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Background Many studies have reported the J-shaped relationship between alcohol consumption and coronary heart disease (CHD) risk; therefore, light-drinkers is generally recognized to be associated with the lower risk of CHD. However, the mechanisms of lower risk for CHD in light-drinkers are still unclear. Alcohol drinking status is likely to be associated with not only CHD risk factors but also dietary intake. Nevertheless, few studies report these relationships in detail. Purpose The purpose of this study is to evaluate the relationships of alcohol drinking status with CHD classical risk factors and the intake of macro- and micro- nutrients in Japanese. Methods Study participants were 1,090 Japanese men and women aged 40–59 years from The INTERLIPID study excepted for 55 individuals who had missing data (n=26) and were past-drinkers (n=29). Alcohol consumption was assessed with two 7-day alcohol records, and average ethanol intake (per week) was calculated. Participants were classified into following 4 groups: non-drinkers (0g/week), light-drinkers ( Results Serum HDL cholesterol levels increased and LDL cholesterol levels decreased with increasing alcohol consumption. Systolic and diastolic BP increased with increasing alcohol consumption. J-shaped relationships with alcohol consumption were observed for the proportion of current smoker, number of cigarettes, and the prevalence of hypertension; that is, light-drinkers was lowest among all groups. The prevalence of dyslipidemia was the highest in non-drinkers, and decreased with increasing alcohol consumption. In heavy-drinkers, total energy (kcal/day) was the highest, but energy intake without alcohol (kcal/day) was the lowest. For macronutrients, the intake of carbohydrate (%kcal) decreased, and the intakes of total and animal protein (%kcal) increased with increasing alcohol consumption. The intakes of total cholesterol (mg/1000kcal) and sodium (mg/1000kcal) increased, and total fiber (g/1000kcal) decreased with increasing alcohol consumption. These associations were similar in men and women. Conclusions Alcohol consumption was related with not only CHD classical risk factors but also the intake of macro- and micro-nutrients. Non-drinkers had a higher proportion of some CHD risk factors than light-drinkers. These results might influence on J-shaped relationship between alcohol consumption and CHD risk. Acknowledgement/Funding 1: Ministry of Education, Science, Sports, and Culture of Japan, 2: National Institutes of Health, Bethesda, MD, USA

High intakes of dietary sodium are associated with elevated blood pressure levels and an increased risk of cardiovascular disease. National and international guidelines recommend reduced sodium intake in the general population, which necessitates population-wide surveillance. We assessed the utility of casual (spot) urine specimens in estimating 24-hour urinary sodium excretion as a marker of sodium intake in the International Cooperative Study on Salt, Other Factors, and Blood Pressure. There were 5,693 participants recruited in 1984–1987 at the ages of 20–59 years from 29 North American and European samples. Participants were randomly assigned to test or validation data sets. Equations derived from casual urinary sodium concentration and other variables in the test data were applied to the validation data set. Correlations between observed and estimated 24-hour sodium excretion were 0.50 for individual men and 0.51 for individual women; the values were 0.79 and 0.71, respectively, for population samples. Bias in mean values (observed minus estimated) was small; for men and women, the values were −1.6 mmol per 24 hours and 2.3 mmol per 24 hours, respectively, at the individual level and −1.8 mmol per 24 hours and 2.2 mmol per 24 hours, respectively, at the population level. Proportions of individuals with urinary 24-hour sodium excretion above the recommended levels were slightly overestimated by the models. Casual urine specimens may be a useful, low-burden, low-cost alternative to 24-hour urine collections for estimation of population sodium intakes; ongoing calibration with study-specific 24-hour urinary collections is recommended to increase validity.

Investigators in the Chicago Healthy Aging Study (CHAS) reexamined 1,395 surviving participants aged 65–84 years (28% women) from the Chicago Heart Association Detection Project in Industry (CHA) 1967–1973 cohort whose cardiovascular disease (CVD) risk profiles were originally ascertained at ages 25–44 years. CHAS investigators reexamined 421 participants who were low-risk (LR) at baseline and 974 participants who were non-LR at baseline. LR was defined as having favorable levels of 4 major CVD risk factors: serum total cholesterol level

Background Association between casual and 24-h urinary sodium-to-potassium (Na/K) ratio is well recognized, although it has not been validated in diverse demographic groups. Our aim was to assess utility across and within populations of casual urine to estimate 24-h urinary Na/K ratio using data from the INTERSALT Study. Methods The INTERSALT Study collected cross-sectional standardized data on casual urinary sodium and potassium and also on timed 24-h urinary sodium and potassium for 10 065 individuals from 52 population samples in 32 countries (1985–87). Pearson correlation coefficients and agreement were computed for Na/K ratio of casual urine against 24-h urinary Na/K ratio both at population and individual levels. Results Pearson correlation coefficients relating means of 24-h urine and casual urine Na/K ratio were r = 0.96 and r = 0.69 in analyses across populations and individuals, respectively. Correlations of casual urine Na/creatinine and K/creatinine ratios with 24-h urinary Na and K excretion, respectively, were lower than correlation of casual and 24-h urinary Na/K ratio in analyses across populations and individuals. The bias estimate with the Bland–Altman method, defined as the difference between Na/K ratio of 24-h urine and casual urine, was approximately 0.4 across both populations and individuals. Spread around, the mean bias was higher for individuals than populations. Conclusion With appropriate bias correction, casual urine Na/K ratio may be a useful, low-burden alternative method to 24-h urine for estimation of population urinary Na/K ratio. It may also be applicable for assessment of the urinary Na/K ratio of individuals, with use of repeated measurements to reduce measurement error and increase precision.

Information on dietary supplements, medications, and other xenobiotics in epidemiologic surveys is usually obtained from questionnaires and is subject to recall and reporting biases. The authors used metabolite data obtained from hydrogen-1 (or proton) nuclear magnetic resonance ( 1H NMR) analysis of human urine specimens from the International Study of Macro-/Micro-Nutrients and Blood Pressure (INTERMAP Study) to validate self-reported analgesic use. Metabolic profiling of two 24-hour urine specimens per individual was carried out for 4,630 participants aged 40-59 years from 17 population samples in Japan, China, the United Kingdom, and the United States (data collection, 1996-1999). 1H NMR-detected acetaminophen and ibuprofen use was low (�4%) among East Asian population samples and higher (>16%) in Western population samples. In a comparison of self-reported acetaminophen and ibuprofen use with 1H NMR-detected acetaminophen and ibuprofen metabolites among 496 participants from Chicago, Illinois, and Belfast, Northern Ireland, the overall rate of concordance was 81%-84%; the rate of underreporting was 15%-17%; and the rate of underdetection was approximately 1%. Comparison of self-reported unspecified analgesic use with 1H NMR-detected acetaminophen and ibuprofen metabolites among 2,660 Western INTERMAP participants revealed similar levels of concordance and underreporting. Screening for urinary metabolites of acetaminophen and ibuprofen improved the accuracy of exposure information. This approach has the potential to reduce recall bias and other biases in epidemiologic studies for a range of substances, including pharmaceuticals, dietary supplements, and foods. © 2012 The Author.

Data indicate an inverse association between dietary calcium and magnesium intakes and blood pressure (BP); however, much less is known about associations between urinary calcium and magnesium excretion and BP in general populations. The authors assessed the relation of BP to 24-hour excretion of calcium and magnesium in 2 cross-sectional studies. The International Study of Macro- and Micro-Nutrients and Blood Pressure (INTERMAP) comprised 4,679 persons aged 40–59 years from 17 population samples in China, Japan, the United Kingdom, and the United States, and the International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT) comprised 10,067 persons aged 20–59 years from 52 samples around the world. Timed 24-hour urine collections, BP measurements, and nutrient data from four 24-hour dietary recalls (INTERMAP) were collected. In multiple linear regression analyses, urinary calcium excretion was directly associated with BP. After adjustment for multiple confounders (including weight, height, alcohol intake, calcium intake, urinary sodium level, and urinary potassium intake), systolic BP was 1.9 mm Hg higher per each 4.1 mmol per 24 hours (2 standard deviations) of higher urinary calcium excretion (associations were smaller for diastolic BP) in INTERMAP. Qualitatively similar associations were observed in INTERSALT analyses. Associations between magnesium excretion and BP were small and nonsignificant for most of the models examined. The present data suggest that altered calcium homoeostasis, as exhibited by increased calcium excretion, is associated with higher BP levels.

BACKGROUND: Cardiovascular risk factor research has recently broadened its focus based on new data indicating the benefits of low risk, i.e. favorable levels of all major risk factors. The aims of this study were to assess further the relation of low risk to coronary heart disease risk, and implications for prevention. DESIGN: We conducted a prospective population-based Italian study, of 7438 men and 13 009 women aged 35-69 years, with a mean follow-up of 10.4 years and validated first coronary events. METHODS: Baseline coronary heart disease risk was classified into three categories: low risk; unfavorable but not high risk; and high risk. To analyze the relation of these risk profiles to coronary heart disease incidence, age-adjusted, sex-averaged coronary heart disease incidence was calculated for persons free of coronary heart disease and stroke, stratified as baseline low risk, unfavorable but not high risk or high risk. To assess the independent relationship of individual risk factors to coronary heart disease incidence, multivariate proportional hazards models were computed for combinations of risk factors. RESULTS: Only 2.7% of participants met low risk criteria; 81.4% were high risk. Age-adjusted coronary heart disease incidence for the whole cohort was 37.1 out of 10000 person-years (men 59.0; women 15.3). No coronary heart disease events occurred in low-risk men, only two in low-risk women. For women and men who were not high risk, the age-sex standardized coronary heart disease rate was 62% lower than for high-risk participants. Blood pressure, need for antihypertensive medication, smoking, hyperglycemia, diabetes, total and high-density lipoprotein cholesterol were independently related to coronary heart disease risk. CONCLUSIONS: Favorable levels of all modifiable readily measured risk factors - rare among Italian adults - assure minimal coronary heart disease risk. Population-wide prevention is needed, especially improved lifestyles, to increase the proportion of the population at low risk. © 2006 The European Society of Cardiology.

Twenty-four-hour urinary albumin excretion (UAE) is considered the gold standard for determining albumin level in epidemiologic studies, but this measure is inconvenient and often unavailable. Simpler alternatives include the albumin:creatinine ratio (ACR) and urinary albumin concentration (UAC) obtained from a single sample. The authors assessed the strengths and weaknesses of ACR and UAC as alternatives to UAE using albumin measurements from two 24-hour urine samples collected in 1996–1999 from 4,678 participants aged 40–59 years in the International Study of Macronutrients and Blood Pressure (17 population samples from four countries). The authors compared ACR and UAC with regard to correlations with UAE, daily within-person variability, and associations with known predictors of UAE. Rank-order correlations of ACR with UAE were 0.949 and 0.942 for men and women, respectively, versus 0.881 and 0.816 for UAC. Mean within-person coefficients of variation were 34.0–40.0% for the three measures, with the smallest values being observed for UAC. Average correlations with blood pressure were similar for UAE, ACR, and UAC, but the correlation with body mass index was lower for ACR (0.118 for ACR and 0.188 for UAC vs. 0.211 for UAE) because of high correlation between body mass index and creatinine level. Thus, UAC and ACR are acceptable alternatives to the more complex UAE, and the simpler UAC may be preferable to ACR in some respects.

It has been suggested that smoking does not influence risk of cardiovascular diseases in populations with low serum cholesterol levels. To determine whether cigarette smoking is an independent risk factor among men with low levels of serum cholesterol, data on 25-year coronary, cardiovascular, and all-cause mortality for 8,816 middle-aged men screened between 1967 and 1973 by the Chicago Heart Association Detection Project in Industry were examined. With Cox multivariate proportional hazards regression, relative risks of coronary heart disease and cardiovascular disease mortality associated with smoking for the two subcohorts with favorable levels of serum total cholesterol, that is, less than 180 and 180-199 mg/dl, were of the same magnitude as those for men with elevated serum cholesterol, that is, 200-239 and 240 mg/dl. In the two lower strata of cholesterol, the absolute risk and absolute excess risk of mortality for current smokers at baseline were substantially higher compared with men who never smoked, with all-cause death rates of 423.0 and 428.0 per 1,000 and absolute excess rates of 209.8 and 225.7 per 1,000. These translate to estimated shorter life expectancies of 5.3 and 5.7 years, respectively. Adverse effects of smoking on risk of coronary, cardiovascular, and all-cause mortality prevail for men with lower as well as higher serum cholesterol levels.

In a prospective cohort study, associations of resting heart rate with risk of coronary, cardiovascular disease, cancer, and all-cause mortality in age-specific cohorts of black and white men and women were examined over 22 years of follow-up. Participants were employees from 84 companies and organizations in the Chicago, Illinois, area who volunteered for a screening examination. Participants included 9,706 men aged 18-39 years, 7,760 men aged 40-59 years, 1,321 men aged 60-74 years, 6,928 women aged 18-39 years, 6,915 women aged 40-59 years, and 1,151 women aged 60-74 years at the baseline examination in 1967-1973. Vital status was ascertained through 1992. For fatal coronary disease, multivariate-adjusted relative risks associated with a 12 beats per minute higher heart rate (one standard deviation) were as follows: for men aged 18-39 years, relative risk (RR) = 1.27 (95% confidence interval (CI) 1.08-1.48); for men aged 40-59 years, RR = 1.13 (95% CI 1.05-1.21); for men aged 60-74 years, RR = 1.00 (95% CI 0.89-1.12); for women aged 40-59 years, RR = 1.21 (95% CI 1.07-1.36); and for women aged 60-74 years, RR = 1.16 (95% CI 0.99-1.37). Corresponding risks for all fatal cardiovascular diseases were similar to those for coronary death alone. Deaths from cancer were significantly associated with heart rate in men and women aged 40-59 years. All-cause mortality was associated with higher heart rate in men aged 18-39 years (RR = 1.11, 95% CI 1.01-1.20), men aged 40-59 years (RR = 1.16, 95% CI 1.11-1.21), and women aged 40-59 years (RR = 1.20, 95% CI 1.13-1.27). Heart rate was not associated with mortality in women aged 18-39 years. In summary, heart rate was a risk factor for mortality from coronary disease, all cardiovascular diseases, and all causes in younger men and in middle-aged men and women, and for cancer mortality in middle-aged men and women.

Background. High salt and nitrate intake are considered as risk factors for stomach cancer, but little is known about possible interactions. This ecological study examines the respective importance of both factors for stomach cancer mortality at the population level using data obtained under standardized conditions and with biochemical analyses performed in the same laboratories. Method. Randomly selected 24-hour urine samples from 39 populations, sampled from 24 countries (N = 5756 people for sodium, 3303 for nitrate) were obtained from the INTERSALT study. Median sodium and nitrate levels were age- and sex-standardized between ages 20-49 years and averaged per country. Ecological correlation-regression analyses were done in relation to national stomach cancer mortality rates. Results. The Pearson correlation of stomach cancer mortality with sodium for the 24 countries was : 0.70 in men and 0.74 in women (both P < 0.001), and with nitrate : 0.63 (P = 0.001) in men and 0.56 (P < 0.005) in women. In multiple regression of stomach cancer mortality, using sodium and nitrate as independent variables, the adjusted R 2 was 0.61 in men and 0.54 in women (both P < 0.001). Addition of the interaction term (sodium x nitrate) to the previous model increased the adjusted R 2 to 0.77 in men, and to 0.63 in women. The analysis of this model showed that the importance of nitrate as risk factor for stomach cancer mortality increased markedly with higher sodium levels. However, the relationship of stomach cancer mortality with sodium was always stronger than with nitrate. Conclusions. Salt intake, measured as 24-hour urine sodium excretion, is likely the rate-limiting factor of stomach cancer mortality at the population level.

In the Western Electric Company Study, carried out in Chicago, Illinois, data on diet and other factors were obtained in 1958 and 1959 for a cohort of 1,556 employed, middle-aged men. Nutrients included vitamin C and beta-carotene. An index that summarized combined intake of both nutrients was constructed. Mean intakes of vitamin C in the lowest and highest tertiles of the index were 66 and 138 mg/day; corresponding values for beta-carotene were 2.3 and 5.3 mg/day. A total of 522 of 1,556 men died during 32,935 person-years of follow-up, 231 from coronary heart disease and 155 from cancer. After adjustment for potentially confounding factors, relative risks (95% confidence intervals) associated with an increment of 19 points in the index (difference between means of the lowest and highest tertiles) were 0.60 (0.39-0.93) for cancer mortality, 0.70 (0.49-0.98) for coronary disease mortality, and 0.69 (0.55-0.87) for all-cause mortality. These results support the hypothesis that consumption of foods rich in vitamin C and beta-carotene reduces risk of death in middle-aged men.

Background Serum cholesterol (TC) levels and coronary heart disease (CHD) are lower in China than in western countries. This report examines the role of diet in determining TC. Methods Data were collected as part of a cross-sectional study of 10,000 men and women, 35-54 years old, conducted in 1983-1984 in four areas in China. A 10% subsample was surveyed for eating patterns and measurement of blood lipids. Six one-day dietary recalls were collected on each participant. Results Mean daily intake of energy from fat was less than 30%. Mean Keys scores ranged from 20.4 to 32.6. In multivariable regression analysis controlling for age, body mass index (BMI), and alcohol, Keys score was statistically associated with serum TC. A 10-unit greater Keys score was associated with 6.3 mg/dl higher TC and 4.0 mg/dl higher low density lipoprotein cholesterol. Conclusions We conclude that in China the relation of dietary factors to serum lipids is similar to that in populations having high serum TC levels.

The hypothesis that lean persons are more responsive than fat persons to the effects of dietary cholesterol was investigated in 1,903 middle-aged employed men who were examined in 1958 and 1959 as participants in the Chicago Western Electric Study. Change in intake of dietary cholesterol was positively associated with change in serum cholesterol for men in the lowest tertile of body mass index (defined as weight (kg)/height (m)2) (24.2) but not for men in the highest tertile (26.6) after adjustment for change in body mass index and change in intakes of energy and saturated and polyunsaturated fatty acids. A decrease of 150 mg/1,000 kcal in dietary cholesterol was associated with mean changes of -0.46, -0.18, and 0.13 mmol/liter in serum cholesterol for men with body mass indices of24.2, 24.2-26.6, and26.6, respectively. Body mass index was strongly correlated with subscapular skinfold thickness; thus, these differences in body mass index reflect true differences in adiposity. These results may help to explain inconsistencies that have occurred in feeding experiments with dietary cholesterol, and they suggest that a reduction in dietary cholesterol should have a more favorable effect on the serum cholesterol levels of fat persons after they have lost weight.

In 1983 and 1984, surveys were conducted in four Chinese population samples, urban and rural for both Beijing and Guangzhou, as part of PRC-USA collaborative research in cardiovascular and cardiopulmonary epidemiology. Serum total cholesterol (TC), HDL-cholesterol (HDL-C), and triglycerides (TG) were measured in 4280 men and 4695 women aged 35-54 years, in laboratories standardized by the US Centers for Disease Control. Age-adjusted mean serum TC was higher in urban than rural samples and generally higher in Beijing than Guangzhou, ranging from 155 mg/dL for Guangzhou rural women to 187 mg/dl for Guangzhou urban women. Group mean values of HDL-C varied from 48 to 59 mg/dl, higher in Beijing than Guangzhou, and higher in women than men. TC/HDL-C ratio ranged from 3.05 to 3.82. Serum TG values were higher for Beijing than Guangzhou; the lowest group mean values of 78 mg/dl and 75 mg/dl were in rural Guangzhou men and women. Mean body mass index (BMI) was uniformly low, ranging from 20 kg/m2 for rural Guangzhou to 24 kg/m2 for urban Beijing. Multiple regression analyses showed that BMI was positively and independently related to serum TC, LDL-C, TG, and TC/HDL-C, and inversely related to HDL-C. Smoking was positively related in both sexes to TG and TC/HDL-C, and inversely related to HDL-C. Smoking was also positively related to TC and LDL-C in men. In men, alcohol was positively related to TC and HDL-C, and was inversely related to TG and TC/HDL-C. Heavy manual work was inversely related to TC, LDL-C, and TC/HDL-C in men, but not related to lipids in women. Thus, for these Chinese population samples, despite their lower serum TC and BMI, the correlates of serum lipids are similar to those in western populations. These variables accounted for only part of the observed urban-rural and north-south differences in serum lipids among these Chinese population samples. The significance of the relatively low serum TC and TG and high HDL-C in relation to low cardiovascular disease in Chinese populations is the object of further investigation in follow-up studies.

While only a small percentage of the population has high blood pressure, a much larger segment of the US population has a high-normal (above optimal) blood pressure, and is at increased risk for hypertension and its cardiovascular sequelae. Hypertension is thus a population-wide problem and must be approached in much the manner of other epidemic diseases. This paper examines some recent population studies and proposes directions for future research.

The hypothesis that dietary cholesterol is positively associated with lung cancer was investigated in a 24-year cohort study of 1,878 middle-aged men who were employed in 1958 by the Western Electric Company in Chicago. The relative risk of lung cancer associated with an increment in dietary cholesterol of 500 mg/day was 1.9 (95 percent confidence interval 1.1-3.4) after adjustment for cigarettes, age, and intake of beta-carotene and fat. Results suggested that the association was specific to cholesterol from eggs. Further research is needed to understand the basis for this association.

The relation of post-load plasma glucose to 12-year cancer mortality was studied in 11,521 white men and 8,591 white women aged 35-64 years at entry in the Chicago Heart Association Detection Project in Industry. There were 298 deaths in which cancer was the underlying cause in men and 186 such deaths in women. Plasma glucose levels at baseline measured one hour after a 50 g oral glucose load were positively related to cancer mortality in men but not in women. This increased mortality in men persisted after controlling for age, body mass index, smoking, serum cholesterol, systolic blood pressure, education, and anti-hypertensive treatment. A site-specific analysis of the male cancer deaths demonstrated higher mean plasma glucose levels for decedents for nearly all sites except oral cancers, liver cancer, and other respiratory cancers. For women, elevations existed for those who died of colon, lung, and hematologic/lymphatic tumors, but not for most other sites. The associations between baseline post-load plasma glucose levels and cancer mortality were similar for earlier and later cancer deaths, which indicates that incipient or occult neoplasm at baseline was not responsible for elevated glucose levels in men who subsequently died of cancer. Cancer mortality rates were also higher for those with a clinical diagnosis of diabetes than for those without, but the numbers of persons with diabetes were small as were the numbers of cancer deaths (19 in the men and 10 in the women).

This paper explores time trends in racial differences in hypertension and in mortality from complications from hypertension in the United States. Mortality data were derived from death certificate data compiled by the National Center for Health Statistics and presented in the 1981 Report of the Working Group on Arteriosclerosis. Prevalence data were obtained from five populations--6,672 people screened in 1960-1962 by the National Health Examination Survey (NHES); 20,749 screened in 1971-1975 by the Health and Nutrition Examination Survey (HANES I); 158,539 screened in 1973-1974 by the Hypertension Detection and Followup Program (HDFP); 1 million persons screened in 1973-1975 by the Community Hypertension Evaluation Clinics (CHEC); and 20,325 screened in 1976-1980 by the second Health and Nutrition Examination Survey (HANES II). Mortality data indicate that the nonwhite/white ratios for mortality from complications of hypertension increased between 1940 and 1967 and decreased between 1968 and 1978. Prevalence data show a corresponding recent decrease in black minus white mean blood pressure. Some of the decrease appears to be due to a greater improvement in hypertension control for blacks than for whites. Time trends in the black/white ratio in prevalence of hypertension were examined with differential treatment effects controlled by inclusion as hypertensive those on drug therapy. The results indicate that in addition to differential changes in therapy, the ratio of black/white prevalence of hypertension may also be decreasing. Additional studies are needed to confirm this finding and to explore time changes in racial patterns of risk factors for hypertension.

The associations between heart rate and death from the cardiovascular diseases (CVD), coronary heart disease (CHD) and sudden death from CHD, along with death from all causes and non-cardiovascular causes, are examined for three groups of middle-aged white males: 1233 men aged 40-59 years followed for 15 years from the Chicago Peoples Gas Company study; 1899 men aged 40-55 years followed for 17 years from the Chicago Western Electric Company study; and 5784 men aged 45-64 years followed an average of five years from the Chicago Heart Association Detection Project in Industry. In univariate analyses, mortality from both cardiovascular and non-cardiovascular causes generally increases with increasing heart rate. In bivariate analyses, using the Cox regression model to control for age, heart rate is significantly related to mortality from all causes in each study, with the associations again due to both cardiovascular and non-cardiovascular causes. In multivariate Cox regression, controlling for age, blood pressure, serum cholesterol, cigarettes smoked per day and relative weight, heart rate is a significant risk factor for sudden CHD death and non-CVD death in two of the three studies, with the association with sudden death being U-shaped in one of the studies. Although heart rate may be an independent risk factor for sudden CHD death, the associations with other CVD death and non-sudden CHD death, in general, appear to be secondary to associations between heart rate and other cardiovascular risk factors.

This study assessed the relationship of per capita coffee imports and consumption, total dietary fat, saturated fat, cholesterol, tobacco, cigarettes, and national income for 1957-1965 to age-adjusted pancreatic cancer death rates of men and women from 22 countries in 1971-1974. With simple correlation analysis, coffee, total dietary fat, saturated fat, and national income were each significantly correlated with both male and female pancreatic cancer mortality. Bivariate partial correlation coefficients of coffee with pancreatic cancer mortality were significant (one-tailed) in 11 of 12 analyses and borderline significant in two-way analyses of variance (ANOVA) (two-tailed) controlling for each of the other variables. Saturated fat and pancreatic cancer were also significantly related in univariate analyses, and in 11 of 12 bivariate partial correlation analyses; in ANOVA, significance was borderline in 10 of 12 analyses. Total fat and pancreatic mortality were also significantly associated in most of the univariate and bivariate correlation analyses, but not in the two-way analyses of variance. The findings of this study are consistent with the hypothesis that coffee and dietary lipid are involved in the etiology of pancreatic cancer.

The relations between coffee consumption and 19-year mortality from all causes, coronary heart disease, and non-coronary causes were assessed in 1,910 white males aged 40-56 years in 1957-1958 from the Chicago Western Electric Company Study. Mortality rates, adjusted for age, serum cholesterol, diastolic blood pressure, and smoking status, were compared for those consuming 0-1, 2-3, 4-5, and 6+ cups of coffee per day; coffee intake, measured at the first anniversary examination, included both caffeinated and decaffeinated intake. Mortality from all causes was greatest in the highest and lowest intake groups. The increased mortality in the 6+ cups per day group was due to coronary heart disease, while the increased mortality in the lowest intake group was due to noncoronary causes. The adjusted relative risk of coronary heart disease death for those drinking 6+ cups of coffee per day compared with those drinking less was 1.71 (95 per cent confidence limits 1.27, 2.30). This increased risk of coronary heart disease death was present in both smokers and nonsmokers, with adjusted relative risks of 1.62 and 2.21, respectively (95 per cent confidence limits 1.17, 2.24 and 1.06, 4.62). The increased mortality from non-coronary causes in the lowest intake group was due primarily to increased mortality from cancer and cardiovascular diseases other than coronary heart disease. The results of this study support the hypothesis that those who drink 6+ cups of coffee per day may be at an increased risk of death from coronary heart disease.

This epidemiologic study explored the sex differential in risk of death from coronary heart disease in persons with or without clinically diagnosed diabetes or asymptomatic hyperglycemia. Use was made of 9-year follow-up data from the Chicago Heart Association Detection Project in Industry for 11,220 white men and 8,030 white women aged 35-64 years at entry to the Project (November 1967-January 1973). Both clinically diagnosed diabetes and asymptomatic hyperglycemia were associated with an increased risk of death from coronary heart disease. The extent of this association was greater in women than in men in regard to relative risk. However, absolute excess risk for both diabetics and those with asymptomatic hyperglycemia was larger for men than for women. Clinical diabetes appeared to be an independent risk factor for coronary heart disease in both men and women based on multivariate Cox regression analyses. On the other hand, for men, no significant independent effect of asymptomatic hyperglycemia was apparent. Women with asymptomatic hyperglycemia had significantly higher coronary heart disease death rates than normoglycemic women, with adjustment for major coronary heart disease risk factors; in multivariate analyses, the relationship of asymptomatic hyperglycemia to risk of coronary heart disease was of borderline significance (p = 0.054). This study indicates the independent associations of diabetes and possibly asymptomatic hyperglycemia with coronary heart disease mortality, with greater relative significance in women than in men.

The relationship between heart rate and cancer mortality was examined in 3 Chicago epidemiologic studies: 1233 white men originally age 40-59 followed 18 years from the Chicago Peoples Gas Company study; 1899 white men originally age 40-55 followed 17 years from the Chicago Western Electric Company study; 5784 white men originally age 45-64 followed 5 years from the Chicago Heart Association Detection Project in Industry. There was a significant association between heart rate and cancer mortality in both univariate and multivariate analyses in men from the Gas Company study and in men from the Chicago Heart Association study, but there was no association between heart rate and cancer mortality in men from the Western Electric study. The relationship persisted in the Gas Company study but not in the Chicago Heart Association study after eliminating deaths within the first 2 years of follow-up. With cancer deaths broken down by the site, mortality from lung and colon cancer in the Gas Company study and mortality from lung cancer in the Chicago Heart Association study were significantly associated with baseline heart rate on univariate analysis and on bivariate analysis controlling for age. Only colon cancer in the Gas Company, however, remained associated with heart rate when other variables were controlled. Thus, in 2 of the 3 studies examined, heart rate appeared to be an independent risk factor for cancer mortality in men.

A total of 417 individuals from all four major sex-race groups were examined for the rate of sodium flux via the countertransport pathway and the sodium concentration within red cells. The age span was from early adolescence to retirement. Males of both races had sizable higher countertransport rates than did women (p less than 0.01), and a slight increase in sodium concentration (p greater than 0.05). Contrariwise, while whites or both sexes had higher countertransport than their black counterparts, sodium concentration was higher in blacks than whites (p less than 0.01). This pattern is not consistent with a direct relationship between both countertransport or sodium concentration and blood pressure which applies across both racial groups. Sex-race differences must be taken into account in any group comparisons of these variables.

Behavior pattern was assessed by interview for 3,110 men at eight centers in the Multiple Risk Factor Intervention Trial (1973-1976). The Type A pattern was not significantly associated with risk of first major coronary events (coronary death and definite nonfatal myocardial infarction) after a mean follow-up of 7.1 years. Crude relative risks for Types A1-A2 versus X-B were 1.08 in usual care, 0.82 in special intervention, and 0.92 overall. Adjustment for age, blood pressure, cigarette smoking, serum cholesterol, consumption of alcohol, and educational attainment yielded relative risks of 0.99 in usual care, 0.81 in special intervention, and 0.87 overall (95% confidence interval = 0.59-1.28). The Jenkins Activity Survey Type A score, obtained for 12,772 men at all 22 centers, was also not significantly associated with risk of first major coronary events. Overall, crude risks in the lowest (Type B) through highest (Type A) quintiles of the score's distribution were 5.0%, 4.4%, 4.0%, 4.3%, and 4.1%, respectively. The proportional hazards regression coefficient, adjusted for the variables listed above, was -0.006 (95% confidence interval = -0.015-0.003). These results raise questions regarding the robustness of the Type A hypothesis in its present form. Further studies are needed to investigate these questions and to evaluate the validity of procedures used to assess behavior patterns.

In the Chicago Western Electric Company study, diet was assessed at the initial examination, in 1957-1958, of 1900 middle-aged men and again at their second examination about one year later. At the first examination, lipid composition of the diet, as summarized by a score based on the formula of Keys, Anderson and Grande (Grande, F. Predicting change in serum cholesterol from change in lipid composition of the diet. In: Lauer RM, Shekelle RB, eds. Childhood Prevention of Atherosclerosis and Hypertension. New York: Raven Press, 1980:145-53), was positively associated with level of serum cholesterol. Between the first and second examinations, however, hypercholesterolemic men were more likely than others to have reduced intake of dietary saturated fatty acids and cholesterol. As a result, at the second examination the cross-sectional linear association between the diet score and serum cholesterol concentration was significantly positive for men with initial levels of serum cholesterol less than 250 mg/dl, significantly negative for men with initial levels of 250 mg/dl or higher and not significantly different from zero for all men together. The bias introduced by change in diet among hypercholesterolemic men differs importantly from bias due to unreliability of measurement and to interindividual differences in intrinsic level of serum cholesterol, because it can produce statistically significant but spurious correlations.

The experience of recent decades demonstrates the varied and rich opportunities for research in international comparisons of patterns, trends and determinants of CHD mortality. Limitations and pitfalls there are too, of course, as with every scientific method, but these can be anticipated and taken into consideration in a reasonable fashion. Particularly when considered along with the totality of the data from epidemiology and the other investigative methodologies, these data from international comparisons are very valuable in throwing light on the aetiological factors influencing CHD mortality trends in different countries, and therefore in illuminating needs for preventive efforts, both national and international.