New Automated Assay of Small Dense Low-Density Lipoprotein Cholesterol Identifies Risk of Coronary Heart Disease The Multi-Ethnic Study of Atherosclerosis

被引:145
作者
Tsai, Michael Y. [1 ]
Steffen, Brian T. [1 ]
Guan, Weihua [2 ]
McClelland, Robyn L. [3 ]
Warnick, Russell [4 ]
McConnell, Joseph [4 ]
Hoefner, Daniel M. [4 ]
Remaley, Alan T. [5 ]
机构
[1] Univ Minnesota, Sch Publ Hlth, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA
[2] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA
[3] Univ Washington, Dept Biostat, Seattle, WA 98195 USA
[4] Hlth Diagnost Lab Inc, Richmond, VA USA
[5] NHLBI, NIH, Mol Dis Branch, Bethesda, MD 20892 USA
关键词
coronary disease; NUCLEAR-MAGNETIC-RESONANCE; INCIDENT CARDIOVASCULAR-DISEASE; ARTERY-DISEASE; PARTICLE-SIZE; CAROTID ATHEROSCLEROSIS; LDL CHOLESTEROL; WOMEN; SPECTROSCOPY; SUBCLASSES; INTERVENTION;
D O I
10.1161/ATVBAHA.113.302401
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:196 / +
页数:12
相关论文
共 27 条
[1]   Small Dense LDL Cholesterol and Coronary Heart Disease: Results from the Framingham Offspring Study [J].
Ai, Masumi ;
Otokozawa, Seiko ;
Asztalos, Bela F. ;
Ito, Yasuki ;
Nakajima, Katsuyuki ;
White, Charles C. ;
Cupples, L. Adrienne ;
Wilson, Peter W. ;
Schaefer, Ernst J. .
CLINICAL CHEMISTRY, 2010, 56 (06) :967-976
[2]   Small Dense Low-Density Lipoproteins Cholesterol can Predict Incident Cardiovascular Disease in an Urban Japanese Cohort: The Suita Study [J].
Arai, Hidenori ;
Kokubo, Yoshihiro ;
Watanabe, Makoto ;
Sawamura, Tatsuya ;
Ito, Yasuki ;
Minagawa, Asako ;
Okamura, Tomonori ;
Miyamato, Yoshihiro .
JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS, 2013, 20 (02) :195-203
[3]   Multi-ethnic study of atherosclerosis: Objectives and design [J].
Bild, DE ;
Bluemke, DA ;
Burke, GL ;
Detrano, R ;
Roux, AVD ;
Folsom, AR ;
Greenland, P ;
Jacobs, DR ;
Kronmal, R ;
Liu, K ;
Nelson, JC ;
O'Leary, D ;
Saad, MF ;
Shea, S ;
Szklo, M ;
Tracy, RP .
AMERICAN JOURNAL OF EPIDEMIOLOGY, 2002, 156 (09) :871-881
[4]   Low-density lipoprotein particle concentration and size as determined by nuclear magnetic resonance spectroscopy as predictors of cardiovascular disease in women [J].
Blake, GJ ;
Otvos, JD ;
Rifai, N ;
Ridker, PM .
CIRCULATION, 2002, 106 (15) :1930-1937
[5]   SUSCEPTIBILITY OF SMALL, DENSE, LOW-DENSITY LIPOPROTEINS TO OXIDATIVE MODIFICATION IN SUBJECTS WITH THE ATHEROGENIC LIPOPROTEIN PHENOTYPE, PATTERN-B [J].
CHAIT, A ;
BRAZG, RL ;
TRIBBLE, DL ;
KRAUSS, RM .
AMERICAN JOURNAL OF MEDICINE, 1993, 94 (04) :350-356
[6]   Value of low-density lipoprotein particle number and size as predictors of coronary artery disease in apparently healthy men and women - The EPIC-Norfolk Prospective Population study [J].
El Harchaoui, Karim ;
van der Steeg, Wim A. ;
Stroes, Erik S. G. ;
Kuivenhoven, Jan Albert ;
Otvos, James D. ;
Wareham, Nicholas J. ;
Hutten, Barbara A. ;
Kastelein, John J. P. ;
Khaw, Kay-Tee ;
Boekholdt, S. Matthijs .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2007, 49 (05) :547-553
[7]   Nuclear magnetic resonance lipoprotein abnormalities in prediabetic subjects in the insulin resistance atherosclerosis study [J].
Festa, A ;
Williams, K ;
Hanley, AJG ;
Otvos, JD ;
Goff, DC ;
Wagenknecht, LE ;
Haffner, SM .
CIRCULATION, 2005, 111 (25) :3465-3472
[8]   Relation of lipoprotein subclasses as measured by proton nuclear magnetic resonance spectroscopy to coronary artery disease [J].
Freedman, DS ;
Otvos, JD ;
Jeyarajah, EJ ;
Barboriak, JJ ;
Anderson, AJ ;
Walker, JA .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1998, 18 (07) :1046-1053
[9]  
Galeano NF, 1998, J LIPID RES, V39, P1263
[10]   Clinical significance of small dense low-density lipoprotein cholesterol levels determined by the simple precipitation method [J].
Hirano, T ;
Ito, Y ;
Koba, S ;
Toyoda, M ;
Ikejiri, A ;
Saegusa, H ;
Yamazaki, J ;
Yoshino, G .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2004, 24 (03) :558-563