CARotid Mri of Atherosclerosis

NCT04835571 | Completed

• 1 other identifier: 756191
• Study Type: interventional
• Target: 52
• Locations: 0 countries
• Sites: N/A

Brief Summary

In the entire world most people die from cardiovascular disease. Death is primarily from myocardial infarction (MI) and stroke which are most often caused by rupture of atherosclerotic plaques. Patients with high-grade, i.e. ≥ 70% carotid artery stenosis are at especially high risk. Magnetic Resonance Imaging (MRI) studies show that two features inside plaques that are associated with the risk of plaque rupture and subsequent cardiovascular events are: lipid rich necrotic core (LRNC) and intraplaque hemorrhage (IPH). MRI studies on carotid artery plaques typically relies on proton-density-weighted fast-spin echo, blood-suppressed T1- and T2-weighted gradient-echo sequences. The end-result is nonquantitative measures, where plaque features are identified due to their relative signal intensity. To address these problems of non-specificity, we developed a quantitative MRI (qMRI) technique based on Dixon sequences. The study intention is to enable in-depth analysis of plaque features and their relation to clinical data. For example there is an insufficient understanding of associations between lipid biomarkers and plaque contents. Our hypothesis is that we can identify quantitative changes in both plaque and lipid biomarkers after one year of optimized cardiovascular risk management (including treatment with lipid lowering drugs), and establish if there is any associations between these features. Because there is a well-established link between systemic inflammation and the presence of atherosclerotic plaques we will also study the relationship between LRNC and IPH as measured by qMRI versus circulating markers of inflammation. Method: Patients with known carotid stenosis are invited for a baseline visit and a 1-year follow up visit. The study visits include clinical assessment, blood tests, patient interview and magnetic resonance imaging of the carotid arteries. All participants are offered optimized cardiovascular risk management through the individual assessment by the study physicians.

Conditions

Carotid Stenosis; Carotid Artery Plaque; Carotid Atherosclerosis

Keywords

Carotid stenosis; Cardiovascular MRI; Atherosclerotic plaque

Outcome Measures

Primary Outcomes (1)

• Changes in fat fraction (FF) and R2* in relation to changes in plasma lipoproteins.

  FF, Fat Fraction. Measured by Dixon MRI sequences, quantitatively corresponding to lipid rich necrotic core. R2\* (= 1/T2\*) is the rate of signal loss, it can be viewed as a measure for the presence of (heme) iron. As we have shown in a previous study, it correlates to the extent of intraplaque hemorrhage.

  Baseline - 1-year follow up

Secondary Outcomes (1)

• Changes in fat fraction (FF) and R2* in relation to changes in inflammatory lymphocyte subtypes

  Baseline - 1-year follow up

Study Arms (1)

CARMA study participants

EXPERIMENTAL

All patients in the study are in the same treatment arm: all were treated for 12 months according to routine care and international guidelines for cardiovascular disease prevention in patients with very high cardiovascular risk. Through study physicians patients received an individual assessment and optimized cardiovascular risk management, including life style advice and adjustments in their medical preventive treatment, based on drugs used in standard care (eg. lipid lowering medication, anti-hypertensive-treatment, anti-thrombotic treatment). All treatment goals were set in accordance with current guidelines at the time for study participation.

Other: Optimization of cardiovascular risk management

Interventions

Optimization of cardiovascular risk management OTHER

Treatment goals were set according to current guidelines (Perk et al. Eur Guidelines on CVD prevention in clinical practice (2012). Eur heart J. 2012;33(13):1635-701): * blood pressure \<140/90 mmHg * Tot cholesterol \<5 mmol/l * LDL \<1,8 mmol/l * Waist circumference: men \<94 cm, women \<80 cm * BMI \<25 kg/m2 * HbA1c without diabetes mellitus \<42 mmol/mol, HbA1c with diabetes mellitus \<52 mmol/mol * Antithrombotic treatment (or anticoagulants, if indicated) * Physical activity 30 min/day, 5 days/week, alternatively high-intensity training at least15 min/day, 5 days/week or a combination of the two. * Healthy diet, including low levels of saturated fats, high intake of vegetables, fruits, whole-grain and fish * Smoking cessation * Low alcohol consumption Patients were encouraged to follow the above recommendations through support of the study physicians, who made individual assessments of all patients and adjusted ongoing medical treatment to reach treatment targets.

CARMA study participants

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Carotid plaques with a cut-off at doppler flow velocity ≥ 1.3 m/sec at a Doppler angle of 50-60°, which corresponds to a ≥ 50% stenosis according to these criteria.

You may not qualify if:

• Performed or planned carotid surgery
• Carotid occlusion
• Renal failure (GFR \<45 ml/h)
• Inflammatory diseases, anti-inflammatory treatment or malignancies
• Stroke \<30 days before admission
• Co-morbidities that disable informed consent or participation in the study investigations (e.g. contraindications for MRI)

Sponsors & Collaborators

• Linkoeping University: lead
• Region Östergötland: collaborator
• Region Jönköping County: collaborator
• FORSS, Forskningsrådet i Sydöstra Sverige: collaborator

Related Publications (3)

• Koppal S, Warntjes M, Swann J, Dyverfeldt P, Kihlberg J, Moreno R, Magee D, Roberts N, Zachrisson H, Forssell C, Lanne T, Treanor D, de Muinck ED. Quantitative fat and R2* mapping in vivo to measure lipid-rich necrotic core and intraplaque hemorrhage in carotid atherosclerosis. Magn Reson Med. 2017 Jul;78(1):285-296. doi: 10.1002/mrm.26359. Epub 2016 Aug 11.

  PMID: 27510300 BACKGROUND

• Good E, Lanne T, Wilhelm E, Perk J, Jaarsma T, de Muinck E. High-grade carotid artery stenosis: A forgotten area in cardiovascular risk management. Eur J Prev Cardiol. 2016 Sep;23(13):1453-60. doi: 10.1177/2047487316632629. Epub 2016 Feb 15.

  PMID: 26879568 BACKGROUND

• Good E, Akerman L, Nystrom S, Jonasson L, Ernerudh J, de Muinck E. Changes in natural killer and T lymphocyte phenotypes in response to cardiovascular risk management. Sci Rep. 2023 Nov 27;13(1):20810. doi: 10.1038/s41598-023-48111-7.

  PMID: 38012327 DERIVED

MeSH Terms

Conditions

Carotid Stenosis; Carotid Artery Diseases; Plaque, Atherosclerotic

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Ebo de Muinck, Professor

  Linkoeping University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Ebo de Muinck

Model Details: Single group, repeated measures design. The treatment is

Study Record Dates

• First Submitted: April 5, 2021
• First Posted: April 8, 2021
• Study Start: January 6, 2017
• Primary Completion: December 12, 2018
• Study Completion: December 31, 2021
• Last Updated: December 8, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share