Serum free fatty acid pattern and risk of myocardial infarction: a case-control study

Abstract. Yli‐Jama P, Meyer HE, Ringstad J, Pedersen JI (Medical Faculty, University of Oslo; National Health Screening Services, Oslo; and Østfold Central Hospital, Norway). Serum free fatty acid pattern and risk of myocardial infarction: a case‐control study. J Intern Med 2002; 251: 19–28. Objectives. To investigate the association between composition of serum free fatty acid (FFA) fraction and risk of a first myocardial infarction (MI). Design. A case‐control design. Setting. The patients were recruited from Ullevål Hospital in Oslo and Østfold Central Hospital in Fredrikstad and Sarpsborg, Norway. Subjects. A total of 103 patients with first MI and 104 population controls, both men and postmenopausal women, age 45–75 years. Results. The mean molar percentage content of docosahexaenoic (DHA), eicosapentaenoic (EPA), stearic and myristic acid in the serum FFA fraction was significantly lower in cases than in controls, whereas that of oleic and linoleic acid was higher in cases. Increased percentage content of total very long‐chain omega‐3 fatty acids (VLC n‐3) in serum FFA was associated with decreased risk of MI. Multivariate odds ratio (OR), adjusted for age, sex, waist‐hip ratio, smoking, family history of coronary heart disease (CHD) and years of education was 0.20 (95% CI 0.06–0.63) for the highest vs. lowest quartile. Also increased content of stearic acid was associated with decreased risk. Multivariate OR adjusted as above was 0.38 (95% CI 0.14–1.04) for the highest versus lowest quartile. After adjustment for oleic acid, however, the inverse linear trend was no longer significant. Conclusions. The percentage content of VLC n‐3 as well as of stearic acid in serum FFA was inversely associated with risk of myocardial infarction. That of VLC n‐3 may reflect diet, but additionally these free fatty acids might in some way be related to the pathogenetic process and not only reflect their content in adipose tissue.     

n-3多不饱和脂肪酸与心房颤动

多不饱和脂肪酸(polyunsaturated fatty acid,PUFA)又称多烯酸.是指分子结构中含有2个或2个以上不饱和双键的脂肪酸.PUFA按照n编号系统(也叫ω,编号系统),即从甲基端开始第1个双键的位置,可分为n-3组、n-6组、n-7组、n-9组,每一组成员都可转化为多不饱和或链更长的脂肪酸.     

A multi-country health-economic evaluation of highly concentrated n-3 polyunsaturated fatty acids in the secondary prevention after myocardial infarction

Patients who survive an acute myocardial infarction (MI) are at increased risk of subsequent major cardiovascular events and cardiac (often sudden) death. The use of highly concentrated and purified omega-3 polyunsaturated fatty acids (n-3 PUFAs), in addition to standard secondary prevention after MI, results in a significant reduction in the risk of sudden death. This study assessed the cost-effectiveness of adding n-3 PUFAs to the current secondary prevention treatment after acute MI in 5 countries: Australia, Belgium, Canada, Germany, Poland. Based on the clinical outcomes of GISSI-Prevenzione (MI, stroke, revascularisation rate and mortality), a decision-model was built in DataPROTM. The implications of adding n-3 PUFAs to standard treatment in patients with a recent history of MI were analysed from the health care payer's perspective. The time horizon was 3.5 years (identical to GISSI-Prevenzione). Event costs were based on literature data. Life expectancy data for survivors of cardiac disease were taken from the Saskatchewan database and then country-adjusted. Results are expressed as extra cost (Euro) per life-year gained (LYG). Annual discounting of 5% was applied to health effects and costs. Treatment with highly concentrated n-3 PUFAs yielded between 0.260 (Poland) and 0.284 (Australia) LYG, at an additional cost of Euro 807 (Canada) to Euro 1,451 (Belgium). The incremental cost-effectiveness ratio (ICER) varied between Euro 2,867 (Canada) and Euro 5,154 (Belgium) per LYG. Sensitivity analyses on effectiveness, cost of complications and discounting proved the robustness of the results. A 2nd order Monte Carlo simulation based on the 95% CIs obtained from GISSI showed that highly concentrated n-3 PUFAs are cost-effective in more than 99% of patients (assuming societal willingness to pay threshold of Euro 20,000/LYG). Including health care costs incurred during the remaining life-years considerably increased total costs, but had no impact on the ICER-based treatment recommendation. Adding highly concentrated n-3 PUFAs to standard treatment in the secondary prevention after MI appears to be cost-effective in the 5 countries studied.     

Effects of n-3 polyunsaturated fatty acid on upper limit of vulnerability shocks

BACKGROUND: Ventricular fibrillation (VF) can be induced when a strong shock is delivered during the vulnerable period of a cardiac cycle. VF, however, cannot be induced if the shock strength is increased to the "upper limit of vulnerability" (ULV) level. Docosahexaenoic acid (DHA) has been shown to prevent the occurrence of VF after coronary occlusion. However, its effects on the ULV have not been verified. We tested the hypothesis that ULV shock strength is decreased after DHA administration. METHODS: In 10 pigs, 10 S1s (square, 5-ms) were delivered from the RV apex electrode at 300 ms cycle length. Shocks (S2, biphasic) were delivered from the RV-SVC electrodes after the last S1. The ULV was determined using an up/down protocol. In group 1 (n = 5), after the control ULV was determined at the beginning of the study, a solution containing 1.0 gm of DHA was infused intravenously within 90 min. The ULV (DHA-ULV) was determined again after the end of infusion. In group 2 (n = 5), the vehicle for DHA was infused instead of DHA to confirm that the vehicle did not have an effect on the ULV. RESULTS: DHA-ULV (412 +/- 58 V, 12 +/- 3 J) was significantly decreased (P < 0.04) compared to the control ULV (478 +/- 32 V, 16 +/- 3 J). The ULV before (483 +/- 28 V, 16 +/- 1 J) and after (463 +/- 28 V, 15 +/- 2 J) the vehicle infusion was not different (P = 0.4). There was no change in the systolic blood pressure as well as heart rate in both groups. CONCLUSION: DHA significantly decreases the ULV (13% by voltage and 25% by energy), suggesting that DHA can help to prevent VF induced by a strong stimulus delivered during the vulnerable period.     

Protective effect of n-3 polyunsaturated fatty acid on primary culture of rat hepatocytes

BACKGROUND AND AIM: Recently, we reported on the beneficial clinical effects of eicosapentaenoic acid (EPA) in patients with primary biliary cirrhosis (PBC) who were unresponsive to ursodeoxycholic acid (UDCA). In this study we examined the effect of EPA on rat hepatocytes in primary culture. METHODS: Hepatocytes were isolated from rat liver by perfusion of collagenase and cultured with or without EPA. Cell damage induced by chenodeoxycholic acid (CDCA) was assessed by WST-8 assay and lactate dehydrogenase (LDH) release. PGE(2) and LTB(4) concentrations in the culture medium were measured by enzyme-linked immunosorbent assay (ELISA). cDNA was made from total RNA that was extracted from hepatocytes, and TaqMan polymerase chain reaction (PCR) was performed to assess the expression of CuZn and Mn superoxide dismutase (SOD) mRNA. RESULTS: When rat hepatocytes were cultured in the presence of EPA, the damage caused by CDCA was significantly decreased compared with cells cultured without EPA. Cytotoxicity significantly decreased in the presence of EPA. Furthermore, SOD mRNA expression was increased by adding EPA. These findings indicated that EPA protects cells by scavenging superoxide radicals ((*)O(2-)) mediated by SOD production. CONCLUSION: EPA has a direct protective effect on rat hepatocytes, which is in agreement with the clinical efficacy of EPA in PBC patients.     

Circulating n-3 fatty acids and linoleic acid as indicators of dietary fatty acid intake in post-myocardial infarction patients

Background and aims

Population-based studies often use plasma fatty acids (FAs) as objective indicators of FA intake, especially for n-3 FA and linoleic acid (LA). The relation between dietary and circulating FA in cardiometabolic patients is largely unknown. We examined whether dietary n-3 FA and LA were reflected in plasma lipid pools in post-myocardial infarction (MI) patients.

Depression as a risk factor for mortality after acute myocardial infarction

The ENRICHD clinical trial, which compared an intervention for depression and social isolation to usual care, failed to decrease the rate of mortality and recurrent acute myocardial infarction (AMI) in post-AMI patients. One explanation for this is that depression was not associated with increased mortality in these patients. The purpose of this study was to determine if depression was associated with an increased risk of mortality in a subsample of the ENRICHD trial's depressed patients compared with a group of nondepressed patients recruited for an ancillary study. Three hundred fifty-eight depressed patients with an acute AMI from the ENRICHD clinical trial and 408 nondepressed patients who met the ENRICHD medical inclusion criteria were followed for up to 30 months. There were 47 deaths (6.1%) and 57 nonfatal AMIs (7.4%). After adjusting for other risk factors, depressed patients were at higher risk for all-cause mortality (hazard ratio 2.4, 95% confidence interval 1.2 to 4.7) but not for nonfatal recurrent infarction (hazard ratio 1.2, 95% confidence interval 0.7 to 2.0) compared with nondepressed patients. In conclusion, depression was an independent risk factor for death after AMI, but it did not have a significant effect on mortality until nearly 12 months after the acute event, nor did it predict nonfatal recurrent infarction.     

A high-cholesterol, n-3 polyunsaturated fatty acid diet causes different responses in rats and hamsters

This study was designed to investigate the response to a high-cholesterol, n-3 polyunsaturated fatty acid (PUFA) or n-6 PUFA diet in rats and hamsters. Animals were fed n-3 or n-6 PUFA with a cholesterol-free diet, or with a diet enriched with cholesterol (0.5%, w/w) for 2 weeks. In rats and hamsters fed a cholesterol-free diet, plasma cholesterol, triglycerides and very-low-density lipoprotein (VLDL)-triglyceride levels in n-3 PUFA group were significantly lower than those in n-6 PUFA group. In contrast, when diets were supplemented with 0.5% cholesterol, the plasma cholesterol- and triglyceride-lowering effect of dietary n-3 PUFA disappeared. In hamsters fed with the atherogenic diet (0.5% dietary cholesterol) for 2 weeks, n-3 PUFA induced hypercholesterolemia more than n-6 PUFA, the increase being in the VLDL and low-density lipoprotein (LDL) fractions. Our data thus indicate that elevation of VLDL- and LDL-cholesterol in hamsters by n-3 PUFA, compared with n-6 PUFA, is dependent on 0.5% dietary cholesterol supplementation. In rats, on the other hand, dietary n-3 PUFA did not induce hypercholesterolemia more than n-6 PUFA when 0.5% cholesterol was supplemented. Although the effects of n-3 PUFA on plasma cholesterol, triglycerides and VLDL-triglycerides were similar in hamsters and rats, the interactive effects of n-3 PUFA and cholesterol on plasma and lipoprotein cholesterol levels differed in the two species. It was also found that plasma triglycerides, cholesterol and lipoprotein cholesterol levels in hamsters are higher than in rats in the presence and absence of dietary cholesterol. In addition, cholesterol feeding induces hypertriglyceridemia and hypercholesterolemia only in hamsters. Moreover, liver triglyceride concentrations increased in rats fed a cholesterol-rich diet and hepatic triglyceride levels of the n-3 PUFA-fed rats were significantly lower than those in the n-6 PUFA-fed rats in the presence and absence of dietary cholesterol. However, triglycerides did not accumulate in the liver in hamsters fed a cholesterol-rich diet and hepatic triglyceride levels of the n-3 PUFA-fed hamsters were not significantly different from those in the n-6 PUFA-fed hamsters in the presence and absence of dietary cholesterol. Therefore, these studies confirm marked species differences in response to the interactive effects of dietary n-3 PUFA and cholesterol.     

Highly purified omega-3 polyunsaturated fatty acids are effective as adjunct therapy for secondary prevention of myocardial infarction

Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione was the first large randomized trial to produce evidence that a pharmaceutical preparation of highly purified omega-3 polyunsaturated fatty acids (PUFAs), administered as an adjunct to other accepted interventions, had a favorable effect on hard clinical end-points in post-myocardial infarction patients. Much of the 20% all-cause mortality benefit recorded during the study could be attributed to a 45% reduction in sudden death--a fatal outcome that traditionally has proved resistant to medical intervention. These results were obtained with an omega-3 PUFA dose of 1 g/day, which is much lower than was routinely being used at the time the study was initiated (e.g. 4 g/day for hypertriglyceridemia). One consequence of this low-dose regimen was that the tolerability profile of omega-3 PUFAs during GISSI-Prevenzione was considered highly satisfactory, with low adverse event incidence rates and low rates of discontinuation due to adverse events. Time-course analysis established that much of the survival benefit of omega-3 PUFA treatment in GISSI-Prevenzione was realized during the early months of the trial. The beneficial effects of omega-3 PUFA treatment were observed on top of standard, secondary pharmacological prevention therapy like anti-platelet agents, statins, beta-blockers and angiotensin-converting enzyme (ACE) inhibitors. The benefits of omega-3 PUFA therapy were also apparent in patients at all standards of adherence to a healthy diet and may have been augmented in patients with the best dietary profile. Patients with diabetes mellitus (approximately 15% of the study cohort) appeared to benefit from omega-3 PUFAs to at least the same extent as the general study population; the treatment effect on sudden death was progressively more pronounced as left ejection fraction declined. Cost-effectiveness analyses undertaken from a third-party payer perspective for Italy revealed that the cost of low-dose treatment with highly purified omega-3 PUFAs was approximately Euro 25,000 per life-year gained.