Discordance of low-density lipoprotein (LDL) cholesterol with alternative LDL-related measures and future coronary events
Open accessAbstract
Background—: Low-density lipoprotein cholesterol (LDL-C) is the traditional measure of risk attributable to LDL. Non–high-density lipoprotein cholesterol (NHDL-C), apolipoprotein B (apoB), and LDL particle number (LDL-P) are alternative measures of LDL-related risk. However, the clinical utility of these measures may only become apparent among individuals for whom levels are inconsistent (discordant) with LDL-C. Methods and Results—: LDL-C was measured directly, NHDL-C was calculated, apoB was measured with immunoassay, and LDL-P was measured with nuclear magnetic resonance spectroscopy among 27 533 healthy women (median follow-up 17.2 years; 1070 incident coronary events). Participants were grouped by median LDL-C (121 mg/dL) and each of NHDL-C, apoB, and LDL-P. Discordance was defined as LDL-C greater than or equal to the median and the alternative measure less than the median, or vice versa. Despite high LDL-C correlations with NHDL-C, apoB, and LDL-P ( r =0.910, 0.785, and 0.692; all P <0.0001), prevalence of LDL-C discordance as defined by median cut points was 11.6%, 18.9%, and 24.3% for NHDL-C, apoB, and LDL-P, respectively. Among women with LDL-C less than the median, coronary risk was underestimated for women with discordant (greater than or equal to the median) NHDL-C (age-adjusted hazard ratio, 2.92; 95% confidence interval, 2.33–3.67), apoB (2.48, 2.01–3.07), or LDL-P (2.32, 1.88–2.85) compared with women with concordant levels. Conversely, among women with LDL-C greater than or equal to the median, risk was overestimated for women with discordant (less than the median) NHDL-C (0.40, 0.29–0.57), apoB (0.34, 0.26–0.46), or LDL-P (0.42, 0.33–0.53). After multivariable adjustment for potentially mediating factors, including HDL cholesterol and triglycerides, coronary risk remained underestimated or overestimated by ≈20% to 50% for women with discordant levels. Conclusions—: For women with discordant LDL-related measures, coronary risk may be underestimated or overestimated when LDL-C alone is used. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00000479.
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These measures do not identify the number of apoB-containing lipoprotein particles as reliably and have been shown to not always accurately predict CV risk.
“However, it should be recognized that these measures do not identify the number of apoB-containing lipoprotein particles as reliably and have been shown to not always accurately predict CV risk.17”
From Association of Apolipoprotein B–Containing Lipoproteins and Risk of Myocardial Infarction in Individuals With and Without Atherosclerosis (2022) · cites this paper as [17]
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- Authors
- Mora, S., Buring, J. E., & Ridker, P. M.
- Affiliations
- Brigham and Women's Hospital (US)
- Venue
- Circulation
- Published
- 2014-02-04
- Volume
- 129
- Issue
- 5
- Pages
- 553-561
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC4501252
- OpenAlex
- W2123027967
- Cited by
- 255
- References
- 31
- Citations by year
- 2026: 17 · 2025: 10 · 2024: 16 · 2023: 30 · 2022: 17 · 2021: 28 · 2020: 26 · 2019: 18 · 2018: 21 · 2017: 16 · 2016: 17 · 2015: 20 · 2014: 17 · 2013: 1
- FWCI
- 18.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r01hl043851-10, HL 43851)
- National Heart, Lung, and Blood Institute (R01HL080467, R01‐HL043851, HL43851, K08HL094375, HL080467)
- National Cancer Institute (CA-47988, R01CA047988)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- LDL cholesterol, non-HDL cholesterol, apolipoprotein B, LDL particle number, coronary heart disease risk, women, LDL particle size, HDL cholesterol, triglycerides, risk prediction model
- MeSH terms
- Coronary Artery Disease, Female, Follow-Up Studies, Humans, Lipoproteins, LDL, Middle Aged, Magnetic Resonance Spectroscopy, Prospective Studies, Surveys and Questionnaires, Risk Factors, Cohort Studies
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