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.

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.

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.