Kouki Watanabe

Effects of probucol and cilostazol alone and in combination on frequency of poststenting restenosis

The present study was conducted to assess the preventive effect of combined treatment with probucol, an antioxidant, and cilostazol, a phosphodiesterase inhibitor, against poststenting restenosis. Study patients were randomized to 4 modality groups 1 week before stenting: control, probucol (500 mg/day), cilostazol (200 mg/day), and probucol plus cilostazol. Treatment on these modalities was conducted from 5 prestent days until the poststenting follow-up evaluation (6 poststenting months). All patients received aspirin (81 mg/day). The efficacy of each modality against restenosis was evaluated in a total 126 patients with 165 coronary arterial lesions, using a quantitative method. The decrease in luminal diameter at the poststenting follow-up was 1.04 +/- 0.57 mm for controls, 0.88 +/- 0.82 mm for those taking probucol, 0.61 +/- 0.59 mm for those taking cilostazol (p <0.05 vs control), and 0.40 +/- 0.52 mm (p <0.01 vs control) for the combined treatment group. Restenosis rate per segment was 31.7% for controls, 16.7% for the probucol group, 12.5% for the cilostazol group (p <0.05 vs control), and 9.5% for the combined treatment group (p <0.05 vs the control). Neither mortality, myocardial infarction, stent thrombosis, or coronary bypass surgery, nor any serious complications were observed in the combined treatment group. Combined treatment with probucol and cilostazol has thus proved safe and effective in preventing acute poststenting complications and suppressing chronic restenosis.

Thallium-201 myocardial tomography with intravenous infusion of adenosine triphosphate in diagnosis of coronary artery disease

OBJECTIVESnThe purpose of this study was to evaluate the feasibility, safety and diagnostic accuracy of thallium-201 myocardial tomography with intravenous adenosine triphosphate (ATP) infusion in patients with suspected coronary artery disease.nnnBACKGROUNDnBoth ATP and adenosine are potent coronary vasodilators with a very short half-life. Several studies have confirmed that the diagnostic accuracy of adenosine thallium-201 scintigraphy is comparable to that with exercise. However, a high incidence of side effects, including atrioventricular (AV) block, has also been reported. Because the appropriate infusion rate for ATP has not yet been determined, this agent has not been tested in combination with myocardial scintigraphy.nnnMETHODSnThe study group included 253 consecutive patients who underwent thallium-201 myocardial tomography with ATP infusion (0.16 mg/kg body weight per min for 5 min). The occurrence of adverse effects was carefully monitored. Of the 120 patients with coronary angiography, 76 had significant coronary artery disease. Tomographic images were assessed visually and by computer-quantified polar maps, and they were compared with the results of coronary angiography.nnnRESULTSnAlthough 56% of the patients had some adverse effects, they were transient and mild. In all patients, the ATP infusion protocol could be completed, and no patient required aminophylline; AV block occurred in only 2% of the patients. The sensitivity and specificity were 88% and 80%, respectively, by visual analysis and 91% and 86%, respectively, by computer quantification.nnnCONCLUSIONSnThallium tomography with ATP is feasible and has a diagnostic value similar to that with adenosine for detecting coronary artery disease. In addition, it may have fewer side effects than adenosine myocardial tomography.

Preventive effects of probucol on restenosis after percutaneous transluminal coronary angioplasty

This protocol was performed to elucidate the preventive effects of probucol on restenosis after percutaneous transluminal coronary angioplasty (PTCA). A total of 118 patients with 134 vessels undergoing successful PTCA was randomly and prospectively assigned to the probucol group (group P) or the control group (group C). The subjects consisted of 91 men and 27 women, with a mean age of 63.4 +/- 2.3 years. Sixty-six vessels of 59 patients in group P and 68 vessels of 59 patients in group C were evaluated by coronary angiography at 3 months after PTCA. Probucol (0.5 mg/day) was administered between >7 days before PTCA and 3 months after PTCA. The serum total cholesterol (TC) level and the formula low-density lipoprotein cholesterol (formula LDL-C) in group P decreased from 203.8 +/- 43.1 to 169.6 +/- 39.4 mg/dl and from 131.4 +/- 0.7 to 108.7 +/- 2.5 mg/dl, whereas in group C, the levels decreased only from 202.3 +/- 32.1 to 194.2 +/- 29.8 mg/dl and from 129.2 +/- 38.1 to 124.3 +/- 31.7 mg/dl, respectively. The restenosis rate was significantly lower in group P (19.7%; 13 of 66 vessels) than in group C (39.7%; 27 of 68 vessels; p < 0.05). In group P, the probucol blood concentration was significantly higher in the subjects without restenosis (31 +/- 9 microg/ml) than in those with restenosis (18 +/- 8 microg/ml; p < 0.01), but the serum TC and formula LDL-C levels were not significantly different between these two groups. In summary, long-term administration of probucol significantly reduces the incidence of restenosis after PTCA. it was suggested that the mechanism of this preventive effect was not reducing the serum TC or formula LDL-C levels, but rather an inhibitory action on smooth muscle cell proliferation.

Effect of insulin resistance on left ventricular hypertrophy and dysfunction in essential hypertension

BACKGROUNDnIn hypertensive patients, the relationships between glucose tolerance and left ventricular hypertrophy (LVH) and left ventricular diastolic function (LVDF) have been described in several reports.nnnOBJECTIVEnIn this study, we examined the relationships between insulin resistance and LVH and LVDF in hypertensive patients from the therapeutic perspective.nnnMETHODS AND RESULTSnThe study participants were essential hypertensive patients with impaired glucose tolerance (IGT-HT, n = 26), hypertensive patients with normal glucose tolerance (NGT-HT, n = 39), and normotensive control individuals (n = 18). Insulin resistance was evaluated by the insulin suppression test by use of the steady-state plasma glucose (SSPG) level. Left ventricular mass index (LVMI) and LVDF, which was determined by the E:A ratio, were estimated by echocardiography. Temocapril, an angiotensin-converting enzyme inhibitor, was administered in an open, non-randomized manner with a mean dose of 2.8+/-0.2 mg/ day, and the mean administration period was 18 weeks. The systolic and diastolic blood pressure, the LVMI, and the SSPG level were significantly higher in the hypertensive patients than in the control individuals. The mean systolic and diastolic blood pressures were significantly decreased by treatment with Temocapril. Before treatment, stepwise regression analysis showed that SSPG is an independent predictor for LVMI and LVDF. After treatment, the changes in LVMI (D-LVMI; %) (-15.1+/-1.5), the changes in LVDF (D-E:A; %) (-38.2+/-4.1), and the changes in insulin resistance (D-SSPG; %) (-13.7+/-1.7) were significantly higher in the IGT-HT group than in the NGT-HT group (-11.4+/-1.1, -18.1+/-1.7, -9.4+/-1.4, respectively), and the D-SSPG was an independent predictor for D-LVMI and D-E :A.nnnCONCLUSIONSnThe results of this study indicate that insulin resistance is an important factor affecting LVH and LVDF.

Relationship between insulin resistance and cardiac sympathetic nervous function in essential hypertension.

BACKGROUNDnIt has been suggested that hyperinsulinemia and insulin resistance participate in the pathogenesis of hypertension, in part by activating sympathetic activity.nnnOBJECTIVEnWe aimed to examine the relationship between insulin resistance and cardiac sympathetic nervous function in patients with essential hypertension using 123I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy.nnnMETHODS AND RESULTSnTwenty-eight patients (18 men) with essential hypertension and 11 (seven men) control individuals with a mean age of 55.8+/-3.3 years were recruited. Patients with diabetes mellitus, congestive heart failure or coronary artery disease were excluded from this study. To evaluate insulin resistance, we used steady-state plasma glucose (SSPG; mg/dl) levels measured by the SSPG method. To evaluate cardiac sympathetic nervous function, we calculated the heart-to-mediastinum ratio from the delayed MIBG image (H:M-D) and the mean washout rate (WOR, %). There were significant differences (P<0.01) in SSPG, H:M-D and WOR between the essential hypertension and control individual groups (125 versus 103 mg/dl, 2.2 versus 2.4, and 32 versus 23%, respectively). Stepwise regression analysis showed that SSPG and plasma norepinephrine level are independent predictors for the cardiac sympathetic nervous function obtained from MIBG scintigraphy.nnnCONCLUSIONSnThese findings indicate that insulin resistance is significantly related to activation of the cardiac sympathetic nervous function associated with left ventricular hypertrophy in patients with essential hypertension.

Clinical Characteristics of Female Patients With Coronary Spastic Angina

There are many patients with vasospastic angina who have minor atherosclerosis, and in Japan the majority of them are male. No data exist concerning sex differences in patients with coronary spastic angina, so the present study sought to clarify the clinical characteristics between male and female patients with vasospastic angina. Between April 1991 and June 1998, 204 consecutive patients were diagnosed with vasospastic angina and of these, 26 (12.7%) were female. An acetylcholine test was performed with incremental doses of 20, 50, and 80 microg injected into the right coronary artery and 20, 50, and 100 microg into the left coronary artery. Ergonovine was injected in a total dose of 40 microg into the right coronary artery and 64 microg into the left coronary artery. Coronary spasm was defined as 99% or more luminal narrowing accompanied by ischemic changes on ECG. Compared with male patients, female patients had less organic stenosis (12 vs 33%, p<0.05), less history of smoking (15 vs 85%, p<0.01), and fewer focal spasms (31 vs 64%, p<0.01). There were no other differences between the 2 groups. In conclusion, Japanese female patients with vasospastic angina had the characteristics of diffuse provoked spasm, less organic stenosis, and less history of smoking, but only 1 in 10 of all patients with vasospastic angina are female.

The influence of left ventricular geometry on coronary vasomotion in patients with essential hypertension

The objective of this study was to assess the influence of left ventricular (LV) geometric pattern on coronary vasomotion in patients with essential hypertension. We studied 34 hypertensive patients, who had never been treated, with angiographically normal coronary arteries. Patients were classified into four LV geometric patterns by echocardiography: normal, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy. The responses of coronary vasomotion in left anterior descending artery to vasoactive agents (acetylcholine, isosorbide dinitrate, adenosine triphosphate) were examined using a Doppler guidewire and quantitative coronary angiography. The percent increase in coronary blood flow evoked with acetylcholine (endothelium-dependent vasomotion) showed lowest in concentric hypertrophy, followed by eccentric hypertrophy, concentric remodeling, and normal geometry. The significant linear relationship between acetylcholine-induced coronary blood flow and LV mass was noted. There was no difference in the percent increase in coronary blood flow evoked with isosorbide dinitrate (endothelium-independent vasomotion of conduit vessel) among the four groups. The percent increase in coronary blood flow evoked with adenosine triphosphate (endothelium-independent vasomotion of resistant vessel) was significantly lower in patients with concentric hypertrophy than in the other three groups. The results in this study suggest that coronary vasomotion may be associated with LV geometry in patients with hypertension. The endothelium-dependent vasodilation is impaired progressively as LV hypertrophy advances. The endothelium-independent vasodilation of microvessels is impaired only in concentric hypertrophy. This advanced abnormality of coronary vasomotion may contribute to the high cardiovascular morbidity and mortality in patients with concentric hypertrophy.