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Low-density lipoprotein and high-density lipoprotein particle subclasses predict coronary events and are favorably changed by gemfibrozil therapy in the Veterans Affairs High-Density Lipoprotein Intervention Trial.
Circulation. 2006 Mar 28; 113(12):1556-63.Circ

Abstract

BACKGROUND

Changes in conventional lipid risk factors with gemfibrozil treatment only partially explain the reductions in coronary heart disease (CHD) events experienced by men in the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT). We examined whether measurement of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle subclasses provides additional information relative to CHD risk reduction.

METHODS AND RESULTS

This is a prospective nested case-control study of 364 men with a new CHD event (nonfatal myocardial infarction or cardiac death) during a 5.1-year (median) follow-up and 697 age-matched controls. Nuclear magnetic resonance (NMR) spectroscopy was used to quantify levels of LDL and HDL particle subclasses and mean particle sizes in plasma obtained at baseline and after 7 months of treatment with gemfibrozil or placebo. Odds ratios for a 1-SD increment of each lipoprotein variable were calculated with adjusted logistic regression models. Gemfibrozil treatment increased LDL size and lowered numbers of LDL particles (-5%) while raising numbers of HDL particles (10%) and small HDL subclass particles (21%). Concentrations of these LDL and HDL particles achieved with gemfibrozil were significant, independent predictors of new CHD events. For total LDL and HDL particles, odds ratios predicting CHD benefit were 1.28 (95% CI, 1.12 to 1.47) and 0.71 (95% CI, 0.61 to 0.81), respectively. Mean LDL and HDL particle sizes were not associated with CHD events.

CONCLUSIONS

The effects of gemfibrozil on NMR-measured LDL and HDL particle subclasses, which are not reflected by conventional lipoprotein cholesterol measures, help to explain the demonstrated benefit of this therapy in patients with low HDL cholesterol.

Authors+Show Affiliations

LipoScience, Inc, Raleigh, NC, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

16534013

Citation

Otvos, James D., et al. "Low-density Lipoprotein and High-density Lipoprotein Particle Subclasses Predict Coronary Events and Are Favorably Changed By Gemfibrozil Therapy in the Veterans Affairs High-Density Lipoprotein Intervention Trial." Circulation, vol. 113, no. 12, 2006, pp. 1556-63.
Otvos JD, Collins D, Freedman DS, et al. Low-density lipoprotein and high-density lipoprotein particle subclasses predict coronary events and are favorably changed by gemfibrozil therapy in the Veterans Affairs High-Density Lipoprotein Intervention Trial. Circulation. 2006;113(12):1556-63.
Otvos, J. D., Collins, D., Freedman, D. S., Shalaurova, I., Schaefer, E. J., McNamara, J. R., Bloomfield, H. E., & Robins, S. J. (2006). Low-density lipoprotein and high-density lipoprotein particle subclasses predict coronary events and are favorably changed by gemfibrozil therapy in the Veterans Affairs High-Density Lipoprotein Intervention Trial. Circulation, 113(12), 1556-63.
Otvos JD, et al. Low-density Lipoprotein and High-density Lipoprotein Particle Subclasses Predict Coronary Events and Are Favorably Changed By Gemfibrozil Therapy in the Veterans Affairs High-Density Lipoprotein Intervention Trial. Circulation. 2006 Mar 28;113(12):1556-63. PubMed PMID: 16534013.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Low-density lipoprotein and high-density lipoprotein particle subclasses predict coronary events and are favorably changed by gemfibrozil therapy in the Veterans Affairs High-Density Lipoprotein Intervention Trial. AU - Otvos,James D, AU - Collins,Dorothea, AU - Freedman,David S, AU - Shalaurova,Irina, AU - Schaefer,Ernst J, AU - McNamara,Judith R, AU - Bloomfield,Hanna E, AU - Robins,Sander J, Y1 - 2006/03/13/ PY - 2006/3/15/pubmed PY - 2006/4/15/medline PY - 2006/3/15/entrez SP - 1556 EP - 63 JF - Circulation JO - Circulation VL - 113 IS - 12 N2 - BACKGROUND: Changes in conventional lipid risk factors with gemfibrozil treatment only partially explain the reductions in coronary heart disease (CHD) events experienced by men in the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT). We examined whether measurement of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle subclasses provides additional information relative to CHD risk reduction. METHODS AND RESULTS: This is a prospective nested case-control study of 364 men with a new CHD event (nonfatal myocardial infarction or cardiac death) during a 5.1-year (median) follow-up and 697 age-matched controls. Nuclear magnetic resonance (NMR) spectroscopy was used to quantify levels of LDL and HDL particle subclasses and mean particle sizes in plasma obtained at baseline and after 7 months of treatment with gemfibrozil or placebo. Odds ratios for a 1-SD increment of each lipoprotein variable were calculated with adjusted logistic regression models. Gemfibrozil treatment increased LDL size and lowered numbers of LDL particles (-5%) while raising numbers of HDL particles (10%) and small HDL subclass particles (21%). Concentrations of these LDL and HDL particles achieved with gemfibrozil were significant, independent predictors of new CHD events. For total LDL and HDL particles, odds ratios predicting CHD benefit were 1.28 (95% CI, 1.12 to 1.47) and 0.71 (95% CI, 0.61 to 0.81), respectively. Mean LDL and HDL particle sizes were not associated with CHD events. CONCLUSIONS: The effects of gemfibrozil on NMR-measured LDL and HDL particle subclasses, which are not reflected by conventional lipoprotein cholesterol measures, help to explain the demonstrated benefit of this therapy in patients with low HDL cholesterol. SN - 1524-4539 UR - https://www.unboundmedicine.com/medline/citation/16534013/Low_density_lipoprotein_and_high_density_lipoprotein_particle_subclasses_predict_coronary_events_and_are_favorably_changed_by_gemfibrozil_therapy_in_the_Veterans_Affairs_High_Density_Lipoprotein_Intervention_Trial_ L2 - https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.105.565135?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -