Unstable coronary artery disease : Studies on inflammation, infection, hemostasis, and the effects of low-molecular-mass heparin treatment

Sammanfattning: The occurrence and prognostic importance, of inflammatory activity, signs of Chlamydia pneumoniae infection. APC resistance, hemostasis, and the effects of low-molecular-mass heparin (LMMH) was evaluated in patients with unstable coronary artery disease (UCAD).Increased inflammatory activity at admission (n=961), evaluated by fibrinogen and C-reactive proteinconcentrations, was associated with a worse outcome during a 150-day follow-up period, independently from the influence of myocardial damage.The prevalence of persistent Chlamydia pneumoniae infection was 36% in individuals with UCAD (n=256) compared to 19% in a reference population (n=190); p<0.001. Increased C. pneumoniae IgA antibody titers were associated with elevated fibrinogen concentrations.Resistance to activated protein C (APC resistance) was identified in 7.2% of 318 patients with UCAD,compared to 5.8% in a reference population (n=69); p=0.16. Despite increased thrombin generation in APCresistance. as indicated by elevated prothrombin fragment 1+2 concentrations, no relationship to the short-term outcome was found.The protective effect of LMMH was more pronounced in women than in men. In the 737 patients treatedwith LMMH there was an increased relative risk (CI) of minor bleeding among females compared to malesduring the acute phase treatment . 2.88 (1.78-4.67), as well as during the following 5 weeks reduced LMMH dose treatment. 2.36 (2.37-2.63). The anticoagulant effect, evaluated by the anti-Xa activity, was higher among females (n= 44) compared to males (n= 131).Markers of coagulation and fibrinolytic activity was determined in a subgroup during the placebo controlled LMMH treatment. In the LMMH treated group (n=42) a more pronounced increase in t-PA levelswas not linked to elevated plasmin antiplasmin (PAP) complex concentrations. as compared to the placebogroup (n=45).In conclusion the results indicate that increased inflammatory activity, to some extent associated withchronic C. pneumonias infection, is linked to a worse outcome in UCAD. Resistance to APC was not moreprevalent in UCAD. LMMH treatment seemed to induce a more prominent anticoagulant effect amongfemales as compared to males. The main mechanism of the antithrombotic effect of LMMH is itsanticoagulant property, while the influence on the fibrinolytic system seems to be without clinicalimportance.