Low-density lipoprotein-dependent and -independent effects of cholesterol-lowering therapies on C-reactive protein: a meta-analysis.

@article{citeulike:2208562, abstract = {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.}, address = {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}, author = {Kinlay, S. }, citeulike-article-id = {2208562}, comment = {This analysis of 23 studies found the vast majority of hs-CRP reduction observed in statin trials tracks with LDL-C lowering. Thus, only a small amount (2-11\%) of hs-CRP change is independent of LDL-C reduction. This non-LDL-C change could be do to weight loss, smoking cessation, or other new healthy behaviours adoped by trial participants. This paper sets the stage for what is going to be a difficult interpretation of the JUPITER trial results with rosuvastatin. This trial will attempt to show that the hs-CRP reduction with a statin reduces cardiovascular outcomes independently from the LDL-C lowering effect. The present study predicts that rosuvastatin will lower LDL-C, lower hs-CRP in most, reduce cardiovascular events, and create controversey over how statins really exert their beneficial effects in the cardiovascular system.--Peter A. McCullough, MD, MPH }, doi = {10.1016/j.jacc.2007.01.083}, issn = {1558-3597}, journal = {J Am Coll Cardiol}, keywords = {crp, hplp, therapy}, month = {May}, number = {20}, pages = {2003--2009}, posted-at = {2008-01-08 18:49:58}, priority = {2}, title = {Low-density lipoprotein-dependent and -independent effects of cholesterol-lowering therapies on C-reactive protein: a meta-analysis.}, url = {http://dx.doi.org/10.1016/j.jacc.2007.01.083}, volume = {49}, year = {2007} }

TY - JOUR ID - citeulike:2208562 L3 - citeulike-article-id:2208562 TI - Low-density lipoprotein-dependent and -independent effects of cholesterol-lowering therapies on C-reactive protein: a meta-analysis. JF - J Am Coll Cardiol VL - 49 IS - 20 SP - 2003 EP - 2009 AD - 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 SN - 1558-3597 N2 - 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. KW - crp KW - hplp KW - therapy N1 - This analysis of 23 studies found the vast majority of hs-CRP reduction observed in statin trials tracks with LDL-C lowering. Thus, only a small amount (2-11%) of hs-CRP change is independent of LDL-C reduction. This non-LDL-C change could be do to weight loss, smoking cessation, or other new healthy behaviours adoped by trial participants. This paper sets the stage for what is going to be a difficult interpretation of the JUPITER trial results with rosuvastatin. This trial will attempt to show that the hs-CRP reduction with a statin reduces cardiovascular outcomes independently from the LDL-C lowering effect. The present study predicts that rosuvastatin will lower LDL-C, lower hs-CRP in most, reduce cardiovascular events, and create controversey over how statins really exert their beneficial effects in the cardiovascular system.--Peter A. McCullough, MD, MPH AU - Kinlay, S PY - 2007/05/22/ UR - http://dx.doi.org/10.1016/j.jacc.2007.01.083 ER -