MISTIC Study: Atherosclerosis, Neurocognition & Cardiovascular Signaling

Official title

Multilevel and Interdisciplinary Assessment of Subclinical to Clinical Atherosclerosis Interactions With Neurocognitive Function and Cardiovascular System Through Endothelial and Inflammatory Cell Signalling: The MISTIC Study

Overview

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.

Interventions

• Diagnostic test Peripheral Vascular Imaging
  Peripheral Vascular Imaging of Carotid and Femoral Arteries by Eco-Doppler Ultrasound
• Diagnostic test Coro-CT
  Coronary Computed Axial Tomography (Coro-TC) with contrast administration
• Diagnostic test Neurocognitive Assesment
  Study of neurocognitive function and decline by pre-established tests
• Procedure Blood Sampling
  Blood sampling for further molecular and cellular analysis

Primary outcome measures

• Carotid Intima-Media Thickness (cIMT) (mm) [Time frame: From enrollment to the end of diagnostic tests at 6 months]
• Agatston Score (RU) [Time frame: From enrollment to the end of treatment at 6 months]
• Montreal cognitive assessment (MoCA) test (points) [Time frame: From enrollment to the end of treatment at 6 months]

Eligibility criteria

Control Group

Inclusion criteria

• 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.

Exclusion criteria

• 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

Inclusion criteria

• Age >= 18 years
• Capacity to provide informed consent

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Case-control

Study locations

Italy · 1 center

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Rome

Publications

• 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):439-4 PMID 31320766
• Tresch DD, Aronow WS. Clinical manifestations and diagnosis of coronary artery disease. Clin Geriatr Med. 1996 Feb;12(1):89-100. PMID 8653666
• 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
• 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
• 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

Identifiers

NCT: NCT07520643 · 13671

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗