T helper 1/T helper 2 balance and HMG-CoA reductase inhibitors in acute coronary syndrome: statins as immunomodulatory agents?
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Cell Differentiation↗
Biomedical subjects
Hiroyuki Daida
Publications and source records attributed to Hiroyuki Daida.
Establishment of a high sensitivity plasma assay for human pentraxin3 as a marker for unstable angina pectoris.
OBJECTIVE: Plasma pentraxin 3 (PTX3) levels are increased in patients with acute myocardial infarction, yet its involvement in unstable angina pectoris (UAP) remains unclear. To critically evaluate the role of PTX3 in UAP, a sensitive and precise measurement of PTX3 concentration is needed. METHODS AND RESULTS: We established a high sensitive plasma ELISA assay system for the detection of PTX3 using monoclonal antibodies. The lower limit of detection of our ELISA was 0.1 ng/mL, sensitivity far greater than the current commercially available kit. Plasma samples were obtained from 162 consecutive patients treated for hypertension, hyperlipidemia, diabetes mellitus, or cardiovascular disease at a physician's office. PTX3 was not associated with any known coronary risk factors. Additionally, we collected plasma samples from 252 consecutive subjects admitted to a university hospital for coronary artery assessment by coronary angiography. PTX3 was significantly increased in patients in whom coronary intervention was performed. We further analyzed the plasma level of PTX3 in 52 patients with effort angina (EAP) and 16 patients with UAP. Compared with the control group, PTX3 were significantly higher in the UAP group. CONCLUSIONS: The levels of plasma PTX3 were increased in patients with arterial inflammation, especially UAP. This PTX3 detection system will be useful for the prediction of UAP.
Adult↗
Amlodipine versus angiotensin II receptor blocker; control of blood pressure evaluation trial in diabetics (ADVANCED-J).
BACKGROUND: The coexistence of type 2 diabetes mellitus and hypertension increases the risk of cardiovascular diseases. The U.K. Prospective Diabetes Study has shown that blood pressure control as well as blood glucose control is efficient for prevention of complications in hypertensive patients with diabetes mellitus. However, some reports have shown that it is difficult to control the blood pressure and the concomitant use of a plurality of drugs is needed in hypertensive patients with diabetes mellitus. In recent years renin-angiotensin system depressants are increasingly used for the blood pressure control in diabetic patients. Particularly in Japan, angiotensin II (A II) antagonists are increasingly used. However, there is no definite evidence of the point of which is efficient for the control, the increase in dose of A II antagonist or the concomitant use of another drug, in hypertensive patients whose blood pressure levels are inadequately controlled with A II antagonist. METHODS/DESIGN: Hypertensive patients of age 20 years or over with type 2 diabetes mellitus who have been treated by the single use of AII antagonist at usual doses for at least 8 weeks or patients who have been treated by the concomitant use of AII antagonist and an antihypertensive drug other than calcium channel blockers and ACE inhibitors at usual doses for at least 8 weeks are included. DISCUSSION: We designed a multi-center, prospective, randomized, open label, blinded-endpoint trial, ADVANCED-J, to compare the increases in dose of A II antagonist and the concomitant use of a Ca-channel blocker (amlodipine) and A II antagonist in hypertensive patients with diabetes mellitus, whose blood pressure levels were inadequately controlled with A II antagonist. This study is different from the usual previous studies in that home blood pressures are assessed as indicators of evaluation of blood pressure. The ADVANCED-J study may have much influence on selection of antihypertensive drugs for treatment in hypertensive patients with diabetes mellitus. It is expected to give an important hint for considering the validity of selection of antihypertensive drugs from the aspects not only of the antihypertensive effect but medical cost-effectiveness.
Adult↗
Insulin and nateglinide reduce monocyte adhesion to endothelial cells in Goto-Kakizaki rats exhibiting repetitive blood glucose fluctuation.
Epidemiological studies demonstrated the importance of postprandial hyperglycemia on the progression of atherosclerosis. However, whether treatment of postprandial hyperglycemia by insulin or insulin secretagogues has a beneficial effect on atherosclerosis has not been elucidated. To elucidate the effects of reduction of postprandial rise of blood glucose by insulin and nateglinide on monocyte adhesion to endothelial cells, we used non-obese type 2 diabetic Goto-Kakizaki (GK) rats fed twice daily, as a model of repetitive postprandial hyperglycemia. We investigated the effects of insulin injection and nateglinide administration just before each meal for 12 weeks on monocyte adhesion to endothelial cells. By setting the doses of insulin and nateglinide, both treatment significantly reduced postprandial hyperglycemia without significant reduction of HbA1c. Nateglinide also reduced serum insulin level just after 1 h meal. Both nateglinide and insulin therapy reduced the number of monocytes adherent to the aortic endothelial layer. Nateglinide, but not insulin, reduced intimal thickness of the thoracic aorta. While increased serum insulin level might be regarded as a factor responsible for the progression of atherosclerosis, our data showed that treatment with pre-meal insulin or nateglinide, which reduces postprandial hyperglycemia, reduced monocyte adhesion to endothelial cells.
Animals↗
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.
Angioplasty, Balloon, Coronary↗
Acarbose, an alpha-glucosidase inhibitor, improves endothelial dysfunction in Goto-Kakizaki rats exhibiting repetitive blood glucose fluctuation.
Several epidemiological studies have revealed that subjects with postprandial hyperglycemia are at increased risk of cardiovascular disease. However, the impact of postprandial hyperglycemia and its treatment on endothelial function has not been clarified yet. In this study, Goto-Kakizaki (GK) rats, a non-obese type 2 diabetes model, fed twice daily were used as a model of repetitive postprandial glucose spikes. We investigated the endothelial function in these rats treated or untreated with acarbose, an alpha-glucosidase inhibitor. Administration of acarbose for 12 weeks markedly improved postprandial hyperglycemia, postprandial insulin level, total cholesterol, triglyceride, and free fatty acid level in GK rats. Furthermore, acarbose efficiently reduced the number of monocytes adherent to aortic endothelial layer, improved acetylcholine-dependent vasodilatation, and reduced intimal thickening of the aorta. While it is generally regarded that repetitive postprandial hyperglycemia is associated with the onset of cardiovascular diseases, our data demonstrated that acarbose treatment efficiently ameliorated endothelial dysfunction and reduced intimal thickening, thus adding support to the protective effect of acarbose against the onset of cardiovascular disease.
Acarbose↗
Low-density lipoprotein apheresis therapy with a direct hemoperfusion column: a Japanese multicenter clinical trial.
Low-density lipoprotein (LDL) apheresis has been applied to patients with familial hypercholesterolemia (FH) with coronary artery disease (CAD). To examine the efficacy and safety of a new type of LDL adsorption column (KLD01, Kaneka, Osaka, Japan), which deals with whole blood without separating plasma, the new system was evaluated in a multicenter trial. The present study included 33 FH patients with CAD (24 males, 9 females, 57 +/- 13 years) who were treated five times with a mean interval of 2.12 +/- 0.60 weeks between treatments. We studied the removal efficacies for serum LDL cholesterol, Lipoprotein(a) (Lp(a)) and triglyceride, the times for the preparation of the system and for treatment, symptoms, and the biochemical data. The scheduled treatments were completed by 31 patients. Serum levels of LDL cholesterol, Lp(a) and triglycerides were all significantly reduced with KLD01; 61.5 +/- 6.2%, 72.4 +/- 5.9% and 69.5 +/- 9.7%, respectively. The times for both setting up the column system (26 +/- 7 min) and treatment (138 +/- 20 min) were shorter with KLD01 than conventional methods. Adverse reactions occurred in eight cases (17 episodes), but the patients fully recovered immediately after each apheresis therapy session. We conclude that the new type of LDL adsorption column, one that deals with whole blood, is a promising apheresis therapy for FH patients in view of its efficacy, reduced time for treatment, and safety.
Adult↗
Prognostic value of the metabolic syndrome for long-term outcomes in patients undergoing percutaneous coronary intervention.
BACKGROUND: The prevalence of metabolic syndrome (MS), regarded as an important risk factor for coronary artery disease, is growing. However, the relationship between MS and long-term outcomes after percutaneous coronary intervention (PCI) in the Japanese patient population remains unknown. METHODS AND RESULTS: Seven-hundred and forty-eight consecutive patients who underwent PCI were assessed. Patients were categorized by the presence or absence of MS using the NCEP-ATPIII definition (for obesity, a body mass index >or=25 kg/m(2) was used). Kaplan-Meier estimation and Cox proportional hazards model were used for unadjusted and adjusted analyses for all cause mortality and cardiac events. The progress of 318 (42.5%) patients with MS and 430 (57.5%) patients without MS was analyzed. The mean follow-up was 12.0+/-3.6 years. Overall, there were 88 (11.8%) deaths from all causes, and there were no significant differences between the 2 groups. The occurrence of cardiac events was significantly higher in the MS group than that in the no MS group (25.5% vs 15.6%, hazard ratio 2.23; 95% confidence interval 1.59-3.11; p<0.001). CONCLUSIONS: The presence of MS significantly increased the risks of subsequent cardiac events among patients who underwent PCI.
Aged↗
Japan assessment of pitavastatin and atorvastatin in acute coronary syndrome (JAPAN-ACS): rationale and design.
BACKGROUND: Many trials have shown that 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors reduce the incidence of cardiovascular events and mortality. One method of decreasing the incidence of cardiovascular events could be to reduce the progression of coronary atherosclerosis, and a recent study found that atorvastatin can cause coronary plaque to regress. To generalize this finding, using conventional HMG-CoA reductase inhibitors at many Japanese centers, randomized trials of pitavastatin and atorvastatin will be conducted with patients with acute coronary syndrome (ACS). METHODS AND RESULTS: Patients with ACS who have undergone successful percutaneous coronary intervention under intravascular ultrasound guidance will be studied. They will be randomly allocated to pitavastatin or atorvastatin groups and followed up for 8-12 months. The primary endpoint will be the percent change in coronary plaque volume, and secondary endpoints will include absolute changes in coronary plaque volume, serum lipid levels and inflammatory markers. The safety profile will also be evaluated. CONCLUSIONS: This study will examine the ability of HMG-CoA reductase inhibitors to regress coronary plaque in Japanese patients with ACS and the findings should help to improve the prognosis of such patients and clarify the involved mechanisms.
Atorvastatin↗
Clinical evaluation of adverse effects during bepridil administration for atrial fibrillation and flutter.
BACKGROUND: Bepridil hydrochloride (Bpd) has attracted attention as an effective drug for atrial fibrillation (AF) and atrial flutter (AFL). However, serious adverse effects, including torsade de pointes (Tdp), have been reported. METHODS AND RESULTS: Adverse effects of Bpd requiring discontinuation of treatment were evaluated. Bpd was administered to 459 patients (361 males, 63+/-12 years old) comprising 378 AF and 81 AFL cases. Mean left ventricular ejection fraction and atrial dimension (LAD) were 66+/-11% and 40+/-6 mm, respectively. Adverse effects were observed in 19 patients (4%) during an average follow-up of 20 months. There was marked QT prolongation greater than 0.55 s in 13 patients, bradycardia less than 40 beats/min in 6 patients, dizziness and general fatigue in 1 patient each. In 4 of 13 patients with QT prolongation, Tdp occurred. The major triggering factors of Tdp were hypokalemia and sudden decrease in heart rate. There were no differences in the clinical backgrounds of the patients with and without Tdp other than LAD and age, which were larger and older in the patients with Tdp. CONCLUSION: Careful observation of serum potassium concentration and the ECG should always be done during Bpd administration, particularly in elderly patients.
Age Factors↗
Impact of aspirin treatment on long-term outcome (over 10 years) after percutaneous coronary intervention.
Aspirin has been shown to reduce cardiovascular morbidity and mortality following percutaneous coronary intervention (PCI). However, its effects on long-term (over 10 years) mortality have not been fully elucidated. This retrospective study recorded the patient characteristics and admission medication for all patients undergoing PCI over an 8-year period from 1984 to 1992. Follow-up information was available for 748 patients (100%) for a mean of 143.6 +/- 43.4 months. A propensity analysis was performed to adjust for presumed selection biases in the administration of aspirin. The baseline clinical characteristics were similar between the group that received aspirin and the group that did not, except for the administration of statins and PCI procedural success rate. Of the 748 patients, 535 (71.5%) received aspirin treatment at the time of PCI. During the 12-year follow-up, 54 patients died from any cause and 20 patients from cardiac death. Kaplan-Meier analysis showed that aspirin treatment led to a significant reduction in all cause mortality (10% versus 16.4%; P = 0.01) and cardiac death (3.7% versus 8.0%; P = 0.02) compared to other antiplatelet drugs. The hazard ratio (HR) for the total mortality and cardiac mortality rates was adjusted using the Cox-proportional hazard model for confounding variables and propensity score. The all cause (HR, 0.49; 95%CI [0.29-0.80], P = 0.005) and cardiac mortality rates (HR, 0.32; 95%CI [0.14-0.72], P = 0.006) for patients receiving aspirin remained lower than for those not receiving aspirin. Aspirin treatment at the time of PCI significantly reduced the risk of death from any cause and cardiac death. The administration of aspirin had a positive impact on the over 10-year long-term outcomes of patients who underwent PCI.
Aged↗
Efficacy and safety of controlled-release isosorbide-5-mononitrate in Japanese patients with stable effort angina pectoris.
A new controlled-release isosorbide-5-mononitrate (CR-ISMN) preparation has been developed to meet the requirement for a low nitrate concentration interval in order to avoid nitrate tolerance. We conducted a randomized, double-blind, placebo-controlled study in 31 Japanese patients with stable effort angina pectoris to investigate the efficacy and safety of CR-ISMN. Patients were randomly assigned to either CR-ISMN (40 mg once daily) or placebo groups for 2 weeks after two consecutive symptom-limited treadmill exercise tests using the Bruce protocol to ascertain the reproducibility of exercise tolerance during the placebo run-in period. Exercise tests were repeated at 5, 12, and 24 hours after administration on the final day. No significant difference in exercise time to moderate angina was identified between the CR-ISMN and placebo groups at 5, 12, or 24 hours after administration. However, the changes in exercise were prolonged at 5 hours but not shortened at 24 hours in the CR-ISMN group. The results of subgroup analysis suggested that the concomitant use of insulin might lead to confounding results. Although headache was the most frequent adverse effect in the CR-ISMN group, all symptoms were mild and at self-limiting levels. The plasma concentrations of CR-ISMN maintained therapeutic levels at 5 and 12 hours, and gradually decreased to less than the minimum therapeutic concentration (100 ng/mL) at 24 hours after administration. This study demonstrates that CR-ISMN improves exercise tolerance during the daytime and is well-tolerated in Japanese patients with stable effort angina pectoris without increasing the number of serious adverse effects.
Aged↗
[Complications related to procedures for acute coronary syndrome].
Recent advances in thrombolytic therapy and percutaneous coronary intervention (PCI) have resulted in dramatic improvements in the outcome of patients with acute coronary syndromes (ACS). Unfortunately, the reduced risk of cardiac and non-cardiac complications associated with advancements in technology has also been paralleled by an increase in the incidence of some complications. The most important complications relate to abrupt vessel closure with PCI, which may result in myocardial infarction or cardiac death. Major bleeding is also a relatively frequent non-cardiac complication of thrombolytic therapy and it is associated with a poor hospital prognosis. Most complication can be prevented or at least minimized with proper strategy, execution, and patient selection.
Angina, Unstable↗
[Positioning of PROactive and its clinical application in Japan--a new direction in diabetes care discussed by diabetology and circulatory disease specialists: discussion].
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Cardiovascular Diseases↗
Efficacy of peroxisome proliferative activated receptor (PPAR)-alpha ligands, fenofibrate, on intimal hyperplasia and constrictive remodeling after coronary angioplasty in porcine models.
Constrictive remodeling and intimal hyperplasia play a prominent role in restenosis after angioplasty. It has been reported that the severity of constrictive remodeling and intimal hyperplasia correlate with adventitial angiogenesis and inflammation. Experimental evidence indicates that inflammation participates in angiogenesis, and therefore inhibition of inflammation may impair neovascularization. We tested whether fenofibrate, peroxisome proliferative activated receptors (PPAR)-alpha specific ligand, inhibits the early inflammation, adventitial angiogenesis, constrictive remodeling and intimal hyperplasia after angioplasty using porcine coronary arteries. Fenofibrate was tested in vivo, in 30 coronary arteries of 10 pigs (1g/day, orally) and was compared to placebo. Quantitative intravascular ultrasound and histopathologic assessment showed that fenofibrate increased lumen (6.28 mm(2) versus 5.15 mm(2)), vessel area (7.34 mm(2) versus 6.69 mm(2)) and inhibited constrictive remodeling. Inflammatory cell infiltration was evaluated with scanning electron microscopy 3 days after angioplasty and was significantly decreased in the treated vessels compared to control. Adventitial angiogenesis 3 days after angioplasty was significantly reduced in the injured vessels derived from the fenofibrate treated group compared to placebo. In conclusion, pharmacological activation of PPAR-alpha inhibited constrictive remodeling and neointimal hyperplasia after angioplasty through inhibition of inflammation and adventitial neovascularization.
Angioplasty, Balloon, Coronary↗
Platelets activated by collagen through the immunoreceptor tyrosine-based activation motif in the Fc receptor gamma-chain play a pivotal role in the development of myocardial ischemia-reperfusion injury.
Platelet activation and the formation of platelet microaggregates in coronary vessels play pivotal roles in myocardial ischemia and reperfusion injury. The Fc receptor gamma-chain (FcR gamma) is coexpressed with glycoprotein (GP) VI, forming a platelet collagen receptor, and the activation of platelets by collagen is closely coupled with tyrosine phosphorylation of the FcRgamma. To examine the functional significance of platelet FcR gamma/GPVI complex in the early phase of myocardial ischemia and reperfusion injury in mice, we performed coronary occlusion and reperfusion experiments using wild type mice and FcRgamma-deficient (FcRgamma(-/-)) mice that lack GPVI. The infarct size was significantly smaller in FcRgamma(-/-) mice subjected to occlusion and reperfusion of the coronary artery than in control FcR gamma(+/+) mice. Twenty-four hours after the reperfusion, electron microscopy of the injured tissue showed substantially more platelet aggregation and occlusive platelet microthrombi in the capillaries of the damaged areas of the wild type mice than in those of the FcR gamma(-/-) mice. Platelet Syk was scarcely activated in the FcR gamma(-/-) mice after myocardial ischemia and reperfusion, but significantly activated in the FcR gamma(+/+) mice. CD11b expression on neutrophils was elevated after myocardial ischemia and reperfusion in both mouse groups, whereas myeloperoxidase activity in the injured areas was significantly lower in the FcRgamma(-/-) mice than in the FcRgamma(+/+) mice. These results suggest that the collagen-induced activation of platelets through the FcR gamma plays a pivotal role in the extension of myocardial ischemia-reperfusion injury. FcRgamma and GPVI may be important therapeutic targets for myocardial ischemia-reperfusion injury.
Animals↗
Granulocyte colony-stimulating factor promotes neovascularization by releasing vascular endothelial growth factor from neutrophils.
The granulocyte colony-stimulating factor (G-CSF) promotes angiogenesis. However, the exact mechanism is not known. We demonstrate that vascular endothelial growth factor (VEGF) was released by Gr-1+CD11b- neutrophils but not Gr-1-CD11b+ monocytes prestimulated with G-CSF in vitro and in vivo. Similarly, in vivo, concomitant with an increase in neutrophil numbers in circulation, G-CSF augmented plasma VEGF level in vivo. Local G-CSF administration into ischemic tissue increased capillary density and provided a functional vasculature and contributed to neovascularization of ischemic tissue. Blockade of the VEGF pathway abrogated G-CSF-induced angiogenesis. On the other hand, as we had shown previously, VEGF can induce endothelial progenitor cell (EPC) mobilization. Here, we show that G-CSF also augmented the number of circulating VEGF receptor-2 (VEGFR2) EPCs as compared with untreated controls. Blocking the VEGF/VEGFR1, but to a much lesser extent, the VEGF/VEGFR2 pathway in G-CSF-treated animals delayed tissue revascularization in a hindlimb model. These data clearly show that G-CSF modulates angiogenesis by increasing myelomonocytic cells (VEGFR1+ neutrophils) and their release of VEGF. Our results indicated that administration of G-CSF into ischemic tissue provides a novel and safe therapeutic strategy to improve neovascularization.
Analysis of Variance↗
[Diagnosis and treatment of acute coronary syndrome].
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Acute Disease↗