Postchallenge glucose concentration and coronary heart disease in men of Japanese ancestry. Honolulu Heart Program.

Since 1965, the Honolulu Heart Program has followed 8006 men of Japanese ancestry, aged 45-70 yr at study entry, for the development of cardiovascular disease. To investigate the role of glucose concentration 1 h after a 50-g challenge on the risk of fatal coronary heart disease (CHD) and nonfatal myocardial infarction (MI), 6394 nondiabetic men were followed for 12 yr for the first development of CHD. The rate of fatal CHD increased linearly with amount of glucose. Men in the fourth quintile of postchallenge glucose (157-189 mg/dl) had twice the age-adjusted risk of fatal CHD of those in the lowest quintile (P less than .05). Relative risk increased to threefold among those in the top quintile and remained statistically significant after adjustment for other risk factors including body mass, total cholesterol, hypertension, left ventricular hypertrophy, and hematocrit (P less than .001). When glucose was considered as a linear term in the proportional hazards model, a highly significant relation was noted with fatal CHD alone and when combined with nonfatal MI (P less than .001). We conclude that a continuously increasing risk gradient exists between postchallenge glucose and subsequent CHD that is independent of other known risk factors.

Lifestyle and biologic factors associated with atherosclerotic disease in middle-aged men. 20-year findings from the Honolulu Heart Program.

OBJECTIVES: To examine the association between a variety of baseline lifestyle and biologic factors in a middle-aged cohort of Japanese-American men and the 20-year incidence rates of total atherosclerotic end points and each of the initial clinical manifestations of this disease, including fatal and nonfatal coronary heart disease, angina pectoris, thromboembolic strokes, and aortic aneurysms. DESIGN: Prospective epidemiologic study. POPULATION: Japanese-American men (N = 2710) between the ages of 55 and 64 years at the time of the initial clinical examination of the Honolulu Heart Program (1965 through 1968) free from evidence of coronary heart disease, cerebrovascular disease, cancer, or aortic aneurysms. RESULTS: Among the men studied, 602 atherosclerotic events developed during the 23-year period of follow-up (1965 through 1988). After adjustment for each of the baseline characteristics examined, significant positive associations between quartile cutoffs of body mass index, systolic blood pressure, serum levels of cholesterol, triglycerides, glucose, and uric acid, as well as cigarette smoking, and the occurrence of any atherosclerotic end point were seen, while an inverse association with alcohol consumption was observed. Characteristics associated with the development of other fatal and nonfatal clinical events in this cohort, including coronary heart disease, thromboembolic stroke, and aortic aneurysms are presented with accompanying relative and attributable risks. CONCLUSIONS: The results of this prospective epidemiologic study provide insights to the long-term predictive utility of the commonly accepted risk factors for coronary heart disease in relation to the different clinical manifestations of atherosclerosis in a middle-aged male cohort followed up for approximately 20 years. These results provide additional support for risk factor modification in middle-aged men and for the encouragement of positive long-term lifestyle changes.

Serum cholesterol level and mortality due to suicide and trauma in the Honolulu Heart Program.

BACKGROUND: Recent results from cholesterol level-lowering trials and some, but not all, observational studies support an intriguing link between low or lowered serum cholesterol levels and violent death. The reasons behind this relationship are far from clear. METHODS: In this report, we further investigate this issue by assessing the relationship of baseline serum cholesterol levels with long-term risk of mortality due to trauma and suicide in a cohort of 7309 middle-aged Japanese-American men. RESULTS: After 23 years of follow-up, a total of 75 traumatic fatalities and 24 deaths by suicide were documented. Rather than an inverse relation, a positive association between serum cholesterol level and risk of suicide death was observed. After controlling for potential confounders, the relative risk of suicide associated with an increment of 0.98 mmol/L (38 mg/dL) in serum cholesterol level (1 SD) was 1.46 (95% confidence interval, 1.04 to 2.05; P = .02). Multivariate analysis of traumatic mortality failed to detect a relation with serum cholesterol level (relative risk = 0.89; 95% confidence interval, 0.70 to 1.13; P = .44). Heavy alcohol consumption (> 1200 mL of alcohol per month, top quintile) was an independent risk factor for trauma death relative to abstinence (relative risk = 1.86; 95% confidence interval, 1.07 to 3.22; P = .02). CONCLUSIONS: These findings contradict the hypothesis of an inverse relation between serum cholesterol level and suicide, but they support the hypothesis that heavy alcohol consumption is a risk factor for traumatic fatal events.

Relationship of magnesium intake and other dietary factors to blood pressure: the Honolulu heart study.

Associations between blood pressure and intakes of 61 dietary variables assessed by 24-h recall method were investigated in 615 men of Japanese ancestry living in Hawaii who had no history of cardiovascular disease or treated hypertension. Magnesium, calcium, phosphorus, potassium, fiber, vegetable protein, starch, vitamin C, and vitamin D intakes were significant variables that showed inverse associations with blood pressure in univariate and a multivariate analyses. Magnesium had the strongest association with blood pressure, which supports recent interest in its relation to blood pressure. Nevertheless, it was not possible to separate the effect of magnesium from that of other variables because of the problem of high intercorrelation among many nutrients. While recommendations based upon cross-sectional studies must be viewed cautiously, these results suggest that foods such as vegetables, fruits, whole grains, and low-fat dairy items are major sources of nutrients that may be protective against hypertension.

Predicting the duration of Guam amyotrophic lateral sclerosis.

During the years of study of amyotrophic lateral sclerosis on Guam we have observed a wide range in clinical signs and rate of progression of the disease. Some patients died within 6 months of onset, while others have lived for 20 years. It was our assumption that some aspects of the early neurologic involvement would be related to length of survival, and hence be of prognostic value. We found that an early age at onset and male sex were associated with longer survival. The detailed analysis of degree of involvement of four major neurologic components of amyotrophic lateral sclerosis (progressive muscular atrophy, lateral sclerosis, bulbar paralysis, and pseudobulbar palsy) showed no meaningful pattern of association with duration of illness that could be useful in predicting the course.

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.

Smoking, pulmonary function, and mortality.

The association of pulmonary function (as percent of predicted forced expiratory volume in 1 second [FEV1]) with total and cause-specific mortality over 15 to 18 years was investigated in a large cohort (5924) of prospectively followed Japanese-American men. Among those who never smoked, pulmonary function was found not to be significantly predictive of total mortality in a multivariate model in which adjustment for variables that might confound the results was made. Among past and current smokers, highly significant associations were found (P < 0.0001). The positive relationship of pulmonary function to mortality in smokers was so strong that it overshadowed these differences in nonsmokers in a model including all smoking groups combined, even after adjusting for smoking. A smoking-pulmonary function interaction term added to this model was statistically significant (P < 0.003). This illustrates the need for attention to the potential for complex interactions between biologic variables when carrying out multivariate statistical analysis. Findings for cardiovascular and noncardiovascular mortality were similar. This analysis indicates that while pulmonary function is associated with subsequent mortality, the relationship is significantly associated with smoking history.

Predictors of myocardial lesions in men with minimal coronary atherosclerosis at autopsy. The Honolulu heart program.

Some cardiovascular risk factors are associated with clinical coronary heart disease but not with autopsy evidence of coronary atherosclerosis. To determine whether these risk factors might operate through mechanisms other than atherosclerosis, we examined associations between cardiovascular risk factors and subsequent intramural myocardial lesions assessed by protocol autopsy between 1965 and 1984 in 120 Japanese-American men from the Honolulu Heart Program who had minimal coronary atherosclerosis (American Heart Association (AHA) panel score < 3 on scale of 1 to 7). Age-adjusted prevalence of myocardial lesions was related to smoking status (P < 0.01), as well as amount, duration, and pack-years of smoking (P < 0.03). In a multiple logistic model, smoking (20 pack-years) was directly associated and fish intake (> or = 2 times/wk) was inversely associated with myocardial lesions independently of age, cholesterol, systolic blood pressure, body mass index, alcohol, diabetes, total calories, and animal protein intake (odds ratio (OR) = 1.5, 95% confidence intervals (CI) = 1.1 to 2.0 and OR = 0.35, 95% CI = 0.2 to 0.9, respectively). The protective effect of fish intake was most evident among men who did not have hypertension at baseline. Indices of obesity, body fat distribution, and physical activity and levels of triglyceride and alcohol intake were not associated with myocardial lesions. Thus, the adverse effects of smoking and the protective effects of fish consumption may extend to individuals relatively free of coronary atherosclerosis, possibly through hemostatic mechanisms or effects on small intramural arteries.

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 noncardiovascular disease and death associated with low cholesterol levels (less than 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 less than 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.

Risk factors in middle age that predict early and late onset of coronary heart disease.

Twelve biological and lifestyle characteristics measured in a group of 5919 middle aged men free of clinical coronary heart disease (CHD), stroke and cancer were analyzed for differences in predicting early and late onset of new cases of definite CHD (non-fatal myocardial infarction and fatal CHD) over a 12-year follow-up period. Among these men, 151 cases of definite CHD occurred early (under age 60) and 135 cases occurred later in life (age 60 and over). Serum triglyceride was the only risk factor that was an independent predictor of early onset disease and not of late onset disease. While cigarette smoking was a predictor for both onset groups, the effect of smoking was greater in people who developed CHD earlier in life. Systolic blood pressure, alcohol intake, serum cholesterol and serum glucose were independent predictors for both onset groups, with no difference in effect between groups. The findings indicate that it is possible for some factors to affect CHD risk differently in terms of premature vs delayed onset of disease. The findings for serum triglyceride may account for some of the inconsistencies in reports regarding it as an independent risk factor for CHD. In general, however, most of the characteristics studied here had a similar effect on both early and late onset and thus remain important in the prevention of both premature and late onset of CHD.

The predictive value of resting electrocardiograms for 12-year incidence of coronary heart disease in the Honolulu Heart Program.

The predictive value of electrocardiographic (ECG) abnormalities at baseline for subsequent risk of fatal and total coronary heart disease (CHD) was analyzed in a 12-year follow-up of 7682 men in the Honolulu Heart Program aged 45-68 who were free of CHD at baseline. Univariate analysis showed that men with major or minor ECG abnormalities, ST depression, high R wave, T-wave inversion, left ventricular hypertrophy or strain and premature ventricular contractions had considerably higher (2-10 fold) CHD incidence rates than those with normal ECG. When blood pressure, cigarette smoking, body mass index, alcohol use, physical activity, serum glucose, serum cholesterol, serum uric acid, age and years lived in Japan were taken into consideration through multivariate analysis, the ECG abnormalities retained significant associations with fatal and total CHD. This study demonstrated that resting ECG abnormalities were independent predictors of both total and fatal CHD.

Mortality and morbidity among blue and white collar workers in the Honolulu Heart Program cohort.

There has been a controversy regarding occupation, as defined by blue and white collar work, and coronary heart disease (CHD). In a large long-term prospective study of the Honolulu Heart Program cohort, there were no significant differences between these two occupational classifications and the incidence rates of fatal and non-fatal CHD. Nor were there significant differences in total mortality, stroke or total cancer although there were very small but significant differences in some CHD risk factors. Unlike the previous studies, this investigation was free of prevalent cases of CHD at baseline and controlled for the major risk factors of CHD. We question the utility of using this occupational classification to investigate the causes of CHD.

Potential bias due to prevalent diseases in prospective studies.

In prospective studies, subjects found to have the disease under investigation at the initial screening examination are commonly excluded from analyses. However, the possibility of bias due to prevalent conditions other than the disease of interest is usually not considered. In the present study, an algebraic development enables analysis of the effects of inclusion and exclusion of subjects with certain prevalent conditions upon risk estimates. Hypothetical data are presented for which an association between a risk factor and an incident disease could become null or even reversed after removing subjects with certain prevalent diseases. Bias appears even when the only association present is between risk factor and total disease incidence. Data from the Honolulu Heart Study also have been used to illustrate this finding, examining the association between coronary heart disease (CHD) incidence and smoking. Decisions regarding the inclusion or exclusion of subjects with prevalent diseases requires prior knowledge of alteration of usual risk factors levels by individuals with these diseases. Simply removing all subjects with prevalent diseases might on the contrary create bias. Therefore, people with prevalent diseases should be screened for potential alteration of their risk factor levels as a result of the diseases. The situation becomes still more complex when several risk factors and prevalent diseases need to be considered at the same time as it happens in multivariate analyses. Because this situation represents a bias, and not confounding or effect modification, controlling for the effect of prevalent diseases is not appropriate.

Can money buy happiness? Depressive symptoms in an affluent older population.

OBJECTIVES: To determine if the inverse association between depressive symptoms and income reported in predominantly low- and middle-income older populations is present in a more affluent population of older adults and to determine if this pattern is independent of other known correlates of depressive symptoms such as medical problems, physical disability, and social support. DESIGN: Cross-sectional analysis within a prospective cohort study. SETTING: An ongoing, community-based cohort study conducted by an independent research institution in an affluent Northern California county. PARTICIPANTS: A total of 1948 randomly selected, noninstitutionalized county residents 55 years of age and older who completed the baseline questionnaire and physical performance tests. MEASUREMENTS: The outcome measure was high level of depressive symptoms (score > or = 16) using the Center for Epidemiologic Studies-Depression scale (CES-D). RESULTS: The prevalence of high levels of depressive symptoms (CES-D score > or = 16) was lower than in most other population-based samples using an identical CES-D scale. In age-adjusted, sex-specific analyses, increasing income level was associated significantly with lower levels of depressive symptoms, but the nature of the relationship appeared quadratic rather than linear (Men: odds ratio (OR) income .80, 95% confidence interval (CI) .68-.94; income2 OR 1.006, 95% CI 1.001-1.011. Women: OR income .80, 95% CI .69-.91; income2 OR 1.007, 95% CI 1.002-1.011). In multivariate regression analyses including potential confounding risk factors, the magnitude of the association between depressive symptoms and income decreased and was not statistically significant when measures of health conditions, physical disability, and social support were included in the model (Men: OR income .90, 95% CI .75-1.06; income2 OR 1.003, 95% CI .998-1.009. Women: OR income .90, 95% CI .78-1.05; income2 OR 1.003, 95% CI .998-1.008). CONCLUSION: These findings suggest that poor health, physical disability, and social isolation are the major factors responsible for the observed inverse relationship between income and symptoms of depression in affluent, as well as economically disadvantaged, older populations.

Plasma lipids and lipoproteins in elderly Japanese-American men.

Knowledge about blood lipids in older individuals is limited. In the Lipoprotein Study of the Honolulu Heart Program, plasma cholesterol, triglyceride, and high-density lipoprotein (HDL) were measured during 1980 and 1981 in Japanese-American men over 60 years of age. In addition, low-density lipoprotein cholesterol (LDL-C) was estimated via a regression model. Age-related differences in mean lipid levels between the youngest (60 to 64 years) and the oldest (75 years and older) groups included a decrease in total cholesterol from 214 to 207 mg/dL and plasma triglyceride from 188 to 144 mg/dL. High density lipoprotein cholesterol rose from 47 to 49 mg/dL and LDL was relatively stable (137 and 135 mg/dL, respectively). Age-adjusted total cholesterol tended to significantly increase with increasing body mass index and hematocrit but was not significantly related with systolic blood pressure, physical activity index, cigarettes per day, or alcohol intake. Among those variables HDL-C decreased significantly with increasing body mass index and hematocrit and increased significantly with increasing alcohol intake. Compared with elderly white men in the Lipid Research Clinic Program, total cholesterol values tended to be slightly higher and triglyceride values were substantially higher, whereas HDL and LDL values were appreciably lower. Both cholesterol and triglyceride values were substantially higher than values reported from Japan from men in these age groups.

Current health problems in the South and Central Pacific.

Tabulation of monthly reports of infectious diseases from 19 countries and territories in the South and Central Pacific for the years 1973 through 1975 indicated that influenza-like illness, dengue, dysentery, measles, and gonorrhoea were the greatest problems. Reports of the leading causes of hospitalisation from 11 areas indicated that infectious respiratory disease, gastroenteritis and accidents were the most common problems requiring hospitalisation in most Pacific countries. The leading causes of death showed a different pattern with striking differences between traditional and modernised areas. It appeared that the major causes of death were changing from infectious diseases in the traditional areas to chronic diseases such as cardiovascular disease and cancer in the modernised areas.

Visualization of compression neuropathies through volume deformation.

This paper describes an interdisciplinary effort to simulate and visualize the mechanisms involved in compression neuropathies, specifically tissue deformation occurring during vaginal delivery. These neuropathies often evolve into chronic pelvic pain. We present our methodologies of using high resolution magnetic resonance acquisitions from submillimeter pulse sequences to develop interactive computer simulations based on physically plausible volume models to drive 3D simulations of childbirth. This effort will elucidate tissue movements and mechanics involved in pain disorders and better explain the etiology of these disorders.

Sugarcane workers: morbidity and mortality.

Sugarcane is, after pineapple, the largest agricultural industry in Hawaii. There have been reports that this industry poses certain health hazards. To investigate this possible hazard in Hawaii, the relationship of employment on a sugarcane plantation to total mortality, the development of definite coronary heart disease (CHD), stroke, cancer, lung cancer and certain risk factors were examined in men of Japanese ancestry participating in the Honolulu Heart Program. After 18 years of follow-up, those men who indicated one or more years working on sugarcane plantations had no significant difference in age-adjusted mortality, nor incidence of CHD, stroke, cancer, or lung cancer. There were no differences in risk factors compared to participants who were never employed on sugarcane plantations, nor were there differences in lung function as measured by FEV1. These findings were unchanged after adjusting for several potential confounding variables. No cases of mesothelioma were observed among those with a history of defined exposure. These findings were not due to a "healthy worker bias" and indicate that employment on a sugarcane plantation in Hawaii is not associated with elevated rates of chronic diseases.

Pharmacology and therapeutic potential of pattern recognition receptors.

Pharmacologists have used pathogen-associated molecular patterns (PAMPs), such as lipopolysaccharide (LPS) for decades as a stimulus for studying mediators involved in inflammation and for the screening of anti-inflammatory compounds. However, in the view of immunologists, LPS was too non-specific for studying the mechanisms of immune signalling in infection and inflammation, as no receptors had been identified. This changed in the late 1990s with the discovery of the Toll-like receptors. These 'pattern recognition receptors' (PRRs) were able to recognise highly conserved sequences, the so called pathogen associated molecular patterns (PAMPs) present in or on pathogens. This specificity of particular PAMPs and their newly defined receptors provided a common ground between pharmacologists and immunologists for the study of inflammation. PRRs also recognise endogenous agonists, the so called danger-associated molecular patterns (DAMPs), which can result in sterile inflammation. The signalling pathways and ligands of many PRRs have now been characterised and there is no doubt that this rich vein of research will aid the discovery of new therapeutics for infectious conditions and chronic inflammatory disease.