Published Online
on December 27, 2005

A more recent version of this article appeared on January 3, 2006

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Submitted on June 5, 2005
Revised on September 16, 2005
Accepted on October 3, 2005

Increased Small Low-Density Lipoprotein Particle Number. A Prominent Feature of the Metabolic Syndrome in the Framingham Heart Study

Sekar Kathiresan MD, James D. Otvos PhD, Lisa M. Sullivan PhD, Michelle J. Keyes MA, Ernst J. Schaefer MD, Peter W.F. Wilson MD, Ralph B. D’Agostino PhD, Ramachandran S. Vasan MD, and Sander J. Robins MD^*

From the National Heart, Lung, and Blood Institute’s Framingham Heart Study (S.K., L.M.S., M.J.K., R.B.D., R.S.V., S.J.R.), Framingham, Mass; the Cardiology Division (S.K.), Massachusetts General Hospital, Harvard Medical School, Boston, Mass; the Broad Institute of Harvard and Massachusetts Institute of Technology (S.K.), Cambridge, Mass; LipoScience, Inc (J.D.O.), Raleigh, NC; the Statistics and Consulting Unit (L.M.S., M.J.K., R.B.D.), Department of Mathematics, Boston University, Boston, Mass; the Lipid Research Laboratory (E.J.S.), Tufts University School of Medicine, Boston, Mass; and the Department of Endocrinology, Diabetes, and Medical Genetics (P.W.F.W.), Medical University of South Carolina, Charleston.

^* To whom correspondence should be addressed. E-mail: sjrobins{at}bu.edu.

Background--Levels of LDL cholesterol (LDL-C) are frequently not elevated in individuals with the metabolic syndrome (MetSyn). However, the atherogenic potential of LDL may depend on the number and size of LDL particles in addition to the cholesterol content of LDL.

Methods and Results--We examined the sex-specific cross-sectional relations of small LDL particle number (determined by nuclear magnetic resonance spectroscopy) to the presence of MetSyn and its components in 2993 Framingham Heart Study participants (mean age, 51 years; 53% women) without cardiovascular disease (CVD) and the relations of small LDL particle number to CVD incidence in people with MetSyn. The MetSyn (3 of 5 traits as defined by the National Cholesterol Education Adult Treatment Panel III) was present in 27% of men and 17% of women. In both sexes, small LDL particle number increased from 0 to 5 MetSyn traits, a pattern partly accounted for by strong correlations between small LDL particle number and serum triglycerides (r=0.61, P<0.0001) and HDL-C (r=-0.55, P<0.0001). Compared with participants without the MetSyn, those with the MetSyn had a higher CVD event rate. However, among participants with the MetSyn, CVD rates were similar for groups with an elevated versus a lower number of small LDL particles (defined by the sex-specific median).

Conclusions--Small LDL particle number is elevated in the MetSyn, increases with the number of MetSyn components, and most prominently is correlated with triglycerides and HDL-C. Whereas increased small LDL particle number identified the MetSyn with high sensitivity, a higher small LDL particle number was not associated with greater CVD event rates in people with the MetSyn.

Key words: cholesterol • lipids • lipoproteins • metabolic syndrome X • risk factors

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