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Aim: Coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFR CT ) accurately diagnoses ischemic lesions of intermediate stenosis severity. However, significant determinants of FFR CT have not been fully evaluated., Methods: This was a sub-analysis of the Treatment of Alogliptin on Coronary Atherosclerosis Evaluated by Computed Tomography-Based Fractional Flow Reserve trial. Thirty-nine diabetic patients (117 vessels) with intermediate coronary artery stenosis [percent diameter stenosis (%DS) ＜70%] in whom FFR CT was measured were included in this study. CCTA-defined, vessel-based volumetric and morphological characteristics of plaques were examined to determine their ability to predict FFR CT ., Results: Patient-based, multivariate linear regression analysis showed that hemoglobinA1c, triglycerides, and the estimated glomerular filtration rate were significant independent factors associated with FFR CT . Vessel-based, univariate linear regression analysis showed that the total atheroma volume (r=－0.233, p=0.01) and the percentage atheroma volume (PAV) (r=－0.284, p=0.002) as well as %DS (r=－0.316, p=0.006) were significant determinants of FFR CT . Among the plaque components, significant negative correlations were observed between FFR CT and low- (r=－0.248, p=0.007) or intermediate-attenuation plaque volume (r=－0.186, p=0.045), whereas calcified plaque volume was not associated with FFR CT . In the left anterior descending coronary artery (LAD), the plaque volume of each component was associated with FFR CT ., Conclusions: Plaque volume, PAV, and %DS were significant determinants of FFR CT . Plaque morphology, particularly in LAD, was associated with FFR CT in diabetic patients with intermediate coronary artery stenosis.

Recently, fractional flow reserve (FFR) derived from coronary computed tomography angiography (CCTA) (FFR CT ) has been developed. However, FFR CT cannot be calculated for all patients from CCTA datasets. The purpose of the present study, therefore, was to evaluate the predictors that results in cases being inappropriate for FFR CT processing. This study was a sub-analysis of the TRACT trial, from which 50 patients were divided into 2 groups according to FFR CT measurability (measurable [group M] or not measurable [group N]) using CCTA examination at baseline. Thirty-nine (78%) patients comprised group M and 11 (22%) comprised group N. Heart rate at CCTA examination (72 beats/min vs. 63 beats/min; p = 0.007) and Agatston score (665 vs. 33; p = 0.002) in group N were significantly higher than those in group M. Multivariate logistic regression analyses revealed that heart rate at CCTA examination (OR 1.348 [95% CI 1.167-1.556]; p < 0.001) and Agatston score (OR 1.002 [95% CI 1.000-1.003]; p = 0.004) were significant, independent factors associated with non-measurability of FFR CT . The frequency of poor image quality was highest in patients with heart rate > 65 beats/min and Agatston score > 400 (p < 0.0001). In conclusions, high heart rate at the time of CCTA examination and higher Agatston score were associated with poor image quality that resulted in cases being inappropriate for FFR CT processing. Heart rate control at CCTA examination is necessary to acquire good-quality images required for computing FFR CT .

Patients with diabetes mellitus are at high risk for developing coronary artery disease (CAD), even if they are treated with statins. Several studies have shown the beneficial effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on the cardiovascular system in an animal model. However, recent clinical trials using DPP-4 inhibitors have shown that these inhibitors fail to reduce the occurrence of cardiovascular events. Therefore, this study will be performed to evaluate the effects of sitagliptin, a DPP-4 inhibitor, on coronary atherosclerosis in patients with type 2 diabetes. This study will be a prospective, open-label, randomized multicenter trial performed in 6 centers in Japan. Stable CAD patients with type 2 diabetes who have undergone successful percutaneous coronary intervention under integrated backscatter (IB)-intravascular ultrasound (IVUS) guidance will be studied. They will be randomly assigned to either the sitagliptin group or a control group. After 48 weeks' treatment, the IVUS examination will be repeated in the same coronary artery as at baseline. The primary end point will be the percentage change in plaque volume measured using grayscale IVUS from baseline to the 48-week follow-up. This study will be the first multicenter trial to evaluate the effects of a DPP-4 inhibitor on coronary atherosclerosis evaluated using IB-IVUS, and the findings will clarify the anti-atherogenic effects of sitagliptin.

Age is a well-established risk factor for cardiovascular disease. Recent trials using intravascular ultrasound (IVUS) have shown that lipid-lowering therapy with statins halts the progression or induces the regression of coronary artery plaques. However, impacts of age on coronary atherosclerosis and vascular response to statin therapy have not been fully evaluated. The effects of 8-month statin therapy on coronary atherosclerosis were evaluated using virtual histology-IVUS. IVUS data were analyzed from 119 patients who were divided into two groups according to age: elderly patients (≥65 years, n = 72) and non-elderly patients (<65 years, n = 47). No patients were taking statins or other lipid-lowering therapies at baseline. At baseline, external elastic membrane (EEM) volume (17.27 vs. 14.95 mm(3)/mm, p = 0.02) and plaque volume (9.49 vs. 8.11 mm(3)/mm, p = 0.03) in the elderly patients were significantly greater than in the non-elderly patients. The EEM volume (-2.4 %, p = 0.007) and plaque volume (-3.1 %, p = 0.007) after 8-month of statin therapy had significantly decreased in the non-elderly patients but not in the elderly patients. A significant positive correlation was observed between age and percentage change in plaque volume (r = 0.265, p = 0.004). A multivariate regression analysis showed that age was a significant predictor of the percentage change in plaque volume during statin therapy (β = 0.223, p = 0.02). Coronary atherosclerosis was more advanced and vascular responses to statin therapy were attenuated in the elderly patients compared to the non-elderly patients.

Objective: Recent trials using intravascular ultrasound (IVUS) have shown that statins induce regression and stabilization of coronary artery plaques. However, there are no reports on whether regression and stabilization in coronary artery plaques associated with statin therapy continue or not. The purpose of the present study was to examine the time course of statin-induced changes in coronary atherosclerosis., Patients and Methods: Coronary atherosclerosis was evaluated using virtual histology-IVUS in 39 patients at the time of a percutaneous coronary intervention, 8 months after statin therapy (mid-term), and at 48-month (long-term) follow-up. IVUS images qualified for evaluation obtained from 30 of these patients at three time points., Results: Significant decreases in low-density lipoprotein cholesterol and high-sensitivity C-reactive protein were observed at 8 months and these decreases continued for 48 months. A decrease in external elastic membrane volume was observed at 8 months (-1.1%) and reached significance at 48 months (-5.9%, P=0.0001). Plaque volume tended to decrease over time, but this was not statistically significant (-1.6% at 8 months and -3.8% at 48 months). An increase in the calcified plaque component was observed at 8 months (0.09±0.34 mm/mm) and reached significance at 48 months (0.21±0.33 mm/mm, P=0.002). Change in the calcified component and change in the external elastic membrane volume showed a significant negative correlation at the long-term follow-up (r=-0.598, P=0.0005)., Conclusion: Continued negative vessel remodeling associated with an increase in the calcified plaque component was observed following prolonged statin therapy by serial virtual histology-IVUS analysis.

Aim: Renal dysfunction is an independent risk factor for cardiovascular events. However, little is known regarding the impacts of renal dysfunction on coronary atherosclerosis., Methods: The effects of 8-month statin therapy on coronary atherosclerosis were evaluated in the TRUTH study using virtual histology intravascular ultrasound in 164 patients with angina pectoris. We analyzed correlations between the estimated glomerular filtration rate (eGFR) and coronary atherosclerosis before and during statin therapy., Results: Baseline eGFR was 64.5 mL/min per 1.73 m(2) . Serum low-density lipoprotein cholesterol level decreased significantly from 132 to 85 mg/dL (-35%, P < 0.0001) after 8 months. Weak, but significant, negative correlations were observed between eGFR and external elastic membrane volume (r = -0.228, P = 0.01) and atheroma volume (r = -0.232, P = 0.01) at baseline. The eGFR was also negatively correlated with fibro-fatty volume (r = -0.254, P = 0.005) and fibrous volume (r = -0.241, P = 0.008) at baseline. Multivariate regression analyses showed that eGFR was a significant independent predictor associated with statin pre-treatment volume in fibro-fatty (β = -0.23, P = 0.01) and fibrous (β = -0.203, P = 0.02) components. Furthermore, eGFR was positively correlated with volume change in the fibro-fatty component during statin therapy (r = 0.215, P = 0.02)., Conclusion: Decreased eGFR is associated with expanding remodelling and a greater atheroma volume, particularly the fibro-fatty and fibrous volume before statin therapy in patients with normal to mild renal dysfunction. Reduction of fibro-fatty volume during statin therapy gradually accelerated with decreasing renal function., (© 2012 The Authors. Nephrology © 2012 Asian Pacific Society of Nephrology.)

Statin therapy produces regression of coronary artery plaques and reduces the incidence of coronary artery disease. However, not all patients show regression of coronary atherosclerosis after statin therapy. The purpose of the present study was to identify differences in clinical characteristics, serum lipid profiles, arterial remodeling, and plaque composition between patients with progression and those with regression of coronary atherosclerosis during statin therapy. The effects of 8-month statin therapy on coronary atherosclerosis were evaluated in the Treatment With Statin on Atheroma Regression Evaluated by Intravascular Ultrasound With Virtual Histology (TRUTH) study using intravascular ultrasound-virtual histology. One hundred nineteen patients were divided into 2 groups according to atheroma volume increase (progressors) or decrease (regressors) during an 8-month follow-up period. Fifty-one patients (43%) were categorized as progressors and the remaining 68 (57%) as regressors. External elastic membrane volume increased, although not significantly (0.8%, p = 0.34), and luminal volume decreased significantly (-5.3%, p = 0.0003) in progressors, while external elastic membrane volume decreased significantly (-3.2%, p <0.0001) and luminal volume increased (2.2%, p = 0.13) in regressors. The fibrous component increased significantly in progressors, while this component decreased in regressors. A strong positive correlation was observed between change in atheroma volume and change in fibrous volume (r = 0.812, p <0.0001). In conclusion, coronary arteries showed negative remodeling during statin-induced plaque regression. The difference in plaque composition between patients with progression and those with regression of coronary atherosclerosis during statin therapy arose from the difference in the change in fibrous component., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Systemic therapy with statin has been shown to lower the risk of coronary events; however, the in vivo effects of statin therapy on plaque volume and composition are less understood., Methods: We conducted a prospective, open-labeled, randomized, multicenter study in 11 centers in Japan. A total of 164 patients were randomized to receive either 4 mg/d of pitavastatin (intensive lipid-lowering therapy) or 20 mg/d of pravastatin (moderate lipid-lowering therapy). Analyzable intravascular ultrasound data were obtained for 119 patients at baseline and at 8-month follow-up. The primary end point was the difference of volume changes in each of the 4 main plaque components (fibrosis, fibrofatty, calcium, and necrosis), assessed by virtual histology intravascular ultrasound, between the 2 groups., Results: The mean low-density lipoprotein cholesterol level at follow-up was significantly lower in the pitavastatin than in the pravastatin group (74 vs 95 mg/dL, P < .0001). During the 8-month follow-up period, statin therapy reduced the absolute and relative amount of fibrofatty component (pitavastatin: from 1.09 to 0.81 mm(3)/mm, P = .001; pravastatin: from 1.05 to 0.83 mm(3)/mm, P = .0008) and increased in the amount of calcium (pitavastatin: from 0.42 to 0.55 mm(3)/mm, P < .0001; pravastatin: from 0.44 to 0.55 mm(3)/mm, P = .005), whereas volume changes in both plaque components were not statistically different between the 2 groups., Conclusions: Both pitavastatin and pravastatin altered coronary artery plaque composition by significantly decreasing the fibrofatty plaque component and increasing the calcified plaque component., (Copyright © 2012 Mosby, Inc. All rights reserved.)