A history of late and very late stent thrombosis is not associated with increased activation of the contact system, a case control study

Background: The pathophysiological pathways resulting in Late Stent Thrombosis (LST) remain uncertain. Findings from animal studies indicate a role of the intrinsic coagulation pathway in arterial thrombus formation, while clinical studies support an association with ischemic cardiovascular disease. It is currently unknown whether differences in the state of the contact system might contribute to the risk of LST or Very Late Stent Thrombosis (VLST). We assessed the relation between levels of several components involved in the contact system and a history of LST and VLST, termed (V)LST in a cohort of 20 patients as compared to a matched control group treated with PCI. Methods and Results: Activated factor XII (FXIIa), FXII zymogen (FXII), FXIIa-C1-esterase inhibitor (C1-inhibitor), Kallikrein-C1-inhibitor, FXIa-C1-inhibitor and FXIa-α1-antitrypsin (AT-inhibitor) complexes were measured by Enzyme-linked immunosorbent assy (ELISA) methodology. Cases and controls showed similar distributions in sex, age, baseline medications and stent type. Patients with a history of (V)LST had a significantly greater stent burden and a higher number of previous myocardial infarctions than the control patients. There were no significant between-group differences in the plasma levels of the components of the contact system. Conclusion: In a cohort of patients with a history of (V)LST, we did not observe differences in the activation state of the intrinsic coagulation system as compared to patients with a history of percutaneous coronary intervention without stent thrombosis

Procollagen type 1 N-terminal propeptide is associated with adverse outcome in acute chest pain of suspected coronary origin

BackgroundExtracellular matrix (ECM) is an integral player in the pathophysiology of a variety of cardiac diseases. Cardiac ECM is composed mainly of collagen, of which type 1 is the most abundant with procollagen type 1 N-terminal Propeptide (P1NP) as a formation marker. P1NP is associated with mortality in the general population, however, its role in myocardial infarction (MI) is still uncertain, and P1NP has not been investigated in acute chest pain. The objective of the current study was to assess the role of P1NP in undifferentiated acute chest pain of suspected coronary origin.Methods and results813 patients from the Risk in Acute Coronary Syndromes study were included. This was a single-center study investigating biomarkers in consecutively enrolled patients with acute chest pain of suspected coronary origin, with a follow-up for up to 7 years. Outcome measures were a composite endpoint of all-cause death, new MI or stroke, as well as its individual components at 1, 2, and 7 years, and cardiac death at 1 and 2 years. In multivariable Cox regression analysis, quartiles of P1NP were significantly associated with the composite endpoint at 1 year of follow-up with a hazard ratio for Q4 of 1.82 (95% CI, 1.12–2.98). There was no other significant association with outcomes at any time points.ConclusionP1NP was found to be an independent biomarker significantly associated with adverse clinical outcome at one year in patients admitted to hospital for acute chest pain of suspected coronary origin. This is the first report in the literature on the prognostic value of P1NP in this clinical setting.Clinicaltrials.ygov IdentifierNCT00521976

Suggested Cut-Off Values for Vitamin D as a Risk Marker for Total and Cardiac Death in Patients with Suspected Acute Coronary Syndrome

Background: Several studies have demonstrated an association between low vitamin D levels and cardiovascular risk. Vitamin D cut-off levels are still under debate.Objectives: To assess two cut-off levels, 40 and 70 nmol/L, respectively, for vitamin D measured as 25-hydroxyvitamin D in chest pain patients with suspected acute coronary syndrome.Methods: We investigated 1853 patients from coastal-Norway and inland NorthernArgentina. A similar database was used for pooling of data. Two-year follow-up data including all-cause mortality, cardiac death, and sudden cardiac death in the total patient population were analyzed, applying univariate and multivariable analysis.Results: Two hundred fifty-five patients with known vitamin D concentrations died. In the multivariable analysis, there was a decrease in total mortality above a cut-off level of 40 nmol/L and a decrease in cardiac death above a cut-off level of 70 nmol/L [HRs of 0.66 (95% CI, 0.50?0.88), p = 0.004 and 0.46 (95% CI, 0.22?0.94), p = 0.034, respectively].Conclusion: Vitamin D cut-off levels of 40 and 70 nmol/L were related to total mortality and cardiac death, respectively.Fil: Naesgaard, Patrycja A.. Stavanger University Hospital; Noruega. University Of Bergen; NoruegaFil: Leon de la Fuente, Ricardo Alfonso. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Stavanger University Hospital; Noruega. University Of Bergen; Noruega. Universidad Católica de Salta; ArgentinaFil: Nilsen, Stein Tore. Stavanger University Hospital; Noruega. University Of Bergen; NoruegaFil: Pönitz, Volker. Stavanger University Hospital; NoruegaFil: Brügger Andersen, Trygve. Stavanger University Hospital; NoruegaFil: Grundt, Heidi. University Of Bergen; Noruega. Stavanger University Hospital; NoruegaFil: Staines, Harry. Sigma Statistical Services; Reino UnidoFil: Nilsen, Dennis W. T.. Stavanger University Hospital; Noruega. University Of Bergen; Norueg

Borderline Values of Troponin-T and High Sensitivity C-Reactive Protein Did Not Predict 2-Year Mortality in TnT Positive Chest-Pain Patients, Whereas Brain Natriuretic Peptide Did

Background: Troponin-T (TnT), high-sensitive C-reactive protein (hsCRP), and Brain Natriuretic Peptide (BNP) have been shown to be independent prognostic indicators of total and cardiac death during short- and long-term follow-up. Methods: We investigated prospectively the prognostic value of admission samples of TnT, hsCRP, and BNP in 871 chest-pain patients from South-Western Norway and 982 patients from Northern Argentina, based on a similar protocol and database setup. Follow-up was 2 years for the pooled population. The prognostic value of the selected biomarkers was investigated in quartiles of 239 patients with TnT values greater than 0.01 and up to and including 0.1 ng/mL, with continuous TnT as a potential confounder. Results: After 24 months, 69 patients had died, of whom 38 died from cardiac causes. In the selected range of TnT, this biomarker was not significantly different between patients who died and survived (mean 0.0452 and 0.0457, p = 0.887). The BNP levels were significantly higher among patients dying than in long-term survivors [340 (142–656) versus 157 (58–367) pg/mL (median, 25 and 75% percentiles), p < 0.001]. In a multivariable Cox regression model for death within 2 years, the hazard ratio (HR) for BNP in the highest quartile (Q4) as compared to the lowest (Q1) was significantly related to total mortality [HR 2.84 (95% confidence interval (CI), 1.13–7.17)], p = 0.027, in addition to age (p ≤ 0.001) and hypercholesterolemia (p = 0.043). For cardiac death, the HR for BNP was 5.18 (95% CI, 1.06–25.3), p = 0.042. Several other variables (age, congestive heart failure, ST elevation myocardial infarction, and study country) were also significantly related to cardiac death. In a multivariable Cox regression model, hsCRP rendered no significant prognostic information for all-cause mortality (p = 0.089) or for cardiac mortality (p = 0.524). Conclusion: In patients with borderline TnT values (greater than 0.01 and up to and including 0.1 ng/mL), this biomarker as well as hsCRP did not render prognostic information, whereas BNP was found to be a strong prognostic indicator of 2-year total and cardiac mortality.Fil: Nilsen, Dennis W. T.. Stavanger University Hospital; Noruega. University Of Bergen; NoruegaFil: Mjelva, Øistein Rønneberg. University Of Bergen; Noruega. Stavanger University Hospital; NoruegaFil: Leon de la Fuente, Ricardo Alfonso. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Católica de Salta; ArgentinaFil: Naesgaard, Patrycja. Stavanger University Hospital; Noruega. University Of Bergen; NoruegaFil: Pönitz, Volker. Stavanger University Hospital; NoruegaFil: Brügger Andersen, Trygve. Stavanger University Hospital; NoruegaFil: Grundt, Heidi. University Of Bergen; Noruega. Stavanger University Hospital; NoruegaFil: Staines, Harry. Sigma Statistical Service; NoruegaFil: Nilsen, Stein Tore. University Of Bergen; Norueg

A history of late and very late stent thrombosis is not associated with increased activation of the contact system, a case control study

Abstract Background The pathophysiological pathways resulting in Late Stent Thrombosis (LST) remain uncertain. Findings from animal studies indicate a role of the intrinsic coagulation pathway in arterial thrombus formation, while clinical studies support an association with ischemic cardiovascular disease. It is currently unknown whether differences in the state of the contact system might contribute to the risk of LST or Very Late Stent Thrombosis (VLST). We assessed the relation between levels of several components involved in the contact system and a history of LST and VLST, termed (V)LST in a cohort of 20 patients as compared to a matched control group treated with PCI. Methods and Results Activated factor XII (FXIIa), FXII zymogen (FXII), FXIIa-C1-esterase inhibitor (C1-inhibitor), Kallikrein-C1-inhibitor, FXIa-C1-inhibitor and FXIa-α1-antitrypsin (AT-inhibitor) complexes were measured by Enzyme-linked immunosorbent assy (ELISA) methodology. Cases and controls showed similar distributions in sex, age, baseline medications and stent type. Patients with a history of (V)LST had a significantly greater stent burden and a higher number of previous myocardial infarctions than the control patients. There were no significant between-group differences in the plasma levels of the components of the contact system. Conclusion In a cohort of patients with a history of (V)LST, we did not observe differences in the activation state of the intrinsic coagulation system as compared to patients with a history of percutaneous coronary intervention without stent thrombosis.</p

B-type natriuretic peptide is a long-term predictor of all-cause mortality, whereas high-sensitive C-reactive protein predicts recurrent short-term troponin T positive cardiac events in chest pain patients: a prognostic study

<p>Abstract</p> <p>Background</p> <p>Few studies have addressed whether the combined use of B-type natriuretic peptide (BNP) and high-sensitive C-reactive protein (hsCRP) improves risk stratification for mortality and cardiovascular events in a population with chest pain and suspected acute coronary syndromes (ACS). Therefore, we wanted to assess the incremental prognostic value of these biomarkers with respect to long-term all-cause mortality and recurrent troponin T (TnT) positive cardiac events in 871 patients admitted to the emergency department.</p> <p>Methods</p> <p>Blood samples were obtained immediately following admission.</p> <p>Results</p> <p>After a follow-up period of 24 months, 129 patients had died. The BNP levels were significantly higher among patients dying than in long-term survivors (401 (145–736) versus 75 (29–235) pq/mL [median, 25 and 75% percentiles], p = 0.000). In a multivariable Cox regression model for death within 2 years, the hazard ratio (HR) for BNP in the highest quartile (Q4) was 5.13 (95% confidence interval (CI), 1.97–13.38) compared to the lowest quartile (Q1) and was associated with all-cause mortality above and beyond age, congestive heart failure and the index diagnosis ST-segment elevation myocardial infarction. HsCRP rendered no prognostic information for all-cause mortality. However, within 30 days, the adjusted HR for patients with recurrent TnT cardiac positive events hsCRP in Q4 was 14.79 (95% CI, 1.89–115.63) compared with Q1 and was associated with recurrent ischemic events above and beyond age, hypercholesterolemia and TnT values at admission.</p> <p>Conclusion</p> <p>BNP may act as a clinically useful biomarker when obtained at admission in an unselected patient population following hospitalization with chest pain and potential ACS, and may provide complementary prognostic information to established risk determinants at long-term follow-up. Our data do not support the hypothesis that the additional assessment of hsCRP will lead to better risk stratification for survival than BNP alone.</p> <p>Trial registration</p> <p>NCT00521976</p