Effect of folic acid supplementation on levels of circulating Monocyte Chemoattractant Protein-1 and the presence of intravascular ultrasound derived virtual histology thin-cap fibroatheromas in patients with stable angina pectoris

PLoS One. 2013 Jul 25;8(7):e70101. doi: 10.1371/journal.pone.0070101. Print 2013.

Abstract

Background: Virtual Histology Intravascular Ultrasound (VH-IVUS) may be used to detect early signs of unstable coronary artery disease. Monocyte Chemoattractant Protein-1 (MCP-1) is linked with coronary atherosclerosis and plaque instability and could potentially be modified by folic acid treatment.

Methods: In a randomized, prospective study, 102 patients with stable angina pectoris (SAP) received percutaneous coronary intervention and established medical treatment as well as either homocysteine-lowering folic acid/vitamin B12 (± B6) or placebo (± B6) for 1 year before VH-IVUS was performed. The presence of VH-Thin-Cap Fibroatheroma (VH-TCFA) in non-intervened coronary vessels was registered and serum levels of MCP-1 were measured. The patients were subsequently followed for incident myocardial infarction (MI).

Results: Patients treated with folic acid/vitamin B12 had a geometric mean (SD) MCP-1 level of 79.95 (1.49) versus 86.00 (1.43) pg/mL for patients receiving placebo (p-value 0.34). VH-TCFA lesions were present in 7.8% of patients and did not differ between intervention arms (p-value 0.47). Serum levels of MCP-1 were 1.46 (95% CI 1.12 to 1.92) times higher in patients with VH-TCFA lesions than in those without (p-value 0.005). Afterwards, patients were followed for median 2.1 years and 3.8% experienced a myocardial infarction (MI), which in post-hoc Cox regression analyses was independently predicted by both MCP-1 (P-value 0.006) and VH-TCFA (p-value 0.01).

Conclusions: In patients with SAP receiving established medical treatment, folic acid supplementation is not associated with either presence of VH-TCFA or levels of MCP-1. MCP-1 is however associated with VH-TCFA, a finding corroborated by increased risk for future MI. ClinicalTrials.gov Identifier: NCT00354081.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angina, Stable / complications
  • Angina, Stable / diagnostic imaging
  • Angina, Stable / diet therapy*
  • Angina, Stable / pathology
  • Chemokine CCL2 / blood*
  • Coronary Vessels / diagnostic imaging
  • Coronary Vessels / pathology*
  • Dietary Supplements*
  • Female
  • Folic Acid / administration & dosage*
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / diagnostic imaging
  • Myocardial Infarction / etiology
  • Myocardial Infarction / pathology
  • Myocardial Infarction / prevention & control*
  • Percutaneous Coronary Intervention
  • Plaque, Atherosclerotic / complications
  • Plaque, Atherosclerotic / diagnostic imaging
  • Plaque, Atherosclerotic / diet therapy*
  • Plaque, Atherosclerotic / pathology
  • Prospective Studies
  • Risk Factors
  • Ultrasonography

Substances

  • CCL2 protein, human
  • Chemokine CCL2
  • Folic Acid

Associated data

  • ClinicalTrials.gov/NCT00354081