Intracoronary Imaging, Cholesterol Efflux, and Transcriptomes After Intensive Statin Treatment: The YELLOW II Study.

BACKGROUND: Despite extensive evidence demonstrating the beneficial effects of statins on clinical outcomes, the mechanisms underlying these effects remain elusive. OBJECTIVES: This study assessed changes in plaque morphology using intravascular imaging, with a comprehensive evaluation of cholesterol efflux capacity (CEC) and peripheral blood mononuclear cell (PBMC) transcriptomics in patients receiving high-dose statin therapy. METHODS: In a prospective study, 85 patients with stable coronary artery disease underwent percutaneous coronary intervention for a culprit lesion, followed by intracoronary multimodality imaging, including optical coherence tomography (OCT) of an obstructive nonculprit lesion. All subjects received 40 mg of rosuvastatin daily for 8 to 12 weeks, when the nonculprit lesion was reimaged and intervention performed. Blood samples were drawn at both times to assess CEC and transcriptomic profile in PBMC. RESULTS: Baseline OCT minimal fibrous cap thickness (FCT) was 100.9 ± 41.7 µm, which increased to 108.6 ± 39.6 µm at follow-up, and baseline CEC was 0.81 ± 0.14, which increased at follow-up to 0.84 ± 0.14 (p = 0.003). Thin-cap fibroatheroma prevalence decreased from 20.0% to 7.1% (p = 0.003). Changes in FCT were independently associated with CEC increase by multivariate analysis (ß: 0.30; p = 0.01). PBMC microarray analysis detected 117 genes that were differentially expressed at follow-up compared to baseline, including genes playing key roles in cholesterol synthesis (SQLE), regulation of fatty acids unsaturation (FADS1), cellular cholesterol uptake (LDLR), efflux (ABCA1 and ABCG1), and inflammation (DHCR24). Weighted coexpression network analysis revealed unique clusters of genes associated with favorable FCT and CEC changes. CONCLUSIONS: The study demonstrated an independent association between fibrous cap thickening and improved CEC that may contribute to morphological changes suggesting plaque stabilization among patients taking intensive statin therapy. Furthermore, the significant perturbations in PBMC transcriptome may help determine the beneficial effects of statin on plaque stabilization. (Reduction in Coronary Yellow Plaque, Lipids and Vascular Inflammation by Aggressive Lipid Lowering [YELLOW II]; NCT01837823).

Refractory angina pectoris: mechanism and therapeutic options.

As the survival of patients with primary coronary events continues to increase, the number of patients presenting with coronary artery disease unsuitable to further revascularization techniques and symptoms refractory to medical therapy also continues to rise. The aims of this review were to define the population of patients with refractory angina pectoris and to present the therapeutic options currently available for this condition. Refractory angina pectoris is defined, and traditional medical therapies are discussed. Then, current therapeutic options for patients with refractory angina are extensively reviewed. A multitude of therapeutic options exist for patients with refractory angina pectoris. Small, uncontrolled studies have shown a potential benefit for additional antiplatelet and antithrombotic therapy. In randomized trials, neurostimulation has been shown to be effective in reducing angina symptoms. Enhanced external counterpulsation is a viable treatment option for select patients with refractory angina. In many randomized trials, laser revascularization has been shown to diminish angina symptoms, although no placebo-controlled studies exist to date. Gene therapy is a promising area of research in this field. Percutaneous in situ coronary venous arterialization is in its infancy, but may be able to treat many patients if proved successful. No data support the role of chelation therapy in this population. Heart transplantation remains a final option for these patients. Further research of the techniques mentioned in this review is warranted. The importance of randomized, double-blinded, placebo-controlled trials cannot be overemphasized, as the placebo effect of these therapies is probably marked.