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on September 23, 2002

Circulation. 2002
Published online before print September 23, 2002, doi: 10.1161/01.CIR.0000033222.75187.B9
A more recent version of this article appeared on October 8, 2002
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*Substance via MeSH

Submitted on May 20, 2002
Revised on July 18, 2002
Accepted on July 19, 2002

Low-Density Lipoprotein Particle Concentration and Size as Determined by Nuclear Magnetic Resonance Spectroscopy as Predictors of Cardiovascular Disease in Women

Gavin J. Blake MB, MSc, MRCPI, James D. Otvos PhD, Nader Rifai PhD, and Paul M Ridker MD, MPH*

From the Center for Cardiovascular Disease Prevention (G.J.B., N.R., P.M.R.), and the Divisions of Preventive Medicine (G.J.B., P.M.R.) and Cardiovascular Disease (G.J.B., P.M.R.), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; and LipoScience, Inc (J.D.O.), Raleigh, NC.

* To whom correspondence should be addressed. E-mail: pridker{at}partners.org.

Background—Nuclear magnetic resonance (NMR) offers an alternative, spectroscopic means of quantifying LDL and of measuring LDL particle size.

Methods and Results—We conducted a prospective nested case-control study among healthy middle-aged women to assess LDL particle size (NMR) and concentration (NMR) as risk factors for future myocardial infarction, stroke, or death of coronary heart disease. Median baseline levels of LDL particle concentration (NMR) were higher (1597 vs 1404 nmol/L; P=0.0001) and LDL particle size (NMR) was lower (21.5 vs 21.8 nm; P=0.046) among women who subsequently had cardiovascular events (n=130) than among those who did not (n=130). Of these 2 factors, LDL particle concentration (NMR) was the stronger predictor (relative risk for the highest compared with the lowest quartile=4.17, 95% CI 1.96-8.87). This compared with a relative risk of 3.11 (95% CI 1.55-6.26) for the ratio of total cholesterol to HDL cholesterol and a relative risk of 5.91 (95% CI 2.65-13.15) for C-reactive protein. The areas under the receiver operating characteristic curves for LDL particle concentration (NMR), total cholesterol to HDL cholesterol ratio, and C-reactive protein were 0.64, 0.64, and 0.66, respectively. LDL particle concentration (NMR) correlated with several traditionally assessed lipid and nonlipid risk factors, and thus adjustment for these tended to attenuate the magnitude of association between LDL particle concentration (NMR) and risk.

Conclusions—In this cohort, LDL particle concentration measured by NMR spectroscopy was a predictor of future cardiovascular risk. However, the magnitude of predictive value of LDL particle concentration (NMR) was not substantively different from that of the total cholesterol to HDL cholesterol ratio and was less than that of C-reactive protein.


Key words: lipoproteins • atherosclerosis • risk factors




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