Changes in eicosapentaenoic acid and docosahexaenoic acid and risk of cardiovascular events and atrial fibrillation: A secondary analysis of the OMEMI trial

Abstract

Background. The cardiovascular benefit from n-3 polyunsaturated fatty acids (PUFAs) after acute myocardial infarction (AMI) is controversial, and the importance of serum eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) concentrations for clinical events is unclear.Objectives. To assess changes in EPA and DHA serum concentrations during n-3 PUFA supplementation and their association with incident cardiovascular events.Methods. In the OMEMI trial, elderly patients with a recent AMI were randomized to 1.8 g/day of EPA/DHA or control (corn oil) for 2 years. The primary outcome was a composite of AMI, coronary revascularization, stroke, heart failure hospitalization, or all-cause death (major adverse cardiovascular event [MACE]) and the secondary outcome was new-onset atrial fibrillation (AF).Results. EPA and DHA measurements were available in 881 (92% of survivors) participants at randomization and study completion. EPA and DHA increased in the active treatment arm (n = 438) by a median of 87% and 16%, respectively. Greater on-treatment increases in EPA and DHA were associated with decreasing triglycerides, increasing high-density lipoprotein cholesterol, and lower baseline EPA and DHA concentrations. Greater on-treatment increases in EPA were associated with lower risk of MACE (adjusted hazard ratio 0.86 [95% confidence interval, CI, 0.75-0.99], p = 0.034), and higher risk of AF (adjusted hazard ratio (HR) 1.36 [95% CI 1.07-1.72], p = 0.011). Although there were similar tendencies for DHA changes and outcomes, these associations were not statistically significant for MACE and 1.39 [0.90-2.13] for AF). Conclusion.Greater on-treatment increases in EPA were associated with lower risk of MACE and higher risk of new-onset AF. These data suggest that the cardiovascular effects of increasing n-3 PUFA levels through supplements are complex, involving both potential benefits and harm.

Epigenetic biomarkers of autoimmune risk and protective antioxidant signaling in methylmercury-exposed adults

“…These damaged cellular components, including damaged mitochondrial DNA and membrane proteins, serve as damage-associated molecular patterns (DAMPs) that activate innate immune responses through the same pathways as pathogen-associated molecular patterns (PAMPs) 32 . However, not all studies of low dose MeHg exposure point to clear autoimmune responses in exposed individuals 33-35 , and there are noted beneficial effects of other nutrients contained within MeHg-contaminated fish and seafood, including polyunsaturated fatty acids (PUFAs) that support healthy brain development in infants and children 9,36 and cardiovascular protection to adults 37,38 . In addition, some communities have strong cultural connections to foodways centered on fish and seafood that should be considered in this cost benefit analysis 39 .…”

Omega-3 and cardiovascular prevention – Is this still a choice?

“…A secondary analysis of the OMEMI study showed that greater on-treatment increases in EPA levels were associated with lower risk of MACE (HR 0.86; 95 %CI 0.75, 0.99), the lowest risk being found in the top three quartiles of EPA increase (HR 0.39; 95 %CI 0.19, 0.79). Conversely, changes in DHA did not associate to CV outcomes (HR 0.84; 95 %CI 0.66, 1.06) [95]. Overall, as elsewhere reviewed, there may be a required threshold of EPA to be reached, namely 100 μg/mL, to achieve a clinical benefit [96].…”

“…Conversely, there was no significant association with changes in DHA [95]. ω-3 FAs (as free fatty acids) cause acute atrial conduction slowing, suppress AF inducibility, at times enhancing atrial flutter inducibility.…”

Clinical significance of polyunsaturated fatty acids in the prevention of cardiovascular diseases

“…Results showed no reduction in clinical events, whereas 7.2% of patients in the omega-3 fatty acid group versus 4.0% in the corn oil group developed atrial fibrillation ( 208 ). A secondary analysis of the OMEMI trial showed that a greater increase in eicosapentaenoic acid during treatment was associated with a higher risk of first-onset AF ( 209 ).…”