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J Am Coll Cardiol. 2013 Nov 19;62(21):1960-1965. doi: 10.1016/j.jacc.2013.07.045. Epub 2013 Aug 21.

Non-high-density lipoprotein cholesterol, guideline targets, and population percentiles for secondary prevention in 1.3 million adults: the VLDL-2 study (very large database of lipids).

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Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio; Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland. Electronic address:
Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland.
Department of Preventive Cardiology, CGH Medical Center, Sterling, Illinois; University of Illinois College of Medicine, Peoria, Illinois.
Atherotech Diagnostics Lab, Birmingham, Alabama.



This study sought to examine patient-level discordance between population percentiles of non-high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C).


Non-HDL-C is an alternative to LDL-C for risk stratification and lipid-lowering therapy. The justification for the present guideline-based non-HDL-C cutpoints of 30 mg/dl higher than the LDL-C cutpoints remains largely untested.


We assigned population percentiles to non-HDL-C and Friedewald-estimated LDL-C values of 1,310,440 U.S. adults with triglyceride levels <400 mg/dl who underwent lipid testing by vertical spin density gradient ultracentrifugation (Atherotech, Birmingham, Alabama) from 2009 to 2011.


LDL-C cutpoints of 70, 100, 130, 160, and 190 mg/dl were in the same population percentiles as non-HDL-C values of 93, 125, 157, 190, and 223 mg/dl, respectively. Non-HDL-C values reclassified a significant proportion of patients within or to a higher treatment category compared with Friedewald LDL-C values, especially at LDL-C levels in the treatment range of high-risk patients and at triglyceride levels ≥150 mg/dl. Of patients with LDL-C levels <70 mg/dl, 15% had a non-HDL-C level ≥ 100 mg/dl (guideline-based cutpoint) and 25% had a non-HDL-C level ≥ 93 mg/dl (percentile-based cutpoint); if triglyceride levels were 150 to 199 mg/dl concurrently, these values were 22% and 50%, respectively.


There is significant patient-level discordance between non-HDL-C and LDL-C percentiles at lower LDL-C and higher triglyceride levels, which has implications for the treatment of high-risk patients. Current non-HDL-C cutpoints for high-risk patients may need to be lowered to match percentiles of LDL-C cutpoints. Relatively small absolute reductions in non-HDL-C cutpoints result in substantial reclassification of patients to higher treatment categories with potential implications for risk assessment and treatment.



CVD; HDL-C; LDL cholesterol; LDL-C; VAP; VLDL; cardiovascular disease; discordance; high-density lipoprotein cholesterol; lipids; low-density lipoprotein cholesterol; non–HDL cholesterol; percentiles; secondary prevention; vertical auto profile; very-low-density lipoprotein cholesterol

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