Hiroo Kato

Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California: Incidence of myocardial infarction and death from coronary heart disease

The incidence of myocardial infarction and death from coronary heart disease was studied in defined samples of 45 to 68 year old Japanese men in Japan, Hawaii and California. The incidence rate was lowest in Japan where it was half that observed in Hawaii (P less than 0.01). The youngest men in the sample in Japan were at particularly low risk. The incidence among Japanese men in California was nearly 50 percent greater than that of Japanese in Hawaii (P less than 0.05). A striking increase in the incidence of myocardial infarction appears to have occurred in the Japanese who migrated to the United States; this increase is more pronounced in California than in Hawaii.

Mercury and methylmercury in fish and human hair from the Tapajós river basin, Brazil

Mercury is being released in the Amazon in an abusive way due to goldmining activities. The Tapajós river basin was the first to be intensively exploited in the modern Amazon gold rush. Fish and hair samples as the best indicators of human methylmercury contamination were investigated in the main cities and villages along the Tapajós river basin. The upper basin has typical fish fauna with much larger carnivorous fish with higher mercury levels reaching an average value of 0.69 microgram.g-1 wet wt. in 43 fish. This was accompanied by high levels in hair of the human population living in the same area. The maximum hair value reach 151 micrograms.g-1 dry wt. with two villages presenting an average value close to 25 micrograms.g-1 dry wt. An analytical laboratory intercalibration exercise was performed between Japanese and Brazilian laboratories for total mercury analysis. Critical fish, areas, and more exposed human groups are identified.

Methylmercury pollution in the Amazon, Brazil

In order to evaluate the extent of environmental mercury pollution due to goldmining activities in the Amazon, concentrations of total mercury and methylmercury were determined for human hair and fish samples from five fishing villages located mainly in the Tapajos river basin. Abnormally high levels of mercury were found in human hair from Jacareacanga and Brasilia Legal located near the main goldmining area as well as from Tres Bocas facing the lake in Amapa state, whereas the levels were much lower in Ponta de Pedras, a long way downstream. The values of male samples were about twice as high as females even in the same family. The predominant form of mercury in hair samples was methylmercury (average 90%), while high hair mercury observed in goldminers and workers in goldshops was mostly in the inorganic form. Longitudinal analyses of long hairs from people in fishing villages showed fairly constant and continuous exposure to methylmercury at least over the last few years with seasonal variations. Fish contained relatively high levels of mercury (up to 3.82 ppm) mostly in the form of methylmercury and most of the fish from upstream and some from downstream exceeded the allowable level of 0.5 ppm in Brazil.

Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California. Coronary heart disease risk factors in Japan and Hawaii.

Various risk factors were evaluated to explain a significantly greater incidence of coronary heart disease in men of Japanese ancestry resident in Hawaii compared with men resident in Japan. The independent predictors of incidence of coronary heart disease in both Japan and Hawaii were systolic blood pressure, serum cholesterol, relative weight and age. These factors appeared to influence incidence similarly in both areas because in each case the correlation coefficients for Japan and Hawaii did not differ significantly. The hypothesis that the greater incidence in Hawaii could be attributed to differences in levels of these risk factors was tested with the Walker-Duncan method. The four variable multiple logistic function describing the probability of coronary heart disease in Japan was applied to the cohort characteristics observed in Hawaii. The estimated incidence thus obtained was not significantly different from that actually observed in the men resident in Hawaii. Therefore the increased coronary risk profile in Hawaii compared with Japan can account for the greater incidence of coronary heart disease in the former. Current cigarette smoking was significantly related to the risk of coronary heart disease in Hawaii but not in Japan. This difference requires further investigation.

Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California: incidence of stroke in Japan and Hawaii.

As part of the Ni-Hon-San Study, stroke incidence was compared in the Japan and Hawaii cohorts. Stroke cases were classified in two types, intracranial hemorrhage (ICH) and thrombo-embolic stroke (T-E). For each type the incidence in Japan was about three times as great as in Hawaii. The ratio ICH/T-E was 1/2.2 and 1/1.6 in Japan and Hawaii, respectively. Blood pressure was the most important risk factor, followed by age for total stroke in both Japan and Hawaii. Proteinuria was also a risk factor in Hawaii. Conversely, an index of animal food intake was inversely related to total stroke, significantly in Hawaii, and at a suggestive level for total and hemorrhagic stroke in Japan. Since the levels of blood pressure do not differ between Japan and Hawaii, one possible explanation for the large difference in stroke incidence between the two cohorts may be the fact that animal protein and saturated fat intake, which is inversely associated with stroke incidence, is much greater in Hawaii than in Japan. This explanation would support epidemiologic and experimental studies in Japan which suggest that dietary animal protein and fat exert an inhibitory effect on the incidence of stroke.

Leukocyte counts and cerebrovascular disease.

Elevated total leukocyte count in a biennial examination period is shown to be a significant (p = 0.001) predictor of cerebral infarction (CI) incidence in the subsequent 2 yr examination period, in a large Japanese cohort study. This association is not explainable on the basis of corresponding age, sex or blood pressure levels. The extent to which the association might be attributable to cigarette smoking habits could not be thoroughly examined with available data. Relative risks associated with a specific elevated leukocyte count may be larger among persons less than 65 yr of age than among older persons. When counts of specific leukocyte cell lines are considered a significant (p = 0.0006) role for neutrophil count emerges, while an additional predictive role for other leukocyte cell types could not be detected. In contrast, there is a suggestion that cerebral hemorrhage (CH) risk may be lower following an elevated leukocyte count. In particular, a negative association between lymphocyte count and CH incidence in the subsequent biennial examination cycle, is nearly significant (p = 0.07), in spite of a rather small number of CH cases in the sample.

Serum cholesterol, other risk factors, and cardiovascular disease in a Japanese cohort

The relationship of serum cholesterol and other risk factors to cardiovascular disease was investigated in a 16-year cohort of 16,711 residents of Hiroshima and Nagasaki. Examined in detail were the relationship of serum cholesterol, and the joint relationships of serum cholesterol, systolic blood pressure, diastolic blood pressure, and other risk factors to coronary heart disease (CHD), cerebral infarction (CI), and cerebral hemorrhage (CH). Baseline and biennially collected risk factor data were analyzed. The latter type of measurement permitted separate investigation of both the short-term and long-term effects of cholesterol measurements. In both types of analyses, both serum cholesterol and blood pressure showed strong associations with CHD incidence. In particular, there were strong associations with short-term and delayed CHD incidence. Furthermore, the association of cholesterol with short-term CHD incidence could not be explained by its association with delayed CHD incidence, or vice versa. Multivariate analyses that also included several other risk factors (smoking habits, clinical diagnosis of diabetes mellitus, left ventricular hypertrophy or strain on electrocardiogram, relative body weight, hematocrit, and proteinuria) for which data were available showed such risk factors to be of lesser, but generally non-negligible, importance in this population. In the case of CH and CI, serum cholesterol was found to be weakly or not at all related to incidence of either disease while blood pressure remained a strong correlate. For CI some suggestion of a statistical interaction between blood pressure and serum cholesterol was found. Discussed are implications for theories of disease pathogenesis for CHD, CI and CH.

Cerebrovascular diseases in a fixed population of Hiroshima and Nagasaki, with special reference to relationship between type and risk factors.

A study was made of the incidence of cerebrovascular disease, the chronological trends, and the relationship between the disease types and risk factors in 16,491 citizens of Hiroshima and Nagasaki. The subjects underwent medical examhiation at least once between 1958-74, and were free of cerebrovascu- lar disease at the initial examination. During the 16-year period, 1.162 cases of cerebrovascular disease developed in the study population!, with diagnosis definite in 621. By type, there were 108 cases of cerebral hemorrhage, 469 cases of cerebral infarction, 33 cases of subarachnoid hemorrhage, and 11 cases of other unclassifiable types. As a risk factor of cerebral hemorrhage, elevation of systolic and diastolic blood pressure was the most closely related to onset, and left ventricular hypertrophy on electrocardiogram (ECG), and proteinuria were also related. However, a tendency was seen for the risk to be higher when the levels of serum cholesterol were lower. In cerebral infarction, aging like systolic blood pressure, was a most important risk factor. Left ventricular hypertrophy on ECG, proteinuria, and diabetes could also be risk factors. However, the relation to blood pressure, especially diastolic blood pressure, was not so great as in the case of cerebral hemorrhage. Stroke Vol 15, No 4, 1984

Serum ferritin and stomach cancer risk among a Japanese population.

Using stored serum samples collected during from 1970 to 1972 and/or 1977 to 1979 from a fixed population in Hiroshima and Nagasaki, Japan, serum ferritin, transferrin, and ceruloplasmin levels were determined immunologically for persons in whom stomach (233 cases) or lung cancer (84 cases) subsequently developed as well as for their controls. An elevated stomach cancer risk was associated with low antecedent serum ferritin levels, with more than a threefold excess among those in the lowest compared with the highest ferritin quintile. The risk did not vary with the time between blood collection and stomach cancer onset, remaining high among those with low ferritin levels 5 or more years before cancer diagnosis. Achlorhydria, diagnosed in a sample of the population about 10 years before the 1970‐to‐1972 blood collection and up to 25 years before cancer, was an independent marker of stomach cancer risk. In combination, low serum ferritin and achlorhydria were associated with a tenfold increase in the subsequent risk. No effect of transferrin or ceruloplasmin, independent of ferritin, was observed in the gastric cancer risk, and the risk of lung cancer was not related to these three serum proteins. These prospective findings indicate that biologic markers of an increased risk of stomach cancer can be detected long before cancer onset.

Relationship between longitudinal changes in blood pressure and stroke incidence.

The relationship of changes in blood pressure with time to stroke incidence was examined on members of the Adult Health Study sample who have participated in biennial clinical examinations at the Radiation Effects Research Foundation since their inception in 1958. The regression coefficient of blood pressure regressed on time (the increase in blood pressure per cycle) was used as an index of the change in blood pressure with time. Coxs regression analysis, a technique which is suitable for follow-up studies was used. The data suggest that a single blood pressure measurement is not sufficient for predicting risk; the accumulated value or average over a period of time should be considered for this purpose. In addition to the actual blood pressure, the increase in blood pressure with time is a risk factor, particularly for cerebral hemorrhage. Cerebral hemorrhage was more strongly related to diastolic than to systolic blood pressure, while cerebral infarction appeared to be more strongly related to systolic than to diastolic blood pressure. Stroke Vol 15, No 5, 1984