Fasting Not Routinely Required for Determination of a Lipid Profile: Implications at Concentration Cut-Points
- Nordestgaard BG, Langsted A, Mora S, et al., on behalf of the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Joint Consensus Initiative.
- Fasting Is Not Routinely Required for Determination of a Lipid Profile: Clinical and Laboratory Implications Including Flagging at Desirable Concentration Cut-Points—A Joint Consensus Statement From the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine. Eur Heart J 2016;Apr 26:[Epub ahead of print].
The following is a summary of key points to remember about this joint consensus statement on the use of nonfasting rather than fasting lipid profiles and the clinical implications at concentration cut-points:
- The aim of the joint initiative between two major European clinical and laboratory societies was to critically evaluate the clinical implications of the use of nonfasting rather than fasting lipid profiles, and to provide guidance for the laboratory reporting of abnormal nonfasting or fasting lipid profiles. Extensive observational data found that the maximal difference between random nonfasting lipids (1-6 hours after a meal) and fasting lipids is not clinically significant: 26 mg/dl for triglycerides; 8 mg/dl for total cholesterol, low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C); and HDL-C, apolipoprotein A-1, apolipoprotein B, and lipoprotein (a) [Lp(a)] do not differ. An additional recommendation in the European lipid guidelines is that Lp(a) should be measured at least once to screen for cardiovascular risk, which is not recommended in US guidelines and considered ‘research’ by many insurers.
- General clinical practice in the United States has been to obtain a fasting lipid profile (at least 8 hours), so as to allow for the accurate calculation of the LDL-C and that treatment decisions are based on randomized lipid-lowering trials that used fasting lipids. But unless on a high-fat diet or patients with hypertriglyceridemia, when adults and children are on a stable diet, the fasting and nonfasting measured and calculated LDL-C are very similar.
- The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines do not require fasting for atherosclerotic cardiovascular disease (ASCVD) risk estimation, which recognize the advantages of nonfasting to the patient and the evidence that nonfasting non-HDL-C and apolipoprotein B appear to be better predictors of ASCVD events both prior to and on-statin therapy and in large population studies. The ACC/AHA guideline recommends fasting lipids prior to initiating statins to calculate the LDL-C and when non-HDL-C is >220 mg/dl or triglycerides are >500 mg/dl, which may be associated with genetic or secondary causes of marked elevation of the triglycerides.
- The consensus statement in this guideline is that to improve patient compliance with lipid testing, nonfasting lipid profiles should be used in the majority of patients (initial profile, CV risk assessment, in children, if preferred by the patient, in diabetics to avoid hypoglycemia, in the elderly, and on stable drug therapy). Fasting lipids may be required for a precise diagnosis of a lipid disorder, with triglycerides >400 mg/dl, severely elevated triglycerides in lipid clinics, recovering from triglyceride-associated pancreatitis, children prior to treatment, prior to starting medications that may cause severe hypertriglyceridemia, or when other fasting samples are required such as glucose or drug monitoring.
- Potential for risk misclassification regarding decisions for statin therapy is important, but minor changes in the lipid profile from fasting to nonfasting conditions will affect only a few individuals regarding the decision to start a statin or not. However, when the LDL-C is used for a treatment decision or goal within a borderline LDL-C, the lower LDL-C observed 1–6 hours after a habitual meal, particularly in diabetics, needs to be considered when using nonfasting lipid profiles. Of note, since the observed reduction in nonfasting LDL-C is due to liberal fluid intake and hemodilution rather than to food consumption, a similar LDL-C reduction is likely to occur when using fasting lipid profiles with no restrictions on fluid intake.
- The recommended laboratory report for nonfasting abnormal values based on desirable concentration cut-points are: triglycerides ≥175 mg/dl, total cholesterol ≥190 mg/dl, LDL-C ≥115 mg/dl, very LDL-C ≥35 mg/dl, non-HDL-C ≥150 mg/dl, Lp(a) ≥50 mg/dl, apo B ≥100 mg/dl, HDL-C ≤40 mg/dl, and apo A-1 ≤125 mg/dl.
- Extreme values warranting referral to a lipid clinic or lipid specialist: triglycerides >880 mg/dl (chylomicronemia syndrome with risk for pancreatitis), LDL-C >500 mg/dl (homozygous familial hypercholesterolemia with extremely high risk), LDL-C >190 mg/dl or >155 mg/dl in children (heterozygous familial hypercholesterolemia and high risk), Lp(a) >150 mg/dl (very high risk for CV events and aortic valve stenosis), LDL-C <10 mg/dl (genetic abetalipoproteinemia), HDL-C <10 mg/dl (genetic hypoalphalipoproteinemia).
- The societies recognize the complexity of implementation of the strategies in individual countries and other populations. They suggest key university hospitals and their laboratories begin using nonfasting lipid profiles and report desirable cut-points to indicate abnormal values, and that national societies of specialists and generalists and clinical chemistry adapt nonfasting lipid profiles. Journalists at key media should tell the story.
Perspective: The concept of nonfasting lipids is gaining popularity, but the process will be slow in countries such as the United States unless physicians begin to apply the recent guidelines for statin therapy in the four groups. Importantly, clinical judgment, patient preference, and other factors drive the decisions, not strict lab cut-points. (1) All patients with ASCVD warrant a statin regardless of lipids, and the assessment of compliance with statin and diet can be done nonfasting. (2,3) In the absence of ASCVD and diabetes, nonfasting lipids are fine, since the risk tool for determining 10-year and life-long ASCVD risk uses the total cholesterol and the HDL-C, which are very similar fasting and during the 1-6 hours after a meal. And the intensity of statin therapy is determined by the risk and not the lipid values. (4) The LDL-C cut-point of ≥190 mg/dl to decide treatment would be fine nonfasting, but could be 10-30 mg/dl lower depending on the nonfasting triglycerides. Of course, if no other data support treatment, a fasting sample can be drawn.
Keywords: Abetalipoproteinemia, Apolipoprotein A-I, Apolipoproteins B, Atherosclerosis, Cardiovascular Diseases, Cholesterol, HDL, Cholesterol, LDL, Cholesterol, VLDL, Diabetes Mellitus, Dyslipidemias, Fasting, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hyperlipoproteinemia Type II, Hypertriglyceridemia, Hypoglycemia, Lipids, Lipoprotein(a), Lipoproteins, HDL, Pancreatitis, Primary Prevention, Risk Assessment
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