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Non-fasting versus fasting cholesterol measurement

Dyce, Evan, DNP, FNP

doi: 10.1097/01.NPR.0000529668.54564.b9
Feature: SCREENING TESTS

Abstract: Fasting for cholesterol measurement has long been the accepted convention. Recent research expounded in clinical guidelines indicates that nonfasting cholesterol measurements predict outcomes at least as well as fasting cholesterol measurements. In most—but not all—clinical scenarios, fasting is not necessary. This article provides clinical recommendations based on the literature.

Fasting for cholesterol measurement has long been the accepted convention. Recent research expounded in clinical guidelines indicates that nonfasting cholesterol measurements predict outcomes at least as well as fasting cholesterol measurements. In most—but not all—clinical scenarios, fasting is not necessary. This article provides clinical recommendations based on the literature.

Evan Dyce is an NP at CentraCare Health, St. Cloud, Minn.

The author has disclosed no financial relationships related to this article.

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Atherosclerosis is a well-known risk factor associated with myocardial infarction (MI), stroke, peripheral vascular disease, kidney disease, and death.1 Elevated cholesterol levels have long been recognized as an important risk factor tied to the development of atherosclerosis and its negative consequences.2 Therefore, accurate measurement of cholesterol levels is crucial.

Conventional wisdom has required cholesterol measurement after fasting; that is, patients were instructed not to consume food or most beverages for 8 to 12 hours prior to measurement.3 This approach presents several problems, as patients may struggle with fasting for the required period of time, leading to dissatisfaction or nonadherence with fasting. If patients presented to the clinic without fasting, cholesterol measurement would at best be delayed, and at worst, be missed entirely because of breakdown in follow-up. Requiring patients to return to the clinic for future testing may present additional time, effort, and cost burdens.

In recent years, a number of clinical practice guidelines have shifted to accept and even promote nonfasting cholesterol measurement.3-6 This poses the question: Is nonfasting cholesterol measurement an effective alternative to fasting cholesterol measurement, and how do they compare in terms of predicting cardiovascular outcomes? This article seeks to answer this question and develop a concise recommendation for NPs in clinical practice.

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Literature review

One large, mixed-methods study (cross-sectional and prospective cohort) including over 40,000 participants analyzed cardiovascular outcomes and their association with fasting and nonfasting lipid measurements.7 The specific cardiovascular outcomes used to define risk were fatal and nonfatal cardiovascular events, including MI and ischemic stroke. The researchers hypothesized that lipid levels vary only minimally after food intake; they also designed the study to analyze cardiovascular risk based on nonfasting versus fasting lipid measurements.

Regarding the variation in lipid levels after normal food intake, the author found that lipids demonstrated only minimal changes after normal intake in the general population. Interestingly, the author found that total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and albumin all demonstrated decreases for 3 to 5 hours after the last meal; in contrast, triglycerides increased for up to 6 hours after the last meal. The researchers theorized this was likely because of dilution from fluid intake. After correcting for likely dilutional effect, only HDL cholesterol was decreased after meal intake; triglycerides remained elevated.7

In terms of patient outcomes, the researchers found that nonfasting lipid measurement predicted future cardiovascular risk as good as or better than fasting lipid measurement.7 This is interesting evidence showing that lipid values can be modified by intake, but it may not be a problem in assessing risk; instead, it may improve estimation of cardiovascular outcomes. This study does not answer the question of whether cutoffs for dyslipidemia should be the same or different for fasting versus nonfasting measurements. The researchers used high versus low tertiles to estimate risk, which works on proportions within the sample and not specific cutoff points. This study is Level IV evidence according to the hierarchy of evidence developed by Ackley and colleagues (see Levels of evidence).8

Moving to the highest level of evidence (Level I), a systematic review completed in 2016 reviews the evidence regarding nonfasting lipid measurement.3,8 The researcher found that lipid levels differed only minimally between fasting and nonfasting lipid measurements.3 While the author noted these are likely clinically insignificant, the actual value differences between the methods of measurement may be helpful to NPs who are considering how to measure lipids or analyzing the results of nonfasting lipid measurement. Expected changes in nonfasting lipid measurement compared with fasting are summarized below:

  • Negligible change in HDL cholesterol
  • Increase up to 8 mg/dL in total cholesterol
  • Increase up to 8 mg/dL in LDL cholesterol
  • Increase up to 25 mg/dL for triglycerides.3
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Table

This review concurs with Langsted and colleagues, finding that cardiovascular risk (based on studies looking at a clinical events and mortality related to MI, stroke, and cardiovascular revascularization) prediction is as good or better for nonfasting lipid measurement compared with fasting lipid measurement.3,7 For NPs prescribing HMG-CoA reductase inhibitor (statin) medications for dyslipidemia, it is important to note that multiple large-scale clinical trials of statin medications involved nonfasting lipid levels; this may provide NPs with comfort for using nonfasting lipid measurement as an indication for medication if it is necessary.3

Additional evidence for the prognostic value of nonfasting lipid measurement comes from Doran and colleagues, who analyzed outcome data (all-cause mortality and cardiovascular mortality) from over 4,000 matched pairs over 14 (±0.22) years.9 Researchers defined cardiovascular mortality as deaths from ischemic heart disease, heart failure, essential hypertensive heart disease, cerebrovascular disease, and atherosclerosis; the findings focused only on the prognostic value of LDL cholesterol. This retrospective cohort study found that nonfasting LDL cholesterol levels had similar prognostic value for both outcomes as fasting LDL cholesterol levels, concluding that recommendations emphasizing fasting lipid measurement may benefit from reevaluation.9 This study is comprised of Level IV evidence.8

A useful, nonsystematic review of the literature summarizes some of the nuances of lipid measurement, finding that several factors completely apart from fasting status may also affect lipid levels:

  • Supine positioning reduces cholesterol levels by 10% and triglyceride levels by 12%.
  • Tourniquet application of 2 to 5 minutes may increase cholesterol levels 5% to 15%.
  • Winter cholesterol levels are slightly elevated compared with summer cholesterol levels.
  • Winter triglyceride levels are slightly lower compared with summer triglyceride levels.
  • Nephrotic syndrome, infection, inflammation, hypothyroidism, MI, and hospital admission affect lipid values.10

This review also finds that nonfasting lipid cutoff points are not well established, and time and content of last meal should be considered when interpreting all lipid levels.10 Another important point is that a nonfasting triglyceride level is the most affected value based on fasting status, but nonfasting triglyceride levels may be superior to fasting for predicting cardiovascular events.10 This review is a relatively low level of evidence and unable to be classified by Ackley and colleagues, as this tool does not have a specific level to categorize literature reviews that are not systematic.8

A large cohort study conducted by Mora and colleagues examined lipid levels in fasting and nonfasting status and the strength of association with cardiovascular disease. The primary outcome studied was a composite incidence of cardiovascular disease defined as nonfatal MI, percutaneous coronary intervention, coronary artery bypass grafting, nonfatal stroke, or cardiovascular death.4

Table

Table

This study found that only triglyceride levels were over 5% different between fasting and nonfasting samples. However, even with changes less than 5%, the prognostic value of fasting and nonfasting lipid measurements differed for various lipoprotein markers. Nonfasting lipid measurements predict cardiovascular disease better than fasting lipid measurements for HDL cholesterol, triglycerides, total/HDL cholesterol ratio, and apolipoprotein A-1. Fasting lipid levels predict cardiovascular disease better than nonfasting levels for total cholesterol, LDL cholesterol, and non-HDL cholesterol.4

NPs should consider these findings when evaluating and following patients for lipid disorders. These findings may suggest that in patients found to have primarily elevated total cholesterol or LDL cholesterol (as opposed to HDL cholesterol or triglycerides), fasting lipid levels may be better for following the patient's cholesterol levels. This study encompasses Level IV evidence.8

Based on the evidence from the aforementioned studies and others, important clinical guidelines—Level I evidence—have incorporated nonfasting lipid measurements to various degrees.8 One of the first clinical guidelines to mention nonfasting lipid measurements was produced jointly by the European Society of Cardiology and the European Atherosclerosis Society in 2011.11 This guideline was only minimally supportive of nonfasting lipid measurements, as it recommended sampling be done after 12 hours of fasting if possible, noting fasting LDL cholesterol measurement as the treatment target for lipid-lowering therapy with the caveat that total and HDL cholesterol levels can be determined in nonfasting samples.11

Of note, the European Atherosclerosis Society updated its recommendations in 2016 based on new evidence.6 This new recommendation was strongly in favor of routine nonfasting lipid measurement. This guideline recommends routine use of nonfasting lipid measurement for screening, prior to starting lipid-lowering therapy, and during lipid-lowering therapy for patients on a stable regimen.6

This guideline also recommends clinicians obtain fasting samples if triglyceride levels are greater than 440 mg/dL. The authors emphasize that nonfasting and fasting lipid measurements should be complementary and not mutually exclusive; fasting may be desirable for follow-up of hypertriglyceridemic pancreatitis prior to starting medications that may cause hypertriglyceridemia and when suspecting genetic hypertriglyceridemia.6 Notably, this guideline provides cutoff points for fasting and nonfasting lipid measurements, recommending values be flagged as abnormal based on these values (see Fasting and nonfasting cutoff values).6

Table

Table

Differing cutoff points between nonfasting and fasting cutoff points are identical for nonfasting and fasting lipid measurements except for triglycerides, remnant cholesterol, and non-HDL cholesterol.6 The researchers suggest identical cutoff points for life-threatening or extremely abnormal levels, necessitating referral to specialty care for fasting and nonfasting lipid measurements (for example, triglycerides over 880 mg/dL).

A clinical guideline produced by the Canadian Cardiovascular Society in 2013 mentions nonfasting lipid measurements only once, stating that non-HDL cholesterol levels may be an alternative to LDL cholesterol levels as the target for lipid-lowering therapy and has the advantage of being able to be obtained in a nonfasting state.12 This guideline does not explicitly recommend nonfasting lipid measurement or provide guidance on interpreting nonfasting lipid levels.

The clinical guideline produced by the American College of Cardiology and the American Heart Association puts forth the position that a fasting lipid panel is preferred, but not required. This guideline does not offer specific diagnostic thresholds for abnormal nonfasting lipid measurement but does assert that nonfasting non-HDL cholesterol levels over 220 mg/dL or triglyceride levels over 500 mg/dL require follow-up with a fasting lipid panel.13

The National Clinical Guideline Centre and Joint British Societies guidelines produced a clinical guideline in 2014.5 This guideline recommends checking a full lipid panel, including total cholesterol, HDL cholesterol, non-HDL cholesterol, and triglyceride levels prior to starting lipid-lowering therapy and clarifies that this sample need not be fasting.5 This guideline also recommends checking annual nonfasting non-HDL cholesterol levels for patients on lipid-lowering therapy. Regardless of fasting status, this guideline recommends obtaining repeat tests with fasting patients and to refer to a specialist for triglyceride levels over 880 mg/dL.5

The guideline produced by the Institute for Clinical Systems Improvement is somewhat in contrast to the aforementioned guidelines. This guideline specifically recommends fasting lipid measurement in monitoring hyperlipidemia treatment; however, readers should note that this guideline is focused solely on management of lipid disorders and does not comment on screening.14

Another guideline reviewed was produced by the Endocrine Society.15 This guideline recommends diagnosing hypertriglyceridemia on fasting rather than nonfasting triglyceride levels. Readers should note that this guideline is specific to triglycerides, which are the most affected by fasting or nonfasting status. This recommendation concurs with Nordestgaard and colleagues (see Summary of recommendations).6

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Gaps in evidence

The evidence regarding nonfasting cholesterol measurement has greatly evolved in the last 10 years, with the strongest clinical guideline support coming out since 2015. The Nordestgaard and colleagues' clinical guideline was the only one that provided reference levels for abnormal nonfasting lipid levels; it would be helpful to have additional studies, systematic reviews, and guidelines providing guidance on this facet of care.6 Additionally, it would be helpful to further research how many patients who initially undergo nonfasting lipid measurement eventually require fasting lipid measurement and what reasons the nonfasting lipid measurement did not suffice.

One of the concerns with nonfasting lipid measurement was the potential impact on LDL cholesterol calculation using the Friedewald formula (which uses triglycerides as a variable). This has largely been negated by the increased use of direct LDL cholesterol estimation with advanced blood testing; however, it would be useful to specifically study how nonfasting lipid measurement affects providers' use or perceptions of the Friedewald formula.10

Additionally, an important consideration in utilizing nonfasting lipid measurement is that the studies utilizing nonfasting lipid measurement did not define a certain “normal” intake for nonfasting participants. Confirmatory studies looking at various levels of intake, dietary components (different foods from diverse cultures), and the impact of alcohol and other substances should be undertaken. Finally, one of the major motivations for obtaining nonfasting lipid measurement is to promote patient adherence with lipid testing. Therefore, research should be done to look at the actual impact of no longer requiring fasting for lipid testing on patient adherence and follow-up.

When incorporating nonfasting lipid measurements into their practices, NPs should be aware of potential differences in cutoff points for lipid values between the recommendations within this article and commercial lab thresholds. NPs should inform patients of these differences in order to prevent confusion when patients view their test results within patient portals or in printouts.

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Conclusion

Nonfasting cholesterol measurement is an effective alternative to fasting cholesterol measurement and predicts clinical outcomes at least as well as fasting cholesterol measurement. In most clinical scenarios, fasting for evaluation of lipids is not required. Fasting lipid measurement should be obtained when nonfasting triglyceride levels are over 440 mg/dL.6,13 NPs should consider obtaining fasting lipid measurement for following hypertriglyceridemic pancreatitis, prior to starting medications that cause hypertriglyceridemia, and for diagnosing hypertriglyceridemia.6,15

The use of nonfasting lipid measurement may improve patient satisfaction and adherence with lipid testing by relieving patients of fasting, which may be unpopular (especially with children), difficult with certain conditions (such as diabetes mellitus), and may delay initiation of important therapy. Nonfasting lipid measurement has the potential to decrease cost by eliminating the need for additional visits and blood samples, reducing transportation costs, and decreasing missed work time.5,6 Furthermore, the literature shows that nonfasting lipid measurement is as effective as fasting lipid measurement for predicting cardiovascular risk, which has led to a proliferation of clinical guidelines recommending their use.3,4,6,7,9

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REFERENCES

1. National Heart Lung, and Blood Institute. What is atherosclerosis? 2016. http://www.nhlbi.nih.gov/health/health-topics/topics/atherosclerosis.
2. Ross R, Harker L. Hyperlipidemia and atherosclerosis. Science. 1976;193(4258):1094–1100.
3. Mora S. Nonfasting for routine lipid testing: from evidence to action. JAMA Intern Med. 2016;176(7):1005–1006.
4. 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.
5. National Institute for Health and Care Excellence. Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. Clinical Guideline 181. 2014. http://www.nice.org.uk/guidance/cg181/evidence/lipid-modification-update-full-guideline-243786637.
6. Nordestgaard BG, Langsted A, Mora S, et al Fasting is not routinely required for determination of a lipid profile: clinical and laboratory implications including flagging at desirable concentration cutpoints—a joint consensus statement from the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine. Clin Chem. 2016;62(7):930–946.
7. Langsted A, Freiberg JJ, Nordestgaard BG. Fasting and nonfasting lipid levels: influence of normal food intake on lipids, lipoproteins, apolipoproteins, and cardiovascular risk prediction. Circulation. 2008;118(20):2047–2056.
8. Ackley BJ, Swan BA, Ladwig G, Tucker S. Evidence-Based Nursing Care Guidelines: Medical-Surgical Interventions. St. Louis, MO: Mosby Elsevier; 2008.
9. 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.
10. Nigam PK. Serum lipid profile: fasting or non-fasting. Indian J Clin Biochem. 2011;26(1):96–97.
11. Reiner Z, Catapano AL, De Backer G, et al ESC/EAS guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J. 2011;32(14):1769–1818.
12. Anderson TJ, Grégoire J, Hegele RA, et al 2012 Update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol. 2013;29(2):151–167.
13. 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 suppl 2):S1–S45. http://circ.ahajournals.org/content/early/2013/11/11/01.cir.0000437738.63853.7a.
14. Woolley T, Canoniero M, Conroy W, et al Healthcare Guidelines: Lipid Management in Adults. Bloomington, IN: Institute for Clinical Systems Improvement; 2017.
15. Berglund L, Brunzell JD, Goldberg AC, et al Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(9):2969–2989.
Keywords:

atherosclerosis; fasting cholesterol measurement; hyperlipidemia; lipids; nonfasting cholesterol measurement

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