CARotid Mri of Atherosclerosis
Condition: Carotid Stenosis; Carotid Artery Plaque; Carotid Atherosclerosis
MeSH terms: Carotid Stenosis; Carotid Artery Diseases; Atherosclerosis
Study type: Interventional

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.
    

Detailed description: 
      Regarding quality assurance plans that address data validation and registry procedures, the
      current study is a single centre investigator-initiated study and therefore there are no
      plans for site monitoring and auditing. The reliability and validity of the MRI data has been
      previously confirmed with comparison to 3D histology data (Koppal et al. Quantitative fat and
      R2* mapping in vivo to measure lipid-rich necrotic core and intraplaque hemorrhage in carotid
      atherosclerosis. Magn Reson Med. 2017;78(1):285-96.).

      Concerning data checks, intraobserver reliability regarding baseline and follow-up
      measurements will be ascertained (Intraclass Correlation Coefficients (ICC), Bland Altman).

      Data is collected from patient medical records (electronic), dedicated study record forms
      (paper) and clinical assessments, resulting in quantitative measures. These external data
      sources are transferred into a study database.

      The current study is a clinical study, using only clinically validated laboratory parameters.
      The source of the lab values and their normal ranges is the electronic patient record. The
      normal ranges have been established by the clinical chemistry and haematology laboratories at
      Linköping University Hospital. Clinical diagnosis and procedures are recorded using the
      International Classification of Diseases (ICD) classification.

      The study was approved by the Swedish Ethical Review Authority (approval nr: 2016-441-31) and
      performed in accordance with the Declaration of Helsinki. Written informed consent has been
      obtained from all study participants.

      Patients are selected based on duplex ultrasound criteria established for the European
      Carotid Surgery Trial. A cut-off at doppler flow velocity has been used to identify eligible
      patients and after considering inclusion and exclusion criteria patients have been contacted
      by the study clinicians dr Elin Good or dr Ebo de Muinck for recruitment. Any registration
      for adverse events follows the same procedures as in routine care.

      Sample size assessment was based on results from previous studies in relation to our primary
      outcome variables. For example, one study with 24 patients and a follow-up time of three
      months experienced a significant reduction of lipid rich necrotic core, using magnetic
      resonance imaging (Alkhalil et al. T2 mapping MRI technique quantifies carotid plaque lipid,
      and its depletion after statin initiation, following acute myocardial infarction.
      Atherosclerosis. 2018;279:100-6.). Therefore, we aimed to include 50 patients who have
      completed both baseline and follow-up, and the follow-up time was set to 12 months.

      Our plan for missing data in situations where variables are missing, unavailable,
      non-reported, uninterpretable etc is to not exclude the study participant, in order to avoid
      bias. For example, in cases where the imaging data from one patient is lost, we will still
      use the remaining clinical data from that patient if the patient has been included in the
      study.

      Regarding Statistical analysis, SPSS Statistics 26 (International Business Machines
      Corporation, New York, NY, USA) is used for statistical analysis. Continuous variables are
      summarized as mean ± standard deviation (SD). To address the primary objectives (the strength
      of the association between fat fraction (FF) and R2*) Pearson correlation coefficient is
      used, and Paired-samples T test is used for analysing changes in quantitative values between
      baseline and follow-up.

      Intra-observer repeatability measurements were calculated using ICC. For ICC evaluation we
      used two-way random effect models, checking for absolute agreement, average measures
      presented.
    

Intervention name(s): Optimization of cardiovascular risk management
Intervention type(s): Other
Intervention description(s): 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.
Intervention model: Single Group Assignment
Intervention model description: Single group, repeated measures design. The treatment is
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Carotid stenosis; Cardiovascular MRI; Atherosclerotic plaque