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The influence of pravastatin and atorvastatin on markers of oxidative stress in hypercholesterolemic humans.
J Am Coll Cardiol. 2008 Apr 29; 51(17):1653-62.JACC

Abstract

OBJECTIVES

The aim of this study was to determine the effects of pravastatin and atorvastatin on markers of oxidative stress in plasma.

BACKGROUND

Hydroxymethylglutaryl coenzyme A reductase inhibitors reduce low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk, but their effects on circulating biomarkers of oxidative stress are not well-defined.

METHODS

Hypercholesterolemic subjects (n = 120, ages 21 to 80 years with LDL-C 130 to 220 mg/dl) were randomized in a double-blind, parallel design to pravastatin 40 mg/day (prava40), atorvastatin 10 mg/day (atorva10), atorvastatin 80 mg/day (atorva80), or placebo. At baseline and 16 weeks, urinary isoprostanes (8, 12-iso-iPF(2 alpha)-VI isoform), plasma lipoprotein-associated phospholipase A2 (Lp-PLA2), Mercodia oxidized LDL (OxLDL) with antibody 4E6, oxidized phospholipids/apolipoprotein B-100 particle (OxPL/apoB) with antibody E06, immunoglobulin (Ig)G/IgM autoantibodies to malondialdehyde (MDA)-LDL, and apolipoprotein B (apoB)-immune complexes (IC) were measured.

RESULTS

After 16 weeks, there were no significant changes in urinary 8, 12-iso-iPF(2 alpha)-VI. The Lp-PLA2 and OxLDL were reduced in statin-treated groups, but after adjusting for apoB, only prava40 led to a reduction in Lp-PLA2 (-15%, p = 0.008) and atorva10 to a decrease in OxLDL (-12.9%, p = 0.01). The OxPL/apoB increased 25.8% (p < 0.01) with prava40 and 20.2% (p < 0.05) with atorva80. There were no changes in MDA-LDL autoantibodies, but significant decreases in IC were noted.

CONCLUSIONS

This study suggests that statin therapy results in variable effects on oxidative stress markers in hypercholesterolemic subjects. Future outcome studies should collectively assess various oxidative markers to define clinical utility.

Authors+Show Affiliations

Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6160, USA.No 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)

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

Language

eng

PubMed ID

18436117

Citation

Ky, Bonnie, et al. "The Influence of Pravastatin and Atorvastatin On Markers of Oxidative Stress in Hypercholesterolemic Humans." Journal of the American College of Cardiology, vol. 51, no. 17, 2008, pp. 1653-62.
Ky B, Burke A, Tsimikas S, et al. The influence of pravastatin and atorvastatin on markers of oxidative stress in hypercholesterolemic humans. J Am Coll Cardiol. 2008;51(17):1653-62.
Ky, B., Burke, A., Tsimikas, S., Wolfe, M. L., Tadesse, M. G., Szapary, P. O., Witztum, J. L., FitzGerald, G. A., & Rader, D. J. (2008). The influence of pravastatin and atorvastatin on markers of oxidative stress in hypercholesterolemic humans. Journal of the American College of Cardiology, 51(17), 1653-62. https://doi.org/10.1016/j.jacc.2008.01.026
Ky B, et al. The Influence of Pravastatin and Atorvastatin On Markers of Oxidative Stress in Hypercholesterolemic Humans. J Am Coll Cardiol. 2008 Apr 29;51(17):1653-62. PubMed PMID: 18436117.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The influence of pravastatin and atorvastatin on markers of oxidative stress in hypercholesterolemic humans. AU - Ky,Bonnie, AU - Burke,Anne, AU - Tsimikas,Sotirios, AU - Wolfe,Megan L, AU - Tadesse,Mahlet G, AU - Szapary,Philippe O, AU - Witztum,Joseph L, AU - FitzGerald,Garret A, AU - Rader,Daniel J, PY - 2007/09/28/received PY - 2008/01/24/revised PY - 2008/01/29/accepted PY - 2008/4/26/pubmed PY - 2008/6/5/medline PY - 2008/4/26/entrez SP - 1653 EP - 62 JF - Journal of the American College of Cardiology JO - J. Am. Coll. Cardiol. VL - 51 IS - 17 N2 - OBJECTIVES: The aim of this study was to determine the effects of pravastatin and atorvastatin on markers of oxidative stress in plasma. BACKGROUND: Hydroxymethylglutaryl coenzyme A reductase inhibitors reduce low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk, but their effects on circulating biomarkers of oxidative stress are not well-defined. METHODS: Hypercholesterolemic subjects (n = 120, ages 21 to 80 years with LDL-C 130 to 220 mg/dl) were randomized in a double-blind, parallel design to pravastatin 40 mg/day (prava40), atorvastatin 10 mg/day (atorva10), atorvastatin 80 mg/day (atorva80), or placebo. At baseline and 16 weeks, urinary isoprostanes (8, 12-iso-iPF(2 alpha)-VI isoform), plasma lipoprotein-associated phospholipase A2 (Lp-PLA2), Mercodia oxidized LDL (OxLDL) with antibody 4E6, oxidized phospholipids/apolipoprotein B-100 particle (OxPL/apoB) with antibody E06, immunoglobulin (Ig)G/IgM autoantibodies to malondialdehyde (MDA)-LDL, and apolipoprotein B (apoB)-immune complexes (IC) were measured. RESULTS: After 16 weeks, there were no significant changes in urinary 8, 12-iso-iPF(2 alpha)-VI. The Lp-PLA2 and OxLDL were reduced in statin-treated groups, but after adjusting for apoB, only prava40 led to a reduction in Lp-PLA2 (-15%, p = 0.008) and atorva10 to a decrease in OxLDL (-12.9%, p = 0.01). The OxPL/apoB increased 25.8% (p < 0.01) with prava40 and 20.2% (p < 0.05) with atorva80. There were no changes in MDA-LDL autoantibodies, but significant decreases in IC were noted. CONCLUSIONS: This study suggests that statin therapy results in variable effects on oxidative stress markers in hypercholesterolemic subjects. Future outcome studies should collectively assess various oxidative markers to define clinical utility. SN - 1558-3597 UR - https://www.unboundmedicine.com/medline/citation/18436117/The_influence_of_pravastatin_and_atorvastatin_on_markers_of_oxidative_stress_in_hypercholesterolemic_humans_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0735-1097(08)00496-8 DB - PRIME DP - Unbound Medicine ER -