Abstract

Abstract Background Coagulation is involved in fibroproliferative responses following acute myocardial infarction (AMI). Left ventricular (LV) remodeling following AMI is closely associated with progression to heart failure. Purpose We aimed to evaluate the association of plasma tissue factor (TF) coagulation activity with LV remodeling prior to heart failure in post-AMI patients. Methods This study was conducted in 228 subjects from the Post-AMI Left Ventricular Remodeling Biomarker Analysis (PAMILA) study and 57 healthy subjects. The post-AMI patients were divided into two age- and sex-matched groups: patients with adverse LV remodeling defined as an increase in LV end systolic volume by ≥15% over 6 months and patients with reverse LV remodeling defined as an decrease in LV end systolic volume by ≥15% over 6 months. TF coagulation activity was determined using human coagulation factor Xa generation based TF chromogenic activity assay and converted into concentrations of active TF (pM). Sodium-citrate anticoagulated plasma was collected at baseline (within 3 days after revascularization), 30 days and 6 months post-AMI. Results are presented as mean±S.E.M. One-way or two-way repeated measures ANOVA or a multiple multi-level longitudinal data analysis with structural equation model was used to assess differences in coagulation activity. P<0.05 was considered statistically significant. Results Plasma from healthy subjects and post-AMI patients at baseline had similar concentrations of active TF (TFa): 29.0±1.4 versus 29.1±0.7 pM. Patients treated with warfarin (15 out of 228 patients) showed lower plasma levels of TFa (mean difference −15.2 pM, [95% CI: −18.7, −11.7], p<0.001). Compared to baseline, plasma levels of TFa in the patients was significantly lower at 30 days post-AMI (mean difference −6.9 pM, [95% CI: −4.8, −8.9], p<0.001) and 6 months post-AMI (mean difference −2.8 pM, [95% CI: −0.8, −4.8], p=0.003). Intriguingly, plasma levels of TFa tended to recover from 30 days to 6 months post-AMI (mean difference 4.1 pM, [95% CI: 2.8, 5.4], p<0.001) toward the baseline level and the level in healthy subjects. Similar trends of temporal changes of plasma TFa levels were observed in patients with adverse LV remodeling and those with reverse LV remodeling although TFa levels were slightly higher in patients with reverse LV remodeling (F(2,448)=3.112, p=0.045 for interaction). After adjusting for age, gender, ethnicity, medications, lipid profile and risk factors, the temporal changes of plasma TFa levels in patients remain significant, however, the difference between patients with adverse versus reverse LV remodeling was not significant. Conclusion Plasma TF coagulation activity decreased post-AMI but did not differ in patients with adverse versus reverse LV remodeling. Acknowledgement/Funding National University Health System Singapore (NUHS O-CRG 2016 Oct-23) to JW Wang

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