Positioning about the Flexibility of Fasting for Lipid Profiling



## Justifications
The review of the need of fasting for lipid profile analysis (total cholesterol, LDL-C, HDL-C, non-HDL-C, and triglycerides is based on the following grounds:
- Since the postprandial state predominates during most of the day, the patient is more exposed to the lipid levels in this condition when compared with the fasting state. Therefore, the postprandial state may represent more effectively the potential impact of the lipid levels on an individual's cardiovascular risk.
- Measurements in the postprandial state are more practical and provide the patient a greater access to the laboratory, decreasing the number of missed working days and medical appointments due to missed tests, allowing a better assessment of the individual's cardiovascular risk.
- Blood collection in the postprandial state is safer in several circumstances and may help prevent hypoglycemia secondary to the use of insulin in patients with diabetes mellitus, or due to prolonged fasting in pregnant women, children, and elderly individuals, minimizing complications and increasing the adherence to the tests and the attendance to medical appointments.
- There are no significant differences in measurements of total cholesterol, HDL-C, non-HDL-C, and LDL-C performed in the postprandial or fasting state. Levels of TG increase in the fed state, but such increase has little relevance as far as a regular meal without fat overload is considered, with the possibility of adjustment in the reference values. [bib_ref] Fasting or nonfasting lipid measurements. it depends on the question, Driver [/bib_ref] [bib_ref] Nonfasting sample for the determination of routine lipid profile: is it an..., Rifai [/bib_ref] [bib_ref] Nonfasting lipid profiles: the way of the future, Langsted [/bib_ref] [bib_ref] Prognostic value of fasting versus nonfasting low-density lipoprotein cholesterol levels on long-term..., Doran [/bib_ref] [bib_ref] Postprandial changes of lipoprotein profile: effect of abdominal obesity, Sabaka [/bib_ref] [bib_ref] Fasting time and lipid levels in a community-based population: a cross-sectional study, Sidhu [/bib_ref] - With a flexibility for lipid profiling, there is a greater amplitude of schedules, thereby reducing congestion in the laboratories, especially early in the morning, bringing more comfort to the patient.
- With the technological advances in diagnostic methods, the main assays available have mitigated the interference caused by increased sample turbidity due to high TG concentrations. However, there are potential limitations, especially related to the calculation of LDL-C, in which performance studies of different methodologies have shown a need for a revision of the practical use of the adopted formulas.

## Clinical and laboratory aspects in the flexibility of fasting for lipid profile analysis
In easing the requirement for fasting in the collection of samples for lipid profile assessment, some clinical and laboratory recommendations become important.
Recommendations for the care of the patient in the laboratory - Nonfasting sample collection for lipid profiling: may be done by the laboratory with the presence of the information about fasting at the time of sample collection in the laboratory report.
- A medical request without a definition of the fasting duration and without other tests known to require fasting: it is recommended to include in the laboratory report the fasting duration informed at the time of the sample collection.
- Presence in the same request of other tests that require fasting: the laboratory may define that the lipid profile should be collected with a 12-hour fasting when other laboratory tests, ordered on the same request, also require this period of fasting. The laboratory is recommended to specify whether or not fasting is required for each exam: no fasting, 12-hour fasting, or according to the definition set by the laboratory.
- When an indication of a specific fasting duration is present: if the request by the physician has a specific fasting duration, the laboratory should follow such recommendation. The calculation of hours of fasting by the "SIL" (Laboratory Information System, Sistema de Informacao Laboratorial) may be used, based on the information of the time elapsed since the last meal.
- When the TG levels in the postprandial state are > 440 mg/dL, or in the presence of special situations such as the recovery from pancreatitis secondary to hypertriglyceridemia, or at the beginning of a treatment with drugs that cause severe hypertriglyceridemia, the prescribing physician is recommended to request a new TG evaluation with a 12-hour fasting and this will be considered as a new TG test by the laboratory.- When the second sample collection for TG measurement occurs: the use of the same code or another specific code for the TG measurement without fasting and after a 12-hour fast will be at the discretion of each laboratory, depending on its system and strategy. Template recommendations for the laboratory's report

## Special article
Scartezini
The report is a responsibility of the laboratory and its technical manager. With the purposes of alignment and harmonization among the institutions, it is recommended the adoption of the following information in the report:
- The reference values and therapeutic target for the lipid profile (adults aged > 20 years) according to the cardiovascular risk assessment estimated by the prescribing physician are described in [fig_ref] Table 1 -: Reference values and therapeutic targets for adults > 20 years according to... [/fig_ref]. [bib_ref] IMPROVE-IT Investigators. Ezetimibe added to statin therapy after acute coronary syndromes, Cannon [/bib_ref] - Insertion of a note in the report referencing that the lipid profile results should be interpreted according to the clinical assessment and evolution of the patient.
The following sentence is recommended: "The clinical interpretation of the results should take into account the reason for indication of the test, the metabolic state of the patient, and the stratification of risk for establishment of the therapeutic goals."
- The target reference values of the lipid profile for children and adolescents are shown in [fig_ref] Table 2 -: Reference values of lipid profile for children and adolescents* Total cholesterol >... [/fig_ref]. [bib_ref] Fasting might not be necessary before lipid screening: A Nationally Representative Cross-sectional..., Steiner [/bib_ref] - Patients with diabetes and no risk factors or evidence of subclinical atherosclerosis should maintain LDL-C levels below 100 mg/dL. Patients with risk factors or subclinical atherosclerotic disease should maintain LDL-C levels below 70 mg/dL. Patients with a history of acute myocardial infarction; stroke; coronary, carotid or peripheral revascularization; or history of amputation should maintain the LDL-C levels below 50 mg/dL.

## Recommendations about formulas and direct ldl-c measurement
The assessment of LDL-C can be performed by direct measurement or estimated by calculation based on Friedewald's or Martin's formula. [bib_ref] Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in..., Colhoun [/bib_ref] The following recommendations are suggested to the laboratories:
- Observe the limitations of nonfasting and TG values > 400 mg/dL when Friedewald's formula 15 is used to estimate LDL-C; in these cases, Martin's formula 16 or direct measurement should be used.
- When collecting postprandial samples, the LDL-C measurement can be performed by direct measurement or calculated using Martin's formula. - Include non-HDL-C in the calculation along with other results of the lipid profile in adults, even without fasting, since the TG levels do not interfere in such calculation. Reporting or not of the VLDL-C calculation may be done at the discretion of the laboratory.
The main purpose of this document is to standardize the clinical and laboratory actions in regards to the flexibility of fasting in the lipid profile analysis across the national territory, contributing to offer security to the decision-making process by physicians and laboratories, grounded by scientific evidence.

# Author contributions

## References

## Potential conflict of interest
No potential conflict of interest relevant to this article was reported.

# Sources of funding
There were no external funding sources for this study.

## Study association
This study is not associated with any thesis or dissertation work.
[fig] : The inclusion of a specific note about the screening of familial hypercholesterolemia (FH) is left at the discretion of the laboratory. The following sentence is recommended: "Values of total cholesterol > 310 mg/dL in adults or  230 mg/dL in children and adolescents may be indicative of familial hypercholesterolemia, if secondary dyslipidemias are excluded."14 [/fig]
[table] Table 1 -: Reference values and therapeutic targets for adults > 20 years according to the patient's cardiovascular risk assessed by the physician requesting the lipid profile * Total cholesterol > 310 mg/dL: consider the likelihood of familial hypercholesterolemia; **When the triglyceride levels are above 440 mg/dL (without fasting), the prescribing physician must request a new triglycerides measurement after 12-hour fasting and the laboratory should consider this as a new triglycerides test. 16. Martin SS, Blaha MJ, Elshazly MB, Toth PP, Kwiterovich PO, Blumenthal RS et al. Comparison of a novel method vs the Friedewald equation for estimating low-density lipoprotein cholesterol levels from the standard lipid profile. JAMA. 2013; 310(19): 2061-681. [/table]
[table] Table 2 -: Reference values of lipid profile for children and adolescents* Total cholesterol > 230 mg/dL: consider the likelihood of familial hypercholesterolemia; **When the triglycerides levels are above 440 mg/dL (without fasting), the prescribing physician must request a new triglycerides measurement after 12-hour fasting and the laboratory should consider this as a new triglycerides test. [/table]