Editorials
Non-Fasting Triglyceride Levels as a Superior Predictor of Cardiovascular Disease
2020 Volume 84 Issue 3 Pages 386-387
Details
2020 Volume 84 Issue 3 Pages 386-387
Hypercholesterolemia is a well-known predictor of cardiovascular disease. Recently, triglyceride (TG) levels have emerged as a predictor and therapeutic target for the reduction of cardiovascular diseases.1,2 Because lipid profiles are affected by food consumption, the measurement of lipid profiles has conventionally been performed in the fasting state, although evidence was lacking that fasting lipid profiles were superior to non-fasting profiles for cardiovascular risk assessment. TG levels are more affected by the duration from the last meal and amount of consumed food; therefore, measuring fasting TG levels has been believed to provide more reliable values. Two major concerns regarding the non-fasting lipid profiles are the similarity between fasting and non-fasting profiles and the predictive value of non-fasting relative to fasting profiles. Several studies have reported small mean variations between fasting and non-fasting lipid values, including TG (e.g., 133 and 115 mg/dL for non-fasting and fasting TG, respectively).3,4 Non-fasting low-density lipoprotein cholesterol (LDL-C) shows a prognostic value similar to that of fasting LDL-C.5 Moreover, recent studies indicate that non-fasting TG can predict cardiovascular events to a similar level as fasting TG.6,7 Therefore, some current guidelines recommend non-fasting tests for determination of the lipid profile for general screening and risk evaluation.8,9 The Reduction of Cardiovascular Events With Icosapent ethyl – Intervention Trial (REDUCE-IT) revealed that icosapent ethyl reduced adverse cardiovascular events regardless of ‘fasting’ TG levels. Although the mechanism was not clearly identified, fasting TG values may not reflect the average daily TG level.10
Article p 509
In this issue of the Journal, Tada et al investigated whether non-fasting TG was associated with cardiovascular events in Japanese diabetic patients with retinopathy, who have advanced stage diabetes and are at relatively high risk of cardiovascular disease.11 Currently, the evidence for non-fasting TG measurement is based primarily on non-inferiority to fasting TG measurement, such as having similar measured values and prognostic value. However, Tada et al suggest that non-fasting TG over fasting TG is more useful for risk discrimination for MACE,11 which is an important point in clinical practice. Moreover, the findings of that study have implications for Asian populations. There are some differences with regard to dietary consumption between Asian and Caucasian populations. Asians eat more carbohydrates and a lower proportion of protein than Caucasians, which is known to exacerbate postprandial chylomicron levels. We cannot confirm the difference between dietary consumption and postprandial TG levels in different ethnic groups. Further studies are needed.
Non-fasting measurement of TG has considerably rationality. Not only are liver-derived lipoproteins present in the plasma during the fasting state, but intestinal-derived lipoproteins are also present in the plasma during the non-fasting period, which present predominantly at different times of the day (Figure).12 Therefore, theoretically, the non-fasting period could reflect the real atherogenic burden better than the fasting period. Non-fasting measurement of TG has benefits. First, most people consume meals or snacks several times a day; therefore, the postprandial state is more common than the fasting state over the course of a day. The non-fasting state is predominant in almost all populations, and fasting TG may not reflect the mean daily plasma TG. Therefore, these conditions need to be considered for risk stratification. Second, non-fasting laboratory measurement may make patients more comfortable. In some cases, patients skip their cardiac medications for fasting laboratory tests by mistake, which sometimes results in arrhythmic events and, rarely but significantly, contributes to inappropriate shock treatment, especially in patients with an implantable cardiac defibrillator.
Non-fasting and fasting periods over a 24-h period with intake of typical meals, and comparison of arguments for and against the use of random, non-fasting, and fasting blood sampling. Non-fasting blood sampling can be performed anytime during the 24-h period, regardless of what and when the individual ate before blood sampling. In contrast, the fasting period is limited to only a few hours after a period without food intake for ≥8 h, which often means a natural small fast of a few hours in the early morning will be extended, possibly until noon, before the blood is drawn. (Reprinted with permission from Elsevier from Nordestgaard BG.12)
From this perspective, the study of Tada et al11 is meaningful in that it revealed the superior cardiovascular predictive value of non-fasting TG levels over fasting TG levels. The significance of hypertriglyceridemia remains unclear in cardiovascular disease. The difference between fasting and non-fasting TG may provide additional information for these unknown mechanisms. Because of the retrospective analysis of the registry, the lack of clear definition of fasting TG and heterogeneous timing of non-fasting TG are limitations of that study. Nevertheless, the study may provide a basis for further research.
