Should Triglyceride Blood Levels be Measured in the Fasting State?
Abstract & Commentary
By Harold L. Karpman, MD, FACC, FACP Clinical Professor of Medicine, UCLA School of Medicine. Dr. Karpman reports no financial relationship to this field of study.
Synopsis: Elevated non-fasting triglyceride levels are associated with incident cardiovascular events independent of traditional cardiac risk factors, levels of other lipids, and markers of insulin resistance; by contrast, fasting triglyceride levels demonstrated little independent relationship to these events.
Source: Bansal S, et al. JAMA. 2007;298:309-316.
In contrast to well-established independent risk factors for cardiovascular disease such as total cholesterol, low-density lipo-protein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)1, the importance of triglycerides has been controversial for many years, but it is now well established that elevated triglyceride levels, especially in patients with low HDL-C levels must be appropriately treated. Patients with massively elevated triglyceride levels (ie, greater than 2200 mg/dL) are usually afflicted with the familial chylomicronemia syndrome and rarely develop atherosclerosis2; however, patients with only a moderate hypertriglyceridemia found in conditions such as familial hypertriglyceridemia, the metabolic syndrome and remnant hyperlipidemia often develop premature atherosclerosis2-5 probably because the smaller triglyceride-rich glycoproteins penetrate the arterial intima and become preferentially trapped within the arterial wall.6-8 Triglycerides are routinely measured in the fasting state as recommended in the current national guidelines because plasma triglyceride levels can increase substantially postprandially1; however, except for the first hours in the early morning, most individuals are in the non-fasting state most of the day and much of the night and, since atherosclerosis may actually be a postprandial phenomena8-10, the nonfasting triglycerides plasma level which reflect increased levels of remnant lipoproteins has been speculated to be a more important predictive measure of myocardial infarction (MI), ischemic heart disease (IHD) and even death than is the fasting triglyceride level.
Two articles which were recently published in JAMA evaluated the hypotheses that very high levels of nonfasting triglycerides would predict MI, IHD, and death11 and as to whether or not there was an association between triglyceride levels (fasting vs nonfasting) and risk of future cardiovascular events.12 Nordestgaard and his associates11 prospectively studied a cohort of 7587 women and 6394 men in Denmark by measuring nonfasting triglyceride levels and found that elevated nonfasting triglyceride levels were associated with an increased risk of MI, IHD, and death in both men and women. The mean follow-up was for 26 years and it should be noted that although a few individuals did take lipid-lowering drugs late in the followup period, when the analyses were adjusted for lipid-lowering drugs, the results changed only minimally. Bansal and his colleagues12 prospectively studied 26,509 initially healthy US women participating in the Women's Health Study13-15 and found that in this cohort, elevated nonfasting triglyceride levels were associated with incident cardiovascular events independent of traditional cardiac risk factors, levels of other lipids, and markers of insulin resistance; by contrast, fasting triglyceride levels demonstrated little independent relationship to these events.
There certainly is no question that elevated serum triglyceride levels are associated with increased risk of developing MI, IHD and death; but in addition, it now appears to be quite clear that a high serum triglyceride level is also frequently associated with abnormal glycoprotein metabolism, as well as with other IHD risk factors including obesity, insulin resistance, diabetes mellitus and lower levels of high-density lipoprotein cholesterol (HDL-C).16 HDL-L serum levels are generally inversely related to the triglyceride level,16 which, if abnormally elevated, has the effect of making the LDL-C and HDL-C particles small and dense, thereby creating a highly atherogenic state.17 The metabolic abnormalities associated with moderate hypertriglyceridemia (ie, levels of 150-800 mg/dL) are likely related to the various types of triglyceride-rich lipoproteins in the presence of small, dense LDL-C and HDL-C particles,17,18 which explains why several prospective cohort studies have found that the number of small, dense LDL-C particles may be a greater predictor of IHD risk than is the measured levels of serum LDL-C.17,18 Some research studies have suggested that coronary atherosclerosis is a postprandial phenomenon since postprandial lipoproteins are generally triglyceride-rich and clearance of these lipoproteins can be delayed for as long as 12 hours or more, especially in those individuals who have a predisposition to producing small dense LDL-C and HDL-C particles.18
For many reasons, further research will obviously be needed to clarify the role of postprandial triglyceride levels and their use in clinical practice, especially because fasting triglyceride measurements are now obtained in a standardized fashion and are therefore more reliable and easier to obtain than are postprandial samples; however, some studies have suggested that triglyceride measurements obtained between 2-4 hours postprandially may be more predictive of IHD than are calculated fasting LDL-C measurements.12 Given the state of our knowledge at the present time, it may be less complicated to simply measure non-HDL-C (ie, total cholesterol minus HDL-C) which is the sum total of all atherogenic glycoproteins,20 which has been demonstrated to be accurate and reliable when measured even in the nonfasting state and which has been recommended by the final report from the Third National Cholesterol Education Program Adult Treatment Panel1 as an important lipid factor because it is more predictive of IHD risk than LDL-C levels, especially when triglyceride levels are found to be elevated. Of course, besides lifestyle interventions, clinical trial evidence increasingly supports the pharmacological approach of treating patients with combined dyslipidemias21 (elevated triglyceride levels and low HDL-C levels)19,20 using combination therapy such as statins plus niacin. Trials which are currently underway funded by the National Heart, Lung, and Blood Institute will further evaluate the role of combination drug therapy in patients with combined dyslipidemias.
In summary, until adequate clinical trials including appropriate outcome studies, which will standardize postprandial triglyceride measurements have been completed, it would appear that clinicians should continue to measure fasting lipid levels and use the results of these studies (including non-HDL-C levels) especially in patients with elevated triglyceride measurements to formulate pharmaceutical therapy based upon the results of published trials and the recommendations of the Adult Treatment Panel III.1
1. National Cholesterol Education Program (NECP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NECP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143-3421.
2. Brunzell JD, et al. Familial glycoprotein lipase deficiency. APO C-ii deficiency, and hepatic lipase deficiency; Scriver CR, et al. The metabolic and molecular basis of inherited disease. 8th ed. New York, NY: McGraw-Hill; 2001:2789-2816.
3. Austin MA, et al. Circulation. 2000;101:2777-2782.
4. Mahley RW, et al. Type III hyperliproteinemia (dysbetalipoproteinemia): the role of apollpoprotein E in normal and abnormal glycoprotein metabolism. In Scrivner et al. The metabolic and molecular bases of Inherited Disease. 8th ed. New York, NY: McGraw-Hill; 2001:2835-2862.
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20. Robins SJ, et al. JAMA. 2001;285:1585-1591.
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