Inflammatory/Antiinflammatory Properties of High-Density Lipoprotein Distinguish Patients From Control Subjects Better Than High-Density Lipoprotein Cholesterol Levels and Are Favorably Affected by Simvastatin Treatment

• Published in: Circulation (New York, N.Y.) Vol. 108; no. 22; pp. 2751 - 2756
• Main Authors: Ansell, Benjamin J., Navab, Mohamad, Hama, Susan, Kamranpour, Naeimeh, Fonarow, Gregg, Hough, Greg, Rahmani, Shirin, Mottahedeh, Rachel, Dave, Ravi, Reddy, Srinivasa T., Fogelman, Alan M.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 02.12.2003; American Heart Association, Inc
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Blood and lymphatic vessels; C-Reactive Protein - analysis; Cardiology. Vascular system; Chemotaxis - drug effects; Cholesterol, HDL - blood; Cholesterol, HDL - immunology; Cholesterol, LDL - blood; Cholesterol, LDL - pharmacology; Coculture Techniques; Coronary Disease - blood; Coronary Disease - drug therapy; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hypolipidemic Agents - therapeutic use; Inflammation - blood; Inflammation - immunology; Lipids - blood; Lipoproteins, HDL - blood; Lipoproteins, HDL - immunology; Lipoproteins, HDL - pharmacology; Male; Medical sciences; Middle Aged; Monocytes - cytology; Monocytes - drug effects; Monocytes - immunology; Predictive Value of Tests; Simvastatin - therapeutic use; Treatment Outcome; Triglycerides - blood; Human; Treatment; Simvastatin; statins; Antiinflammatory agent; Lipids; Cardiovascular disease; Inflammation; Statin derivative; Lipoprotein; Cholesterol; lipoproteins
• ISSN: 0009-7322; 1524-4539; 1524-4539
• DOI: 10.1161/01.CIR.0000103624.14436.4B

Background— The inflammatory/antiinflammatory properties of HDL were compared with HDL cholesterol in 2 groups of patients and in age- and sex-matched control subjects. Methods and Results— Group 1 consisted of 26 patients not yet taking a statin who presented with coronary heart disease (CHD) or CHD equivalents by National Cholesterol Education Program Adult Treatment Panel III criteria studied before and 6 weeks after 40 mg/d of simvastatin. Group 2 consisted of 20 patients with documented CHD and HDL cholesterol ≥84 mg/dL. The inflammatory/antiinflammatory properties of HDL were determined by the ability of the subject’s HDL to alter LDL-induced monocyte chemotactic activity (MCA) in a human artery wall coculture. Induction of MCA by a control LDL was determined in the absence or presence of the subject’s HDL. Values in the absence of HDL were normalized to 1.0. Values >1.0 after the addition of HDL indicated proinflammatory HDL; values <1.0 indicated antiinflammatory HDL. Group 1 values before simvastatin were LDL cholesterol, 118±24 mg/dL; HDL cholesterol, 57±13 mg/dL; triglycerides, 125±64 mg/dL; and high-sensitivity C-reactive protein (hs-CRP), 1.7±1.9 mg/L; and MCA values were 1.38±0.91, compared with 0.38±0.14 for control subjects ( P =1.5×10 −5 ). After simvastatin, values were LDL cholesterol, 73±24 mg/dL; HDL cholesterol, 61±14 mg/dL; triglycerides, 99±52 mg/dL; and hs-CRP, 1.3±1.3 mg/L; and MCA values were 1.08±0.71. In group 2, values were LDL cholesterol, 108±34 mg/dL; HDL cholesterol, 95±14 mg/dL; triglycerides, 89±44 mg/dL; and hs-CRP, 0.8±0.7 mg/L; and MCA values were 1.28±0.29, compared with 0.35±0.11 for control subjects ( P =1.7×10 −14 ). Similar results were obtained with the cell-free assay. Conclusions— The inflammatory/antiinflammatory properties of HDL distinguished patients from control subjects better than HDL cholesterol and were improved with simvastatin.