It is a common sequence of dialogue in clinic: “I’d like to draw some blood for cholesterol,” says the doctor. “Have you eaten today?” With downcast eyes, the patient replies, “Yes, I had a snack. I just got so hungry.” The well-intentioned physician concedes, “That’s okay. Another time, then.”
Patients requiring lipid panels frequently report to their clinic appointments in the non-fasting state. These patients often leave clinic without having their blood drawn for lipids, with instructions to return early the next morning while fasting. This can present many issues for patients, not the least of which is the additional work they must forego to come in again the next day. Thus, a question is posed: is it necessary to get fasting lipids on our patients, or are non-fasting lipids acceptable?
The preference for fasting lipids in primary hyperlipidemia screening is decades old. It is deep-seated in the use of the Friedewald calculation of low density lipoprotein (LDL) cholesterol in former guidelines for hyperlipidemia screening and treatment.1,2 The equation utilizes total cholesterol, high density lipoprotein (HDL) cholesterol, and triglycerides to calculate LDL cholesterol:
LDL cholesterol= total cholesterol – HDL cholesterol – [triglycerides/5]
Former guidelines, including the Adult Treatment Panel III of 2001, emphasized specific LDL cholesterol goals based on cardiovascular risk in primary prevention patients.3 Recent food intake significantly raises triglycerides and has very little effect on the other components of the lipid panel. In a cross-sectional study of over 200,000 individuals, mean triglyceride levels were statistically different from an 8-hour fast for up to 6 hours after a meal for males and up to 5 hours after a meal for females.4 The mean triglyceride levels varied up to 20% between these different fasting intervals. In a study of 33,391 individuals from the Copenhagen General Population Study, Langsted and colleagues showed that overall lipid profiles changed only minimally following normal food intake.5 If accurate LDL is a requirement for screening, then fasting triglycerides are necessary in order to use the Friedewald calculation.
The current American College of Cardiology/American Heart Association (ACC/AHA) guidelines do not focus on risk-based LDL cholesterol goals for primary prevention but, rather, place an emphasis on 10-year atherosclerotic cardiovascular disease (ASCVD) risk.6 Calculation of 10-year ASCVD risk utilizes total cholesterol, HDL cholesterol, systolic blood pressure, and other risk factors. Depending on the calculator one uses, LDL may or may not be included as a risk factor. Thus, an argument can be made that fasting lipids are not absolutely necessary for primary prevention screening.
Evidence has come to light that suggests that non-fasting lipids may be at least as good as fasting lipids in determining cardiovascular risk.5,7 In a study by Nordestgaard and colleagues, 7587 women and 6394 men were stratified according to their baseline non-fasting triglyceride level and followed for an average of 26 years. They found that non-fasting triglyceride levels independently predict myocardial infarction, ischemic heart disease, and death.8 This may be due postprandial triglyceride-rich lipoprotein metabolism. The remnants of chylomicrons and very-low-density lipoproteins (VLDL) are most present in blood in the postprandial state, and they have been shown to have a direct role in atherosclerosis.9 This is clinically useful because high non-fasting triglyceride levels are directly associated with remnant lipoprotein levels.10 Other components of the lipid panel are also worthwhile to check in the non-fasting state. In a prospective study of 26,330 healthy women, Mora and colleagues demonstrated that non-fasting triglycerides, HDL cholesterol, total/HDL cholesterol ratio, and apolipoprotein A-1 levels were predictive of cardiovascular disease.11 Given the evidence that non-fasting lipids predict cardiovascular risk and that atherosclerosis is at least partially a postprandial process, non-fasting lipids may have practical advantages in the clinical setting.
The lipid panel has clinical implications beyond just primary prevention, however. Driver and colleagues looked at whether non-fasting lipid levels were appropriate in 6 distinct clinical scenarios.1 They note that fasting lipids are only absolutely required when screening and following patients with a family history of genetic hyperlipidemia or premature cardiovascular disease. In this case, fasting lipids combined with apolipoprotein B levels can help distinguish between different genetic conditions.
There are 3 situations in which fasting lipids are preferred: when estimating residual risk during statin therapy, assessing pancreatitis risk, and diagnosing hypertriglyceridemia. With patients on statin therapy, fasting levels are preferred because accurate LDL-cholesterol must be calculated to determine response to therapy. Fasting levels are preferred in assessing pancreatitis risk and hypertriglyceridemia because they are defined by triglyceride levels; however, in the case of hypertriglyceridemia, a non-fasting threshold of 200 mg/dL may be used.1
Finally, they list 2 situations in which non-fasting lipids are acceptable: when assessing cardiovascular risk in primary prevention patients and when clarifying the diagnosis of metabolic syndrome. In the latter scenario, a non-fasting triglyceride threshold of 200 mg/dL can be used for diagnosis.
In the case of fasting versus non-fasting lipids, it appears that the answer depends on the clinical scenario. The evidence suggests that when screening for ASCVD risk in a primary prevention patient, either a fasting or non-fasting lipid panel is appropriate. With time, more physicians will adopt this practice and fewer patients will be turned away for having their mid-morning snack.
Dr. Anthony Marte is a 3rd year medical student at NYU Langone Health
Peer reviewed by Michael Tanner, MD, Associate Editor, Clinical Correlations
Image courtesy of Wikimedia Commons
- Driver SL, Martin SS, Gluckman TJ, Clary JM, Blumenthal RS, Stone NJ. Fasting or nonfasting lipid measurements: it depends on the question. J Am Coll Cardiol. 2016:67(10):1227-1234. https://www.ncbi.nlm.nih.gov/pubmed/26965545
- Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical Chemistry. 1972:18(6):499-502.
- Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002:106(25):3143-3421. https://www.ncbi.nlm.nih.gov/pubmed/12485966
- Sidhu D, Naugler C. Fasting time and lipid levels in a community-based population: a cross-sectional study. Arch Intern Med. 2012:172(22):1707-1710. https://www.ncbi.nlm.nih.gov/pubmed/23147400
- Langsted A, Freiberg JJ, Nordestgaard BG. Fasting and nonfasting lipid levels: influence of normal food intake on lipids, lipoproteins, apolipoproteins, and cardiovascular risk prediction. 2008:118(20):2047-2056.
- Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014:129(25):S1-S45. http://circ.ahajournals.org/content/circulationaha/early/2013/11/11/01.cir.0000437738.63853.7a.full.pdf
- Doran B, Guo Y, Xu J, et al. Prognostic value of fasting versus nonfasting low-density lipoprotein cholesterol levels on long-term mortality: insight from the National Health and Nutrition Examination Survey III (NHANES-III). Circulation. 2014:130(7):546-553.
- Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007:298(3):299-308.
- Kolovou G, Ooi TC. Postprandial lipaemia and vascular disease. Curr Opin Cardiol. 2013:28(4):446-451. https://www.ncbi.nlm.nih.gov/pubmed/23591556
- Nordestgaard BG, Freiberg JJ. Clinical relevance of non-fasting and postprandial hypertriglyceridemia and remnant cholesterol. Curr Vasc Pharmacol. 2011:9(3):281-286.
- Mora S, Rifai N, Buring JE, Ridker PM. Fasting compared with nonfasting lipids and apolipoproteins for predicting incident cardiovascular events. Circulation. 2008:118(10):993-1001.