Omega-3 fatty acids: antiarrhythmic, proarrhythmic or both?

Abstract

This review focuses on developments after 2008, when the topic was last reviewed by the author. Pertinent publications were found by medline searches and in the author's personal data base. Prevention of atrial fibrillation (AF) was investigated in a number of trials, sparked by one positive report on the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), considerations of upstream therapy, data from electrophysiologic laboratories and animal experiments. If EPA + DHA prevent postoperative AF, the effect is probably smaller than initially expected. The same is probably true for maintenance of sinus rhythm after cardioversion and for new-onset AF. Larger trials are currently ongoing. Prevention of ventricular arrhythmias was studied in carriers of an implanted cardioverterdefibrillator, with no clear results. This might have been due to a broad definition of the primary endpoint, including any ventricular arrhythmia and any action of the device. Epidemiologic studies support the contention that high levels of EPA + DHA prevent sudden cardiac death (SCD). However, since SCD is a rare occurrence, it is difficult to conduct an adequately powered trial. In patients with congestive heart failure, EPA + DHA reduced total mortality and rehospitalizations, but not SCD or presumed arrhythmic death. Of three trials in patients after a myocardial infarction, two were inadequately powered, and in one, the dose might have been too low. Taken together, while epidemiologic studies support an inverse relation between EPA + DHA and occurrence of SCD or arrhythmic death, demonstrating this effect in intervention trials remained elusive so far. A pro-arrhythmic effect of EPA + DHA has not been seen in intervention studies, and results of epidemiologic and animal studies also rather argue against such an effect. A different, and probably more productive, perspective is provided by a standardized analytical assessment of a person's status in EPA + DHA by use of the omega-3 index, EPA + DHA in red cell fatty acids. In populations with a high omega-3 index, SCD is rare. Intervention trials can become more effective by including a low omega-3 index into the inclusion criteria, thus creating a study population more likely to demonstrate an effect of EPA + DHA. This is especially relevant in case of rare endpoints, like new-onset AF or SCD.

Mechanisms of Action of (n-3) Fatty Acids,

“…They have been demonstrated to beneficially modify a number of risk factors for cardiovascular disease. Risk factors improved include blood pressure (11), platelet reactivity and thrombosis (12), plasma TG concentrations (13), vascular function (14), cardiac arrhythmias (15), heart rate variability (15), and inflammation (16). Due to these effects, increased intake of very long-chain (n-3) fatty acids is associated with a reduced risk of cardiovascular morbidity and mortality (17,18).…”

Диабетическая Кардиальная Автономная Нейропатия: Каковы Перспективы В Лечении?

“…Длинноцепочеч-ные -3 ПНЖК применяются в связи с их влиянием на гомеостаз глюкозы и ИР (снижение ИР в мыш-цах > жировой ткани >> печени; предположительно ингибируют секрецию инсулина и задерживают разви-тие СДТ2); влиянием на состояние липидного обмена (уменьшение концентрации ТГ, вероятно, увеличение концентрации холестерина ЛПВП, улучшение липид-ного профиля у пациентов с СДТ2 и ДЛП); умеренным снижением артериального давления (АД); улучшением функции эндотелия; уменьшением воспаления и улуч-шением антиоксидантной защиты [38][39][40][41].…”

Current Treatment of Dyslipidemia: Evolving Roles of Non-Statin and Newer Drugs

“…Over a 4.6-year period, JELIS reported a 19 % relative reduction in MACE. One double-blinded, placebo-controlled clinical trial randomized 6624 patients either at high risk of or having known CVD to 1 g of n-3 PUFA or olive oil, Table 3 Potentially favorable properties of omega-3 polyunsaturated long-chain fatty acids Lower blood pressure [107] Decrease resting heart rate [108] and increase heart rate variability to lower arrhythmias [109] Lower risk of sudden cardiac death in primary and secondary prevention patients [110] Increase myocardial filling, improve function, and lower myocardial oxygen demand [109] Lower ischemia-induced resting membrane depolarization [110] Reduce risk of ischemia-related ventricular fibrillation [111][112][113] High omega-3 levels retard development of heart failure and increase survival [114] Incorporation in membranes increases fluidity [111] Potent effects upon ion channels and signaling proteins [111,112] Modulate downstream metabolites that control inflammation, lower CRP [112,113] Lower cellular oxidative stress [115][116][117] Precursors of prostaglandins, leukotrienes, and resolvins [111,116] Regulate gene expression mediated by nuclear receptors and transcription factors, including inhibition of synthesis of cytokines and mitogens [111] Hypolipidemic actions-lower triglyceride and triglyceride-rich lipoprotein levels [111,118,119] Raise adiponectin levels, may decrease insulin resistance (but dose-related), overall favorable impact in DM [116,120] Antithrombotic and antiplatelet actions [109,116] Improve endothelial and small arterial function, in part due to decreased adhesion molecule expression and increased availability of nitric oxide [118,121] Raise Treg modulation of Toll-like receptors to retard progression of ath...…”