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Mora S. Nonfasting for Routine Lipid Testing: From Evidence to Action. JAMA Intern Med. 2016;176(7):1005–1006. doi:10.1001/jamainternmed.2016.1979
Relevant English-language peer-reviewed studies were identified through a literature search of MEDLINE and specific health economic journals through 2016. Bibliographies from these references as well as meta-analyses and applicable guideline statements were also reviewed.
Lipid testing plays a major role in cardiovascular risk stratification and the assessment of responses to clinical interventions. Historically, it has been recommended that blood samples for lipid testing should be obtained after an 8- to 12-hour fast. Despite that we spend the vast majority of our time in nonfasting conditions, fasting samples have been the standard for measurement of triglycerides and cholesterol because measuring lipids in the fasting state is believed to reduce variability and allow for a more accurate derivation of the commonly used Friedewald-calculated low-density lipoprotein (LDL) cholesterol. However, if postprandial effects do not substantially alter lipid levels or their association with cardiovascular risk, then a nonfasting blood draw has many practical advantages.1 Indeed, recent studies suggest that postprandial effects do not weaken, and even may strengthen, the risk associations of lipids with cardiovascular disease (CVD).
Most lipid levels differed minimally when measurements were performed nonfasting or fasting, with clinically insignificant changes: negligible changes for high-density lipoprotein (HDL) cholesterol; slight changes (up to 8 mg/dL) for total cholesterol, LDL cholesterol, and non-HDL cholesterol; and modest changes (up to 25 mg/dL) for triglycerides.2 For CVD risk associations, studies from numerous large prospective studies performed over the past several decades have consistently found that nonfasting lipids suffice for general screening of cardiovascular risk.3,4 These studies have examined both clinical events (eg, myocardial infarction, stroke, and coronary revascularization) and mortality, finding consistent associations for nonfasting lipids with CVD. Studies that included both fasting and nonfasting groups of individuals showed either similar—or sometimes even stronger—CVD risk associations for nonfasting lipids, including for LDL cholesterol and triglycerides, compared with fasting. A meta-analysis4 that analyzed the association of lipids and CVD risk from 68 prospective studies found no attenuation of lipid relationships with predicting incident events in the 20 studies that used nonfasting blood collections (n = 103 354; number of events 3829).4 Finally, nonfasting lipid testing was used in at least 3 large statin clinical trials (involving nearly 43 000 patients).4
Recommendations regarding the clinical use of nonfasting lipids (Table) have evolved over the past decade with the growing evidence base for nonfasting lipid testing. Practice guidelines uniformly allow for the measurement of nonfasting total and HDL cholesterol (and hence the calculated values of non-HDL cholesterol and the total/HDL cholesterol ratio),9 because levels of these lipids are essentially unaltered when measured in fasting or nonfasting specimens. In the United States, the third report of the Adult Treatment Panel (ATP III, 2001)9 and the 2013 American College of Cardiology and American Heart Association (ACC/AHA) cholesterol guidelines6 recommended that initial screening should include a fasting lipid profile, although they allowed for measuring nonfasting total cholesterol, HDL cholesterol, and non-HDL cholesterol.9 In 2014, the National Clinical Guideline Center (NICE) and Joint British Societies recommended that a fasting sample is not needed for routine clinical care.5 Most recently, in 2016, the European Atherosclerosis Society and the European Federation of Laboratory Medicine recommended using nonfasting lipid testing for routine clinical practice and provided specific cutpoints for desirable fasting and nonfasting lipid levels.2 They defined elevated nonfasting triglycerides as greater than or equal to 175 mg/dL (≥2 mmol/L [to convert mg/dL to mmol/L, multiply by 0.0259]),2,10 and allowed for repeat measurement of fasting triglycerides when nonfasting levels are greater than approximately 400 mg/dL.2 Until recently, most guidelines focused on targeting primarily LDL cholesterol for the prevention and treatment of CVD, but they now recognize that non-HDL cholesterol (or apolipoprotein B, the molecule carried by non-HDL particles) is a better predictor of risk.
No articles were found that assessed the cost-effectiveness of fasting vs nonfasting lipid testing. In the Danish experience2 (where a nonfasting lipid profile has been the standard since 2009), only 10% of patients who underwent nonfasting lipid profiles needed repeat laboratory testing for a fasting panel. The economic effect of making patients return for fasting lipid panels in this small proportion of patients is unknown. On the other hand, it is well-known that fasting is not always practical for patients, especially for patients with diabetes or other conditions that make it difficult to fast, and for children. Furthermore, most patients are not fasting when they are initially evaluated by their health care providers, meaning that a repeat visit and further follow-up is necessary if a fasting blood draw is mandated. Patients often expend additional resources to return to a laboratory while fasting, and some may forgo coming back altogether. In clinical practice, there are numerous incidences of patients forgetting to perform their lipid test, which results in follow-up visits where key laboratory data are not available. These visits consume health care dollars and resources and also potentially take away resources from other patients. Health care practitioners who send patients for fasting blood work on an alternate day bear the responsibility of ensuring these tests occur, something many busy health care practitioners simply do not have time to do. From a laboratory perspective, requiring routine fasting lipid samples reduces workflow efficiency due to the early morning congestion of visits for lipid testing. All of these factors would contribute to lack of efficiency in the health care system and to increased health care costs.
While prospective studies have shown that nonfasting lipids are similar to fasting lipids or better for predicting CVD among groups of individuals, no studies to date have examined the predictive value of lipids measured both fasting and nonfasting from the same individuals, and no randomized outcomes trials or cost-effectiveness analyses have been done. More data are also needed among individuals from nonwhite ethnic origins.
Robust evidence supports the use of nonfasting blood draws for routine clinical practice, as this would be highly effective, practical and offer many advantages for cardiovascular risk screening and treatment in most people compared with a mandate to fast. The time has come to move this strong evidence into action.
Corresponding Author: Samia Mora, MD, MHS, Center for Lipid Metabolomics, Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, 900 Commonwealth Ave, Boston, MA 02215 (email@example.com).
Published Online: April 27, 2016. doi:10.1001/jamainternmed.2016.1979.
Conflict of Interest Disclosures: Dr Mora has served as a scientific consultant to Lilly, Pfizer, Quest Diagnostics, Amgen, and Cerenis Therapeutics.
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