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Comparative Study
. 2014 Jan;34(1):196-201.
doi: 10.1161/ATVBAHA.113.302401. Epub 2013 Nov 14.

New automated assay of small dense low-density lipoprotein cholesterol identifies risk of coronary heart disease: the Multi-ethnic Study of Atherosclerosis

Michael Y Tsai  1 , Brian T Steffen, Weihua Guan, Robyn L McClelland, Russell Warnick, Joseph McConnell, Daniel M Hoefner, Alan T Remaley
Affiliations
Comparative Study

New automated assay of small dense low-density lipoprotein cholesterol identifies risk of coronary heart disease: the Multi-ethnic Study of Atherosclerosis

Michael Y Tsai et al. Arterioscler Thromb Vasc Biol. 2014 Jan.

Abstract

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.

Approach and 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.

Keywords: coronary disease.

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Conflict of interest statement

Disclosures

M.Y. Tsai received consulting fees from the manufacturer of the small dense low-density lipoprotein cholesterol (sdLDL-C) assay (Denka Seiken). R. Warnick, D.M. Hoefner, and J. McConnell are associated with Health Diagnostic Laboratory, Inc, the clinical laboratory responsible for obtaining sdLDL-C data in the present study. J. McConnell serves as the chief medical officer, R. Warnick serves as the chief scientific officer, and D.M. Hoefner serves as the director of Technology and Development. The other authors report no conflicts.

Figures

Figure
Figure
Distributions of (A) small low-density lipoprotein (LDL) particle concentrations derived from nuclear magnetic resonance (NMR) and (B) small dense low-density lipoprotein cholesterol content (sdLDL-C) among Multi-Ethnic Study of Atherosclerosis participants (n=4387).
See this image and copyright information in PMC

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