New automated assay of small dense low-density lipoprotein cholesterol identifies risk of coronary heart disease: the Multi-ethnic Study of Atherosclerosis.
OBJECTIVE
Coronary heart disease (CHD) is the leading cause of death in the United States, yet assessing risk of its development remains challenging. The present study evaluates a new automated assay of small dense low-density lipoprotein cholesterol content (sdLDL-C) and whether sdLDL-C is a risk factor for CHD compared with LDL-C or small LDL particle concentrations derived from nuclear magnetic resonance spectroscopy.


RESULTS
sdLDL-C was measured using a new automated enzymatic method, and small LDL concentrations were obtained by nuclear magnetic resonance in 4387 Multi-Ethnic Study of Atherosclerosis participants. Cox regression analysis estimated hazard ratios for developing CHD for 8.5 years after adjustments for age, race, sex, systolic blood pressure, hypertension medication use, high-density lipoprotein cholesterol, and triglycerides. Elevated sdLDL-C was a risk factor for CHD in normoglycemic individuals. Those in the top sdLDL-C quartile showed higher risk of incident CHD (hazard ratio, 2.41; P=0.0037) compared with those in the bottom quartile and indicated greater CHD risk than the corresponding quartile of LDL-C (hazard ratio, 1.75; P=0.019). The association of sdLDL-C with CHD risk remained significant when LDL-C (<2.57 mmol/L) was included in a multivariate model (hazard ratio, 2.37; P=0.012). Nuclear magnetic resonance-derived small LDL concentrations did not convey a significant risk of CHD. Those with impaired fasting glucose or diabetes mellitus showed higher sdLDL-C and small LDL concentrations but neither was associated with higher CHD risk in these individuals.


CONCLUSIONS
This new automated method for sdLDL-C identifies risk for CHD that would remain undetected using standard lipid measures, but only in normoglycemic, nondiabetic individuals.
From the Department of Laboratory Medicine and Pathology (M.Y.T., B.T.S.) and Division of Biostatistics (W.G.), University of Minnesota School of Public Health, Minneapolis, MN; Department of Biostatistics, University of Washington, Seattle, WA (R.L.M.); Health Diagnostic Laboratory, Inc, Richmond, VA (R.W., J.M., D.M.H.); and National Institutes of Health Molecular Disease Branch, National Heart, Lung, and Blood Institute, Bethesda, MD (A.T.R.).
Michael Y
MY
Tsai
Brian T
BT
Steffen
Weihua
W
Guan
Robyn L
RL
McClelland
Russell
R
Warnick
Joseph
J
McConnell
Daniel M
DM
Hoefner
Alan T
AT
Remaley
D000368:Aged; D057205:Automation, Laboratory; D015415:Biomarkers / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood* / Q000175:diagnosis / Q000208:ethnology; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017711:Nonlinear Dynamics; D010316:Particle Size; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D014481:United States / Q000453:epidemiology
D015415:Biomarkers; D008078:Cholesterol, LDL; D014280:Triglycerides
coronary disease