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.
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.
Department of Clinical Science, University of Bergen, Bergen, Norway. kjetil.loland@gmail.com
Kjetil H
KH
Løland
Øyvind
Ø
Bleie
Elin
E
Strand
Per M
PM
Ueland
Jan E
JE
Nordrehaug
Hector M
HM
Garcia-Garcia
Patrick W
PW
Serruys
Ottar
O
Nygård
D000368:Aged; D060050:Angina, Stable / Q000150:complications / Q000000981:diagnostic imaging / Q000178:diet therapy* / Q000473:pathology; D018932:Chemokine CCL2 / Q000097:blood*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000473:pathology*; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D062645:Percutaneous Coronary Intervention; D058226:Plaque, Atherosclerotic / Q000150:complications / Q000000981:diagnostic imaging / Q000178:diet therapy* / Q000473:pathology; D011446:Prospective Studies; D012307:Risk Factors; D014463:Ultrasonography
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D005492:Folic Acid