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Baseline Very Low-Density Lipoprotein Cholesterol is Associated with the Magnitude of Triglyceride Lowering on Statins, Fenofibric Acid, or Their Combination in Patients with Mixed Dyslipidemia

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Abstract

Fibric acid derivatives like fenofibric acid (FA) decrease hepatic production of very low-density lipoprotein (VLDL)-associated triglycerides (TG). Hepatic VLDL production can be estimated from VLDL-associated cholesterol (VLDL-C). We assessed if the degree of TG reduction observed with FA, statins, or their combination is associated with baseline VLDL-C. Overall, 2,715 patients with mixed dyslipidemia in three randomized, controlled studies were assigned to one of six treatment strategies: FA, low-dose statin (LDS), FA + LDS, moderate-dose statin (MDS), FA + MDS, and high-dose statin (HDS). Patients were dichotomized into low- or high-baseline VLDL-C groups. Pooled data were used to compare the degree of TG reduction in patients with low- vs. high-baseline VLDL-C for each treatment arm, using unpaired, two-sided t test. Additionally, the association between baseline VLDL-C level and percentage TG reduction from baseline was evaluated by linear regression. Diagnostic performance of baseline VLDL-C levels in predicting 5, 10, 15, and 20 % TG reduction was assessed by receiver operating characteristics (ROC) analysis. In all treatment groups, following 12 weeks of therapy, a significantly greater percent change from baseline in TG was observed in the high-baseline VLDL-C group as compared with the low-baseline VLDL-C group. Linear regression analysis indicated that approximately 6 to 13 % of the decrease in TG could be explained by baseline VLDL-C. ROC-derived cut points for baseline VLDL-C were obtained for 5, 10, 15, and 20 % TG reduction. Baseline VLDL-C levels are associated with the degree of TG lowering using FA, statins, or their combination, thereof.

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Abbreviations

CAD:

Coronary artery disease

HDL:

High-density lipoprotein

IDL:

Intermediate-density lipoprotein

HDL-C:

High-density lipoprotein cholesterol

LDL-C:

Low-density lipoprotein cholesterol

VLDL-C:

Very low-density lipoprotein cholesterol

TG:

Triglyceride

FA:

Fenofibric acid

Apo:

Apoprotein

LPL:

Lipoprotein lipase

LDS:

Low-dose statin

MDS:

Moderate-dose statin

HDS:

High-dose statin

PPAR:

Peroxisome proliferator-activated receptor

TC:

Total cholesterol

hs-CRP:

High-sensitivity C-reactive protein

ANOVA:

Analysis of variance

r 2 :

Coefficient of determination

ROC:

Receiver-operator characteristic

SD:

Standard deviation

AUC:

Area under curve

MTP:

Microsomal transfer protein

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Acknowledgments

The authors would like to acknowledge Carolyn Setze, MS, and Maureen Kelly, MD, of AbbVie for assistance with the development and interpretation of the analyses for this manuscript.

Grant Funding

There was no specific funding for this project. The original studies were funded by AbbVie, North Chicago, IL.

Conflicts of Interest

AbbVie was involved in study design, research, analysis, data collection, interpretation of data and writing, review, and approval of this manuscript. Kamlesh Thakker and Aditya Lele are AbbVie employees and stockholders. Dr. Szilard Voros had received research funding from AbbVie as well as Merck, Inc. in the past, but not in the past 12 months. Dr. Voros has served on Scientific Advisory Boards for Abbott (now AbbVie). In addition, Dr. Voros is Founder and Chief Executive Office of Global Genomics Group, LLC and serves as Chief Academic Officer for Health Diagnostic Laboratory, Inc. Drs. Sharma, Rinehart, and Joshi have nothing to disclose.

Author information

Authors and Affiliations

  1. University of Missouri, 5100 Rockhill Rd, Kansas City, MO, 64110, USA

    Abhinav Sharma

  2. Johns Hopkins School of Medicine, Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA

    Parag H. Joshi

  3. Piedmont Heart Institute, Atlanta, GA, USA

    Sarah Rinehart

  4. AbbVie, North Chicago, IL, USA

    Kamlesh M. Thakker & Aditya Lele

  5. Stony Brook University, Stony Brook, NY, USA

    Szilard Voros

Authors
  1. Abhinav Sharma
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  2. Parag H. Joshi
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  3. Sarah Rinehart
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  4. Kamlesh M. Thakker
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  5. Aditya Lele
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  6. Szilard Voros
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Corresponding author

Correspondence to Abhinav Sharma.

Additional information

Associate Editor Angela Taylor oversaw the review of this article

Abhinav Sharma (work performed at Piedmont Heart Institute Atlanta, GA)

Parag H. Joshi (work performed at Piedmont Heart Institute Atlanta, GA)

Szilard Voros (work performed at Piedmont Heart Institute Atlanta, GA)

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Sharma, A., Joshi, P.H., Rinehart, S. et al. Baseline Very Low-Density Lipoprotein Cholesterol is Associated with the Magnitude of Triglyceride Lowering on Statins, Fenofibric Acid, or Their Combination in Patients with Mixed Dyslipidemia. J. of Cardiovasc. Trans. Res. 7, 465–474 (2014). https://doi.org/10.1007/s12265-014-9559-3

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  • DOI: https://doi.org/10.1007/s12265-014-9559-3

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