Biomedical subjects

D S Sharp

Publications and source records attributed to D S Sharp.

At least 37 records · Page 2Linked to original sources

PubMed1998

Orthostatic hypotension predicts mortality in elderly men: the Honolulu Heart Program.

BACKGROUND: Population-based data are unavailable concerning the predictive value of orthostatic hypotension on mortality in ambulatory elderly patients, particularly minority groups. METHODS AND RESULTS: With the use of data from the Honolulu Heart Program's fourth examination (1991 to 1993), orthostatic hypotension was assessed in relation to subsequent 4-year all-cause mortality among a cohort of 3522 Japanese American men 71 to 93 years old. Blood pressure was measured in the supine position and after 3 minutes of standing, with the use of standardized methods. Orthostatic hypotension was defined as a drop in systolic blood pressure (SBP) of >/=20 mm Hg or in diastolic blood pressure of >/=10 mm Hg. Overall prevalence of orthostatic hypotension was 6.9% and increased with age. There was a total of 473 deaths in the cohort over 4 years; of those who died, 52 had orthostatic hypotension. Four-year age-adjusted mortality rates in those with and without orthostatic hypotension were 56.6 and 38.6 per 1000 person-years, respectively. With the use of Cox proportional hazards models, after adjustment for age, smoking, diabetes mellitus, body mass index, physical activity, seated systolic blood pressure, antihypertensive medications, hematocrit, alcohol intake, and prevalent stroke, coronary heart disease and cancer, orthostatic hypotension was a significant independent predictor of 4-year all-cause mortality (relative risk 1.64, 95% CI 1.19 to 2.26). There was a significant linear association between change in systolic blood pressure from supine position to standing and 4-year mortality rates (test for linear trend, P<0.001), suggesting a dose-response relation. CONCLUSIONS: Orthostatic hypotension is relatively uncommon, may be a marker for physical frailty, and is a significant independent predictor of 4-year all-cause mortality in this cohort of elderly ambulatory men.

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PubMed1998

Changes in total and high-density lipoprotein cholesterol over 10- and 20-year periods (the Honolulu Heart Program).

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.

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PubMed1998

Factors of the insulin resistance syndrome in nondiabetic and diabetic elderly Japanese-American men.

Factor analysis has previously identified four independent factors that characterize the insulin resistance syndrome in women, interpreted as 1) weight/waist, 2) lipids, 3) insulin/glucose, and 4) systolic and diastolic blood pressure. Because it is not known whether similar factors emerge for men, or for diabetics, factor analysis was used to investigate the clustering of features characterizing the insulin resistance syndrome using data from 3,159 elderly (71-93 years) Japanese-American men participating in the fourth examination of the Honolulu Heart Program during 1991-1993. Consistent with previous results, factor analysis reduced eight risk factors (insulin, glucose, systolic blood pressure, diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol, weight, and waist circumference) to four uncorrelated factors that explained 78.2% and 74.7% of the variance in nondiabetics (n = 2,760) and diabetics (n = 399), respectively. These factors were interpreted as 1) weight/waist, 2) blood pressure, 3) lipids, and 4) insulin/glucose. Modest differences in the associations between fasting insulin and factors 1, 3, and 4 were noted for diabetics. These consistently identified composite factors may represent markers for underlying pathophysiologic mechanisms of the insulin resistance syndrome and risk of non-insulin-dependent diabetes mellitus.

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PubMed1998

Relative weight, weight change, and risk of coronary heart disease in the Honolulu Heart Program.

Risk of coronary heart disease (CHD) among the Honolulu Heart Program participants was examined in relation to body mass index (BMI) at age 25 and two subsequent periods of weight change: age 25 to examination I (1965-1968) and examination I to examination III (1971-1974). During a maximum follow-up period of 17 years after examination III, there were 479 incident cases of CHD among the study sample of 6,176 Japanese-American men. Levels of BMI at age 25 were positively related to CHD incidence after statistical control for age, smoking, and subsequent weight change. Relative risk between the lowest and highest BMI categories was 2.44 (95% confidence interval (CI) 1.61-3.69). Compared with a weight change of less than 2.5 kg between age 25 and examination I, relative risks were 1.41 (95% CI 1.00-1.97) for a weight gain between 2.6 and 5 kg, 1.60 (95% CI 1.22-2.11) for a weight gain between 5.1 and 10 kg, and 1.75 (95% CI 1.32-2.33) for a weight gain of more than 10 kg. During the examination I-III period, in contrast, the highest risk of CHD was found in men who lost the greatest amount of weight; the relative risk of CHD for men who lost more than 2.5 kg was 1.25 (95% CI 0.98-1.60). The authors conclude that levels of relative weight in early adulthood were positively related to risk of CHD occurring much later in the lives of these men. The association between CHD incidence and weight change appeared to be modified by age, with higher risks for earlier weight gain and later weight loss in the lives of these men.

Adult↗

PubMed1998

Coffee consumption in hypertensive men in older middle-age and the risk of stroke: the Honolulu Heart Program.

OBJECTIVE: To examine the association between coffee consumption and the development of stroke in men at high risk for cardiovascular disease. METHODS: Coffee intake was observed from 1965 to 1968 in a cohort of men enrolled in the Honolulu Heart Program with follow-up for incident stroke over a 25-year period. Subjects were 499 hypertensive men (having systolic or diastolic blood pressures at or above 140 and 90 mm Hg, respectively) in older middle-age (55 to 68 years) when follow-up began. Past and current cigarette smokers were excluded from follow-up. RESULTS: In the course of follow-up, 76 men developed a stroke. After age-adjustment, risk of thromboembolic stroke increased significantly with increases in coffee consumption (P = 0.002). No relationships were observed with hemorrhagic stroke. When adjusted for other factors, the risk of thromboembolic stroke was more than doubled for men who consumed three cups of coffee per day as compared to nondrinkers of coffee (RR = 2.1; 95% CI = 1.2-3.7). CONCLUSIONS: Although in need of further confirmation, consumption of coffee appears to be positively associated with an increased risk of thromboembolic stroke in hypertensive men in older middle-age. Findings suggest that it may be prudent to advise older middle-aged men with hypertension who consume large amounts of coffee to consider reducing their coffee intake.

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PubMed1998

Prolonged QTc interval, impaired pulmonary function, and a very lean body mass jointly predict all-cause mortality in elderly men.

PURPOSE: Assess the joint impact of prolonged QTc interval (QT interval corrected for heart rate), impaired lung function, and low body weight on all-cause mortality. METHODS: This is a population-based, prospective study of the Honolulu Heart Program cohort, performed in Oahu Island, Hawaii, during the 1991-1993 fourth examination of cohort survivors. The participants were 3056 Japanese-American men, 71 to 93 years of age. The measurement consisted of: 1) instrument calculated, heart rate corrected QT interval; 2) one second forced expiratory volume (FEV1) as a percentage of age- and height-predicted FEV1; and 3) body mass index (BMI, kg/m2). Relations of subsequent 3 1/2 year, on average, mortality rates with high risk states of these variables are determined. High risk states are QTc > 440 msec, percent predicted FEV1 < or = 80%, and BMI < or = 21 kg/m2. RESULTS: Mortality rates synergistically increase among groups with one, two, or three high risk states. Men having all three high risk states are seven times more likely to die in the follow-up period than men with no high risk conditions. Very thin men having one other high risk state, pulmonary impairment or prolonged QTc, are four times more likely to die. Excluding diabetics, active smokers, or men taking drugs affecting QT interval does not alter findings. Excluding prevalent coronary heart disease decreases mortality rates among joint high risk groups. CONCLUSION: Results are consistent with clinical studies identifying an autonomic neuropathy associated with wasting chronic lung disease, prolonged QTc, and mortality. Aging populations in developed nations will increase the prevalence of diseases associated with these conditions in decades to come.

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PubMed1998

Association of insulin levels with lipids and lipoproteins in elderly Japanese-American men.

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.

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PubMed1998

Hyperinsulinemia and cardiovascular disease in elderly men: the Honolulu Heart Program.

Hyperinsulinemia has been associated with cardiovascular disease (CVD), but whether this relation is independent of other CVD risk factors is uncertain. Most studies have focused on coronary heart disease (CHD), but few have included peripheral vascular disease (PVD) and stroke. Moreover, evidence in elderly and minority populations is limited. Between 1991 and 1993, 3562 elderly (71 to 93 years) Japanese-American men from the Honolulu Heart Program were examined and had fasting insulin levels measured. Hyperinsulinemia, defined as a fasting insulin > or =95th percentile among nonobese men with normal glucose tolerance and no diabetic history or medication use, was observed in 22% of the population. Subjects with hyperinsulinemia had a more adverse CVD risk factor profile and had higher age-adjusted prevalences of CHD, angina, PVD, thromboembolic stroke, and hemorrhagic stroke compared with those without hyperinsulinemia. Age-adjusted fasting insulin levels but not 2-hour levels were also significantly elevated (P<.01) in those with prevalent CVD compared with those without. In logistic regression analyses, adjustment for multiple CVD risk factors attenuated the relations of hyperinsulinemia with CHD, angina, and PVD to nonsignificant levels, whereas those involving thromboembolic and hemorrhagic stroke were strengthened and remained significant (odds ratios=2.27 and 7.53, 95% confidence intervals=1.25 to 4.13 and 1.65 to 34.25, respectively). When multivariate analyses were restricted to nondiabetic subjects, associations were slightly weaker and in general nonsignificant. Nondiabetic men with thromboembolic stroke were twice as likely to have hyperinsulinemia as those who were stroke-free, although this association was of borderline significance (odds ratio= 1.99, 95% confidence interval=0.95 to 4.17, P=.069). In subjects with elevated total cholesterol levels, somewhat stronger associations were observed for PVD and stroke but not for CHD. Although further prospective studies are indicated, particularly for PVD and stroke, these cross-sectional results are consistent with an indirect role for insulin in CVD, wherein hyperinsulinemia or an underlying insulin-resistant state may adversely affect other CVD risk factors or serve as a marker for an atherogenic or thrombogenic state.

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PubMed1998

Relationship of HDL and coronary heart disease to a common amino acid polymorphism in the cholesteryl ester transfer protein in men with and without hypertriglyceridemia.

Plasma triglyceride (TG) levels are inversely related to HDL-cholesterol levels and subjects with high TG and low HDL cholesterol have increased coronary heart disease (CHD) risk. Plasma cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from HDL to TG-rich lipoproteins. In this study we determined the relationship between a common CETP amino acid polymorphism (I405V) and CETP and HDL levels and CHD prevalence in 576 men of Japanese ancestry in the Honolulu Heart Program cohort. This conservative substitution was associated with altered plasma CETP concentration (1.95 +/- 0.54, 1.91 +/- 0.57, and 1.77 +/- 0.57 microg/ml for the II, IV and VV genotypes, respectively). The distribution of plasma CETP concentrations among the VV, but not II, men appeared bimodal (P < 0.01), suggesting the presence of a functionally significant CETP gene mutation(s) in a subset of V alleles. HDL-C levels were higher in VV than IV for II men (55.4 +/- 17.4, 51.3 +/- 16.6, 51.1 +/- 17.0 mg/dl, P < 0.04). However, the increase in HDL was only significant in VV men with plasma TG > 165 mg/dl. Although CHD prevalence was not significantly different among the three genotypes in this population, in the subpopulation with high plasma TG, CHD prevalence appeared higher among VV than IV or II subjects (38% vs. 27% vs. 18%, P < 0.05 for an interaction of genotype and plasma TG levels). In fresh plasma from a separate group of normolipidemic subjects, the V/I polymorphism was not associated with any change in plasma CETP specific activity. The data suggest that a widespread and common CETP gene mutation(s) in linkage disequilibrium with 405V causes low CETP. Among hypertriglyceridemic men this is associated with higher HDL and possibly with increased CHD.

Amino Acids↗

PubMed1997

Obesity, alcohol consumption, smoking, and mortality.

PURPOSE: The goals of this study were to assess prospectively the impact of obesity, alcohol use, and smoking on total mortality and to test the etiologic hypothesis that subjects with two or more of these risk factors may experience an elevated risk of overall mortality. METHODS: Information on body mass index (BMI), alcohol intake, cigarette smoking, and other life-style factors was obtained from a cohort of 8006 Japanese-American men living in Hawaii. They were between 45 and 68 years of age at the initial examination (1965-1968). After 22 years of follow-up that included nearly 159,000 person-years of observation, 2667 deaths from all causes were identified. RESULTS: There was a significant quadratic (J-shaped) relation between BMI and overall mortality. A weaker J-shaped pattern in risk was also present for the intake of alcohol. A strong positive association was observed with pack-years of cigarette smoking. A synergistic interaction between BMI and alcohol was statistically significant (P = 0.0017). Specifically, men who had the lowest body mass (BMI < 21.21 kg/m2) and drank moderately to heavily (> or = 25 oz/mo) experienced a 63% excess risk (relative risk, 1.63; 95% confidence interval; 1.33 - 1.99) compared to a reference group composed of men who had intermediate body mass (BMI, 21.21 - 26.30 kg/m2) and drank occasionally to lightly (0.01 - 24.99 oz/mo). The increase in risk due to the interactive effect of low BMI and high alcohol intake was stronger (and statistically significant) than when each of these risk factors was considered separately (excess risk, 28% and 2%, respectively). There was no significant interaction for BMI and cigarette smoking, for alcohol and cigarette smoking, or for the three factors combined. CONCLUSIONS: The most important finding of this study was that, in addition to confirming that cigarette smoking could shorten life, extreme (high or low) BMI values and high alcohol consumption are each potentially harmful to health, but even more so if moderate or heavy drinking is concomitant with low body mass, a possible indicator for low intake of nutrients.

Age Distribution↗

PubMed1997

Cross-sectional and longitudinal changes in total and high-density-lipoprotein cholesterol levels over a 20-year period in elderly men: the Honolulu Heart Program.

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.

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PubMed1997

Associations of adiposity with prevalent coronary heart disease among elderly men: the Honolulu Heart Program.

OBJECTIVE: To assess associations of adiposity with prevalent coronary heart disease (CHD) among elderly men. DESIGN: A cross-sectional epidemiologic study conducted between 1991 and 1993. SUBJECTS: 3741 Japanese-American men from the Honolulu Heart Program who were 71-93 y of age. MEASUREMENTS: CHD included documented myocardial infarction (electrocardiographic and enzyme criteria), acute coronary insufficiency, angina pectoris leading to surgical treatment identified through hospital surveillance, and reported history of heart attach or angina pectoris requiring hospitalization or surgical treatment. BMI was calculated as weight in kg divided by height in square meters. Waist circumference was measured at the horizontal level of the umbilicus and WHR was a ratio of waist circumference to hip circumference measured at the horizontal level of the maximal protrusion of the gluteal muscles. RESULTS: An elevated prevalence of CHD was observed in the elderly men with high BMI, WHR and waist circumference. The significant associations of BMI and waist circumference with CHD persisted after adjustment for fasting glucose, physical activity and pack-years of cigarette smoking but were no longer significant (odds ration (OR) = 1.03, 95% confidence level (CI) 0.94-1.12 and OR = 1.09, CI = 0.99-1.20, respectively) after adjustment for high density lipoprotein cholesterol (HDL-C). Also, the association of BMI with CHD was not found to be independent of abdominal adiposity. However, the associations of WHR and waist circumference remained significant (OR = 1.20, CI = 1.08-1.33 and OR = 1.17, CI = 1.01-1.37, respectively) after additional adjustment for BMI. In addition, the association of WHR with CHD was consistently significant and independent of fasting glucose, physical activity, smoking and HDL-C (OR = 1.11, CI = 1.00-1.23). CONCLUSION: WHR is associated with CHD independent of HDL-C and BMI, whereas the relation of BMI and waist circumference with CHD may be mediated through a relation of BMI and waist circumference with HDL-C level.

Aged↗

PubMed1997

The synergy of low lung function and low body mass index predicting all-cause mortality among older Japanese-American men.

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.

Aged↗

PubMed1997

Factors associated with variations in pulmonary function among elderly Japanese-American 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.

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PubMed1996

Fish intake may limit the increase in risk of coronary heart disease morbidity and mortality among heavy smokers. The Honolulu Heart Program.

BACKGROUND: Research has shown that fish consumption limits damage to the lungs caused by cigarette smoking, possibly by the effects of fish on arachidonic acid metabolism. We explored this fish-smoking interaction using coronary heart disease (CHD) incidence and mortality as the outcome. METHODS AND RESULTS: The Honolulu Heart Program began in 1965 to follow a cohort of 8006 Japanese-American men aged 45 to 65 years who lived on Oahu, Hawaii, in 1965. Fish intake was measured at baseline by use of a questionnaire. For current smokers at baseline (n = 3310) who reported low fish intake (< 2 times/wk), age-adjusted 23-year CHD mortality rates increased with the number of cigarettes smoked per day (2.3, 3.1, and 6.9 per 1000 person-years for men who smoked < 20, 20 to 30, and > 30 cigarettes/d, respectively; trend test P < .0001). Among current smokers whose fish intake was high (> or = 2 times/wk), CHD mortality rates showed no relation with cigarettes/d (3.7, 3.2, and 3.7 per 1000 person-years for the corresponding levels of smoking). A Cox proportional hazards model based on current smokers, adjusted for age, years in Japan, calories/d, alcohol intake, physical activity index, years smoked, hypertension, and serum cholesterol, blood glucose, and uric acid levels, was examined. In the high-smoking group, the risk factor-adjusted relative risk (RR) for CHD mortality among those with high fish intake was half that of those with low fish consumption (RR = 0.5, 95% confidence interval = 0.28 to 0.91). A Cox model that adjusted for similar risk factors confirmed a significant interaction of cigarettes/d and fish intake (P < .01) on CHD mortality. Analyses for CHD incidence showed similar results. CONCLUSIONS: Despite the findings of this investigation, the public health message for smokers continues to be to stop smoking. However, an interaction between fish intake and cigarette smoking is biologically plausible and deserves further investigation. The study of this phenomenon may shed light on the biological mechanisms by which cigarette smoking leads to CHD.

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PubMed1996

Increased coronary heart disease in Japanese-American men with mutation in the cholesteryl ester transfer protein gene despite increased HDL levels.

Plasma high density lipoprotein (HDL) levels are strongly genetically determined and show a general inverse relationship with coronary heart disease (CHD). The cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to other lipoproteins and is a key participant in the reverse transport of cholesterol from the periphery to the liver. A high prevalence of two different CETP gene mutations (D442G, 5.1%; intron 14G:A, 0.5%), was found in 3,469 men of Japanese ancestry in the Honolulu Heart Program and mutations were associated with decreased CETP (-35%) and increased HDL chol levels (+10% for D442G). However, the overall prevalence of definite CHD was 21% in men with mutations and 16% in men without mutations. The relative risk (RR) of CHD was 1.43 in men with mutations (P < .05); after adjustment for CHD risk factors, the RR was 1.55 (P = .02); after additional adjustment for HDL levels, the RR was 1.68 (P = .008). Similar RR values were obtained for the D442G mutation alone. Increased CHD in men with mutations was primarily observed for HDL chol 41-60 mg/dl; for HDL chol > 60 mg/dl men with and without mutations had low CHD prevalence. Thus, genetic CETP deficiency appears to be an independent risk factor for CHD, primarily due to increased CHD prevalence in men with the D442G mutation and HDL cholesterol between 41 and 60 mg/dl. The findings suggest that both HDL concentration and the dynamics of cholesterol transport through HDL (i.e., reverse cholesterol transport) determine the anti-atherogenicity of the HDL fraction.

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PubMed1996

Mean red cell volume as a correlate of blood pressure.

BACKGROUND: Clinical studies suggest that hypertensives have lower mean corpuscular volume (MCVs) than do normotensives. Epidemiological studies show no relation or higher MCVs. In the present study of elderly men (71 to 93 years of age) of the Honolulu Heart Program, elements of both findings are confirmed. METHODS AND RESULTS: Three groups are identified: (1) those receiving no hypertension treatment, (2) those receiving treatment with any diuretic, and (3) those receiving treatment with nondiuretics only. MCV is lower in group 3 than in group 1 (-0.85 fL, P<.001) but the same in groups 1 and 2. Within groups 1 and 3, inverse relations of -0.22 and -0.09 mm Hg/fL (P<.05) are noted for systolic (SBP) and diastolic (DBP) blood pressures. No relations are observed in group 2. MCV and red blood cell count (RBC) are inversely correlated (r=-.45). In group 2, adjustment for RBC unmasks a direct relation between MCV and SBP (0.5 mm Hg/fL, P=.02) and DBP (0.3 mm Hg/fL, P=.02). In groups 1 and 3, relations between SBP and MCV are lost after adjustment for RBC (0.005 mm Hg/fL). For DBP, adding RBC plus an MCV x RBC interaction is significant (P<.001). DBP is 5 mm Hg greater in the highest RBC quartile than in the lowest. A +3 mm Hg difference between extreme MCV quartiles is noted only at high RBC levels. CONCLUSIONS: The relation between blood pressure and red cell measures is probably mediated by whole blood viscosity. Hematocrit is a determinant of whole blood viscosity. Viscosity affects peripheral resistance to blood flow, and peripheral resistance affects DBP. At high RBC levels, MCV may be "downregulated." This may lower whole blood viscosity and partially reduce DBP without compromising flow.

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PubMed1996

Pulmonary function measures as predictors and correlates of cognitive functioning in later life.

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.

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