High pre-beta1 HDL concentrations and low lecithin: cholesterol acyltransferase activities are strong positive risk markers for ischemic heart disease and independent of HDL-cholesterol.
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 >or=735 mg/L; men >or=619 mg/L) or low HDL-C (n = 42; women <or=387 mg/L; men <or=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-beta(1) 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-beta(1) 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) micromol x L(-1) x h(-1); P = 0.002] and low [93.4 (8.3) vs 113.5 (4.9) micromol x L(-1) . h(-1); P = 0.03] HDL-C groups. ROC curves for pre-beta(1) 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-beta(1) HDL was observed (r(2) = 0.30; P < 0.0001) in IHD participants, which was stronger in the low HDL-C group (r(2) = 0.56; P < 0.0001).


CONCLUSIONS
IHD was associated with high pre-beta(1) 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-beta(1) HDL concentration and LCAT activity level potentially useful diagnostic markers for cardiovascular disease.
Sethi
Amar A
AA
NIH, National Heart Lung and Blood Institute, Lipoprotein Metabolism Section, Bethesda, MD, USA. amars@pacbio.com
Sampson
Maureen
M
Warnick
Russell
R
Muniz
Nehemias
N
Vaisman
Boris
B
Nordestgaard
Børge G
BG
Tybjaerg-Hansen
Anne
A
Remaley
Alan T
AT
D015415:Biomarkers / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D053442:High-Density Lipoproteins, Pre-beta / Q000097:blood*; D006801:Humans; D054709:Lecithins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood* / Q000175:diagnosis; D012307:Risk Factors; D002785:Sterol O-Acyltransferase / Q000097:blood*
D015415:Biomarkers; D008076:Cholesterol, HDL; D053442:High-Density Lipoproteins, Pre-beta; D054709:Lecithins; D002785:Sterol O-Acyltransferase