Effect of lipid-lowering therapies on C-reactive protein levels: a comprehensive meta-analysis of randomized controlled trials

Cardiovasc Res. 2024 Mar 30;120(4):333-344. doi: 10.1093/cvr/cvae034.

Abstract

Chronic low-degree inflammation is a hallmark of atherosclerotic cardiovascular (CV) disease. To assess the effect of lipid-lowering therapies on C-reactive protein (CRP), a biomarker of inflammation, we conducted a meta-analysis according to the PRISMA guidelines. Databases were searched from inception to July 2023. Inclusion criteria were: (i) randomized controlled trials (RCTs) in human, Phase II, III, or IV; (ii) English language; (iii) comparing the effect of lipid-lowering drugs vs. placebo; (iv) reporting the effects on CRP levels; (v) with intervention duration of more than 3 weeks; (vi) and sample size (for both intervention and control group) over than 100 subjects. The between-group (treatment-placebo) CRP absolute mean differences and 95% confidence intervals were calculated for each drug class separately. A total of 171 668 subjects from 53 RCTs were included. CRP levels (mg/L) were significantly decreased by statins [-0.65 (-0.87 to -0.43), bempedoic acid; -0.43 (-0.67 to -0.20), ezetimibe; -0.28 (-0.48 to -0.08)], and omega-3 fatty acids [omega3FAs, -0.27 (-0.52 to -0.01)]. CRP was reduced by -0.40 (-1.17 to 0.38) with fibrates, although not statistically significant. A slight increase of CRP concentration was observed for proprotein convertase subtilisin/kexin type 9 inhibitors [0.11 (0.07-0.14)] and cholesteryl-ester transfer protein inhibitors [0.10 (0.00-0.21)], the latter being not statistically significant. Meta-regression analysis did not show a significant correlation between changes in CRP and LDL cholesterol (LDL-C) or triglycerides. Statins, bempedoic acid, ezetimibe, and omega3FAs significantly reduce serum CRP concentration, independently of LDL-C reductions. The impact of this anti-inflammatory effect in terms of CV prevention needs further investigation.

Keywords: C-reactive protein; Cardiovascular disease; Inflammation; Lipid-lowering therapies.

Publication types

  • Meta-Analysis

MeSH terms

  • Anticholesteremic Agents* / therapeutic use
  • Atherosclerosis* / drug therapy
  • C-Reactive Protein
  • Cardiovascular Diseases* / prevention & control
  • Cholesterol, LDL
  • Dicarboxylic Acids*
  • Ezetimibe / adverse effects
  • Fatty Acids*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / adverse effects
  • Inflammation / drug therapy
  • Randomized Controlled Trials as Topic

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Anticholesteremic Agents
  • 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
  • Cholesterol, LDL
  • C-Reactive Protein
  • Ezetimibe
  • Dicarboxylic Acids
  • Fatty Acids