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Lipids, apolipoproteins, and their ratios in relation to cardiovascular events with statin treatment.
Circulation. 2008 Jun 10; 117(23):3002-9.Circ

Abstract

BACKGROUND

Low-density lipoprotein (LDL) cholesterol is the principal target of lipid-lowering therapy, but recent evidence has suggested more appropriate targets. We compared the relationships of on-treatment levels of LDL cholesterol, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B, as well as ratios of total/HDL cholesterol, LDL/HDL cholesterol, and apolipoprotein B/A-I, with the occurrence of cardiovascular events in patients receiving statin therapy.

METHODS AND RESULTS

A post hoc analysis was performed that combined data from 2 prospective, randomized clinical trials in which 10,001 ("Treating to New Targets") and 8888 ("Incremental Decrease in End Points through Aggressive Lipid Lowering") patients with established coronary heart disease were assigned to usual-dose or high-dose statin treatment. In models with LDL cholesterol, non-HDL cholesterol and apolipoprotein B were positively associated with cardiovascular outcome, whereas a positive relationship with LDL cholesterol was lost. In a model that contained non-HDL cholesterol and apolipoprotein B, neither was significant owing to collinearity. Total/HDL cholesterol ratio and the apolipoprotein B/A-I ratio in particular were each more closely associated with outcome than any of the individual proatherogenic lipoprotein parameters.

CONCLUSIONS

In patients receiving statin therapy, on-treatment levels of non-HDL cholesterol and apolipoprotein B were more closely associated with cardiovascular outcome than levels of LDL cholesterol. Inclusion of measurements of the antiatherogenic lipoprotein fraction further strengthened the relationships. These data support the use of non-HDL cholesterol or apolipoprotein B as novel treatment targets for statin therapy. Given the absence of interventions that have been proven to consistently reduce cardiovascular disease risk through raising plasma levels of HDL cholesterol or apolipoprotein A-I, it seems premature to consider the ratio variables as clinically useful.

Authors+Show Affiliations

Academic Medical Center, Department of Vascular Medicine, University of Amsterdam, Amsterdam, the Netherlands. j.j.kastelein@amc.uva.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18519851

Citation

Kastelein, John J P., et al. "Lipids, Apolipoproteins, and Their Ratios in Relation to Cardiovascular Events With Statin Treatment." Circulation, vol. 117, no. 23, 2008, pp. 3002-9.
Kastelein JJ, van der Steeg WA, Holme I, et al. Lipids, apolipoproteins, and their ratios in relation to cardiovascular events with statin treatment. Circulation. 2008;117(23):3002-9.
Kastelein, J. J., van der Steeg, W. A., Holme, I., Gaffney, M., Cater, N. B., Barter, P., Deedwania, P., Olsson, A. G., Boekholdt, S. M., Demicco, D. A., Szarek, M., LaRosa, J. C., Pedersen, T. R., & Grundy, S. M. (2008). Lipids, apolipoproteins, and their ratios in relation to cardiovascular events with statin treatment. Circulation, 117(23), 3002-9. https://doi.org/10.1161/CIRCULATIONAHA.107.713438
Kastelein JJ, et al. Lipids, Apolipoproteins, and Their Ratios in Relation to Cardiovascular Events With Statin Treatment. Circulation. 2008 Jun 10;117(23):3002-9. PubMed PMID: 18519851.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lipids, apolipoproteins, and their ratios in relation to cardiovascular events with statin treatment. AU - Kastelein,John J P, AU - van der Steeg,Wim A, AU - Holme,Ingar, AU - Gaffney,Michael, AU - Cater,Nilo B, AU - Barter,Philip, AU - Deedwania,Prakash, AU - Olsson,Anders G, AU - Boekholdt,S Matthijs, AU - Demicco,David A, AU - Szarek,Michael, AU - LaRosa,John C, AU - Pedersen,Terje R, AU - Grundy,Scott M, AU - ,, AU - ,, Y1 - 2008/06/02/ PY - 2008/6/4/pubmed PY - 2008/7/9/medline PY - 2008/6/4/entrez SP - 3002 EP - 9 JF - Circulation JO - Circulation VL - 117 IS - 23 N2 - BACKGROUND: Low-density lipoprotein (LDL) cholesterol is the principal target of lipid-lowering therapy, but recent evidence has suggested more appropriate targets. We compared the relationships of on-treatment levels of LDL cholesterol, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B, as well as ratios of total/HDL cholesterol, LDL/HDL cholesterol, and apolipoprotein B/A-I, with the occurrence of cardiovascular events in patients receiving statin therapy. METHODS AND RESULTS: A post hoc analysis was performed that combined data from 2 prospective, randomized clinical trials in which 10,001 ("Treating to New Targets") and 8888 ("Incremental Decrease in End Points through Aggressive Lipid Lowering") patients with established coronary heart disease were assigned to usual-dose or high-dose statin treatment. In models with LDL cholesterol, non-HDL cholesterol and apolipoprotein B were positively associated with cardiovascular outcome, whereas a positive relationship with LDL cholesterol was lost. In a model that contained non-HDL cholesterol and apolipoprotein B, neither was significant owing to collinearity. Total/HDL cholesterol ratio and the apolipoprotein B/A-I ratio in particular were each more closely associated with outcome than any of the individual proatherogenic lipoprotein parameters. CONCLUSIONS: In patients receiving statin therapy, on-treatment levels of non-HDL cholesterol and apolipoprotein B were more closely associated with cardiovascular outcome than levels of LDL cholesterol. Inclusion of measurements of the antiatherogenic lipoprotein fraction further strengthened the relationships. These data support the use of non-HDL cholesterol or apolipoprotein B as novel treatment targets for statin therapy. Given the absence of interventions that have been proven to consistently reduce cardiovascular disease risk through raising plasma levels of HDL cholesterol or apolipoprotein A-I, it seems premature to consider the ratio variables as clinically useful. SN - 1524-4539 UR - https://www.unboundmedicine.com/medline/citation/18519851/Lipids_apolipoproteins_and_their_ratios_in_relation_to_cardiovascular_events_with_statin_treatment_ L2 - http://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.107.713438?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -