Background A number of national and international guidelines recommend treatment to low-density lipoprotein cholesterol (LDL-C) <70 mg/dL. Comparing the performance of the Friedewald and a novel LDL-C estimate at these concentrations in a nationally representative and clinical cohorts can inform best practices. Objectives The objectives of the study were to evaluate concordance between Friedewald-estimated LDL-C and novel-estimated LDL-C and compare with other atherogenic parameters when the estimated LDL-C is <70 mg/dL. Methods Atherogenic lipid parameters were assessed in a cross-sectional analysis among participants with a Friedewald-estimated LDL-C <70 mg/dL from National Health and Nutrition Examination Survey (NHANES) 2011–2012 (n = 334), Johns Hopkins (n = 896), and Mayo Clinic (n = 1151). Novel LDL-C was estimated using an individualized factor to account for heterogeneity in the triglyceride to very low-density lipoprotein cholesterol ratio. Participants were classified as concordant if their LDL-C was <70 mg/dL by both equations and discordant if ≥70 mg/dL by the novel equation. Results Among NHANES participants not on statin therapy, 10% had LDL-C <70 mg/dL by both the Friedewald and novel equations. Overall, 15% of participants from NHANES, 20% from Johns Hopkins, and 20% from Mayo Clinic had discordant LDL-C values. In all 3 cohorts, nearly one-fourth of participants in the discordant group had an LDL-C estimate of ≥80 mg/dL (ie, ≥10 mg/dL higher) by the novel equation. Compared with the concordant group, the discordant group had significantly higher median concentrations of non-high-density lipoprotein cholesterol (HDL-C; 101–104 mg/dL vs 74–79 mg/dL) and apolipoprotein B (apoB; 65–72 mg/dL vs 47–57 mg/dL). In NHANES, wherein statins use was recorded, a similarly higher atherogenic burden by non-HDL-C and apoB levels was observed on and off statin therapy in the discordant group. Conclusions In a nationally representative sample, a hospital laboratory, and a reference laboratory, approximately one-fifth of individuals with Friedewald-estimated LDL-C <70 mg/dL have a value ≥70 mg/dL using the novel LDL-C equation. These individuals also have significantly higher non-HDL-C and apoB concentrations, conferring an increased risk for cardiovascular disease. Accordingly, ongoing use of Friedewald estimation may lead to the misclassification of high-risk individuals and subsequent under-utilization of lipid-lowering therapies. Further investigations are necessary to confirm these findings in patients using proprotein convertase subtilisin-kexin type 9 inhibitors.
Bibliographical noteFunding Information:
This study did not receive specific funding. S.P.W. is supported by the Pollin Cardiovascular Prevention Fellowship. S.S.M. has received research support from the American Heart Association, Aetna Foundation, CASCADE FH, Google, and Apple. Authors' contributions:J.W.M., L.J.D., A.S.J., A.M., L.J.S., and S.R.J. contributed to acquisition of data; S.P.W. and S.S. M. drafted the article; S.P.W., J.W.M., L.J.D., A.S.J., A.S., L.S., R.S.B., and S.R.J. analyzed and interpreted the data; R.S.B. made the critical revision of the article; S.S.M. contributed to study conception and design.
© 2017 National Lipid Association