Nonfasting Sample for the Determination of Routine Lipid Profile: Is It an Idea Whose Time Has Come?

For many years the determination of a routine lipid profile (total, LDL, and HDL cholesterol and triglycerides) has been done routinely in the clinical laboratory using a blood specimen that is collected in the fasting state. The rationale for such a requirement includes 1) the postprandial changes in lipoprotein composition known to occur, particularly the increases in triglycerides (TG)10 concentration which have a direct relation to the meal fat and carbohydrate content, 2) the clinically significant effects of increased TG (>400 mg/dL; 4.5 mmol/L) on the calculation of LDL cholesterol (LDL-C) when using the Friedewald equation, and 3) the use of fasting samples for lipid measurement in many clinical trials and epidemiological studies on which treatment goals are based. However, because most of each person's lifetime is spent in the postprandial state, the wisdom of collecting a fasting sample to determine future risk of cardiovascular disease has been challenged. In addition, recent evidence has demonstrated that nonfasting TG concentrations are a better predictor of future coronary events compared to fasting TG, in both men and women. The Danish Society for Clinical Biochemistry, in 2009, and the UK National Institute of Clinical Excellence (NICE), in 2014, recommended the use of a nonfasting specimen for the determination of routine lipid profile; both entities acknowledge that in certain situations a fasting sample is required. The European Atherosclerosis Society and the European Federation of Clinical Chemistry and Laboratory Medicine will be making a similar recommendation. In contrast, the 2013 guidelines released by the American College of Cardiology/American Heart Association (ACC/AHA) preferred a fasting specimen for lipid testing. Such inconsistencies in published guidelines will complicate the interpretation of the literature and confound metaanalyses. The decision of whether to use a fasting or nonfasting sample, however, will be driven not only by the strong epidemiologic and clinical evidence and the convenience to clinicians and patients but also by the reliability of the analytical techniques used in the measurement of these analytes. To address this issue, we invited a group of experts consisting of cardiologists, epidemiologists, clinical researchers, and clinical chemists to share their views on this topic. What is the evidence that fasting samples are better than nonfasting samples for clinical use? Anthony S. Wierzbicki: Fasting samples are superior for assessment of severe hypertriglyceridemia as they reduce postprandial variation, which is substantial for this lipid fraction, ranging from 20% to 40%. They are also preferred if LDL-C is to be calculated using the Friedewald equation. Recent data from the Very Large Database of Lipids study show that even a mild increase of TG (>220 mg/dL; 2.5 mmol/L) can have a significant impact on calculated LDL-C. This is an important clinical problem as calculated LDL-C underestimates real LDL-C in patients with type 2 diabetes, the metabolic syndrome, or other hypertriglyceridemic states. Børge G. Nordestgaard: I am not aware of any. Hubert Vesper: Only a few studies have compared fasting and nonfasting specimens in the context of classification of risk for atherosclerotic cardiovascular diseases (ASCVD) and related health outcomes. Collectively, the findings reported in these studies do not show higher accuracy of ASCVD risk assessment when using fasting samples. ASCVD risk is commonly assessed by measuring total cholesterol (TC), HDL-C, TG, and LDL-C, with LDL-C either calculated using the Friedewald equation or measured using direct homogenous assays. The Friedewald equation is based on the observation that the mass ratio of TG to cholesterol in VLDL is relatively constant in the fasting state. Thus, risk estimations using LDL-C calculated with the Friedewald equation require fasting samples. Use of direct homogenous assays can overcome the limitations associated with the Friedewald equation. However, data suggest that direct homogenous assays can also be affected by feeding to an extent that may affect clinical decisions. Other approaches for ASCVD risk assessment include analytes such as non–HDL-C and apolipoproteins, which appear less affected by recent food intake and therefore may not require a fasting specimen. The choice of using specimens from fasting or nonfasting patients depends on the intended analytes and the ASCVD risk assessment approach used. Samia Mora: Lipid testing plays a major role in ASCVD risk screening, prediction, and treatment. For cardiovascular risk screening and prediction, there is no convincing evidence that a lipid panel is better when done on a fasting blood sample. In fact, a nonfasting lipid panel may even be better than a fasting panel. In the past decade, several pivotal studies (including the Women's Health Study, the Copenhagen City Heart Study, and the Copenhagen General Population Study) found that nonfasting TG were at least as good, if not better, than fasting TG in predicting future risk of cardiovascular events. Importantly, in a metaanalysis from the Emerging Risk Factors Collaboration that included data from over 300 000 individuals from 68 prospective studies, LDL-C and non—HDL-C were significantly more predictive of cardiovascular events when measured nonfasting. For treatment, most guidelines are emphasizing treating the high-risk patient rather than the high LDL-C value. Even so, several landmark randomized clinical trials of statin therapy [including the Heart Protection Study, ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm), and the SEARCH (Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine) trials] used nonfasting lipid measures for treatment. Neil J. Stone: It truly depends on the question you ask. If you ask, will a nonfasting specimen suffice to determine global ASCVD risk assessment, the answer is yes. The pooled cohort equations, the Reynolds Risk Score and the QRISK score, for example, only require a TC and HDL-C as lipid inputs. On the other hand, a fasting sample helps greatly in the diagnosis of genetic dyslipidemia and helps determine response to therapy of those with hyperlipidemic pancreatitis. Moreover, fasting TG are one of the 5 markers for metabolic syndrome, a useful construct in those patients who require lifestyle counseling. Also, in secondary prevention patients prescribed statins, a fasting lipid panel can provide valuable information on adherence to the statin (their LDL-C concentration) and adherence to lifestyle (fasting TG also may be useful here) and on-treatment fasting TG <150 mg/dL (1.7 mmol/L) can indicate a lower risk of recurrent coronary events. Jacques Genest: None really, from a scientific point of view. The accuracy of the Friedewald formula for the determination of LDL-C has been shown to be very dependent on TG concentrations. However, within a broad range of serum TG values, this calculation is clinically valid. What are the advantages of using nonfasting samples? Børge G. Nordestgaard: The most obvious advantage is that it simplifies blood sampling for patients, laboratories, and clinicians and is also likely to improve patient compliance with lipid testing. Certainly, patients are often inconvenienced by having to return on a separate visit for a fasting lipid profile, laboratories are burdened by a large number of patients attending for tests in the morning, and clinicians are burdened by having to review and make decisions on the findings in the lipid profile at a later date. Anthony S. Wierzbicki: Nonfasting samples are more convenient for the patient and the physician. They can be used to derive non–HDL-C, a measure that is superior to LDL-C for risk assessment as it includes atherogenic TG-rich lipoproteins. Hubert Vesper: The advantages of collecting nonfasting specimens are typically related to convenience of scheduling patients and concerns related to the accuracy of determining the time to last meal. To obtain fasting specimens, patients are normally scheduled in the morning after an overnight fast or are asked to abstain from eating for at least 8 hours. In routine patient care, the assessment of patient compliance with this request is difficult to perform. Research findings suggest that information on postprandial lipid concentrations can provide valuable information for ASCVD risk assessment that cannot be obtained with fasting samples. However, more data are needed to further validate these findings. Samia Mora: The main advantage is the practicality of measuring nonfasting lipids, for the patient, the healthcare provider, and the laboratory. Compliance has always been an issue with fasting blood tests, in particular for children or individuals who may not be able to fast. Patients may not know ahead of their appointment that they should have fasted, or they may forget and often expend additional resources to return to a laboratory while fasting, and some may forgo coming back altogether. The healthcare provider or the laboratory then must decide whether to make the patient return another time (which is costly, and which the patient may or may not comply with) or rely on a nonfasting sample. Neil J. Stone: In my clinic, most important is the convenience factor for those who are seen in the clinic later in the day. It is expensive for patients to return to the medical center or laboratory to get additional testing, especially if a nonfasting specimen will suffice. Greg Miller: The only advantage is convenience for patients. The practical reality is a large proportion of lipid profiles are likely already in the nonfasting What are the situations for which a fasting sample is Børge G. Nordestgaard: I am not aware of any. Anthony S. Wierzbicki: Fasting samples are to determine TG concentrations in patients with TG in the range of mg/dL If the of high concentrations is and by or is then patients with severe hypertriglyceridemia may require additional lipid therapy or in to Hubert Vesper: such as the Friedewald equation and risk that are based on fasting specimens require fasting Patients with hypertriglyceridemia in nonfasting specimens require using fasting specimens for This is with ASCVD risk assessment guidelines that use of nonfasting specimens for Samia Mora: It is to nonfasting lipid testing in most individuals who for a routine clinic with the of individuals with TG mg/dL in the Friedewald equation for LDL-C may not be However, even in such individuals with high TG, cardiovascular risk using TC and HDL-C be the as that is is used in risk using or of which be measured be over LDL-C for treatment decisions in these as they are better of the of atherogenic in these individuals compared with LDL-C or Jacques Genest: The in the Friedewald formula by increased TG may an of LDL-C if a patient has increased nonfasting TG mg/dL a should be done in the fasting for at least and no for a nonfasting Børge G. Nordestgaard: Nonfasting and fasting TG should be as the the is clinically at only mg/dL are in changes in TG of mg/dL mmol/L) and a high TG to high fat intake will be by other lower concentrations. Anthony S. Wierzbicki: Nonfasting TG with fasting The of nonfasting concentrations the of important increases in atherogenic lipoproteins. Samia Mora: TG are the main lipid that may be affected by food a to know the TG that should be used for and treating increased TG in the nonfasting state. TG increase after routine food intake by on in some individuals by LDL-C, HDL-C, or which often have clinically changes For clinical it is important to have for and treating increased nonfasting In a large prospective study from the Women's Health Study, we that a nonfasting TG concentration of mg/dL 2 mmol/L) the clinical for increased TG in the nonfasting state. This also to the nonfasting recommended by the European Atherosclerosis Society and an Importantly, this is mg/dL mmol/L) lower than the recommended by the for high nonfasting TG mmol/L) which a substantial of individuals with high Neil J. Stone: The on and nonfasting TG in fasting concentrations <150 mg/dL; of a fat blood sampling not be to postprandial TG mg/dL In these no further testing for hypertriglyceridemia is further of lifestyle measures may be on the of that of However, if nonfasting TG concentrations or mg/dL a fasting lipid panel is recommended within a time Jacques Genest: a of time and has been spent on postprandial TG as a cardiovascular risk this response is often associated with the metabolic the of clinical trials using in to has to a of the of treating TG concentrations. Greg Miller: TG will be increased to a and extent when measured using nonfasting samples. from studies may not to the on an will not be able to determine the extent of the of for an patient, the will to of The to HDL-C and LDL-C. recommended for triglycerides are based on assays that for clinical laboratories use that do you a higher of in triglycerides the approaches when nonfasting samples are Børge G. Nordestgaard: for the in and the TG concentration by more than and mg/dL and such are clinically and there is no evidence that this should fasting and nonfasting samples. Anthony S. Wierzbicki: with released is significant can in patients with increased TG values, those with type 2 diabetes, significant concentrations or those on Hubert Vesper: TG are by measuring after of Thus, TG is affected by their to with some assays measuring total and measuring only to of total is from in certain diseases and can be increased such as in disease or after The impact of using nonfasting specimens on the of TG and impact on patient is studies are needed to this issue as as to better total and a ASCVD risk classification using both fasting and nonfasting Samia Mora: This is a very In the Women's Health that an nonfasting TG of mg/dL 2 the not To my clinical epidemiological and studies that measured (including using laboratories also have used a for similar to the clinical for TG are also based on In the of and that are in the of to total TG is 5 mg/dL Greg Miller: For fasting is a of TG in a number of typically those with genetic in lipoprotein have increased TG that it is the of will assessment of risk for is a in and is also used as a Nonfasting samples will have a increased of that will be measured as TG by most clinical laboratory because they do not for a postprandial TG measurement will be than a fasting because of as as fat in the The of will be it depends on the food and the time a sample is collected after a meal. What are the concerns the use of a nonfasting these concerns Børge G. Nordestgaard: 1) Fasting a lipid profile measurement is to provide more however, a high of is not needed 2) Fasting is to be needed to make calculation of LDL-C the Friedewald however, this equation also with nonfasting as as TG are mg/dL 3) It is should be as however, the can be for of the lipid profile to use TG mg/dL mmol/L) when using nonfasting and mg/dL (1.7 mmol/L) when using fasting lipid Anthony S. Wierzbicki: are with nonfasting samples as most LDL-C. This is less of a problem if the laboratory has a to direct LDL-C measurement in the of increased In addition, nonfasting samples may on laboratory by or if are at concentrations. Hubert Vesper: studies suggest that the for LDL-C and TG is higher in nonfasting samples compared to fasting samples. The the LDL-C assays in of the reported increase in LDL-C is not known and the for such increases are not analytes that are less or only affected by fasting such as or non–HDL-C in with the use of risk assessment overcome concerns related to nonfasting Jacques Genest: The major in the and accuracy of the LDL-C some to non–HDL-C as the preferred measurement and clinical trials at LDL-C. The is that even a in the measurement of LDL-C to a of risk and a in approach a in of Greg Miller: of the lipid profile is to the of the serum after 8 or more at on the is with and a serum is with an increased of In nonfasting samples these will be by the of these TG-rich from of fat in the For example, it will not be to determine if the of a genetic in of from the or a nonfasting sample. approach to this is to lipid profile testing on a fasting sample when an is LDL-C is most calculated using the Friedewald equation, which should not be used when TG mg/dL mmol/L) because the TG by 5 are in no the are several that the Friedewald of LDL-C is by TG mg/dL mmol/L) and the mg/dL mmol/L) a point at which the nonfasting samples will have increased and of the Friedewald calculation will be less even when TG are the mg/dL mmol/L) increase of mg/dL mmol/L) TG from will a mg/dL mmol/L) in the LDL-C that is large to classification of risk for cardiovascular the Friedewald equation is not for use when are because the equation has no factor for the cholesterol of Nonfasting samples are likely to on the fat of a meal and the time for a Friedewald LDL-C. The of nonfasting samples on the accuracy of HDL-C and LDL-C will be difficult to for an The measurement will and the clinical provider will not be able to determine if the laboratory were by the nonfasting the in guidelines to with at relatively of the of laboratory may be difficult to because a large of are In addition, from large studies typically the of the group and may not whether individuals be risk for ASCVD when laboratory testing is by nonfasting samples. are no for the of nonfasting on measurement of lipoproteins. data show that the analytical of total cholesterol and triglycerides is but not for HDL-C and LDL-C. you the of the to further with the use of nonfasting samples? Anthony S. Wierzbicki: of most HDL-C assays is not affected TG mg/dL LDL-C is affected by TG values, especially if calculated LDL-C is the laboratory with direct LDL-C but significant will affect the TG concentrations mg/dL Hubert Vesper: The for the HDL-C and LDL-C assays are not The of assays for lipid in the Nonfasting samples may have compared to fasting which may a HDL-C and LDL-C assays. have shown that the analytical of HDL-C and LDL-C is for some but not patients, particularly those with the use of fasting specimens can the it will not these assays in certain patients. Jacques Genest: major question for the this that a measurement of is an in a laboratory. the for laboratory is especially when at over a of patient Greg Miller: for both HDL-C and LDL-C are by of and other lipoprotein in a sample. direct measurement use and to or the in the of lipoprotein the of the to the of for Nonfasting samples have of lipoprotein from in to and the will be on the meal and the time after the meal a sample is direct HDL-C are for on fasting samples from with lipid and of lipoprotein HDL-C more and when of such as VLDL and are from direct HDL-C will be more and less for nonfasting samples to increased of VLDL and from the The direct measurement for LDL-C have to the National Cholesterol recommended and goals for with lipid and are by the of of other lipoprotein found in at increased risk of nonfasting samples will have increased VLDL and from the direct LDL-C will less and even for with relatively lipid LDL-C are a choice for with TG mg/dL mmol/L) when the Friedewald equation is not because of the large by and of lipoproteins. nonfasting samples for lipid profile testing is likely to increase the number of samples that will to have LDL-C measured by an approach such as or lipoprotein the guidelines the use of fasting over nonfasting sample for routine lipid Neil J. Stone: The guidelines preferred not For global ASCVD risk assessment, the pooled cohort that were in the risk assessment require fasting samples as they use total cholesterol and HDL-C as lipid inputs. Thus, the determination of the risk in the 2013 cholesterol guidelines can be done with nonfasting of the statin by the literature review of the panel used LDL-C in their (fasting For example, those with LDL-C mg/dL those years of with and LDL-C mg/dL and lower risk prevention individuals with a ASCVD risk of to have an LDL-C mg/dL I that in the prevention statin but on a risk The guidelines further that an additional factor to if a risk decision is is an LDL-C mg/dL in LDL-C is used to determine if the response to either a or statin is The guidelines point that response to statin therapy and should be assessed and this should include a fasting lipid panel within after or and Thus, nonfasting for ASCVD risk assessment but for other there is a role for fasting It depends on the question you are What are the of using nonfasting of fasting samples for lipid testing on the healthcare if Anthony S. Wierzbicki: Nonfasting are for the healthcare as a as they reduce patient at the of a in the laboratory in with a few samples with increased Nonfasting samples are more convenient for patients and health screening to be on an rather than additional scheduling and of a fasting to the Børge G. Nordestgaard: It will likely to as the number of patient to laboratories and will be Samia Mora: I am not aware of studies that have assessed the of using nonfasting samples for routine clinical testing or those data are in of measuring nonfasting concerns and be to reduce to patients and and healthcare Neil J. Stone: of the global cardiovascular risk use nonfasting total cholesterol and HDL-C, the to get for screening patients having to additional time a fasting Fasting may be as a but the assessment of ASCVD risk can be with nonfasting you that nonfasting samples should be used for routine lipid Børge G. Nordestgaard: we have already done that in Anthony S. Wierzbicki: Hubert Vesper: Fasting samples should be used for lipid profiles that LDL-C using the Friedewald equation and in risk assessment that are based on fasting Fasting for certain that affect Use of fasting specimens in patients with fasting specimens may the use of of risk those and those not fasting Thus, lipid profile data obtained from fasting specimens may in of their use for a ASCVD risk However, nonfasting specimens may provide information a person's ASCVD risk additional to that obtained with fasting apolipoproteins, lipid and other may overcome some of the limitations of the lipid This to risk assessment and patient Samia Mora: I have been using it for a while to that recent guidelines or from the UK and the on cardiovascular risk and the European Atherosclerosis Society are nonfasting as the the several major laboratories, and even some have already the approach of no fasting when measuring routine lipid In this of increased and on and testing, the time has for guidelines to also nonfasting lipid testing for routine clinical Neil J. Stone: I they should be used for the lipid I that clinicians based on their Fasting TG, HDL-C, LDL-C, non–HDL-C, or Nonfasting or HDL-C, non–HDL-C, and if I use nonfasting in my clinic but for For example, 5 of individuals one in a of with genetic lipid nonfasting TC and HDL-C is a screening but as in the if the nonfasting non–HDL-C is mg/dL it is useful to with a fasting lipid panel some additional to in a more diagnosis of either a genetic or a secondary of with metabolic who are at risk for and fasting TG that is increased mg/dL; mmol/L) is a for increased to lifestyle as as to that be The metabolic construct can greatly in patients on are of this construct because it is not the as and not as a risk predictor as a global risk for ASCVD or measures of for however, to that lifestyle 5 of the metabolic with or greatly at risk for hyperlipidemic pancreatitis. patient with in the with a nonfasting TG mg/dL mmol/L) is likely to have hyperlipidemic pancreatitis. Fasting TG are useful in patient with in the of the The very high concentrations seen with hyperlipidemic while patients are prevention patients. For risk assessment, a nonfasting TC and HDL-C are that is nonfasting TG be useful if patient a meal as prevention patients. fasting lipid panel you to LDL-C by the Friedewald equation. fasting TG to an assessment of on-treatment risk if it is or mg/dL (1.7 If mg/dL (1.7 these patients may greatly from more lifestyle as a This can greatly improve of the metabolic risk is that LDL-C by the Friedewald equation is not mg/dL Thus, there are in determining lower you get when you in secondary prevention patients. that this is may be a useful measurement for those on therapy with Jacques Genest: I have been treating patients for the past years in a with many of my I have seen of lipoprotein that require the of fasting lipid and lipoprotein lipid for the of my patients, we these tests in the context of ASCVD which not require a fasting sample. Greg Miller: I will to provide a fasting sample for my lipid testing because there are in risk for ASCVD nonfasting on the accuracy of the laboratory triglycerides LDL cholesterol National Institute of Clinical Excellence American College of Cardiology/American Heart Association atherosclerotic cardiovascular disease total

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.