TY - JOUR
T1 - LDL-C calculated by Friedewald, Martin-Hopkins, or NIH equation 2 versus beta-quantification
T2 - Pooled alirocumab trials
AU - Ginsberg, Henry N.
AU - Rosenson, Robert S.
AU - Kees Hovingh, G.
AU - Letierce, Alexia
AU - Samuel, Rita
AU - Poulouin, Yann
AU - Cannon, Christopher P.
N1 - Funding Information: The authors thank the patients, their families, and all investigators involved in the ODYSSEY studies included in this analysis. Medical writing support under the direction of the authors was provided by Rachel Dunn, PhD, Susanne Ulm, PhD, and Rob Campbell, PhD, of Prime Global (Knutsford, UK), funded by Regeneron Pharmaceuticals, Inc., according to Good Publication Practice guidelines (http://annals.org/ aim/article/2424869/good-publication-practice-communi cating-company-sponsored-medical-research-gpp3). Publisher Copyright: © 2021 THE AUTHORS.
PY - 2022/1/1
Y1 - 2022/1/1
N2 - Accurate assessment of LDL-C levels is important, as they are often used for treatment recommendations. For many years, plasma LDL-C levels were calculated using the Friedewald equation, but there are limitations to this method compared with direct measurement via beta-quantification (BQ). Here, we assessed differences between the Friedewald, Martin-Hopkins, and NIH equation 2 methods of calculating LDL-C and the "gold standard"BQ method using pooled phase 3 data with alirocumab. All randomized patients were included irrespective of the treatment arm (n = 6,122). We compared pairs of LDL-C values (n = 17,077) determined by each equation and BQ. We found that BQ-derived LDL-C values ranged from 1 to 397 mg/dl (mean 90.68 mg/dl). There were strong correlations between Friedewald-calculated, Martin-Hopkins-calculated, and NIH equation 2-calculated LDL-C with BQdetermined LDL-C values (Pearson's correlation coefficient = 0.985, 0.981, and 0.985, respectively). Importantly, for BQ-derived LDL-C values =70 mg/ dl, only 3.2%, 1.4%, and 1.8% of Friedewald-calculated, Martin-Hopkins-calculated, and NIH equation 2-calculated values were <70 mg/dl, respectively. When triglyceride (TG) levels were <150 mg/dl, differences between calculated and BQ-derived LDL-C values were minimal, regardless of the LDL-C level (<40, <55, or <70 mg/dl). However, when TG levels were >150 mg/dl, NIH equation 2 provided greater accuracy than Friedewald or Martin-Hopkins. When TGs were >250 mg/dl, inaccuracies were seen with all three methods, although NIH equation 2 remained the most accurate. In conclusion, LDL-C calculated by any of the three methods can guide treatment decisions for most patients, including those treated with proprotein convertase subtilisin/kexin type 9 inhibitors.
AB - Accurate assessment of LDL-C levels is important, as they are often used for treatment recommendations. For many years, plasma LDL-C levels were calculated using the Friedewald equation, but there are limitations to this method compared with direct measurement via beta-quantification (BQ). Here, we assessed differences between the Friedewald, Martin-Hopkins, and NIH equation 2 methods of calculating LDL-C and the "gold standard"BQ method using pooled phase 3 data with alirocumab. All randomized patients were included irrespective of the treatment arm (n = 6,122). We compared pairs of LDL-C values (n = 17,077) determined by each equation and BQ. We found that BQ-derived LDL-C values ranged from 1 to 397 mg/dl (mean 90.68 mg/dl). There were strong correlations between Friedewald-calculated, Martin-Hopkins-calculated, and NIH equation 2-calculated LDL-C with BQdetermined LDL-C values (Pearson's correlation coefficient = 0.985, 0.981, and 0.985, respectively). Importantly, for BQ-derived LDL-C values =70 mg/ dl, only 3.2%, 1.4%, and 1.8% of Friedewald-calculated, Martin-Hopkins-calculated, and NIH equation 2-calculated values were <70 mg/dl, respectively. When triglyceride (TG) levels were <150 mg/dl, differences between calculated and BQ-derived LDL-C values were minimal, regardless of the LDL-C level (<40, <55, or <70 mg/dl). However, when TG levels were >150 mg/dl, NIH equation 2 provided greater accuracy than Friedewald or Martin-Hopkins. When TGs were >250 mg/dl, inaccuracies were seen with all three methods, although NIH equation 2 remained the most accurate. In conclusion, LDL-C calculated by any of the three methods can guide treatment decisions for most patients, including those treated with proprotein convertase subtilisin/kexin type 9 inhibitors.
KW - Alirocumab
KW - Beta-quantification
KW - Calculated LDL-C
KW - Cholesterol
KW - Drug therapy/hypolipidemic drugs
KW - Friedewald
KW - LDL
KW - Martin-Hopkins
KW - NIH equation 2
KW - PCSK9
UR - http://www.scopus.com/inward/record.url?scp=85123289714&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/J.JLR.2021.100148
DO - https://doi.org/10.1016/J.JLR.2021.100148
M3 - Article
C2 - 34774485
SN - 0022-2275
VL - 63
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 1
M1 - 100148
ER -