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STATE-OF-THE-ART PAPER

Beyond Low-Density Lipoprotein Cholesterol

Defining the Role of Low-Density Lipoprotein Heterogeneity in Coronary Artery Disease

James O. Mudd, MD^_*, Barry A. Borlaug, MD^_*, Peter V. Johnston, MD^_*, Brian G. Kral, MD, MPH^_*, Rosanne Rouf, MD^_*, Roger S. Blumenthal, MD^_* and Peter O. Kwiterovich, Jr, MD^,_*

^_* Johns Hopkins Ciccarone Preventive Cardiology Center, Baltimore Maryland
Johns Hopkins University Lipid Clinic, Baltimore, Maryland.

Manuscript received April 30, 2007; revised manuscript received July 16, 2007, accepted July 17, 2007.

^_* Reprint requests and correspondence: Dr. Peter O. Kwiterovich, Jr., University Lipid Clinic, Suite 310, 550 North Broadway Building, Baltimore, Maryland 21205. (Email: pkwitero{at}jhmi.edu).

Recent clinical trials in patients with coronary artery disease (CAD) provide evidence that low-density lipoprotein cholesterol (LDL-C) levels should be lowered even further to prevent recurrent CAD. However, despite more aggressive interventions for lowering LDL-C levels, the majority of CAD events go undeterred, perhaps related to the fact that intervention was not started earlier in life or that LDL-C levels represent an incomplete picture of atherogenic potential. Nevertheless, LDL-C remains the contemporary standard as the primary goal for aggressive LDL reduction. If triglycerides are >200 mg/dl, the measurement of non–high-density lipoprotein cholesterol (HDL-C) is recommended. Measurement of apolipoprotein (apo)B has been shown in nearly all studies to outperform LDL-C and non–HDL-C as a predictor of CAD events and as an index of residual CAD risk. This is because apoB reflects the total number of atherogenic apoB-containing lipoproteins and is a superior predictor of the number of low-density lipoprotein particles (LDL-P). Estimates of LDL-P and size can also be made by nuclear magnetic resonance spectroscopy, density gradient ultracentrifugation, and gradient gel electrophoresis. Although a number of studies show that such estimates predict CAD, LDL-P, and size often accompany low HDL-C and high triglyceride levels, and therefore such additional lipoprotein testing has not been recommended for routine screening and follow-up. Because apoB is a superior predictor of LDL-P, we recommend that apoB and the apoB/apoA-I ratio be determined after measurement of LDL-C, non–HDL-C, and the ratio of total cholesterol/HDL-C to better predict CAD and assess efficacy of treatment.

Abbreviations and Acronyms   apo = apolipoprotein   CAD = coronary artery disease   CE = cholesteryl esters   DGU = density-gradient ultracentrifugation   GGE = gradient gel electrophoresis   HDL-C = high-density lipoprotein cholesterol   LDL-C = low-density lipoprotein cholesterol   LDL-P = total number of low-density lipoprotein particles   Lp(a) = lipoprotein (a)   NMR = nuclear magnetic resonance   TC = total cholesterol   TG = triglycerides