Dwayne Reed

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 (Ml), 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 < .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 < .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 Ml (P < .001). We conclude that a continuously increasing risk gradient exists between postchallenge glucose and subsequent CHD that is independent of other known risk factors.

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.

Are aortic aneurysms caused by atherosclerosis

BackgroundThe emerging controversy concerning the causal role of atherosclerosis in the development of aortic aneurysms was examined using the accumulated clinical and autopsy data obtained during a 20-year follow-up of a cohort of more than 8,000 men of Japanese ancestry in Hawaii. Methods and ResultsAnalyses of 174 clinical incident events indicated that there were two types of aneurysmal disease, 151 aortic aneurysms and 23 aortic dissections. The baseline risk factors that predicted the clinical aortic aneurysms were the same factors that predicted aortic atherosclerosis in the same cohort, namely, high blood pressure, high serum cholesterol, and cigarette smoking. These same risk factors were also significantly associated with the occurrence of 27 aortic aneurysms among 293 autopsied men. The less common aortic dissections had an age-specific incidence pattern indicative of an innate susceptibility precipitated by an exposure to another factor. This pattern was consistent with the findings that the incidence of aortic dissections was predicted mainly by baseline high blood pressure. Conclusionsperspective of prevention, it appears that the risk factors for aortic atherosclerosis and probably atherosclerosis itself are necessary elements in the causal pathway for the great majority of aortic aneurysms in this cohort.

Religion and mortality among the community-dwelling elderly.

OBJECTIVES This study analyzed the prospective association between attending religious services and all-cause mortality to determine whether the association is explainable by 6 confounding factors: demographics, health status, physical functioning, health habits, social functioning and support, and psychological state. METHODS The association between self-reported religious attendance and subsequent mortality over 5 years for 1931 older residents of Marin County, California, was examined by proportional hazards regression. Interaction terms of religion with social support were used to explore whether other forms of social support could substitute for religion and diminish its protective effect. RESULTS Persons who attended religious services had lower mortality than those who did not (age- and sex-adjusted relative hazard [RH] = 0.64; 95% confidence interval [CI] = 0.52, 0.78). Multivariate adjustment reduced this relationship only slightly (RH = 0.76; 95% CI = 0.62, 0.94), primarily by including physical functioning and social support. Contrary to hypothesis, religious attendance tended to be slightly more protective for those with high social support. CONCLUSIONS Lower mortality rates for those who attend religious services are only partly explained by the 6 possible confounders listed above. Psychodynamic and other explanations need further investigation.

Diet, blood pressure, and multicollinearity.

Recent reports of an inverse association between dietary calcium intake and hypertension stimulated this analysis of the relationship of blood pressure to more than 20 dietary factors among a group of 8000 Japanese men in Hawaii. Reported intakes of potassium, calcium, protein, and milk were all inversely associated with blood pressure levels when examined one at a time while controlling for other risk factors. Alcohol intake was directly associated with blood pressure, and was treated as a confounding variable in the analysis. The association of potassium intake with blood pressure was relatively stronger than the associations for other nutrients, but the intake of potassium was so highly correlated with intakes of calcium, milk, and protein that it was not statistically possible to identify the independent association of potassium and blood pressure. Calcium intake was strongly correlated with milk and potassium intakes, and only calcium from dairy sources was associated with blood pressure. These data thus indicate that several dietary factors are inversely related to blood pressure levels independently of other risk factors such as age, body mass, and alcohol intake. The high degree of intercorrelation (multicollinearity) among these dietary factors, however, indicates that the independent role of any specific nutrient cannot be conclusively separated from the possible effects of other nutrients in this type of study.

Physical activity and coronary heart disease in middle-aged and elderly men: the Honolulu Heart Program.

The relationship of physical activity to the development of definite coronary heart disease was examined separately in middle-aged (45-64 years) and elderly men (65-69 years) participating in the Honolulu Heart Program. After 12 years of follow-up, results indicate that increased levels of physical activity reported at study entry were inversely related to the risk of definite coronary heart disease in both age groups. In particular, among those aged 45 to 64 years, the rate of definite coronary heart disease in men who led active life styles was 30 per cent lower than the rate experienced by those who were less active (relative risk, 0.69; 95% confidence interval, 0.53, 0.88). In those older than 64 years, the rate of definite coronary heart disease in active men was less than half the rate experienced by those who led more sedentary life styles (relative risk, 0.43; 95% CI, 0.19, 0.99). These results continued to hold up when controlling for several cardiovascular risk factors and potentially confounding variables, supporting earlier observations that physical activity is beneficial in middle-age, and further suggesting that benefits may extend to the elderly male population as well.

Low Serum Cholesterol and Mortality Which Is the Cause and Which Is the Effect

BACKGROUND Many studies have reported an association between a low or lowered blood total cholesterol (TC) level and subsequent nonatherosclerotic disease incidence or death. The question of whether low TC is a true risk factor or alternatively a consequence of occult disease at the time of TC measurement remains unsettled. To shed new light onto this problem, we analyzed TC change over a 6- year period (from exam 1 in 1965 through 1968 to exam 3 in 1971 through 1974) in relation to subsequent 16-year mortality in a cohort of Japanese American men. METHODS AND RESULTS The study was based on 5941 men 45 to 68 years of age without prior history of coronary heart disease, stroke, cancer, or gastrointestinal-liver disease at exam 1 who also participated in exam 3 of the Honolulu Heart Program. The association of TC change with mortality end points was investigated with two different approaches (continuous and categorical TC change) with standard survival analysis techniques. Falling TC level was accompanied by a subsequent increased risk of death caused by some cancers (hemopoietic, esophageal, and prostate), noncardiovascular noncancer causes (particularly liver disease), and all causes. The risk-factor-adjusted rate of all-cause mortality was 30% higher (relative risk, 1.30; 95% CI, 1.06 to 1.59) among persons with a decline from middle (180 to 239 mg/dL) to low (< 180 mg/dL) TC than in persons remaining at a stable middle level. By contrast, there was no significant increase in all-cause mortality risk among cohort men with stable low TC levels. Nonillness mortality (deaths caused by trauma and suicide) was not related to either TC change or the average of TC levels in exams 1 and 3. CONCLUSIONS These results add strength to the reverse-causality proposition that catabolic diseases cause TC to decrease.

A prospective study of cerebral artery atherosclerosis.

Atherosclerosis in the circle of Willis and its major branches was studied prospectively in 198 men in the Honolulu Heart Program who were free of cardiovascular disease at the entry examination. The level of atherosclerosis was greater in the large arteries of the circle of Willis than in the small arteries, and autopsy-verified cerebral infarction was strongly associated with increasing severity of atherosclerosis in both. Analyses of the association of atherosclerosis scores with biologic and lifestyle characteristics measured at entry into the study indicated that atherosclerosis in the large arteries was consistently related to age, diastolic blood pressure, serum cholesterol, and height (inversely). Weak trends of association were also found with increasing serum glucose concentration, increasing cigarette use, and decreasing alcohol intake. Atherosclerosis scores in the small arteries were associated with diastolic blood pressure and serum triglyceride concentration. Analysis of dietary intake indicated that atherosclerosis scores were higher for men who reported low intakes of fat and animal protein and high intakes of vegetable protein and total carbohydrates. These patterns were consistent with similar findings on the incidence of clinical stroke in this cohort. Age-adjusted and -specific atherosclerosis scores from both the large and small arteries declined significantly during the period 1965-1983.

Biological and social correlates of blood pressure among Japanese men in Hawaii.

A cohort of more than 8000 Japanese men living in Hawaii was studied for factors associated with blood pressure levels, with an emphasis on biological and sociocultural variables. Bivariate and multivariate analyses of more than 50 variables indicated that obesity, age, hematocrit, heart rate, forced vital capacity, serum triglyceride, serum uric acid, cigarette consumption, and family history of hypertension were independently associated with both cross-sectional levels and longitudinal changes in blood pressure. Serum glucose and alcohol consumption were associated with cross-sectional levels only. There was little evidence of association for specific dietary items, type of diet, diet changes, or use of salt. Furthermore, there was no support for the psychosocial hypotheses of elevated blood pressure from the stress of migration, acculturation, or status incongruity. (Hypertension 4: 406–414, 1982)

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.