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Inflammation, platelet aggregation and prognosis in acute myocardial infarction
Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The incidence of stroke and re-infarction is noticeably high in the first few days following acute myocardial infarction. This finding has raised questions whether the systemic inflammatory reaction secondary to myocardial necrosis is involved. The inflammation might affect the activation of platelets leading to insufficient effect of the antiplatelet treatment given. Furthermore, the importance of platelet reactivity and inflammation in terms of long-term prognosis is not fully understood. The prognostic importance of C-reactive protein (CRP) in relation to clinical variables also needs to be clarified.

The present studies are aimed at describing the dynamics of platelet function during the first days of an acute myocardial infarction, in relation to diabetes and inflammation. We also investigated whether increased platelet reactivity or the increased concentration of CRP in blood were related to a worse outcome. Finally, we examined if CRP levels contributed to a predictive model using clinical variables known to affect outcome in patients with AMI.

 We used two novel platelet function tests to measure platelet reactivity; the PA-200 (a laser light aggregometer) and the PFA-100 (measures primary haemostasis in whole blood).

Platelet aggregation increased during the initial course of an acute myocardial infarction. The increase in platelet aggregation was most pronounced in diabetics and in patients showing higher systemic inflammatory reaction, assessed by measuring the concentration of CRP in blood. The pronounced platelet aggregation occurred despite ongoing antiplatelet and antithrombotic treatment.

There was a significant association between the levels of CRP and the degree of platelet reactivity. However, while the CRP levels were associated with a worse outcome (AMI, stroke and death), the results of the platelet function tests were not. The importance of CRP in predicting prognosis depended on which adjustments were made for confounding factors.

CRP and prognostic variables in a statistical model predicting death, however, showed that CRP was excluded. Thus CRP did not predict outcome beyond clinical prognostic variables.

The results of these studies reinforce the importance of clinical variables such as heart failure, age, atrial fibrillation, smoking status, diabetes and impaired kidney function - all of which were associated with worse prognosis in multivariable analysis.

Place, publisher, year, edition, pages
2010. , 49 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1343
Keyword [en]
Myocardial infarction, C-reactive protein, platelet aggregation, prognosis
National Category
Cardiac and Cardiovascular Systems
Research subject
Medicine
Identifiers
URN: urn:nbn:se:umu:diva-32519ISBN: 978-91-7264-845-6 (print)OAI: oai:DiVA.org:umu-32519DiVA: diva2:303983
Public defence
2010-04-29, Sal B, 9 trappor, By 1D, Tandläkarhögskolan, Umeå universitets sjukhus, Umeå, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2010-03-19 Created: 2010-03-16 Last updated: 2010-03-19Bibliographically approved
List of papers
1. Platelet aggregation and aspirin non-responsiveness increase when an acute coronary syndrome is complicated by an infection
Open this publication in new window or tab >>Platelet aggregation and aspirin non-responsiveness increase when an acute coronary syndrome is complicated by an infection
2007 (English)In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 5, no 3, 507-511 p.Article in journal (Refereed) Published
Abstract [en]

Background: Epidemiologic studies have shown that there is an association between acute respiratory infection and acute coronary syndrome. The aim of this study was to analyze the thrombotic risk, assessed by platelet aggregation and aspirin non-responsiveness, in patients with an acute coronary syndrome complicated by an infection.

Methods: Patients with an acute coronary syndrome who were admitted to the intensive care unit and hospitalized for at least 3 days in 2002 and 2003 were eligible for the study. Three hundred and fifty-eight patients were included, of whom 66 had an infection during their hospital stay. Platelet aggregation was analyzed by an aggregometer using laser light (PA-200, laser light scattering). Aspirin non-responsiveness was defined as a closure time of ≤193 s measured by PFA-100.

Results: Platelet aggregation was more pronounced during an infectious complication (P < 0.001). The subgroups of patients with persistent fever, urinary tract infection, and pneumonia all had a higher level of aggregates than the group of patients without an infection (P = 0.007, P = 0.04, and P = 0.01, respectively). Aspirin non-responsiveness was more frequent in the group of subjects with pneumonia compared with those without an infection, 90% vs. 46% (P = 0.006). The CRP levels were independently associated with platelet aggregation and aspirin non-responsiveness (P < 0.001, P < 0.001, respectively).

Conclusion: An infectious complication during the course of an acute coronary syndrome leads to more pronounced platelet aggregation. Aspirin non-responsiveness is more frequent in severe infections, such as pneumonia. CRP is an independent predictor of platelet aggregation and aspirin non-responsiveness in the setting of an acute coronary syndrome.

Keyword
Acute Disease, Aged, Aged; 80 and over, Aspirin/pharmacology/*therapeutic use, Biological Markers/blood, C-Reactive Protein/metabolism, Drug Resistance, Female, Humans, Linear Models, Male, Middle Aged, Myocardial Ischemia/blood/complications/*drug therapy, Platelet Aggregation/*drug effects, Platelet Aggregation Inhibitors/pharmacology/*therapeutic use, Platelet Function Tests, Pneumonia/blood/*complications, Predictive Value of Tests, Prognosis, Risk Assessment, Severity of Illness Index, Syndrome, Thrombosis/blood/etiology/*prevention & control, Treatment Failure, Urinary Tract Infections/blood/*complications
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-16344 (URN)10.1111/j.1538-7836.2007.02378.x (DOI)17319905 (PubMedID)
Available from: 2007-09-12 Created: 2007-09-12 Last updated: 2017-12-14Bibliographically approved
2. Dynamics of platelet activation in diabetic and non-diabetic subjects during the course of an acute myocardial infarction
Open this publication in new window or tab >>Dynamics of platelet activation in diabetic and non-diabetic subjects during the course of an acute myocardial infarction
2007 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 121, no 2, 269-273 p.Article in journal (Refereed) Published
Abstract [en]

Introduction

The dynamics of platelet activation during the course of a myocardial infarction is unknown but of great importance in terms of risk assessment and anti-thrombotic therapy. The aim of the present study was sequentially to analyse platelet activation in diabetic and non-diabetic subjects with an acute myocardial infarction.

Materials and methods

We used a sensitive laser light scattering technique to assess platelet aggregation as a measure of activation. Measurements were made on the first, second, third and fifth day in-hospital. Two hundred and forty-three patients with an acute myocardial infarction, of whom 48 had diabetes, were included.

Results

Platelet activation increased until the third in-hospital day in both diabetic and non-diabetic subjects, despite intense anti-thrombotic therapy. The activation was more pronounced in diabetic subjects from the time of hospital admission. Platelet activation tended to decrease after the third in-hospital day.

Conclusions

We conclude that platelet activation increases rapidly at the onset of a myocardial infarction, despite aggressive anti-thrombotic treatment. The activation is more pronounced in diabetic subjects and tends to decrease within a few days. More targeted and effective anti-platelet therapy has the potential further to reduce cardiac and cerebral ischemic events following myocardial infarction and ongoing clinical trials are addressing this issue.

Keyword
Myocardial infarction; Diabetes mellitus; Platelet aggregation; Antiplatelet agents
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-16345 (URN)10.1016/j.thromres.2007.04.011 (DOI)17543372 (PubMedID)
Available from: 2007-09-12 Created: 2007-09-12 Last updated: 2017-12-14Bibliographically approved
3. The impact of platelet function or C-reactive protein, on cardiovascular events after an acute myocardial infarction
Open this publication in new window or tab >>The impact of platelet function or C-reactive protein, on cardiovascular events after an acute myocardial infarction
2009 (English)In: Thrombosis Journal, ISSN 1477-9560, E-ISSN 1477-9560, Vol. 7, no 12Article in journal (Refereed) Published
Abstract [en]

Background Recurrent cardiovascular events following acute myocardial infarction (AMI) are common. The purpose of this study was to evaluate the impact of platelet aggregation, PFA-100 closure times and peak C-reactive protein (CRP), respectively, on the occurrence of death, myocardial infarction and ischemic cerebral events after an AMI. Furthermore, to examine the relationship between the platelet function tests and peak CRP.

Methods Three hundred and thirty-four patients with AMI were included in the study. Platelet aggregation was analyzed by an aggregometer using laser light (PA-200). The state of high residual platelet reactivity was defined as normal closure times (PFA-100) during treatment with antiplatelet and antithrombotic drugs.

Results The fourth quartile of peak CRP was associated with poorer outcome as compared to the first quartile in a multivariate Cox-regression analysis, with a hazard ratio of 2.0 (95% CI 1.1-3.7) for the occurrence of death, myocardial infarction and ischemic cerebral events. The fourth quartile of peak CRP (>64.6 mg/l) was associated with platelet aggregation (p < 0.001, adjusted R² = 0.13) and high residual platelet reactivity, in a multivariable model, with an odds ratio of 2.9 (CI 95% 1.3-6.8), as compared to the first quartile. Neither the highest quartile of platelet aggregation nor the state of high residual platelet reactivity predicted new cardiovascular events.

Conclusions In patients with myocardial infarction, measured peak CRP is associated with new cardiovascular events. Despite an association with peak CRP neither more pronounced platelet aggregation nor PFA-100 closure times independently predict new cardiovascular events.

Place, publisher, year, edition, pages
BioMed Central, 2009
Keyword
C-reactive protein, Myocardial infarction, Platelets, Aggregation, PFA-100, Outcome
National Category
Cardiac and Cardiovascular Systems
Research subject
Medicine
Identifiers
urn:nbn:se:umu:diva-31869 (URN)10.1186/1477-9560-7-12 (DOI)19583836 (PubMedID)
Projects
Inflammation, platelet aggregation and prognosis after acute myocardial infarction
Available from: 2010-03-08 Created: 2010-02-19 Last updated: 2017-12-12Bibliographically approved
4. Prognosis after acute myocardial infarction as predicted by CRP and clinical variables
Open this publication in new window or tab >>Prognosis after acute myocardial infarction as predicted by CRP and clinical variables
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Objective. Raised concentrations of C-reactive protein (CRP) have been reported to be strongly related to an adverse long term prognosis in patients with acute myocardial infarction (AMI). However, adjustments for possible confounders have often been incomplete. Thus the clinical usefulness of CRP to predict long term survival in absolute figures has not been clarified. The aims of this study were to examine the predictive value of baseline concentrations of CRP for mortality after adjustment for the most important clinical variables and to compare the clinical usefulness of CRP with easily available clinical variables in the prediction of long term survival.

Design. Five hundred and thirty-one patients with AMI were included. A blood sample for CRP was obtained on admission. All patients were followed for a minimum of two years and death of any cause was recorded as the study end point.

Results. In logistic regression analysis the interaction term age by Killip class > 1 and the variables glomerular filtration rate, intervention and atrial fibrillation were retained. The resulting model correctly predicted death or not in 82% of the patients. CRP did not contribute to the final model.

Conclusions. An elevated C-reactive protein concentration is reported to be associated with death in patients with AMI, but the association is absent after adjustment for an important interaction among the variables in the model. CRP has no value beyond clinical variables in predicting death after AMI.

Keyword
C-reactive protein, Myocardial infarction, Prognosis, Death
National Category
Cardiac and Cardiovascular Systems
Research subject
Medicine
Identifiers
urn:nbn:se:umu:diva-32518 (URN)
Available from: 2010-03-16 Created: 2010-03-16 Last updated: 2016-05-23Bibliographically approved

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