A Biochemical View: Plasma Free Fatty Acids and Risk of Stroke in the Cardiovascular Health Study

We read with great interest the recently published article by Khawaja et al. in which the authors aimed to examine the association between plasma free fatty acids (FFAs) and incident stroke (1). They concluded that there was not an association of plasma FFAs with incident stroke among community dwelling older adults. However, we think that there are some points that should be emphasized about this study. First, typically, plasma/serum samples are more commonly analyzed for assessment of an individual’s FA status because the FA compsition of plasma reflects recent dietary fat intake (2). However, plasma FAs levels are subject to multiple different dietary influences. The plasma FA profile may be determined not only by the time elapsed between the ingestion of fat-containing foods, but also by the type of dietary lipids ingested (3). Consequently, because erythrocytes have a rather long lifespan (∼120 days), the FA profile is considered a better indicator of long-term FA intake compared with the intermediate lifespan (max ∼3 weeks) of platelet or plasma lipids (2–4). In this respect, the erythrocytes are more stable, and it would be more valuable/proper to measure their FA concentration to assess the functional activity of FAs. Second, FFAs concentrations in plasma were measured by enzymatic method in the original study. However, chromatographic analysis of FFAs could provide more significant results. Accordingly, measurement of concentration of FA subtypes (saturated/polyunsaturated FAs), calculation of percentage of FA fractions or ratio of some fractions of FAs might be a better indicator to understand the process in stroke (5,6). Accordingly, detailed analysis of FA subtypes can provide valuable information in management of dietary intake or supplementation of FAs, which are deficient in patients with stroke (7). In conclusion, erythrocytes should have been preferred as a specimen to evaluate FA profile, and chromatographic analysis of FFAs could provide more significant results in the original study.