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Circulation. 2019;139:e1082–e1143. DOI: 10.1161/CIR.0000000000000625 June 18/25, 2019 e1089 CLINICAL STATEMENTS AND GUIDELINES

I B-NR 2.  In adults who are 20 years of age or older and in whom an initial nonfasting lipid profile reveals a triglycerides level of 400 mg/dL or higher (≥4.5 mmol/L), a repeat lipid profile in the fasting state should be performed for assessment of fasting triglyceride levels and baseline LDL-C.S2.2-1–S2.2-4

IIa C-LD 3.  For adults with an LDL-C level less than 70 mg/dL (<1.8 mmol/L), measurement of direct LDL-C or modified LDL-C estimate is reasonable to improve accuracy over the Friedewald formula.S2.2-7–S2.2-9

IIa C-LD 4.  In adults who are 20 years of age or older and without a personal history of ASCVD, but with a family history of premature ASCVD or genetic hyperlipidemia, measurement of a fasting plasma lipid profile is reasonable as part of an initial evaluation to aid in the understanding and identification of familial lipid disorders.

Synopsis

The standard calculation method for LDL-C is the Friedewald formula: LDL-C=(TC)–(triglycerides/5)– (HDL-C). When triglyceride levels are not elevated, this equation is sufficiently accurate. In hypertriglyceridemia, however, Friedewald-calculated LDL- C can be erroneous. After normal food intake, LDL-C differs minimally with time.S2.2-10 Fasting and nonfasting TC and HDL-C levels appear to have fairly similar prognostic value and associations with CVD outcomes.S2.2-1–S2.2-6,S2.2-11 Thus, nonfasting samples can be used for risk assessment in primary prevention and for assessment of baseline LDL-C levels before the initiation of a statin in primary and secondary prevention. If more precision is necessary, fasting lipids can be measured, but a nonfasting sample is reasonable for most situations. The unreliability of the Friedewald-calculated LDL-C levels appears to be greatest at lower levels of LDL-C, particularly <70 mg/dL (<1.8 mmol/L).S2.2-7 Martin et al. have validated an approach to estimating LDL- C levels from a standard lipid panel when LDL-C levels is <70 mg/dL (<1.8 mmol/L) and triglycerides levels are >150 mg/dL (>1.7 mmol/L).S2.2-7–S2.2-9

Recommendation-Specific Supportive Text

1.	 If an individual has ingested an extremely high-fat meal in the preceding 8 hours, it may be prudent to assess lipids on another day after counseling the patient to avoid such meals. Documentation of the baseline LDL-C level will be useful in assessing the patient’s response to the initiation of statin therapy, if that is undertaken.S2.2-1–S2.2-6 Similarly, given relatively modest differences in LDL-C levels associated with the postprandial state, use of a nonfasting sample is effective to document baseline lipid levels before initiation of statin therapy in individuals with clinical ASCVD.S2.2-1–S2.2-6 In adults with a family history of premature ASCVD or genetic hyperlipidemia, a fasting lipid profile is reasonable for initial evaluation. 2.	 Given relatively modest differences in LDL-C levels between fasting and non-fasting samples, the latter is generally adequate to document baseline lipid levels prior to initiation of statin therapy.S2.2-1–S2.2-6

3.	 The unreliability of the Friedewald-calculated LDL-C levels rises at lower levels of LDL-C, particularly <70 mg/dL (<1.8 mmol/L). If accurate measurements of LDL-C levels are needed at very low LDL-C, calculation adjustments can be used.S2.2-7–S2.2-9 Measurement of apoB may be useful in determining whether hypertriglyceridemia is an atherogenic condition.S2.2-12,S2.2-13 4.	 In adults with a family history of premature ASCVD or genetic hyperlipidemia, a fasting lipid profile is reasonable for initial evaluation to aid in the understanding and identification of familial lipid disorders.S2.2-12,S2.2-13

2.3 Measurements of Apolipoprotein B

and Lipoprotein (a)

Two lipoprotein entities related to LDL-C are apoB and lipoprotein (a) [Lp(a)]. Because apoB is the major apolipoprotein embedded in LDL and VLDL, several investigators identify strength of association between apoB and ASCVD.S2.3-1 Others report a high correlation between apoB and non–HDL-C.S2.3-2 Under certain circumstances, particularly in patients with hypertriglyceridemia, the measurement of apoB may have advantages.S2.3-3 Nevertheless, apoB measurement carries extra expense, and its measurement in some laboratories may not be reliable.S2.3-4 A relative indication for its measurement would be triglyceride ≥200 mg/dL. A level >130 mg/dL corresponds to an LDL-C level ≥160 mg/dL and constitutes a risk-enhancing factor. A persistent elevation of apoB can be considered a risk-enhancing factor. Separately, Lp(a) is a modified form of LDL that appears to possess atherogenic potential.S2.3-5 Relative indications for its measurement are family history of premature ASCVD or personal history of ASCVD not explained by major risk factors. Lp(a) increases ASCVD risk especially at higher levels. Thus, if a decision is made to measure Lp(a), an Lp(a) ≥50 mg/dL or ≥125 nmol/L, Lp(a) may be considered a risk-enhancing factor.S2.3-6 Current evidence shows that it should be considered in women only in the presence of hypercholesterolemia and

Recommendations for Measurements of LDL-C and Non–HDL-C (Continued)

COR LOE Recommendations

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