Low-density lipoprotein-dependent and -independent effects of cholesterol-lowering therapies on C-reactive protein: a meta-analysis.
OBJECTIVE
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.
Kinlay
Scott
S
Veteran's Affairs Boston Healthcare System, West Roxbury Campus, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts 02132, USA. skinlay@partners.org
D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001384:Azetidines / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000032:analysis / Q000187:drug effects*; D008078:Cholesterol, LDL / Q000097:blood*; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015999:Multivariate Analysis; D016032:Randomized Controlled Trials as Topic
D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002097:C-Reactive Protein; D000069438:Ezetimibe