Jan Eritsland

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.

Increased levels of asymmetric dimethylarginine in populations at risk for atherosclerotic disease. Effects of pravastatin.

The aim of the present study was to investigate plasma levels of asymmetric dimethylarginine (ADMA), an important endogenous inhibitor of nitric oxide synthase, in populations at high risk for atherosclerosis as compared to healthy controls, and furthermore to evaluate the effect of cholesterol lowering therapy in individuals with hypercholesterolemia. The present study consisted of 32 men with untreated hypercholesterolemia (HC group), 38 individuals with well-controlled insulin-dependent diabetes mellitus (DM group) and 20 healthy individuals (controls). The HC subjects were randomly allocated into a double blinded, placebo-controlled cross-over designed study with 8 weeks treatment with pravastatin (40 mg/day) or matching placebo. ADMA levels were statistically significantly higher in DM and HC individuals as compared to controls (P<0.001 for both), and the L-arginine/ADMA ratios were significantly lower in both groups (P<0.001 and P<0.005, respectively). Significant reductions in total cholesterol (TC) and LDL-C levels on pravastatin were obtained (P<0.001 for both), whereas no changes were observed in the levels of ADMA or the L-arginine/ADMA ratios. Statistically significant correlations between ADMA and TC and LDL-C were found (r=0.41, P<0.001 for both). In conclusion, significantly elevated ADMA levels and reduced L-arginine/ADMA ratios were found in individuals with diabetes type-1 as well as in hypercholesterolemia. Treatment with pravastatin 40 mg/day for 8 weeks had no effect on the levels of ADMA in hypercholesterolemic men.

Abnormal glucose regulation in patients with acute ST- elevation myocardial infarction-a cohort study on 224 patients

BackgroundA high prevalence of impaired glucose tolerance and unknown type 2-diabetes in patients with coronary heart disease and no previous diagnosis of diabetes have been reported. The aims of the present study were to investigate the prevalence of abnormal glucose regulation (AGR) 3 months after an acute ST-elevation myocardial infarction (STEMI) in patients without known glucometabolic disturbance, to evaluate the reliability of a 75-g oral glucose tolerance test (OGTT) performed very early after an acute STEMI to predict the presence of AGR at 3 months, and to study other potential predictors measured in-hospital for AGR at 3 months.MethodsThis was an observational cohort study prospectively enrolling 224 STEMI patients treated with primary PCI. An OGTT was performed very early after an acute STEMI and was repeated in 200 patients after 3 months. We summarised the exact agreement observed, and assessed the observed reproducibility of the OGTTs performed in-hospital and at follow up. The patients were classified into glucometabolic categories defined according to the World Health Organisation criteria. AGR was defined as the sum of impaired fasting glucose, impaired glucose tolerance and type 2-diabetes.ResultsThe prevalence of AGR at three months was 24.9% (95% CI 19.1, 31.4%), reduced from 46.9% (95% CI 40.2, 53.6) when measured in-hospital. Only, 108 of 201 (54%) patients remained in the same glucometabolic category after a repeated OGTT. High levels of HbA1c and admission plasma glucose in-hospital significantly predicted AGR at 3 months (p < 0.001, p = 0.040, respectively), and fasting plasma glucose was predictive when patients with large myocardial infarction were excluded (p < 0.001).ConclusionThe prevalence of AGR in STEMI patients was lower than expected. HbA1c, admission plasma glucose and fasting plasma glucose measured in-hospital seem to be useful as early markers of longstanding glucometabolic disturbance. An OGTT performed very early after a STEMI did not provide reliable information on long-term glucometabolic state and should probably not be recommended.

Effect of Ischemic Postconditioning on Infarct Size in Patients With ST-Elevation Myocardial Infarction Treated by Primary PCI Results of the POSTEMI (POstconditioning in ST-Elevation Myocardial Infarction) Randomized Trial

Background Reduction of infarct size by ischemic postconditioning (IPost) has been reported in smaller proof‐of‐concept clinical studies, but has not been confirmed in other smaller studies. The principle needs to be evaluated in larger groups of ST‐elevation myocardial infarction (STEMI) patients before being implemented in clinical practice. This study assessed the effect of ischemic postcoditioning (IPost) on infarct size in patients with STEMI treated by primary percutaneous coronary intervention (PCI). Methods and Results Patients with first‐time STEMI, <6 hours from symptom onset, referred to primary PCI were randomized to IPost or control groups. IPost was administered by 4 cycles of 1‐minute reocclusion and 1‐minute reperfusion, starting 1 minute after opening, followed by stenting. In the control group, stenting was performed immediately after reperfusion. The primary endpoint was infarct size measured by cardiac magnetic resonance after 4 months. A total of 272 patients were randomized. Infarct size (percent of left ventricular mass) after 4 months (median values and interquartile range) was 14.4% (7.7, 24.6) and 13.5% (8.1, 19.3) in the control group and IPost group, respectively (P=0.18). No significant impact of IPost was found when controlling for baseline risk factors of infarct size in a multivariate linear regression model (P=0.16). The effects of IPost on secondary endpoints, including markers of necrosis, myocardial salvage, and ejection fraction, as well as adverse cardiac events during follow‐up, were consistently neutral. Conclusions In contrast to several smaller trials reported previously, we found no significant effects of IPost on infarct size or secondary study outcomes. Clinical Trial Registration URL: http://www.clinicaltrials.gov Unique identifier: NCT.No.PO1506.

Levosimendan in acute heart failure following primary percutaneous coronary intervention-treated acute ST-elevation myocardial infarction. Results from the LEAF trial: a randomized, placebo-controlled study.

The calcium sensitizer levosimendan may counteract stunning after reperfusion of ischaemic myocardium, but no randomized placebo‐controlled trials exist regarding its use in PCI‐treated ST‐segment elevation infarction (STEMI). We evaluated the efficacy and safety of levosimendan in patients with a primary PCI‐treated STEMI complicated by symptomatic heart failure (HF).

Gender differences in management and outcome of acute myocardial infarctions treated in 2006-2007.

Objectives: Women with acute myocardial infarction (AMI) previously received less invasive evaluation and experienced higher mortality than men. After improvements in AMI care it is unclear whether gender differences still exist in management and outcome of AMI. Methods: All patients admitted to Ullevål University Hospital for AMI during 2006 and 2007 were included in this cohort study. Predefined data were recorded during the hospital stay, and the survival status of the patients was ascertained on June 30, 2008. Results: A total of 931 women and 2,174 men were included. No gender differences were observed in treatment delay or age-adjusted odds ratio (OR) of invasive evaluation in ST-elevation myocardial infarction (STEMI). In non-ST-elevation myocardial infarction (NSTEMI), women were less likely than men to undergo coronary angiography (adjusted OR 0.72, 95% CI 0.53–0.99, p = 0.044) and percutaneous coronary intervention (adjusted OR 0.60, 95% CI 0.47–0.76, p = 0.0001). Age-adjusted in-hospital mortality and long-term survival were similar between men and women. Conclusions: Women with STEMI experienced similar treatment delays and odds of invasive evaluation as men. However, gender differences in invasive evaluation were still observed in NSTEMI patients. No sex differences were observed in age-adjusted early and long-term mortality.

Bradycardia during therapeutic hypothermia is associated with good neurologic outcome in comatose survivors of out-of-hospital cardiac arrest.

Objective: Comatose patients resuscitated after out-of-hospital cardiac arrest receive therapeutic hypothermia. Bradycardia is frequent during therapeutic hypothermia, but its impact on outcome remains unclear. We explore a possible association between bradycardia during therapeutic hypothermia and neurologic outcome in comatose survivors of out-of-hospital cardiac arrest. Design: Retrospective cohort study, from January 2009 to January 2011. Setting: University hospital medical and cardiac ICUs. Patients: One hundred eleven consecutive comatose out-of-hospital cardiac arrest patients treated with therapeutic hypothermia. Interventions: Patients treated with standardized treatment protocol after cardiac arrest. Measurements and Main Results: All out-of-hospital cardiac arrest patients’ records were reviewed. Hemodynamic data were obtained every fourth hour during the first days. The patients were in temperature target range (32–34°C) 8 hours after out-of-hospital cardiac arrest and dichotomized into bradycardia and nonbradycardia groups depending on their actual heart rate less than or equal to 60 beats/min or more than 60 beats/min at that time. Primary endpoint was Cerebral Performance Category score at hospital discharge. More nonbradycardia group patients received epinephrine during resuscitation and epinephrine and norepinephrine in the early in-hospital period. They also had lower base excess at admission. Survival rate with favorable outcome was significantly higher in the bradycardia than the nonbradycardia group (60% vs 37%, respectively, p = 0.03). For further heart rate quantification, patients were divided into quartiles: less than or equal to 49 beats/min, 50–63 beats/min, 64–77 beats/min, and more than or equal to 78 beats/min, with respective proportions of patients with good outcome at discharge of 18 of 27 (67%), 14 of 25 (56%), 12 of 28 (43%), and 7 of 27 (26%) (p = 0.002). Patients in the lowest quartile had significantly better outcome than the higher groups (p = 0.027), whereas patients in the highest quartile had significantly worse outcome than the lower three groups (p = 0.013). Conclusions: Bradycardia during therapeutic hypothermia was associated with good neurologic outcome at hospital discharge. Our data indicate that bradycardia should not be aggressively treated in this period if mean arterial pressure, lactate clearance, and diuresis are maintained at acceptable levels. Studies, both experimental and clinical, are warranted.

Influence of highly concentrated n-3 fatty acids on serum lipids and hemostatic variables in survivors of myocardial infarction receiving either oral anticoagulants or matching placebo

Forty patients with previous myocardial infarction were given 4 capsules with 1 g concentrated fish oil preparation daily for 4 weeks. No special diet was applied. The supplementation was equivalent to 3.4 grams of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) daily. Twenty-two of the 40 subjects received concomitant treatment with long-term oral anticoagulants (OAC). The fatty acid composition of serum after the supplementation period showed a significant increase in the proportion of EPA and DHA, while arachidonic acid (AA) remained essentially constant. This resulted in a rise of the EPA/AA ratio from 0.59 to 1.49 (p less than 0.001), confirming satisfying absorption of the concentrate. Blood lipids showed an overall decrease of triglycerides (TG) by 25% (p = 0.02), while total cholesterol rose by 5% (p = 0.03) and HDL-cholesterol was unaffected. Blood glucose and the TG associated factors plasminogen activator inhibitor and factor VII-phospholipid complex revealed trends towards reduction. Ivy bleeding time showed a significant prolongation, the median increasing from 240 to 270 seconds. A significant increase of fibrinogen was seen, as was a decrease of clotting time in the combined prothrombin test in patients receiving concomitant OAC. Thus, given for 4 weeks, the investigated concentrate of n-3 fatty acids exerts not merely beneficial effects as far as the risk profile for atherosclerotic disease is concerned. The results also point towards interactions with OAC that may be of clinical relevance.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of serum lipoprotein(a) and homocyst(e)ine levels on graft patency after coronary artery bypass grafting

High serum levels of lipoprotein(a) and homocyst(e)ine are considered independent risk factors for atherothrombotic disease. In a prospective study in patients undergoing coronary artery bypass grafting, the preoperatively determined lipoprotein(a) and homocyst(e)ine levels were related to the frequency of 1-year graft occlusion. A cohort of 610 patients who underwent coronary artery bypass surgery was followed through the first postoperative year. Shunt angiography was performed in 581 patients (95%) at a mean of 12.1 +/- 1.5 months after the operation. The serum levels of lipoprotein(a) (n = 570) and homocyst(e)ine (n = 565) in patients with occluded internal mammary artery (IMA) grafts were not significantly different from the levels in those with open IMA grafts. Also, the serum lipoprotein(a) and homocyst(e)ine levels in patients with > or = 1 occluded vein graft were not significantly different from those in patients with all vein grafts patent. This study also determined the incidence of graft occlusion in quartiles of the lipoprotein(a) and homocyst(e)ine levels, respectively, and tested for linear trends. No significant trends in the incidence of graft occlusion were found, but the number of patients with vein graft occlusions was higher in the lowest quartile of lipoprotein(a) than that in the upper 3 quartiles (odds ratio, 1.82, 95% confidence interval, 1.21 to 2.74, p = 0.0025). Controlling for background variables in multivariate models only slightly modified the results. Thus, apart from an unexplained excess of vein graft occlusions in the lowest quartile of lipoprotein(a) levels, no association between the preoperative serum lipoprotein(a) or homocyst(e)ine levels and the frequency of 1-year graft occlusion could be demonstrated.

Activated protein C resistance and graft occlusion after coronary artery bypass surgery

A defect in the anticoagulant response to activated protein C (APC resistance) has been identified in a high proportion of patients with familial thrombophilia (1-4). APC resistance is caused by an inherited defect in the anticoagulant function of factor V (5) and is most often caused by a point mutation in the factor V molecule (6). The role of APC resistance as a risk factor for arterial thrombosis is not yet clear. Thrombotic mechanisms are involved in the pathogenesis of graft occlusion after coronary artery bypass grafting (CABG) (7). We determined the incidence of one-year graft occlusion in a large cohort of patients undergoing CABG and related this to the occurrence of APC resistance, measured in blood samples taken preoperatively.