Azelnidipine and amlodipine anti-coronary atherosclerosis trial in hypertensive patients undergoing coronary intervention by serial volumetric intravascular ultrasound analysis in Juntendo University (ALPS-J).

BACKGROUND: A previous study reported that amlodipine retarded coronary plaque progression in patients with coronary artery disease. The goal of this multicenter study was to determine which calcium-channel blockers (CCBs) other than amlodipine attenuated the progression of plaque volume (PV) accessed by intravascular ultrasound (IVUS). METHODS AND RESULTS: ALPS-J was a prospective, randomized open-label study conducted at 5 centers. Patients who had hypertension and were scheduled for coronary intervention were enrolled. Subjects were randomly assigned to receive 16 mg/day of azelnidipine or 5mg/day of amlodipine administered for 48 weeks. The primary endpoint was the percent change in coronary PV measured by IVUS. Between 2007 and 2009, 199 patients were enrolled; 115 had evaluable IVUS images at both baseline and after 48 weeks of treatment. Blood pressure significantly reduced to 128/68 mmHg at follow-up. The lipid profiles in the 2 groups were comparable (low-density lipoprotein cholesterol: 97 mg/dl). The %change in PV showed a significant regression of 4.67 and 4.85% in the azelnidipine and amlodipine groups, respectively. The upper limit of the 95% confidence interval of the mean difference in %change PV between the 2 groups (0.18%, 95% confidence interval 4.62 to 4.98%) did not exceed the pre-defined non-inferiority margin of 6.525%. CONCLUSIONS: ALPS-J demonstrated that azelnidipine was not inferior to amlodipine for primary efficacy. In addition to standard medical therapy, dihydropyridine CCBs will retard PV progression in hypertensive patients.

Effects of fenofibrate on lipid profiles, cholesterol ester transfer activity, and in-stent intimal hyperplasia in patients after elective coronary stenting.

BACKGROUND: The association between modulation of detailed lipoprotein profiles and cholesterol ester transfer (CET) activity by peroxisome proliferator-activated receptor (PPAR)-a agonists in patients with coronary artery disease remains unclear. We assessed lipid profiles, plasma CET activity, and in-stent intimal hyperplasia after fenofibrate treatment in patients who underwent elective coronary stenting. METHODS: Forty-three consecutive patients who underwent elective coronary stenting were randomized to the fenofibrate group (300 mg/day for 25 weeks, n = 22) or the control group (n = 21). At baseline and follow up, CET activity and lipoprotein profiles were measured, and quantitative coronary angiography was performed. RESULTS: In the fenofibrate group, the levels of large very low-density lipoprotein cholesterol, and small low-density lipoprotein (LDL) cholesterol decreased and those of small high-density lipoprotein (HDL) cholesterol increased. Besides, CET activity decreased independent of the effect of fenofibrate on total and LDL cholesterol. The reduction of CET activity significantly correlated with the increase in LDL particle size (r = 0.47, P = 0.03) and the decrease of triglycerides in large HDL subclasses (r = 0.48, P = 0.03). Although there were no significant differences in restenosis parameters between the two groups, low CET activity significantly correlated with the inhibition of neointimal hyperplasia (r = 0.56, P = 0.01). CONCLUSIONS: Fenofibrate inhibited CET activity and thereby improved atherogenic lipoprotein profiles, and reduced intimal hyperplasia after coronary stenting.

Azelnidipine and amlodipine anti-coronary atherosclerosis trial in hypertensive patients undergoing coronary intervention by serial volumetric intravascular ultrasound analysis in Juntendo university (ALPS-J).

PURPOSE: Many trials have shown that calcium channel blockers (CCBs) can reduce the cardiovascular (CV) events in patients with coronary artery disease (CAD). The mechanisms of this effect could be associated with plaque regression due to the anti-atherosclerotic properties of CCBs. The goal of this study is to determine the effects of CCB on volumetric quantitative changes of coronary plaques accessed by intravascular ultrasound (IVUS). To confirm this hypothesis, a multicenter randomized trial of CCBs treatment with azelnidipine or amlodipine will be conducted in hypertensive CAD patients undergoing elective percutaneous coronary intervention (PCI). METHODS AND RESULTS: Patients who have hypertension and are scheduled for PCI will be enrolled. Subjects will be randomized to azelnidipine or amlodipine and observed for 48 weeks. The primary endpoint will be the percent change of coronary plaque volume. The secondary endpoint will include inflammatory markers, antioxidant activity, and incidence of composite cardiovascular events. CONCLUSIONS: In this study, we will investigate the improvement of coronary plaque with IVUS by treatment with two dihydropyridine CCBs in hypertensive patients undergoing elective PCI. This result will lead to the discovery of more effective drug therapy for inhibition of coronary events.

Acute myocardial infarction with myocardial perfusion defect detected by contrast-enhanced computed tomography.

The first case was a 68-year-old woman who had acute migratory pain from back to anterior chest and the second case was 66-year-old man with a cardiac tamponade. Two cases were demonstrated with a low density area of the left ventricular postero-lateral wall with conventional contrast-enhanced computed tomography (CE-CT) performed to differentiate the diagnosis of acute coronary syndrome and acute aortic dissection. Subsequent coronary angiograms showed the lesions of left circumflex. These cases of early contrast-defect corresponded to a decreased myocardial blood flow with AMI. CE-CT image facilitated the diagnosis of AMI preceding CAG examination.

Long-term (11-year) statin therapy following percutaneous coronary intervention improves clinical outcome and is not associated with increased malignancy.

BACKGROUND: Statins have been proven to reduce cardiac events and mortality. However, there are few studies dealing with the long-term efficacy of statin therapy following percutaneous coronary intervention (PCI). METHODS: We collected data from 575 consecutive patients who underwent PCI between 1987 and 1992. The baseline data, mortality and incidence of cardiovascular events of patients given statins and those not given statins at the time of PCI were compared. RESULTS: There were 243 patients in the statin group and 332 patients in the non-statin group. During follow-up (11.0+/-3.0 years), 68 patients died. At about 10 years, statin use was significantly associated with lower all-cause mortality (8.2% versus 14.5%, P=0.023) and cardiac death (2.5% versus 6.9%, P=0.017). After adjusting for variables, statin use was found to be an independent predictor of death from all causes (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.29-0.99, P=0.048) and cardiac death (HR 0.24, 95% CI 0.07-0.80, P=0.02). CONCLUSION: Statin use at the time of PCI was associated with a significantly reduced risk of death from all causes and cardiac death. Furthermore, this study provides evidence of a clinical benefit at about 10 years of statin use in patients who underwent PCI.

Serial angiographic follow-up beyond 10 years after coronary artery bypass grafting.

BACKGROUND: The long-term prognosis and serial angiographic follow-up beyond 10 years in patients who underwent coronary artery bypass grafting (CABG) have not been fully studied in Japan. METHODS AND RESULTS: In the present study data from 71 patients who underwent CABG before 1992 were analyzed. Thirty patients had a saphenous vein graft (SVG) only group, and the remaining 41 had a left internal thoracic artery graft to the left anterior descending coronary artery (LITA) group; 6 patients died from malignancy, which was the most common cause of death after CABG. The major adverse cardiac events (MACE) were defined as cardiac death, Q-wave or nonQ-wave myocardial infarction, and congestive heart failure. The MACE-free rate was significantly higher in the LITA group than in the SVG group (p < 0.05). However, among the patients with an ejection fraction < 0.40, there was no significant difference in MACE-free rate between the 2 groups. The LITA patency rate was significantly higher than that for SVG (p < 0.05) and the SVG patency rate was lower in the patients with hyperlipidemia (p < 0.05); cholesterol-lowering therapy improved the SVG patency rate. CONCLUSION: The long-term outcome of CABG was favorable, particularly if using an arterial graft. Although the patency rate was lower for the SVG than LITA, the patient's lipid profile might be an important factor in the SVG patency rate.

Promoter polymorphism in the CD14 gene and concentration of soluble CD14 in patients with in-stent restenosis after elective coronary stenting.

BACKGROUND: Activated monocytes/macrophages, neutrophils, endothelial cells and smooth muscle cells participate in the restenosis processes. Monocytes/macrophages and neutrophils are activated by lipopolysaccharide (LPS) via CD14. Endothelial cells and smooth muscle cells are also stimulated by soluble CD14 (sCD14)-LPS complexes. METHODS: We tested the hypothesis that C(-260)-->T polymorphism of the CD14 gene and sCD14 might be predictors for in-stent restenosis. We analyzed 129 consecutive patients who underwent elective coronary stenting. The restenosis was defined as > or =50% diameter stenosis at follow-up angiography. RESULTS: The prevalence of the T/T genotype and the concentration of sCD14 were significantly higher in the restenosis group than in the no-restenosis group. This CD14 polymorphism also affected the levels of sCD14, therefore, we divided the patients into four groups. The loss index was 24.8% in C/C or C/T and < or =50th percentile of sCD14, 35.9% in T/T and < or =50th percentile of sCD14, 44.2% in C/C or C/T and >50th percentile of sCD14, and 49.1% in T/T and >50th percentile of sCD14 (P=0.02). The restenosis rate was 10.0%, 26.7%, 26.2% and 50.0% in each group, respectively (P=0.003). In the multivariate analysis, T/T and >50th percentile of sCD14 was the independent predictor for in-stent restenosis. CONCLUSIONS: This study showed that the T/T genotype with a high level of sCD14 is an independent predictor of in-stent restenosis. The activation of monocytes/macrophages, endothelial cells and smooth muscle cells mediated by CD14 and/or sCD14 may play an important role in the restenosis processes.

Clinical features of acute pulmonary thromboembolism in younger patients.

The incidence of acute pulmonary thromboembolism (APTE) in younger patients is extremely low compared with older patients, so the clinical features of these younger patients with APTE is unknown. In the present study, 8 patients with APTE who were less than 40 years old (YG) were compared with 40 patients who were more than 41 years of age (OG). All YG patients had coagulopathy compared with 3 patients in the OG (p<0.01). Deep venous thrombosis (DVT) occurred in all 8 patients in the YG compared with 19 patients in the OG (p<0.01). A higher incidence of patients whose symptoms occurred gradually was noted in the YG (p<0.05). There were no significant differences in clinical characteristics, initial symptoms, past history or other predisposing factors for venous thromboembolism between the 2 groups. Residual pulmonary hypertension was not noted in the YG. However, 1 patient in the YG had recurrent APTE, despite good warfarin control. This study demonstrated the frequency of gradual onset, coagulopathy and clinical signs of DVT in the YG and therefore more careful and long-term observation is necessary in such patients.