What are the causes of falsely elevated calculated Low-Density Lipoprotein (LDL)?

From the Guidelines

Falsely elevated calculated Low-Density Lipoprotein (LDL) is commonly caused by methodological errors in the Friedewald equation, particularly in patients with high triglycerides or low LDL-C levels.

Causes of Falsely Elevated Calculated LDL

• High triglyceride levels: The Friedewald equation assumes a constant cholesterol/triglyceride ratio in VLDL, which may not be accurate in patients with high triglyceride levels 1.
• Low LDL-C levels: The Friedewald equation can significantly underestimate LDL-C in patients with low LDL-C levels (<70 mg/dL) 1.
• Lp(a) particles: Most LDL-C determining methods, including ultracentrifugation and Friedewald-calculated LDL-C, incorrectly count the cholesterol present in Lp(a) particles as 'LDL-C', thus overestimating LDL-C levels 1.
• Methodological errors: The Friedewald equation necessitates three separate analyses of total cholesterol, triglycerides, and HDL-C, which can lead to accumulated methodological errors 1.
• Non-fasting conditions: The use of Friedewald's formula is not indicated when blood is obtained under non-fasting conditions 1.

Important Considerations

• Alternative calculation methods: The Martin/Hopkins method and Sampson's method are novel, practical, indirect LDL-C calculation equations that can provide more accurate results, especially in patients with low LDL-C levels or high triglyceride levels 1.
• Direct LDL-C measurement: Direct LDL-C measurement with preparative ultracentrifugation (beta quantification) is the most accurate approach, but it is costly and time-consuming 1.

From the Research

Causes of Falsely Elevated Calculated Low-Density Lipoprotein (LDL)

• The Friedewald equation, commonly used to estimate LDL-C, has several recognized limitations, especially inaccurate results for triglycerides (TG) >4.5 mmol/l (>400 mg/dl) 2.
• The Martin/Hopkins equation and the Sampson equation are alternative methods that have been developed to provide more accurate LDL-C calculations, especially in patients with elevated TG levels 2.
• Studies have shown that calculated LDL-C levels can frequently underestimate directly measured LDL-C determinations, even in patients with serum triglyceride levels ≤4.52 mmol/l 3.
• The degree of underestimation of calculated LDL-C compared to direct LDL-C measurement increases as the triglyceride level increases 4, 3.
• Other factors that can contribute to discrepancies between calculated and directly measured LDL-C include age, sex, and body mass index 4.
• The use of different equations, such as the Martin/Hopkins equation and the Sampson equation, can result in varying degrees of underestimation or overestimation of LDL-C 5.

Factors Influencing LDL-C Calculation

• Triglyceride levels: High TG levels can lead to inaccurate results using the Friedewald equation 2, 4, 3.
• Age: Age can affect the accuracy of LDL-C calculation, with older adults potentially having larger discrepancies between calculated and directly measured LDL-C 4.
• Sex: Female sex has been associated with increased discrepancies between calculated and directly measured LDL-C 4.
• Body mass index (BMI): Elevated BMI can also contribute to discrepancies between calculated and directly measured LDL-C 4.

Comparison of LDL-C Calculation Methods

• The Friedewald equation is a widely used method for estimating LDL-C, but it has limitations, particularly at high TG levels 2, 4, 3.
• The Martin/Hopkins equation and the Sampson equation are alternative methods that have been developed to improve the accuracy of LDL-C calculation 2, 5.
• Direct measurement of LDL-C is considered the gold standard, but it is not always feasible in clinical practice 4, 3, 5.