Laboratory Implications of Non Obstructive Atherosclerotic Plaques Identified by Multiple Detector Coronary Angiotomography

Cardiovascular Risk Factor Clinical Trial

Official title:

Laboratory Implications of Non Obstructive Atherosclerotic Plaques Identified by Multiple Detector Coronary Angiotomography

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03632785
• Other study ID #: FAPESP 2014/01021-4 - Subp. 1
• Status: Completed
• Start date: March 27, 2017
• Est. completion date: December 10, 2019

Study information

• Verified date: November 2020
• Source: University of Sao Paulo
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Approximately 50% of coronary events occur in previously asymptomatic patients. Thus, the early detection of the individuals at higher risk became an important research target within the current cardiology. The various clinical scores used present a predictive accuracy for ischemic events, evaluated by the ROC curve, which ranges from 0.73 to 0, 79. Therefore, the introduction of new non-invasive techniques for the detection of atherosclerosis aims to allow a more adequate classification of risk. The development of radiological techniques, fundamentally coronary angiotomography of multiple detectors (CAMD) and electron beam computed tomography-EBCT‖, demonstrated that the degree of coronary calcification correlates with endothelial lesion and individual prognosis in the long term. Notably, the calcium score has a weak correlation with the severity of coronary stenosis per se, possibly due to variations in arterial remodeling due to coronary calcification. On the other hand, the CAMD allows the detection of a small magnitude atheromatous disease, not diagnosed clinically, nor by tests provoking ischemia, or even by coronary catheterization. The clinical relevance of the small magnitude atheromatous disease diagnosed by the ACMD and its correlation with plaque vulnerability markers, mainly platelet aggregation, vascular reactivity, and inflammation are still not well determined. This is a case and control study and we will enrolled 90 patients with low and medium risk of cardiovascular event whose cases should present discrete plaques in the CAMD e controls should present none plaque in coronary stenosis

Description:

Coronary atherosclerotic disease often begins in the transition from childhood to adolescence, progressing slowly and quietly. Its clinical manifestation occurs in the majority of cases from the 4th decade of life. However, it is important to remember that necropsy studies conducted in the 1970s identified the presence of non-obstructive atherosclerotic plaques in the aorta of individuals from the second decade of life. From its first description to the present day, the subject has been deeply studied, providing reliable information on several mechanisms involved in atherogenesis, disease progression and plaque unstabilization, which may occur in a silent manner or lead to a clinical picture of unstable myocardial ischemic syndrome (UMIS). In this period, classic risk factors for coronary artery disease (age, sex, diabetes mellitus, systemic arterial hypertension, hypercholesterolemia and smoking, among others) were described, and risk scores were developed that aid in the individual prediction of the probability of disease manifestation coronary artery disease (CAD). The most widespread of these scores is that developed from the population of Framingham, which was started in the United States of the same name after 1948. Subjects with no evidence of cardiovascular disease were followed prospectively with biannual evaluations. The data obtained allowed the elaboration of an algorithm of prediction of individual risk that is included in the most recent recommendations of evaluation of cardiovascular risk. However, these traditional clinical assessment scores tend to underestimate cardiovascular risk in some populations, especially in women and young individuals. In the global population, the various clinical scores used have a predictive accuracy for ischemic events, as assessed by the ROC (Receiver Operating Characteristic) curve, ranging from 0.73 to 0.79. In this way, the concept of "detection interval" is proposed. Defined by the difference between cases of coronary disease or cardiovascular events detected and the actual total prevalence of atherosclerotic disease in the population, such detection interval opens a new field for the introduction of new non-invasive atherosclerosis investigation techniques. Taking into account that approximately 50% of coronary events occur in previously asymptomatic patients, the early detection of these individuals at greater risk has become an important research target within the current cardiology. More recently, the development of radiologic techniques, fundamentally coronary angiography of multiple detectors (CAMD) and electron beam computed tomography (EBCT), have demonstrated that the degree of coronary calcification correlates with endothelial lesion and individual prognosis in the long term, allowing to refine the clinical classification of a patient's risk for a greater or lesser chance of fatal and non-fatal events. Notably, the calcium score has a weak correlation with the severity of coronary stenosis per se, possibly due to variations in the arterial remodeling due to coronary calcification. On the other hand, calcification of the coronary arteries is known to be associated with lower myocardial blood flow even in the absence of significant stenosis. This means that calcification is not merely a marker of obstructive coronary disease and may predispose patients to myocardial ischemia by mechanisms other than those traditionally known and may therefore be a marker of endothelial dysfunction. On the other hand, the application of CAMD allowed the detection of a small magnitude atheromatosis , not diagnosed clinically by the tests provoking ischemia or even by contrast-enhanced coronary angiography. The clinical relevance of these alterations, evaluated by their correlation with the presence of plaque vulnerability markers, mainly platelet aggregation, vascular reactivity, and inflammation, is still very little studied, being the main objective of this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: December 10, 2019
• Est. primary completion date: September 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Low or Medium Risk of cardiovascular disease assessed by the Framingham criteria;
• That agrees to sign the Consent Form;
• Absence of known atherosclerotic disease;
• Patients in the case group should additionally present discrete plaques (s) evaluated by coronary angiotomography of multiple detectors (CAMD). Patients in the control group should be absent from any coronary atherosclerotic process to CAMD.

Exclusion Criteria:

• Known atherosclerotic disease manifest;
• Previous acute coronary syndrome (ACS);
• Use of antiplatelet agents and / or anticoagulants;
• Use of NSAIDs and/or corticosteroids
• Known platelet dysfunction or platelets <100,000 / µL or> 450,000 / µL
• Hematocrit <33% and > 52%
• Hematological diseases;
• Liver disease;
• Known malignant neoplasm;
• Refusal to sign free and informed consent.

Related Conditions & MeSH terms

• Cardiovascular Risk Factor
• Coronary Angiography of Multiple Detectors
• Coronary Stenosis
• Discrete Coronary Artery Stenosis
• Plaque, Atherosclerotic
• Platelet Aggregation, Spontaneous

Locations

Country	Name	City	State
Brazil	José Carlos Nicolau	São Paulo	Sao Paulo

Sponsors (2)

Lead Sponsor	Collaborator
University of Sao Paulo	Fundação de Amparo à Pesquisa do Estado de São Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (22)

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* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Genetic polymorphisms	Comparing the presence of genetic polymorphisms in the case and control groups;	1day
Other	Transport of lipids to HDL	Comparing Transport of lipids to HDL in the case and control group	1 day
Other	Correlate results	Correlate platelet aggregability with inflammatory markers and presence of polymorphisms; and. Comparing platelet aggregation among patients with or without calcium (in the ACMD) of the case group	through study completion, an average of 1 year
Other	Comparing platelet aggregation in subgroups	Comparing platelet aggregation in the case and control groups in the following subgroups: Diabetics and non-diabetics; Elderly (=65 years) and not elderly; Feminine and masculine genres; With renal dysfunction (Clearance Creatinine <60) and without renal dysfunction; With statin and without statin.; Obese (IMC=30) and non-obese; Smoking / non-smoking	through study completion, an average of 1 year
Other	Global Risk Score	Comparing Global Risk Score (global risk of coronary heart disease - is a calculation of the absolute risk of having a coronary heart disease event in 10 years. Some variables are analyzed: Age (40-79 years), Gender (male or female), Total cholesterol (130-320mg/dL), HDL cholesterol(20-100mg/dL), Systolic blood pressure (90-200mmHg), Diastolic blood pressure (30-140mmHg), Treated for high blood pressure (Yes ou Not), Diabetes (Yes or Not) and Smoker (Yes or Not). After calculation we have a final number and its respective risk (%) of developing cardiovascular disease. With this, we classify the patient in Low risk(< 5% to have coronary disease in 10 years), Moderate Risk ( Men = 5% e = 20% and Woman = 5% e = 10%) and High risk ( Men >20% and Woman > 10%). We will compare this Global Risk Score in case and control group.	through study completion, an average of 1 year
Primary	Platelet aggregation by VerifyNow System - P2Y12®	Comparing platelet aggregation by VerifyNow System - P2Y12® (An equipment from Accriva Diagnostics that evaluates platelet aggregation) in case and control groups.	1 day
Secondary	Platelet aggregation by Multiplate-ADP®, Multiplate-ASPI®	Comparing platelet aggregation by Adenosine Diphosphate pathway (ADP test) and by Arachidonic Acid pathway (ASPI test). Theses methods will be analyzed in case and control groups.	1day
Secondary	Endothelial function	Comparing endothelial function by ENDOPAT 2000 method (is the leading medical device for noninvasive endothelial function assessment. It was developed and is distributed by Itamar Medical, Caesarea, Israel) in case and control groups	1 day
Secondary	Platelet-reticulated	comparing platelet-reticulated analysis in the case and control groups;	1day
Secondary	Inflammatory activity	Comparing the inflammatory activity by Interleukin 6 (IL-6) and by Ultra-Sensitive C-Reactive Protein (us-CRP) in the case and control groups	1day