (TIVA) after surgery. METHODS: We measured monocyte chemotactic protein 1 (MCP-1), matrix metalloproteinase 9 (MMP-9), C-reactive protein (CRP), vascular cell adhesion molecule 1 (VCAM-1), interleukin (IL)-6 and IL-8 perioperatively and evaluated if the anaesthetic regimen affected these mediators. Our hypothesis was that sevoflurane-based anaesthesia is associated with a reduced release of biomarkers of inflammation compared with TIVA with propofol/remifentanil. RESULTS: In the total population, MCP-1, MMP-9, IL-6 and IL-8 increased 30 min after arrival intensive care unit, compared with before surgery (P < 0.001), whereas CRP and VCAM-1 transiently declined (P < 0.001). From 30 min after arrival intensive care unit to 1st post-operative day, MCP-1 and IL-6 levels declined (P < 0.001), CRP and VCAM-1 increased (P < 0.001), whereas MMP-9 and IL-8 were not significantly altered. Pre-operatively there were no significant differences in any variables between the two anaesthetic groups. Lower levels of MCP-1 and IL-8 (P < 0.001) and higher levels of IL-6 and MMP-9 (P = 0.003) were found in the sevoflurane group, compared with the TIVA group 30 min post-operatively. CRP and VCAM-1 levels did not differ. There were no significant differences between the two anaesthetic groups before surgery or at 1st post-operative day. CONCLUSION: We found an inflammatory response during the observation period, which was modified by the anaesthetic regimen in the early phase. This short-lasting difference is probably too short to support a cardioprotective effect of sevoflurane compared with TIVA in open abdominal aortic surgery.

Genes expressed in coronary thrombi are associated with ischemic time in patients with acute myocardial infarction.

INTRODUCTION: Reports on the content of aspirated coronary thrombi have until now mainly focused on cellular components. We investigated the genetic expression of selected mediators and proteases actively involved in the pathophysiological process of acute myocardial infarction in aspirated coronary thrombi. MATERIALS AND METHODS: In this cross-sectional study, RNA from coronary thrombi in 67 subjects with acute myocardial infarction was isolated. Gene expression arrays of selected markers were performed by RT-PCR with relative quantification. RESULTS: Twenty of 22 markers were expressed in >50% of the samples. The relative quantification of P-selectin correlated negatively to total ischemic time (p=0.01), while genes related to fibrinolysis (t-PA, u-PA, PAI-1), inflammation (PTX3, CXCL9, MCP-1, IL18, TNFα) and plaque instability (MMP-2 and TIMP-1) correlated positively to total ischemic time (all<0.05). Long ischemic time (>4.0 hours) associated with a relative reduction in the expression of P-selectin and a relative increase in the expression of t-PA, u-PA, PAI-1, PTX3, CXCL9, MCP-1, IL-18, TNFα, MMP-2 and TIMP-1. The presence of type 2 diabetes associated with 3.2-fold increased PAI-1 expression (adjusted p=0.033), while the presence of hypertension associated with about 50% reduction of IL-8 and TIMP-1. Smoking and overweight did not affect any markers. CONCLUSIONS: The gene expression profile from coronary thrombi differed according to ischemic time, shown by reduced content of platelet markers and increased content of fibrinolytic, inflammatory and plaque instability mediators over time. Patients with type 2 diabetes showed increased expression of PAI-1, indicative of reduced fibrinolysis.

Effects of anthocyanins on cardiovascular risk factors and inflammation in pre-hypertensive men: a double-blind randomized placebo-controlled crossover study.

High intake of fruits and vegetables is associated with reduced cardiovascular risk. A number of fruits and vegetables are rich in anthocyanins, which constitute a subgroup of the flavonoids. Anthocyanins have demonstrated anti-inflammatory and anti-oxidative properties, and anthocyanin-rich interventions have indicated beneficial effects on blood pressure and other cardiovascular risk factors. We assessed whether a purified anthocyanin supplement improves cardiovascular metabolic risk factors and markers of inflammation and oxidative stress in prehypertensive participants, and whether plasma polyphenols are increased 1-3 h following intake. In all, 31 men between 35-51 years with screening blood pressure >140/90 mm Hg without anti-hypertensive or lipid-lowering medication, were randomized in a double-blinded crossover study to placebo versus 640 mg anthocyanins daily. Treatment durations were 4 weeks with a 4-week washout. High-density lipoprotein (HDL)-cholesterol and blood glucose were significantly higher after anthocyanin versus placebo treatment (P=0.043 and P=0.024, respectively). No effects were observed on inflammation or oxidative stress in vivo, except for von Willebrand factor, which was higher in the anthocyanin period (P=0.007). Several plasma polyphenols increased significantly 1-3 h following anthocyanin intake. The present study strengthens the evidence that anthocyanins may increase HDL-cholesterol levels, and this is demonstrated for the first time in prehypertensive and non-dyslipidemic men. However, no other beneficial effects in the short term were found on pathophysiological markers of cardiovascular disease.

Kiwifruit decreases blood pressure and whole-blood platelet aggregation in male smokers.

Lifestyle modifications to reduce risk factors for cardiovascular diseases such as blood pressure (BP) and smoking have been emphasized. Fruits and vegetables may modify such risk factors. The major aim of this randomized, controlled trial was to investigate the effects of (1) kiwifruits and (2) an antioxidant-rich diet compared with (3) a control group on BP and platelet aggregation (that is, whole-blood platelet aggregation) after 8 weeks in male smokers (age 44-74 years, n=102). The kiwifruit group received 3 kiwifruits per day, whereas the antioxidant-rich diet group received a comprehensive combination of antioxidant-rich foods. In the kiwifruit group, reductions of 10 mm Hg in systolic BP and 9 mm Hg in diastolic BP were observed (P=0.019 and P=0.016 (change from baseline in the kiwifruit group compared with change from baseline in the control group)). In the antioxidant-rich diet group, a reduction of 10 mm Hg in systolic BP was observed among hypertensives (P=0.045). Additionally, a 15% reduction in platelet aggregation and an 11% reduction in angiotensin-converting enzyme activity was observed in the kiwifruit group (P=0.009 and P=0.034). No effects on these parameters were observed in the antioxidant-rich diet group. This study suggest that intake of kiwifruit may have beneficial effects on BP and platelet aggregation in male smokers.

Adipose tissue pro-inflammatory gene expression is associated with cardiovascular disease.

BACKGROUND: Obese patients are at high risk of developing cardiovascular disease. Several studies suggest obesity as an independent risk factor. Adipose tissue is now accepted as an endocrine organ that produces and secretes a variety of cytokines, hormones and other metabolic players involved in the pathogenesis of atherosclerosis. Among this versatile group of mediators and effectors of inflammation and atherothrombosis, we have studied the expression of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), plasminogen activator inhibitor-1 (PAI-1), interleukin-18 (IL-18) and interleukin-6 (IL-6). All these markers, in their circulatory form, have been associated with cardiovascular disease. However, there is no much data available on their expression in adipose tissue in human subjects with and without cardiovascular disease. MATERIAL AND METHODS: We successfully isolated RNA from subcutaneous fat biopsies of 61 patients with or without cardiovascular disease. We then measured the RNA expression of MMP-9, TIMP-1, PAI-1, IL-18 and IL-6 with Real-Time PCR, using relative quantification. RESULTS: Albeit not statistically significant, all inflammatory mediators - except IL-18 - were highly expressed in patients with cardiovascular disease (n = 16) compared with those without (n = 45). Pooling the gene expression data, trying to capture the overall inflammatory activity in adipose tissue in a score system, we observed a highly significant association with CVD. CONCLUSIONS: Trying to capture the overall inflammatory activity, in addition to the mass of adipose tissue, could provide useful hints towards a pathogenetic link between obesity and presence of cardiovascular disease.

Elevated levels of PAI-1 activity and t-PA antigen are associated with newly diagnosed abnormal glucose regulation in patients with ST-elevation myocardial infarction.

BACKGROUND: Both Type 2 diabetes and cardiovascular disease have been associated with enhanced coagulation and suppressed fibrinolysis. OBJECTIVES: To investigate a possible relationship between selected hemostatic variables and abnormal glucose regulation (AGR) in patients with acute ST-elevation myocardial infarction (STEMI) without known diabetes and to study changes in selected hemostatic variables from baseline to follow-up in STEMI patients with or without AGR. METHODS: Plasminogen activator inhibitor-1 (PAI-1) activity, tissue plasminogen activator (t-PA) antigen, prothrombin fragment 1+2 (F(1+2)) and von Willebrand factor (vWF) were measured in fasting blood samples from 199 STEMI patients 16.5 h (median time) after admission and 3 months later. All patients were classified into normal glucose regulation (NGR) or AGR based on an oral glucose tolerance test at follow-up, according to the WHO criteria. RESULTS: High PAI-1 activity (≥ 75th percentile) measured in-hospital was associated with AGR (n = 49) with an adjusted odds ratio of 2.2 (95% confidence interval, 1.1, 4.4). In addition, high levels of t-PA antigen (≥ 75th percentile) were associated with AGR (adjusted odds ratio, 3.5; 95% confidence inteval, 1.5, 8.2), but only in men. Changes in the levels of F(1+2) were significantly more pronounced in patients with AGR compared with NGR (adjusted P = 0.04). CONCLUSION: Elevated levels of PAI-1 activity and t-PA antigen measured in-hospital in STEMI patients were associated with AGR classified at 3-month follow-up. Additionally, changes in the levels of F(1+2) were more pronounced in patients with AGR compared with NGR. The data suggest an enhanced prothrombotic state after an acute STEMI in patients with AGR without known diabetes.

Studies on very long chain marine n-3 fatty acids in patients with atherosclerotic heart disease with special focus on mechanisms, dosage and formulas of supplementation.

Based on experience from randomised trials with n-3 PUFA we intend to answer some relevant questions in patients with coronary heart disease. In the SHOT study supplementation with 3.4 g/day of highly concentrated n-3 PUFA for 1 year significantly reduced the occlusion rate of venous aortocoronary bypass grafts, and this effect correlated significantly to the change in serum levels of n-3 fatty acids. In the CART study 5.1 g/day of highly concentrated n-3 PUFA did not reduce the incidence of restenosis after 6 months. If anything, a negative effect was observed. The background for this was probably a pro-oxidative and proinflammatory mechanism as elucidated in substudies. In the OVITES trial the addition of vitamin E did not counteract the proinflammatory effect of high amounts of n-3 PUFA supplementation as observed in CART, although circulating oxidative substances were unaffected. In the "Fiord-to-table" study replacement of fish oils by vegetable oils in the feed of farmed Atlantic salmon was mirrored in the fatty acid profile of the salmon fillets as well as in that of serum from patients after ingesting about 700 g/week for six weeks. A parallel reduction of the proinflammatory profile was observed only in patients who ingested salmon fed on fish oil.

Endogenous thrombin potential (ETP) in plasma from patients with AMI during antithrombotic treatment.

BACKGROUND: The beneficial impact of warfarin in preventing new events after AMI is well established. Decrease in thrombin generation seems to be the key element in anticoagulant treatment. OBJECTIVES: The aims were to investigate the effect of warfarin and platelet inhibition on thrombin generation, assessed by the endogenous thrombin potential (ETP), and study the relation between coagulation parameters and ETP in patients with AMI. PATIENTS/METHODS: In the present sub-study of the WARIS II trial, patients with AMI were randomly assigned to treatment with aspirin 160 mg/d (n=57), aspirin 75 mg/d and warfarin (INR 2.0-2.5) (n=68) or warfarin (INR 2.8-4.2) (n=61). Fasting blood samples were collected from patients at discharge from hospital and after 6 weeks treatment. RESULTS: Correlation analyses showed that both ETP and peak thrombin levels were significantly correlated with Factor VII Ag (r=0.38 and 0.36 respectively, p<0.01 for both) and with F1+2 (r=0.26 and 0.23 respectively, p=0.01 for both) at baseline. Antithrombotic treatment for 6 weeks caused a highly significant inhibition of ETP in patients treated with warfarin (-28%+/-5%, p<0.001), and patients treated with aspirin/warfarin (-24%+/-8%, p=0.04). Similarly, peak thrombin levels were reduced in patients treated with warfarin (-18%+/-7%, p=0.049) and aspirin/warfarin (-19%+/-5%, p=0.029), whereas an increase (12%+/-4%, p=0.029) occurred during aspirin treatment alone. F1+2 levels decreased by 64% and 58% in the warfarin and aspirin/warfarin groups, respectively (p=0.001 for both). CONCLUSIONS: In patients with AMI, warfarin significantly reduced the endogenous thrombin generation and the potential to generate thrombin in plasma ex vivo, whereas aspirin alone had no effect on thrombin generation in vivo or ex vivo, assessed by ETP.

Long-term influence of diet and/or omega-3 fatty acids on matrix metalloproteinase-9 and pregnancy-associated plasma protein-A in men at high risk of coronary heart disease.

BACKGROUND: Matrix metalloproteinases (MMPs) are important in the atherosclerotic process. The relationship between MMPs and traditional risk factors for cardiovascular disease (CVD) and any influence of lifestyle changes are largely unknown. OBJECTIVES: In a factorial design, we studied the effects of 3 years of dietary counselling and/or n-3 PUFA supplementation (2.4 g/d) on the levels of MMP-9, tissue inhibitor of metalloproteinase (TIMP-1) and pregnancy-associated plasma protein (PAPP-A) in a population of elderly men at high risk of CVD (n = 563, age 70+/-6 years). We further explored the association between these markers and different disease entities, carotid intima media thickness (IMT) and traditional risk factors for CVD. RESULTS: Smokers had significantly higher levels of MMP-9 (p<0.0001), and TIMP-1 levels were lower in subjects with previous AMI (p = 0.021). MMP-9 was significantly correlated with LDL-C and inversely with HDL-C (both p<0.0001). There were no significant correlations between the measured variables and IMT. Significant reductions in MMP-9 and PAPP-A levels after 36 months were found in all study groups, however, with no between-group differences. CONCLUSIONS: The elevated levels of MMP-9 in smokers and the reduced levels of TIMP-1 in patients with previous AMI reflect an importance of MMPs in the development of CVD. Intervention with diet and/or n-3 PUFA supplementation did not influence the levels of MMP-9, TIMP-1 or PAPP-A in the present population.

Consumption of fruit and berries is inversely associated with carotid atherosclerosis in elderly men.

Epidemiological data suggest that fruit and vegetable consumption is associated with a lowered risk of CVD. We assessed the association between the intima-media thickness (IMT) of the carotid artery and dietary intake of vegetables, fruit and berries in elderly men with a high risk of CVD. Subjects (age 70 +/- 5 years) were survivors from a cohort of 1232 men that participated in the Oslo Diet and Antismoking Study in 1972-3. Measurements of the carotid IMT by high resolution B-mode ultrasound, risk factor assessment and dietary data based on an FFQ were collected in 1997-9. Complete dietary and ultrasound data were available for 547 subjects. The carotid IMT in the highest quartile of dietary intake of fruit and berries was 0.89 (SE 0.18) mm compared with 0.96 (SE 0.25) mm in the lowest quartile, giving a mean difference of 0.075 (SE 0.027) mm (P = 0.033). In multivariate regression analysis increased intake of fruit and berries remained inversely associated with IMT after adjustment for age, cigarette smoking, dietary cholesterol and saturated fat, consumption of milk, cream and ice cream and energy intake (multivariate regression coefficient 0.257; R(2) 0.066; SE 0.209; P < 0.001). The difference of 348 g of fruit and berries per d between the lowest and highest quartile of intake was associated with a 5.5 % adjusted difference in mean IMT. These findings suggest that consumption of fruit and berries may be protective against carotid atherosclerosis in elderly men at high risk of CVD.

Beneficial effects of 1-year optimal medical treatment with and without additional PTA on inflammatory markers of atherosclerosis in patients with PAD. Results from the Oslo Balloon Angioplasty versus Conservative Treatment (OBACT) study.

The influence of optimal medical treatment (OMT) with or without additional percutaneous transluminal angioplasty (PTA) on vascular inflammation in peripheral arterial occlusive disease (PAD) patients was investigated. Patients with intermittent claudication (IC) and angiographically verified PAD were randomized to OMT (n = 28) or OMT + PTA (n = 28) and followed for 12 months. Ankle-brachial index (ABI), treadmill walking distances (WD), visual analogue scale (VAS), and blood sampling for the determination of selected soluble biomarkers were undertaken at baseline and after 3 and 12 months. After both 3 and 12 months, ABI, WD and VAS were highly significantly improved in favour of OMT + PTA (p < 0.05 for all). Significant improvements were recorded in both groups in serum lipids (p < 0.01 for all), except for triglycerides, and in the inflammatory markers P-selectin, interleukin-6, interleukin-10, monocyte chemoattractant protein-1 and fibrinogen (p < 0.05 for all). There were, however, no differences in the changes from baseline between the groups in any variable. Intervention with OMT alone or in combination with PTA did not differ with regard to the effects on serum lipids and markers of inflammation in our population of PAD patients. The combined treatment was, however, better for the treadmill walking distance.

Effects of an antiatherogenic diet during pregnancy on markers of maternal and fetal endothelial activation and inflammation: the CARRDIP study.

OBJECTIVE: To study the effect of an antiatherogenic diet on maternal and cord blood concentrations of systemic biomarkers of endothelial cell activation, haemostasis and inflammation. DESIGN: Single blinded randomised controlled clinical trial. SETTING: Obstetric outpatient clinic and maternity unit of a university hospital in Norway. POPULATION: Nonsmoking pregnant women aged 21-38 years carrying a single fetus and with no previous pregnancy-related complications. METHODS: Subjects (n = 290) were randomised to continue their usual diet or to adopt a diet low in saturated fat and cholesterol from gestational week 17-20 to birth. Soluble forms of cellular adhesion molecules, high-sensitivity C-reactive protein (CRP) and haemostatic markers were measured at 17-20 weeks of gestation (baseline) and subsequently up to week 36. All the above, except CRP, were also measured in cord blood. MAIN OUTCOME MEASURES: Concentrations of maternal and fetal biomarkers and maternal CRP. RESULTS: All biomarkers except CRP levels increased significantly during the study period in both the intervention and control groups. None of the maternal or fetal biomarkers were influenced by the intervention (P > 0.05) except for a tendency to lower concentrations of cord blood tissue plasminogen activator antigen in the intervention group compared with the control group, median (interquartile range) 5.4 ng/ml (3.1-7.7) versus 5.8 ng/ml (3.5-11.8), P = 0.05. CONCLUSION: An antiatherogenic diet in pregnancy did not significantly influence maternal or fetal blood concentrations of a range of biomarkers for inflammation. Thus, the previously reported effects of a cholesterol-lowering diet on maternal lipid profile and preterm delivery (<37 complete weeks of gestation) do not seem to involve changes in the systemic inflammatory responses of pregnancy.

The Oslo balloon angioplasty versus conservative treatment study (OBACT)--the 2-years results of a single centre, prospective, randomised study in patients with intermittent claudication.

OBJECTIVES: To compare the effect of optimal medical treatment only (OMT) with OMT combined with percutaneous transluminal angioplasty (OMT+PTA) in patients with intermittent claudication (IC). DESIGN: A single centre prospective, randomised study. Quality of life (QoL) was the primary outcome measure. Secondary measures were ankle-brachial-index (ABI), treadmill walking distances and mortality. METHODS: From a total of 434 patients considered for inclusion into the trial, only 56 patients with disabling IC fulfilled the inclusion criteria. The patients were randomised into treatment groups consisting of 28 patients each and followed for 2 years. ABI and treadmill walking distances were measured in addition to the visual analogue scale (VAS) for pain evaluation, and QoL assessment using the Short Form (SF-36 and Claudication Scale (CLAU-S). RESULTS: The demographic data in the 2 groups were almost identical. After 2 years of follow-up the ABI, the treadmill walking distances and the VAS were significant improved in the group treated with OMT+PTA, compared to the group treated with OMT only (p<0.01 for all). Furthermore, some variables from the QoL assessment also showed a significant improvement in favour of the OMT+PTA group (p<0.05 for all). CONCLUSION: The advantage of conducting a single centre study and adhering to very strict inclusion criteria was illustrated by the homogenous demographic data of the two groups. This partly outweighed the disadvantage of having included a relatively small number of patients. Early intervention with PTA in addition to OMT seems to have a generally more positive effect compared to OMT only, on haemodynamic, functional as well as QoL aspects during the first 2 years in patients with IC.

Markers of vascular inflammation are associated with the extent of atherosclerosis assessed as angiographic score and treadmill walking distances in patients with peripheral arterial occlusive disease.

The importance of inflammation in atherosclerosis is well established in cardiovascular disease. However, limited data exist on the relationship between vascular inflammation and the severity of peripheral arterial occlusive disease (PAD). We investigated the relationship between biochemical markers of vascular inflammation and the diagnostic measures of PAD: ankle-brachial pressure index (ABI), maximum treadmill walking distance and angiographic score. In 127 patients (mean age 66 years; 64% males) with angiographically verified PAD, fasting blood samples were drawn for determination of selected soluble cell adhesion molecules, cytokines and chemokines. Tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and CD40 ligand (CD40L) were all significantly correlated with the angiographic score (p < 0.05 for all). After adjustment for relevant co-variates, MCP-1 and CD40L remained statistically significant (p < 0.01 for both). IL-6 was, independent of other risk factors, inversely correlated with the maximum treadmill walking distance (p < 0.01). Our cross-sectional study in PAD patients showed that the vascular inflammatory markers MCP-1, CD40L and IL-6 were significantly associated with the extent of atherosclerosis, assessed by angiographic score and maximum treadmill walking distance. These findings indicate that vascular inflammation is implicated in PAD, which might be of importance in future diagnosis and treatment of the disease.

Blood glucose lowering by means of lifestyle intervention has different effects on adipokines as compared with insulin treatment in subjects with type 2 diabetes.

AIMS/HYPOTHESIS: Adipokines may be important in mediating signals from adipocytes to insulin-sensitive tissue and vasculature. We studied the effect of different glucose-lowering therapies on serum levels of plasminogen activator inhibitor-1 (PAI-1), high-sensitivity C-reactive protein (hs-CRP), TNF-alpha, leptin, adiponectin and ghrelin in patients with type 2 diabetes. SUBJECTS AND METHODS: Twenty-eight patients with poorly controlled type 2 diabetes who were receiving oral hypoglycaemic agents were allocated to one of the following groups, and treated for 1 year: (1) lifestyle intervention (L); (2) insulin treatment (I); and (3) combined treatment (L+I). RESULTS: Similar improvements in glycaemic control occurred in all three groups. There was a reduction in body weight of 3.0 kg (median) (95% CI -5.9 to -2.0) in group L, whereas in groups L+I and I body weight increased by 3.5 kg (95% CI 1.5-4.9) and 4.9 kg (95% CI -3.1 to 8.2), respectively. By trend analyses, group L had reduced levels of PAI-1 (p=0.002), hs-CRP (p<0.0001) and TNF-alpha (p=0.006), while no significant changes were observed in the levels of leptin or adiponectin. In group I, the median levels of PAI-1 (p=0.008), TNF-alpha (p=0.058) and leptin (p=0.004) increased. In the L+I group there was a reduction in PAI-1 levels (p=0.014) and an increase in levels of leptin (p<0.001). The differences in changes in the levels of PAI-1, hs-CRP, TNF-alpha and leptin between groups were also significant (all p<0.01). CONCLUSIONS/INTERPRETATION: Improvement of glycaemic control through lifestyle intervention in type 2 diabetes had more beneficial effects on adipokine levels than when the same lowering of HbA(1c) was achieved with insulin treatment.