Purpose: Coronary plaque progression despite very low levels of LDL-C has been reported in the patients with coronary artery disease (CAD) who received intensive statin therapy (IST). Coronary CT Angiography (CCTA) has been applied to evaluate vulnerable coronary plaques having low attenuation of CT value. The major function of PCSK9 is the binding to hepatic LDL receptors, leading to their degradation. PCSK9 is produced also in vascular smooth muscle cells constituting the atherosclerotic lesion in addition to hepatocytes. PCSK9 promotes foam cell formation by suppressing the excretion of cholesterol from macrophages. Statin is demonstrated to promote PCSK9 production. PCSK9 has been proposed to play a crucial role in the pathogenesis of IST resistance. The present study was performed to establish a novel therapeutic approach to IST resistant vulnerable plaque of coronary artery in diabetic patients. Methods: The present study included 142 T2DM patients with non-FHC asymptomatic CAD who developed vulnerable coronary plaques despite IST over 2 years. CCTA by use of 320-slice CT was applied to evaluate vulnerable coronary plaques. During the administration of anti-PCSK9 antibody, changes in serum lipids and CT value of vulnerable coronary plaques were determined. Results: During 1 year administration of anti-PCSK9 antibody, 74% decrease in serum LDL-C was observed. Also, improvement of vulnerable coronary plaque, e.g., rise in the CT value of plaque (from 43.2 ±12.0 HU to 128.5 ± 52.3 HU, p<0.0001) was observed. Of the 142 patients, 95 patients finished the administration of the drug. Conclusion: One year administration of anti-PCSK9 antibody produced a significant stabilization of vulnerable coronary plaques in the patients with asymptomatic CAD who are resistant to IST. An analysis of the plaque quality by CCTA is useful method for the evaluation of the effect of the drug on vulnerable coronary plaques. Disclosure A. Hirai: None. K. Fujimura: None. K. Hirai: None. S. Kondo: None. A. Shirakami: None. T. Sakai: None. K. Murata: None. H. Taniai: None. K. Okuzaki: None. T. Kageyama: None.

Purpose: Long-term injection of insulin preparations causes subcutaneous amyloid deposits called "insulin balls", leading to impaired blood glucose control due to delayed absorption of the drugs. In order to get therapeutic effects of insulin, proper selection of the injection site is quite essential. Subcutaneous amyloid deposition in abdominal wall can be detected by CT examination. The present study was conducted to establish a method for detection of insulin-derived amyloid deposits and the management of insulin injection site by the combination of continuous blood glucose monitoring (CGM) and abdominal wall CT examination. Methods: The present study included 120 T2DM patients who were treated with insulin preparations over 5 years. Two weeks CGM was performed using Free Style Libre Pro. In case of significant day-to-day variation in blood glucose control, abdominal wall CT was performed to detect amyloid deposition. Results: As shown in Figure, abdominal wall CT revealed that subcutaneous amyloid deposition is caused not by ultra-short acting insulin but by long-acting insulin. Blood glucose control was stabilized by insulin injection avoiding amyloid deposits detected by CGM and CT. Conclusion: CGM and abdominal wall CT examination are useful tools for early detection of amyloid deposition by insulin and optimization of injection site. Disclosure A. Hirai: None. K. Hirai: None. H. Nishihara: None. J. Sasaki: None. T. Sudo: None. K. Fujimura: None. T. Kageyama: None.

Purpose: Coronary plaque progression despite very low levels of LDL-C has been reported in the patients with coronary artery disease (CAD) who received intensive statin therapy (IST). CCTA has been applied to detect vulnerable coronary plaques having low attenuation of CT value. The best characterized function of PCSK9 is the binding to hepatic LDL receptors, leading to their degradation. PCSK9 is produced also in vascular smooth muscle cells constituting the atheriosclerotic lesion in addition to hepatocytes. PCSK9 promotes foam cell formation by suppressing the excretion of cholesterol from macrophages. Recently, statin is demonstrated to promote PCSK9 production. PCSK9 has been proposed to play a crucial role in the pathogenesis of IST resistance. The present study was performed to establish a novel therapeutic approach to IST resistant vulnerable plaque of coronary artery in diabetic patients. Methods: The present study included 1T2DM patients with non-FHC asymptomatic CAD who developed vulnerable plaques in coronary artery despite IST over 1 year. CCTA by use of 320-slice CT was applied to evaluate vulnerable plaques in coronary artery. During the administration of anti-PCSK9 antibody, changes in serum lipids and CT value of vulnerable coronary plaques were determined. Results: After the administration of anti-PCSK9 antibody, 72% decrease in serum LDL-C was observed. Also, improvement of vulnerable coronary plaque e.g., rise in the CT value of plaque (from 45.2 ± 12.0 HU to 107.5 ± 42.3 HU, p<0.0001) was observed in 6 months after administration of the drug. Conclusion: A significant improvement in vulnerable coronary plaques was observed in the patients with asymptomatic CAD who are resistant to IST after 6 months administration of anti-PCSK9 antibody. An analysis of the plaque quality by CCTA is useful method for the evaluation of the effect of the drug on vulnerable coronary plaques. Disclosure A. Hirai: None. K. Fujimura: None. S. Kondo: None. T. Sakai: None. S. Ikejima: None. H. Taniai: None. K. Hirai: None. K. Murata: None. A. Shirakami: None. K. Okuzaki: None. T. Kageyama: None.