Rosuvastatin Effect on Atherosclerotic Plaque Metabolism - a Subclinical Atherosclerosis Imaging Study With 18F-NaF PET-CT
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Variation in 18F-NaF uptake in coronary, aortic and carotid plaques (tissue to background ratio - TBR)
研究概览
简要总结
Atherosclerotic plaque uptake of 18F-sodium fluoride (NaF) in positron emission tomography with computed tomography (PET-CT) was recently shown to correlate with clinical instability in patients with CV disease. We hypothesize that rosuvastatin reduces 18F-NaF plaque uptake.
Our group will scan coronary, aortic and carotid arteries of high-risk CV subjects with 18F- NaF-PET-CT. Individuals with 18F-NaF-positive plaques will be treated with rosuvastatin for six months, followed by 18F-NaF-PET-CT re-evaluation.
详细描述
Background:
Cardiovascular diseases (CVD) are the main cause of mortality in developed countries; its prevention is challenging. Advances in molecular imaging of the atherosclerotic plaque enhanced the study of its pathophysiology, including the positron emission tomography with computed tomography (PET-CT) scan. The marker 18F-sodium fluoride (NaF) has been studied in peripheral arteries plaque imaging as an in vivo marker of on-going calcification. The 18F ions deposit in the bone by exchange of hydroxyl group on the surface of the hydroxyapatite matrix to form fluoroapatite, so this tracer detects areas of active calcification and osteogenic remodeling. Coronary imaging with 18F-NaF labelled PET-CT was recently described and proposed to be able to discriminate between active and inactive coronary calcification, possibly identifying high-risk patients.
Statin therapy is approved for primary and secondary CVD prevention due to both its cholesterol-lowering effect and positive pleiotropic properties in the plaque. In particular, rosuvastatin diminishes mortality and vascular events when used in primary and secondary prevention. High doses of rosuvastatin resulted in atherosclerosis regression as assessed with coronary intravascular ultrasound, carotid intima-media thickness (CIMT) and lipid content reduction of the atherosclerotic plaque (near-infrared spectroscopy analysis).
We do not know the effects of statins in the 18F-NaF uptake.
Design:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- Double (Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Older than 40 years;
- •Written informed consent;
- •Considered to be at high or very high CV risk according to the European Society of Cardiology guidelines, fulfilling any of the following criteria:
- •predicted fatal CV event at 10 years ≥5% (SCORE tables for low-risk countries);
- •chronic kidney disease with glomerular filtration rate (GFR) under 60 mL/min (Modification of Diet in Renal Disease equation - MDRD);
- •diabetes mellitus (type 1 or 2);
- •markedly elevated single risk factors.
排除标准
- •Previous CV events;
- •GFR under 30 mL/min;
- •Known hepatic dysfunction or alanine amino-transferase level more than twice the upper limit of the normal (ULN) range;
- •Creatine kinase level more than three times the ULN;
- •Known myopathy;
- •Statin hypersensivity;
- •Hormone replacement therapy;
- •Malignant neoplasms in the past five years (excluding basal-cell skin carcinoma);
- •Uncontrolled hypothyroidism;
- •Chronic inflammatory disease (such as rheumatoid arthritis, inflammatory bowel disease);
- •Pregnancy or women in child bearing age without contraceptive;
研究组 & 干预措施
Patients with positive 18F-NaF plaques
Patients with 18F-NaF-positive plaques (coronary, aortic or carotid) with TBR > 1.5
干预措施: Rosuvastatin Oral Tablet (Drug)
结局指标
主要结局
Variation in 18F-NaF uptake in coronary, aortic and carotid plaques (tissue to background ratio - TBR)
时间窗: 6 months
* Whole body 18F-NaF-PET-CT for identification of coronary, carotid, thoracic and abdominal aorta arteries plaques: * administration of 125 MBq 18F-NaF intravenously, followed by an attenuation correction CT scan and PET imaging after 60 min. Coronary images will be reconstructed according with the usual protocol of PET-CT. Two-dimensional regions of interest will be drawn around all major epicardial coronary vessels and around the major vessels on three millimetres axial slices. * Quantification of 18F-NaF uptake at baseline and after optimal treatment including statins: * ratio of the maximum standard uptake value (SUV) in the region of interest (the decay corrected tissue concentration of the tracer divided by the injected dose per bodyweight) and blood pool activity in the superior vena cava: tissue-to-background ratio (TBR). * Primary outcome: variation in maximum TBR at any vascular territory (coronary, carotid or aortic)
次要结局
- Variation in 18F-NaF uptake in coronary, aortic and carotid plaques (corrected uptake per lesion - CUL)(6 months)
研究者
Manuel Oliveira Santos
MD
University of Coimbra