Ignite Creation Date:
2024-10-26 @ 3:35 PM
Last Modification Date:
2024-10-26 @ 3:35 PM
Study NCT ID:
NCT06513611
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-07-16
Brief Title:
Cellular Immunity Neuroendocrine and Inflammatory Factors for Clinical Prognosis in Acute Coronary Syndrome
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Identificación de la relación Entre Componentes de la Inmunidad Celular y Factores Inflamatorios y neuroendócrinos Como Determinantes Del pronóstico clínico en el síndrome Coronario Agudo
Status:
RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
In acute coronary syndrome ACS there is an increase in cortisol levels as an expression of the stress response and C-reactive protein as an expression of the inflammatory response which are in turn associated with changes in the components of cellular immunity and ultimately are predictors of clinical events The objective of this study is to demonstrate that within the frame of reference of ACS beyond the thrombotic phenomenon that leads to ischemia and myocardial necrosis there is an activation of an inflammatory and stress response evidenced by an elevation of CRP and cortisol respectively and sequentially modifications in the components of cellular immunity in peripheral blood that convey prognostic value during hospitalization and after discharge A prospective observational analytical unicentric study of consecutive patients with ACS with telephone follow-up to 6 months will be carried out For 2 years all eligible patients admitted with a diagnosis of ACS to the Coronary Care Unit of the Hospital de Clínicas José de San Martín in Buenos Aires will be registered consecutively
Detailed Description:
Introduction According to data from the World Health Organization cardiovascular disease is the leading cause of death worldwide It is estimated that in 2015 18 million people died from this cause representing 31 of all deaths recorded globally The majority of these deaths 74 million were due to coronary heart disease Additionally cardiovascular disease represents the highest burden of disease defined by disability-adjusted life years DALY with 4800 DALY per 100000 inhabitants
From a clinical perspective the topic that concerns us within cardiovascular disease is acute coronary syndrome ACS which refers to a group of signs and symptoms compatible with acute myocardial ischemia In this context for decades to optimize diagnosis and provide timely treatment ACS has been subclassified into acute myocardial infarction with STEMI and without ST-segment elevation NSTEMI and unstable angina UA
Among the broad spectrum of ACS the least severe form is UA where symptoms suggest myocardial ischemia but there is no biochemical evidence of myocardial infarction At the other extreme is acute myocardial infarction whose clinical definition is based on the presence of acute myocardial damage detected by the elevation of cardiac biomarkers troponin in the context of evidence of acute myocardial ischemia It is classified into five types with type 1 caused by atherothrombotic coronary disease being the focus of this study This type is often precipitated by the rupture or erosion of an atherosclerotic plaque
Background and Rationale Years of exhaustive clinical research have resulted in therapies that reduced mortality and complication rates of ACS ranging from the creation of the Coronary Care Unit anticoagulation therapies beta-blockers renin-angiotensin-aldosterone system inhibitors antiplatelet therapies to reperfusion whether mechanical or pharmacological However in recent years we have not been able to make a qualitative leap in the pathophysiological approach to coronary disease to create new paradigms in therapeutics Thus it is imperative to seek new horizons new pathophysiological hypotheses addressing topics such as inflammation immune response immunothrombosis and stress response in the context of ACS
It is undeniable that inflammation and stress are risk factors for developing ACS Additionally ACS triggers both an acute inflammatory response and a stress response with cortisol being one of the main effectors of the latter possessing anti-inflammatory effects However we currently lack a deep understanding of the mechanisms governing this interesting dialogue between inflammation and stress in the context of ACS Some authors have described that a higher degree of inflammation is associated with worse outcomes in ACS patients Recently we described that this poor outcome is related to plasma cortisol levels
We know that stress has complex effects on the immune system influencing both innate and adaptive immunity Glucocorticoids and catecholamines in the acute phase of the stress response can influence the trafficking andor function of leukocytes neutrophil demargination induce a systemic shift from a TH1 cellular immunity to a TH2 humoral immunity response Additionally acute stress can increase circulating pro-inflammatory cytokine levels such as IL-6 IL-1b and C-reactive protein CRP
This bidirectional interaction between stress response effectors and the immune system is evident as pro-inflammatory cytokines stimulate the stress system at multiple levels including the central and peripheral nervous systems hypothalamus pituitary and adrenal glands increasing glucocorticoid levels
The literature extensively supports the utility of leukocyte indices in ACS One of the most widely used is the neutrophil-to-lymphocyte ratio NLR which has demonstrated its association with the severity of clinical presentation and coronary lesions as well as its ability to predict events during hospitalization and after discharge However we lack studies explaining the mechanisms underlying this index with certainty
We know that exogenous glucocorticoids can cause transient neutrophilia by recruiting the marginal pool and lymphopenia through apoptosis Recently other mechanisms have been proposed that could explain the lymphopenia associated with severe acute stress events linked to transient immunodepression although evidence is scarce Similarly although limited there is interesting information regarding eosinopenia as a prognostic marker in severe acute diseases with studies published on its utility in stroke sepsis and one in ACS We know that exogenous glucocorticoid administration can induce eosinopenia and apoptosis is proposed as one of the mechanisms causing it which is why corticosteroids have been part of the first-line treatment for autoimmune and allergic diseases where these cells play a predominant role
Currently we lack human studies demonstrating the association of these cellular immunity components behavior with stress and inflammation response markers in the context of ACS
Research Objectives and Hypotheses Hypothesis In ACS there is an increase in cortisol levels as an expression of the stress response and CRP as an expression of the inflammatory response associated with changes in cellular immunity components which are predictors of clinical events
Objectives
Describe the leukocyte neutrophil lymphocyte and eosinophil counts and their association with the clinical presentation of ACS patients
Describe the leukocyte neutrophil lymphocyte and eosinophil counts and their association with the presence of heart failure in ACS patients
Describe the leukocyte neutrophil lymphocyte and eosinophil counts and their association with clinical events during hospitalization in ACS patients
Describe the leukocyte neutrophil lymphocyte and eosinophil counts and their association with clinical events post-discharge in ACS patients
Correlate the leukocyte neutrophil lymphocyte and eosinophil counts with maximum levels of high-sensitivity troponin CPK and CPK-MB as expressions of tissue damage in ACS
Correlate the leukocyte neutrophil lymphocyte and eosinophil counts with total serum cortisol levels as a marker of stress response in ACS
Correlate the leukocyte neutrophil lymphocyte and eosinophil counts with CRP levels as a marker of inflammation in ACS
Methodology A prospective observational analytical single-center study will be conducted on successive patients with acute coronary syndrome with a follow-up of 6 months For two years all eligible patients admitted with a diagnosis of ACS to the Coronary Unit of Hospital de Clínicas José de San Martín in Buenos Aires will be successively registered
All included patients will undergo a baseline electrocardiogram and physical examination at admission and appropriate therapeutic measures will be implemented according to their condition as indicated by the treating physician without influence from study protocol inclusion
Demographic and clinical data will be obtained from the medical history Additionally a blood sample will be taken at admission for the measurement of ultra-sensitive CRP and cortisol
During hospitalization the evolution curve of necrosis markers troponin CPK and CPK-MB will be evaluated from admission until the peak is confirmed and the decline begins Total leukocyte lymphocyte and eosinophil counts will be recorded at patient admission
Post-discharge a telephone follow-up will be conducted for 6 months
Sample Size Calculation Considering an event incidence of 20 and an alpha error of 05 and beta error of 05 the number of patients to be included should be equal to or greater than 150
For statistical analysis categorical variables will be presented as frequencies and continuous variables as mean with standard deviation if normally distributed or median with interquartile ranges if not Pearsons chi-square or Fishers exact test and Students t-test or Wilcoxon rank-sum test will be used for comparisons depending on whether variables are categorical or continuous and normally distributed or not Correlations will be assessed using Pearson or Spearman coefficients Intraobserver and interobserver variability will be analyzed using the intraclass correlation coefficient Statistical significance will be set at a two-tailed p-value less than 005 All calculations will be performed using R version 351
From a clinical perspective the topic that concerns us within cardiovascular disease is acute coronary syndrome ACS which refers to a group of signs and symptoms compatible with acute myocardial ischemia In this context for decades to optimize diagnosis and provide timely treatment ACS has been subclassified into acute myocardial infarction with STEMI and without ST-segment elevation NSTEMI and unstable angina UA
Among the broad spectrum of ACS the least severe form is UA where symptoms suggest myocardial ischemia but there is no biochemical evidence of myocardial infarction At the other extreme is acute myocardial infarction whose clinical definition is based on the presence of acute myocardial damage detected by the elevation of cardiac biomarkers troponin in the context of evidence of acute myocardial ischemia It is classified into five types with type 1 caused by atherothrombotic coronary disease being the focus of this study This type is often precipitated by the rupture or erosion of an atherosclerotic plaque
Background and Rationale Years of exhaustive clinical research have resulted in therapies that reduced mortality and complication rates of ACS ranging from the creation of the Coronary Care Unit anticoagulation therapies beta-blockers renin-angiotensin-aldosterone system inhibitors antiplatelet therapies to reperfusion whether mechanical or pharmacological However in recent years we have not been able to make a qualitative leap in the pathophysiological approach to coronary disease to create new paradigms in therapeutics Thus it is imperative to seek new horizons new pathophysiological hypotheses addressing topics such as inflammation immune response immunothrombosis and stress response in the context of ACS
It is undeniable that inflammation and stress are risk factors for developing ACS Additionally ACS triggers both an acute inflammatory response and a stress response with cortisol being one of the main effectors of the latter possessing anti-inflammatory effects However we currently lack a deep understanding of the mechanisms governing this interesting dialogue between inflammation and stress in the context of ACS Some authors have described that a higher degree of inflammation is associated with worse outcomes in ACS patients Recently we described that this poor outcome is related to plasma cortisol levels
We know that stress has complex effects on the immune system influencing both innate and adaptive immunity Glucocorticoids and catecholamines in the acute phase of the stress response can influence the trafficking andor function of leukocytes neutrophil demargination induce a systemic shift from a TH1 cellular immunity to a TH2 humoral immunity response Additionally acute stress can increase circulating pro-inflammatory cytokine levels such as IL-6 IL-1b and C-reactive protein CRP
This bidirectional interaction between stress response effectors and the immune system is evident as pro-inflammatory cytokines stimulate the stress system at multiple levels including the central and peripheral nervous systems hypothalamus pituitary and adrenal glands increasing glucocorticoid levels
The literature extensively supports the utility of leukocyte indices in ACS One of the most widely used is the neutrophil-to-lymphocyte ratio NLR which has demonstrated its association with the severity of clinical presentation and coronary lesions as well as its ability to predict events during hospitalization and after discharge However we lack studies explaining the mechanisms underlying this index with certainty
We know that exogenous glucocorticoids can cause transient neutrophilia by recruiting the marginal pool and lymphopenia through apoptosis Recently other mechanisms have been proposed that could explain the lymphopenia associated with severe acute stress events linked to transient immunodepression although evidence is scarce Similarly although limited there is interesting information regarding eosinopenia as a prognostic marker in severe acute diseases with studies published on its utility in stroke sepsis and one in ACS We know that exogenous glucocorticoid administration can induce eosinopenia and apoptosis is proposed as one of the mechanisms causing it which is why corticosteroids have been part of the first-line treatment for autoimmune and allergic diseases where these cells play a predominant role
Currently we lack human studies demonstrating the association of these cellular immunity components behavior with stress and inflammation response markers in the context of ACS
Research Objectives and Hypotheses Hypothesis In ACS there is an increase in cortisol levels as an expression of the stress response and CRP as an expression of the inflammatory response associated with changes in cellular immunity components which are predictors of clinical events
Objectives
Describe the leukocyte neutrophil lymphocyte and eosinophil counts and their association with the clinical presentation of ACS patients
Describe the leukocyte neutrophil lymphocyte and eosinophil counts and their association with the presence of heart failure in ACS patients
Describe the leukocyte neutrophil lymphocyte and eosinophil counts and their association with clinical events during hospitalization in ACS patients
Describe the leukocyte neutrophil lymphocyte and eosinophil counts and their association with clinical events post-discharge in ACS patients
Correlate the leukocyte neutrophil lymphocyte and eosinophil counts with maximum levels of high-sensitivity troponin CPK and CPK-MB as expressions of tissue damage in ACS
Correlate the leukocyte neutrophil lymphocyte and eosinophil counts with total serum cortisol levels as a marker of stress response in ACS
Correlate the leukocyte neutrophil lymphocyte and eosinophil counts with CRP levels as a marker of inflammation in ACS
Methodology A prospective observational analytical single-center study will be conducted on successive patients with acute coronary syndrome with a follow-up of 6 months For two years all eligible patients admitted with a diagnosis of ACS to the Coronary Unit of Hospital de Clínicas José de San Martín in Buenos Aires will be successively registered
All included patients will undergo a baseline electrocardiogram and physical examination at admission and appropriate therapeutic measures will be implemented according to their condition as indicated by the treating physician without influence from study protocol inclusion
Demographic and clinical data will be obtained from the medical history Additionally a blood sample will be taken at admission for the measurement of ultra-sensitive CRP and cortisol
During hospitalization the evolution curve of necrosis markers troponin CPK and CPK-MB will be evaluated from admission until the peak is confirmed and the decline begins Total leukocyte lymphocyte and eosinophil counts will be recorded at patient admission
Post-discharge a telephone follow-up will be conducted for 6 months
Sample Size Calculation Considering an event incidence of 20 and an alpha error of 05 and beta error of 05 the number of patients to be included should be equal to or greater than 150
For statistical analysis categorical variables will be presented as frequencies and continuous variables as mean with standard deviation if normally distributed or median with interquartile ranges if not Pearsons chi-square or Fishers exact test and Students t-test or Wilcoxon rank-sum test will be used for comparisons depending on whether variables are categorical or continuous and normally distributed or not Correlations will be assessed using Pearson or Spearman coefficients Intraobserver and interobserver variability will be analyzed using the intraclass correlation coefficient Statistical significance will be set at a two-tailed p-value less than 005 All calculations will be performed using R version 351
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?: