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Atherogenic Lipoprotein Determinants of Cardiovascular Disease and Residual Risk Among Individuals With Low Low-Density Lipoprotein Cholesterol.

Publication ,  Journal Article
Lawler, PR; Akinkuolie, AO; Chu, AY; Shah, SH; Kraus, WE; Craig, D; Padmanabhan, L; Glynn, RJ; Ridker, PM; Chasman, DI; Mora, S
Published in: J Am Heart Assoc
July 21, 2017

BACKGROUND: Levels of LDL (low-density lipoprotein) cholesterol in the population are declining, and increasing attention is being focused on residual lipid-related pathways of atherosclerotic cardiovascular disease risk beyond LDL cholesterol. Among individuals with low (<130 mg/dL) LDL cholesterol, we undertook detailed profiling of circulating atherogenic lipoproteins in relation to incident cardiovascular disease in 2 populations. METHODS AND RESULTS: We performed proton nuclear magnetic resonance spectroscopy to quantify concentrations of LDL and VLDL (very low-density lipoprotein) particle subclasses in 11 984 JUPITER trial participants (NCT00239681). Adjusted Cox models examined cardiovascular disease risk associated with lipoprotein measures according to treatment allocation. Risk (adjusted hazard ratio [95%CI] per SD increment) among placebo-allocated participants was associated with total LDL particles (1.19 [1.02, 1.38]) and total VLDL particles (1.21 [1.04, 1.41]), as well as apolipoprotein B, non-high-density lipoprotein cholesterol, and triglycerides, but not LDL-c. Rosuvastatin reduced LDL measures but had variable effects on triglyceride and VLDL measures. On-statin levels of the smallest VLDL particle subclass were associated with a 68% per-SD (adjusted hazard ratio 1.68 [1.28, 2.22]) increase in residual risk-this risk was related to VLDL cholesterol and not triglyceride or larger VLDL particles. There was evidence that residual risk prediction during statin therapy could be significantly improved through the inclusion of key VLDL measures (Harrell C-index 0.780 versus 0.712; P<0.0001). In an independent, prospective cohort of 4721 individuals referred for cardiac catheterization (CATHGEN), similar patterns of lipoprotein-related risk were observed. CONCLUSIONS: Atherogenic lipoprotein particle concentrations were associated with cardiovascular disease risk when LDL cholesterol was low. VLDL lipoproteins, particularly the smallest remnant subclass, may represent unused targets for risk prediction and potential therapeutic intervention for reducing residual risk. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.

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Published In

J Am Heart Assoc

DOI

EISSN

2047-9980

Publication Date

July 21, 2017

Volume

6

Issue

7

Location

England

Related Subject Headings

  • Time Factors
  • Rosuvastatin Calcium
  • Risk Factors
  • Risk Assessment
  • Proton Magnetic Resonance Spectroscopy
  • Proportional Hazards Models
  • Prognosis
  • Primary Prevention
  • Middle Aged
  • Male
 

Citation

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Lawler, P. R., Akinkuolie, A. O., Chu, A. Y., Shah, S. H., Kraus, W. E., Craig, D., … Mora, S. (2017). Atherogenic Lipoprotein Determinants of Cardiovascular Disease and Residual Risk Among Individuals With Low Low-Density Lipoprotein Cholesterol. J Am Heart Assoc, 6(7). https://doi.org/10.1161/JAHA.117.005549
Lawler, Patrick R., Akintunde O. Akinkuolie, Audrey Y. Chu, Svati H. Shah, William E. Kraus, Damian Craig, Latha Padmanabhan, et al. “Atherogenic Lipoprotein Determinants of Cardiovascular Disease and Residual Risk Among Individuals With Low Low-Density Lipoprotein Cholesterol.J Am Heart Assoc 6, no. 7 (July 21, 2017). https://doi.org/10.1161/JAHA.117.005549.
Lawler PR, Akinkuolie AO, Chu AY, Shah SH, Kraus WE, Craig D, et al. Atherogenic Lipoprotein Determinants of Cardiovascular Disease and Residual Risk Among Individuals With Low Low-Density Lipoprotein Cholesterol. J Am Heart Assoc. 2017 Jul 21;6(7).
Lawler, Patrick R., et al. “Atherogenic Lipoprotein Determinants of Cardiovascular Disease and Residual Risk Among Individuals With Low Low-Density Lipoprotein Cholesterol.J Am Heart Assoc, vol. 6, no. 7, July 2017. Pubmed, doi:10.1161/JAHA.117.005549.
Lawler PR, Akinkuolie AO, Chu AY, Shah SH, Kraus WE, Craig D, Padmanabhan L, Glynn RJ, Ridker PM, Chasman DI, Mora S. Atherogenic Lipoprotein Determinants of Cardiovascular Disease and Residual Risk Among Individuals With Low Low-Density Lipoprotein Cholesterol. J Am Heart Assoc. 2017 Jul 21;6(7).
Journal cover image

Published In

J Am Heart Assoc

DOI

EISSN

2047-9980

Publication Date

July 21, 2017

Volume

6

Issue

7

Location

England

Related Subject Headings

  • Time Factors
  • Rosuvastatin Calcium
  • Risk Factors
  • Risk Assessment
  • Proton Magnetic Resonance Spectroscopy
  • Proportional Hazards Models
  • Prognosis
  • Primary Prevention
  • Middle Aged
  • Male