Letter by Jones et al regarding article, "Elevated remnant cholesterol causes both low-grade inflammation and ischemic heart disease, whereas elevated low-density lipoprotein cholesterol causes ischemic heart disease without inflammation".

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HomeCirculationVol. 129, No. 24Letter by Jones et al Regarding Article, “Elevated Remnant Cholesterol Causes Both Low-Grade Inflammation and Ischemic Heart Disease, Whereas Elevated Low-Density Lipoprotein Cholesterol Causes Ischemic Heart Disease Without Inflammation” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Jones et al Regarding Article, “Elevated Remnant Cholesterol Causes Both Low-Grade Inflammation and Ischemic Heart Disease, Whereas Elevated Low-Density Lipoprotein Cholesterol Causes Ischemic Heart Disease Without Inflammation” Steven R. Jones, MD and Seth S. Martin, MD Eliot A. Brinton, MD Steven R. JonesSteven R. Jones Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD Search for more papers by this author and Seth S. MartinSeth S. Martin Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD Search for more papers by this author Eliot A. BrintonEliot A. Brinton Utah Foundation for Biomedical Research and Utah Lipid Center, Salt Lake City, UT, For the Very Large Database of Lipids (VLDL) Investigators Search for more papers by this author Originally published17 Jun 2014https://doi.org/10.1161/CIRCULATIONAHA.113.005954Circulation. 2014;129:e655To the Editor:Two recent studies published by Varbo et al1,2 report causal associations of remnant lipoprotein cholesterol (RLP-C) with cardiovascular outcomes. The most recent report shows the effects of low-density lipoprotein (LDL) cholesterol (LDL-C) acting directly to promote ischemic heart disease and suggests a causal relationship of RLP-C with low-grade systemic inflammation. We applaud the authors for these contributions supporting the importance and causal role of triglyceride (TG)-rich lipoproteins in atherogenesis and subsequent atherothrombotic risk.However, we believe that it is important to clarify that the measure of RLP-C used in these studies does not conform to the generally accepted definition, which is the cholesterol carried in dense subfractions of very-low-density lipoprotein (VLDL) and intermediate-density lipoprotein. These subfractions include incompletely metabolized lipoprotein moieties intermediate between larger hepatically secreted VLDL and mature, more delipidated LDL. These are the principal lipoproteins that are in excess in Fredrickson-Levy type III dyslipidemia.3In these articles,1,2 RLP-C was generally defined as the difference between non–high-density lipoprotein cholesterol (HDL-C) and LDL-C as estimated by the Friedewald relationship,4 unless TG was elevated, in which case direct measures of LDL-C were used in lieu of the Friedewald estimate. The Friedewald estimate of LDL-C results from an estimate of VLDL cholesterol (VLDL-C) as TG/5 subtracted from non–HDL-C. Thus, the definition of RLP-C used as the basis of these studies is as follows:Download figureBecause the Friedewald estimate of VLDL-C is simply TG/5, the associations shown in these studies are primarily with TG or VLDL-C in those with elevated TG levels, precluding use of the Friedewald LDL-C, not the formal definition of RLP-C. Moreover, the common Friedewald definition of LDL-C as commonly used in clinical practice is in fact the sum of cholesterol carried in 3 discrete lipoprotein classes: biochemically defined LDL, lipoprotein(a), and intermediate-density lipoprotein; intermediate-density lipoprotein is more correctly considered as a component of RLP-C.We submit that the important causal relationships in these articles would be more accurately attributed to TG than RLP-C, a very important result in any case.Steven R. Jones, MDSeth S. Martin, MDJohns Hopkins Ciccarone Center for thePrevention of Heart DiseaseBaltimore, MDEliot A. Brinton, MDUtah Foundation for Biomedical Research and Utah Lipid CenterSalt Lake City, UTFor the Very Large Database of Lipids (VLDL) InvestigatorsDisclosuresNone.