永井 良三

Background: Actual data regarding coronary artery disease (CAD) patients in Japan is scarce, so in the present study a large database of Japanese patients with significant CAD was constructed for analysis of the relationship between medical treatments and outcomes in this cohort. Methods and Results: The present study enrolled 15,628 patients who underwent coronary angiography and were diagnosed as having significant stenosis in at least 1 coronary artery. Of these, 13,812 patients were followed up and included in the analysis: 10,626 (77%) men and 3,186 (23%) women. Diagnosis at the time of registration was acute myocardial infarction (AMI) for 2,955 patients, old myocardial infarction for 3,913 patients and unstable angina pectoris for 2,049 patients. Patients were followed up for an average of 2.7 years. At the start of the follow-up, 37.4% of the patients were prescribed statins, 50.2% calcium-channel blockers (CCB), 31.6% angiotensin-converting enzyme inhibitors (ACEI), 13.5% angiotensin II receptor blockers (ARB) and 60.2% nitrates. Univariate Cox regression model analysis showed that the hazard ratio (HR) of statins was 0.780 (95% confidence intervals (CI), 0.710-0.856 p&lt 0.001) fibrates, 0.580 (95%CI, 0.425-0.790 p=0.001) CCB, 1.067 (95%CI, 0.976-1.166 p=0.153) ACEI, 1.062 (95%CI, 0.968-1.166 p=0.202) ARB, 1.036 (95%CI, 0.914-1.174 p=0.581) nitrates, 1.147 (95%CI, 1.043-1.260 p=0.005). When the data were adjusted for background data and all cardiovascular medications, the HR of statins was 0.809 (95%CI, 0.726-0.901 p&lt 0.001), CCB 1.031 (95%CI, 0.937-1.135 p=0.535), ACEI 1.023 (95%CI, 0.924-1.132 p=0.663), ARB 0.991 (95%CI, 0.867-1.132 p=0.890), nitrates 1.074 (95%CI, 0.973-1.186 p=0.155). For patients presenting with AMI at the time of registration, the HR of CCB was 1.340 (95%CI, 1.084-1.655 p=0.007) and that of nitrates was 0.862 (95%CI, 0.703-1.059 p=0.157). Conclusion: In a cohort of CAD patients in Japan, the prescription pattern differed from that of Western studies. Statins and fibrates were shown to be significantly beneficial in the whole cohort. In the AMI subgroup, CCB showed a deleterious effect and nitrates showed a non-significant tendency for beneficial effect, which should be investigated in future randomized control trials.

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INTRODUCTION: Recent advances in our understanding of the pathophysiological and molecular mechanisms involved in pulmonary arterial hypertension have led to the development of novel and rational pharmacological therapies. In addition to conventional therapy (i.e., supplemental oxygen and calcium channel blockers), prostacyclin or endothelin receptor antagonists have been recommended as a first-line therapy for pulmonary arterial hypertension. However, these treatments have potential limitations with regard to their long-term efficacy and improvement in survival. Furthermore, intravenous prostacyclin (epoprostenol) therapy, which is recommended by most experts for patients with New York Heart Association (NYHA) functional class IV, is complicated, uncomfortable for patients, and expensive because of the cumbersome administration system. Considering these circumstances, it is necessary to develop additional novel therapeutic approaches that target the various components of this multifactorial disease. CASE REPORT: In this short review, we present an overview of the current treatment options for pulmonary arterial hypertension and describe a case report with primary pulmonary hypertension. A male patient with NYHA functional class IV and showing no response to calcium channel blockers and prostacyclin exhibited significantly improved exercise tolerance and hemodynamics and long-term survival for more than 2.5 years after receiving an oral combination therapy of a phosphodiesterase type 5 inhibitor (sildenafil), phosphodiesterase type 3 inhibitor (pimobendan), and nicorandil. FUTURE PERSPECTIVE: We also discuss the background and plausible potential mechanisms involved in this case, as well as future perspectives in the treatment of pulmonary arterial hypertension.

Statins not only reduce serum cholesterol but they also improve vascular endothelial function independent of their lipid-lowering effects. However, except for the mechanism of nitric oxide induction via calveolin, the physiologic basis for the pleiotropic effect of statins remains unknown. In the present study, we investigated the relationship between the effects of statins on vascular endothelial cell function and heat shock proteins. We found that, in vascular endothelial cells, simvastatin increased the steady-state levels of heat shock proteins 90 and 70, and heme oxygenase-1 and caused the nuclear translocation of heat shock factor 1. A decoy oligonucleotide encoding the heat shock element inhibited statin-induced expression of heat shock protein 70, endothelial nitric oxide synthase, and thrombomodulin. This decoy oligonucleotide also inhibited the ability of statin to reduce endothelin-1 and plasminogen activator inhibitor-1 expression. These results indicate that statins improve vascular endothelial function via heat shock factor 1, which may contribute to their ability to improve cardiovascular disease. © 2005 Elsevier Ireland Ltd. All rights reserved.