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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.
NIH LDL-C equation Implementation toolkit:
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):
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
Transition Reporting Comments
The following comments can be considered, based on laboratory and IT resources. Depending on transition time, one or more comments may be appropriate.
| 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. |
Key verification conditions and template to verify correct calculation by NIH LDL-C Equation
Key Verification Conditions:
| 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. |
Template for testing:
| 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 |