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

Circulation. 2003 Dec 2;108(22):2751-6. doi: 10.1161/01.CIR.0000103624.14436.4B. Epub 2003 Nov 24.

Abstract

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 > or =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=1.5x10(-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=1.7x10(-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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • C-Reactive Protein / analysis
  • Chemotaxis / drug effects
  • Cholesterol, HDL / blood
  • Cholesterol, HDL / immunology*
  • Cholesterol, LDL / blood
  • Cholesterol, LDL / pharmacology
  • Coculture Techniques
  • Coronary Disease / blood
  • Coronary Disease / drug therapy*
  • 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
  • Middle Aged
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / immunology
  • Predictive Value of Tests
  • Simvastatin / therapeutic use*
  • Treatment Outcome
  • Triglycerides / blood

Substances

  • Cholesterol, HDL
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypolipidemic Agents
  • Lipids
  • Lipoproteins, HDL
  • Triglycerides
  • C-Reactive Protein
  • Simvastatin