Takashi Hitsumoto

Preheparin serum lipoprotein lipase mass is negatively related to coronary atherosclerosis

In preheparin serum, there exists lipoprotein lipase (LPL) mass with little activity. The clinical significance of this preheparin serum LPL mass (preheparin LPL mass) is unclear. We studied the levels of preheparin LPL mass in patients with coronary atherosclerosis, comparing the results with those in healthy men. We also evaluated the correlation between preheparin LPL mass and the severity of coronary atherosclerosis by comparing with other risk factors such as age, smoking, family history, hypertension, hyperuricemia, diabetes mellitus, total cholesterol, triglyceride, high density lipoprotein-cholesterol and body mass index. The subjects, 70 men presenting with symptoms of coronary artery disease, underwent coronary angiographic examination. Significant narrowness was defined as > or = 75%. Control group comprised 77 men who had annual health checks and showed no abnormal findings. Preheparin LPL mass in the stenosis group was lower than normal coronary group and also than the control group. Multivariate analysis showed that preheparin LPL mass had the highest t-value (-2.53) for the number of lesions among the risk factors listed above. These results suggest that low preheparin LPL mass may be deeply involved in the progression of coronary atherosclerosis.

Preventive effects of an antiallergic drug, pemirolast potassium, on restenosis after percutaneous transluminal coronary angioplasty

BACKGROUND We recently confirmed that pemirolast potassium, an antiallergic agent, markedly inhibits migration and proliferation of vascular smooth muscle cells. It has also been reported that pemirolast inhibits intimal hyperplasia in animal experiments. METHODS AND RESULTS To elucidate the preventive effects of pemirolast on restenosis after percutaneous transluminal coronary angioplasty (PTCA), 227 patients were enrolled in this prospective, randomized trial. A total of 205 patients who were compatible with the protocol were analyzed (pemirolast group, 104 patients with 140 lesions; control group, 101 patients with 133 lesions). Patients in the pemirolast group received 20 mg/d of pemirolast from 1 week before PTCA until the time of follow-up angiography (4 months after PTCA). Angiographic restenosis was defined as diameter stenosis >/=50% at follow-up. Restenosis rates were significantly lower in the pemirolast group than in the control group (24.0% vs 46.5% of patients, 18.6% vs 35.3% of lesions, P <.01, respectively). During 8 months of follow-up, there were no coronary events (death, myocardial infarction, coronary artery bypass surgery, or repeated PTCA) in 81.7% of the pemirolast group and in 63.4% of the control group (P =.013). CONCLUSIONS This study suggested that pemirolast would be useful in the clinical setting to prevent restenosis after PTCA.

Factors affecting impairment of blood rheology in obese subjects

OBJECTIVES Impairment of blood rheology has been reported to be associated with cardiovascular diseases. Recently, visible micro channel methods [micro channel array flow analyzer (MC-FAN)] have been developed to clinically evaluate blood rheology. The aim of this cross-sectional study is to clarify the factors important for impairment of blood rheology in obese subjects using MC-FAN. METHODS One hundred and fifty-nine obese subjects and 100 non-obese subjects with no history of cardiovascular diseases were enrolled. Blood passage time (BPT) was measured using MC-FAN and relationships between BPT and various clinical parameters were examined. RESULTS BPT was significantly higher in obese subjects than in non-obese subjects (obesity vs. non-obesity: 62.8 ± 17.9s vs. 54.1 ± 14.6s, p<0.001); however, there were no significant relationships between BPT and body mass index or waist circumference in obese subjects. BPT was significantly related to systolic blood pressure levels (r=0.21; p<0.001), high-sensitivity C-reactive protein concentrations (r=0.37; p<0.001), a marker of inflammation, and derivatives of reactive oxygen metabolites test (r=0.38; p<0.001), a marker of oxidative stress, smoking, and exercise habits in obese subjects. Furthermore, multivariate analysis revealed that derivatives of reactive oxygen metabolites test (t=5.2; p<0.001), high sensitivity C-reactive protein concentration (t=3.6; p<0.01), smoking (t=3.2; p<0.001), and exercise habits (t=-2.4; p<0.05) were independent variables for BPT. CONCLUSION Data indicate that inflammation, oxidative stress, and lifestyle choices are more important factors for impairment of blood rheology, which is evaluated by MC-FAN, than the degree of adiposity in obese subjects.

Factors affecting high-sensitivity cardiac troponin T elevation in Japanese metabolic syndrome patients

Purpose The blood concentration of cardiac troponin T (ie, high-sensitivity cardiac troponin T [hs-cTnT]), measured using a highly sensitive assay, represents a useful biomarker for evaluating the pathogenesis of heart failure or predicting cardiovascular events. However, little is known about the clinical significance of hs-cTnT in metabolic syndrome. The aim of this study was to examine the factors affecting hs-cTnT elevation in Japanese metabolic syndrome patients. Patients and methods We enrolled 258 metabolic syndrome patients who were middle-aged males without a history of cardiovascular events. We examined relationships between hs-cTnT and various clinical parameters, including diagnostic parameters of metabolic syndrome. Results There were no significant correlations between hs-cTnT and diagnostic parameters of metabolic syndrome. However, hs-cTnT was significantly correlated with age (P<0.01), blood concentrations of brain natriuretic peptide (P<0.01), reactive oxygen metabolites (markers of oxidative stress, P<0.001), and the cardio–ankle vascular index (marker of arterial function, P<0.01). Furthermore, multiple regression analysis revealed that these factors were independent variables for hs-cTnT as a subordinate factor. Conclusion The findings of this study indicate that in vivo oxidative stress and abnormality of arterial function are closely associated with an increase in hs-cTnT concentrations in Japanese metabolic syndrome patients.

Angioscopic Evaluation of Stabilizing Effects of Bezafibrate on Coronary Plaques in Patients With Coronary Artery Disease

Background Since long-term administrations of anti-hyperlipidemic agents result in reduction in % stenosis or increase in minimum lumen diameter (MLD) of stenotic coronary segments, it is generally believed that anti-hyperlipidemic agents stabilize vulnerable coronary plaques. However, recent pathologic and angioscopic studies revealed that vulnerability of coronary plaques is not related to severity of stenosis and the rims rather than top of the plaques disrupt, and therefore, angiography is not adequate for evaluation of vulnerability. Angioscopy enables macroscopic pathological evaluation of the coronary plaques. Therefore, we carried out a prospective angioscopic open trial for evaluation of the stabilizing effects of bezafibrate on coronary plaques. Methods From April, 1997 to December, 1998, 24 patients underwent coronary angioscopy of the plaques in the non-targeted vessels during coronary interventions and 6 months later. The patients were divided into control (10 patients, 14 plaques) and bezafibrat (14 patients, 21 plaques) groups. Oral administration of bezafibrate (Bezatol SR, 400mg/day) was started immediately after the interventions and was continued for 6 months. The vulnerability score was determined based on angioscopic characteristics of plaques and it was compared before and 6 months later. Results Six months later, vulnerability score was reduced (from 1.6 to 0.8;p < 0.05) in bezafibrate group and unchanged (from 1.4 to 1.3; NS) in control group. In bezafibrate group, the changes in vulnerability score was not correlated with those in % stenosis or MLD. Conclusion The results indicate that bezafibrate can stabilize coronary plaques.

Percutaneous dye image cardioscopy for detection of endocardial lesions.

Endocardial lesions are caused not only by inflammatory processes but also by myocardial ischemia, resulting in endocardial thrombosis and cerebral embolism. We deviced a method for direct visualization of endocardial damages by a novel dye image cardioscopy with Evans blue and examined its feasibility in patients with heart disease. The dye was injected into the left ventricle before and after endomyocardial biopsy. Endocardial surface was stained in dark blue in 63% of patients with angina pectoris before biopsy. After biopsy, the biopsied portions were stained in blue in all. The results indicate that endocardium is damaged even in apparently intact LV in patients with ischemic heart disease and that endomyocardial biopsy causes severe endocardial damages.

Relatioship Between Serum 7-Ketocholesterol Concentrations and Coronary Artery Disease

Coronary artery disease is a major health problem and a major cause of death in most industrialized and developing countries. On the other hand, recent basic and clinical studies have illustrated that oxidative stress plays an important role in the progression of coronary atherosclerosis (Kunsch C & Medford RM., 1999; Azumi H et al., 2002). Oxidative stress leads to oxidation of products in vivo and numerous oxidation products have been investigated and their significance examined in atherosclerotic disease (Steinberg D et al., 1997; Ehara S et al., 2001). 7-Ketocholesterol is known to be a major component of the cholesterol oxidation product, oxysterols, and is found in high concentrations in atherosclerotic plaques which contribute to the development of atherosclerosis (Brown AJ & Jessup W., 1998; Smith LL et al., 1996). Thus, 7-ketocholesterol is considered to be an important target factor in the prevention of coronary events and reflects the pathogenesis of coronary artery disease, and therefore has clinical applications. However, the clinical significance of blood 7-ketocholesterol concentrations (7KCHO) are not fully understood, because it is difficult to analyze these concentrations accurately. In the present study, we established a measuring system for serum 7-ketocholesterol concentrations (s-7KCHO) using gas chromatography mass spectrometry technique and attempted to clarify the clinical significance of s-7KCHO in the progression of coronary atherosclerosis using coronary angiography and intra-vascular ultrasound (IVUS).