CLINICAL RESEARCH: STATINS AND HYPERCHOLESTEROLEMIA
The Influence of Pravastatin and Atorvastatin on Markers of Oxidative Stress in Hypercholesterolemic Humans
Bonnie Ky, MD*,
Anne Burke, MD*,
Sotirios Tsimikas, MD ,
Megan L. Wolfe, BS*,
Mahlet G. Tadesse, ScD*,
Philippe O. Szapary, MD*,
Joseph L. Witztum, MD ,
Garret A. FitzGerald, MD* and
Daniel J. Rader, MD*,*
* Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania
University of California San Diego, La Jolla, California.
Manuscript received September 28, 2007;
revised manuscript received January 24, 2008,
accepted January 29, 2008.
* Reprint requests and correspondence: Dr. Daniel J. Rader, University of Pennsylvania, 421 Curie Boulevard, Room 654 BRB, Philadelphia, Pennsylvania 19104-6160. (Email: rader{at}mail.med.upenn.edu).
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-iPF2 -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-iPF2 -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.
|
Abbreviations and Acronyms
| | atorva10 = atorvastatin 10 mg/day | | atorva80 = atorvastatin 80 mg/day | | CHD = coronary heart disease | | ELISA = enzyme-linked immunosorbent assay | | HDL-C = high-density lipoprotein cholesterol | | IC = immune complexes | | LDL-C = low-density lipoprotein cholesterol | | Lp(a) = lipoprotein(a) | | Lp-PLA2 = lipoprotein-associated phospholipase A2 | | MDA = malondialdehyde | | OxLDL = oxidized low-density lipoprotein | | OxPL = oxidized phospholipids | | OxPL/apoB = oxidized phospholipids onapolipoprotein B-100 particles | | prava40 = pravastatin 40 mg/day | | TC = total cholesterol |
|
This article has been cited by other articles:

|
 |

|
 |
 
N. S. Rajendra, S. Ireland, J. George, J. J. F. Belch, C. C. Lang, and A. D. Struthers
Mechanistic Insights Into the Therapeutic Use of High-Dose Allopurinol in Angina Pectoris
J. Am. Coll. Cardiol.,
August 16, 2011;
58(8):
820 - 828.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Faghihnia, S. Tsimikas, E. R. Miller, J. L. Witztum, and R. M. Krauss
Changes in lipoprotein(a), oxidized phospholipids, and LDL subclasses with a low-fat high-carbohydrate diet
J. Lipid Res.,
November 1, 2010;
51(11):
3324 - 3330.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Dayangku Fatiha Pengiran Burut, Y. Karim, and G. A. A. Ferns
The Role of Immune Complexes in Atherogenesis
Angiology,
October 1, 2010;
61(7):
679 - 689.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Tsimikas, Z. Mallat, P. J. Talmud, J. J. P. Kastelein, N. J. Wareham, M. S. Sandhu, E. R. Miller, J. Benessiano, A. Tedgui, J. L. Witztum, et al.
Oxidation-Specific Biomarkers, Lipoprotein(a), and Risk of Fatal and Nonfatal Coronary Events
J. Am. Coll. Cardiol.,
September 14, 2010;
56(12):
946 - 955.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Z.-h. Wang, X.-l. Liu, M. Zhong, L.-p. Zhang, Y.-y. Shang, X.-y. Hu, L. Li, Y. Zhang, J.-t. Deng, and W. Zhang
Pleiotropic Effects of Atorvastatin on Monocytes in Atherosclerotic Patients
J. Clin. Pharmacol.,
March 1, 2010;
50(3):
311 - 319.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. E. Fraley, G. G. Schwartz, A. G. Olsson, S. Kinlay, M. Szarek, N. Rifai, P. Libby, P. Ganz, J. L. Witztum, S. Tsimikas, et al.
Relationship of Oxidized Phospholipids and Biomarkers of Oxidized Low-Density Lipoprotein With Cardiovascular Risk Factors, Inflammatory Biomarkers, and Effect of Statin Therapy in Patients With Acute Coronary Syndromes: Results From the MIRACL (Myocardial Ischemia Reduction With Aggressive Cholesterol Lowering) Trial
J. Am. Coll. Cardiol.,
June 9, 2009;
53(23):
2186 - 2196.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. H. SHISHEHBOR and S. L. HAZEN
JUPITER to Earth: A statin helps people with normal LDL-C and high hs-CRP, but what does it mean?
Cleveland Clinic Journal of Medicine,
January 1, 2009;
76(1):
37 - 44.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|