Abstract 467: Lipoproteins and Cardiovacular Disease Risk

Abstract

Objectives: Elevated serum levels of low density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C), remnant lipoprotein cholesterol (RLP-C), and lipoprotein (a) or Lp(a) and low high density lipoprotein cholesterol (HDL-C) have all been associated with increased cardiovascular disease (CVD) risk. Our goal was to assess direct measurements of these lipoproteins as compared to standard risk factors (age, gender, hypertension, hypertension treatment, diabetes, smoking, total cholesterol, and HDL-C) in the Framingham Offspring Study (FOS). Methods: Stored frozen plasma samples (-80 degrees C) obtained after an overnight fast from male and female participants free of CVD at cycle 6 of FOS were used (n=3,147, mean age 58 years, with 677 (21.5%) developing CVD over 16 years. Total cholesterol, HDL-C, direct LDL-C, sdLDL-C, remnant lipoprotein cholesterol (RLP-C), Lp(a), and high sensitivity C reactive protein (hsCRP) were measured by standardized automated analysis. Large buoyant LDL-C (lbLDL-C) (direct LDL-C - sdLDL-C) and calculated LDL-C (total cholesterol-HDL-C - TG/5) were also calculated. Results: For all CVD risk on univariate analysis significant factors with p values in parentheses in order of significance were: age (8.1x10 -41 ), hypertension (3.2x10 -23 ), HDL-C (4.2x10 -16 ), sdLDL-C (4.2x10 -14 ), hypertension treatment (1.5x10 -14 ), gender (1.7x10 -10 ), diabetes (5.1x10 -9 ), direct LDL-C (8.2x10 -9 ), body mass index (9.2x10 -7 ), calculated LDL-C (6.2X10 -6 ), RLP-C (8.0 X 10 -4 ) cholesterol medication (1.8 X 10 -4 ), total cholesterol (0.00081) smoking (0.0024), hsCRP (0.005), and Lp(a) (0.024). On multivariate analysis sdLDL-C, direct LDL-C, hsCRP, and Lp(a) were still significant using the model including all standard risk factors. All four parameters significantly improved the model C statistic and net risk reclassification. Conclusions: Our data indicate that for CVD risk prediction in FOS direct LDL-C is significantly better than calculated LDL-C, that HDL-C, sdLDL-C, direct LDL-C, RLP-C, and Lp(a) are all atherogenic, and that after standard risk factors, sdLDL-C, direct LDL-C, Lp(a), and hsCRP all add significant information.