TY - JOUR
T1 - Hypertriglyceridemia and cardiovascular risk
T2 - a cautionary note about metabolic confounding
AU - Sniderman, Allan D.
AU - Couture, Patrick
AU - Martin, Seth S.
AU - DeGraaf, Jacqueline
AU - Lawler, Patrick R.
AU - Cromwell, William C.
AU - Wilkins, John T.
AU - Thanassoulis, George
N1 - Funding Information:
A.D.S., J.D., J.T.W, and P.R.L. report that they have no conflicts of interest. P.C. has received funding in the last 5 years from the Canadian Institutes for Health Research, Agriculture and Agri-Food Canada (Growing Forward program supported by the Dairy Farmers of Canada, Canola Council of Canada, Flax Council of Canada, Dow Agrosciences, Dairy Research Institute, Dairy Australia, Danone Institute, Merck, Pfizer, Atrium Innovations, and Kaneka Corporation. S.S.M. is listed as a co-inventor on a pending patent filed by Johns Hopkins University for an algorithm to estimate LDL cholesterol; has served on scientific advisory boards for Quest Diagnostics, Sanofi/Regeneron, Amgen, and Akcea Therapeutics; and has received research support from the PJ Schafer Cardiovascular Research Fund, the David and June Trone Family Foundation, the American Heart Association, the Aetna Foundation, CASCADE FH, the Maryland Innovation Initiative, Google, and Apple. W.C.C. is self-employed and is in private practice at the Lipoprotein and Metabolic Disorders Institute, PLLC, and is also an employee of LabCorp and is a consultant and lecturer for Amarin, Amgen, and Kiowa. G.T. is a consultant for Ionis Pharma; on the Advisory boards of Ionis Pharma, Amgen, and Servier Canada; a member of the Speaker’s Bureau of Amgen, Sanofi, Servier Canada, and Boerhinger Ingelheim; and has received a research grant from Ionis Pharma. Manuscript received 30 November 2017 and in revised form 14 May 2018. Published, JLR Papers in Press, May 16, 2018 DOI https://doi.org/10.1194/jlr.R082271
Publisher Copyright:
Copyright © 2018 by the American Society for Biochemistry and Molecular Biology, Inc.
PY - 2018
Y1 - 2018
N2 - Triglycerides are the conventional tool to measure VLDLs, whereas LDL cholesterol (LDL-C) is the conventional tool to measure LDLs. Multiple epidemiological studies, including a series of genetically based analyses, have demonstrated that cardiovascular risk is related to triglycerides independently of LDL-C, and this has led to a series of new therapeutic agents designed specifically to reduce plasma triglycerides. The triglyceride hypothesis posits that increased levels of triglycerides increase cardiovascular risk and decreasing plasma triglycerides decreases cardiovascular risk. In this work, we will examine the validity of the triglyceride hypothesis by detailing the biological complexities associated with hypertriglyceridemia, the genetic epidemiological evidence in favor of hypertriglyceridemia, the evidence from the fibrate randomized clinical trials relating triglycerides and clinical outcomes, and the completeness of the evidence from the initial studies of novel mutations and the therapeutic agents based on these mutations that lower triglycerides. Because of the multiple metabolic links between VLDL and LDL, we will try to demonstrate that measuring triglycerides and LDL-C alone are inadequate to document the lipoprotein profile. We will try to demonstrate that apoB must be measured, as well as triglycerides and cholesterol, to have an accurate estimate of lipoprotein status.—Sniderman, A. D., P. Couture, S. S. Martin, J. DeGraaf, P. R. Lawler, W. C. Cromwell, J. T. Wilkins, and G. Thanassoulis. Hypertriglyceridemia and cardiovascular risk: a cautionary note about metabolic confounding.
AB - Triglycerides are the conventional tool to measure VLDLs, whereas LDL cholesterol (LDL-C) is the conventional tool to measure LDLs. Multiple epidemiological studies, including a series of genetically based analyses, have demonstrated that cardiovascular risk is related to triglycerides independently of LDL-C, and this has led to a series of new therapeutic agents designed specifically to reduce plasma triglycerides. The triglyceride hypothesis posits that increased levels of triglycerides increase cardiovascular risk and decreasing plasma triglycerides decreases cardiovascular risk. In this work, we will examine the validity of the triglyceride hypothesis by detailing the biological complexities associated with hypertriglyceridemia, the genetic epidemiological evidence in favor of hypertriglyceridemia, the evidence from the fibrate randomized clinical trials relating triglycerides and clinical outcomes, and the completeness of the evidence from the initial studies of novel mutations and the therapeutic agents based on these mutations that lower triglycerides. Because of the multiple metabolic links between VLDL and LDL, we will try to demonstrate that measuring triglycerides and LDL-C alone are inadequate to document the lipoprotein profile. We will try to demonstrate that apoB must be measured, as well as triglycerides and cholesterol, to have an accurate estimate of lipoprotein status.—Sniderman, A. D., P. Couture, S. S. Martin, J. DeGraaf, P. R. Lawler, W. C. Cromwell, J. T. Wilkins, and G. Thanassoulis. Hypertriglyceridemia and cardiovascular risk: a cautionary note about metabolic confounding.
KW - Angiopoietin-like 3 protein
KW - Apolipoprotein B
KW - Apolipoprotein CIII
KW - Apolipoprotein CIII inhibitor
KW - Low density lipoprotein
KW - Triglycerides
KW - Very low density lipoprotein
UR - http://www.scopus.com/inward/record.url?scp=85049383931&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049383931&partnerID=8YFLogxK
U2 - 10.1194/jlr.R082271
DO - 10.1194/jlr.R082271
M3 - Article
C2 - 29769239
AN - SCOPUS:85049383931
SN - 0022-2275
VL - 59
SP - 1266
EP - 1275
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 7
ER -