Implications of the Presence of Non-obstructive Atherosclerotic Plaques on Platelet and Vascular Reactivity

March 17, 2026 updated by: Jose Carlos Nicolau, University of Sao Paulo

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 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 predispos

Study Overview

Status

Completed

Conditions

Detailed Description

The VerifyNow P2Y12® assay provides established cut-off values that allow discrimination of patients with low responsiveness to antiplatelet therapy, with higher PRU values being associated with adverse clinical outcomes.

Based on this concept, it is possible to assess the impact of potential platelet hyperreactivity by analyzing the proportion of patients exceeding a predefined clinically relevant threshold. Data collected in this manner allow non-parametric statistical analysis using the McNemar test.

A PRU cut-off value of 208 has been widely used in patients treated with clopidogrel and was therefore selected in the present study as the threshold defining inadequate response to the drug.

Assuming a 15% difference between the case and control groups, with a statistical power of 95% and a two-sided alpha level of 0.05, a minimum sample size of 82 patients was calculated. Considering an estimated 10% rate of non-inclusion (e.g., refusal to sign informed consent or exclusion due to high Framingham risk score), the final planned sample size for the study was set at 90 participants.

Study Type

Observational

Enrollment (Actual)

90

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • São Paulo
      • São Paulo, São Paulo, Brazil, 05403-900
        • José Carlos Nicolau

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Patients older than 18 years, male and female with low and medium risk of cardiovascular disease without atherosclerotic disease manifest.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Platelet aggregation by VerifyNow System - P2Y12®
Time Frame: 1 day
Comparing platelet aggregation by VerifyNow System - P2Y12® (An equipment from Accriva Diagnostics that evaluates platelet aggregation) in case and control groups.
1 day

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Platelet aggregation by Multiplate-ADP®, Multiplate-ASPI®
Time Frame: 1day
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
Endothelial function
Time Frame: 1 day
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
Platelet-reticulated
Time Frame: 1day
comparing platelet-reticulated analysis in the case and control groups;
1day
Inflammatory activity
Time Frame: 1day
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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Genetic polymorphisms
Time Frame: 1day
Comparing the presence of genetic polymorphisms in the case and control groups;
1day
Transport of lipids to HDL
Time Frame: 1 day
Comparing Transport of lipids to HDL in the case and control group
1 day
Correlate results
Time Frame: through study completion, an average of 1 year
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
Comparing platelet aggregation in subgroups
Time Frame: through study completion, an average of 1 year

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
Global Risk Score
Time Frame: through study completion, an average of 1 year
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Sao Paulo

Collaborators

Fundação de Amparo à Pesquisa do Estado de São Paulo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 27, 2017

Primary Completion (Actual)

September 30, 2019

Study Completion (Actual)

December 10, 2019

Study Registration Dates

First Submitted

August 5, 2018

First Submitted That Met QC Criteria

August 10, 2018

First Posted (Actual)

August 15, 2018

Study Record Updates

Last Update Posted (Actual)

March 20, 2026

Last Update Submitted That Met QC Criteria

March 17, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FAPESP 2014/01021-4 - Subp. 1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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