MISTIC Study: Atherosclerosis, Neurocognition & Cardiovascular Signaling

NCT07520643 | Not Yet Recruiting

• 1 other identifier: 13671
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

The MISTIC study is a non-profit, cross-sectional clinical research project aimed at investigating the relationship between atherosclerosis and both cardiovascular and cognitive function in adult populations. Atherosclerosis is a progressive condition characterized by the accumulation of material within arterial walls, leading to vascular narrowing and impaired blood flow. While its most recognized consequences are acute events such as myocardial infarction or stroke, earlier stages of the disease, often asymptomatic, may already be associated with functional changes affecting multiple organ systems. This study focuses on evaluating the association between vascular health and cognitive performance at a single time point. Atherosclerotic burden will be assessed using non-invasive imaging techniques, including carotid intima-media thickness and coronary calcium scoring. Cognitive performance will be measured using standardized neuropsychological tests. Approximately 1000 participants will be enrolled and divided into two groups: a control group without clinically established cardiovascular disease, and a group of patients with coronary artery disease (CAD). All participants will undergo clinical evaluation, vascular imaging, cognitive testing, and analysis of biological samples. The primary objective is to determine whether increasing atherosclerotic burden is associated with measurable differences in cognitive and cardiovascular function. Secondary aims include identifying patterns that may help improve early detection and risk stratification of vascular disease. The results of this study are expected to contribute to a better understanding of atherosclerosis as a systemic condition and to support the development of preventive strategies targeting early stages of vascular disease.

Conditions

Subclinical Atherosclerotic Cardiovascular Disease; Neurocognitive Decline

Keywords

Atherosclerosis; Neurocognitive Decline; Inflammation

Outcome Measures

Primary Outcomes (3)

• Carotid Intima-Media Thickness (cIMT) (mm)

  The Carotid Intima-Media Thickness (cIMT) is a non-invasive ultrasound measurement used to assess the thickness of the inner two layers (intima and media) of the carotid artery wall. It is commonly used as a marker of subclinical atherosclerosis and cardiovascular risk. The measurement is typically obtained from the common carotid artery using high-resolution B-mode ultrasound. Increased cIMT values are associated with a higher risk of cardiovascular events such as stroke and myocardial infarction. cIMT is measured in millimeters (mm).

  From enrollment to the end of diagnostic tests at 6 months

• Agatston Score (RU)

  The Agatston Score is a quantitative measure of coronary artery calcification obtained from non-contrast cardiac CT scans. It is used to estimate the burden of coronary atherosclerosis and predict the risk of future cardiovascular events. The score is calculated by identifying areas of radiodense (hyperdense) calcium in the coronary arteries (attenuation ≥130 Hounsfield units), multiplying the area by a density factor, and summing the results across all coronary arteries. The Agatston Score is expressed in Agatston Units (AU). It is a dimensionless index, not a physical unit, even though it is sometimes abbreviated as "RU" (risk units) in some contexts. 0 AU → no detectable calcification 1-99 AU → mild calcification 100-399 AU → moderate calcification ≥400 AU → extensive calcification

  From enrollment to the end of treatment at 6 months

• Montreal cognitive assessment (MoCA) test (points)

  The Montreal Cognitive Assessment (MoCA) is a brief screening tool used to detect mild cognitive impairment and early dementia. It evaluates multiple cognitive domains, including: Attention and concentration, Executive functions, Memory (delayed recall), Language, Visuospatial skills, Abstraction and Orientation. The test typically takes about 10 minutes to administer and consists of a series of short tasks (e.g., word recall, clock drawing, naming, and serial subtraction). The MoCA is scored as a total point-based scale, with a maximum of 30 points. Scores are expressed simply as "points" (no physical units). A score of 26 or above (≥26/30) is generally considered normal, although this may vary with age and education.

  From enrollment to the end of treatment at 6 months

Study Arms (2)

Control Individuals

Diagnostic Test: Peripheral Vascular Imaging; Diagnostic Test: Coro-CT; Diagnostic Test: Neurocognitive Assesment; Procedure: Blood Sampling

Patients with Coronary Artery Disease

Diagnostic Test: Peripheral Vascular Imaging; Diagnostic Test: Coro-CT; Diagnostic Test: Neurocognitive Assesment; Procedure: Blood Sampling

Interventions

Peripheral Vascular Imaging DIAGNOSTIC_TEST

Peripheral Vascular Imaging of Carotid and Femoral Arteries by Eco-Doppler Ultrasound

Control Individuals; Patients with Coronary Artery Disease

Coro-CT DIAGNOSTIC_TEST

Coronary Computed Axial Tomography (Coro-TC) with contrast administration

Control Individuals; Patients with Coronary Artery Disease

Neurocognitive Assesment DIAGNOSTIC_TEST

Study of neurocognitive function and decline by pre-established tests

Control Individuals; Patients with Coronary Artery Disease

Blood Sampling PROCEDURE

Blood sampling for further molecular and cellular analysis

Control Individuals; Patients with Coronary Artery Disease

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study includes 1000 participants recruited at Fondazione Policlinico Gemelli: 500 patients with advanced atherosclerosis undergoing PCI with ≥50% stenosis or documented coronary artery disease, and 500 control subjects from the Primary Cardiovascular Prevention Clinic with indications for CAC scoring, without prior acute coronary events. About 22% of controls may have subclinical atherosclerosis. Cognitive impairment is expected in 12-20% of patients and 4-10% of controls. All participants will undergo a single-timepoint assessment including clinical, imaging, molecular, and neurocognitive evaluations to study the association between vascular burden and cognitive function.

You may qualify if:

• Age \>= 18 years
• Capacity to provide informed consent
• Documented coronary artery stenosis ≥ 50 % through peripheral vascular ultrasound imaging.Documented coronary artery stenosis ≥ 50 % through peripheral vascular ultrasound imaging.

You may not qualify if:

• Prior ischemic cardiac events (e.g., myocardial infarction, unstable angina).
• Major electrophysiological disorders.
• History of stroke or transient ischemic attack.
• Ongoing renal replacement therapy (dialysis).
• Use of systemic immunosuppressive or anti-inflammatory medications (beyond low-dose aspirin).
• Any chronic inflammatory or autoimmune disease.
• Active infectious disease at the time of enrolment.
• Active malignancy or cancer treatment within the past 5 years.
• Coronary Artery Disease Group
• Age \>= 18 years
• Capacity to provide informed consent
• Prior ischemic cardiac events (e.g., myocardial infarction, unstable angina).
• Major electrophysiological disorders.
• History of stroke or transient ischemic attack.
• Ongoing renal replacement therapy (dialysis).

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, Lazio, 00168, Italy

Location

Related Publications (5)

• Casolo G, Abrignani MG, Amico AF, Cademartiri F, Caporale R, Di Lenarda A, Domenicucci S, Gabrielli D, Geraci G, Indolfi C, Limbruno U, Midiri M, Murrone A, Musumeci G, Nardi F, Nistri S, Privitera C, Gulizia MM. [ANMCO/SIC/GISE/ARCA/SIRM Consensus document: Description of coronary atherosclerosis for diagnostic, prognostic and therapeutic purposes]. G Ital Cardiol (Rome). 2019 Jul-Aug;20(7):439-468. doi: 10.1714/3190.31688. Italian.

  PMID: 31320766 BACKGROUND

• Tresch DD, Aronow WS. Clinical manifestations and diagnosis of coronary artery disease. Clin Geriatr Med. 1996 Feb;12(1):89-100.

  PMID: 8653666 BACKGROUND

• Ajoolabady A, Pratico D, Lin L, Mantzoros CS, Bahijri S, Tuomilehto J, Ren J. Inflammation in atherosclerosis: pathophysiology and mechanisms. Cell Death Dis. 2024 Nov 11;15(11):817. doi: 10.1038/s41419-024-07166-8.

  PMID: 39528464 BACKGROUND

• Gimbrone MA Jr, Garcia-Cardena G. Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis. Circ Res. 2016 Feb 19;118(4):620-36. doi: 10.1161/CIRCRESAHA.115.306301.

  PMID: 26892962 BACKGROUND

• Libby P, Buring JE, Badimon L, Hansson GK, Deanfield J, Bittencourt MS, Tokgozoglu L, Lewis EF. Atherosclerosis. Nat Rev Dis Primers. 2019 Aug 16;5(1):56. doi: 10.1038/s41572-019-0106-z.

  PMID: 31420554 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, Plasma, Serum, PBMCs

MeSH Terms

Conditions

Atherosclerosis; Inflammation

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Target Duration: 6 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor, Cardiologist - Head of the Acute Coronary Syndromes Unit - Head of the Molecular and Cellular Cardiology Laboratory

Study Record Dates

• First Submitted: March 26, 2026
• First Posted: April 9, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): April 30, 2030
• Study Completion (Estimated): April 30, 2030
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)