NIH LDL-c Equation Tool Kit

Group Photo Of Professional Colleagues Working Together In Clinical Analysis Laboratory

Practice Update from the CSCC Reference Interval Harmonization Working Group:

Recommendations on LDL-C Calculation & Reporting

Key Recommendation: All clinical laboratories in Canada should use the NIH LDL-equation to calculate and report LDL-C instead of the Friedewald LDL-C equation A toolbox has been created to aid in the implementation of the NIH LDL-C equation that consists of (1) a communication template to distribute to clinical users, (2) report comments to use when reporting LDL-C during the transition phase, and (3) a template to verify correct calculation by NIH LDL-C Equation.

Click here for the complete CSCC Harmonized Clinical Laboratory Lipid Reporting Recommendations.

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Communication Template

Key Message

Effective [DATE], LDL-C will be reported as calculated by the NIH LDL-equation instead of the Friedewald LDL-C equation.

Current Friedewald LDL-C Equation (SI units):

Cscc Nih Ldl Current Equation

New NIH LDL-C equation (SI units):

Background

Friedewald equation has traditionally been used to calculate LDL-C, was developed in 1972 and is not valid in patients who are non-fasting, have triglycerides >4.5 mmol/L or have type III hyperlipoproteinemia; it is inaccurate when LDL-C <1.5 mmol/L
NIH equation was developed in 2020 and validated in a Canadian population; it accurately estimates LDL-C when patients are non-fasting and when triglycerides are up to 9.0 mmol/L
NIH equation should not be used for patients with type III hyperlipoproteinemia and is inaccurate when LDL-C <0.5 mmol/L
NIH equation correlates well with Friedewald equation for most patients, but correlates better with β-quantification (LDL-C reference method) when triglycerides are high and LDL-C is low
Reporting LDL-C as calculated by the NIH equation is in accordance with the Harmonized Lipid Reporting Recommendations from the CSCC Harmonized Reference Interval Working Group (CSCC hRI-WG)

Why this is important:

The NIH equation provides a more accurate estimation than the Friedewald equation for LDL-C:
- In the non-fasting state, which is becoming more common when ordering the lipid panel
- When triglycerides are high (between 4.5 and 9.0 mmol/L), which is becoming more common with the increased prevalence of dyslipidemia
- When LDL-C is low (between 0.5 – 1.5 mmol/L), which is becoming more common with more aggressive LDL-C targets

References:

Friedewald, et al. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical Chemistry 1972;18(6):499-502
Sampson M, et al. A new equation for calculation of low-density lipoprotein cholesterol in patients with normolipidemia and/or hypertriglyceridemia. JAMA Cardiology 2020;5(5):540-548
Higgins V, et al. Validating the NIH LDL-C equation in a specialized lipid cohort: Does it add up? Clinical Biochemistry. 2022;99:60-68
White-Al Habeeb N & Higgins V, et al. Harmonized Lipid Reporting for Clinical Laboratories based on the 2021 Canadian Lipid Guidelines. Canadian Journal of Cardiology. 2022;S0828-282X(22)00215-X

Circumstance	Comment
Prior to change, with unknown implementation date	LDL-C result is based on the Friedewald LDL-C equation. The laboratory will be changing to the new NIH LDL-C equation that has improved accuracy when triglycerides are high and/or LDL-C is low.
Prior to change, with known implementation date	LDL-C result is based on the Friedewald LDL-C equation. As of [DATE], the laboratory will change to the new NIH LDL-C equation that has improved accuracy when triglycerides are high and/or LDL-C is low.
After change	LDL-C result is based on the NIH LDL-C equation.

Condition	Expected Result
LDL-C LoD of 0.50 mmol/L	LDL-C results 0-0.49 mmol/L are reported as <0.50 mmol/L
Triglycerides >4.52 mmol/L	LDL-C result is reported
Triglycerides >9.04 mmol/L	LDL-C result is not reported. The comment “Unable to calculate“ is added to the report.
At least one component parameter not available	LDL-C result is not reported. The comment “Unable to calculate“ is added to the report.

Age (years)	Sex	Total Cholesterol (mmol/L)	HDL-C (mmol/L)	Triglycerides (mmol/L)	NIH LDL-C Equation Calculation (mmol/L)
10	Male	2.30	0.60	5.20	<0.50
10	Female	2.30	0.60	5.20	<0.50
10	Male	3.90	0.60	5.00	1.55
10	Female	3.90	0.60	5.00	1.55
10	Male	7.10	0.70	1.00	6.00
10	Female	7.10	0.70	1.00	6.00
10	Male	4.20	0.50	10.2	Unable to calculate
10	Female	4.20	0.50	10.2	Unable to calculate
10	Male	Not available	0.80	1.30	Unable to calculate
10	Female	Not available	0.80	1.30	Unable to calculate
10	Male	3.90	Not available	1.30	Unable to calculate
10	Female	3.90	Not available	1.30	Unable to calculate
10	Male	3.90	0.80	Not available	Unable to calculate
10	Female	3.90	0.80	Not available	Unable to calculate
40	Male	2.30	0.60	5.20	<0.50
40	Female	2.30	0.60	5.20	<0.50
40	Male	3.90	0.60	5.00	1.55
40	Female	3.90	0.60	5.00	1.55
40	Male	7.10	0.70	1.00	6.00
40	Female	7.10	0.70	1.00	6.00
40	Male	4.20	0.50	10.2	Unable to calculate
40	Female	4.20	0.50	10.2	Unable to calculate
40	Male	Not available	0.80	1.30	Unable to calculate
40	Female	Not available	0.80	1.30	Unable to calculate
40	Male	3.90	Not available	1.30	Unable to calculate
40	Female	3.90	Not available	1.30	Unable to calculate
40	Male	3.90	0.80	Not available	Unable to calculate
40	Female	3.90	0.80	Not available	Unable to calculate

NIH LDL-c Equation Tool Kit

Practice Update from the CSCC Reference Interval Harmonization Working Group:

Recommendations on LDL-C Calculation & Reporting

Communication Template

Transition Reporting Comments

Key verification conditions and template to verify correct calculation by NIH LDL-C Equation