Relation between plasma fibrinogen level and coronary plaque morphology in patients with stable angina pectoris

SummaryElevated plasma fibrinogen levels are associated with an increased risk for cardiac events. Ticlopidine is a drug that inhibits the ADP-induced aggregation of blood platelets and it also has been described that ticlopidine can decrease the plasma fibrinogen level in patients with vascular diseases. The mechanism of this decrease has not yet been elucidated and therefore mechanisms that are known to affect fibrinogen levels were studied, viz. the acute phase reaction, total fibrin plus fibrinogen degradation (TDP) levels and the polymorphisms of the fibrinogen β-gene.The fibrinogen lowering effect of ticlopidine was studied in 26 healthy volunteers, selected on genotype of the BclI polymorphism of the fibrinogen β-gene, and in 26 patients with stable angina pectoris in a double blind, randomized cross-over study. Functional plasma fibrinogen levels were measured with the Clauss assay. Fibrinogen antigen, C-reactive protein (CRP) and TDP levels were measured using an enzyme immuno assay (EIA).In the healthy volunteers the functional fibrinogen levels had decreased by 0.20 g/l (9%, p = 0.005 using the paired Student t-test) after 4 weeks of 250 mg bid ticlopidine administration, whereas fibrinogen antigen, CRP and TDP levels were not significantly changed. In the stable angina pectoris patients the pre-treatment fibrinogen, CRP and TDP levels were significantly higher than in the volunteer group. After four weeks 250 mg bid ticlopidine administration the functional fibrinogen levels had decreased by 0.38 g/l (11%, p < 0.005), whereas the fibrinogen antigen, CRP and TDP levels were not significantly changed. The levels of functional and antigen fibrinogen, CRP and TDP did not change significantly during the placebo period in the volunteers or the patients. Neither in the volunteers nor in the patients was the effect of ticlopidine on the fibrinogen levels associated with the fibrinogen β-gene polymorphisms.Therefore, the fibrinogen lowering effect of ticlopidine is likely to be a modulation of the functionality of the molecule and unlikely to be modulated by the acute phase reaction, TDP-levels or the fibrinogen β-gene polymorphisms.

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Abstract 2511: Impact of Olmesartan on Progression of Coronary Atherosclerosis; - A Serial Volumetric IVUS Analysis from the OLIVUS Trial -

Circulation ◽

10.1161/circ.118.suppl_18.s_735-a ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Atsushi Hirohata ◽

Hirosuke Yamaji ◽

Masaaki Murakami ◽

Eiki Hirose ◽

Keisuke Ohkawa ◽

...

Keyword(s):

Angina Pectoris ◽

Stable Angina ◽

Coronary Atherosclerosis ◽

Coronary Plaque ◽

Stable Angina Pectoris ◽

Plaque Volume ◽

Receptor Blocking ◽

Percent Change ◽

Angiotension Ii

Prior intravascular ultrasound (IVUS) trials suggest slowing of coronary plaque progression with some medicines but have not shown convincing evidence of regression using angiotension-II receptor blocking agents (ARB). A prospective, double-blind, randomized, multicenter trial (Impact of OLmesartan on progression of coronary atherosclerosis; evaluation by IntraVascular UltraSound [OLIVUS]) was performed in 247 stable angina pectoris patients with native coronary artery lesions. When these patients underwent percutaneous coronary intervention for culprit lesions, IVUS was performed in their non-culprit vessels (without angiographically documented coronary stenosis [<50%]). Patients were randomly assigned to receive 20 mg of Olmesartan or control, and treated with a combination of β-blockers, calcium channel blockers, diuretics, nitrates, glycemic control agents and/or statins per physician’s guidance. Patients already on ACE inhibitors or other ARBs were excluded. Serial IVUS examinations (baseline and 14-months follow-up) were performed to assess coronary plaque volume. Volumetric IVUS analyses (mean measured length:41.2 ± 8.7mm) included lumen (LV), plaque (PV), vessel volume (VV), percent plaque volume (% PV), percent change in total PV (PCPV) and percent change in % PV (PC%PV). At baseline, patient characteristics and all IVUS parameters were identical between the two groups. However, follow-up IVUS showed significantly decreased PCPV and PC%PV in the Olmesartan group, despite similar blood pressure (table ). In addition, multivariate analysis identified Olmesartan administration as one of the factors that decreased plaque volume (β-coefficient −0.29 (95%CI, −0.7 to 0.4), p<0.01). These observations suggest a positive role in potential plaque regression through the administration of Olmesartan, an angiotension-II receptor blocking agent, for patients with stable angina pectoris.

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