Erik Berg Schmidt

Cardiovascular effects of marine omega-3 fatty acids.

Much evidence shows that the marine omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid have beneficial effects in various cardiac disorders, and their use is recommended in guidelines for management of patients after myocardial infarction. However, questions have been raised about their usefulness alongside optimum medical therapies with agents proven to reduce risk of cardiac events in high-risk patients. Additionally, there is some evidence for a possible pro-arrhythmic effect in subsets of cardiac patients. Some uncertainly exists about the optimum dose needed to obtain beneficial effects and the relative merit of dietary intake of omega-3 polyunsaturated fatty acids versus supplements. We review evidence for the effects of omega-3 polyunsaturated fatty acids on various cardiac disorders and the risk factors for cardiac disease. We also assess areas of uncertainty needing further research.

Effect of fish oil on heart rate variability in survivors of myocardial infarction: a double blind randomised controlled trial

Marine n-3 polyunsaturated fatty acids may protect against ischaemic heart disease.1 In the diet and reinfarction trial patients with an acute myocardial infarction advised to eat fish rich in n-3 polyunsaturated fatty acids had a 29% reduction in two year all cause mortality compared with controls.2 The authors hypothesised that dietary n-3 polyunsaturated fatty acids might reduce malignant ventricular arrhythmias and sudden cardiac death, as reported in animals.3 We investigated a possible antiarrhythmic effect of dietary n-3 polyunsaturated fatty acids in survivors of myocardial infarction. Patients were eligible for study if they had been discharged from the department of cardiology at Aalborg Hospital between November 1991 and August 1993 after a myocardial infarction and had a ventricular ejection fraction below 0.40. We excluded patients aged over 75, patients with pacemakers or permanent tachyarrhythmias, and those with serious non-cardiac disease. Eighty one patients fulfilled the inclusion criteria and 55 gave informed consent to a double blind placebo controlled trial. Patients were randomly …

Fish Consumption, n-3 Fatty Acids in Cell Membranes, and Heart Rate Variability in Survivors of Myocardial Infarction With Left Ventricular Dysfunction

To elucidate a possible antiarrhythmic effect of long-chained n-3 polyunsaturated fatty acids, heart rate variability was assessed in 52 patients with a previous myocardial infarction and left ventricular dysfunction. The content of n-3 polyunsaturated fatty acids in platelets was closely associated with the patients fish-consuming habits, and a significant positive correlation was observed between the n-3 fatty acid docosahexaenoic acid and heart rate variability.

Marine n-3 Fatty Acids, Wine Intake, and Heart Rate Variability in Patients Referred for Coronary Angiography

Background —Dietary n-3 polyunsaturated fatty acids (PUFAs) derived from fish may reduce the incidence of sudden cardiac death (SCD). In addition, wine drinking is suggested to have a protective effect against cardiovascular death. Methods and Results —We included 291 patients referred for coronary angiography in whom ischemic heart disease was suspected and all of whom completed a food questionnaire regarding fish and wine intake. The n-3 PUFA composition of granulocyte membranes and of adipose tissue was measured. In addition, 24-hour heart rate variability (HRV) was analyzed. Fish intake was positively associated with the level of n-3 PUFAs in adipose tissue. Significant positive correlation coefficients were found between HRV indices and the levels of n-3 PUFAs in granulocytes. Wine intake was also significantly positively related to HRV, but the patients with the highest wine intake also had the highest intake of fish, as documented by a high n-3 PUFA content in adipose tissue. Multiple linear regression analysis revealed that traditional factors such as treatment with &bgr;-blockers, smoking, age, and previous myocardial infarction were independently related to HRV, and furthermore that n-3 PUFAs (but not wine intake) were significantly independently associated with HRV. Conclusions —The close positive association between n-3 PUFAs and HRV in patients suspected of having ischemic heart disease may indicate a protective effect of n-3 PUFAs against SCD. This may partly explain the reduction in SCD observed in humans with a modest intake of n-3 PUFA. Wine intake was also positively correlated with HRV, but this correlation was no longer significant after controlling for the cellular level of n-3 PUFA.

Intake of carbohydrates compared with intake of saturated fatty acids and risk of myocardial infarction: importance of the glycemic index

BACKGROUND Studies have suggested that replacing saturated fatty acids (SFAs) with carbohydrates is modestly associated with a higher risk of ischemic heart disease, whereas replacing SFAs with polyunsaturated fatty acids is associated with a lower risk of ischemic heart disease. The effect of carbohydrates, however, may depend on the type consumed. OBJECTIVES By using substitution models, we aimed to investigate the risk of myocardial infarction (MI) associated with a higher energy intake from carbohydrates and a concomitant lower energy intake from SFAs. Carbohydrates with different glycemic index (GI) values were also investigated. DESIGN Our prospective cohort study included 53,644 women and men free of MI at baseline. RESULTS During a median of 12 y of follow-up, 1943 incident MI cases occurred. There was a nonsignificant inverse association between substitution of carbohydrates with low-GI values for SFAs and risk of MI [hazard ratio (HR) for MI per 5% increment of energy intake from carbohydrates: 0.88; 95% CI: 0.72, 1.07). In contrast, there was a statistically significant positive association between substitution of carbohydrates with high-GI values for SFAs and risk of MI (HR: 1.33; 95% CI: 1.08, 1.64). There was no association for carbohydrates with medium-GI values (HR: 0.98; 95% CI: 0.80, 1.21). No effect modification by sex was observed. CONCLUSION This study suggests that replacing SFAs with carbohydrates with low-GI values is associated with a lower risk of MI, whereas replacing SFAs with carbohydrates with high-GI values is associated with a higher risk of MI.

C-reactive protein, dietary n-3 fatty acids, and the extent of coronary artery disease

The acute-phase reactant C-reactive protein (CRP) has emerged as an independent risk factor for coronary artery disease. Experimental and clinical studies provide evidence of anti-inflammatory effects of n-3 polyunsaturated fatty acids (PUFA) derived from fish. We have studied the effect of marine n-3 PUFA on CRP levels in 269 patients referred for coronary angiography because of clinical suspicion of coronary artery disease. All patients filled out a food questionnaire regarding fish intake. The n-3 PUFA content of granulocyte membranes was determined and the concentration of CRP in serum was measured using a highly sensitive assay. The results were related to angiographic findings. CRP was significantly higher in patients with significant coronary stenoses than in those with no significant angiographic changes (p <0.001), but the CRP levels were not associated with the number of diseased vessels. Subjects with CRP levels in the lower quartile had a significantly higher content of docosahexaenoic acid (DHA) in granulocytes than subjects with CRP levels in the upper quartile (p = 0.02), and in a multivariate linear regression analysis, DHA was independently correlated to CRP (R(2) = 0.179; p = 0.003). The inverse correlation between CRP and DHA may reflect an anti-inflammatory effect of DHA in patients with stable coronary artery disease and suggest a novel mechanism by which fish consumption may decrease the risk of coronary artery disease.

Bioavailability of marine n-3 fatty acid formulations.

The use of marine n-3 polyunsaturated fatty acids (n-3 PUFA) as supplements has prompted the development of concentrated formulations to overcome compliance problems. The present study compares three concentrated preparations - ethyl esters, free fatty acids and re-esterified triglycerides - with placebo oil in a double-blinded design, and with fish body oil and cod liver oil in single-blinded arms. Seventy-two volunteers were given approximately 3.3g of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) daily for 2 weeks. Increases in absolute amounts of EPA and DHA in fasting serum triglycerides, cholesterol esters and phospholipids were examined. Bioavailability of EPA+DHA from re-esterified triglycerides was superior (124%) compared with natural fish oil, whereas the bioavailability from ethyl esters was inferior (73%). Free fatty acid bioavailability (91%) did not differ significantly from natural triglycerides. The stereochemistry of fatty acid in acylglycerols did not influence the bioavailability of EPA and DHA.

Omega-3 fatty acids. Current status in cardiovascular medicine.

SummaryOmega-3 polyunsaturated fatty acids (PUFA) reduce fasting and postprandial triglycerides, decrease platelet and leucocyte reactivity, and may slightly decrease blood pressure. Omega-3 PUFA may also beneficially influence vessel wall characteristics and blood rheology. Furthermore, these compounds have been shown to inhibit ventricular tachyarrhythmias in animals. Omega-3 PUFA may impair fibrinolysis and could lead to increased oxidation of lipoproteins. Potential adverse effects must not be neglected, but should be viewed in light of the beneficial effects of these agents.Clinical studies investigating the effects of dietary omega-3 PUFA in the prevention and treatment of cardiovascular disease (CVD) are beginning to emerge. The results have offered some promise, but further studies are needed to define the role of these agents in CVD.Long term trials and studies using omega-3 PUFA as adjuvants to conventional therapy in patients with coronary artery disease, hyperlipidaemia and hypertension may be of particular interest.

N-3 Fatty Acids as Secondary Prevention against Cardiovascular Events in Patients Who Undergo Chronic Hemodialysis: A Randomized, Placebo-Controlled Intervention Trial

Patients who are treated with chronic hemodialysis (HD) experience premature cardiovascular disease and an increased mortality. N-3 polyunsaturated fatty acids (PUFA) may be effective in the secondary prevention of cardiovascular disease, but the effects of n-3 PUFA has not previously been examined in HD patients. It was hypothesized that secondary prevention with n-3 PUFA would reduce the number of cardiovascular events and death in patients who are treated with chronic HD. A randomized, double-blind, placebo-controlled intervention trial compared the effect of n-3 PUFA and a control treatment as secondary prevention of cardiovascular events in HD patients. The primary outcome was a composite of total cardiovascular events and death. A total of 206 patients were randomly assigned to treatment with n-3 PUFA or control treatment and followed for 2 yr or until reaching a predefined end point. During the trial, 121 (59%) of 206 patients reached a primary end point. N-3 PUFA had no significant effect on the primary composite end point of cardiovascular events and death (62 versus 59; NS). In the n-3 PUFA group, a significant reduction was seen in the number of myocardial infarctions (four versus 13; P = 0.036). This trial was limited by a relatively small number of patients and a large number of withdrawals. However, it is concluded that treatment with n-3 PUFA did not reduce the total number of cardiovascular events and death in this high-risk population. N-3 PUFA significantly reduced the number of myocardial infarctions as a secondary outcome, a finding that might be of clinical interest.

The effects of dietary supplementation with n‐3 polyunsaturated fatty acids in patients with rheumatoid arthritis: a randomized, double blind trial

Abstract. Study objective: To determine the effect of dietary supplementation with n‐3 polyunsaturated fatty acids (n‐3 PUFA) on disease variables in patients with rheumatoid arthritis. Design: Multicenter, randomized, placebo controlled, double blind. Setting: Three Danish hospital Departments of Rheumatology. Patients: Fifty‐one patients with active rheumatoid arthritis. Intervention: Random allocation to 12 weeks of treatment with either six n‐3 PUFA capsules (3–6 g) or six capsules with fat composition as the average Danish diet. Main results: Significant improvement of morning stiffness and joint tenderness. No significant effect on the four other assessed clinical parameters. No serious side effects. Conclusions: Dietary supplementation with n‐3 PUFA in patients with rheumatoid arthritis improved two out of six patient reported disease parameters. Further studies are needed to clarify the more precise role of n‐3 PUFA in the treatment of rheumatoid arthritis.