As LDL levels majorly contribute towards CVD, Hypertension, Type 2 diabetes, Obesity and the Metabolic Syndrome – Ensuring that we get the accurate and precise measurements of LDL is of paramount importance. An error in the value of LDL could misguide treatment planning and outcomes
Indirect or calculated LDL is derived by the Friedwald formula
Total Cholesterol = HDL + LDL + VLDL
VLDL = Triglyceride / 5
LDL = Total cholesterol – (HDL + Triglyceride / 5)
The Direct LDL measurement uses a homogenous assay based on a beta quantification kit that directly measures the LDL component from a serum sample; without needing to rely on TC, TG or HDL levels.
The drawbacks of using the Friedwald Formula for determining levels of LDL cholesterol are:
Ref: Indian J EndocrinolMetab. 2014 Jul-Aug; 18(4): 502–504.
Pharmacotherapy. 2004 Feb;24(2):167-72.
Pak J Med Sci. 2016 Jul-Aug; 32(4): 955–960
Recommend using only direct LDL methods, especially when the LDL is below 70 mg/dL and TG is higher than the range of 15 to 200 mg/dL
LDL values can come from either a fasting lipoprotein panel or a direct LDL test. The lipoprotein panel indirectly calculates LDL cholesterol by using the Friedewald equation (LDL = TC-HDL-TG/). In general, either test can be used, but be aware that the Friedewald equation tends to underestimate LDL when LDL is low (-70) or triglycerides are high (> 150-200). In these cases, the true LDL value can be 10-20 points higher. So, in such cases, consider using a direct LDL test or ensuring that the patient is well below target.
The NCEP ATP III report recognizes the benefit of a truly accurate direct LDL-C that could be used in the non-fasting state.
Third Report of the National Cholestrol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II).
INDIAN STUDY SPANNING APPROX. 15,000 PATIENTS SUPPORTS THE USE OF DIRECT LDL IN TG > 200 AND LDL 130 mg/dL https://www.ncbi.nlm.nih.gov/pmc/articles/PMC413 8905/ Original Article
Subramanian Kannan, Shriraam Mahadevan , Bharath 2 3 4 Ramji , Muthukumaran Jayapaul , V. Kumaravel Consultant, Endocrinology Diabetes and Bariatric Medicine, 1 Narayan Health City, Banglore, Karnataka, Endocrine and 2 Speciality Clinic, Chennai, Assistant Professor Endocrinology, Chettinad Medical College, Chennai, 3Consultant Endocrinologist, Arka Cenre for Hormonal 4 Health, Chennai, Department of Clinical Endocrinolgy, Alpha Hospital and Research Centre, Anuppanady, Madurai, Tamil Nadu, India Background: Validity of Friedwald Formula (FF) in patients with serum triglycerides (TGs)
Results: LDL by FF correlateed with directly measured LDL with correlation coefficient of 0.89 with the best correlation seen in TG levels 100-150. Higher level of TG (>200) underestimates the LDL calculated by FF particularly at LDL values 130 mg/dl. Conclusion: We suggest repeating the LDL by direct assay techniques particularly in patients with TG 200 and when LDL 130. This helps in correctly stratifying the coronary artery disease’ (CADs’) risk and goals of treatment
We performed an in-house retrospective analysis of around 1 lakh samples that were tested at our labs for lipid profile. We performed the LDL test for these samples by both the direct and the calculated methods. The objective was to understand the correlation of results between the two methods. Summary of Results:
|Triglycerides Category||Number of Bookings||Mean of LDL Cholesterol Direct||Mean of LDL Cholesterol Calculated|
|Less than 200||88962||114||105|
|400 or more||1628||118||77|
Across all ranges of TG, the LDL value was under-reported by the calculated or indirect estimation. At the level of TG >200, the calculated LDL method seemed inefficient in reporting the actual LDL and gave consistently lower values. These findings seem consistent with the findings of other larger studies that have shown an underestimation of 20 mg/dL with calculated LDL as compared to direct LDL (Lindsey et al. Pharmacotherapy. 2004;24(2))
As per recommendations of international guidelines, for TG levels more than 200 and for LDL levels less than 70 mg/dL, the calculated or indirect method of LDL estimation is not accurate as it provides an underestimated value.
Guidelines recommend opting for the direct LDL measurement in such cases. Direct LDL is an automated assay with controls and provides an accurate estimation of LDL values regardless of TG levels