Journal of Lipid Research (Jan 2022)

LDL-C calculated by Friedewald, Martin-Hopkins, or NIH equation 2 versus beta-quantification: pooled alirocumab trials

  • Henry N. Ginsberg,
  • Robert S. Rosenson,
  • G. Kees Hovingh,
  • Alexia Letierce,
  • Rita Samuel,
  • Yann Poulouin,
  • Christopher P. Cannon

Journal volume & issue
Vol. 63, no. 1
p. 100148

Abstract

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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 BQ-determined 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 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.

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