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Volume 1, Issue 6, Pages 583-592 (December 2007)


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LDL particle number and risk of future cardiovascular disease in the Framingham Offspring Study—Implications for LDL management

William C. Cromwell, MDabCorresponding Author Informationemail address, James D. Otvos, PhDc, Michelle J. Keyes, PhDde, Michael J. Pencina, PhDe, Lisa Sullivan, PhDf, Ramachandran S. Vasan, MDdg, Peter W.F. Wilson, MDh, Ralph B. D’Agostino, PhDde

Received 19 June 2007; accepted 11 October 2007. published online 22 October 2007.

Background

The cholesterol content of low-density lipoprotein (LDL) particles is variable, causing frequent discrepancies between concentrations of LDL cholesterol (LDL-C) and LDL particle number (LDL-P). In managing patients at risk for cardiovascular disease (CVD) to LDL target levels, it is unclear whether LDL-C provides the optimum measure of residual risk and adequacy of LDL-lowering treatment.

Objective

To compare the ability of alternative measures of LDL to provide CVD risk discrimination at relatively low levels consistent with current therapeutic targets.

Methods

Concentrations of LDL-C and non–HDL-C were measured chemically and LDL-P and VLDL-P were measured by nuclear magnetic resonance in 3066 middle-aged white participants (53% women) without CVD in the Framingham Offspring cohort. The main outcome measure was incidence of first CVD event.

Results

At baseline, the cholesterol content per LDL particle was negatively associated with triglycerides and positively associated with LDL-C. On follow-up (median 14.8 years), 265 men and 266 women experienced a CVD event. In multivariable models adjusting for nonlipid CVD risk factors, LDL-P was related more strongly to future CVD in both genders than LDL-C or non–HDL-C. Subjects with a low level of LDL-P (<25th percentile) had a lower CVD event rate (59 events per 1000 person-years) than those with an equivalently low level of LDL-C or non–HDL-C (81 and 74 events per 1000 person-years, respectively).

Conclusions

In a large community-based sample, LDL-P was a more sensitive indicator of low CVD risk than either LDL-C or non–HDL-C, suggesting a potential clinical role for LDL-P as a goal of LDL management.

a Division of Lipoprotein Disorders, Presbyterian Center for Preventive Cardiology, 125 Baldwin Avenue, Suite 200, Charlotte, NC 28204, USA

b Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA

c LipoScience, Inc., Raleigh, NC, USA

d The Framingham Study, Boston University School of Medicine, Framingham, MA, USA

e Department of Mathematics and Statistics, Boston University, Boston, MA

f Department of Biostatistics, Boston University, Boston, MA

g Department of Preventive Medicine, Cardiology Section, Boston University, Boston, MA

h Cardiology Division, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA

Corresponding Author InformationCorresponding author.

PII: S1933-2874(07)00283-8

doi:10.1016/j.jacl.2007.10.001


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