Øyvind Hetland

Reduction in Homocysteine by n-3 Polyunsaturated Fatty Acids after 1 Year in a Randomised Double-Blind Study following an Acute Myocardial Infarction: No Effect on Endothelial Adhesion Properties

We hypothesized that n–3 polyunsaturated fatty acids (n–3 PUFAs) as compared to corn oil administered for 1 year following an acute myocardial infarction (MI) may reduce plasma total homocysteine (p-tHcy), ultrasensitive C-reactive protein (µCRP), and the adhesive properties of the endothelium, expressed as soluble E-selectin (sE-selectin) and soluble intercellular adhesion molecule-1 (sICAM-1). In a prospective, randomised, double-blind study, 300 acute MI patients were allocated to highly concentrated n–3 PUFAs (n = 150) or corn oil (n = 150). After 1 year on treatment there was an intergroup difference in p-tHcy in favour of the n–3 group (n = 118), p = 0.022. However, sE-selectin, sICAM-1 and µCRP were unaffected by the treatment. In conclusion, reduction of p-tHcy by long-term n–3 PUFAs treatment was not associated with demonstrable effects on markers of endothelial adhesion properties.

Long term influence of regular intake of high dose n-3 fatty acids on CD40-ligand, pregnancy-associated plasma protein A and matrix metalloproteinase-9 following acute myocardial infarction

Pregnancy-associated plasma protein A (PAPP-A) and matrix metalloproteinase 9 (MMP-9), both zinc-binding endopeptidases, are abundantly expressed in ruptured and eroded plaques in patients with acute coronary syndromes (ACS). The adhesion molecule CD-40 ligand (CD40L), expressed on activated platelets and T-lymphocytes, can activate metalloproteinases and thereby promote plaque-rupture. N-3 fatty acids, through their anti-inflammatory and anti-thrombotic properties, might reduce the levels of these proatherosclerotic markers and thereby the development of ACS. 300 patients were randomized on day 4 to 6 following an acute myocardial infarction (MI) to receive either 4 g of n-3 fatty acids or a similar daily dose of corn oil for at least one year. We compared levels of PAPP-A, MMP-9 and sCD-40 L at baseline and 12 months in each group, and also looked for inter-group changes. In the omega-3 group, the median level of PAPP-A rose from 0.47 mU/l to 0.56 mU/l (p < 0.001). In the same group, sCD-40 L decreased from a mean baseline value of 5.19 ng/ml to 2.45 ng/ml (p < 0.001) and MMP-9 decreased nonsignificantly from 360.50 ng/ml to 308.00 ng/ml. Corresponding values for the corn oil group were 0.54 mU/l to 0.59 mU/l for PAPP-A (p = 0.007), 5.27 ng/ml to 2.84 ng/ml for sCD-40 L (p < 0.001) and 430.00 ng/ml to 324.00 ng/ml for MMP-9 (p = ns), respectively. In conclusion; both interventions resulted in a significant rise in PAPP-A, a significant decrease in sCD40L and a non-significant decrease in MMP-9 after 12 months of treatment in MI survivors. No inter-group differences were noted.

Characteristics and prognostic impact of plasma fibrin monomer (soluble fibrin) in patients with coronary artery disease.

We measured fibrin monomer (FM), soluble fibrin, as a marker of thrombin activity in plasma samples obtained in parallel with the first two routine samples for cardiac markers in 165 patients with acute chest pain admitted consecutively to our hospital. A reference limit of FM in a healthy population was set at 3.0 mg/l. Elevated plasma FM was observed in 48.8% of patients with acute coronary syndromes, in 42.3% of patients with specific non-coronary disease, in 31.5% of those with stable angina pectoris and in 18.2% of patients with non-specific chest pain. No significant difference was observed between sample 1 and sample 2 in patients not receiving thrombolytic treatment during the sampling period (P = 0.46). In patients with coronary artery disease, FM was significantly related to the level of cardiac troponin T (P = 0.001), but no correlation was observed between the individual plasma FM and cardiac troponin T values. Outcome analysis during the following 30 months after the index event in patients with acute coronary syndromes revealed higher FM levels in those with coronary re-events or death than in patients without new events (P = 0.001). This observation indicates a prognostic potential of FM in risk evaluation of patients with coronary artery disease.

The prognostic utility of D-dimer and fibrin monomer at long-term follow-up after hospitalization with coronary chest pain.

D-dimer and fibrin monomer both reflect a prothrombotic potential. There are limited data available comparing these two markers of activated coagulation in a prospective manner in an unselected patient population presenting to the emergency department with chest pain. In addition, their role in risk stratification in patients with acute coronary syndrome is still under evaluation. Therefore, we wanted to assess the prognostic value of these markers with respect to long-term all-cause mortality in 871 patients admitted to the emergency department. Blood samples were obtained immediately following admission. After a follow-up period of 24 months, 123 patients had died. In the univariate analysis, both D-dimer and fibrin monomer predicted all-cause mortality within 2 years with an odds ratio of 7.78 (95% confidence interval, 3.95–15.33) and 4.19 (95% confidence interval, 2.42–7.28), respectively, in the highest quartile (Q4) compared with the lowest quartile (Q1). However, in the multivariable logistic regression model for death within 2 years, the odds ratio of D-dimer and fibrin monomer was 1.80 (95% confidence interval, 0.81 to 3.97) and 1.04 (95% confidence interval, 0.53 to 2.04) in Q4 compared with Q1, respectively, and added no prognostic information above and beyond age, known coronary heart disease, B-type natriuretic peptide and the index diagnoses of ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction and unstable angina pectoris. In an unselected patient population hospitalized with chest pain and potential acute coronary syndrome, neither D-dimer nor fibrin monomer provided complementary prognostic information to established risk determinants during long-term follow-up.