MACCE in Hospitalized Patients With Community-acquired Pneumonia

Study Overview
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Brief Summary
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Community-acquired pneumonia is the most common infection leading to hospitalization in intensive care units and the most common cause of death associated with infection disease. Epidemiological studies have shown that respiratory tract infections are associated with an increased risk for the development of acute cardiovascular and cerebrovascular events. This link is further supported by studies indicating that influenza vaccination is associated with a reduced risk of hospitalization for pneumonia as well as heart disease and cerebrovascular disease. Data connecting acute respiratory tract infections and cardiovascular events stem almost exclusively from cross-sectional or retrospective studies. Thus the real incidence and the prognostic impact of AMI, as well as the pathophysiological relationship between pneumonia and cardiovascular damage is still elusive. Inflammation plays a major role in the pathogenesis of coronary artery disease. The increased concentrations of proinflammatory cytokines together with the activation of coagulation, the down-regulation of anticoagulant mechanisms and the enhanced platelet aggregation may trigger atheroma's instability, plaque rupture and thrombus formation. Inflammation and coagulopathy are also considered universal host responses to infection in patients with severe sepsis. Thus far limited data are available on the changes in these high regulated systems, together with platelet activity in patients with CAP and their potential relationship with cardiovascular risk. This project will consist in a prospective multicenter study to investigate the incidence of major adverse cardiac and cerebrovascular events (MACCE) in hospitalized patients with CAP, its prognostic relevance and the potential relationship between enhanced cardiovascular risk and the activation of inflammation, coagulation and platelet aggregation in this setting.

Detailed Description
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Community-acquired pneumonia (CAP) is the most common infection leading to hospitalization in intensive care units and the most common cause of death associated with infection disease. Epidemiological studies have shown that respiratory tract infections are associated with an increased risk for the development of acute cardiovascular and cerebrovascular events. This link is further supported by studies indicating that influenza vaccination is associated with a reduced risk of hospitalization for pneumonia as well as heart disease, cerebrovascular disease and the risk of death from all causes during influenza seasons in elderly. Data connecting acute respiratory tract infections and cardiovascular events stemmed almost exclusively from cross-sectional or retrospective studies and the pathophysiological relationship between pneumonia and cardiovascular damage is still elusive. The first aim of the study will be to analyze the prevalence of major adverse cardiac and cerebrovascular events (MACCE) in patients hospitalized for CAP, followed up for two years after hospitalization. During hospitalization myocardial damage will be strictly monitored by measuring cardiac troponins until discharge. Cardiac troponins are established markers of myocardial damage. Cardiac troponin elevation is seen not only in the setting of acute coronary syndromes but also in a variety of conditions not directly related to flow-limiting coronary stenosis or occlusion of the coronary arteries, such as pulmonary embolism, sepsis, heart failure and stroke. In these settings, it is well documented that elevated circulating levels of troponins are associated with poor prognosis, regardless of underlying disease. Sparse information exists concerning the significance of troponin elevation during respiratory tract infections. Most of the studies investigated the role of troponin elevation in patients admitted in hospital for acutely exacerbated chronic obstructive pulmonary disease (COPD); only a recent study investigates specifically CAP, showing a correlation between troponin elevation and oxygenation impairment; however, the underlying mechanism was not explored. Inflammation plays a major role in the pathogenesis of coronary artery disease. The increased concentrations of proinflammatory cytokines together with the activation of coagulation, the down-regulation of anticoagulant mechanisms and the enhanced platelet aggregation may trigger atheroma's instability, plaque rupture and thrombus formation. Systemic coagulation abnormalities including clotting activation and inhibition of anticoagulant factors have been observed in patients with severe sepsis; in patients with CAP similar changes have been detected only in the lung compartment. Changes of clotting system activation are of potential relevance as they could elicit myocardial damage with several mechanisms including coronary ischemia and/or direct inflammation of cardiac cells. Concerning this last point it is of interest that Protein C, an anticoagulant factor with anti-inflammatory property, is reduced in severe sepsis where it correlates with disease severity and mortality. Accordingly, infusion of recombinant human activated Protein C improves survival of patients with severe sepsis due to pneumococcal pneumonia. Until now no data exists about the behavior of Protein C in patients with CAP and its interplay with myocardial damage. Moreover no data on platelet reactivity and activation during pneumonia exist. Very limited data is only available on common viral respiratory tract infections in which enhanced platelet reactivity has been shown. The investigators speculated that inhibition of Protein C as well as enhanced platelet activity may be implicated in myocardial damage in patients with CAP. Therefore the investigators will perform a prospective study to investigate whether this relationship exist. Data obtained could have important clinical consequences: new therapeutic strategies targeting these systems could prevent myocardial damage and eventually MACCEs in these patients.

Official Title
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Major Adverse Cardiac and Cerebrovascular Events in Hospitalized Patients With Community-acquired Pneumonia

Conditions
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Community-acquired Pneumonia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: community-acquired pneumonia Exclusion Criteria: presence of immunosuppression (HIV infection, high dose of immunosuppressive agents such as prednisone, chemotherapy); presence of malignancy; pregnancy or breast feeding; health care-associated pneumonia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 95 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet activation, clotting abnormalities, myocardial damage and inflammation in CAP patients | Platelet and serum thromboxane, F2-isoprostanes, NOX2-activation, serum high-sensitivity cardiac troponin T, protein C and protein S at hospital admission and at hospital discharge | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major adverse cardiac and cerebrovascular events | Major adverse cardiac and cerebrovascular events will be assessed during hospitalization and during the follow-up | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Community-acquired pneumonia, Acute myocardial infarction, Platelet activation, Coagulation abnormalities,, Thrombosis, Isoprosantes, NADPH oxidase, Major adverse cardiac and cerebrovascular events