![Quantification of Atherosclerotic Plaque Activity and Vascular Inflammation using [18-F] Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography FDG-PET/CT](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F3777.jpg&w=3840&q=50)
Coronary Plaque Morphology and the Anti-Inflammatory Impact of Atorvastatin: A Multicenter 18F-Fluorodeoxyglucose
Parmanand Singh1, Hamed Emami1, Sharath Subramanian1
1From the Division of Cardiology, New York Presbyterian Hospital and Weill Cornell Medical College (P.S.); Cardiac MR PET CT Program, Division of Cardiac Imaging (H.E., S.S., P.M.-H., G.M.-S., Amr Abdelbaky, U.H., A.T.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; MTA-SE Cardiovascular Imaging Research Group, Semmelweis University, Budapest, Hungary (P.M.-H.); Fundacion Cardio-Infantil, Bogota, Colombia (H.M.M.); Merck and Company, Inc, Kenilworth, NJ (Achilles Alon, S.S.S.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (Z.A.F.).
Insights
Statins reduce coronary inflammation more effectively in plaques with high-risk morphology (HRM). This suggests statins offer greater benefits for individuals with advanced atherosclerosis and nonobstructive coronary plaques.
Area of Science:
- Cardiovascular Medicine
- Atherosclerosis Research
- Interventional Cardiology
Background:
- Nonobstructive coronary plaques with high-risk morphology (HRM) are linked to increased cardiovascular events.
- Statins are a cornerstone therapy for cardiovascular disease prevention.
- The anti-inflammatory effects of statins within coronary plaques require further elucidation.
Purpose of the Study:
- To investigate whether statins exert a greater anti-inflammatory effect on coronary plaques exhibiting high-risk morphology (HRM).
- To explore the impact of atorvastatin on coronary arterial inflammation in relation to plaque characteristics.
Main Methods:
- Prospective multicenter study involving 55 subjects at high risk for atherosclerosis.
- 18F-fluorodeoxyglucose positron emission tomographic/computed tomographic imaging (FDG-PET/CT) was used to assess coronary arterial inflammation.
- Contrast-enhanced computed tomographic angiography characterized HRM (noncalcified or partially calcified plaques) in the left main coronary artery (LMCA).
Main Results:
- Coronary arterial inflammation (assessed by FDG uptake) was significantly higher in LMCA segments with HRM compared to those without (P=0.04).
- Atorvastatin treatment (12 weeks) led to a greater reduction in coronary inflammation in segments with HRM versus those without (P=0.02).
- This differential anti-inflammatory effect of statins remained significant after adjusting for baseline LDL and statin dose (P=0.038).
Conclusions:
- The anti-inflammatory impact of statins is substantially greater within coronary plaques featuring HRM.
- These findings suggest a mechanism by which statins provide disproportionate benefits to patients with more advanced atherosclerotic disease.
- This study is the first to demonstrate the differential effect of statins on coronary inflammation based on plaque morphology.
Background:
Nonobstructive coronary plaques manifesting high-risk morphology (HRM) associate with an increased risk of adverse clinical cardiovascular events. We sought to test the hypothesis that statins have a greater anti-inflammatory effect within coronary plaques containing HRM.
Methods And Results:
In this prospective multicenter study, 55 subjects with or at high risk for atherosclerosis underwent 18F-fluorodeoxyglucose positron emission tomographic/computed tomographic imaging at baseline and after 12 weeks of treatment with atorvastatin. Coronary arterial inflammation (18F-fluorodeoxyglucose uptake, expressed as target-to-background ratio) was assessed in the left main coronary artery (LMCA). While blinded to the PET findings, contrast-enhanced computed tomographic angiography was performed to characterize the presence of HRM (defined as noncalcified or partially calcified plaques) in the LMCA. Arterial inflammation (target-to-background ratio) was higher in LMCA segments with HRM than those without HRM (mean±SEM: 1.95±0.43 versus 1.67±0.32 for LMCA with versus without HRM, respectively; P=0.04). Moreover, atorvastatin treatment for 12 weeks reduced target-to-background ratio more in LMCA segments with HRM than those without HRM (12 week-baseline Δtarget-to-background ratio [95% confidence interval]: -0.18 [-0.35 to -0.004] versus 0.09 [-0.06 to 0.26]; P=0.02). Furthermore, this relationship between coronary plaque morphology and change in LMCA inflammatory activity remained significant after adjusting for baseline low-density lipoprotein and statin dose (β=-0.27; P=0.038).
Conclusions:
In this first study to evaluate the impact of statins on coronary inflammation, we observed that the anti-inflammatory impact of statins is substantially greater within coronary plaques that contain HRM features. These findings suggest an additional mechanism by which statins disproportionately benefit individuals with more advanced atherosclerotic disease.
Clinical Trial Registration:
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00703261.
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