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Background: Recently, high-density lipoprotein particles (HDL-P) have been found to be more strongly inversely associated with coronary artery disease (CAD) risk than their counterpart, HDL cholesterol (HDL-C). Given that lifestyle is among the first targets in CAD prevention, we compared the associations of HDL-P and HDL-C with selected lifestyle factors. Methods and Results: We examined 789 Japanese participants of the INTERLIPID Study: men (n=386) and women (n=403) aged 40-59 years in 1996-1998. Participants treated for dyslipidemias were excluded. Lifestyle factors included alcohol intake, smoking amount, and body mass index (BMI). Multivariable linear regression was used for cross-sectional analyses of these factors with HDL-P, HDL-C, HDL-P size subclasses (small, medium and large) and mean HDL-P size. In men, higher alcohol intake was associated with higher HDL-P and higher HDL-C. The associations of alcohol, however, were strongest with HDL-P. A higher smoking amount tended to be associated with lower HDL-P and HDL-C. In contrast, BMI was not associated with HDL-P, but was strongly inversely associated with HDL-C. While alcohol intake favored larger mean HDL-P size, smoking and BMI favored a lipid profile with smaller HDL-P subclasses and overall smaller mean HDL-P size. Similar, but generally weaker results were observed in women., Conclusions: Although both HDL-P and HDL-C are parameters of HDL, they have different associations with alcohol, smoking and BMI.

Background: We recently reported that protection against coronary artery disease (CAD) mortality is the major contributor to longer life associated with FOXO3 genotype. The present study examined this relation in more detail., Methods: We performed a 15-year observational study of 3,584 older American men of Japanese ancestry from the Kuakini Honolulu Heart Program cohort and 1,595 White and 1,067 Black elderly individuals from the Health Aging and Body Composition study., Results: Multivariate Cox regression models demonstrated that carriage of the longevity-associated G allele of FOXO3 single nucleotide polymorphisms rs2802292 was a protective factor against CAD mortality in all three populations. In Japanese and Whites, but not in Blacks, the protective effect of the G allele was little changed in models adjusted for other major risk factors. Population-attributable risk (PAR) models found that the nonprotective TT genotype contributed 15%, 9%, and 3% to CAD mortality risk in Japanese, White, and Black Americans, respectively, and was one of the top three contributing factors to CAD mortality. In Japanese, this effect size was comparable with hypertension (15%), but in Whites and Blacks PAR for hypertension was higher (29% and 26%, respectively). G-allele carriers had lower plasma TNF-α than noncarriers, suggesting inflammation as a potential mediating factor for CAD mortality risk., Conclusion: FOXO3 genotype is an important risk factor for CAD mortality in older populations. More research is needed to identify potential mechanisms and targets for intervention., (© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: A few studies have examined the longitudinal association of blood pressure (BP) with arterial stiffness progression, and the results were inconsistent. The objective of this study was to investigate the roles of initial BP and its longitudinal change on the progression of arterial stiffness measured using brachial-ankle pulse wave velocity (baPWV)., Method: Study participants (n = 656) were from population-based samples of healthy men aged 40-49 years at baseline (213 White Americans, 47 African-Americans, 152 Japanese Americans and 244 Japanese in Japan). BP measures, baPWV and other factors were examined at baseline and 4-7 years later. General linear regression was applied for statistical analyses., Result: Annual change in SBP (standardized coefficient: 0.33, P < 0.001), but not its baseline level (standardized coefficient: 0.03, P = 0.495), had a positive significant association with the progression of baPWV after adjusting for a wide range of standard cardiovascular risk factors. Similarly, annual changes in DBP (standardized coefficient: 0.35, P < 0.001), pulse pressure (standardized coefficient: 0.15, P = 0.001) and mean arterial pressure (standardized coefficient: 0.37, P < 0.001) were positively associated with the progression of baPWV. None of the baseline measures were related to the progression of baPWV., Conclusion: Our findings imply that, regardless of initial BP, effective monitoring and controlling of BP is important to slow down arterial wall stiffening and hence reduce cardiovascular risk.

Purpose: Low-carbohydrate diets (LCD) are a popular dietary strategy for weight reduction. The effects of LCD on long-term outcome vary depending on type of LCD, possibly due to the fact that effects on cardiometabolic risk factors may vary with different types of LCD. Accordingly, we studied these relations., Methods: We assessed serum concentrations of high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), high-sensitivity C-reactive protein (CRP), total cholesterol, glycated hemoglobin, and uric acid, and nutrient intakes by standardized methods in men and women ages 40-59 years from four population samples of Japanese in Japan (553 men and 544 women, combined). For people consuming usual, animal-based, and plant-based LCDs, we calculated LCD scores, based on relative level of fat, protein, and carbohydrate, by modifying the methods of Halton et al. Instead of calculating scores based on animal or vegetable fat, we used saturated fatty acids (SFA) or monounsaturated fatty acids (MUFA) + polyunsaturated fatty acids (PUFA)., Results: In multivariate regression analyses with adjustment for site, age, sex, BMI, smoking, alcohol intake, physical activity, and years of education, all three LCD scores were significantly positively related to HDLc (all P < 0.001), but not to LDLc. The plant-based LCD score was significantly inversely related to log CRP (coefficient = -0.010, P = 0.018)., Conclusions: All three LCD scores were significantly positively related to HDLc. The plant-based LCD score was significantly inversely related to CRP. Carbohydrate intake below 50 % of total energy with higher intakes of vegetable protein and MUFA + PUFA, and lower intakes of SFA may be favorable for reducing cardiometabolic risk factors.

Background: The Seven Countries Study in the 1960s showed very low mortality from coronary heart disease (CHD) in Japan, which was attributed to very low levels of total cholesterol. Studies of migrant Japanese to the USA in the 1970s documented increase in CHD rates, thus CHD mortality in Japan was expected to increase as their lifestyle became Westernized, yet CHD mortality has continued to decline since 1970. This study describes trends in CHD mortality and its risk factors since 1980 in Japan, contrasting those in other selected developed countries., Methods: We selected Australia, Canada, France, Japan, Spain, Sweden, the UK and the USA. CHD mortality between 1980 and 2007 was obtained from WHO Statistical Information System. National data on traditional risk factors during the same period were obtained from literature and national surveys., Results: Age-adjusted CHD mortality continuously declined between 1980 and 2007 in all these countries. The decline was accompanied by a constant fall in total cholesterol except Japan where total cholesterol continuously rose. In the birth cohort of individuals currently aged 50-69 years, levels of total cholesterol have been higher in Japan than in the USA, yet CHD mortality in Japan remained the lowest: >67% lower in men and > 75% lower in women compared with the USA. The direction and magnitude of changes in other risk factors were generally similar between Japan and the other countries., Conclusions: Decline in CHD mortality despite a continuous rise in total cholesterol is unique. The observation may suggest some protective factors unique to Japanese., (© The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Purpose: It has been hypothesized that leptin-induced appetite suppression is impaired in obese individuals, but little human evidence is available documenting this. We investigated relations between serum leptin and total energy intake using INTERLIPID/INTERMAP data on Japanese-Americans in Hawaii and Japanese in Japan., Methods: Serum leptin and nutrient intakes were examined by standardized methods in men and women aged 40-59 years from two population samples, one Japanese-American in Hawaii (88 men, 94 women), the other Japanese in central Japan (123 men, 111 women). Multiple linear regression analyses stratified by BMI category (<25 kg/m(2), 25-29.9 kg/m(2), and ≥ 30 kg/m(2)) with adjustment for possible confounders were used to examine the relation between log-leptin and total dietary energy intake., Results: In multivariate regression analyses, in those with BMI < 25 kg/m(2) and in those with BMI between 25 and 29.9 kg/m(2), log-leptin was not significantly related to total dietary energy intake; in those with BMI ≥ 30 kg/m(2), it was significantly inversely related to total dietary energy intake (P = 0.029), independent of body weight and physical activity. Physical activity score was significantly positively related to total dietary energy intake only in participants with BMI < 25 kg/m(2) (P < 0.001)., Conclusion: Leptin was significantly inversely associated with dietary energy intake in obese persons, but not in overweight and normal-weight persons.

Background: The purpose of this prospective study was to examine whether fibrinogen level is associated with Parkinson disease (PD) for both prevalent and incident cases., Methods: The Honolulu Asia-Aging Study is a longitudinal study of Japanese-American men based on the Honolulu Heart Study birth cohort. The original cohort consisted of 8,006 participants with selective service records who were living on the island of Oahu, Hawaii, in 1965. For this analysis, baseline was defined as the 1991-1993 examination (n = 3,845) when men were aged 71-93 years old. Multivariate logistic regression and Cox proportional hazards models were used, adjusting for potential confounders., Results: We identified 61 prevalent cases and 61 incident cases of PD during the follow-up. High fibrinogen level (presence in the top quintile) was associated with higher frequency of PD for both prevalent (OR = 2.07, 95% CI = 1.10-3.88, p = 0.024) and incident cases (HR = 3.05, 95% CI = 1.34-6.97, p = 0.008) among men aged 76-93 years, after adjusting for age, smoking, and low-density lipoprotein cholesterol., Conclusions: These results suggest high fibrinogen level is associated with increased risk of PD among men over 75 years., (2009 S. Karger AG, Basel.)

Data from animal studies clearly indicate an association between leptin and hypertension; results of human studies are less concordant. We investigated the role of leptin in obesity-related higher blood pressure (BP) in Japanese Americans living in Hawaii and Japanese in Japan. Serum leptin and BP were examined by standardized methods in men and women ages 40 to 59 years from 2 population samples, one Japanese American in Hawaii (88 men and 94 women) and the other Japanese in central Japan (123 men and 111 women). Multiple linear regression models were used to assess role of leptin in obesity-related higher BP. Across quartiles of leptin, there were significantly higher mean body mass index levels, systolic BP, and diastolic BP for both sexes and sites (P<0.01 to 0.02). In multivariate regression analyses using all of the data combined, relations of body mass index and leptin to systolic BP and diastolic BP remained significant with the interaction term (body mass index x log-leptin) in the models (P<0.01 to <0.05). These findings are consistent with the inference that leptin may be an independent mediator for obesity-related elevations in BP.

Background: In initial analyses, we found significant differences between serum adiponectin in Japanese living in Japan and Hawaii., Objective: We investigated whether differences in dietary and other lifestyle factors explain higher serum adiponectin concentrations in Japanese in Japan compared with Japanese emigrants living a Western lifestyle in Hawaii., Design: Serum adiponectin and nutrient intakes were examined by standardized methods in men and women aged 40-59 y from 2 population samples, one Japanese American in Hawaii (99 men, 104 women), the other Japanese in central Japan (124 men, 125 women). Multiple linear regression models were used to assess the role of dietary and other lifestyle traits in accounting for serum adiponectin difference between Hawaii and Japan., Results: Mean adiponectin was significantly higher in Japan than in Hawaii (10.5 +/- 5.5 mug/mL compared with 6.7 +/- 3.2 mug/mL in men, P = 0.002; 12.9 +/- 5.9 mug/mL compared with 9.4 +/- 4.2 in women, P < 0.0001). In men, the difference in body mass index (BMI; in kg/m(2)) in the 2 populations explained approximately 90% of the difference in serum adiponectin; in women, only 29%. In multiple linear regression analyses in women further adjustment for physical activity and 4 nutrients (nonvegetable protein, n-3 polyunsaturated fatty acid, arachidonic acid, dietary cholesterol) produced a further reduction in the coefficient for the difference (total 56%); P value for the difference became 0.074., Conclusions: The significantly higher mean serum adiponectin concentration in Japan than in Hawaii may be attributable largely to differences in BMI. Differences in nutrient intake in the 2 samples were associated with only modest relation to the adiponectin difference.

Type 2 diabetes is a common disorder associated with obesity. Lower plasma levels of adiponectin were associated with type 2 diabetes. Candidate regions on chromosomes 1 ( approximately 70 cM) and 14 ( approximately 30 cM) were evaluated for replication of suggestive linkage results for type 2 diabetes/impaired glucose homeostasis in an independent sample of Japanese Americans. Replication of independent linkage evidence for serum levels of adiponectin on chromosome 14 was also evaluated. We investigated 529 subjects from 175 sibships who were originally part of the Honolulu Heart Program. Analyses included nonparametric linkage and association using SAGE (Statistical Analysis for Genetic Epidemiology) and FBAT (family-based test of association) programs and Monte Carlo simulation of Fisher's exact test in SAS. For type 2 diabetes/impaired glucose metabolism, nominal linkage evidence (P < 0.02) followed-up by genotypic association (P = 0.016) was found with marker D14S297 at 31.8 cM; linkage analyses using only diabetes phenotype were also nominally significant at this marker (P < 0.02). Nominal evidence for genotypic association to adiponectin serum level phenotype (P = 0.04) was found with the marker D14S1032 at 23.2 cM. The present study was limited by relatively small sample size. Nevertheless, these results corroborate earlier studies, suggesting that further research is warranted in the candidate region approximately 30 cM on chromosome 14.

Adiponectin is secreted by adipocytes and is thought to have insulin-sensitizing and antiatherogenic effects. Two previous genome scans for plasma adiponectin have identified different regions for European and Pima Indian populations. We here present multipoint linkage analysis of adiponectin levels using a variance-components model for 1007 siblings (from 360 nuclear families) of Chinese origin and 352 siblings (from 147 nuclear families) of Japanese origin. We found heritability for adiponectin concentrations was 0.70 for Chinese and 0.48 for Japanese. Autosomal genome scan was performed using microsatellite markers span at an interval of approximately 10 cM. Suggestive linkage of adiponectin, after adjusting for age and sex, was found on chromosome 15 at 39 cM (maximal LOD score = 3.19, P = 6.3 x 10(-5)) for Chinese; and on chromosome 18 at 28 cM (maximal LOD score = 2.40, P = 4.4 x 10(-4)) for Japanese. There were tentative loci of weak linkage on chromosomes 3, 18, and 20 in Japanese. We provide novel loci on chromosomes 15, 18, and 20 and confirm a region on chromosome 3 as reported in Pima Indians, which may influence differentially on circulating adiponectin concentrations in Chinese and Japanese populations. Further fine mapping of these regions will help to identify the gene(s) that might affect adiponectin levels.

Protein tyrosine phosphatase 1beta (PTP-1beta) is involved in the regulation of several important physiological pathways. It regulates both insulin and leptin signaling, and interacts with the epidermal- and platelet-derived growth factor receptors. The gene is located on human chromosome 20q13, and several rare single nucleotide polymorphisms (SNPs) have been shown to be associated with insulin resistance and diabetes in different populations. As part of our ongoing investigations into the genetic basis of hypertension, we examined common sequence variants in the gene for association with hypertension, obesity and altered lipid profile in two populations of Japanese and Chinese descent. We re-sequenced all exons, selected intronic sequences and the promoter region in 24 individuals from our cohort. Fourteen SNPs were discovered, and six of these spanning 78 kb were genotyped in 1553 individuals from 672 families. All six SNPs were in linkage disequilibrium, and we found strong association of common risk haplotypes with hypertension in Chinese and Japanese (P<0.0001). In addition, individual SNPs showed association to total plasma cholesterol, LDL-cholesterol and VLDL-cholesterol levels, as well as obesity measures (body mass index). This analysis supports that PTP-1beta affects plasma lipid levels, and may lead to obesity and hypertension in Japanese and Chinese. Given similar associations found in other populations to insulin resistance and diabetes, this gene may play a crucial role in the development of the characteristic metabolic changes seen in patients with the metabolic syndrome., (Copyright 2004 Oxford University Press)

The purpose of the study is to assess the relative impact of lifestyle factors including physical inactivity, cigarette smoking, and alcohol intake on insulin resistance in hypertensive patients. In total, 872 hypertensive patients, of Chinese and Japanese origin, from the Stanford Asia and Pacific Program for Hypertension and Insulin Resistance were included for the current analysis. Homeostasis model assessment for insulin resistance (HOMA-IR) and the insulin sensitivity index ISI0,120 were chosen as surrogate measures of insulin resistance. Standardized interview-administered questionnaires were used to obtain information on demographic and lifestyle characteristics. The sedentary hypertensive patients were more insulin resistant than the non-sedentary hypertensive. There were significant differences in Log (HOMA-IR) (0.06-unit increases, p < 0.01) and Log (ISI0,120) (0.05-unit decreases, p < 0.01) between sedentary and non-sedentary hypertensive patients after controlling demographic variables. There were no differences in insulin sensitivity in subjects with different smoking status. Neither smoking nor alcohol intake was persistently associated with insulin resistance in the analysis. Our results suggest that physical inactivity is an important lifestyle determinant of insulin resistance in hypertensive patients. The influences of smoking and alcohol intake on insulin resistance are less significant than physical inactivity in hypertensive subjects.

Despite increase in serum total cholesterol, high smoking rate, and frequency of adverse blood pressure levels in Japan, coronary heart disease (CHD) incidence and mortality apparently remain substantially lower at all ages in Japan than in the US and other Western societies. To better understand these differences, we compared CHD biomedical risk factors and dietary variables in Japanese living in Japan and 3rd and 4th generation Japanese emigrants living a primarily Western lifestyle in Hawaii, in an ancillary study of the INTERMAP. Men and women aged 40-59 years were examined by common standardized methods-four samples in Japan (574 men, 571 women) and a Japanese-American sample in Hawaii (136 men, 131 women). Average systolic (SBP) and diastolic (DBP) blood pressures were significantly higher in men in Japan than in Hawaii; there were no significant differences in women. The treatment rate of hypertension was much lower in Japan than Hawaii. Smoking prevalence was higher, markedly so for men, in Japan than Hawaii. Body mass index, serum total and low-density lipoprotein cholesterol, HbA1c, and fibrinogen were significantly lower in Japan than in Hawaii; high-density lipoprotein cholesterol was higher in Japan. Total fat, saturated fatty acid intake, and Keys dietary lipid score were lower in Japan than in Hawaii. Polyunsaturated/saturated fatty acid ratio and omega-3 fatty acid intake were higher in Japan than in Hawaii. In conclusion, levels of several, especially lipid, CHD risk factors were generally lower in Japanese in Japan than in Japanese in Hawaii. These differences were smaller for women than men between Japan and Hawaii. They may partly explain lower CHD incidence and mortality in Japan than Western industrialized countries.

Despite similar traditional risk factors, morbidity and mortality rates from coronary heart disease in western and non-western cohorts remain substantially different. Careful study of such cohorts may help identify novel risk factors for CHD, and contribute to the formulation of new preventive strategies

Objective: To examine the predictive value of psychosocial factors as risk factors for all-cause mortality., Design: A community-based longitudinal cohort study: The Honolulu Heart Program., Setting: Population-based study conducted in Oahu, Hawaii., Participants: Three thousand four hundred and ninety-seven men age 71 to 93 were examined and followed prospectively for all-cause mortality for an average of 6 years., Measurements: Psychosocial data were obtained using the Lubben Social Networks Scale (LSNS). The LSNS consists of 10 items-family relationships (three items), relationships with friends (three items), and interdependent social supports and living arrangements (four items). We divided the LSNS score into quartiles for comparison, with the first quartile representing the lowest social support and the fourth quartile representing the highest social support., Results: A significant dose-response relationship was noted with LSNS score and total mortality: 33.8% in the first quartile died over the follow-up period, 23.4% in the second, 18% in the third, and 15.7% in the fourth (P < .001). Six-year age-adjusted mortality rates were 66.2, 45.7, 37.8, and 33.7 per 1,000 person years in the first, second, third, and fourth, respectively (P < .001). Using age-adjusted Cox proportional hazards models, with the first quartile of LSNS as the reference group, relative risk for mortality was 0.69 (95% confidence interval (CI) = 0.58-0.82), 0.57 (95% CI = 0.47-0.70), and 0.52 (95% CI = 0.43-0.64) in the second, third, and fourth quartiles, respectively. Cox models were repeated, controlling for age and smoking status, and low LSNS scores remained significantly associated with higher mortality (P = .0001)., Conclusions: Our findings suggest that social networks were significantly independently associated with 6-year all-cause mortality in this cohort of older Japanese-American men. Social interventions in old age may reduce early mortality.

The relation between plasma fibrinogen and total and cause-specific mortality was investigated in a cohort of 3571 Japanese-American men aged 71 to 93 years during a median follow-up of 4.4 years. There were a total of 728 deaths, of which 37% were accounted for by cardiovascular disease and 27% by cancer. The age-adjusted relative risk (RR) for total mortality in the top quintile of fibrinogen (>3.51 g/L) compared with the bottom quintile (<2.57 g/L) was 4.3 (P<0.0001) in the first year of follow-up. RR was reduced to 1.7 in the second year but remained significantly and slightly increased in subsequent years. After adjustment for age and confounding risk factors, the RRs (and 95% confidence intervals) associated with a 1-SD increment of fibrinogen (0.64 g/L) for all-cause, cardiovascular disease, cancer, and other-cause mortality were 1.3 (1.2 to 1.4), 1.2 (1.1 to 1.4), 1.3 (1.2 to 1.5), and 1.3 (1.2 to 1.5), respectively. Preexisting diseases did not influence the significant association of fibrinogen with mortality. There was a significant interaction of fibrinogen with white blood cell count but not with cigarette smoking. We conclude that plasma fibrinogen is an independent risk factor for mortality from a broad spectrum of diseases in elderly men and that this universal effect of fibrinogen on mortality may be mediated partly through inflammation.

Decreased low-density lipoprotein (LDL) particle size is associated with coronary heart disease (CHD) risk among middle-aged Caucasian populations, and has been consistently correlated with increased plasma levels of triglyceride and decreased levels of high-density lipoprotein (HDL) cholesterol. This study examines whether these risk factors predict CHD among older Japanese-American men. With use of the Honolulu Heart Program Lipoprotein Exam 3 (1980 to 1982) as baseline, and 12-year follow-up for CHD events, a nested, case-control study was designed. One hundred forty-five incident CHD cases were identified and matched to 2 controls each. LDL particle diameter (size) was determined by gradient gel electrophoresis. A 10-angstrom (A) decrease in LDL size at baseline was associated with increased risk of incident CHD (relative risk 1.28, 95% confidence interval 1.01 to 1.63). After adjustment for baseline risk factors, the LDL size association was no longer statistically significant (relative risk 1.13, 95% confidence interval 0.86 to 1.49). When principal components analysis was used to define a composite variable for LDL size, triglycerides, and HDL cholesterol, this component predicted CHD independent of smoking, alcohol consumption, physical activity, body mass index, hypertension, diabetes, and beta-blocker use (p <0.01). Therefore, this prospective analysis of data from older, Japanese-American men demonstrated that decreased LDL size is a univariate predictor of incident CHD, and that a composite risk factor of LDL size, triglyceride, and HDL cholesterol was a risk factor for CHD independent of other risk factors.

Objectives: 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., Design: A cross-sectional study., Setting/participants: A total of 3734 Japanese American men, aged 71-93 years, who were first- or second-generation migrants and living on Oahu Island, Hawaii., Measurements: 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., Results: 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., Conclusions: 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.

Efficient use of cholesterol measurements to screen for coronary heart disease in the elderly is not well defined. The purpose of this report is to examine such screening based on national guidelines in a sample of older men. Since relations between cholesterol and coronary heart disease are better established in those who are younger, screening in the elderly will also consider levels of cholesterol that existed earlier in life. Data are from a prospective study of 1,170 men enrolled in the Honolulu Heart Program who were followed over a 12-year period for coronary heart disease. Follow-up began from 1980 to 1982, when cholesterol levels were determined in men who were aged 61 to 81 years. Past cholesterol levels were measured 10 years earlier (1970-1972). During the course of follow-up, coronary heart disease developed in 117 of the men. Risk of disease rose significantly (P = 0.003) with increases in past cholesterol levels (1970-1972) but not with more recent levels (1980-1982). For men with current cholesterol levels that were desirable (<5.2 mmol/L [200 mg/dl], as defined by guidelines from the National Cholesterol Education Program), disease incidence continued to rise with increasing past cholesterol levels (P<0.001). Accounting for high-density lipoprotein cholesterol and other screening factors did little to alter these findings. We conclude that desirable cholesterol levels in the elderly may not be a marker of a healthy risk profile if past cholesterol levels were high. Screening for coronary heart disease in the elderly could be improved by considering past cholesterol levels, rather than just a single measurement in later life.

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.

Background: Effects of walking on the risk of coronary heart disease morbidity and mortality have not been identified in the elderly. The purpose of this study was to determine whether walking is associated with a reduced risk of coronary heart disease in a sample of elderly men., Methods and Results: For this study, distance walked (mile/d) was examined at a baseline examination that occurred from 1991 to 1993 in the Honolulu Heart Program. Incident coronary heart disease from all causes was observed over a 2- to 4-year follow-up period. Subjects followed up were 2678 physically capable elderly men aged 71 to 93 years. During the course of follow-up, 109 men developed coronary heart disease. Men who walked <0.25 mile/d had a 2-fold increased risk of coronary heart disease versus those who walked >1. 5 mile/d (5.1% versus 2.5%; P<0.01). Men who walked 0.25 to 1.5 mile/d were also at a significantly higher risk of coronary heart disease than men who walked longer distances (4.5% versus 2.5%; P<0. 05). Adjustment for age and other risk factors failed to alter these findings., Conclusions: Findings from the Honolulu Heart Program, which targeted physically capable elderly men, suggest that the risk of coronary heart disease is reduced with increases in distance walked. Combined with evidence that suggests that an active lifestyle reduces the risk of cardiovascular disease in younger and more diverse groups, this suggests that important health benefits could be derived by encouraging the elderly to walk.

Limited data are available on patterns of change in lipids and lipoproteins as persons age. The purpose of this report is to describe the 10-year change in total and high-density lipoprotein (HDL) cholesterol according to suspected determinants in 898 Japanese-American men enrolled in the Honolulu Heart Program. Data are based on examinations that occurred from 1970 to 1972 and at repeat examinations received 10 and 20 years later. At the last examination, men were aged 71 to 93 years. Mean reductions in total cholesterol in the second 10 years of follow-up (24 mg/dl) were more than double the reductions observed in the first 10 years (9 mg/dl). Levels of total cholesterol declined and levels of HDL cholesterol increased regardless of beginning levels of systolic blood pressure, body mass index, physical activity, cigarette smoking status, or the use of treatment for hypertension or elevated total cholesterol. Men with prevalent coronary heart disease experienced greater reductions (p <0.05) in total cholesterol during the second 10 years of follow-up (32 mg/dl) versus men without coronary heart disease (22 mg/dl). Adjustment for baseline covariates failed to alter these findings appreciably. We conclude that alterations in total and HDL cholesterol with advancing age may be expected to occur regardless of risk factor status, disease prevalence, or pharmacologic intervention. In the presence of such effects, evaluation of treatment programs to alter levels of total and HDL cholesterol in older persons should consider the possibility that even in the absence of intervention, changes could also occur due to aging alone.

Purpose: Elevated insulin levels have been associated with cardiovascular disease, but the relationship of insulin with other risk factors and its position in the atherosclerotic pathway is uncertain. A cross-sectional study was conducted to determine whether insulin concentrations were associated with lipids and lipoproteins independently of adiposity and other cardiovascular risk factors., Methods: Subjects included 3417 Japanese-American men from the Honolulu Heart Program who completed a follow-up examination between 1991 and 1993 and were 71-93 years of age. Men were categorized by quintiles of fasting and 2-hour insulin concentration., Results: Age-adjusted mean high-density lipoprotein (HDL) cholesterol and triglyceride levels varied significantly across quintiles of fasting and 2-hour insulin (P < 0.001, tests for trend), but insulin was not related to total cholesterol and low-density lipoprotein (LDL) cholesterol. HDL cholesterol decreased from 59.3 to 43.7 mg/dL and triglycerides increased from 95.6 to 175.8 mg/dL comparing lowest to highest quintiles of fasting insulin, respectively. These associations were slightly stronger in lean than obese subjects and in nondiabetic versus diabetic individuals particularly for 2-hour insulin levels. Multiple linear regression analysis adjusting for several adiposity measures separately (body mass index (BMI), subscapular skinfold thickness, waist circumference, and waist/hip ratio) and other cardiovascular risk factors attenuated associations slightly but they still remained statistically significant. Estimated differences in HDL cholesterol across extreme quintiles of fasting insulin were reduced slightly from 15.6 mg/dL with adjustment for age to 12.5 mg/dL with adjustment for age and BMI, and to 11.3 mg/dL with adjustment for age, BMI, and cardiovascular risk factors., Conclusions: Insulin concentration was strongly and independently associated with HDL cholesterol and triglycerides in this cohort of elderly Japanese-American men. Since this study was cross-sectional, further investigation is required to determine whether elevated insulin levels are causally related to dyslipidemia.

Objective: To assess the joint characteristics of low standardized weight and compromised pulmonary function in predicting all-cause mortality., Design: A population-based, prospective cohort study., Setting: Oahu Island, Hawaii., Participants: Surviving Japanese-American men of the Honolulu Heart Program cohort, 71 to 93 years of age (N = 3059)., Measurements: Body mass index (BMI-weight in kilograms/square of height in meters) and 1-second forced expiratory volume (FEV1) as a percentage of age- and height-predicted FEV1 from the 1991 to 1993 examination of the cohort. Mortality data derived from the ongoing tracking of deaths of the cohort. Relations of selected risk factors among joint levels of BMI (< or = 21, > 21 to < 25, > or = 25 kg/m2) and percent predicted FEV1 (< or = 70%, > 70%) were determined. The impact of these covariates on relations between joint BMI/percent predicted FEV1 levels and subsequent all-cause mortality was assessed., Results: The highest age-adjusted mortality rate (91.9 deaths per 1000 person-years) was noted among men characterized by the joint conditions of percent predicted FEV1 < or = 70% and BMI < or = 21 kg/m2. This rate was 4.0 times the mortality rate of a "healthy" reference group characterized by percent predicted FEV1 > 70% and 21 < BMI < 25 kg/m2. This rate ratio is attenuated to 3.2 upon statistical control for measures of current and past smoking behavior. Among the three strata of BMI, statistical interaction is reflected in a heterogeneity of mortality rate differences (49.7, 21.8, -9.6 deaths/person-year, respectively) and rate ratios (2.18, 1.98, .66, respectively) comparing men with percent predicted FEV1 < or = 70% to > 70%., Conclusion: Joint loss of pulmonary function and relative weight is predictive of subsequent all-cause mortality in excess of additive or multiplicative effects of each condition separately. Smoking behavior may contribute to this observation.

Purpose: The purpose of this report is to describe levels of total cholesterol and high-density-lipoprotein cholesterol (HDL-C) in a group of elderly men and to compare these levels to those that were observed 20 years earlier., Methods: From 1965-1968, the Honolulu Heart Program began following 8006 men of Japanese ancestry living on the island of Oahu, Hawaii, in a prospective study of coronary heart disease and stroke. This report presents data for 971 men who participated in a separate fasting study of lipids and lipoproteins that first occurred from 1970-1972 and in those who received repeat examinations 10 and 20 years later. Men were aged 71-93 years at the last examination., Results: Over the 20-year period, total cholesterol declined by 1.6-1.8 mg/dL per year (P < 0.001), from average baseline values of 219-222 mg/dL. Levels of HDL-C rose 0.2-0.3 mg/dL per year (P < 0.001), from average baseline values of 44-46 mg/dL. After adjustment for baseline cholesterol levels, men with prevalent coronary heart disease at the end of the 20-year follow-up experienced significantly greater reductions in total cholesterol levels than men without disease (P < 0.001). Men who developed coronary heart disease within the first 10 years of follow-up had the greatest yearly decline in total cholesterol (1.9 mg/dL), followed by men who developed heart disease later (1.8 mg/dL) and men who remained disease free (1.5 mg/dL). Differences between men with recent and earlier disease were not statistically significant, although men without coronary disease experienced a significantly smaller decrease in total cholesterol than either of these groups (P < 0.05)., Conclusions: Changes in total cholesterol and HDL-C levels with advancing age may be part of a natural aging process. Some changes, however, such as large reductions in total cholesterol, may signal occult disease or declines in overall health. Selective survival may contribute to these findings since improvements in lipid and lipoprotein levels that are beneficial in younger ages were common in this long-lived cohort of men.

Objective: To identify lifestyle, anthropometric, biochemical, and clinical characteristics associated with pulmonary function in elderly men., Design: Cross-sectional population-based study., Participants: Japanese-American men (n=3,111) aged 71 to 93 years, who completed spirometry at the fourth examination of the Honolulu Heart Program (1991 to 1993)., Methods: Pulmonary function measurements (FEV1 and FVC) were obtained using American Thoracic Society guidelines. Potential factors associated with pulmonary function were examined using Pearson correlation coefficients and general linear models. Age- and height-adjusted mean levels of FEV1 and FVC were compared across quintiles of continuous variables and by status of prevalent disease and medication or vitamin use. Stepwise multiple linear regression was used to identify factors independently associated with pulmonary function overall and among never smokers., Results: A number of correlates of pulmonary function were initially identified. In multivariate analyses, age, current smoking, pack-years of smoking, emphysema, asthma, wheezing without colds, subscapular skinfold thickness, ECG abnormality, heart rate, WBC count, and eosinophil count were all negatively and independently associated with FEV1, while height, grip strength, physical activity, and mean corpuscular hemoglobin concentration were positively associated. With a few exceptions, similar relations were observed with FVC and among never-smokers., Conclusion: Cigarette smoking, respiratory symptoms and disease, and several cardiovascular risk factors were independently associated with pulmonary function in elderly Japanese-American men. In most cases, inadequate control for smoking does not appear to account for these associations. Results suggest that a number of factors that are correlates of FEV1 and FVC in younger age groups are also associated with pulmonary function beyond the age of 70 years.

The association between acculturation to a Western lifestyle and prevalence of diabetes was examined among 8,006 Japanese-American men in Hawaii with varying degrees of exposure to traditional Japanese social and cultural lifestyles in 1965-1968. A reduced prevalence of diabetes was observed among the men who had retained a more Japanese lifestyle. These men also reported higher levels of physical activity and consumed more carbohydrates and less fat and animal protein in their diet. An inverse association between diabetes and being born in Japan was observed independent of age, body mass index, physical activity, and percentages of calories from fat or carbohydrates (odds ratios = 0.67 and 0.66, 95% confidence intervals 0.49-0.93 and 0.48-0.91, respectively). The number of total years lived in Japan was inversely associated with prevalent diabetes after controlling for age, body mass index, and physical activity (odds ratio = 0.81, 95% confidence interval 0.68-0.96). Current Oriental diet (compared with Western diet) was inversely associated with prevalent diabetes after controlling for age, body mass index, and physical activity (odds ratio = 0.71, 95% confidence interval 0.50-0.98). These findings suggest that living a Japanese lifestyle is associated with a reduced prevalence of diabetes.

Objective: 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., Design and Setting: 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., Participants: Subjects were 3734 Japanese-American men (80% of surviving cohort) aged 71 through 93 years, living in the community or in institutions., Main Outcome Measures: 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., Results: 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., Conclusions: 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.

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.

Background and Purpose: Evidence suggests that dietary calcium is protective against hypertension. This report examines whether the effect has an influence on thromboembolic stroke., Methods: Since 1965, the Honolulu Heart Program has followed a cohort of men in a study of cardiovascular disease. This report examines the effect of baseline dietary calcium and milk intake on stroke risk in 22 years of follow-up in 3150 older middle-aged men (55 to 68 years)., Results: Men who were nondrinkers of milk experienced stroke at twice the rate (P < .05) of men who consumed 16 oz/d or more (7.9 versus 3.7 per 100, respectively). While the rate of stroke decreased with increasing milk intake (P < .05), the decline in stroke risk with increased consumption was modest for those who consumed under 16 oz/d. Intake of dietary calcium was also associated with a reduced risk of stroke (P < .01), although its association was confounded with milk consumption. Calcium intake from nondairy sources was not related to stroke, suggesting that other constituents or covariates related to milk consumption may be important., Conclusions: We conclude that an association between milk consumption and a reduced risk of stroke in older middle-aged men cannot be explained by intake of dietary calcium. Since milk is often part of a diverse pattern of dietary intake, it is difficult to determine whether milk consumption has a direct role in reducing the risk of stroke. Data suggest that consumption of milk in older middle age is not harmful, and when combined with a balanced diet, weight control, and physical activity, reductions in the risk of stroke may occur.

Cigarette smoking is known to accelerate decline of pulmonary function; however, the role of other factors is less clear. Characteristics of individuals who experienced rapid decline in forced expiratory volume in 1-sec (FEV1) were examined in 4451 Japanese-American men from the Honolulu Heart Program who were aged 45 to 68 years at baseline (1965-1968) and who produced three acceptable FEV1 measures over a 6-year period. Average annual rates of FEV1 decline were calculated by use of within-person regression and were categorized as rapid (> or = 60 ml/y), moderate (30 to 59 ml/y) or slow (< 30 ml/y). Lifestyle and biologic factors were compared by FEV1 decline categories after adjustment for age. A logistic regression model showed that continued smoking during follow-up, cigarette pack-years, wheezing, coronary heart disease, alcohol intake, and reduced subscapular skinfold were significantly associated with rapid FEV1 decline, after adjustment for age, height, cholesterol, an indicator of Japanese diet, and education. When analyses were restricted to continuous smokers, cigarette pack-years, wheezing, and reduced subscapular skinfold were found to be independent predictors. Among never smokers, lower educational attainment was a predictor of rapid FEV1 decline, and the association involving subscapular skinfold approached significance (P < 0.07). These characteristics may be useful in identifying subgroups of the population who are at increased risk of accelerated decline in pulmonary function and thus would be most likely to benefit from appropriate intervention.

The relation between pulmonary function and cognitive functioning was investigated in a cohort of 3,036 Japanese-American men living in Hawaii. Pulmonary function, as indicated by forced expiratory volume in 1 second (FEV1), was measured at the baseline examination from 1965 to 1968. Cognitive function was assessed by the Cognitive Abilities Screening Instrument (CASI) test at least 23 years later (1991-1993). Baseline FEV1 was significantly correlated with follow-up CASI score (r = 0.22, p = 0.0001). Although the strength of the association was reduced by controlling for the effects of other factors, stepwise multiple linear regression showed that FEV1 during middle age was a significant predictor of CASI in later life, after taking into account the effects of age, education, stroke, sedentary job activity, nonmanual occupation, height, generation, and Japanese speaking ability. The mean CASI value was significantly greater for men whose FEV1 exceeded 2.8 liter compared with those whose FEV1 levels were in the lowest (<2.5 liters) quartile. Furthermore, the test on the effect of interaction between FEV1 and age was statistically significant (p = 0.0024), with subjects less than 55 years of age at the baseline examination showing a stronger direct association of FEV1 with CASI than the men aged 55 or older. These findings suggest that pulmonary function impairment may be associated with cognitive function impairment in later life.

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.

Clinical and epidemiological studies consistently indicate that elevations in plasma fibrinogen concentration are associated with the presence and development of coronary heart disease (CHD). These elevations are strongly correlated with smoking behavior and may play a significant role in mediating a relation of smoking to CHD. This cross-sectional survey of 3571 elderly Japanese-American men, aged 71 through 93 years, represents survivors of the Honolulu Heart Program cohort. Active smokers are almost twice as likely to be represented in the highest quintile of the fibrinogen distribution compared with the lowest quintile (9.8% versus 5.3%, respectively). The highest prevalence of CHD (34%) was noted in past and current smokers who were in the highest quintile of fibrinogen. The age-adjusted relative odds of prevalent CHD comparing the average fibrinogen levels in the first and fifth quintiles were 1.36 (95% confidence interval, 1.13 to 1.64). After adjustment for smoking status, blood pressure, total and HDL cholesterol, diabetes status, hematocrit, and white cell count, the association between fibrinogen and CHD was changed slightly and remained statistically significant (P < .05). These findings in an elderly cohort of Japanese-American men are consistent with previous studies among middle-aged adults demonstrating fibrinogen to be associated with indicators of clinical CHD and CHD risk factors. Because of the cross-sectional nature of this study, it is not possible to distinguish whether the observed relation of fibrinogen to prevalent CHD is causal or whether it represents a marker of active and progressive disease.

Pulmonary function was assessed by spirometry in 3,076 elderly Japanese-American men of the Honolulu Heart Program (HHP) cohort. The assessment was done with a stringent quality assurance program that adhered to American Thoracic Society (ATS) recommendations for spirometry. Less than 6% of the participants were unable to perform three acceptable spirometry maneuvers. A "healthy" subgroup of 528 men between the ages of 71 and 90 yr was identified by excluding almost all smokers and subjects with lung disease and other factors negatively influencing FEV1. Reference equations and normal ranges for FEV1, FVC, and the FEV1/FVC ratio were derived from the healthy group. Use of prediction equations from the Cardiovascular Health Study (CHS) of elderly European-American men consistently overpredicted FVC by 0.3 to 0.4 L and FEV1 by 0.15 L. Men in the HHP were on average 11 cm shorter than those in the CHS. Use of a prediction equation derived from the HHP cohort when the men in the cohort were on average 22.6 yr younger consistently overpredicted FEV1 by 0.2 to 0.3 L. These results underscore the importance of using prediction equations appropriate to the ethnicity, age, and height characteristics of the subjects being studied.

The role of insulin in cardiovascular disease is uncertain, and studies in elderly or minority populations are infrequent. Fasting and 2-hour insulin concentrations and their cross-sectional associations with cardiovascular risk factors were examined in 3562 elderly (aged 71 to 93 years) Japanese American men from the Honolulu Heart Program who were reexamined between 1991 and 1993. Insulin distributions were skewed (mean and median: 16.8 and 12 microU/mL for fasting; 117.2 and 93 microU/mL for 2-hour); fasting but not 2-hour insulin levels declined significantly with age (P < .0001 and P = .54, respectively). Factors most strongly correlated with insulin included measures of obesity, fat distribution, and levels of triglyceride, glucose (r = .38 to r = .50 fasting, r = .21 to r = .27 2-hour), and HDL cholesterol (r = -.41 and r = -.22, respectively). Other correlates included fibrinogen, hematocrit, heart rate, blood pressure, cigarettes per day (all positive), alcohol, physical activity, and forced vital capacity (negative). Associations were also evident across risk factor quintiles. Insulin levels were significantly elevated in men with hypertension and diabetes. In multiple linear regression analyses, log10 fasting insulin was positively and independently associated with body mass index, triglycerides, glucose, fibrinogen, hematocrit, heart rate, diabetes, and hypertension and negatively associated with HDL cholesterol, physical activity, and forced vital capacity. In general, results were similar for log10 2-hour insulin and when subjects who fasted < 12 hours or had diabetes were excluded. Substitution of medication use and blood pressure for hypertension indicated independent associations of medication use but not blood pressure with insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Whether the combination of a low level of HDL cholesterol (HDL-C) and high level of triglyceride (TG) confers increased risk of cardiovascular disease and whether risk varies across levels of total cholesterol (TC) are not well established. Combined effects of HDL-C, TG, and TC on the incidence of atherosclerotic disease were examined prospectively in Japanese-American men from the Honolulu Heart Program., Methods and Results: Among 1,646 men aged 51 to 72 years who were free of coronary heart disease (CHD), stroke, and cancer and were not taking lipid-lowering medication, 318 developed atherosclerotic events (angina, coronary insufficiency, aortic aneurysm, definite CHD, or thromboembolic stroke) and 170 developed definite CHD between 1970 and 1988. Subjects were stratified by TC level (desirable, < 200 mg/dL; borderline high, 200 to 239 mg/dL; high, > or = 240 mg/dL), HDL-C level (< 35 and > or = 35 mg/dL), and TG level (< 200 and > or = 200 mg/dL). With Cox regression with high HDL-C and low TG as reference, age-adjusted relative risks (RR) of atherosclerotic events were significantly elevated in men with low HDL-C and high TG at borderline-high (RR, 2.46; 95% CI, 1.48 to 4.09) and high (RR, 2.21; 95% CI, 1.34 to 3.66) TC levels but not in men with desirable TC levels (RR, 0.89; 95% CI, 0.38 to 2.09). Elevated risks were independent of blood pressure, obesity, fat distribution, diabetes, smoking, and alcohol. Results were not materially altered by exclusion of subjects with angina alone and were similar but somewhat weaker for CHD., Conclusions: Risk of atherosclerotic disease appears elevated in subjects with low HDL-C and high TG levels when TC is borderline high or high, independent of other cardiovascular risk factors. These findings support recent cholesterol screening recommendations and suggest that joint effects of HDL-C and TG may be important to consider.

Effects of cigarette smoking and smoking cessation on rate of FEV1 decline over 6 yr were examined in 4,451 Japanese-American men from the Honolulu Heart Program who were 45 to 68 yr of age at baseline (1965-1968). Within-person regression was used to calculate annual change in FEV1. Rates of FEV1 decline varied strongly with smoking status and increased significantly with age. Overall, men who continued to smoke experienced steeper rates of decline compared with men who never smoked (-33 ml/yr versus -22 ml/yr, respectively; p = 0.0001). Rates of decline for those who quit smoking during the first 2 yr (-32 ml/yr) were nearly the same as those who continued smoking (-34 ml/yr). After quitting, their rates of decline diminished to a level (-19 ml/yr) similar to that of men who had never smoked (-21 ml/yr). FEV1 decline in continuing smokers was significantly associated with duration of smoking, whereas associations with intensity and pack-years were of borderline significance. Among 216 men with impaired pulmonary function, those who quit smoking had significantly slower rates of FEV1 decline than did those who continued smoking. Potential reasons for quitting included respiratory conditions and stroke. These results extend previous reports of accelerated rates of FEV1 decline in the persons who continue to smoke, and they indicate that smoking cessation leads to less steep rates of decline in pulmonary function over a short period of time in middle-aged men, as well as in men with established pulmonary impairment.

Background: Diabetes and glucose intolerance have been shown to increase the risk of cardiovascular mortality in a number of different populations. Most studies have been based on short follow-up periods, and few have had sufficient numbers to allow researchers to look at sudden death as an outcome., Methods and Results: The relation of sudden death, defined as unexpected death occurring within either 1 or 24 hours of first symptoms, to glucose intolerance measured by a nonfasting 1-hour postload measurement made in 1965 or history of diabetes was examined by use of 23 years of follow-up on the 8006 participants enrolled in the Honolulu Heart Program. After adjustment for baseline body mass index, hypertension, cholesterol, triglycerides, smoking, alcohol consumption, and left ventricular hypertrophy or strain, the relative risks for sudden death within 24 hours in individuals with high-normal (151 to 224 mg/dL), asymptomatic high glucose values (> or = 225 mg/dL), and diabetes compared with those with lower glucose values (< 151 mg/dL) were 1.59, 2.22, and 2.76, respectively. All these relative risks were statistically significant (P < or = .05). Trends for sudden death in 1 hour were similar. Among men with sudden death < 1 hour after onset of symptoms, the strength of the association between diabetes and sudden death was stronger among those classified as having died of unknown causes who thus were more likely to have died of an arrhythmia than among those classified as having died of coronary heart disease., Conclusions: The relations seen in these analyses indicate that individuals with glucose intolerance or diagnosed diabetes are at increased risk for sudden death.

Few prospective studies have assessed the relation between physical activity and diabetes. The authors examined this relation prospectively among 6,815 Japanese-American men in the Honolulu Heart Program who were aged 45-68 years and initially free of diagnosed diabetes in 1965-1968. A physical activity index was calculated based on time spent per day in different activity levels and a weighting factor correlated with estimated oxygen consumption. Incidence of clinically recognized diabetes was based on self-reported use of diabetic medication at one of two subsequent examinations. The age-adjusted 6-year cumulative incidence of diabetes decreased progressively with increasing quintile of physical activity from 73.8 to 34.3 per 1,000 (p < 0.0001, trend) in all men and from 53.9 to 21.7 per 1,000 (p < 0.0001, trend) among men with a non-fasting glucose level < 225 mg/dl one hour after a 50-gm load, the latter group being less likely to have unrecognized diabetes at baseline. When stratified by tertile of baseline glucose, trends in incidence across physical activity quintiles were statistically significant in the low and middle tertiles but not in the high tertile. Similar inverse trends were observed for men in the lower four quintiles of body mass index, however, these trends were weaker and not significant for men in the upper quintile of body mass index. Age-adjusted odds ratios for diabetes comparing the upper with the lower four quintiles of physical activity were 0.55 (95% confidence interval (CI) 0.41-0.75) for all men and 0.50 (95% CI 0.33-0.74) for men with glucose < 225 mg/dl. After adjustment for age, body mass index, subscapular/triceps skinfold ratio, systolic blood pressure, triglycerides, glucose, hematocrit, and parental history of diabetes, odds ratios were still statistically significant and similar in magnitude. Restriction of analyses to men who remained free of cardiovascular disease during the study period produced similar results, which suggests that inactivity due to subclinical cardiovascular disease is unlikely to be responsible for these findings. Risk factor-adjusted odds ratios for older men (55-68 years) demonstrated that physical activity confers at least the same degree of protection as in younger men (45-54 years). These results indicate that physical activity is associated inversely with incident diabetes and that the beneficial effect does not appear to be mediated through improvements in other risk factors assessed in this study.

Reports on the incidence and predictors of diabetes in minority populations are infrequent. The 6-year cumulative incidence of diabetes between 1965 and 1974 was estimated among 7210 Japanese-American men aged 45 to 68 years who were enrolled in the Honolulu Heart Program and were free of clinically recognized diabetes at baseline. The incidence of "possible" diabetes (based on history, medication, or hospital diagnosis) was 12.8% and the incidence of "probable" diabetes (based on diabetic medication) was 5.7%. Estimates of incidence in subjects with a nonfasting glucose concentration less than 225 mg/dL 1 hour after a 50-g load were 9.7 and 4.0%, respectively. Multivariate adjusted odds ratios (ORs) for probable diabetes in all subjects comparing the upper quintile with the lower four quintiles combined for continuous variables indicated statistically significant direct associations with body mass index (OR, 1.69; 95% confidence interval (CI), 1.31 to 2.18), 1-hour postchallenge glucose level (OR, 5.79; 95% CI, 4.58 to 7.33), triglyceride levels (OR, 1.47; 95% CI, 1.14 to 1.91), systolic blood pressure (OR, 1.36; 95% CI, 1.05 to 1.76), and parental history of diabetes (OR, 1.73; 95% CI, 1.29 to 2.33), and an inverse association with physical activity (OR, 0.49; 95% CI, 0.34 to 0.72), using logistic regression models including these variables as well as age, subscapular/triceps skinfold ratio, and hematocrit simultaneously. Associations were similar but slightly weaker in men with glucose levels less than 225 mg/dL and in those who remained free of cardiovascular disease. When older men (55 to 68 years old) were compared with younger (45 to 54 years old) men, associations among the older group were stronger for body mass index, physical activity, and systolic blood pressure and they were weaker for glucose levels, triglyceride values, and parental diabetes. Results suggest that body mass index, physical inactivity, glucose level, and parental diabetes appear to be independent risk factors for diabetes, while triglyceride and systolic blood pressure levels may be markers for an adverse cardiovascular risk factor profile associated with diabetes and may reflect an insulin resistance syndrome.

High fish consumption is characteristic of Japanese-American men of the Honolulu Heart Program (HHP). Analyses of data from the Atherosclerosis Risk in Communities (ARIC) study suggest high fish intake protects the lung against smoking damage. Measurements of forced expiratory volume in 1 s (FEV1) and smoking status in the HHP cohort were done at the first examination in 1965-68. Among 8,006 men, 45 to 68 yr, 6,346 had acceptable spirograms. Within current smokers, 1,545 men consumed fish less than twice a week, and 1,264 ate fish twice a week or more. Controlling for cigarettes/d, age, height, and daily calories, separate regression models indicated an average decrease of -10.1 ml for each additional yr of smoking (95% Confidence Interval [CI]: -13.6, -6.5) at low levels of fish intake, and a decrease of -4.4 ml (95% CI: -8.2, -0.6) at high levels. The coefficients were significantly different (p = 0.03). These differences reflect a predicted FEV1 144 ml (95% CI: 62, 227) higher in the high fish group at > or = 40 yr of smoking, but no difference at < or = 35 yr. Similar analyses were conducted for cigarettes/d. On average, the FEV1 decline for each additional cigarette/d was not significantly different among subjects with low versus high fish intake. However, the predicted FEV1 at < or = 30 cigarettes/d was 52 ml (95% CI: 17, 87) higher in the high fish consumption group. No significant difference in FEV1 was noted between groups at > 30 cigarettes/d. These findings suggest that the protective role of fish is "saturated" at higher "doses" of cigarette smoking.

The Honolulu Heart Program continues to follow a cohort of Japanese-American men initially aged 45-68 years, of whom 4,000 had three acceptable measurements of forced expiratory volume in 1 second (FEV1) between 1965 and 1974 and were free of cardiovascular disease and cancer. The 6-year rate of change (slope) in FEV1 was calculated using a within-person linear regression method. Men were divided into tertiles based on the rate of change in FEV1. During 17 subsequent years of follow-up, 796 deaths occurred. The tertile with the greatest rate of decline in FEV1 (mean, -61 ml/year) had the highest age-adjusted total mortality rate (17.3/1,000 person-years), followed by rates of 13.2 for the middle tertile (mean, -25 ml/year) and 11.0 for men with the smallest change in FEV1 (mean, +9 ml/year) (test for trend, p < 0.0001). Using the Cox model, comparing the tertile with the smallest change in FEV1 as a reference group with the tertile with the greatest decline in FEV1, and after adjusting for age, hypertension, smoking, body mass index, alcohol intake, diabetes mellitus, and cholesterol, the authors found the relative risk (RR) for total mortality to be 1.48 (95% confidence interval (CI) 1.24-1.77). After stratification by smoking status, this association remained significant for past smokers (RR = 1.79, 95% CI 1.31-2.14), as well as for the low, < or = 42 (RR = 1.46, 95% CI 1.05-2.03), and high, > 42 (RR = 1.56, 95% CI 1.20-2.02), pack-year groups. An increased risk was also present for current smokers (RR = 1.29), but it was of borderline significance (p = 0.08). No association was found among never smokers. These data suggest that the rate of decline in FEV1 is a predictor of total mortality among smokers.

Background: The purpose of the study was to examine the association between physical activity and 23-year incidence of coronary heart disease morbidity and mortality. This cohort study continues to follow 8006 Japanese-American men who were 45 to 68 years of age and living on Oahu, Hawaii, in 1965, for the development of coronary heart disease morbidity and mortality., Methods and Results: The Framingham physical activity index was calculated by summing the product of average hours spent at each activity level and a weighting factor based on oxygen consumption. Study subjects were divided into tertiles of physical activity index at baseline. Relative risks and 95% confidence intervals (CI) for incidence of coronary heart disease morbidity and mortality were obtained using the Cox model. After age adjustment and using the lowest physical activity index tertile as a reference group, the relative risk for coronary heart disease incidence for the highest tertile of physical activity was 0.83 (CI, 0.70 to 0.99). After adjusting for age, hypertension, smoking, alcohol intake, diabetes, cholesterol, and body mass index, the relative risk was 0.95 and CI included 1 (CI, 0.80 to 1.14). For coronary heart disease mortality, the age-adjusted relative risk was 0.74 (CI, 0.56 to 0.97) and 0.85 (CI, 0.65 to 1.13) after risk factor adjustment., Conclusions: The results suggest that the impact of physical activity index on coronary heart disease is mediated through its effects on hypertension, diabetes, cholesterol, and body mass index. These findings support the hypothesis that physical activity is inversely associated with coronary heart disease morbidity and mortality and suggest that physical activity interventions in middle-aged men, by improving cardiovascular risk factor levels, may have significant public health implications in the prevention of coronary heart disease.