Hirofumi Noike

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.

Enhanced circulating soluble LR11 in patients with coronary organic stenosis.

LR11, an LDL receptor family member, is expressed in intimal smooth muscle cells. It was found that the soluble form of LR11 (sLR11) is detected in serum, and the circulating sLR11 levels are positively correlated with intima-media thickness of carotid arteries in dyslipidemic subjects. To clarify the significance of serum sLR11, the circulating sLR11 levels in patients with organic coronary stenosis and the contributing risk factors for them were studied. The subjects, 150 patients with symptoms of coronary artery disease, underwent coronary angiographic examination, and were divided into sex- and age-matched two groups; one is organic coronary stenosis group (OCS) and the other is normal coronary group (NC). Serum sLR11 levels were significantly higher in OCS than in NC (4.9+/-2.7 U vs 3.6+/-1.8 U, p<0.05). Multivariate regression analysis showed that circulating sLR11 is independent contributing factor for the OCS, as well as diabetes mellitus and dyslipidemia. Among various coronary risk factors for sLR11 level, HbA1c showed the highest correlation coefficient (p<0.01). These results suggest that the circulating sLR11 might reflect coronary organic stenosis, and that hyperglycemic condition might be promoting factor for expression of LR11 in intimal smooth muscle cells.

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.

Waon Therapy for Managing Chronic Heart Failure – Results From a Multicenter Prospective Randomized WAON-CHF Study –

BACKGROUND Waon therapy improves heart failure (HF) symptoms, but further evidence in patients with advanced HF remains uncertain. METHODSANDRESULTS In 19 institutes, we prospectively enrolled hospitalized patients with advanced HF, who had plasma levels of B-type natriuretic peptide (BNP) >500 pg/ml on admission and BNP >300 pg/ml regardless of more than 1 week of medical therapy. Enrolled patients were randomized into Waon therapy or control groups. Waon therapy was performed once daily for 10 days with a far infrared-ray dry sauna maintained at 60℃ for 15 min, followed by bed rest for 30 min covered with a blanket. The primary endpoint was the ratio of BNP before and after treatment. In total, 76 Waon therapy and 73 control patients (mean age 66 years, men 61%, mean plasma BNP 777 pg/ml) were studied. The groups differed only in body mass index and the frequency of diabetes. The plasma BNP, NYHA classification, 6-min walk distance (6MWD), and cardiothoracic ratio significantly improved only in the Waon therapy group. Improvements in NYHA classification, 6MWD, and cardiothoracic ratio were significant in the Waon therapy group, although the change in plasma BNP did not reach statistical significance. No serious adverse events were observed in either group. CONCLUSIONS Waon therapy, a holistic soothing warmth therapy, showed clinical advantages in safety and efficacy among patients with advanced HF.

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.

Effect of nitroglycerin administration on cardio-ankle vascular index

Purpose The purpose of this study was to clarify the difference between effects of nitroglycerin (NTG) on the functional stiffness in patients with and without coronary artery disease (CAD) using a newly developed stiffness index, cardio-ankle vascular index (CAVI). Subjects and methods The two subject groups in this study were normal controls (n=31) and CAD patients (n=25). The normal controls had no medical history and were not on regular medications. On the other hand, the CAD patients had received various treatments like antihypertensive drugs, hypoglycemic agents, and statins. This study was conducted in CAD patients under medications. After a single sublingual administration of NTG 0.3 mg, CAVI, blood pressure (BP), and heart rate (HR) were measured every 5 minutes for 20 minutes. Comparisons of each parameter before and after taking NTG were evaluated for statistical significance using analysis of variance and post hoc tests. Tukey–Kramer test was used for post hoc comparisons. Results In the normal controls, CAVI significantly decreased from baseline after 5, 10, and 15 minutes (from 6.5±0.9 to 5.2±0.9, 5.5±0.9, and 5.7±0.9, respectively). Systolic BP and HR were not significantly changed. Diastolic BP significantly decreased from baseline after 5 and 10 minutes (from 72±8 to 64±9 and 63±9 mmHg, respectively). On the other hand, CAVI, HR, and diastolic BP were not changed significantly in CAD patients. Systolic BP was significantly decreased from baseline after 5, 10, and 15 minutes (from 147±16 to 131±14, 129±12, and 129±13 mmHg, respectively). In the comparison of the two groups, ΔCAVI was not significantly different between the normal controls and CAD patients (−1.4±0.7 vs −1.4±0.9, −1.1±0.7 vs −1.4±1.0, −0.8±0.7 vs −1.2±1.0, and −0.5±0.7 vs −1.1±1.0 at 5, 10, 15, and 20 minutes, respectively). ΔHR was not significantly different between the two groups. ΔSystolic BP in the CAD patients was significantly higher than in the normal controls at 5, 10, 15, and 20 minutes (normal controls vs CAD; −3±7 vs −10±11, −3±5 vs −10±11, −3±6 vs −13±10, and −1±6 vs −11±10 mmHg, respectively). ΔDiastolic BP in the normal controls was significantly higher than in the CAD patients at 5 and 10 minutes (normal controls vs CAD; −8±6 vs −4±4 and −9±4 vs −6±5 mmHg, respectively). Conclusion After NTG administration, the stiffness of the arteries from the origin of the aorta to the ankle as measured by CAVI decreased in both the normal controls and CAD patients, indicating that the response of arterial smooth muscle cells to nitric oxide is preserved even in CAD patients under medication.

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.

Subfraction analysis of circulating lipoproteins in a patient with Tangier disease due to a novel ABCA1 mutation

Tangier disease, characterized by low or absent high-density lipoprotein (HDL), is a rare hereditary lipid storage disorder associated with frequent, but not obligatory, severe premature atherosclerosis due to disturbed reverse cholesterol transport from tissues. The reasons for the heterogeneity in atherogenicity in certain dyslipidemias have not been fully elucidated. Here, using high-performance liquid chromatography with a gel filtration column (HPLC-GFC), we have studied the lipoprotein profile of a 17-year old male patient with Tangier disease who to date has not developed manifest coronary atherosclerosis. The patient was shown to be homozygous for a novel mutation (Leu1097Pro) in the central cytoplasmic region of ATP-binding cassette transporter A1 (ABCA1). Serum total and HDL-cholesterol levels were 59mg/dl and 2mg/dl, respectively. Lipoprotein electrophoretic analyses on agarose and polyacrylamide gels showed the presence of massively abnormal lipoproteins. Further analysis by HPLC-GFC identified significant amounts of lipoproteins in low-density lipoprotein (LDL) subfractions. The lipoprotein particles found in the peak subfraction were smaller than normal LDL, were rich in triglycerides, but poor in cholesterol and phospholipids. These findings in an adolescent Tangier patient suggest that patients in whom these triglyceride-rich, cholesterol- and phospholipid-poor LDL-type particles accumulate over time, would experience an increased propensity for developing atherosclerosis.

Frequency of coronary artery stenosis in patients with asymptomatic familial hypercholesterolemia and its association with carotid intimal thickness and cardio-ankle vascular index [Corrigendum]

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PS 02-09 Effect of nicorandil administration on arterial stiffness monitored with the cardio-ankle vascular index (CAVI) after coronary intervention

Objective: Nicorandil improves coronary arterial dysfunction and improves clinical outcome in patients with ischemic heart disease. But, the precise mechanism was not fully clarified. Cardio-ankle vascular index (CAVI) represents arterial stiffness of the aorta, femoral artery and tibial artery as a whole, and its feature is independency from blood pressure at measuring time. Then, the effect of intravenous nicorandil on arterial stiffness monitored with CAVI, were studied after percutaneous coronary intervention (PCI) in patients with stable angina pectoris (SAP). Design and Method: Study subjects were 45 consecutive patients with SAP underwent successful PCI. Patients were randomized to the control (n = 15), or nicorandil group (n = 30). In the nicorandil group, nicorandil was administrated over 12 hours after PCI (2 or 4 mg/h). CAVI was measured just after PCI and after administration of nicorandil (every 10 minutes for first 30 minutes, 60 minutes, and over 12 hours later). At the same time, stroke volume was measured using electrical bio-impedance method (Aesculon), and various circulation factors were calculated. Results: CAVI was significantly decrease in nicorandil group (9.90 ± 1.00 to 8.68 ± 1.10, p < 0.05), whereas there were no significantly change in control group (9.71 ± 1.22 to 9.39 ± 1.37, p = 0.30). Systolic blood pressure (sBP) and systemic vascular resistance index (SVRI) were significantly decrease only in nicorandil group (sBP; 146.8 ± 15.2 to 118.9 ± 13.7 mmHg, p < 0.05, SVRI; 3725.5 ± 1076.7 to 2632.8 ± 765.9 dyne sec cm−5, p < 0.05). Cardiac index (CI) increased in nicorandil, but not significant (2.31 ± 0.63 to 2.55 ± 0.60 l/min/m2, p = 0.13). CAVI during nicorandol administration significantly correlated with each factors (vs SBP, r = 0.37, vs SVRI, r = 0.29, vs CI, r = -0.21, p < 0.05 in each). Conclusions: In this study, intravenous administration of nicorandil decrease the arterial stiffness monitored with CAVI, indicating that nicorandil decreased an afterload after successful PCI. Improvement of clinical outcome in patients with ischemic heart disease by nicorandil might be due to a decrease of afterload in addition to improvement of coronary arterial dysfunction.