Comparison of LDL cholesterol concentrations by Friedewald calculation and direct measurement in relation to cardiovascular events in 27,331 women
Open accessAbstract
Background: National Cholesterol Education Program (NCEP) guidelines recommend development of direct assays for LDL cholesterol (LDL-C) measurement, but it is unclear how these assays compare with Friedewald calculation in predicting cardiovascular disease (CVD). Methods: In a study of 27 331 healthy women with triglycerides ≤4.52 mmol/L (≤400 mg/dL), baseline fasting Friedewald LDL-C was compared with fasting and nonfasting direct homogenous measurement for incident CVD during an 11-year period. Results: Fasting LDL-C measurements obtained by the 2 methods were highly correlated (r = 0.976, P < 0.001). Compared with fasting Friedewald LDL-C, mean fasting direct LDL-C was 0.15 mmol/L (5.6 mg/dL) lower and nonfasting direct LDL-C 0.30 mmol/L (11.5 mg/dL) lower, both P < 0.0001. The adjusted hazard ratio per 1-SD increment was 1.23 [95% CI 1.15–1.32; 1-SD 0.88 mmol/L (34.1 mg/dL)] for fasting direct LDL-C and 1.22 [95% CI 1.14–1.30; 1-SD 0.90 mmol/L (34.9 mg/dL)] for fasting Friedewald. Nonfasting LDL-C was not associated with CVD by either method. Fasting LDL-C measurements fell into the same NCEP risk category with either method for 79.3% of participants, whereas they differed by 1 NCEP category for 20.7% of participants, with most classified into a lower-risk category by direct LDL-C. Conclusions: The association of LDL-C with CVD by the 2 methods was nearly identical in fasting samples. However, the lower direct LDL-C concentrations may misclassify many individuals into a lower NCEP category. Moreover, the lack of association of nonfasting direct LDL-C with CVD raises questions regarding the clinical utility of a direct assay for LDL-C in nonfasting blood samples.
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Even in normotriglyceridemic samples and in samples with moderately elevated TG concentrations 2.0-4.5 mmol/L, dLDLC may not always agree with Friedewald cLDLC and translate to discrepant risk classifications as observed in fasting as well as nonfasting individuals.
“Even in normotriglyceridemic samples and in samples with moderately elevated TG concentrations 2.0-4.5 mmol/L, dLDLC may not always agree with Friedewald cLDLC and translate to discrepant risk classifications as observed in fasting as well as nonfasting individuals [51].”
From Quantifying atherogenic lipoproteins for lipid-lowering strategies: Consensus-based recommendations from EAS and EFLM (2020) · cites this paper as [51]
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Experimental — accuracy not yet measuredThere can be significant discrepancies between directly measured and calculated LDL-C levels within the same sample, especially at lower LDL-C levels.
“Nonetheless, the committee acknowledges that there can be significant discrepancies in levels of directly measured versus calculated LDL-C within the same sample, especially at lower LDL-C levels (19,20).”
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- Authors
- Mora, S., Rifai, N., Buring, J. E., & Ridker, P. M.
- Affiliations
- Brigham and Women's Hospital (US)
- Boston Children's Hospital (US)
- Harvard University (US)
- Corresponding author
- Mora, Samia
- Venue
- Clinical Chemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-05-01
- Volume
- 55
- Issue
- 5
- Pages
- 888-894
- ISSN
- 0009-9147 (ISSN-L)
- 1530-8561
- PMC
- PMC2692888
- OpenAlex
- W2002172809
- Cited by
- 176
- References
- 18
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 8 · 2023: 13 · 2022: 10 · 2021: 10 · 2020: 13 · 2019: 14 · 2018: 13 · 2017: 13 · 2016: 11 · 2015: 9 · 2014: 13 · 2013: 8 · 2012: 7
- FWCI
- 12.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-43851, CA-47988, K08 HL094375)
- National Cancer Institute
- Donald W. Reynolds Foundation
- Doris Duke Charitable Foundation
- AstraZeneca
- Novartis
- Merck
- American Heart Association (0670007N)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Keywords
- LDL cholesterol, Friedewald formula, cardiovascular risk, women, triglycerides, method comparison, cardiovascular events
- MeSH terms
- Aspirin, Cardiovascular Diseases, Fasting, Female, Humans, Hypercholesterolemia, Cholesterol, LDL, Middle Aged, Predictive Value of Tests, Prospective Studies, Triglycerides, Vitamin E, Cohort Studies, Randomized Controlled Trials as Topic, Statistics, Nonparametric
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