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Platelet aggregation and aspirin non-responsiveness increase when an acute coronary syndrome is complicated by an infection
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. (Kardiologi)
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.

Place, publisher, year, edition, pages
2007. Vol. 5, no 3, 507-511 p.
Keyword [en]
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: urn:nbn:se:umu:diva-16344DOI: 10.1111/j.1538-7836.2007.02378.xPubMedID: 17319905OAI: oai:DiVA.org:umu-16344DiVA: diva2:156017
Available from: 2007-09-12 Created: 2007-09-12 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Inflammation, platelet aggregation and prognosis in acute myocardial infarction
Open this publication in new window or tab >>Inflammation, platelet aggregation and prognosis in acute myocardial infarction
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.

Publisher
49 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1343
Keyword
Myocardial infarction, C-reactive protein, platelet aggregation, prognosis
National Category
Cardiac and Cardiovascular Systems
Research subject
Medicine
Identifiers
urn:nbn:se:umu:diva-32519 (URN)978-91-7264-845-6 (ISBN)
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
2. Platelet reactivity and comorbidities in acute coronary syndrome
Open this publication in new window or tab >>Platelet reactivity and comorbidities in acute coronary syndrome
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Trombocytreaktivitet och komorbiditet vid akut koronart syndrom
Abstract [en]

Background In the event of an acute coronary syndrome (ACS), the risk of death and complications such as stroke and re-infarction is high during the first month. Diabetes, impaired kidney function, elevated markers of systemic inflammation and high level of platelet reactivity have all been associated with worsened prognosis in ACS patients. Impaired kidney function is a condition with high cardiovascular morbidity and there is an established association between level of kidney function and outcome in the event of an ACS.

Aims We sought to investigate the level of platelet reactivity during the first days of an ACS and specifically the level of platelet reactivity in patients with different conditions associated with worsened prognosis in the event of an ACS. We also wanted to investigate the prognostic impact of baseline levels of cystatin C as well as the importance of decreasing kidney function during the first days of an ACS.

Methods We included 1028 unselected patients with ACS or suspected ACS during the years 2002 and 2003, of which 534 were diagnosed with an acute myocardial infarction (AMI). Blood samples for measuring platelet aggregation, cystatin C levels and other clinically important biomarkers were collected day 1, 2, 3 and 5 following admission.

Platelet reactivity was measured using 2 different methods. Platelet aggregation was measured using Pa-200, a particle count method, based on scattering of laser light. PFA 100 is a method of measuring primary hemostasis in whole blood.

Results

Platelet aggregation and comorbidities.

We found an increase in platelet aggregation when an ACS was complicated by an infection and there was an increased frequency of aspirin non-responsiveness in patients suffering from pneumonia during the first days of an ACS. Furthermore, we found an independent association between levels of C-reactive protein and platelet aggregation.

During the first 3 days following an acute myocardial infarction, platelet aggregation increased despite treatment with anti-platelet agents.

Platelet aggregation was found to be more pronounced in patients with diabetes.

Patients with impaired kidney function, showed increased platelet aggregation compared to patients with normal renal function, however, this difference was explained by older age, higher prevalence of DM and levels of inflammatory biomarkers. We found no independent association between chronic kidney disease (CKD) and levels of platelet aggregation.

Kidney function and outcome

Serum levels of cystatin C on admission had an independent association with outcome following an acute myocardial infarction. With a mean follow-up time of 2.9 years, the adjusted HR for death was 1.62 (95% CI 1.28-2.03; p<0.001) for each unit of increase in cystatin C on admission.

The level of dynamic changes in cystatin C during admission for an acute myocardial infarction was independently associated with prognosis in patients with normal or mild impairment of renal function. The adjusted HR for death was 10.1 (95% CI 3.4-29.9; p<0.001).

Conclusion In patients suffering from an AMI platelet aggregation increases during the first days, despite anti-platelet treatment. Diabetes, age and biomarkers of inflammation are independently associated with platelet aggregation.

Admission levels of cystatin C as well as changes in cystatin C levels during hospitalisation are independently associated with outcome.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2012. 53 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1477
Keyword
acute coronary syndrome, myocardial infarction, platelet reactivity, platelet aggregation, Inflammation, infection, diabetes mellitus, chronic kidney disease, acute kidney injury
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:umu:diva-51096 (URN)978-91-7459-361-7 (ISBN)
Public defence
2012-02-17, Hörsalen, Östersunds Sjukhus, Östersund, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2012-01-27 Created: 2012-01-10 Last updated: 2012-01-27Bibliographically approved

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