Japanese-American Men In Hawaii Research Articles

Abstract 9935: Association of Hypertension and Growth Differentiation Factor 15 With Incident Coronary Heart Disease: The Kuakini Honolulu Heart Program

Introduction: Hypertension is a pathophysiological stress. Growth differentiation factor 15 (GDF15) is a stress-response protein, and a predictor for heart disease. The effects of the longevity genotype of FOXO3, a stress-response and prominent longevity-associated gene, on mortality vary in normotensive and hypertensive men. Hypothesis: The effect of GDF15 concentration on the risk of incident coronary heart disease (CHD) is different in men with different hypertension status. Methods: The Kuakini Honolulu Heart Program (KHHP) is a longitudinal study of cardiovascular diseases that started in 1965 involving 8,006 Japanese-American men in Hawaii. Proteomic analyses were performed using serum from KHHP exam 4 (1991-1993, ages 71-93) in a random sample (n=1,000) of men who in mid-life had been free of chronic diseases such as CHD, stroke, cancer, and diabetes. Participants were followed for incident CHD event (first event of MI, coronary insufficiency, angina, CABG, angioplasty, silent MI and CHD death) through December 1999. The Cox proportional hazards model was used to assess potential association of GDF15 concentration and hypertension (SBP/DBP≥160/95 mmHg or on anti-hypertensives) with incident CHD. Results: We excluded 5 men missing GDF15 data and 221 men with diseases including CHD, CHF, atrial fibrillation, LVH and stroke at baseline (KHHP exam 4). During 9 years of follow-up (median 7.92 years), 60 men developed CHD. To eliminate the possible recursive-effect of preclinical CHD on GDF15 at baseline, 6 CHD cases diagnosed within the first year of follow-up were excluded. So, there were 768 men available for analysis. Participants were divided, using tertiles of GDF15 concentration, into two groups: low-medium GDF15 (in low or middle tertile) and high GDF15 (in upper tertile). Multivariate Cox model adjusting for age, BMI, smoking (pack-years), cholesterol, HDL, diabetes and serum glucose showed a significant interaction effect of hypertension and high GDF15 on incident CHD (p=0.019); HR (95%CI) of high GDF15 vs low-medium GDF15 on CHD was 4.56 (1.51-13.76; p=0.007) in normotensive men, and 0.97 (0.49-1.92; p=0.93) in hypertensive men. Conclusions: High GDF15 concentration increases CHD risk in normotensive men, but not in hypertensive men.

Low Dietary Vitamin D Predicts 34-Year Incident Stroke

Vitamin D deficiency has been reported to contribute to the risk of cardiovascular disease, especially stroke. We examined the relationship between dietary vitamin D intake and 34-year incident stroke. The Honolulu Heart Program is a prospective population-based cohort study of 8006 Japanese-American men in Hawaii who were 45 to 68 years old at the baseline examination in 1965 to 1968. Dietary vitamin D intake was calculated using the Nutritionist IV Version 3 software from a 24-hour dietary recall. Subjects with prevalent stroke were excluded, leaving 7385 men followed through 1999 for incident stroke. Subjects were divided into quartiles of dietary vitamin D for analyses. During 34 years of follow-up, 960 subjects developed stroke. Age-adjusted rates of incident stroke were significantly higher in the lowest dietary vitamin D quartile compared with the highest (all stroke: 6.38 versus 5.14 per 1000 person-years follow-up, P=0.030; thromboembolic stroke: 4.36 versus 3.30, P=0.033). Using Cox regression, adjusting for age, total kilocalories, body mass index, hypertension, diabetes mellitus, pack-years smoking, physical activity index, serum cholesterol, and alcohol intake, those in the lowest quartile had a significantly increased risk of incident stroke (all stroke hazard ratio, 1.22; 95% CI, 1.01-1.47; P=0.038; thromboembolic stroke hazard ratio, 1.27; 95% CI, 1.01-1.59; P=0.044) with the highest as the reference. We found no significant associations between dietary vitamin D and hemorrhagic stroke. Low dietary vitamin D intake was an independent risk factor for 34-year incidence of all stroke and thromboembolic stroke in Japanese-American men. Additional research is needed on vitamin D supplementation to prevent stroke.

The Relation between Apolipoprotein A-I and Dementia: The Honolulu-Asia Aging Study

The association between apolipoproteins and neurodegeneration is unclear. The authors examined the association of dementia with serum levels of apolipoprotein A-I (ApoA-I) alone and in combination with the apolipoprotein E genotype (ApoE). Subjects were Japanese-American men in Hawaii followed since 1965 in the Honolulu Heart Program cohort and the Honolulu-Asia Aging Study. Lipid levels were assessed in 1980-1982. Dementia was diagnosed in 1991-1993, 1994-1996, and 1997-1999 by using a multistep procedure and international guidelines. The sample consisted of 929 men (107 dementia cases). The relation between ApoA-I and dementia was examined by using Cox proportional hazards models adjusted for age, education, and cardiovascular risk factors. Compared with men in the lowest quartile, men in the highest quartile of ApoA-I concentration had a significantly lower risk of dementia (hazard ratio = 0.25, 95% confidence interval: 0.08, 0.78). Compared with men with both risk factors, those with a high ApoA-I concentration and no ApoE epsilon4 had a significantly lower risk of dementia (hazard ratio = 0.21, 95% confidence interval: 0.08, 0.52). Previous work has demonstrated an inverse relation between ApoA-I and cardiovascular disease, and the authors extended these findings to the risk of dementia. These results raise the possibility that different lipoprotein components of cholesterol may be differentially associated with dementia.

Abstract 4205: Cardiovascular Risk Profiles Measured at the Same Age in American Immigrant Fathers and Offspring

The changes in risk profiles which occur with immigration to new cultural environments are well known. However, there have been few instances where the magnitude of these changes can be examined by measurements of cardiovascular risk factors in parents and offspring at the same age. Vital statistics indicate that Japanese-Americans in Hawaii have substantially lower CVD (cardiovascular disease) rates than are present in U.S. Caucasians, but markedly higher rates than those seen in Japanese in Japan. The Honolulu Heart Program (HHP) first measured CVD risk in first and second generation Japanese-American men in Hawaii from 1965 to 1968. From 2001 to 2004, similar measures were made in offspring from a random sample of families of these HHP men as part of the NHLBI Family Blood Pressure Program. This analysis uses data from 987 offspring (505 male and 482 female) between 39 to 77 years of age. At the time of examination, the mean age for the fathers was 53.7 years and for the offspring was 56.5 years. For some risk factors, the offspring had lower age-adjusted mean values than their fathers. The mean total cholesterol in the fathers was 218 mg/dl compared to 198.9 mg/dl in sons [p<0.001] and 212 mg/dl in daughters [p<0.001]. Current smoking was seen in 38% of fathers as compared to 15% of sons [p<0.001] and 8% of daughters [p<0.001]. However, for other risk factors, the offspring levels were higher. Hypertension (BP <140/90 or on meds) was present in 39% of fathers as compared to 51% of sons [p<0.001] and 43% of daughters [ns, p=0.27]. The fathers were much leaner, with an age-adjusted mean Body Mass Index (BMI) of 23.9, compared to 27.2 for sons [p<0.0001] and 25.5 for daughters [p<0.0001]. Although defined in slightly different ways in fathers vs. offspring, diabetes was present in 15% of fathers as compared to 24% of sons [p<0.01] and 17% of daughters [ns, p=0.59]. While one must consider temporal trends as well as acculturation in making these comparisons, these data offer remarkable insight into changes in cardiovascular risk which immigrant populations face in the U.S. today.

The impact of westernization on the risk of atherosclerotic vascular disease among Japanese-American men in Hawaii

Purpose: To assess the impact of westernization on the risk of CHD and stroke among first- and second-generation Japanese-American men in Hawaii. Methods: The length of time spent in Japan during childhood was used as a negative indicator of westernization. A total of 7479 men, aged 45–68, and free of CHD and stroke were followed up for 33 years (1965–1998). The association of childhood years in Japan with CHD and stroke risk was estimated using the Cox proportional hazards models, adjusted for age, confounding lifestyle variables, and traditional risk factors for CVD. Results: Childhood years in Japan were significantly and inversely associated with CHD risk, even after multivariate adjustment. However, there was no significant or consistent association of childhood years in Japan with stroke risk. Conclusions: Longer exposure to Japanese traditional culture and lifestyle during childhood reduced the risk of CHD later in life, but did not increase the risk of stroke. This protective effect could not be fully explained by lifestyle variables or traditional CVD risk factors.

Obesity and the risk of Parkinson's disease.

Dopamine is involved in the regulation of food intake, and obese persons have decreased dopamine D2 receptor availability in the striatum. Furthermore, midlife triceps skinfold thickness has been found to be positively associated with the risk of Parkinson's disease (PD) among Japanese-American men in Hawaii. The authors prospectively investigated whether obesity was associated with PD risk in two large cohorts of US men and women. They documented 249 cases of PD in men (1986-2000) and 202 cases in women (1976-1998). Neither baseline body mass index (weight (kg)/height (m)(2)) nor early adult body mass index was associated with PD risk. The multivariate relative risk for a baseline body mass index of > or = 30 versus <23 was 0.8 (95% confidence interval (CI): 0.6, 1.2; p for trend = 0.3). Overall, waist circumference and waist-to-hip ratio were not related to PD risk. However, among never smokers, both variables showed significantly positive associations with PD risk. The relative risks for comparisons of extreme quintiles were 1.9 (95% CI: 1.0, 3.4; p for trend = 0.03) for waist circumference and 2.0 (95% CI: 1.1, 3.6; p for trend = 0.03) for waist-to-hip ratio. The results do not support a role of overall obesity in PD pathogenesis; however, central obesity may be associated with higher PD risk among never smokers, and this finding merits further investigation.

1FS02-6 The impact of westernization on the risk of atherosclerotic vascular disease among Japanese-American men in Hawaii

1FS02-6 The impact of westernization on the risk of atherosclerotic vascular disease among Japanese-American men in Hawaii

Variability in midlife systolic blood pressure is related to late-life brain white matter lesions: the Honolulu-Asia Aging study.

Although white matter lesions (WMLs) on brain MRI in older persons are common, the mechanisms are unclear. Besides the associations with advanced age and high blood pressure (BP), variability in systolic BP (SBP) and the resulting changes in blood flow to the deep arteries of the brain may be contributing factors. Japanese-American men in Hawaii have participated in a long-term study of cardiovascular disease, including midlife BP measurements at 3 clinical examinations in the period from 1965 to 1974. In the period from 1991 to 1993, dementia status was added to the fourth examination, and a brain MRI was completed in a fifth examination, which was from 1994 to 1996, on a subset of 575 men, who averaged 82 years. WMLs and ventricular atrophy were determined as the upper fifth in a standardized semiquantitative measure. Excess SBP variability was defined as greater than average increases in BP measurements from up to 3 examinations over 6 years. Logistic regression was used for the association of this variability with WMLs and atrophy, controlling for age, apolipoprotein E4 status, dementia diagnosis, and history of stroke. There were significant (2-fold) increased risks for WMLs among those with moderate and high SBP variability (third and fifth quintiles compared with the lowest quintile). Those in the highest SBP variability category (the fifth quintile) also had significantly more atrophy. These SBP variability-MRI relationships suggest that variation in SBP in midlife may be a contributing factor to the development of WMLs and ventricular atrophy in late life.

The effects of childhood residence in Japan and testing language on cognitive performance in late life among Japanese American men in Hawaii.

To examine the association of years spent in Japan during childhood with cognitive test performance in late life among Japanese American men, and to assess the influence of the language used for testing on this association. A cross-sectional study. A total of 3734 Japanese American men, aged 71-93 years, who were first- or second-generation migrants and living on Oahu Island, Hawaii. The outcome variable was cognitive test performance assessed using the Cognitive Abilities Screening Instrument (CASI), which was developed for cross-cultural studies of cognitive impairment. The explanatory variable of main interest was the number of years spent in Japan during school-age childhood years (ages 6-17). The associations of CASI scores with childhood years in Japan was evaluated using a stepwise multiple linear regression model in which a total of 40 potential confounders were included as covariates. In the total sample, there was an inverse association between CASI scores and middle childhood years in Japan. This association remained significant after controlling for age, education, socioeconomic status, traditional Japanese food consumption, pulmonary function, apolipoprotein E4, proficiency in speaking Japanese, and other possible confounders. When data were analyzed separately for subgroups according to the language preferred at testing (English or Japanese), associations between childhood years in Japan and CASI scores were in opposite directions negative for the group tested in English and positive for the group tested in Japanese. The interaction between the testing language and childhood years in Japan was statistically significant. There was an inverse association between years spent in Japan during school-age years of childhood and cognitive test performance in late life. This association could not be accounted for by age, education, or other confounding factors. However, this finding was not observed in participants who preferred being tested in Japanese. To assess cognitive test performance in older people, it is of prime importance to use the most optimal language for testing, usually the subject's native language.

Plasma Fibrinogen and Its Correlates in Elderly Japanese Men Living in Japan and Hawaii

Plasma fibrinogen levels were determined using comparable methods for 329 Japanese men in Hiroshima Japan, and 3571 Japanese-American men in Honolulu Hawaii, aged 71–93 years. The age-adjusted mean fibrinogen level in Japanese-American men (307 mg/dl) was significantly higher (p < 0.0001) than in native Japanese men (270 mg/dl). In multiple linear regression models, the fibrinogen level was associated significantly and positively with white blood cell count (WBC) and total cholesterol, and inversely with HDL cholesterol and hematocrit in both study samples. The strongest association with fibrinogen was shown for WBC, and this association was not mediated through cigarette smoking. The observed difference in fibrinogen levels could not be fully explained by WBC, total and HDL cholesterol, triglyceride, hematocrit, body mass index, and diabetes. Some unmeasured environmental or lifestyle variables such as diet and physical activity may be partly responsible for the observed difference in fibrinogen levels between native Japanese men and Japanese-American men in Hawaii.

Prevalence of Dementia in Older Japanese-American Men in Hawaii

To determine prevalence of dementia and its subtypes in Japanese-American men and compare these findings with rates reported for populations in Japan and elsewhere. The Honolulu Heart Program is a prospective population-based study of cardiovascular disease established in 1965. Prevalence estimates were computed from cases identified at the 1991 to 1993 examination. Cognitive performance was assessed using standardized methods, instruments, and diagnostic criteria. Subjects were 3734 Japanese-American men (80% of surviving cohort) aged 71 through 93 years, living in the community or in institutions. Age-specific, age-standardized, and cohort prevalence estimates were computed for dementia (all cause) defined by 2 sets of diagnostic criteria and 4 levels of severity. Prevalence levels for Alzheimer disease and vascular dementia were also estimated. Dementia prevalence by Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised ranged from 2.1% in men aged 71 through 74 years to 33.4% in men aged 85 through 93 years. Age-standardized prevalence was 7.6%. Prevalence estimates for the cohort were 9.3% for dementia (all cause), 5.4% for Alzheimer disease (primary or contributing), and 4.2% for vascular dementia (primary or contributing). More than 1 possible cause was found in 26% of cases. The Alzheimer disease/vascular dementia ratio was 1.5 for cases attributed primarily to Alzheimer disease or vascular dementia. Prevalence of Alzheimer disease in older Japanese-American men in Hawaii appears to be higher than in Japan but similar to European-ancestry populations. Prevalence of vascular dementia appears to be slightly lower than in Japan, but higher than in European-ancestry populations. Further cross-national research with emphasis on standardized diagnostic methods is needed.

Prevalence of dementia in older Japanese-American men in Hawaii: The Honolulu-Asia Aging Study

Prevalence of dementia in older Japanese-American men in Hawaii: The Honolulu-Asia Aging Study

377 Prevalence of dementia in Japanese-American men in Hawaii: The Honolulu-Asia aging study

377 Prevalence of dementia in Japanese-American men in Hawaii: The Honolulu-Asia aging study

Determinants of sex hormone levels in men as useful indices in hormone-related disorders

Because the determinants of serum sex hormone levels in men have been infrequently studied, we investigated the relation of several personal characteristics to serum levels of testosterone (T), dihydrotestosterone (DHT), estrone (El), estradiol (E2) and sex hormone-binding globulin (SHBG) among 98 Japanese American men in Hawaii, aged 52–74. The SHBG levels and T/(El + E2) ratios decreased progressively with increasing body mass index. The SHBG levels were also inversely associated with hematocrit levels. Serum androgen and estrogen levels did not correlate with smoking, alcohol intake, serum cholesterol, serum uric acid and blood pressure. Some of the associations observed in the present study may be implicated in the etiology of hormone-related neoplasms in men.

Will lowering population levels of serum cholesterol affect total mortality? Expectations from the honolulu heart program

Major campaigns now underway to reduce the serum cholesterol levels of entire national populations have not given serious consideration to the high rates of non-cardiovascular disease and death associated with low cholesterol levels (< 190 mg/dl). To explore this problem, the relationships between serum cholesterol levels, measured in 1965–1968 in 7478 Japanese American men in Hawaii, and subsequent total and cause-specific mortality through 1985, were analyzed by multivariate Cox regression to control for potential confounders. Total mortality rates for 1648 deaths showed a U-shaped curve by baseline cholesterol level, with significant inverse trends ( p < 0.03) for deaths due to hemorrhagic stroke, all cancer, benign liver disease, chronic obstructive lung disease and “unknown cause”. Only the inverse trends for cancer and benign liver disease showed flattening when 227 deaths in the first 5 years of follow-up were deleted from the analysis. Simulation models using three different strategies of cholesterol reduction in this cohort revealed that none of these approaches had any substantial impact on predicted total mortality over 15 years. However, the population-based approach might theoretically increase mortality for 60% of the cohort with baseline cholesterol levels less than 225 mg/dl.

Body fat, coronary heart disease, and stroke in Japanese men

The Honolulu Heart Program (HHP) is a prospective study of heart disease and stroke in Japanese-American men in Hawaii. Body weight, height, and subscapular and triceps skinfold thicknesses were measured by using standard methods at the baseline exam held in 1965-1968. The relationship of measures of body fatness to the 20-y follow-up for coronary heart disease (CHD) and stroke of these men was explored. Body mass index (BMI), subscapular skinfold thicknesses, and centrality index (subscapular skinfold thickness/triceps skinfold thickness) were predictors of CHD in this population, even after other risk factors were added to a multivariate model, indicating an independent contribution of body fat to CHD risk. Neither BMI nor centrality index was related to stroke. However, subscapular skinfold thickness was an independent predictor of stroke. The implications of these findings are that lifestyle changes that lead to an increase in obesity of Japanese men in Hawaii may increase risk for cardiovascular disease.

Serum cholesterol and hemorrhagic stroke in the Honolulu Heart Program.

During an average 18 years of follow-up for 7,850 Japanese-American men in Hawaii who were free of stroke at entry, 116 developed hemorrhagic stroke (subarachnoid hemorrhage or intracerebral hemorrhage). There was a significant (p = 0.001) inverse association between serum cholesterol and the risk of intracerebral hemorrhage but not of subarachnoid hemorrhage. This inverse association was nonlinear, with a higher incidence rate only for men with serum cholesterol in the lowest quintile (less than 189 mg/dl). The relative risk (lowest quintile/other four quintiles) was 2.55 (95% confidence interval 1.58-4.12) after controlling for age, blood pressure, serum uric acid, cigarette smoking, and alcohol consumption. There was no evidence for an interaction between blood pressure and serum cholesterol, although the inverse association was stronger for normotensive than for hypertensive men. Public health implications would differ in different countries depending on the relative frequency of intracerebral hemorrhage and on the distribution of serum cholesterol levels in the population.

The Incidence and Prognosis of Unrecognized Myocardial Infarction in the Honolulu, Hawaii, Heart Program

The incidence of clinically unrecognized myocardial infarctions among 7331 Japanese-American men in Hawaii, aged 45 to 68 years and free of coronary heart disease at entry, was studied on the basis of electrocardiographic changes between successive examinations during 6 years of follow-up. The proportion of asymptomatic myocardial infarction accounted for 33% of transmural (Q-wave) myocardial infarctions identified by temporal changes on electrocardiogram and 22% of all nonfatal infarctions ascertained by either repeated examinations or hospital surveillance. The 10-year prognosis of unrecognized infarction, in terms of mortality from all causes, cardiovascular disease, and coronary heart disease, was worse (with risk ratios of 1.5 to 1.7) than that of recognized infarction, even after adjusting for age and other possible determinants, although the differences were not statistically significant. These findings suggest that regular health check-ups with an electrocardiogram would be important to detect asymptomatic myocardial infarction and to increase the opportunity of taking secondary preventive measures. However, the conclusion should await further studies based on intervention trials to determine the comparative effects of the secondary prevention on the prognosis of clinically recognized vs unrecognized infarction.

Postmortem findings in sudden and non-sudden deaths among Japanese-American men in Hawaii

Analyses were made of the cause of death and major pathologic findings among 1,085 autopsied Japanese-American men in Hawaii to determine the differences between the 167 men who experienced sudden death within 24 hours of being well and the 918 men with non-sudden death. Sudden deaths were further divided into three subgroups according to the interval from the onset of symptoms to death: (less than one hour; one to six hours; more than six hours). Nearly 90 percent of sudden deaths and 25 percent of non-sudden deaths were attributed to cardiovascular disease. The proportion of deaths due to coronary heart disease was highest in sudden deaths less than one hour (72 percent) and lowest in sudden deaths more than six hours (49 percent), whereas the proportion of stroke deaths was highest in sudden deaths more than six hours (37 percent) and lowest in sudden deaths less than one hour (9 percent). The prevalence of myocardial infarction and the grade of coronary atherosclerosis were also significantly greater for sudden deaths (especially sudden deaths less than one hour) than for non-sudden deaths.

Characteristics of joggers among Japanese men in Hawaii.

In a population-based cohort of Japanese American men in Hawaii, the 450 joggers differed from 6,171 nonjoggers in being younger, taller, heavier, and more obese; in having larger vital capacity, higher socioeconomic status, and a higher prevalence of certain electrocardiographic abnormalities; and in being more health conscious as demonstrated by less smoking and a higher frequency of special diets. Blood pressure, serum total cholesterol, hematocrit and high density lipoprotein cholesterol (HDL-C) did not differ significantly between the two groups. Multiple regression analysis showed HDL-C to be inversely related to obesity and cigarettes, and directly related to alcohol consumption but to have no relationship to jogging or age. Temporal analyses suggested that initiation of jogging was followed by a reduction in heart rate, but there was no significant change in other measured parameters. Coronary heart disease (CHD) prevalence was increased in joggers, perhaps because the diagnosis of CHD predisposes to this activity. We conclude that jogging has probably had little impact on the health of this cohort.