Inaccuracy of Calculated LDL-Cholesterol in Type 2 Diabetes: Consequences for Patient Risk Classification and Therapeutic Decisions

LDL-cholesterol (LDLc) is the main lipid marker in cardiovascular risk estimation and the principal therapeutic target in both diabetic and nondiabetic subjects (1)(2). The designated comparison method for the determination of LDLc, using ultracentrifugation and precipitation, known as “β-quantification” (3), is cumbersome and time-consuming and requires expensive instrumentation and trained personnel. The Friedewald equation (4) {LDLc = total cholesterol − HDLc − [triglycerides (in mmol/L)/2.17 or triglycerides (in mg/dL)/5]}, the most frequently used method for the calculation of LDLc, assumes that VLDL particles maintain a nearly constant cholesterol:triglyceride ratio. However, this assumption is invalid in the presence of chylomicronemia and increased VLDL or intermediate-density lipoprotein particles (4)(5)(6)(7). Because diabetic dyslipidemia includes quantitative and qualitative abnormalities in lipoprotein particles, including VLDL and their remnants (8)(9)(10), the use of the Friedewald equation in diabetic patients has been questioned (11)(12)(13). HDL-cholesterol (HDLc), often determined after chemical precipitation of apolipoprotein B (apoB)-containing lipoproteins, has technical drawbacks that could interfere with the accuracy of LDLc calculation (14). New homogeneous, direct methods have improved HDLc determination (15). However, the consequences on patient classification and therapy of using direct, more precise methods for HDLc in the estimation of LDLc by the Friedewald equation have, to our knowledge, not been assessed. We previously proposed an equation that included total triglycerides and cholesterol, and apoB that was more accurate than the Friedewald equation in estimating LDLc (16). Because diabetic dyslipidemia includes hyperapoB (17), an equation that includes apoB in the estimation of LDLc could be of special interest in these patients. Thus, our aims were to ascertain whether a direct HDLc method increases the accuracy of the Friedewald formula, to evaluate an equation that includes apoB in the estimation of LDLc, and …