| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2010 American Association for Clinical Chemistry, Inc.
Lipids, Lipoproteins, and Cardiovascular Risk Factors |
High Pre-β1 HDL Concentrations and Low Lecithin: Cholesterol Acyltransferase Activities Are Strong Positive Risk Markers for Ischemic Heart Disease and Independent of HDL-Cholesterol
1 NIH, National Heart Lung and Blood Institute, Lipoprotein Metabolism Section and 2 Clinical Center, Department of Laboratory Medicine, Bethesda, MD; 3 Berkeley HeartLab, Burlingame, CA; 4 Quantimetrix, Redondo Beach, CA; 5 Herlev Hospital, 6 Copenhagen City Heart Study, and 7 Rigshospitalet, Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
aAddress correspondence to this author at: Pacific Biomarkers, 220 West Harrison St., Seattle, WA 98119. Fax 206-298-9838; e-mail amars{at}pacbio.com.
Background: We hypothesized that patients with high HDL-cholesterol (HDL-C) and ischemic heart disease (IHD) may have dysfunctional HDL or unrecognized nonconventional risk factors.
Methods: Individuals with IHD (Copenhagen University Hospital) and either high HDL-C (n = 53; women 
735 mg/L; men 619 mg/L) or low HDL-C (n = 42; women 
387 mg/L; men 341 mg/L) were compared with individuals without IHD (Copenhagen City Heart Study) matched by age, sex, and HDL-C concentrations (n = 110). All participants had concentrations within reference intervals for LDL-C (<1600 mg/L) and triglyceride (<1500 mg/L), and none were treated with lipid-lowering medications. Pre-β1 HDL and phospholipid transfer protein concentrations were measured by using commercial kits and lecithin:cholesterol acyltransferase (LCAT) activity by using a proteoliposome cholesterol esterification assay.
Results: Pre-β1 HDL concentrations were 2-fold higher in individuals with IHD vs no IHD in both the high [63 (5.7) vs 35 (2.3) mg/L; P < 0.0001] and low HDL-C [49 (5.0) vs 27 (1.5) mg/L; P = 0.001] groups. Low LCAT activity was also associated with IHD in the high [95.2 (6.7) vs 123.0 (5.3) µmol · L–1 · h–1; P = 0.002] and low [93.4 (8.3) vs 113.5 (4.9) µmol · L–1 · h–1; P = 0.03] HDL-C groups. ROC curves for pre-β1 HDL in the high–HDL-C groups yielded an area under the curve of 0.71 (95% CI: 0.61–0.81) for predicting IHD, which increased to 0.92 (0.87–0.97) when LCAT was included. Similar results were obtained for low HDL-C groups. An inverse correlation between LCAT activity and pre-β1 HDL was observed (r2 = 0.30; P < 0.0001) in IHD participants, which was stronger in the low HDL-C group (r2 = 0.56; P < 0.0001).
Conclusions: IHD was associated with high pre-β1 HDL concentrations and low LCAT levels, yielding correct classification in more than 90% of the IHD cases for which both were measured, thus making pre-β1 HDL concentration and LCAT activity level potentially useful diagnostic markers for cardiovascular disease.