Role of hypertension, dyslipidemia and diabetes mellitus in the development of coronary atherosclerosis in Japan.

The present study evaluated the effect of hypertension (HT), dyslipidemia and diabetes mellitus (DM) on the development of coronary atherosclerosis in the Japanese population, using a cross-sectional study of 433 patients (254 men and 179 women) aged 30 years or older who underwent coronary angiography for suspected or known coronary heart disease angina at 5 cardiology departments in the Fukuoka area between September 1996 and August 1997. Patients with a disease duration of 6 months or more were excluded. The main outcome measure was angiographically defined coronary artery stenosis and was found to a significant degree in 146 patients (33.7%). HT, DM, low levels of high-density lipoprotein cholesterol (HDL-C) and hypertriglyceridemia remained as significant coronary artery disease (CAD) risk factors even after controlling for age, sex, hospital, smoking, alcohol use, body mass index and leisure time physical activity. However, hypercholesterolemia was not a significant risk factor after adjusting for these variables. After controlling for these variables, DM, low HDL-C and hypertriglyceridemia were significant CAD risk factors for men, but only DM was a significant CAD risk factor in women. These results indicate that in Japan DM, low HDL-C and hypertriglyceridemia may be more important CAD risk factors than hypercholesterolemia.

Deep venous thrombosis and pulmonary thromboembolism associated with a huge uterine myoma--a case report.

A 51-year-old woman with a large uterine myoma suffered from acute pulmonary thromboembolism. Venography revealed thrombosis in the right common iliac vein and almost complete obstruction of the left common iliac vein. The ascending lumbar vein showed collateral drainage. Treatment was initiated with continuous intravenous heparin sodium, and a Greenfield filter was inserted to prevent the extension of the pulmonary embolism during and after hysterectomy. After a total hysterectomy, venography revealed restoration of patency in the bilateral common iliac veins, and no flow was seen in the ascending lumbar vein. Thorough clinical examinations failed to identify any other prothrombotic conditions. These results suggest that a large uterine myoma compressed veins in the pelvis, and the resulting impaired blood flow caused deep venous thrombosis and pulmonary thromboembolism.

Increased chymase activity in internal thoracic artery of patients with hypercholesterolemia.

Apart from ACE, various angiotensin II (Ang II)-forming serine proteinases (eg, chymase, kallikrein, and cathepsin G) are known to exist in human tissues, but their clinical significance or the regulatory mechanisms that control their activities are not well established. A recent clinical study has shown that chymase activity was significantly increased in human atherosclerotic or aneurysmal aorta. The association between vascular Ang II-forming activities (AIIFAs) in the human internal thoracic artery (ITA) and various clinical parameters was studied with the use of ITAs obtained from 32 patients who underwent coronary artery bypass graft surgery. Total and ACE- and chymase-dependent AIIFAs in homogenates of ITAs were determined. Total AIIFA was 8.67+/-0.86 (nmol Ang II formed. min(-1). mg protein(-1) [U]), and approximately 95% of the activities were due to chymase. Serum total cholesterol level, but no other risk factors, significantly correlated with chymase- (r=0. 60, P<0.001) and ACE- (r=0.35, P<0.05) dependent AIIFAs, respectively. LDL cholesterol level was also correlated with chymase-dependent AIIFAs (r=0.47, P<0.05). Mast cells identified through the use of toluidine blue or immunohistochemical staining appeared in the adventitia but not in the intima or media of ITAs. Our results suggest that an increased plasma LDL cholesterol level may induce increased arterial chymase and ACE activity.

Increased chymase-dependent angiotensin II formation in human atherosclerotic aorta.

Locally formed angiotensin II (Ang II) and mast cells may participate in the development of atherosclerosis. Chymase, which originates from mast cells, is the major Ang II-forming enzyme in the human heart and aorta in vitro. The aim of the present study was to investigate aortic Ang II-forming activity (AIIFA) and the histochemical localization of each Ang II-forming enzyme in the atheromatous human aorta. Specimens of normal (n=9), atherosclerotic (n=8), and aneurysmal (n=6) human aortas were obtained at autopsy or cardiovascular surgery from 23 subjects (16 men, 7 women). The total, angiotensin-converting enzyme (ACE)-dependent, and chymase-dependent AIIFAs in aortic specimens were determined. The histologic and cellular localization of chymase and ACE were determined by immunocytochemistry. Total AIIFA was significantly higher in atherosclerotic and aneurysmal lesions than in normal aortas. Most of AIIFA in the human aorta in vitro was chymase-dependent in both normal (82%) and atherosclerotic aortas (90%). Immunocytochemical staining of the corresponding aortic sections with antichymase, antitryptase or anti-ACE antibodies showed that chymase-positive mast cells were located in the tunica adventitia of normal and atheromatous aortas, whereas ACE-positive cells were localized in endothelial cells of normal aorta and in macrophages of atheromatous neointima. The density of chymase- and tryptase-positive mast cells in the atherosclerotic lesions was slightly but not significantly higher than that in the normal aortas, and the number of activated mast cells in the aneurysmal lesions (18%) was significantly higher than in atherosclerotic (5%) and normal (1%) aortas. Our results suggest that local Ang II formation is increased in atherosclerotic lesions and that chymase is primarily responsible for this increase. The histologic localization and potential roles of chymase in the development of atherosclerotic lesions appear to be different from those of ACE.

[A case of idiopathic hyperaldosteronism diagnosed by adrenal imaging].

We report a case of idiopathic hyperaldosteronism (IHA) which was differentiated from an aldosterone producing adenoma by the adrenal imaging techniques with computed tomography (CT) and scintigraphy. In this patient, the high basal aldosterone level with the suppressed plasma renin activity typically indicated the diagnosis of primary aldosteronism. However, the differentiation from an aldosterone producing adenoma by responses of plasma aldosterone levels to upright posture, captopril or adrenocorticotropic hormone (ACTH) administration was not definitive. Abdominal CT revealed bilateral adrenal swelling. Adrenal scintillation scanning with 131I-iodocholesterol showed bilateral uptake even after the administration of dexamethasone. Blood sampling from the right adrenal vein was unsuccessful. Blood pressure and serum potassium levels remained unchanged during dexamethasone administration (2 mg/day) over ten days. After the administration of spironolactone and nisoldipine blood pressure and serum potassium levels were normalized. Adrenal imaging is considered to be very useful for the diagnosis of IHA.

Role of locally formed angiotensin II and bradykinin in the reduction of myocardial infarct size in dogs.

OBJECTIVE: The aim was to investigate the role of local formation of angiotensin II and bradykinin in the reduction of myocardial infarct size. METHODS: Bilaterally nephrectomised male mongrel dogs were used. Effects were compared of pretreatment with three inhibitors of angiotensin II forming enzyme-captopril (an angiotensin converting enzyme inhibitor), nafamostat (a serine protease inhibitor), and chymostatin (a cysteine protease inhibitor)--on left anterior descending coronary artery occlusion. Haemodynamic variables were monitored and blood was collected from the anterior interventricular vein and the aorta. Angiotensin I, angiotensin II, and bradykinin were measured by radioimmunoassay. After 90 min of occlusion, infarct sizes were determined by a macroscopic enzyme technique. RESULTS: Angiotensin II release into the anterior interventricular vein increased from 0.03(SEM 1.19) pg.min-1 (before coronary occlusion) to 4.64(1.37) pg.min-1 (n = 14, p < 0.05), while angiotensin I release and plasma renin activity remained unchanged. The increase in angiotensin II release was inhibited by nafamostat and chymostatin, but not by captopril. Bradykinin release increased from -3.18(2.72) (before coronary occlusion) to 34.7(12.3) pg.min-1 (n = 14 p < 0.05) by 30 min after occlusion. This increase was augmented by captopril, from 4.10(2.86) before occlusion to 97.8(39.6) pg.min-1 at 5 min after occlusion (n = 12, p < 0.05), but not by nafamostat or chymostatin. Infarct size was smaller (p < 0.05) in the captopril group than in the control group. CONCLUSIONS: Angiotensin II is locally produced in the ischaemic heart by both serine protease(s) and chymostatin inhibitable protease(s), but not by angiotensin converting enzyme. From the reduction in myocardial infarct size produced by angiotensin converting enzyme inhibition, it seems that bradykinin accumulation may play a more important role than the suppression of angiotensin II formation.

Mild exercise decreases plasma endogenous digitalislike substance in hypertensive individuals.

Changes in a plasma endogenous digitalislike substance were investigated in relation to the antihypertensive mechanism of mild exercise. Fifteen women with mild essential hypertension and seven normotensive female volunteers were divided into exercised hypertensive (n = 10), nonexercised hypertensive (n = 5), and nonexercised normotensive (n = 7) groups. A 4-week general clinical observation period preceded the study period of 10 weeks. The exercised hypertensive individuals were treated with a lactate threshold exercise that corresponded to approximately 50% of the maximum oxygen consumption three times a week, whereas the nonexercised groups were observed at the outpatient clinic as control groups. In the exercised group, systolic blood pressure fell by 7 mm Hg (p = 0.05), diastolic by 6 mm Hg (p less than 0.01), and mean blood pressure by 7 mm Hg (p less than 0.01) after 10 weeks. The reduction in the plasma endogenous digitalislike substance was significant after 7 (-1.02 ng/ml, p less than 0.05) and 10 (-1.04 ng/ml, p less than 0.05) weeks in this group. It positively correlated with the reduction in diastolic (r = 0.70, p less than 0.05) or mean (r = 0.66, p less than 0.05) blood pressure and with changes in plasma norepinephrine (r = 0.76, p less than 0.05). The mean corpuscular volume of erythrocytes decreased (-1.7 fl, p less than 0.01) after 10 weeks of exercise, and the plasma volume index tended to decrease (-108 ml/m2, p = 0.28). In the control groups, significant changes in blood pressure and plasma endogenous digitalislike substance were not observed.(ABSTRACT TRUNCATED AT 250 WORDS)

A case of a clinically "silent" pheochromocytoma.

A case of a clinically "silent" pheochromocytoma is presented. The adrenal mass was incidentally discovered by abdominal ultrasonography and computed tomography. In the course of hospitalization, the patient was normotensive and asymptomatic. Plasma catecholamine levels were nearly normal, whereas urinary levels of catecholamine metabolites were slightly elevated. A glucagon provocative test and 131I-metaiodobenzylguanidine scintigram were useful for diagnosing such an atypical pheochromocytoma. A discussion of clinically-unsuspected pheochromocytoma is also presented.

High-renin malignant hypertension secondary to an aldosterone-producing adenoma.

Malignant hypertension and high plasma renin activity was found in a 39-year-old woman with an aldosterone-producing adenoma. Only 3 similar cases have been previously reported, and all patients died before or after identification of the adenoma. The present paper documents the first reported case of a successfully managed high-renin malignant hypertension secondary to an aldosterone-producing adenoma. Regardless of its sporadic occurrence and common presence with low plasma renin activity, primary aldosteronism should be considered as a possible underlying cause of high-renin malignant hypertension.

An accelerated hypertension with neither malignant nephrosclerosis nor elevation of plasma renin activity.

A case of accelerated hypertension, which was unique in a resistance to an angiotensin antagonist, and a lack of the elevation of plasma renin activity (PRA) is reported. Non-elevated PRA was coincided with non-malignant nephrosclerosis in renal histology. The acceleration was attributed to the neurological cause i.e., cerebral hemorrhage in the right hypothalamus which extended to the ventricle and subarachnoid space. The case therefore clinically seemed malignant-like, but it was not malignant hypertension in the sense of Volhard's classical definition. This does not conflict with the usefulness of the determination of PRA in the diagnosis of malignant hypertension with nephrosclerosis.