C-reactive protein is not only an inflammatory marker but also a direct cause of cardiovascular diseases

Med Hypotheses. 2004;62(4):499-506. doi: 10.1016/j.mehy.2003.12.014.


Inflammatory processes play a pivotal role in the pathogenesis of atherosclerosis and mediate many of the stages of atheroma development from initial leukocyte recruitment to eventual rupture of the unstable atherosclerotic plaque. C-reactive protein (CRP), an acute phase reactant that reflects different degree of inflammation, has been indicated an independent risk factor in a variety of cardiovascular disease (CVD), especially in unstable coronary syndrome. Our data have showed that increased level of CRP in patients with unstable angina was associated with short-term clinical outcomes, response for conventional therapy, and activation of nuclear factor-kappa B (NF-kappaB), but it is not correlated to coronary artery stenosis as well as lipid profile. Traditionally, CRP has been thought of as a bystander marker of vascular inflammation, without playing a direct role in the CVD. More recently, accumulating evidence suggest that CRP may have direct proinflammatory effects, which is associated with all stages of atherosclerosis. In our recent study, the results demonstrate that monocytes exhibit an enhanced production of interleukin-6 (IL-6) in response to CRP, and this response is significantly inhibited by simvastatin in a dose-dependent manner. This may be of important interest in the connection between CVD and CRP. Based on those evidence, we hypothesis that CRP is not only an inflammatory marker but also a direct cause of CVD, and treatments that reduce CRP should be benefit for primary and secondary prevention of CVD. Administration of several agents, especially statin has been showed to modify CRP concentrations with a concurrent fall in cardiovascular events. Our clinical investigation suggested that treatment with a single high-dose or a short-term common dose of simvastatin could rapidly reduce CRP level. Those data indicated that the benefit to the vascular endothelium might occur quickly in patients with CVD, which is critical issue for high-risk subgroup. Other interventions, such as lifestyle changes, weight loss, and stop smoking are also warrant attention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Reaction
  • Aspirin / therapeutic use
  • Atorvastatin
  • Biomarkers
  • C-Reactive Protein / drug effects
  • C-Reactive Protein / metabolism*
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / prevention & control*
  • Clinical Trials as Topic
  • Coronary Artery Disease / epidemiology
  • Coronary Artery Disease / etiology
  • Coronary Artery Disease / prevention & control
  • Heptanoic Acids / therapeutic use
  • Humans
  • Incidence
  • Inflammation / immunology
  • Inflammation / metabolism*
  • Interleukin-6 / metabolism
  • Lovastatin / therapeutic use
  • Pravastatin / therapeutic use
  • Predictive Value of Tests
  • Pyrroles / therapeutic use
  • Risk Factors
  • Simvastatin / therapeutic use


  • Biomarkers
  • Heptanoic Acids
  • Interleukin-6
  • Pyrroles
  • C-Reactive Protein
  • Lovastatin
  • Atorvastatin
  • Simvastatin
  • Pravastatin
  • Aspirin