α1-antichymotrypsin complex (SERPINA3) is an independent predictor of all-cause but not cardiovascular mortality in patients hospitalized for chest pain of suspected coronary origin.

INTRODUCTION: SERPINA3 is an acute phase protein triggered by inflammation. It is upregulated after an acute myocardial infarction (AMI). Data on its long-term prognostic value in MI patients are scarce. We aimed to assess the utility of SERPINA3 as a prognostic marker in patients hospitalized for chest pain of suspected coronary origin. METHODS: A total of 871 consecutive patients, 386 diagnosed with AMI, were included. Stepwise Cox regression models, applying continuous loge-transformed values, were fitted for the biomarker with all-cause mortality and cardiac death within 2-years or all-cause mortality within median 7 years as dependent variables. An analysis of MI and stroke, and combined endpoints, respectively, was added. The hazard ratio (HR) (95% CI) was assessed in a univariate and multivariable model. RESULTS: Plasma samples from 847 patients were available. By 2 years follow-up, 138 (15.8%) patients had died, of which 86 were cardiac deaths. The univariate analysis showed a significant association between SERPINA3 and all-cause mortality [HR 1.41 (95% 1.19-1.68), p<0.001], but not for cardiac death. Associations after adjustment were non-significant. By 7 years follow-up, 332 (38.1%) patients had died. SERPINA3 was independently associated with all-cause mortality from the third year onwards. The HR was 1.14 (95% CI, 1.02-1.28), p=0.022. Similar results applied to combined endpoints, but not for MI and stroke, respectively. The prognostic value of SERPINA3 was limited to non-AMI patients. No independent associations were noted among AMI patients. CONCLUSIONS: SERPINA3 predicts long-term all-cause mortality, but failed to predict outcome in AMI patients.

Total Bilirubin Yields Prognostic Information Following a Myocardial Infarction in the Elderly.

Total bilirubin consists of an unconjugated form, solubilized by its binding to albumin, and a conjugated form representing a minor part of the circulating bilirubin. As total bilirubin in physiological concentrations is a powerful antioxidant, its concentration gradient may reflect the health status of an individual, and serve as a prognostic indicator of outcome in primary and secondary cardiovascular disease prevention. The aim of this study was to assess the association between total bilirubin and incident cardiovascular events following a myocardial infarction. Total bilirubin in serum was measured at baseline 2-8 weeks after hospitalization for an MI in 881 patients, aged 70 to 82 years, included in the OMEMI (Omega-3 Fatty acids in Elderly with Myocardial Infarction) study, where patients were followed-up for up to 2 years. The first major adverse clinical event (MACE) was the primary endpoint and consisted of nonfatal MI, unscheduled coronary revascularization, stroke, hospitalization for heart failure or all-cause death. As total bilirubin was non-normally distributed, log-transformed values and quartiles of bilirubin were analyzed using Cox regression models. The median (Q1, and Q3) baseline concentration of bilirubin was 11 (9, and 14) µmol/L, and higher log-transformed concentrations were associated with male sex, lower New York Heart Association (NYHA) class and non-smoking. MACE occurred in 177 (20.1%) patients during the follow-up. Higher concentrations of bilirubin were associated with a lower risk of MACE: HR 0.67 (95%CI 0.47-0.97) per log-unit increase, p = 0.032. Patients in the lowest quartile of bilirubin (<9 µmol/L) had the highest risk with HR 1.61 (95%CI 1.19-2.18), p = 0.002, compared to quartiles 2-4. This association remained significant even after adjusting for age, sex, body mass index (BMI), smoking status, NYHA class and treatment allocation: HR 1.52 (1.21-2.09), p = 0.009. Low concentrations of bilirubin (<9 µmol/L) are associated with increased nonfatal cardiovascular events or death in elderly patients with a recent myocardial infarction.

Serum Levels of Dihomo-Gamma (γ)-Linolenic Acid (DGLA) Are Inversely Associated with Linoleic Acid and Total Death in Elderly Patients with a Recent Myocardial Infarction.

Dihomo-gamma-linolenic acid (DGLA) is an n-6 polyunsaturated fatty acid (PUFA) derived from linoleic acid (LA). The LA:DGLA ratio reflects conversion from LA to DGLA. Low levels of DGLA in serum have been related to poor outcome in myocardial infarction (MI) patients. Aims: To assess the association of DGLA and LA:DGLA with total death as a primary aim and incident cardiovascular events as a secondary objective. Methods: Baseline samples from 1002 patients, aged 70 to 82 years, included 2-8 weeks after an MI and followed for 2 years, were used. Major adverse clinical events (MACE) consisted of nonfatal MI, unscheduled coronary revascularization, stroke, hospitalization for heart failure or all-cause death. Cox regression analysis was used to relate serum n-6 PUFA phospholipid levels (%wt) to the risk of MACE, adjusting for the following: (1) age, sex and body mass index (BMI); (2) adding baseline cod liver oil supplementation; (3) adding prevalent hypertension, chronic kidney disease and diabetes mellitus. Results: Median DGLA level in serum phospholipids was 2.89 (Q1-Q3 2.43-3.38) %wt. DGLA was inversely related to LA and LA:DGLA ratio. There were 208 incident cases of MACE and 55 deaths. In the multivariable analysis, the hazard ratio (HR) for the total death in the three higher quartiles (Q2-4) of DGLA as compared to Q1 was 0.54 (0.31-0.95), with p = 0.03 (Model-1), 0.50 (0.28-0.91), with p = 0.02 (Model-2), and 0.47 (0.26-0.84), with p = 0.012 (Model-3), and non-significant for MACE. Risk of MACE (Model 3) approached borderline significance for LA:DGLA in Q2-4 vs. Q1 [HR 1.42 (1.00-2.04), p = 0.052]. Conclusions: Low levels of DGLA were related to a high LA:DGLA ratio and risk of total death in elderly patients with recent MI.

Activated factor 12 (FXIIa) predicts recurrent coronary events after an acute myocardial infarction.

BACKGROUND: Activated factor XII (FXIIa) is involved in vascular injury and repair, participating in inflammation, thrombosis, and fibrinolysis. We wanted to test the hypothesis that FXIIa may predict an acute coronary syndrome (ACS) after a myocardial infarction (MI) and to evaluate whether FXIIa is related to global markers of end-stage coagulation and inflammation, including fibrin monomer (FM) and ultrasensitive C-reactive protein (microCRP). METHODS: In a prospective study of 300 patients with acute MI, we evaluated the predictive value of FXIIa in blood samples drawn 4 to 6 days after admission. Cardiac death, re-MI, and troponin-T-positive unstable angina pectoris were registered during a median follow-up period of 1.5 years. RESULTS: In the upper quartile of FXIIa (Q4) (> or =2.23 ng/mL) 32.0% of patients had an ACS as compared with 16.9% of patients with FXIIa in the three lower quartiles (Q1-3, P =.008). Relative risk of recurrent ACS for patients with FXIIa in the Q4 as compared with Q1-3 was 1.89 (95% CI, 1.22 to 2.93). A secondary ACS occurred earlier in patients with FXIIa in the Q4 as compared with those with FXIIa in the Q1-3 (P =.0039). Conventional risk factors as potential confounders were not associated with time to event. FXIIa did not correlate with FM or microCRP, and the FM and microCRP levels were of a similar magnitude in the Q4 as compared with the Q1 and the Q1-3 of FXIIa. CONCLUSIONS: FXIIa predicts recurrent coronary events after MI. The prognostic ability of FXIIa was not reflected by markers of hypercoagulability or inflammation.

Changes of plasma activated Factor XII type A (XIIaA) concentrations following percutaneous coronary intervention (PCI).

BACKGROUND: Recent research has demonstrated that in-vivo XIIa exists in a number of different types and that treatment with tenecteplase increases the plasma concentration of XIIaA. Only limited data exist on changes in activated Factor XII (XIIa) levels following mechanical revascularisation, such as percutaneous coronary intervention (PCI). METHODS: Citrated blood samples were obtained from 31 PCI-treated patients admitted with ST-elevation myocardial infarction (STEMI) and 20 patients undergoing elective PCI. Samples were taken immediately before the invasive procedure, 30-90 min after PCI and (in patients undergoing primary PCI) 4-6 days following intervention. Additional samples were taken after angiography, just prior to the follow-on PCI procedure, in 16 of the patients undergoing elective PCI, to investigate possible effects of contrast fluid and heparin. XIIa measurements were performed using 2 ELISA assays designed to preferentially measure different types of XIIa; XIIaA and XIIaR. RESULTS: In the group undergoing primary PCI, XIIaA showed a significant increase from 68 (48-93) pM in the pre-treatment sample to 100 (75-123) pM [median and 25- and 75% percentiles] in the 30-90-min post-treatment sample (p < 0.001), returning to pre-intervention levels by day 4-6. A similar increase in XIIaA was obtained in patients undergoing elective PCI. In contrast, no significant changes in XIIaR concentration were observed. Whilst XIIaA concentrations remained unchanged in 6 non-heparinised patients undergoing elective coronary angiography, XIIaA levels rose significantly from 56 (51-75) pM to 98 (71-125) pM [median and 25- and 75% percentiles], (p < 0.01) in 10 patients after the addition of heparin. CONCLUSION: A significant short-lasting increase in specific types of XIIa (namely XIIaA) was observed following PCI. These increases are most likely induced by the concomitant treatment with heparin.

Specific types of activated Factor XII increase following thrombolytic therapy with tenecteplase.

BACKGROUND: Activated Factor XII (XIIa) is believed to participate in a number of pathophysiological processes including inflammation, thrombosis and fibrinolysis. Increasing XIIa levels following thrombolytic therapy have previously been reported. In contrast to other thrombolytics, tenecteplase (TNK-tpa) does not show paradoxical thrombin activation, indicating a lower procoagulant effect of this fibrin-selective thrombolytic agent. Recent research has demonstrated that in-vivo XIIa exists in a number of different types, and the aim of this study was to investigate plasma variations of different types of XIIa following thrombolytic treatment with TNK-tpa. METHODS: Citrated blood samples were obtained from 34 patients admitted with acute ST-elevation myocardial infarction (STEMI) treated with TNK-tpa. Samples were taken immediately prior to treatment, 30-90 min after and 4 days post-treatment. XIIa measurements were performed using 2 ELISA assays designed to preferentially measure different types of XIIa; XIIaA and XIIaR. Both assays utilised a monoclonal antibody 2/215, which is highly specific for XIIa, as the solid phase capture antibody. The assay for XIIaA used a conjugate based on a polyclonal antibody against the entire XIIa molecule, whilst the assay for XIIaR incorporated a reagent to release otherwise unavailable XIIa and used a conjugate based on a monoclonal antibody against beta-XIIa. RESULTS: Changes in plasma XIIaA concentration as a result of therapy were more evident than changes in XIIaR concentration. XIIaA showed a significant increase from 67.1 (49.0-84.4) pM to 97.8 (75.5-133.1) pM [median and 25 and 75% percentiles] in the 30-90 min sample (P < 0.001), returning to pre-intervention levels 61.5 (47.5-81.0) pM by day 4. In contrast, no significant change in XIIaR concentration was observed following thrombolytic therapy with TNK-tpa. CONCLUSION: In patients admitted with STEMI, thrombolytic therapy with TNK-tpa resulted in a significant short-lasting increase in specific types of XIIa (namely XIIaA), whereas other types of XIIa (XIIaR) were largely unaffected by this intervention.