Charles J. Maclean

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.

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.

Age-Related Changes in Stroke Risk in Men With Hypertension and Normal Blood Pressure

BACKGROUND AND PURPOSE Stroke is a major contributor to total morbidity and mortality in older individuals, and hypertension is an important risk factor for stroke. Relatively few data exist on whether this relationship changes with age. METHODS To examine age-related changes in the relationships between risk of stroke and hypertension, we examined the 6-year incidence of stroke among men aged 45 to 81 years using updated blood pressure data from three examinations of Japanese-American men from the Honolulu Heart Program. RESULTS Both the prevalence of hypertension (systolic blood pressure > or = 160 mm Hg or diastolic blood pressure > or = 95 mm Hg or the use of antihypertensive medication) and the 6-year incidence of stroke increased significantly with increasing age (P < .01). The increase in thromboembolic stroke incidence with age was more marked in those who were normotensive at baseline (2.7/1000 in those aged 45 to 54 years to 23.9/1000 in those > or = 65 years; P < .001) than in hypertensive men (20.6/1000 in those aged 45 to 54 years to 33.5/1000 in those > or = 65 years; P < .01). The age-related increase in risk of thromboembolic stroke among normotensive men resulted in a decrease in the percentage of strokes attributable to hypertension (50% in those aged 45 to 54 years to 18% in those > or = 65 years; P < .05). Similar trends were seen for hemorrhagic stroke. There were no age-related changes in the relationships of other major atherosclerotic risk factors with stroke. The hypertension/stroke relationships were present after multivariate adjustment for age, smoking, cholesterol, and other factors. CONCLUSIONS In view of the greater prevalence of hypertension and the proven efficacy of treatment in the elderly, these findings do not negate the value of aggressive screening and treatment of hypertension in this age group. However, it appears that other unidentified factors have an increasing role in the causation of stroke with advancing age.

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.

Trends in stroke incidence and mortality in Hawaiian Japanese men.

Background and Purpose Vital statistics show a sharp decline in stroke mortality since the late 1960s. It is not clear whether this has been associated with a decline in stroke incidence. Methods Since 1966 the Honolulu Heart Program has monitored the incidence and mortality of coronary heart disease and stroke in a target population of 11 136 men of Japanese ancestry living on Oahu. Trends were analyzed from January 1, 1969, through December 31, 1988. Results Of 7893 men aged 45 to 68 years and free of stroke at entry examination, 530 developed first episodes of stroke in the period 1969 to 1988 (389 cases of thromboembolic stroke, 124 cases of hemorrhagic stroke, and 17 cases of stroke of unknown type). Age-adjusted annual stroke incidence declined from 5.1 per 1000 person-years in 1969 to 1972 to 2.4 in 1985 to 1988. The incidences of thromboembolic stroke, hemorrhagic stroke, and total stroke decreased 3.5%, 4.2%, and 4.4% per year, respectively. The 1-month case-fatality rates for thromboembolic stroke decreased moderately; those for hemorrhagic stroke fell dramatically. Conclusions These findings suggest that the decline in stroke mortality in the past two or three decades results from a decline in both incidence rates and early case-fatality rates in thromboembolic and hemorrhagic stroke and stroke of unknown type. The decreases may be related to changes in risk factors, such as the decline in blood pressure and the decrease in cigarette smoking, as well as improvements in diagnosis and treatment.

Methodological issues in comparing genetic and environmental influences on bone mass

Measurements of bone mineral content (BMC), bone width (BW) and BMC/BW (BMA) at the proximal radius were compared for both Japanese and Japanese-American men and women, after adjusting for measurement technique differences. Within each nationality, men had greater values than women at all ages. Japanese-Americans had substantially greater values of BMC (6-10%) and BMA (16-17%), but lower BW (-12 to -15%), relative to Japanese. Adjustment for body size (height and weight) reduced the magnitude of these differences by approximately one-half for BMC, but had a smaller effect on BMA, and slightly increased the difference in BW. Comparison of these results to published data suggests that environmental factors may have influences on bone mass that are similar in magnitude to the effects of race. The need for additional studies to address potential methodological problems is discussed, using this and other reports as examples.

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.

A Comparison of the 12-Year Mortality and Predictive Factors of Coronary Heart Disease Among Japanese Men in Japan and Hawaii

The mortality and predictive factors of coronary heart disease among men of Japanese ancestry in Japan and Hawaii were compared on the basis of 12 years follow-up data using comparable methods of case ascertainment and risk factor measurements. Among 1,687 men (Japan) and 7,536 men (Hawaii) who were free of coronary heart disease and aged 45-69 at baseline examination in 1965-1968, 20 (Japan) and 123 (Hawaii) cases of fatal coronary heart disease were identified. The age-adjusted mortality rate was 40% higher in Hawaii than in Japan. The difference was not statistically significant, but consistent with earlier studies. More than half of this difference in mortality rate was attributed to different levels of known risk factors in the two cohorts. In multivariate analysis using the combined population, age, blood pressure, serum cholesterol, serum glucose, cigarette smoking, and alcohol intake (inversely) remained as significant predictors of coronary heart disease mortality. Although the associations of risk factors with coronary heart disease tended to be stronger in Hawaii than in Japan, there was no statistically significant difference in regression coefficient for any of the risk factors studied. These findings cannot be claimed to be definitive because of the small number of cases, especially in Japan.