Association of apolipoprotein E phenotype with hypertension in Japanese-Americans: data from the Hawaii-Los Angeles-Hiroshima Study.

We evaluated the association between the phenotypes or alleles of apolipoprotein E and hypertension in Japanese-Americans living in Hawaii or Los Angeles. The study consisted of 932 nondiabetic participants aged 40-79 years. Of these participants, 315 were hypertensive, while the remainder were normotensive. The prevalence of hypertension was higher in subjects with the e2 allele than in those without. Using a multivariable prediction model that included age, serum glucose, insulin, lipids, and body mass index, we found the epsilon2 allele to be associated with hypertension in men (odds ratio (OR), 1.53; 95% confidence interval (CI), 1.05-2.24) and for both sexes combined (OR, 1.35; 95% CI, 1.05-1.73). In a follow-up study, 37 of the 352 (11%) normotensive subjects had developed hypertension 4 years after the baseline examination. The frequencies of the apolipoprotein E phenotype E3/2 and the epsilon2 allele were higher in the subjects who became hypertensive than in those who remained normotensive. The E3/2 phenotype was associated with incidence of hypertension after adjustment for age, sex, baseline body mass index, and systolic blood pressure (OR, 1.75; 95% CI, 1.01-2.90). When serum lipids, glucose, and insulin were included in this analysis, the E3/2 phenotype tended to be associated with the incidence of hypertension. In conclusion, the epsilon2 allele of apolipoprotein E was associated with hypertension in Japanese-Americans. This association may be mediated via high levels of serum triglycerides that in turn are mediated in part by the epsilon2 allele. Nonlipid mechanisms may also be responsible for the effect of the epsilon2 allele on hypertension.

Hyperinsulinemia for the development of hypertension: data from the Hawaii-Los Angeles-Hiroshima Study.

The present study was to assess the association of metabolic factors including hyperinsulinemia, with the development of hypertension in Japanese-Americans. One hundred forty normotensive (<140/90 mmHg) subjects aged 40 to 69 years old from the Hawaii-Los Angeles-Hiroshima study were followed for 15 years. Patients with cardiovascular disease were excluded. Body mass index (BMI), blood pressure (BP), serum total cholesterol (TC), triglycerides (TG), uric acid (UA), and glucose and insulin responses at baseline, 1 h, and 2 h after a glucose load were analyzed. Seventeen subjects became hypertensive (systolic BP > or = 160 mmHg, diastolic BP > or = 95 mmHg, or received drug treatment) during follow-up. Age- and sex-adjusted BMI, BP, serum UA, TG, insulin, and changes in fasting glucose during follow-up were higher in subjects who later became hypertensive than in those who did not. There was no difference in the change in BMI. Age- and sex-adjusted relative risks for the development of hypertension by quartiles of BMI, serum UA, TG, and the sum of insulin values (sigmainsulin) during a glucose load were highest in highest quartile of the distribution. When age, sex, systolic BP, BMI, serum UA, TC, TG, fasting glucose, sigmainsulin, and the change in BMI were used in a proportional hazard analysis, hyperinsulinemia, hyperuricemia, and systolic BP were found to be significant risk factors for hypertension. In conclusion, hyperinsulinemia, as well as obesity, hyperuricemia, and hypertriglyceridemia were associated with hypertension in Japanese-Americans. Hyperinsulinemia and hyperuricemia were independent predictors of the development of hypertension.

[Estimation of healthy reference intervals for elderly people through the use of outpatient data].

It is important to determine transferable reference intervals as well as uniformity in measured values for inter-regional and inter-institutional availability of clinical test results. For that purpose, the National Committee for Clinical Laboratory Standards (NCCLS) issued forth guidelines in 1995. Some regional institutions in Japan are making efforts to determine normal reference intervals based on these guidelines. We, the Fukuoka Five Hospitals Group, have selected 3,375 healthy reference individuals and have determined the normal reference intervals for the age groups of 20-29, 30-39, 40-49, and 50-59 years old. The rapidly increasing percentage of elderly people gives rise to ever increasing health-care needs for the elderly, which requires normal reference intervals for older age groups. However, we were unable to collect the required number of the reference individuals above 60 years of age. To obtain reference intervals with adequate reliability and usefulness temporally, we made use of the laboratory data of outpatients at Kyushu University Hospital, and were then easily able to collect the required number of elderly individuals. By performing a very simple selection from among the outpatients, our outpatient group became virtually indistinguishable from the group of healthy reference individuals established by us, with regard to many clinical tests, thus enabling us to estimate reference intervals for older age groups. This approach could be adopted in other regions.

[Clinical laboratory data and reference intervals standardized in Fukuoka].

In Fukuoka whose population is approximately five million inhabitants, surveys on the accuracy of laboratory data have been performed by the Fukuoka Prefecture Medical Association for the last 30 years. We have been attempting to evaluate the data for routine use since 1988, and it has become possible to share laboratory data between all institutions in Fukuoka prefectures. As a result, reference intervals for 23 clinical chemistry analytes were established in 1995, to which were added in 1996 five serum protein constituents that have been utilized for clinical examinations. Methods for documentations and monitorings the data obtained in the prefecture were also established, standardization of the above analytes extended to 97% of the institutions in the prefecture. Results for 14 of the 23 clinical chemistry analytes have become highly reliable and clinically useful as differences between institutions in terms of results have narrowed. Standardization of other analytes is now in progress.

Clinical significance of the disappearance of septal Q waves after the onset of myocardial infarction: correlation with location of responsible coronary lesions.

We investigated the relationship between the disappearance of septal Q waves after myocardial infarction (MI) and the location of the culprit lesion. We studied 82 patients following their first anteroseptal MI who had an electrocardiogram performed before the MI. Septal Q waves were detectable before MI in 56 patients and disappeared after MI in 17 of those patients. The culprit lesion was located proximal to the origin of the first septal branch (S1) in 13 patients (76%). Disappearance of septal Q waves following MI predicted that the culprit lesion was proximal to the origin of S1 (sensitivity, 42%; specificity, 84%; predictive value, 76%; and accuracy, 61%). If septal Q waves that were detected before MI disappeared after MI, the culprit lesion was located proximal to the origin of S1 in 76% of the patients. This finding may be clinically useful in caring for patients following MI.

Coronary artery aneurysms detected with ultrafast computed tomography.

A 25-year-old Japanese woman was admitted due to acute inferior myocardial infarction. Coronary angiography showed complete occlusion of the proximal right coronary artery and vague calcification distal to the complete occlusion. Using ultrafast computed tomography, two coronary artery aneurysms in the right coronary artery that could not be detected by coronary angiography were visualized.

Exercise-induced ST elevation in patients with arrhythmogenic right ventricular dysplasia.

To test the hypothesis that local or diffuse wall motion abnormalities in the right ventricle in patients with arrhythmogenic right ventricular dysplasia (ARVD) may induce the ST-segment elevation in response to exercise, we examined exercise electrocardiograms in patients with ARVD. In 17 patients with ARVD, who demonstrated right ventricular wall motion abnormalities without organic coronary lesions, we conducted a treadmill exercise test. Significant exercise-induced ST-segment elevation (ESTE) was defined as a 0.1 mV or more ST-segment elevation at J point. ESTE was observed in 11 patients (65%). It manifested most frequently in right-sided precordial leads. Severe right ventricular asynergy was seen in all but one (91%) among 11 with ESTE, whereas it was seen only in two (33%) among six without ESTE (P<.05). The maximal magnitude of ESTE inversely correlated with right ventricular ejection fraction (r = -0.58, P<.05). ESTE was seen in two thirds of ARVD patients, helping us noninvasively diagnose ARVD. The fact that ventricular wall motion abnormalities could cause ESTE in the absence of organic coronary lesions suggested the critical role of mechanical factors in the genesis of ESTE.

Hyperinsulinemia as a risk factor for restenosis after coronary balloon angioplasty.

The present study evaluated whether hyperinsulinemia is a predictor of restenosis after coronary balloon angioplasty in 69 patients who underwent elective coronary balloon angioplasty; patients were excluded if they were known diabetics being treated with insulin. Quantitative coronary angiography was performed before and after angioplasty and at follow-up. Restenosis was defined as the presence of > or = 50% stenosis at follow-up. Plasma insulin responses before, 30, 60, and 120 min after 75 g glucose load (OGTT) were measured. Plasma insulin levels were higher in patients with restenosis than in patients without restenosis. Minimal lumen diameter at follow-up was smaller, and percent diameter stenosis at follow-up was higher and late loss was greater in the highest sum of insulin levels during OGTT (sigma insulin) quartile (0.95+/-0.15 vs 1.47+/-0.09 mm, p=0.005; 66.3+/-5.8 vs 40.5+/-3.3%, p=0.0003; 0.90+/-0.15 vs 0.49+/-0.08 mm, p=0.02). Even after adjustment for coronary risk factors and administration of angiotensin converting enzyme inhibitors, the association of hyperinsulinemia with restenosis leads to the conclusion that hyperinsulinemia is a strong risk factor for restenosis.

[Acute myocardial infarction in young Japanese women].

Women appear to be protected, until the menopause, from the development of coronary artery disease. The incidence of acute myocardial infarction in young women is very low, so there is little information on the etiology, clinical features, and prognosis for such patients. We studied 24 young female patients with acute myocardial infarction (< 50 years) among 2,457 consecutive patients with acute myocardial infarction admitted to the coronary care unit of the National Cardiovascular Center from December 1977 through August 1994. Their clinical features and in-hospital mortality were compared with 100 consecutive young male patients (< 50 years) with acute myocardial infarction. The fraction of patients of age younger than 50 years among all age groups was lower in female than in male acute myocardial infarction patients (5% vs 13%, p < 0.01). The increase of the coronary risk factors, hypercholesterolemia (25% vs 55%, p < 0.05) and cigarette smoking (17% vs 96%, p < 0.05) were less common in women. In female patients, the serum total cholesterol level was lower (195 +/- 50 vs 216 +/- 48 mg/dl, p = 0.06), and the serum high-density lipoprotein cholesterol level was higher (50 +/- 12 vs 39 +/- 12 mg/dl, p < 0.05) than in male patients. Other risk factors did not differ significantly between the two groups. Angiography 1 month after myocardial infarction showed fewer diseased coronary arteries (> 75% stenosis) in female than male patients (0.8 +/- 0.9 vs 1.8 +/- 1.0, p < 0.01), and normal coronary arteries were seen in 35% of female patients (male 6%, p < 0.05). Ten female patients (42%) had obviously non-atherosclerotic causes of acute myocardial infarction: Takayasu aortitis in three patients, coronary embolism in two, acute dissection of the aorta in two, and idiopathic coronary artery dissection, Kawasaki disease, and systemic lupus erythematosus in one each. In contrast, among male patients, only one had coronary embolism (1%). In-hospital mortality was higher in women (17%) than in men (2%, p < 0.05). Young female patients (< 50 years) with acute myocardial infarction have a low incidence of hyperlipidemia and normal coronary arteries or involvement of the left main trunk are more common compared with male patients (< 50 years). Although 42% of female patients had obvious non-atherosclerotic etiology of acute myocardial infarction, the causes varied widely.

Quinapril with high affinity to tissue angiotensin-converting enzyme reduces restenosis after percutaneous transcatheter coronary intervention.

Experimental studies have demonstrated that vascular injury resulted in an induction of vascular angiotensin-converting enzyme (ACE), and have suggested that inhibition of vascular ACE might be important in the prevention of restenosis. The present study aimed to determine the effect of quinapril, an ACE inhibitor with high affinity to tissue ACE, on restenosis following coronary intervention. The design of this study was a prospective, randomized, open, and non-placebo controlled trial. Patients with ischemic heart disease were enrolled after successful percutaneous transluminal coronary angioplasty or stent implantation at 7 participating institutions. Two hundred and fifty-three patients with 294 lesions were randomly assigned to the quinapril (10-20 mg per day) group or control group. Administration of quinapril was continued for 3-6 months of the follow-up. Quantitative coronary angiography was performed before and after angioplasty and at follow-up. Core laboratory measurements were performed independently and blinded. Follow-up angiography was performed in 108 patients with 124 lesions in the quinapril group and in 107 patients with 130 lesions in the control group. The baseline characteristics and findings of angioplasty showed no significant differences between the two groups. However, in the quinapril group, restenosis per patient and per lesion was significantly lower (34.3% vs. 47.7%, p < 0.05 and 30.6% vs. 43.8%, p < 0.05). Multivariable analysis revealed that administration of quinapril independently contributed to reducing the restenosis per patient and per lesion (odds ratio, 0.73; 95% confidence interval, 0.54-0.99 and odds ratio, 0.75; 95% confidence interval, 0.57-0.99). In conclusion, quinapril significantly reduces restenosis following coronary intervention.

Cardiac disease late after chest radiotherapy for Hodgkin's disease: a case report.

This report presents a case of occult constrictive pericarditis and mitral valve insufficiency following chest radiotherapy. A 44-year-old man had received radiotherapy for the treatment of Hodgkin's disease 8 years ago. At age 40 years, effusive pericarditis occurred and he was treated with intrapericardial drainage. Biopsy revealed a fibrotic and thickened pericardium. He developed congestive heart failure 3 years later. The patient was found to have occult constrictive pericarditis and mitral valve insufficiency. He underwent mitral valve replacement, tricuspid annul plasty, and pericardiectomy. Although there is the benefit of cure for the Hodgkin's disease, the prognosis after treatment is affected by radiotherapy-induced heart disease. After radiotherapy of the chest and mediastinum, long-term cardiological follow-up is recommended in order to detecting patients with radiation-induced heart disease, such as the present case.

Standardization of laboratory data and establishment of reference intervals in the Fukuoka Prefecture: a Japanese perspective.

Standardization of 22 clinical chemistry analytes and five serum protein constituents has been performed in the Fukuoka Prefecture, which has a population of approximately five million. The standardization project was established to determine reference intervals for these analytes by educating physicians, medical technologists and staff of medical institutions, and by daily or monthly monitoring the use of common control samples through e-mail. Standardization extended to 97% of the institutions in the prefecture. Results for 14 of the 22 clinical chemistry analytes have become highly reliable and differences between institutions decreased. Standardization of other analytes is now in progress. Regional collaboration based on international guidelines led to a significant improvement in interlaboratory comparability. Areas where further improvements are needed have been identified.