Are increased plasma non-esterified fatty acid concentrations a risk marker for coronary heart disease and other chronic diseases?

Among the strongest of the many risk markers for coronary heart disease (CHD) are elevated concentrations of blood lipids, cholesterol and (more controversially) triacylglycerol (TAG). It is not usual to associate increased concentrations of another plasma lipid constituent, the non-esterified fatty acids (NEFAs), with increased risk of cardiovascular disease. In fact, the condition is not even credited with a common name, although hyperNEFAnaemia has been proposed [ l ] (we prefer the term hyperNEFA-aemia which rolls off the tongue more easily). However, there is increasing evidence for a central role of increased plasma NEFA concentrations in the ‘insulin resistance syndrome’ or metabolic syndrome [2], and in the associated predisposition to CHD and other chronic diseases including non-insulin-dependent diabetes mellitus (NIDDM), hypertension and possibly even some forms of cancer. One reason for the lack of appearance of elevated NEFA concentrations as a risk marker for CHD may be simply that they are not often measured in epidemiological studies. Another reason, however, is that plasma NEFA concentrations are highly variable with time within one individual, according to nutritional state, exercise, smoking and stress level, making them less reliable as metabolic markers in large scale epidemiological studies in which control of such factors may be difficult. In addition, the potential role of N EFAs may be overlooked because of their low plasma concentration in relation to other potential risk markers (Table 1). Such a view ignores their extremely rapid turnover (Table 1). One aim of this review is to bring together evidence suggesting that elevated NEFA concentrations may play an important role, in the hope of drawing attention to the possibility of including them in future studies. The review will concentrate on data from human studies.