Plasma nonesterified fatty acid concentration as a risk factor for sudden cardiac death: the Paris Prospective Study.

Abstract

In the 1960s and 1970s, at the time the study by Jouven et al1 was initiated, there was much interest among cardiologists regarding the likelihood that elevated concentrations of free fatty acids in plasma occurring with myocardial ischemia might initiate ventricular arrhythmias resulting in sudden cardiac death. Nevertheless, it required far-sighted investigators to launch an epidemiological study with 5250 middle-aged men without known cardiovascular disease and the persistence to follow this cohort for a mean follow-up time of 22 years, making this a unique and valuable reference for the natural history of cardiovascular disease over a recent period in Western industrialized countries. See p 756 Nonesterified fatty acids, or free fatty acids, are highly hydrophobic, shunning the aqueous medium of body fluids. They are generally toxic to cells and are kept at low nanomolar or micromolar concentrations in plasma; these levels can vary greatly depending on the hormonal, metabolic, and nutritional state of the individual. Some 99.9% of free fatty acids are carried in plasma bound to proteins, mainly serum albumin, which has some 5 to 8 or more binding sites per molecule ranging from high to low affinity. The low concentration of fatty acids is maintained in plasma by the competition between the affinity of albumin-binding sites and cell membrane phospholipids for free fatty acids. In heart cell membranes, concentrations in turn are kept low by the cells, which constitute a sink for the fatty acids they consume as metabolic fuel. The free fatty acid levels in plasma result from the regulated turnover of lipid stores in adipose tissue by lipolysis and from phospholipids by phospholipases and is little affected by the immediate dietary consumption of fat. …