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Is the Size of Low-Density Lipoprotein Particles Related to the Risk of Coronary Heart Disease?—Reply

Hannia Campos, PhD; Frank M. Sacks, MD
JAMA. 2002;287(6):712-713. doi:10.1001/jama.287.6.711.
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In Reply: In response to Dr Krauss, we wish to dispel any inference from our study that small LDL is somehow benign. We judge from multiple lines of evidence that all LDL particles are atherogenic irrespective of their size. However, on a relative scale, our study shows that large LDL is more closely linked to CHD than is medium or small LDL. We found a strong linear relationship between LDL size and coronary events. We also reviewed the epidemiological literature on LDL size, and concluded that the relationship between small LDL and CHD found in some studies is probably due to its correlation with other lipoprotein risk factors. This is because small LDL has not remained a significant predictor of coronary disease after adjustment for total cholesterol and triglycerides,1 or the total to high-density lipoprotein (HDL) cholesterol ratio,2 which were significant predictors despite the inclusion of LDL size in the model. Even in the often-cited Quebec Cardiovascular Study3 also noted by Krauss, small LDL size did not contribute significantly to the risk of CHD either when analyzed as a continuous variable, or in tertiles. In fact, as stated by the authors, "apoB came out as the best and only significant predictor of [ischemic heart disease] risk in multivariate stepwise logistic analysis (P = .002)."

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