[Study of the echocardiographic diagnosis of acute pulmonary thromboembolism and risk factors for venous thromboembolism].

OBJECTIVES: To identify the relationship of risk factors for atherosclerosis with venous thromboembolism (VTE) and the utility of transthoracic echocardiography in acute pulmonary thromboembolism (APTE). METHODS: In 75 patients with VTE (VTE group), 101 patients with suspected VTE (N group), and 50 control subjects (control group), the frequency of atherosclerosis risk factors such as hyperlipidemia, obesity, hypertension, smoking, and diabetes mellitus and the number of risk factors were evaluated. Transthoracic echocardiographic findings such as tricuspid regurgitation, right ventricular dilation, pulmonary hypertension, and right ventricular dysfunction were evaluated in 15 patients with APTE (APTE group) and 38 patients in the N group (NC group). RESULTS: The incidence of hyperlipidemia in the VTE group was statistically higher than that in the control group (odds ratio 2.16, 95% confidence interval 1.43-3.08). Additionally, the incidence of obesity was higher in the VTE and N groups than in the control group (odds ratio was 2.76, 95% confidence interval 1.67-4.37). Risk factors other than obesity and hyperlipidemia and the number of risk factors were not significant. The incidence of tricuspid regurgitation, right ventricular dilation, and pulmonary hypertension in APTE was statistically greater than that in NC group. Right ventricular dilation and right ventricular dilation + tricuspid regurgitation are reliable findings in echocardiography. However, even combining with tricuspid regurgitation, right ventricular dilation is insufficient to identify or screen patients with APTE. CONCLUSIONS: Hyperlipidemia and obesity may be risk factors for VTE. However, obese patients can manifest similar findings to VTE. Although transthoracic echocardiograpghy is not recommended as a diagnostic or screening test in APTE, it should be used as an ancillary test.

[Relationship between insulin resistance and oxidative stress in vivo].

OBJECTIVES: The relationship between oxidative stress in vivo and insulin resistance was examined. METHODS: This study included 87 patients, 46 males and 41 females (mean age 63 +/- 10 years), without coronary artery disease. The homeostasis assessment insulin resistance (HOMA-IR) (fasting blood sugar x fasting immunoreactive insulin/405), a marker for insulin resistance, was measured. The patients were divided into three groups: the noninsulin resistance group (N-IR group) without diabetes mellitus (DM) and with fasting blood glucose level of 126 mg/dl and HOMA-IR < or = 1.73 (n = 44), the insulin resistance group (IR group) without diabetes mellitus and with fasting blood glucose level of 126 mg/dl and HOMA-IR > 1.73 (n = 29), and the DM group (type 2 diabetes mellitus) (n = 14). Urinary 8-iso-prostaglandin F2 alpha (U-8-iso-PGF2 alpha) excretion was measured as a marker of in vivo oxidative stress. RESULTS: There were significantly more obese patients in the IR group than in the N-IR group (62% vs 25%, p = 0.001), and the remnant-like particle cholesterol level was significantly higher in the IR group than in the N-IR group (7.6 +/- 5.2 vs 4.6 +/- 1.5 mg/dl, p < 0.01). Patients in the IR group had a significantly larger number of coronary risk factors. U-8-iso-PGF2 alpha excretion was significantly higher in the IR group and DM groups (201 +/- 86, 191 +/- 136 vs 129 +/- 50 pg/mg. Cr, p < 0.0001, p = 0.01), and there was a significantly positive correlation between the number of coronary risk factors, fasting blood sugar and U-8-iso-PGF2 alpha concentration (correlation coefficient = 0.32, 0.37, p = 0.002, p = 0.0003). Multiple regression analysis showed that remnant-like particle cholesterol, fasting blood sugar and insulin resistance were independent factors for U-8-iso-PGF2 alpha concentration (p < 0.0001, p = 0.0007, p = 0.02). CONCLUSIONS: Insulin resistance, remnant lipoprotein and hyperglyceridemia are deeply involved in oxidative stress in vivo.

Preventive effect of an antiallergic drug, pemirolast potassium, on restenosis after stent placement: quantitative coronary angiography and intravascular ultrasound studies.

OBJECTIVES: The preventive effect of pemirolast against restenosis after coronary stent placement was evaluated. METHODS: Eighty-four patients with 89 de novo lesions who underwent successful coronary stenting were assigned to the pemirolast group(40 patients, 45 lesions) and the control group(44 patients, 44 lesions). Administration of pemirolast(20 mg/day) was initiated from the next morning after stenting and continued for 6 months of follow-up. Quantitative coronary angiography was performed immediately after stenting and at follow-up. Angiographic restenosis was defined as diameter stenosis > or = 50% at follow-up. Intravascular ultrasound study conducted at follow-up angiography was used to measure vessel cross-sectional area(CSA), stent CSA, lumen CSA, neointima CSA(stent CSA--lumen CSA), and percentage neointima CSA(neointima CSA/stent CSA x 100%) at the minimal lumen site. RESULTS: There were no significant differences in baseline characteristics between the two groups. Restenosis rate was significantly lower in the pemirolast group than in the control group(15.0% vs 34.1% of patients, 13.3% vs 34.1% of lesions, p < 0.05, respectively). The intravascular ultrasound study at follow-up(36 lesions in the pemirolast group, 33 in the control group) found no significant differences in vessel CSA and stent CSA between the two groups(17.3 +/- 2.2 vs 16.8 +/- 2.4 mm2, 8.6 +/- 1.9 vs 8.4 +/- 1.7 mm2, respectively). However, lumen CSA was significantly larger in the pemirolast group than in the control group(5.5 +/- 1.3 vs 4.4 +/- 1.1 mm2, p < 0.05). Moreover, neointima CSA and percentage neointima CSA were significantly smaller in the pemirolast group(3.1 +/- 1.1 vs 4.0 +/- 1.2 mm2, p < 0.05 and 36.2 +/- 15.9% vs 47.4 +/- 15.6%, p < 0.01). CONCLUSIONS: Pemirolast has a preventive effect against restenosis after stent placement, possibly by inhibiting neointimal hyperplasia.

[Headache due to nitroglycerin administration and its clinical significance].

OBJECTIVES: This study assessed the side effects of nitroglycerin administration and their clinical significance. METHODS: Adverse reactions associated with sublingual nitroglycerin administration were investigated in 103 patients, 71 men and 32 women (mean age 56 +/- 11 years), 32 patients with coronary artery stenosis and 71 without coronary artery stenosis. RESULTS: Fifty-one percent of patients experienced headache and 30% experienced other adverse reactions, whereas 19% experienced no adverse reactions. The relationship was investigated between headache, the most common adverse reaction, and the following eight clinical background factors: coronary angiographic findings, sex, age, hyperlipidemia, hypertension, diabetes mellitus, smoking and drinking. Multiple regression analysis was conducted by treating sublingual nitroglycerin-induced headache as an object variable and the clinical background factors as explanatory variables. Statistically, the onset of headache correlated most closely to coronary angiographic findings, followed by smoking, hypertension, diabetes mellitus and drinking. The first four factors suppressed the onset of headache, whereas drinking facilitated the onset of headache. CONCLUSIONS: There is a close relationship between the onset of headache following sublingual nitroglycerin administration and coronary angiographic findings. Sublingual nitroglycerin-induced headache as a predictor of coronary angiographic findings has a sensitivity and specificity of 81% and 66%, respectively, for patients without coronary artery stenosis based on the absence of headache.

Angioscopic evaluation of stabilizing effects of an antilipemic agent, bezafibrate, on coronary plaques in patients with coronary artery disease: a multicenter prospective study.

To evaluate the stabilizing effects of an antilipemic agent, bezafibrate, on coronary plaques, we carried out a prospective angioscopic and angiographic open trial. From April 1997 to December 1998, 24 patients underwent coronary angioscopy of plaques in non-targeted vessels during coronary interventions and then again 6 months later. The patients were divided into control (10 patients, 14 plaques) and bezafibrate (14 patients, 21 plaques) groups. Oral administration of bezafibrate (400 mg/day) was started immediately after the intervention and was continued for 6 months. The vulnerability score was determined based on the angioscopic characteristics of plaques and compared before and 6 months later. Six months later, the vulnerability score was reduced (from 1.6 to 0.8; P<0.05) in the bezafibrate group and unchanged (from 1.4 to 1.3; NS) in the control group. In the bezafibrate group, the changes in the vulnerability score were not correlated with those in % stenosis or minimal lumen diameter. The plasma total cholesterol level (T-C) was unchanged, triglyceride level (TG) was decreased, and high density lipoprotein cholesterol level (HDL-C) was increased in the bezafibrate group, but were unchanged in the control group. In the bezafibrate group, T-C and TG were decreased and HDL-C was increased in patients with a reduced vulnerability score but were unchanged in those with an unchanged score. These results indicate that 6 month administration of bezafibrate stabilizes coronary plaques and that the stabilization is not correlated with angiographic changes.

Association between preheparin serum lipoprotein lipase mass and acute myocardial infarction in Japanese men.

A sensitive immunoassay system using a specific monoclonal antibody against lipoprotein lipase (LPL) recently demonstrated the presence of an LPL mass in preheparin serum. We reported that a preheparin serum LPL mass (pre-LPL mass) reflected the level of functioning LPL activity in the whole body and could be deeply involved in the progression of coronary atherosclerosis of stable organic angina pectoris. We examined the relation between the pre-LPL mass and acute myocardial infarction (AMI). We studied 44 males with AMI (AMI group) and 16 males with a normal coronary artery (NCA group), and measured the pre-LPL mass by enzyme-linked immunosorbent assay. Coronary risk factors including the pre-LPL mass were compared between the two groups and multiple regression analysis was performed for AMI. There were no significant differences in the lipid data, but the pre-LPL mass level was significantly low in the AMI group (52 +/- 16 vs 41 +/- 14 ng/ml, p = 0.01), and a low pre-LPL mass concentration was observed in the small sized LDL group and/or the Midband positive group. Multiple regression analysis revealed that a low pre-LPL mass and hypertriglyceridemia were independent risk factors for AMI (t value = 2.1, 2.4). The result indicates that a low pre-LPL mass may be an important risk factor for AMI and stable organic angina pectoris.

[Clinical significance of preheparin serum lipoprotein lipase mass in normocholesterolemic patients with coronary artery disease].

OBJECTIVES: Some normocholesterolemic patients have coronary artery disease (CAD) in Japan. This study evaluated the clinical significance of preheparin lipoprotein lipase mass as a risk factor for normocholesterolemic patients with CAD. METHODS: This study included 89 normocholesterolemic male patients with CAD (CAD group, 40 with stable organic angina pectoris, 19 with vasospastic angina pectoris, and 30 with acute myocardial infarction), and 13 normocholesterolemic males with normal coronary arteries (control group) with no stenotic lesion and negative reaction to intracoronary administration of acetylcholine. Preheparin lipoprotein lipase mass was measured by enzyme-linked immunosorbent assay. Coronary risk factors including preheparin lipoprotein lipase mass were compared between the two groups. Low-density lipoprotein (LDL) particle size and presence of midband were estimated by polyacrylamide gel disc electrophoresis. RESULTS: Mild hypertriglyceridemia and low high-density lipoprotein (HDL) cholesterolemia were observed in the CAD group, and small particle size LDL and presence of midband were also common in the CAD group. Preheparin lipoprotein lipase mass level was significantly lower in the CAD group than the control group (52 +/- 18 vs 40 +/- 13 ng/ml, p = 0.005) as well as in each type of patient in the CAD group. Multiple regression analysis showed that small particle size LDL, low preheparin lipoprotein lipase mass and smoking were independent risk factors for CAD (p < 0.001, p = 0.007, p = 0.037). Low preheparin lipoprotein lipase mass concentration was observed in the small particle size LDL group and/or the midband positive group. CONCLUSIONS: These results indicate that low preheparin lipoprotein lipase mass reflects insulin resistance and may be deeply involved in the progression of coronary arteriosclerosis.