In ischemic conditions, concentration of circulating nonesterified fatty acids (NEFA) is increased and has a proarrhythmic effect that is responsible for ventricular tachyarrhythmias. In nonischemic patients, high NEFA plasma concentration has been shown to be associated with frequent premature ventricular complexes and increased familial risk of cardiovascular disease, but its relation to sudden death has not been studied. We assessed the role of circulating NEFA in sudden death in asymptomatic men in a long-term cohort study.Above is the abstract for the study. Something that might not be alarming to some. The association could be due to a co-correlation with insulin resistance, for example.
In the discussion section, the DIRECT effect of NEFA are elaborated:
Sudden death remains a critical problem in industrially developed countries, and treatment of sudden death victims frequently is unsuccessful.1,2 Therefore, early identification of subjects at high risk of sudden death is essential to preventive treatment strategies. Circulating nonesterified fatty acids (NEFA), also called free fatty acids, have been described as responsible for ventricular arrhythmias and sudden death after myocardial infarction.3–6 However, a possible arrhythmogenic role of NEFA has not been investigated in nonischemic patients. The main source of circulating NEFA is release from adipose tissue. A higher frequency of premature ventricular complexes was found to be associated with increased circulating NEFA concentration in patients with non-insulin-dependent diabetes mellitus.7 A recent study observed an association between high NEFA concentration in offspring and increased risk of cardiovascular disease in their parents.8 Additionally, direct arrhythmogenic action of an experimental high concentration of NEFA was described in nonischemic isolated perfused rat hearts.9
If elevated circulating NEFA concentration has a direct arrhythmogenic effect in asymptomatic subjects, these subjects may be predisposed to sudden death. We used the long follow-up period of the Paris Prospective Study I (>20 years) to assess the role of circulating NEFA concentration as a risk factor for sudden death in middle-aged men without known cardiovascular disease.
This graphic of the results is interesting. Notice the almost normal distribution of MI (heart attack) v. NEFA while SCD & NEFA show a pretty stark correlation.
Some more from the Discussion:
Proarrhythmic Mechanisms of Increased Circulating NEFA
Proarrhythmic mechanisms of toxicity of increased NEFA are numerous and complex.17 NEFA have been shown to modulate the ATP-sensitive K+ channel and to activate ATP-insensitive K+ channels in rat heart cells.18 This may contribute to extracellular K+ accumulationand shortening of action-potential duration observed during early ischemia and anoxia. Even in absence of ischemia, a perfusion of high molar ratios of albumin-bound NEFA in isolated rat hearts has been shown to have a direct arrhythmogenic effect that could be mediated by Ca2+ overload in myocardial cells.9,19 Increased intracellular Ca2+ concentration induces uncoupling between cells, which supports occurrence of electrical reentry.
NEFA also may inhibit the Na+,K+ ATPase pump, thereby leading to high intracellular sodium and calcium,20 activating protein kinase and affecting Na+, K+, and Ca2+ currents.21 Arrhythmogenic effects of lysophospholipids, derived from the breakdown of membrane lipids during ischemia, and of acylcarnitine, derived at least in part from circulating NEFA, may be added. Accumulation of acylcarnitine can activate Ca2+ channels directly21 to produce arrhythmias through Ca2+ overload.22
Suspected Hyperadrenergic Tone
Level of circulating NEFA is mediated largely by adrenergic stimulation, which may enhance its arrhythmogenic effect. A rise in plasma catecholamine concentration leads to increased release of NEFA from adipose tissue stores13; in the present study, NEFA were relatively strongly correlated with heart rate and blood pressure. After inclusion of NEFA concentration into the multiadjusted model, heart rate was no longer an independent risk factor for sudden death. However, suspected hyperadrenergic tone is likely to play a direct role in arrhythmogenicity beyond causing a possible proarrhythmic effect of NEFA.
Presented without comment at this time.