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Platelet reactivity and comorbidities in acute coronary syndrome
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)Alternative title
Trombocytreaktivitet och komorbiditet vid akut koronart syndrom (Swedish)
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 [en]
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: urn:nbn:se:umu:diva-51096ISBN: 978-91-7459-361-7 (print)OAI: oai:DiVA.org:umu-51096DiVA: diva2:475151
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
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. Association of level of kidney function and platelet aggregation in acute myocardial infarction
Open this publication in new window or tab >>Association of level of kidney function and platelet aggregation in acute myocardial infarction
2009 (English)In: American Journal of Kidney Diseases, ISSN 0272-6386, E-ISSN 1523-6838, Vol. 54, no 2, 262-269 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Decreased kidney function has been established as an important risk factor in patients presenting with acute coronary syndrome. In acute coronary syndrome, increased platelet aggregation is associated with vascular complications. The aim of this study is to examine whether decreased kidney function is associated with altered platelet function in patients presenting with acute myocardial infarction. STUDY DESIGN: Prospective cohort.

SETTING & PARTICIPANTS: 413 patients presenting with acute myocardial infarction admitted to the cardiac intensive care unit at Ostersund Hospital, Ostersund, Sweden.

PREDICTORS: Glomerular filtration rate less than 60 mL/min/1.73 m(2) estimated from serum cystatin C level, comorbidity, medications, and markers of inflammation and hemostasis.

OUTCOMES & MEASUREMENTS: Platelet aggregation was assessed by measuring the formation of small platelet aggregates (SPAs) by using a laser light scattering method. A greater SPA level indicates greater platelet aggregation. Platelet aggregation analysis was performed on days 1, 2, 3, and 5 in-hospital. RESULTS: We observed a significant increase in platelet aggregation during the first 3 days in the hospital regardless of kidney function (P < 0.001). Platelet aggregation was more pronounced in patients with estimated glomerular filtration rate less than 60 mL/min/1.73 m(2) on day 2 (SPA count, 65,000 versus 47,000; P = 0.01) and day 3 (SPA count, 77,000 versus 52,000; P = 0.02). In a multiple linear regression analysis, decreased kidney function was no longer significantly associated with increased platelet aggregation. Older age, greater plasma fibrinogen level, and diabetes mellitus were associated with increased platelet aggregation in the multivariable model.

LIMITATIONS: During the study period, 78 patients presenting with acute myocardial infarction were not eligible for inclusion. Differences in treatment with antiplatelet medication between the 2 groups might have affected our findings.

CONCLUSIONS: Platelet aggregation increases during the first days after acute myocardial infarction regardless of kidney function. There is no difference in platelet aggregation in patients according to level of kidney function.

Keyword
Platelet aggregation; myocardial infarction; chronic kidney disease
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-32936 (URN)10.1053/j.ajkd.2009.04.023 (DOI)19560852 (PubMedID)
Available from: 2010-03-31 Created: 2010-03-31 Last updated: 2017-12-12Bibliographically approved
4. Prognostic impact of admisson level and dynamic change of cystatin C during an acute myocardial infarction
Open this publication in new window or tab >>Prognostic impact of admisson level and dynamic change of cystatin C during an acute myocardial infarction
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Introduction: Impaired kidney function has emerged as an important risk factor for developing cardiovascular disease. The level of kidney function is also associated with outcome following an acute coronary syndrome. Acute kidney injury during hospitalisation for an acute coronary syndrome has been associated with worsened prognosis. The aim of this study was to investigate the prognostic impact of kidney function on admission and sign of worsening kidney function during hospitalisation as measured by levels of cystatin C.

Materials and methods: Five hundred and thirty-four patients admitted for an acute myocardial infarction were included. Cystatin C and other biochemical markers were obtained on day 1, 2, 3 and 5 depending on length of hospital stay.

Results:  At a median follow-up of 2.9 years, the endpoint (death) had occurred in 176 (33%) patients. High admission level of cystatin C was independently associated with increased risk of death, at a hazard ratio of 1.62 (95% CI 1.28-2.03). The maximum recorded difference between levels of cystatin C in-hospital, were independently associated with outcome in patients with estimated glomerular filtration rate on admission>60 ml/(min*1.73m²). Hazard ratio for death at follow-up were 10.14 (95% CI 3.44-29.92) in this patient group.

Conclusion: Level of kidney function on admission, as estimated by serum level of cystatin C, is independently associated with death at long-term follow up. In patients without chronic kidney disease, changing levels of cystatin C during admission for an AMI, have a strong impact on long-term prognosis. We found no additional information provided by dynamic changes in cystatin C, besides established predictors, in patients with chronic kidney disease.

Keyword
myocardial infarction, cystatin C, acute kidney injury, chronic kidney disease
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:umu:diva-51094 (URN)
Available from: 2012-01-10 Created: 2012-01-10 Last updated: 2016-05-23Bibliographically approved

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