Statins and High-Intensity Plaques on T1-Weighted Imaging

Study Questions:

High-T1 signal intensity is known to be a marker of high-risk coronary plaques. Does this characteristic improve with high-intensity statin therapy?

Methods:

The AQUAMARINE (Attempts at Plaque Vulnerability Quantification with Magnetic Resonance Imaging Using Noncontrast T1-weighted Technique) authors conducted a nonrandomized open-label study of 53 subjects with known coronary artery disease (CAD) treated with 4 mg/day of pitavastatin. Cardiac magnetic resonance imaging with coronary T1-weighted imaging and coronary computed tomography angiography were performed at baseline and at 12 months after statin therapy was initiated. Changes in plaque T1-signal were characterized by the plaque-to-myocardial signal-intensity ratio (PMR). Because randomization of CAD patients to no statin was thought to be unethical, a cohort of 48 propensity-matched subjects who had previously been imaged (prior to this study) and had not been treated with statins or other low-density lipoprotein (LDL)-lowering agents was used. In addition to imaging markers, high-sensitivity C-reactive protein (hs-CRP) was measured at baseline and at 1 year.

Results:

Pitavastatin was associated with a 42% (p < 0.001) decrease compared to baseline in LDL cholesterol compared to no change in the matched controls (-3%, p = 0.79). Similar changes in hs- CRP were also seen (-47% [p < 0.001] vs. 2% [p = 0.77]). Although baseline PMR was comparable between statin-treated patients and controls (1.38 vs. 1.22, p = 0.92), at 1 year, PMR was dramatically lower in the statin group (1.11 vs. 1.49) due to significant decrease (p < 0.001) in the statin group and significant increase in the control group (p < 0.001). Changes in PMR were correlated with changes in LDL cholesterol (R = 0.53) and change in hs-CRP (R = 0.35). Similar results were seen with a per-plaque analysis. tatin therapy also had a favorable effect on total atheroma volume and low attenuation plaque volume.

Conclusions:

Statin therapy results in a reduction in high-T1 signal intensity plaque, which is likely related to the mechanism whereby statin therapy reduces risk of CAD complications.

Perspective:

High-T1 signal intensity plaque, previously shown to be associated with worse prognosis, improves with 1 year of high-intensity statin therapy. The physiological significance of high-T1 signal intensity is not fully known, but may be related to the amount of lipid core, intraplaque hemorrhage, and thrombus. Consequently, this study offers insights into noninvasive techniques, which may help explain the plaque stabilization effects of statin, which may be even more substantial than the plaque regression effects. Although the clinical niche for this imaging tool remains unclear, it is likely that improvement in high-T1 signal intensity plaque is a useful imaging biomarker for the study of natural history and emerging CAD therapies.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Nonstatins, Novel Agents, Statins, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Magnetic Resonance Imaging, Nuclear Imaging

Keywords: Angiography, Biological Markers, C-Reactive Protein, Cholesterol, LDL, Coronary Artery Disease, Dyslipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lipoproteins, LDL, Magnetic Resonance Imaging, Plaque, Atherosclerotic


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