This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: j.jacc.2007.01.083v1 49/20/2003    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Kinlay, S. Search for Related Content PubMed Articles by Kinlay, S. Related Collections Related Article

CLINICAL RESEARCH: CORONARY ARTERY DISEASE

Low-Density Lipoprotein-Dependent and -Independent Effects of Cholesterol-Lowering Therapies on C-Reactive Protein

A Meta-Analysis

Veteran’s Affairs Boston Healthcare System, West Roxbury Campus, Brigham and Women’s Hospital, and Harvard Medical School, Boston, Massachusetts.

Manuscript received January 19, 2006; revised manuscript received December 19, 2006, accepted January 3, 2007.

^_* Reprint requests and correspondence: Dr. Scott Kinlay, Cardiovascular Division, VA Boston Healthcare System, 1400 VFW Parkway, West Roxbury, Massachusetts 02132. (Email: skinlay{at}partners.org).

Objectives: This study sought to assess the contribution of low-density lipoprotein (LDL)–dependent and LDL–independent effects of LDL-lowering therapies to changes in C-reactive protein (CRP) in healthy or stable subjects.

Background: Correlations of change in LDL and CRP in individuals are lowered by their measurement variability. By using average changes in LDL and CRP in study groups, meta-analysis reduces this variability to better assess their correlation.

Methods: A systematic search for randomized placebo-controlled trials reporting change in LDL and CRP with LDL-lowering interventions retrieved 23 studies with 57 groups treated with a variety of statins, nonstatin drugs, or other regimens. Meta-analysis techniques assessed the relationships between average mean differences (placebo – treatment) in change in CRP and LDL.

Results: The overall reduction in CRP was 28% (95% confidence interval 26% to 30%). Significantly greater CRP reduction occurred in statin and statin-ezetimibe interventions, interventions using 80 mg/day of statins, and with greater LDL lowering. Meta-regression analysis showed a strong correlation between the change in LDL and CRP (r = 0.80, p < 0.001). Statin therapies had no significant effect on CRP after adjusting for the change in LDL. In a multivariate model applied to a range of LDL reduction typically seen with statins (20% to 60%), 89% to 98% of CRP change was related to LDL lowering and 2% to 11% was related to non-LDL effects of statins.

Conclusions: In clinical practice, most of the anti-inflammatory effect of LDL-lowering therapies is related to the magnitude of change in LDL. The potential non-LDL effects of statins on inflammation are much smaller in magnitude.

Abbreviations and Acronyms   CRP = C-reactive protein   LDL = low-density lipoprotein   RCT = randomized controlled trial

Related Article

Statins: Targeting Inflammation by Lowering Low-Density Lipoprotein?

E. Murat Tuzcu and Stephen J. Nicholls
J. Am. Coll. Cardiol. 2007 49: 2010-2012. [Full Text] [PDF]

This article has been cited by other articles:

				F. J. Al Badarin, I. J. Kullo, S. L. Kopecky, and R. J. Thomas Impact of Ezetimibe on Atherosclerosis: Is the Jury Still Out? Mayo Clin. Proc., April 1, 2009; 84(4): 353 - 361. [Abstract] [Full Text] [PDF]

				A. D. Hingorani, T. Shah, J. P. Casas, S. E. Humphries, and P. J. Talmud C-Reactive Protein and Coronary Heart Disease: Predictive Test or Therapeutic Target? Clin. Chem., February 1, 2009; 55(2): 239 - 255. [Abstract] [Full Text] [PDF]

				T. B. Grammer, W. Marz, W. Renner, B. O. Bohm, and M. M. Hoffmann C-reactive protein genotypes associated with circulating C-reactive protein but not with angiographic coronary artery disease: the LURIC study Eur. Heart J., January 2, 2009; 30(2): 170 - 182. [Abstract] [Full Text] [PDF]

				M. Settergren, F. Bohm, L. Ryden, and J. Pernow Cholesterol lowering is more important than pleiotropic effects of statins for endothelial function in patients with dysglycaemia and coronary artery disease Eur. Heart J., July 2, 2008; 29(14): 1753 - 1760. [Abstract] [Full Text] [PDF]

				S. Kinlay Vascular form and function: two mechanisms for cardiovascular prevention Eur. Heart J., July 2, 2008; 29(14): 1711 - 1713. [Full Text] [PDF]

				A. N. DeMaria, J. J. Bax, O. Ben-Yehuda, P. Clopton, G. K. Feld, G. S. Ginsburg, B. H. Greenberg, J. D. Knoke, W. Y.W. Lew, J. A.C. Lima, et al. Highlights of the year in JACC 2007. J. Am. Coll. Cardiol., January 29, 2008; 51(4): 490 - 512. [Full Text] [PDF]

				O. Ben-Yehuda High-Sensitivity C-Reactive Protein in Every Chart?: The Use of Biomarkers in Individual Patients J. Am. Coll. Cardiol., May 29, 2007; 49(21): 2139 - 2141. [Abstract] [Full Text] [PDF]

				E. M. Tuzcu and S. J. Nicholls Statins: Targeting Inflammation by Lowering Low-Density Lipoprotein? J. Am. Coll. Cardiol., May 22, 2007; 49(20): 2010 - 2012. [Full Text] [PDF]