Tesi etd-01292024-070745 |
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Tipo di tesi
Tesi di laurea magistrale LM6
Autore
DI VENANZIO, LUDOVICA
URN
etd-01292024-070745
Titolo
Predictors of Major Adverse Cardiovascular Events in Follow-Up of Patients Undergoing Carotid Endarterectomy: The MCAT (Mayo Clinic Carotid Artery Atherosclerosis Trial) Study
Dipartimento
RICERCA TRASLAZIONALE E DELLE NUOVE TECNOLOGIE IN MEDICINA E CHIRURGIA
Corso di studi
MEDICINA E CHIRURGIA
Relatori
relatore Prof. Taddei, Stefano
correlatore Prof. Lerman, Amir
correlatore Prof. Lerman, Amir
Parole chiave
- Acid Acetylsalicylic (ASA)
- Amaurosis Fugax (AF)
- Antigen Presenting Cell (APC)
- Blood Pressure (BP)
- Cardiovascular (CV)
- Cardiovascular Disease (CVD)
- Carotid Endarterectomy (CEA)
- Cerebrovascular Accidents (CVA)
- Common Carotid Artery (CCA)
- Computed Tomography Angiography (CTA)
- Diabetes Mellitus (DM)
- Digital subtraction angiography (DSA)
- Duplex Ultrasound (DUS)
- External Carotid Artery (ECA)
- Hematoxylin and Eosin (H&E)
- High-Density Lipoprotein (HDL)
- Imaging Mass Cytometry (IMC).
- Immunohistochemistry (IHC)
- Internal Carotid Artery (ICA)
- Intraplaque Hemorrhage (IPH)
- Low-Density Lipoprotein (LDL)
- Magnetic Resonance Angiography (MRA)
- Major Adverse Cardiovascular Events (MACE)
- Major Histocompatibility Complex (MHC)
- Myocardial Infarction (MI)
- Nitric Oxide (NO)
- Standardized Mortality Ratio (SMR)
- Transient Ischemic Attack (TIA)
Data inizio appello
13/02/2024
Consultabilità
Non consultabile
Data di rilascio
13/02/2094
Riassunto
Background
Atherosclerotic carotid artery disease may be associated with a high risk of Major Adverse Cardiovascular Events (MACE). We aimed to assess the rate of MACE and possible predictors of events after carotid endarterectomy (CEA). We hypothesized that cardiovascular risk factors are not predictive of MACE and that MACE may be related to plaque’s features such as intraplaque hemorrhage (IPH). We also aimed to determine whether IPH is associated with an inflammatory shift of the plaque environment by assessing the levels of inflammatory cytokines and mapping the immune cell microenvironment.
Methods
We enrolled patients undergoing CEA. The primary outcome was the rate of overall MACE including cardiac events, cerebrovascular accidents (CVA), and all-cause mortality. Univariate and multivariable analysis were performed to identify predictors of overall MACE and each endpoint separately. Furthermore, we compared the standardized mortality ratio (SMR) of our population with the SMR of the age-sex-matched Minnesota population. Cytokines levels in atherosclerotic plaque tissue were obtained using multiplex ELISA and Imaging Mass Cytometry (IMC) was used to define the site-specific immune cell microenvironment in CEA specimens.
Results
A total of 710 patients were followed for a median of 7.1 [2.9-11.9] years after CEA. MACE occurred in 442 (62.3%) patients: all-cause mortality (N=198, 27.0%), cardiac events (N=169, 23.1%), and CVA (N=75,10.2%). In the multivariable models, history of cardiac events was predictive of overall MACE (HR 2.09 [95%CI 1.34-3.27]; p=0.001), age was an independent predictor of all-cause mortality (HR 1.02 [95%CI 1.00-1.04]; p=0.023), and only a history of cardiac events was predictive of future cardiac events (HR 1.75 [95%CI 1.30-2.37]; p<0.001).The SMR was significantly higher at 10-year and 21-year follow-up than the Minnesota population. In plaques with IPH vs. those without IPH, the levels of cytokines such as MCP-1, IL6, IL8, and TNFalpha were significantly higher and immune cells and immune checkpoints were more expressed.
Conclusions
Patients with carotid artery disease have a high rate of MACE following CEA, which is not predicted by most of the conventional cardiovascular risk factors. In response, we propose a paradigm shift, speculating that carotid plaque characteristics may provide further insight into the risk stratification of this patient population in addition to clinical risk factors.
Atherosclerotic carotid artery disease may be associated with a high risk of Major Adverse Cardiovascular Events (MACE). We aimed to assess the rate of MACE and possible predictors of events after carotid endarterectomy (CEA). We hypothesized that cardiovascular risk factors are not predictive of MACE and that MACE may be related to plaque’s features such as intraplaque hemorrhage (IPH). We also aimed to determine whether IPH is associated with an inflammatory shift of the plaque environment by assessing the levels of inflammatory cytokines and mapping the immune cell microenvironment.
Methods
We enrolled patients undergoing CEA. The primary outcome was the rate of overall MACE including cardiac events, cerebrovascular accidents (CVA), and all-cause mortality. Univariate and multivariable analysis were performed to identify predictors of overall MACE and each endpoint separately. Furthermore, we compared the standardized mortality ratio (SMR) of our population with the SMR of the age-sex-matched Minnesota population. Cytokines levels in atherosclerotic plaque tissue were obtained using multiplex ELISA and Imaging Mass Cytometry (IMC) was used to define the site-specific immune cell microenvironment in CEA specimens.
Results
A total of 710 patients were followed for a median of 7.1 [2.9-11.9] years after CEA. MACE occurred in 442 (62.3%) patients: all-cause mortality (N=198, 27.0%), cardiac events (N=169, 23.1%), and CVA (N=75,10.2%). In the multivariable models, history of cardiac events was predictive of overall MACE (HR 2.09 [95%CI 1.34-3.27]; p=0.001), age was an independent predictor of all-cause mortality (HR 1.02 [95%CI 1.00-1.04]; p=0.023), and only a history of cardiac events was predictive of future cardiac events (HR 1.75 [95%CI 1.30-2.37]; p<0.001).The SMR was significantly higher at 10-year and 21-year follow-up than the Minnesota population. In plaques with IPH vs. those without IPH, the levels of cytokines such as MCP-1, IL6, IL8, and TNFalpha were significantly higher and immune cells and immune checkpoints were more expressed.
Conclusions
Patients with carotid artery disease have a high rate of MACE following CEA, which is not predicted by most of the conventional cardiovascular risk factors. In response, we propose a paradigm shift, speculating that carotid plaque characteristics may provide further insight into the risk stratification of this patient population in addition to clinical risk factors.
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