Michael Abdelnoor

Effect of dietary supplementation with n-3 fatty acids on coronary artery bypass graft patency

Epidemiologic and experimental data suggest that a high dietary intake of long-chain polyunsaturated n-3 fatty acids may reduce the risk of atherothrombotic disease. In a randomized, controlled study, 610 patients undergoing coronary artery bypass grafting were assigned either to a fish oil group, receiving 4 g/day of fish oil concentrate, or to a control group. All patients received antithrombotic treatment, either aspirin or warfarin. Their diet and serum phospholipid fatty acid profiles were monitored. The primary end point was 1-year graft patency, which was assessed by angiography in 95% of patients. Vein graft occlusion rates per distal anastomoses were 27% in the fish oil group and 33% in the control group (odds ratio 0.77, 95% confidence interval, 0.60 to 0.99, p = 0.034). In the fish oil group, 43% of the patients had > or = 1 occluded vein graft(s) compared with 51% in the control group (odds ratio 0.72, 95% confidence interval, 0.51 to 1.01, p = 0.05). Moreover, in the entire patient group, there was a significant trend to fewer patients with vein graft occlusions with increasing relative change in serum phospholipid n-3 fatty acids during the study period (p for linear trend = 0.0037). Thus, in patients undergoing coronary artery bypass grafting, dietary supplementation with n-3 fatty acids reduced the incidence of vein graft occlusion, and an inverse relation between relative change in serum phospholipid n-3 fatty acids and vein graft occlusions was observed.

Efficacy and Safety of Immediate Angioplasty Versus Ischemia-Guided Management After Thrombolysis in Acute Myocardial Infarction in Areas With Very Long Transfer Distances Results of the NORDISTEMI (NORwegian study on DIstrict treatment of ST-Elevation Myocardial Infarction)

OBJECTIVES The goal of this study was to compare a strategy of immediate transfer for percutaneous coronary intervention (PCI) with an ischemia-guided approach after thrombolysis in patients with very long transfer distances to PCI. BACKGROUND Thrombolysis remains the treatment of choice in ST-segment elevation myocardial infarction (STEMI) when primary PCI cannot be performed within 90 to 120 min. The optimal treatment after thrombolysis is still unclear. METHODS A total of 266 patients with acute STEMI living in rural areas with more than 90-min transfer delays to PCI were treated with tenecteplase, aspirin, enoxaparin, and clopidogrel and randomized to immediate transfer for PCI or to standard management in the local hospitals with early transfer, only if indicated for rescue or clinical deterioration. The primary outcome was a composite of death, reinfarction, stroke, or new ischemia at 12 months, and analysis was by intention to treat. RESULTS The primary end point was reached in 28 patients (21%) in the early invasive group compared with 36 (27%) in the conservative group (hazard ratio: 0.72, 95% confidence interval: 0.44 to 1.18, p = 0.19). The composite of death, reinfarction, or stroke at 12 months was significantly reduced in the early invasive compared with the conservative group (6% vs. 16%, hazard ratio: 0.36, 95% confidence interval: 0.16 to 0.81, p = 0.01). No significant differences in bleeding or infarct size were observed. CONCLUSIONS Immediate transfer for PCI did not improve the primary outcome significantly, but reduced the rate of death, reinfarction, or stroke at 12 months in patients with STEMI, treated with thrombolysis and clopidogrel in areas with long transfer distances. (Norwegian Study on District Treatment of ST-Elevation Myocardial Infarction; NCT00161005).

Increased insulin sensitivity and fibrinolytic capacity after dietary intervention in obese women with polycystic ovary syndrome

In overweight women with polycystic ovary syndrome (PCOS), increased insulin resistance has been observed. Since abdominal obesity is associated with impaired fibrinolytic capacity and elevated levels of plasminogen activator inhibitor (PAI-1) and since PAI-1 seems to be related to insulin resistance, we investigated the possible effects of dietary intervention on lipids, fibrinolysis, coagulation, and insulin sensitivity in obese PCOS women. Nine women aged 22 to 39 years (median weight, 97 kg) ate a protein-rich very—low-calorie diet (VLCD) (Nutrilett, Nycomed Pharma, Oslo, Norway; 421 kcal/d) for 4 weeks (part 1). After significant reductions of body fat (13%, P < .01), two of nine women achieved regular menstruation and became pregnant. Six of the remaining women continued on a conventional low-calorie diet (1,000 to 1,500 kcal/d) for the next 20 weeks (part 2), during which time they were generally able to preserve the body fat loss obtained in part 1 of the study. During part 1, significant reductions of total serum cholesterol (29%, P = .001) and fasting triglyceride ([TG] 31%, P < .05) levels were observed, as well as significant reductions of fasting glucose (6%, P < .05) and insulin (20%, P < .05). Insulin sensitivity (glucose disposal rate [GDR]) was increased by 93% (P < .05). After finishing part 2, insulin sensitivity was still significantly increased (86%, P < .05) and PAI-1 activity was significantly reduced (54%, P < .05). Moreover, overall fibrinolytic activity was significantly improved (serum d-dimer concentration increased by 75%, P < .05). In conclusion, through intensive dietary intervention with adequate loss of weight it is possible to change an unfavorable atherothrombogenic risk profile in overweight (PCOS) women. Most convincingly, significantly increased insulin sensitivity and fibrinolytic capacity were observed.

Autologous stem cell transplantation in acute myocardial infarction: The ASTAMI randomized controlled trial. Intracoronary transplantation of autologous mononuclear bone marrow cells, study design and safety aspects

Objectives Intracoronary transplantation of different cell populations has been used in acute myocardial infarction (AMI) with promising results. The primary objective of the Autologous Stem cell Transplantation in Acute Myocardial Infarction (ASTAMI) study is to test whether intracoronary transplantation of autologous mononuclear bone marrow cells (mBMC) improves left ventricular ejection fraction (LVEF) after anterior wall AMI. Design The ASTAMI study is a randomized, controlled, prospective study. One hundred patients with acute anterior wall ST-elevation myocardial infarction (STEMI) treated with acute percutaneous coronary intervention (PCI) are randomized in a 1:1 way to either intracoronary transplantation of autologous mBMC 5–8 d after PCI or to control. Left ventricular function, exercise capacity, biochemical status, functional class, quality of life and complications are validated at baseline and during a 12-month follow-up. Results By August 2004, out of 1004 patients with STEMI, 49 patients have been included in the study. Twenty-four patients have been randomized to intracoronary mBMC transplantation. Twenty patients had chest pain and 16 patients had ischemic ECG changes during the mBMC transplantation procedure. One patient had ventricular fibrillation 24 h after transplantation. Conclusions Intracoronary transplantation of autologous mBMC in the acute phase after AMI is feasible and seems safe in the short term.

n-3 fatty acids do not prevent restenosis after coronary angioplasty: results from the CART study ☆

Abstract OBJECTIVES The aim of the study was to investigate whether omega-3 fatty acids (n-3 FA) reduce the occurrence of restenosis after percutaneous transluminal coronary angioplasty. BACKGROUND Meta-analyses have shown significant reduction of restenosis after coronary angioplasty upon supplementation with n-3 FA. METHODS In a prospective, placebo-controlled, double-blind study, 500 patients were randomly allocated to treatment with n-3 FA (Omacor™, Pronova AS, Oslo, Norway) 5.1 g/day or corn oil (placebo) starting at least two weeks prior to elective coronary angioplasty. The treatment was continued until restenosis evaluation by quantitative coronary angiography after six months. Stenosis was defined as a minimal luminal diameter (MLD) 50% or an increase in stenosis of ≥0.7 mm. Three-hundred ninety-two patients fulfilled the criteria for initial stenosis and successful coronary angioplasty, and, except four patients who died, none were lost for follow-up. RESULTS Restenosis occurred in 108/266 (40.6%) of the treated stenoses in the Omacor group and in 93/263 (35.4%) in the placebo group (odds ratio [OR] 1.25, 95% confidence interval [CI] [0.87–1.80] p = 0.21). In the Omacor group one or more restenoses occurred in 90/196 (45.9%) patients as compared with 86/192 (44.8%) in the placebo group (OR 1.05, 95% CI [0.69–1.59] p = 0.82). CONCLUSIONS Supplementation with 5.1 g n-3 FA/day for six months, initiated at least two weeks prior to coronary angioplasty did not reduce the incidence of restenosis.

Antiphospholipid antibodies after myocardial infarction and their relation to mortality, reinfarction, and non-haemorrhagic stroke

Antiphospholipid antibodies have been suggested as markers for a high risk of recurrent cardiovascular events in young survivors of an acute myocardial infarction. However, there are few data to confirm or refute this hypothesis. In a cohort study, we have measured anticephalin (aCEPHA) and anticardiolipin (aCL) antibodies in a group of patients surviving an acute infarct. Of 597 patients studied, 13.2% were IgG or IgM aCEPHA positive compared with 4.4% of a reference population (n = 158; p = 0.002). In a multivariate analysis, adjusted for major cardiovascular risk factors, neither aCEPHA (IgG or IgM) nor a CL (IgG or IgM) was an independent risk factor for mortality, reinfarction, or non-haemorrhagic stroke. Although an increased proportion of survivors of a myocardial infarction have antiphospholipid antibodies, the presence of such antibodies is not a risk factor for subsequent coronary or cerebrovascular thrombosis.

Invasive versus conservative strategy in patients aged 80 years or older with non-ST-elevation myocardial infarction or unstable angina pectoris (After Eighty study): an open-label randomised controlled trial

BACKGROUND Non-ST-elevation myocardial infarction (NSTEMI) and unstable angina pectoris are frequent causes of hospital admission in the elderly. However, clinical trials targeting this population are scarce, and these patients are less likely to receive treatment according to guidelines. We aimed to investigate whether this population would benefit from an early invasive strategy versus a conservative strategy. METHODS In this open-label randomised controlled multicentre trial, patients aged 80 years or older with NSTEMI or unstable angina admitted to 16 hospitals in the South-East Health Region of Norway were randomly assigned to an invasive strategy (including early coronary angiography with immediate assessment for percutaneous coronary intervention, coronary artery bypass graft, and optimum medical treatment) or to a conservative strategy (optimum medical treatment alone). A permuted block randomisation was generated by the Centre for Biostatistics and Epidemiology with stratification on the inclusion hospitals in opaque concealed envelopes, and sealed envelopes with consecutive inclusion numbers were made. The primary outcome was a composite of myocardial infarction, need for urgent revascularisation, stroke, and death and was assessed between Dec 10, 2010, and Nov 18, 2014. An intention-to-treat analysis was used. This study is registered with ClinicalTrials.gov, number NCT01255540. FINDINGS During a median follow-up of 1·53 years of participants recruited between Dec 10, 2010, and Feb 21, 2014, the primary outcome occurred in 93 (40·6%) of 229 patients assigned to the invasive group and 140 (61·4%) of 228 patients assigned to the conservative group (hazard ratio [HR] 0·53 [95% CI 0·41-0·69], p=0·0001). Five patients dropped out of the invasive group and one from the conservative group. HRs for the four components of the primary composite endpoint were 0·52 (0·35-0·76; p=0·0010) for myocardial infarction, 0·19 (0·07-0·52; p=0·0010) for the need for urgent revascularisation, 0·60 (0·25-1·46; p=0·2650) for stroke, and 0·89 (0·62-1·28; p=0·5340) for death from any cause. The invasive group had four (1·7%) major and 23 (10·0%) minor bleeding complications whereas the conservative group had four (1·8%) major and 16 (7·0%) minor bleeding complications. INTERPRETATION In patients aged 80 years or more with NSTEMI or unstable angina, an invasive strategy is superior to a conservative strategy in the reduction of composite events. Efficacy of the invasive strategy was diluted with increasing age (after adjustment for creatinine and effect modification). The two strategies did not differ in terms of bleeding complications. FUNDING Norwegian Health Association (ExtraStiftelsen) and Inger and John Fredriksen Heart Foundation.

Mediastinitis After Coronary Artery Bypass Grafting Risk Factors and Long-Term Survival

BACKGROUND Mediastinitis is a severe complication of coronary artery bypass grafting. The aim of the present study was to determine incidence of mediastinitis, its risk factors, and its effect on early and long-term survival. METHODS The study has a dual design, a case-control, and a retrospective cohort, using a source population of 18,532 consecutive patients who underwent coronary artery bypass grafting from January 1989 to December 2000. The closing date was February 1, 2008. Median follow-up was 10.3 (range 8.1 to 18.9) years. Patients with mediastinitis were compared with a random control group without mediastinitis issued from the same source population in a ratio 1:4. The crude effect of mediastinitis was estimated using rate ratio and 95% confidence limits. Adjustment for multiconfounders was done with the Cox model. A logistic model was used to pinpoint risk factors of mediastinitis. Calibration and discrimination of a prognostic model was done. RESULTS One hundred seven patients (0.6%) developed mediastinitis. Diagnosis was made 12 (9 to 19) days postoperatively. Independent risk factors of mediastinitis using the logistic model were advanced age, male gender, left main stenosis, body mass index 30 kg/m(2) or greater, chronic obstructive pulmonary disease, diabetes, and increased amount of blood transfusion. There was no increased risk of early mortality (odds ratio = 0.58; 95% confidence interval 0.13 to 2.61) (p = 0.48) but there was increased risk of morbidity (intraaortic balloon pump, ventricular and supraventricular arrhythmia, stroke, inotrope, and myocardial infarction). Follow-up had a median observation time of 10.3 years. Survival for patients with mediastinitis was 49.5 +/- 5.0% versus 71.0 +/- 2.2% for controls (p < 0.01). Analysis of specific death causes documented that cardiac deaths were significantly more frequent in mediastinitis patients than in control patients. When controlling for the confounding effect of the other variables (age, cardiopulmonary bypass time, body mass index, chronic obstructive pulmonary disease), the hazard ratio associated with mediastinitis on long-term mortality was 1.59, 95% confidence limits (1.16 and 2.70) (p = 0.003). CONCLUSIONS The incidence of mediastinitis in 18,532 patients undergoing coronary artery bypass grafting surgery was low. The major preventable risk factor of mediastinitis was amount of blood transfusion. Mediastinitis had an excess risk of early morbidity and was associated with a significant reduced long-term survival. Most deaths were considered to be cardiac.

Sequential intrapulmonary and systemic activation of coagulation and fibrinolysis during and after total hip replacement surgery

Hip joint replacement surgery, using acrylic cement for prosthesis fixation, is associated with intraoperative cardiorespiratory dysfunction, and a high frequency of postoperative proximal deep vein thrombosis (DVT). Levels of prothrombin fragments 1+2 (F1+2), tissue plasminogen activator antigen (t-PA), plasminogen activator inhibitor 1 activity (PAI-1), D-dimer and interleukin 6 (IL-6) were measured in arterial (AB) and mixed venous blood (MVB) in five patients during and after total hip replacement operation with acrylic cement prosthesis fixation. Sequential peaks of F1+2, t-PA, PAI-1 and IL-6 appeared, starting with activation of coagulation during preparation of bone, closely followed by activation of fibrinolysis. Later, this was counteracted by an antifibrinolytic response and increase of IL-6. After a fibrinolytic shutdown on the third postoperative day as evidenced by a drop in t-PA and D-dimer concentrations, a second wave of coagulation was seen at the end of the first week. The present model, with frequent sampling of blood entering and leaving the lungs, confirms our earlier findings of the lung as a key organ in promoting coagulation following traumatic activation.

Hemostatic variables as independent predictors for fetal growth retardation in preeclampsia

BACKGROUND Preeclampsia is a major contributor to perinatal disease and fetal growth retardation (FGR). It has been suggested that increased intravascular coagulation, fibrin deposition in spiral arteries and hypoperfusion of the placenta are involved in these pregnancy complications. METHODS Multiple variables of the hemostatic system and lipid metabolism, as well as clinical features, were entered into univariate and multivariate models in order to examine the association with preeclampsia and FGR. RESULTS Two hundred women with preeclampsia and 97 normotensive pregnant women were examined. Plasma levels of the thrombin-antithrombin complex (TAT), tissue factor pathway inhibitor free antigen (TFPI-Fag), protein S free antigen, plasminogen activator inhibitor type-1 (PAI-1) activity and serum levels of triglycerides were significantly increased, whereas plasma levels of antithrombin (AT), fibrinogen, C4b-binding protein (C4b-BP), PAI-2 antigen and serum HDL-cholesterol levels were decreased in the presence of preeclampsia. In the multivariate regression analysis, high TFPI-Fag plasma levels were associated with the presence of preeclampsia. The presence of FGR was in the univariate analysis associated with decreased PAI-1 activity and lower concentrations of fibrin, fibrinogen, factor VII antigen and PAI-2 antigen, as well as with evidence of macroscopic placental infarction. In a multivariate regression model, low maternal weight, placental infarction and low PAI-2 levels were predictors for low birth weight. In a logistic regression model, with the presence or absence of FGR as the dependent variable, male sex of the infant, placental infarction, low PAI-1 activity and factor VII antigen or PAI-2 antigen levels were independent predictors. CONCLUSIONS Our results are consistent with activated coagulation in the placental vessels in preeclampsia. A low concentration of PAI-2 antigen in plasma emerged as the most consistent risk factor for preeclampsia and FGR.