Fasting versus Nonfasting Triglycerides: Implications for Laboratory Measurements

G. R. Warnick, K. Nakajima
2007 Clinical Chemistry  
2 ) report the superiority of the measurement of nonfasting over conventional fasting triglycerides in predicting risk for cardiovascular events, observations consistent with previous studies (3, 4 ) . For decades the usual practice has been to measure triglycerides in blood samples obtained after patients have fasted 8 -12 h, a procedure consistent with population studies that specified fasting blood collections to decrease variability and achieve consistency of metabolic state in patients at
more » ... ate in patients at the time of sample collection (5 ). Triglyceride values fluctuate widely over time, with a CV of biological variability averaging about 23% and ranging up to 40%, and this variability can confound estimation of the associated cardiovascular disease (CVD) risk (6 ). Fasting blood collection is thought to decrease this variability (7 ), a theory supported by the observed correlation between fasting and nonfasting values (8 ). Nevertheless, because postprandial nonfasting values are more representative of the usual metabolic state, the observed improved prediction of the associated CVD risk is not unexpected. A change in practice to nonfasting collections, however, might affect other applications of the triglyceride determination or other measurements made on the specimens. Triglycerides are measured in clinical practice not only to assess CVD risk, but also to detect the extreme increases that can contribute to pancreatitis. For this purpose the question of fasting vs nonfasting is largely irrelevant; in fact such high levels could be detected by visual observation of the extent of turbidity and/or a floating fat layer associated with the larger triglyceriderich lipoprotein (TRL) particles. Triglyceride-associated turbidity, likely increased in nonfasting specimens, can interfere with other laboratory determinations, necessitating thorough studies with various instrument/reagent systems. Triglyceride values are also used to calculate LDL cholesterol (LDL-C) by difference using the Friedewald equation, which was derived using fasting specimens. Hence, the equation might require revision and validation for specimens collected under nonfasting conditions. On the other hand, the calculation has been shown to be less reliable with increasing triglycerides even with fasting (9 ) and there are alternative measures of atherogenic particles that do not require fasting collections, such as non-HDL-C as recommended by current guidelines (10 ) , total-C to HDL-C ratio as supported by recent studies (11 ), and apoB, the major protein constituent of VLDL and LDL, shown in many studies to be superior to LDL-C (12 ). Before considering alternatives to the current practice it is instructive to consider the complex heterogeneous nature of trglyceride as an analyte. Triglycerides, as the name implies, consist of 3 fatty acids linked through ester bonds to a glycerol backbone (13 ). Fatty acids, the body's major fuel source, are heterogeneous, typically ranging in size from the 12-carbon saturated lauric acid through the 18-carbon monounsaturated oleic acid to the 22-carbon polyunsaturated (omega 3) docosahexaenoic acid. Triglycerides of dietary origin enter the circulation as chylomicrons, the largest of lipoprotein particles (80 -1000 nm) packaged together with the truncated form of apolipoprotein B, apoB-48, whereas fatty acids originating in the liver are secreted as VLDL (25-80 nm) with apoB-100. In the circulation these nascent TRL particles are usually rapidly remodeled through lipolysis by various lipases (lipoprotein, hepatic, and endothelial lipases), transitioning through remnant lipoprotein particles (22-24 nm), resulting eventually in LDL particles ranging in size from 19 to 23 nm, which are relatively depleted in triglycerides but carry about 70% of circulating cholesterol. The other major lipoprotein class, the HDLs, provides proteins that facilitate and regulate the processing of the TRL particles and also accept triglycerides into their core in exchange with remnants for cholesteryl esters through the action of cholesteryl ester transfer protein. Most of the common triglyceride assays employed today measure triglycerides in terms of their glycerol content, employing lipase enzymes to hydrolyze the triglycerides and any di-and monoglycerides; the latter 2 forms typically present in serum at levels representing 5% to 10% of total glycerides. The tri-and diglycerides are readily hydrolyzed by general lipases and the monoglycerides less so; newer assays may add
doi:10.1373/clinchem.2007.098863 pmid:18039717 fatcat:23yew6mmprcippugc67yajmzve