What is the method for calculating Low-Density Lipoprotein (LDL) cholesterol?

From the Guidelines

To calculate LDL cholesterol, the Friedewald formula is recommended: LDL-C = (TC) - (triglycerides/5) - (HDL-C), as stated in the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1. When using this formula, it is essential to consider the levels of triglycerides, as the calculation may not be accurate when triglyceride levels are elevated, particularly above 150 mg/dL (>1.7 mmol/L) and LDL-C levels are <70 mg/dL (<1.8 mmol/L) 1.

• The formula requires the following values from a standard lipid panel blood test:
  • Total Cholesterol (TC)
  • HDL Cholesterol (HDL-C)
  • Triglycerides
• For example, if your total cholesterol is 200 mg/dL, HDL is 50 mg/dL, and triglycerides are 150 mg/dL, your LDL would be calculated as: LDL-C = 200 - (150/5) - 50 = 200 - 30 - 50 = 120 mg/dL.
• It is also important to note that 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, as fasting and nonfasting TC and HDL-C levels appear to have fairly similar prognostic value and associations with CVD outcomes 1.
• However, if more precision is necessary, fasting lipids can be measured, but a nonfasting sample is reasonable for most situations, according to the guideline 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Calculating LDL Cholesterol

To calculate LDL cholesterol, several methods can be used, including the Friedewald equation and a novel equation.

• The Friedewald equation calculates LDL cholesterol as: (total cholesterol) - (non-high-density lipoprotein cholesterol [non-HDL-C]) - (triglycerides [TGs]/5) 2.
• A novel equation uses an adjustable factor, the median TG:very-low-density lipoprotein cholesterol ratio in strata defined by levels of TG and non-HDLC, as divisor for TGs, and has been shown to provide more accurate estimates of LDL-C compared with the Friedewald equation 2.
• Another modified Friedewald equation calculates LDL as: (total cholesterol) - (HDL) - (1/6 triglyceride), which has been shown to be more accurate than the standard Friedewald equation, especially when triglyceride levels are less than 300 mg/dl 3.

Considerations for Calculation

When calculating LDL cholesterol, it is essential to consider the triglyceride levels, as high levels can affect the accuracy of the calculation.

• The Friedewald equation is not valid for patients with triglycerides ≥400 mg/dL 2.
• For patients with triglyceride levels less than 300 mg/dl, the modified Friedewald equation can be used to calculate LDL with an accuracy of 83.8% compared to direct measured LDL 3.
• The novel equation provides a higher estimation of exact LDL-C values than the Friedewald equation, particularly in patients with low LDL-C levels 2.

Clinical Implications

The calculation of LDL cholesterol has significant clinical implications, as it is used to assess cardiovascular risk and guide treatment decisions.

• Accurate estimation of LDL-C is required to risk-stratify patients and determine the need for lipid-lowering therapy 2.
• The use of LDL cholesterol calculations can help identify patients who may benefit from intensive lipid-lowering therapy, even those with lower baseline LDL-C levels 4.