Association Between Baseline, Achieved, and Reduction of CRP and Cardiovascular Outcomes After LDL Cholesterol Lowering with Statins or Ezetimibe: A Systematic Review and Meta-Analysis

J Am Heart Assoc. 2019 Aug 20;8(16):e012428. doi: 10.1161/JAHA.119.012428. Epub 2019 Aug 14.


Background Several lipid-lowering therapies reduce CRP (C-reactive protein) independently of LDL-C (low-density lipoprotein cholesterol) reduction, but the association between CRP parameters and benefits from more-intensive LDL-C lowering is inconclusive. We aimed to determine whether the benefits of more- versus less-intensive LDL-C lowering on cardiovascular events related to baseline, achieved, or magnitude of reduction in CRP concentrations. Methods and Results PubMed, EMBASE, and Cochrane were searched through July 2, 2018. We included randomized controlled cardiovascular outcome trials of LDL-C lowering with statins or ezetimibe. Two reviewers independently extracted study data and rated study quality. Data were analyzed using meta-analysis and metaregression analysis. Rate ratios of mortality and cardiovascular outcomes associated with baseline, achieved, and magnitude reduction of CRP concentration were calculated. Twenty-four trials were included, with 171 250 patients randomly assigned to more- or less-intensive LDL-C-lowering treatments. Median follow-up duration was 4.2 years. More-intensive LDL-C lowering resulted in a significant reduction in incidences of all outcomes. Compared with less-intensive LDL-C lowering, more-intensive LDL-C lowering was associated with less reductions in myocardial infarction with a higher baseline CRP concentration (change in rate ratios per 1-mg/L increase in log-transformed CRP, 1.12 [95% CI, 1.04-1.22; P=0.007]), but not other outcomes. Similar risk reductions occurred for more- versus less-intensive LDL-C-lowering therapy regardless of the magnitude of CRP reduction or the achieved CRP level for all outcomes. Conclusions Baseline CRP concentrations might be associated with the benefits of LDL-C lowering on myocardial infarction, but no other outcomes, whereas the achieved and magnitude of reduction in CRP did not seem to have an important association.

Keywords: C‐reactive protein; LDL‐cholesterol; cardiovascular outcomes; lipid lowering; meta‐analysis; randomized controlled trials.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Anticholesteremic Agents / therapeutic use*
  • C-Reactive Protein / metabolism*
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / mortality
  • Cholesterol, LDL / metabolism*
  • Ezetimibe / therapeutic use*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / metabolism
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / metabolism
  • Myocardial Revascularization / statistics & numerical data
  • Stroke / epidemiology
  • Stroke / metabolism
  • Treatment Outcome


  • Anticholesteremic Agents
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • C-Reactive Protein
  • Ezetimibe