Introduction Directory UMM :Data Elmu:jurnal:A:Atherosclerosis:Vol154.Issue1.Jan2001:

Atherosclerosis 154 2001 229 – 236 Remnant-like particle RLP cholesterol is an independent cardiovascular disease risk factor in women: results from the Framingham Heart Study Judith R. McNamara a,b,c, , Paulesh K. Shah b , Katsuyuki Nakajima d , L. Adrienne Cupples e , Peter W.F. Wilson f , Jose M. Ordovas c , Ernst J. Schaefer b,c a Lipid Research Laboratory, New England Medical Center, 750 Washington Street, Box 216 , Boston, MA 02111 , USA b Lipid Research Laboratory, Di6ision of Endocrinology, Diabetes, Metabolism, and Molecular Medicine, New England Medical Center, Boston, MA, USA c Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts Uni6ersity, Boston, MA, USA d Otsuka America Pharmaceutical Incorporated, Rock6ille, MD, USA e Department of Epidemiology and Biostatistics, Boston Uni6ersity School of Public Health, Boston, MA, USA f National Heart, Lung, and Blood Institute ’ s Framingham Heart Study, National Institutes of Health, Framingham, MA, USA Received 9 December 1999; received in revised form 16 March 2000; accepted 23 March 2000 Abstract Remnants of triglyceride-rich lipoproteins TRL of both intestinal and liver origin are considered to be atherogenic, but separation of remnant lipoproteins from other TRL is difficult. An assay has been developed that allows immunoseparation of remnant-like particles RLP and measurement of cholesterol RLP-C and triglyceride RLP-TG. We measured RLP-C and RLP-TG in fast plasma samples obtained from 1567 women participating in cycle 4 of the Framingham heart study FHS. When values from 83 women with cardiovascular disease CVD were compared with the values from 1484 women without disease, concentrations in women with CVD were found to be significantly higher for both RLP-C 0.215 9 0.102 vs. 0.186 9 0.162 mmoll; + 15.6; P B 0.0001 and RLP-TG 0.319 9 0.352 vs. 0.251 9 0.716 mmoll; + 27.0; P B 0.0002. Logistic regression analysis revealed that RLP-C was significantly associated with prevalent CVD in women P B 0.002 after adjustment with other major risk factors. In conclusion, we have documented that RLP-C is an independent risk factor for CVD in women, and provides significantly more information than do triglycerides. © 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords : Lipoproteins; Very low density lipoproteins; Chylomicrons; Triglycerides; Apolipoprotein B; Cardiovascular disease www.elsevier.comlocateatherosclerosis

1. Introduction

Elevated serum triglyceride concentrations are fre- quently observed in patients with cardiovascular disease CVD, and are significantly associated with CVD in most univariate analyses. Associations frequently do not remain significant, however, after adjustment with other CVD risk factors [1,2]. Triglyceride concentration repre- sents a measure of triglyceride-rich lipoproteins TRL, but it does not distinguish among the various subspecies of TRL, which may have varying degrees of atherogenic- ity. Partially hydrolyzed lipoprotein remnants of both intestinal chylomicron and hepatic very low density lipoproteins VLDL origin have been implicated as the subspecies that may be particularly important in poten- tiating CVD risk [3 – 9]. Studies have shown that these particles can remain in circulation for extended periods of time postprandially, even in individuals with normal fasting triglyceride concentrations [10 – 14]. Routine isolation and measurement of lipoprotein remnants has not been feasible, because of the difficulty in distinguishing among particles with similar apolipo- protein composition and overlapping size ranges. Al- though direct methods for isolation and measurement of cholesterol in low density lipoproteins LDL, high density lipoproteins HDL, and even lipoproteina Corresponding author. Tel.: + 1-617-5563104; fax: + 1-617- 5563103. E-mail address : mcnamara –lihnrc.tufts.edu J.R. McNamara. 0021-915001 - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S0021-91500000484-6 [Lpa] are available [15 – 20], assays for remnant lipo- protein isolation and measurement have not previously been available. An assay that separates remnant-like particles RLP has recently been developed, however [21,22], utilizing immunoseparation to isolate partially hydrolyzed, apolipoprotein apo E-enriched, RLP from other TRL. The relationship between CVD and triglycerides is much stronger in women than in men in most of the studies [23,24], and so in the current study we have tried to assess the atherogenic potential of RLP in women by isolation and measurement of the cholesterol RLP-C and triglyceride RLP-TG concentrations in these parti- cles in plasma obtained from the female offspring partic- ipants of the Framingham heart study FHS, allowing comparisons between individuals who have been previ- ously diagnosed with CVD, and those with no evidence of disease.

2. Methodology