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Objective: To investigate whether average intake of antioxidants, fruits, vegetables and fish may help to explain international differences in chronic obstructive pulmonary disease (COPD) mortality., Design: Ecological analysis using information on baseline diet and the 25-year COPD mortality rate in the 16 cohorts of the Seven Countries Study., Setting: Population-based cohorts., Subjects: Men aged 40-59 years at baseline., Methods: Dietary information was collected at baseline in small random samples of each cohort. In 1987 the reported foods were bought locally and analysed chemically. After 25 years of follow-up the underlying cause of death of those who died was established centrally. COPD mortality rate ratios were calculated, for a change equivalent to 10% of the overall mean consumption of a dietary factor., Results: We observed independent inverse associations between 25-year COPD mortality and baseline consumption of fruits (rate ratio 0.49; 95% confidence interval 0.36-0.67) and fish (rate ratio, 0.97; 95% confidence interval 0.93-1.00), after adjustment for potential confounders. COPD mortality showed no statistically significant association with intake of antioxidants or vegetables. Fruit and fish consumption together explained about 67% of the variance in the COPD mortality rates of the cohorts., Conclusions: Fruit and fish consumption may partly explain population differences in COPD mortality. This is in accordance with suggestions for a relationship between fruit and fish consumption and COPD observed in studies in individuals.

Objective: To relate dietary patterns to cognitive function in elderly men., Design: Cross-sectional study., Setting: Population based., Subjects: 1049 men aged 70-91 years around 1990 in five cohorts from the Seven Countries Study: Finland (2 cohorts), the Netherlands (1 cohort), and Italy (2 cohorts)., Interventions: Food intake was estimated by a cross-check dietary history. Based on the WHO guidelines for the prevention of chronic diseases, a healthy diet indicator was calculated (HDI). A higher HDI indicates a diet more in accordance with the WHO guidelines, and previously we showed that HDI predicted reduced all-cause mortality in our cohorts. Cognitive function was measured using the Mini-Mental State Examination (MMSE), and a score of 23 or lower was used to indicate cognitive impairment., Results: The prevalence of cognitive impairment varied from 14.4% in Zutphen (The Netherlands) to 42.1% in Crevalcore (Italy). There was a tendency towards a lower prevalence of cognitive impairment associated with increased HDI in four out of five cohorts (not in East Finland). In Zutphen this association was borderline significant (OR=0.81; 95% CI 0.63-1.04) after adjustment for age, education, cigarette smoking, alcohol consumption and energy intake. In Crevalcore the association was statistically significant (OR = 0.75; 95% CI 0.58-0.97)., Conclusions: A healthy diet might be associated with a better cognitive function in elderly men. However, since the results were not consistent over all five cohorts, further research is needed to confirm this finding and to decide whether this association is causal.

Background: Little is known about physical activity and mortality risk in the elderly. Therefore, we describe the associations between the physical activity pattern of elderly men and the mortality from cardiovascular diseases (CVDs), particularly coronary heart disease (CHD) and stroke, and all causes., Methods: Self-reported physical activity was assessed with a validated questionnaire for retired men in a population-based sample of 802 Dutch men, aged 64 to 84 years at baseline. Relative risks were estimated for 10-year mortality from CVD (199 deaths), CHD (90), stroke (47), and all causes (373) for tertiles of time spent on physical activity (reference, lowest tertile). Adjustments were made for baseline age, relevant major chronic diseases, cigarette smoking, and alcohol consumption., Results: Mortality risks from CVD and all causes decreased with increasing physical activity (P for trend = .04) with adjusted relative risks of 0.70 (95% confidence interval, 0.48-1.01) and 0.77 (95% confidence interval, 0.59-1.00) in the highest tertile of total physical activity, respectively. Except for CHD, time spent in more intense activities (> or = 4 kcal/kg per hour) was more strongly associated with all mortality outcomes than less intense activities, but no single type of activity was particularly protective. Walking or cycling at least 3 times per week for 20 minutes (our definition of activity based on general health recommendations) was associated with reduced mortality from CVD (adjusted relative risk, 0.69; 95% confidence interval, 0.50-0.88) and all causes (relative risk, 0.71; 95% confidence interval, 0.58-0.88). Additional adjustment for biological cardiovascular risk factors did not affect the strength of any association., Conclusion: In a general population of elderly men, physical activity may protect against mortality from CVDs and all causes.

Objective: To describe the characteristics of patients with diabetes mellitus type 2 who were referred to an outpatient department for insulin therapy., Setting: Hospital De Weezenlanden, Department of Internal Medicine, Zwolle, the Netherlands., Design: Descriptive., Method: Referred patients with diabetes mellitus type 2 visited a diabetes team consisting of internist, diabetes specialist nurse, dietician, and ophthalmologist. After maximizing oral therapy according to the dosage scheme of the national guidelines of the Dutch College of General Practitioners, patients were switched over to insulin therapy if glycaemic regulation remained poor. After improvement and stabilisation of glucose values, patients were discharged to their general practitioners. Initial baseline characteristics of those who were switched over to insulin therapy within 6 months and those who were not were compared., Results: Forty-eight men and 51 women were included. Mean age was 61.2 years (SD: 10.9) (range: 31-84) with a mean duration of diabetes of 8.9 years (SD: 8.3). Oral hypoglycaemic agents (OHA) had been used for 6.7 years (SD: 5.4). Mean glycohaemoglobin content was 10.4% (SD: 2.7) and 47 patients had hyperglycaemic complaints at baseline. Patients switched over to insulin within six months (n = 60; 61%) differed significantly from the non-insulin group (n = 38) in glycohaemoglobin (10.9% (SD: 2.5) versus 9.6% (SD: 3.0)), duration OHA use (7.7 years (SD: 5.6) versus 5.0 years (SD: 4.5)), and body mass index (26.5 kg/m2 (SD: 3.9) versus 29.1 kg/m2 (SD: 5.6)). In women, only the body mass index was significantly different. Main reasons for not switching over to insulin were achieving acceptable control by optimizing OHA, education by diabetes specialist nurse and dietician, treatment of underlying disease or acceptable glycohaemoglobin percentage at baseline. Within six months 62 patients (63%) were discharged to their general practitioners., Conclusion: Referral to secondary care led to improved glycaemic control through maximizing oral therapy, education by the diabetes specialist nurse and dietician, switching over to insulin and diagnosis and treatment of underlying disease.

Background: Data regarding the nature of change in physical activity as elderly people become progressively older are scarce. The present study describes changes in the physical activity pattern of a cohort of elderly Dutch men between 1985 and 1995., Methods: Self-reported physical activity was assessed with a reliable and valid questionnaire designed for retired men. In 1985, 863 men (aged 65-84 years) were examined, in 1990, 520 surviving men, and in 1995, 343 men. Three analytical perspectives (cross-sectional, longitudinal, and time-series) were used concurrently to untangle effects of aging, period, and birth cohort on the 10-year change in physical activity., Results: Mean total time spent on physical activity decreased by 33% (28 min/day) during 10 years of follow-up. Time spent on bicycling, gardening, and total activity decreased with aging. A period effect was observed for time spent on bicycling and total activity in 1990 (increase) and gardening in 1995 (decrease). No differences in physical activity between birth cohorts were observed. Time spent on walking remained stable during follow-up, but its relative contribution to total time spent on physical activity increased with aging. The pattern of change in total activity was not affected by functional status., Conclusions: Mean total time spent on physical activity by elderly men clearly decreased during follow-up. This could not be fully explained by declining functional status, but was partly explained by aging. In contrast to other physical activity parameters, time spent on walking was not affected by aging. These results suggest an increasingly restrictive physical activity pattern with aging.

To test the hypothesis that chronic infection with Chlamydia pneumoniae, Helicobacter pylori or cytomegalovirus is associated with coronary heart disease risk in elderly men, a nested case-control study in a cohort investigated in 1985 and 1990 in the town of Zutphen, The Netherlands, was designed. Fifty-four cases with a first diagnosed coronary event between 1985 and 1990, and 108 age-matched control subjects free of coronary heart disease during follow up were included in the study. The overall prevalence of antibodies to cytomegalovirus was 74.7%, to H. pylori 75.9% and to C. pneumoniae 84.0%. A high level of antibodies to C. pneumoniae was associated with an increased coronary heart disease risk (OR = 2.76; 95% CI = 1.31-5.81). This association was stronger in cases developing both myocardial infarction and angina pectoris, than in cases developing only one of these. This association was independent of potential confounders. Antibodies to cytomegalovirus or H. pylori were not associated with coronary heart disease risk. These results support the hypothesis of a role of chronic C. pneumoniae infections in the immunopathogenesis of atherosclerosis.

The aims of this study were to establish the associations of stature, body mass index, waist to hip ratio, and waist circumference with Type 2 (non-insulin-dependent) diabetes mellitus in a random sample of 5887 men and 7018 women aged 20-59 years in a cross-sectional study set in The Netherlands. The crude prevalence of Type 2 diabetes (overall 1.58% in men, 0.94% in women) was significantly (p < 0.01) higher in shorter subjects and those with high body mass index, high waist to hip ratio, and larger waist circumference. Odds ratios and 95% confidence intervals (95% CI) were adjusted for age, cigarette smoking, alcohol consumption, physical activity, and education. Compared to the tallest tertile of height, odds ratios for Type 2 diabetes were 4.4 (95% CI: 1.3 to 11.5) in men and 1.6 (95% CI: 0.8 to 3.2) in women whose height was in the shortest tertile. Compared to the lowest tertile, odds ratios for Type 2 diabetes were 18.4 (95% CI: 4.3 to 78.5) in men and 5.3 (95% CI: 2.0 to 14.0) in women with waist to hip ratio in the highest tertile, 4.1 (95% CI: 2.0 to 8.4) in men and 2.1 (95% CI: 1.0 to 4.2) in women with body mass index in the highest tertile, and 4.9 (95% CI: 2.1 to 11.7) in men and 2.7 (95% CI: 1.2 to 5.9) in women with waist circumference in the highest tertile. In conclusion, although in longitudinal studies waist is a powerful predictor of diabetes incidence, Type 2 diabetes in a cross-sectional survey is associated with shortness in stature, as well as large waist circumference and high body mass index, and particularly strongly with high waist to hip ratio, suggesting that the development of Type 2 diabetes may modify hip circumference independently of body fat.

To elucidate the role of modifiable factors and the apolipoprotein E polymorphism in explaining lipid profiles reflecting low, average and high risk for coronary heart disease, we selected subjects from a large population-based study. Subjects with low total cholesterol (TC) (< 15th percentile) and high HDL-cholesterol levels (> 85th percentile) were randomly selected (n = 99) and represent subjects with a low risk lipid profile. Additionally, 95 subjects with total and HDL-cholesterol levels in the 15% around the population-median (median risk lipid profile) and 100 subjects with high TC (> 85th percentile) and low HDL-cholesterol levels (< 15th percentile) (high risk lipid profile) were selected. Compared with E3/3 subjects, the likelihood for a low risk lipid profile was considerably higher (odds ratio 14.3; 2.6-79) in female, but not in male E2-carriers (1.5; 0.3-6.7). Smoking and alcohol consumption were independently associated with a low risk lipid profile in both genders, physical inactivity only in women. The odds ratio for a high risk lipid profile was elevated in male E4-carriers (4.9; 1.1-23) only. In addition to the E4 isoform, smoking and physical inactivity, overweight was the main determinant for a high risk lipid profile (odds ratio 16.8; 3.4-82). Male overweight E4-carriers had a 50 times higher likelihood of a high risk lipid profile than E3/3 men of normal weight. In women, only overweight was independently associated with a high risk lipid profile. Our results suggest that both modifiable factors and the apolipoprotein E polymorphism contribute to a lipid profile, reflecting low, average and high risk for coronary heart disease, but effects may be gender-specific.

Within the Seven Countries Study, we investigated whether population differences in 25-year cancer mortality and mortality due to cancer of the lung, stomach, and colorectum could be explained by population differences in adherence to the European Code Against Cancer. Baseline surveys were carried out around 1960 on 12,763 middle-aged men constituting 16 cohorts in seven countries; small samples of the cohorts kept dietary records. In 1987, food equivalent composites representing the average food intake of each cohort at baseline were collected locally and analyzed in one central laboratory. The vital status of all participants was verified after 25 years of follow-up. Overall adherence to the first four recommendations of the European Code Against Cancer was inversely related to 25-year total cancer mortality but not to all-cause mortality. The association with cancer mortality was essentially due to the inverse association for adherence to the guideline on smoking only. Each decrease in the percentage of smokers of 3.4% (10% of range) was associated with a relative risk of 0.93 of dying from cancer. Adherence to the recommendation on consumption of vegetables, fruits, and fiber-rich cereals was inversely related to stomach cancer mortality, whereas adherence to the recommendation on body weight, physical activity, and intake of fat was associated with higher stomach cancer mortality.

Objectives: To investigate to what extent differences in health status between respondents and drop-outs affected the associations between cardiovascular diseases and functional status and self-rated health in a population-based longitudinal health survey in elderly men., Methods: During the 1993 survey of the Zutphen Elderly Study, a non-response survey was carried out. The prevalence of myocardial infarction and stroke, disabilities in basic activities of daily living (BADL) and mobility, and self-rated health were compared between non-respondents (n = 99) and respondents (n = 381). Associations between myocardial infarction and stroke on the one hand and functional status and self-rated health on the other were calculated for the total population and for the respondents to assess the amount of under- or overestimation of these associations., Results: The health of non-respondents was worse than that of respondents in terms of stroke, disabilities in BADL and mobility and self-rated health. Due to this selective non-response, the associations between cardiovascular diseases and functional status and self-rated health were biased. Although most of the associations were slightly overestimated, the most important bias was the underestimation by 57% of the association between stroke and disabilities in BADL [total population: odds ratios (OR) = 6.1, 95% confidence interval (CI) = 2.7-13.9; respondents only: OR = 2.6, CI = 0.7-9.9]., Conclusion: Selective non-response might lead to bias in the prevalence of disease, disabilities and self-rated health as well as in the associations between disease and functional status and self-rated health. The direction and magnitude of this bias varies according to type of disease and health outcome and is therefore difficult to predict. The need to minimize non-response and to investigate its implications is recommended in every study.

Background: The reproducibility of a performance-based and a self-reported measure of functional status was investigated, as well as the impact of age and cognitive function on the reproducibility., Methods: Of a random sample of 114 men of the 1995 survey of the Zutphen Elderly Study, 105 men (aged 79.9 +/- 4.5 years) participated in a test-retest study. They filled out a questionnaire on disabilities and carried out performance tests twice, in a 2-week interval. Four performance tests were administered (standing balance, walking speed, chair stand, and external shoulder rotation), and a summary performance score was constructed. The number of self-reported disabilities in basic activities of daily living, mobility, and instrumental activities of daily living were assessed. Kappa statistics and Pearson correlation coefficients between test and retest measurements were computed for the total group and stratified by age and cognitive function., Results: Three performance tests and the summary performance score had fair to good reproducibility (walking speed: Pearsons r = .90, chair stand: r = .82, shoulder rotation: kappa = .49, summary score: kappa = .52). Only the test for standing balance was poorly reproducible (kappa = .29). The self-reported functional status was fairly to good reproducible (kappa = .63, r = .87). Self-reported functional status was significantly less reproducible in very old and cognitively impaired than in younger and nonimpaired individuals., Conclusions: In the elderly male subjects, performance tests and self-reported disabilities had moderate to good reproducibility, with the exception of the test for standing balance. In very old or cognitively impaired populations, self-reported functional status may have a lower reproducibility.

Objectives: Patients with non-insulin-dependent diabetes mellitus (NIDDM) have been shown to be more obese and have higher waist-to-hips circumference ratios compared to nondiabetics. In this study, we tried to dissociate obesity, waist and hip circumference from NIDDM., Design: A cross-sectional population-based case-control study., Setting: General population., Controls: 5887 men and 7018 women, aged 20-59 years, without known diabetes or hyperglycaemia., Cases: 93 men and 66 women were diagnosed with NIDDM., Main Outcome Measures: We predicted waist and hips' circumference from the body mass index, weight/height2, (BMI) on the basis of linear regression. Differences between observed and expected values (residuals) of waist and hip circumference were categorized into tertiles. The relative odds of having NIDDM in tertiles of waist and hip residuals (middle tertile as reference) were calculated by multiple logistic regression analysis adjusted for each other and for age, smoking, physical activity, alcohol consumption and education., Results: NIDDM was most prevalent in men and women who had larger waists and in those who had smaller hip circumferences than expected from their BMI. Adjusted odds ratios (95% CI) for NIDDM were 2.9 (1.6-5.1) in men and 2.8 (1.5-5.1) in women who had a larger than expected waist, and were 3.7 (2.1-6.5) in men and 2.1 (1.1-3.8) in women who had smaller than expected hips., Conclusions: Our findings suggest that diabetics have larger waists and smaller hips compared to nondiabetics, irrespective of their degree of obesity, age and life-style factors. One possibility is that besides abdominal fatness, peripheral muscle atrophy is one of the factors associated with NIDDM.

Functional status (measured as functional limitations or disabilities) is an important determinant of self-rated health in the elderly. Several issues which are not yet clear in this association are addressed in this study: (i) the modifying effect of age on the association; (ii) the effect of recent changes in disability level on the current level of self-rated health, and (iii) the effect of functional limitations on self-rated health, independent of disabilities. Data were derived from the 1990, 1993 and 1995 surveys of the Zutphen Elderly Study, a longitudinal health study in men born between 1900 and 1920. Analyses of repeated measurements were performed with self-rated health as dependent variable and disabilities, functional limitations, age, survey year, and interaction terms as independent variables. Odds ratios were calculated from these models. Men with disabilities in instrumental activities of daily living had no different health ratings than men without disabilities. Those with disabilities in mobility and basic activities of daily living, however, had an odds ratio on poor self-rated health of 4.7 (95% confidence interval: 2.7-7.9) and 8.9 (4.6-17.1) respectively. This association became weaker with increasing age, leading to an absence of a significant association in the oldest group. The current level of self-rated health was only associated with the current level of disabilities. Information on previous levels of disabilities did not contribute to current self-rated health. Functional limitations had a small, but significant, effect on self-rated health when disabilities were taken into account. This study helps in enhancing insight in the complex relationship between functional status and self-rated health in the elderly.

Objectives: This study investigated age-related changes in functional status and self-rated health in elderly men, taking into account changes over time and differences between birth cohorts., Methods: The Zutphen Elderly Study is a longitudinal study of men born in the Netherlands between 1900 and 1920. Functional status and self-rated health were measured in 513 men in 1990, in 381 men in 1993, and in 340 men in 1995. Age, time, and cohort effects were analyzed in a mixed longitudinal model., Results: Longitudinal analyses showed that during 5 years of follow-up, the proportion of men without disabilities decreased from 53% to 39%, whereas the percentage who rated themselves as healthy decreased from 50% to 35%. Cross-sectional analyses confirmed changes in functional status, suggesting an age effect. Time-series analyses confirmed changes in self-rated health, suggesting a time effect. No birth-cohort effects were found., Conclusions: Functional status deteriorates with age, whereas self-rated health is not related to age in men aged 70 years and older. The observed 5-year decline in self-rated health seemed to be due to a secular trend.

Vitamin D status was assessed in 142 elderly Dutchmen participating in a prospective population-based study of environmental factors in the aetiology of non-insulin-dependent diabetes mellitus. Of the men aged 70-88 years examined between March and May 1990, 39% were vitamin D depleted. After adjustment for confounding by age, BMI, physical activity, month of sampling, cigarette smoking and alcohol intake the 1-h glucose and area under the glucose curve during a standard 75-g oral glucose tolerance test (OGTT) were inversely associated with the serum concentration of 25-OH vitamin D (r = -0.23, p < 0.01; r = -0.26, p < 0.01, respectively). After excluding newly diagnosed diabetic patients total insulin concentrations during OGTT were also inversely associated with the concentration of 25-OH vitamin D (r = -0.18 to -0.23, p < 0.05). Hypovitaminosis D may be a significant risk factor for glucose intolerance.

The authors studied the intake of vegetables, fruits, beta-carotene, and vitamins C and E in relation to the incidence of lung cancer. For 561 men from the town of Zutphen, the Netherlands, dietary history information was obtained in 1960, 1965, and 1970. During 1971-1990, 54 new cases of lung cancer were identified. The data were analyzed using Cox proportional hazard analyses, adjusting for age, pack-years of cigarettes, and energy intake. No relation between intake of vitamin E and lung cancer risk was seen. For vitamin C intake, the results pointed to an inverse association, although not entirely consistently. Furthermore, it was observed that participants with low stable intakes (i.e., low in 1960, 1965, and 1970) of vegetables, fruits, and beta-carotene experienced more than twofold increased relative risks of lung cancer than those with high stable intakes. For participants with low average intakes, relative risks were much lower and not statistically significant. The authors conclude that there is no apparent relation of vitamin E to lung cancer risk; however, for beta-carotene, vitamin C, vegetables, and fruit, most studies, including the present one, suggest weak inverse associations. The use of repeated intake measurements to select subgroups with stable, highly contrasting intakes may be a promising approach for studying diet-cancer relations.

Atherosclerosis and thrombosis may lead to cognitive impairment through cerebral infarcts or white matter hyperintensities. Oxidative stress is now seen as a major contributor to the process of atherogenesis. High intake of polyunsaturated fatty acids, e.g., linoleic acid, or low intake of antioxidants can increase oxidative stress. High intake of n-3 polyunsaturated fatty acids and its main source, fish, may reduce the risk of thrombosis. Little is known, however, about the relation between these dietary factors and cognitive function. The authors investigated this relation with data derived from a cohort of men, aged 69-89 years, who were participants in the Zutphen Elderly Study. The 30-point Mini-Mental State Examination was used to assess cognitive impairment in 1990 (score < or = 25 in 153/476 men, 32%) and cognitive decline from 1990 to 1993 (drop > 2 points in 51/342 men, 15%). Food intake was estimated in 1985 and 1990 by the cross-check dietary history method. High linoleic acid intake was associated with cognitive impairment after adjustment for age, education, cigarette smoking, alcohol consumption, and energy intake (odds ratio (OR) for highest vs. lowest tertile = 1.76, 95% confidence interval (CI) 1.04-3.01). Intake of n-3 polyunsaturated fatty acids was not associated with cognitive impairment, whereas high fish consumption tended to be inversely associated with cognitive impairment (OR = 0.63, 95% CI 0.33-1.21) and cognitive decline (OR = 0.45, 95% CI 0.17-1.16). Intakes of beta-carotene, vitamins C and E, and flavonoids were not inversely associated with cognitive impairment or decline. This study raises the possibility that high linoleic acid intake is positively associated with cognitive impairment and high fish consumption inversely associated with cognitive impairment.

We investigated associations of serum albumin with the incidence and mortality of coronary heart disease among men from the Zutphen Elderly Study. In 1985, 820 men were randomly selected from a population age 64-84 years and were followed for 5 years. We adjusted relative risks for traditional risk factors (age, body mass index, diastolic blood pressure, total and high-density lipoprotein cholesterol, smoking, and alcohol consumption) and also for baseline health status indicators (white blood cell count, physician's health score, self-rated health, and history of relevant diseases). Albumin was inversely associated with the incidence of coronary heart disease only among men with elevated total cholesterol levels (> or = 6.5 mmol per liter). The relative risk for a 1-standard deviation increase (2.5 gm per liter) in albumin was 0.60 [95% confidence interval (CI) = 0.38-0.96] and was not altered after additional adjustment for baseline health status. In all men, the relative risk for death due to coronary heart disease was 0.67 (95% CI = 0.49-0.92), and the relative risk was reduced to 0.84 (95% CI = 0.61-1.15) after adjustment for health status. We found comparable health status-adjusted relative risks for mortality from cardiovascular diseases (relative risk = 0.83; 95% CI = 0.67-1.02) and for mortality from all causes (relative risk = 0.86; 0.73-0.99). Independent of traditional risk factors, moderately low serum albumin is predictive of coronary heart disease and all-cause mortality in elderly men. Only part of this relation could be explained by baseline health status.

Background and Purpose: Cerebrovascular disease and the apolipoprotein e4 (APOE*4) allele are both important risk factors for cognitive decline. We investigated the combined effect of APOE*4 and cerebrovascular disease on cognitive decline., Methods: Data are from a cohort of 353 men, aged 69 to 89 years at baseline, living in Zutphen, Netherlands. The 30-point Mini-Mental State Examination (MMSE) was used to measure cognitive decline (drop of > 2 points) from 1990 to 1993 (14% of the sample). Odds ratios (OR [95% confidence interval]) for cognitive decline were adjusted for age, education, and baseline MMSE score., Results: Compared with those without APOE*4 and without a history of cerebrovascular disease, the adjusted OR was 4.7 (1.7 to 12.7) for subjects without APOE*4 but with cerebrovascular disease, 3.3 (1.6 to 6.8) for those with APOE*4 and no cerebrovascular disease, and 17.2 (2.7 to 110.0) for those with both risk factors. The risk for cerebrovascular disease and APOE*4 combined was more than expected from the separate effects. The combined risk of coronary heart disease and APOE*4 was 6.1 (1.7 to 22.3). The analysis of cardiovascular risk factors showed that the risk of cognitive decline was highest in subjects with both APOE*4 and a high cholesterol level, high fibrinogen level, normal blood pressure, or diabetes mellitus., Conclusions: Cerebrovascular disease and APOE*4 may have a synergistic effect on cognitive decline.

Objective: Intake of alpha-linolenic acid may have a beneficial effect on coronary heart disease, but little information is available on the intake and sources of alpha-linolenic acid (C18:3 n-3) in populations. We therefore assessed intake and sources of alpha-linolenic acid in Dutch elderly men., Design and Subjects: Dietary histories were obtained from participants of the Zutphen Elderly Study, a Dutch cohort study. Food consumption data were available from 876 men in 1985 and from 541 of the same men in 1990. Daily intakes of alpha-linolenic acid were assessed using a food table developed for this purpose. Alpha-linolenic acid content of edible fats, seafood and some commonly eaten dishes were mainly derived from chemical analyses of Dutch foods, and other values were obtained from published food tables., Results: Alpha-linolenic acid provided 0.5 +/- 0.1% of energy intake (mean +/- s.d.) or 1.30 +/- 0.46 g/day in 1985, and 1.21 +/- 0.52 g/day in 1990. The Pearson correlation coefficient for intake of alpha-linolenic acid in 1985 and 1990 was 0.34. Margarines were the main source (25.4%), followed by meat and the fats used in cooking meat (10.8%), bread (9.8%) and vegetables (7.8%)., Conclusions: An increase in intake of alpha-linolenic acid, is most easily realized by the use of unhydrogenated oils rich in alpha-linolenic acid such as rapeseed and soybean oil, and of margarines and other fats containing such oils.

Objective: To determine the extent to which reducing the saturated fatty acid composition of a ubiquitously used cooking oil influenced changes in cholesterol concentration in the population during a five year intervention programme in Mauritius., Design: Cross sectional surveys in 1987 and 1992 determined mean total cholesterol concentrations in the population. A random sample of respondents in the 1992 survey completed a nutrition questionnaire that included questions on diet in the previous 24 hours., Setting: Mauritius., Intervention: In 1987 the government of Mauritius changed the composition of the commonly used cooking oil from being mostly palm oil (high in saturated fatty acids) to being wholly soya bean oil (high in unsaturated fatty acids)., Subjects: 5080 and 5162 subjects in 1987 and 1992 cross sectional surveys. 2059 subjects aged 30-64 years were randomly selected from the respondents of the 1992 survey to take part in the nutrition survey., Main Outcome Measures: Fatty acid composition of phospholipids in pooled serum samples from men and women from the two surveys; measured and predicted change in serum cholesterol concentration., Results: From 1987 to 1992 total cholesterol concentrations fell significantly by 0.79 mmol/l (P < 0.001) in men and 0.82 mmol/l (P < 0.001) in women. The estimated intake of saturated fatty acids decreased by 3.5% of energy intake in men and by 3.6% in women, and the intake of polyunsaturated fatty acids increased by 5.5% and 5.6% of energy intake, respectively. These changes were reflected in changes in the fatty acid composition of serum phospholipids, and according to Keys' formula these changes explained much of the decrease in serum cholesterol concentrations (predicted decrease of 0.38 mmol/l in men and by 0.40 mmol/l in women)., Conclusion: Dietary changes that entailed a reduction in the saturated fat content of a ubiquitous cooking oil explained most of the observed decrease in serum cholesterol concentration over five years in the population of Mauritius.

We investigated cross-sectional as well as longitudinal associations between performance-based measures of functional status and self-reported measures of functional status. In the Zutphen Elderly Study, 494 men, born between 1900 and 1920, were examined in 1990, of whom 303 were reexamined in 1993. A performance score was constructed on the basis of four tests: standing balance, walking speed, ability to rise from a chair, and external shoulder rotation. Self-reported functional status was based on disabilities in basic activities of daily living, mobility, and instrumental activities of daily living. A hierarchic disability scale was constructed. Cross-sectional correlation coefficients between the performance score and the disability scale were 0.22 in 1990 and 0.39 in 1993. Correlations were highest between the test for walking speed and self-reported mobility and IADL, and between the test for external shoulder rotation and self-reported disabilities in basic activities of daily living. The correlation between the 3-year changes in performance and in self-report was 0.20 (p < 0.001). Both performance and self-report at baseline predicted performance and self-report after 3 years. Performance-based measures of functional status are cross-sectionally and longitudinally associated at modest levels with self-reported disabilities. Performance measures and self-reported measures are complementary, but do not measure the same construct.

Objective: To investigate the associations of diastolic blood pressure (DBP) and systolic blood pressure (SBP) with the risk of coronary heart disease, sudden cardiac and all-cause death in elderly men., Design: A cohort study., Setting: The Dutch town of Zutphen., Subjects: Eight hundred and eighty-five randomly selected men, aged 64-84 years., Main Outcome Measures: Relative risks adjusted for age, body mass index, total and high-density lipoprotein cholesterol, cigarette smoking, alcohol consumption, use of blood pressure-lowering medications without a specific indication for hypertension, and the physician who measured the blood pressure., Results: Neither DBP nor SBP was associated significantly with the incidence of a first coronary heart disease event and no clear associations were observed with mortality from coronary heart disease. However, positive associations with sudden cardiac death were observed. The adjusted relative risk for men with definite isolated systolic hypertension was 9.20. The risk of dying from coronary heart disease not recorded additionally as sudden death was highest in men at the lower end of the DBP and SBP distributions and in men using antihypertensives. DBP and SBP were positively associated with all-cause mortality when possible comorbidity at the time of the blood pressure measurement was accounted for. Overall, the highest risk for all endpoints was observed in men on antihypertensive medication, who formed a distinct group with a clustering of cardiovascular risk factors., Conclusion: Elevated DBP and SBP, and especially isolated systolic hypertension, are important predictors of sudden cardiac death in elderly men. The highest risk of non-sudden coronary heart disease mortality was found at the lower end of the blood pressure distributions and among men on antihypertensive medication.

The association between plasma fibrinogen, factor VII, factor X, activated partial thromboplastin time, antithrombin III and the lifestyle factors cigarette smoking, alcohol use, fat intake and physical activity was assessed in 802 men aged 70-90 years in Zutphen (The Netherlands), Montegiorgio and Crevalcore (Italy). Smoking was positively associated with fibrinogen, also after adjustment for other lifestyle factors, age, use of anticoagulants and aspirin like drugs, body mass index, and history of myocardial infarction. Alcohol use was associated with increased levels of factor X and decreased levels of antithrombin III. Fat intake was positively associated with antithrombin III. Between cohorts, considerable differences were observed in levels of haemostatic parameters and the lifestyle factors. Compared to the mediterranean cohorts the Zutphen cohort showed the highest levels of fibrinogen and factor VII. Differences in lifestyle factors could, however, not explain differences between cohorts in levels of any of the haemostatic parameters, despite the observed associations between lifestyle factors and haemostatic parameters.

Background: Within the Seven Countries Study data we investigated whether population differences in 25-year mortality rates from coronary heart disease could be explained by population differences in alcohol, fish, fibre and antioxidant intake., Methods: Baseline surveys were carried out between 1958 and 1964, on 12 763 middle-aged men constituting 16 cohorts in seven countries. In 1987 and 1988 equivalent food composites representing the average food intake of each cohort at baseline were collected locally and analysed for their fibre and antioxidant content in one central laboratory. The vital status of all participants was verified at regular intervals over 25 years., Results: Alcohol and fish intake were inversely related to 25-year mortality from coronary heart disease in univariate analyses. These associations became non-significant when the confounding effects of saturated fatty acids, flavonoids and smoking were taken into account. Fibre and antioxidant vitamins intake were not related to coronary heart disease mortality in either uni- or multivariate analysis., Conclusion: These cross-cultural analyses show that alcohol, fish, fibre and antioxidant vitamins do not explain population differences in coronary heart disease mortality, independently of saturated fatty acids and flavonoids intake and cigarette smoking.

Objectives: This study investigated changes in total and high-density-lipoprotein cholesterol (HDL) concentrations with age and time in elderly men., Methods: A cohort of men born between 1900 and 1920 from the Dutch town of Zutphen was examined in 1977 and 1978 (n = 571), 1985 (n = 885), 1990 (n = 555), and 1993 (n = 345). Linear regression analysis and random-effects models were used to assess cross-sectional and longitudinal age- and time-related changes in cholesterol concentrations., Results: In both cross-sectional and longitudinal analyses, total cholesterol decreased by 0.04 mmol/L a year with age. The longitudinal change was observed in the entire population as well as in men who participated in all four examinations (n = 135) and in a subgroup of men who were free of common chronic diseases, were not on cholesterol-lowering medication or a prescribed diet, and rated themselves as being "healthy" (n = 64). HDL cholesterol did not change significantly with age neither on a cross-sectional nor on a longitudinal basis., Conclusions: Among elderly men, total cholesterol diminishes with age both on a cross-sectional and on a longitudinal basis; HDL cholesterol does not vary with age in any way.

Because the importance of established risk factors for coronary heart disease (CHD) is unclear in older people, the associations of white blood cell (WBC) count with the risk for CHD and all-cause mortality were investigated in an elderly cohort that was followed up for 5 years. In 1985, complete information on the risk factors of interest was available for 884 randomly selected men, aged 64 to 84 years, from the Dutch town of Zutphen (participation rate, 74%). Relative risks (RRs) for each 10(9)/L increase in WBC count were obtained for the 5-year incidence of and mortality from CHD and all causes. RRs were adjusted for age, body mass index, systolic blood pressure, total and high density lipoprotein cholesterol levels, and cigarette smoking habit. The WBC count was 6.7 +/- 1.8 X 10(9)/L (means +/- SD) at baseline. An increased WBC count was independently associated with mortality due to CHD, and the RR amounted to 1.32 (95% confidence interval [95% CI], 1.15 to 1.51). For the incidence of CHD the RR was 1.14 (95% CI, 0.98 to 1.32). These associations were observed regardless of cigarette smoking habit. Regarding all-cause mortality, the RR amounted to 1.25 (95% CI, 1.17 to 1.35). This association was especially noticeable among former smokers and those who had never smoked. In conclusion, during 5 years of follow-up WBC count predicted CHD and all-cause mortality in elderly men, independent of the conventional risk factors for CHD.

Background: Heredity, obesity and fat distribution may interact with each other in their association with diabetes risk. Therefore we tried to elucidate the role of familial diabetes as effect modifier in the association of obesity, glucose metabolism and lipoproteins with non-insulin-dependent diabetes mellitus., Methods: A cross-sectional study was carried out among 468 elderly men. Within strata of family history, men with diabetes and normal glucose tolerance were compared with respect to anthropometry, characteristics of glucose metabolism and serum lipids., Results: Of the participants, 14.5 percent were diabetic. In diabetic men a family history of diabetes occurred more often (22.1 percent) than in men with normal (6.8 percent, P < 0.001) or impaired glucose tolerance (8.5 percent). In diabetic men with a family history, the ratio of fasting insulin to glucose and the ratio of areas under the insulin and glucose curves during oral glucose tolerance testing were lower compared to men with normal glucose tolerance. In men without a family history, these differences were smaller (interaction P = 0.06). In diabetic men without a family history, fasting insulin levels were markedly elevated (P < 0.001), whereas in men with a family history there was only a slight elevation. The presence of a family history resulted in more severe deteriorations in lipids, especially in fasting triglycerides (interaction P = 0.075). No interaction between indices of obesity and a family history was observed., Conclusions: Our findings suggest that elderly diabetic men with a family history of diabetes represent a different subgroup than elderly men without such a history, characterized by larger deteriorations in indices for beta-cell function and higher triglyceride levels.

Background: Epidemiological studies suggested that consumption of fruit and vegetables may protect against stroke. The hypothesis that dietary antioxidant vitamins and flavonoids account for this observation is investigated in a prospective study., Methods: A cohort of 552 men aged 50 to 69 years was examined in 1970 and followed up for 15 years. Mean nutrient and food intake was calculated from cross-check dietary histories taken in 1960, 1965, and 1970. The association between antioxidants, selected foods, and stroke incidence was assessed by Cox proportional hazards regression analysis. Adjustment was made for confounding by age, systolic blood pressure, serum cholesterol, cigarette smoking, energy intake, and consumption of fish and alcohol., Results: Forty-two cases of first fatal or nonfatal stroke were documented. Dietary flavonoids (mainly quercetin) were inversely associated with stroke incidence after adjustment for potential confounders, including antioxidant vitamins. The relative risk (RR) of the highest vs the lowest quartile of flavonoid intake ( > or = 28.6 mg/d vs <18.3 mg/d) was 0.27 (95% confidence interval [CI], 0.11 to 0.70). A lower stroke risk was also observed for the highest quartile of beta-carotene intake (RR, 0.54; 95% CI, 0.22 to 1.33). The intake of vitamin C and vitamin E was not associated with stroke risk. Black tea contributed about 70% to flavonoid intake. The RR for a daily consumption of 4.7 cups or more of tea vs less than 2.6 cups of tea was 0.31 (95% CI, 0.12 to 0.84)., Conclusion: The habitual intake of flavonoids and their major source (tea) may protect against stroke.

Physical activity pattern and its relation with cardiovascular risk factors was investigated in 1,402 men aged 69-90 years who participated in the 30-year follow-up survey of the Finnish (Eastern and Western Finland), Italian (Montegiorgio and Crevalcore), and Dutch (Zutphen) cohorts of the Seven Countries Study. Physical activity was assessed with a validated self-administered questionnaire designed for retired men. Total physical activity varied largely within cohorts. Median total reported physical activity ranged from 50 minutes/day in Montegiorgio to 89 minutes/day in Crevalcore. Walking, gardening, and bicycling together contributed more than 70% of total physical activity in all cohorts. Depending on the definition of physical inactivity, the estimated prevalence of inactivity varied between 5% and 33% in Zutphen and between 18% and 68% in Montegiorgio. Total physical activity was inversely associated with resting heart rate (r= -0.11, p < 0.001) and was positively associated with high density lipoprotein (HDL) cholesterol (r = 0.08, p < 0.01) in pooled data. These associations remained statistically significant after adjustment for age, cohort, smoking, body mass index, and alcohol intake. Total activity was not associated with total cholesterol, non-HDL cholesterol, blood pressure, or body mass index. The authors conclude that physical activity may have a beneficial effect on HDL cholesterol levels in elderly men. Walking, gardening, and bicycling contribute substantially to their physical activity pattern.

Prolongation of heart rate-adjusted QT length (corrected QT interval [QTc]) is associated with elevated risk of coronary heart disease and sudden death. This may have to do with autonomic cardiac control. Because insulin is known to stimulate sympathetic activity, we studied the association of insulin level and glucose tolerance with QTc. In 1990, 383 elderly men 70-89 years of age without previous myocardial infarctions or known diabetes had a 12-lead electrocardiogram recorded and glucose tolerance determined in the frame of an ongoing follow-up study. QTc was significantly associated with fasting glucose, insulin, and C-peptide and glucose levels 60 and 120 min after an oral glucose load. For fasting C-peptide and the area under the glucose curve (AUGC), this association could not be explained by the concomitant occurrence of other risk factors of coronary heart disease. Furthermore, fasting C-peptide and the AUGC were independently additive predictors of QTc duration. The difference in QTc between men in the extreme quintiles of both variables was 22 ms. QTc prolongation seems to be part of the insulin resistance syndrome. The association may be explained by increased sympathetic activity induced by high insulin levels. An additional explanation could be an effect of high insulin, impaired glucose utilization, or both on membrane activity of myocardial cells.

The authors examine the cross-sectional and longitudinal relation of smoking habits and current alcohol intake to cognitive status and decline over a 3-year period as well as the extent to which these relations are modified by the presence of clinical conditions indicating atherosclerosis (cardiovascular disease (CVD)/diabetes). Data are from the cohort of men followed in the longitudinal Zutphen Elderly Study in 1990 (n = 489) and 1993 (n = 333). Cognitive function was measured in 1990 and 1993 with the 30-point Mini-Mental State Examination (MMSE). After adjustment for age, education, and alcohol intake, current smokers made 20% more errors on the MMSE than never smokers in the cross-sectional analyses. Cognitive decline was greatest in those with CVD/diabetes who currently smoked and never smoked (-1.9 and -1.3 points, respectively). After adjustment for age, education, and smoking status, men with CVD/diabetes and low-to-moderate alcohol intake had a significantly lower risk for poor cognitive function (MMSE < or = 25) than abstainers (odds ratios of 0.3 for less than one drink and 0.2 for one to two drinks per day). Alcohol intake was not associated with cognitive decline. These findings do not support the hypothesis of a protective effect of smoking on cognitive function; they suggest that smoking may be harmful among those with CVD/diabetes. Alcohol may result in an acute beneficial effect on cognitive function among those with CVD/diabetes. However, selection bias and unmeasured confounding should be of concern when evaluating these results.

The associations of serum total and high density lipoprotein (HDL) cholesterol with coronary heart disease were investigated in men aged 64-84 years from the Dutch town of Zutphen during 5 years of follow-up. In 1985, 885 randomly selected men, 710 of whom did not have a history of clinical coronary heart disease, participated in the study. Associations were adjusted for age, body mass index, systolic blood pressure, cigarette smoking, and alcohol consumption. Total cholesterol was not significantly associated with the incidence of coronary heart disease, but for mortality the relative risk corresponding to a 1.00 mmol/liter increase was 1.40 (95 percent confidence interval (CI) 1.07-1.83). HDL cholesterol was not associated with mortality from coronary heart disease. The relative risk for the incidence of the disease, corresponding to a 0.26 mmol/liter increase, was 0.80 (95 percent CI 0.60-1.08). For the ratio of HDL cholesterol to total cholesterol, the relative risk for coronary heart disease incidence corresponding to a 0.05 increase amounted to 0.70 (95 percent CI 0.51-0.95). These results show that in elderly men followed for 5 years, both total and HDL cholesterol are important in predicting coronary heart disease. Total cholesterol seems to be a stronger risk factor for mortality from the disease, whereas HDL cholesterol is more strongly associated with the incidence of a first coronary heart disease event.

The associations between serum total and HDL cholesterol and three lifestyle factors--consumption of Turkish coffee, consumption of alcohol, and cigarette smoking--were examined in two Serbian cohorts of the Seven Countries Study. In 1988 and 1989, 319 men from Zrenjanin and Belgrade, 65 to 84 years old and free of myocardial infraction, participated. The men from Zrenjanin were originally working in a large cooperative, and the men from Belgrade were faculty members of the university. HDL cholesterol, alcohol consumption, and cigarette smoking were significantly higher in Zrenjanin than in Belgrade. Serum total cholesterol levels and coffee consumption were not different. ANCOVA showed that serum total cholesterol levels were 8.2% higher (P < .05) in men consuming two small cups of coffee per day compared with abstainers, and this was also seen after adjustment for cigarette smoking, age, body mass index, cohort, and alcohol consumption. In men consuming one or more alcoholic drinks per day (more than 10 g/d alcohol), HDL cholesterol levels were increased by 0.19 mmol/L (15.4%) compared with men consuming no alcohol (P < .001). This association was stronger in the Zrenjanin cohort than in the Belgrade cohort (P < .05). Smoking was not associated with total cholesterol or with HDL cholesterol levels. In Serbian men, boiled Turkish coffee and alcohol consumption are independently associated with serum total and HDL cholesterol levels, respectively.

Objective: To obtain insight into dietary habits of elderly people and how these habits have evolved from middle to old age., Design: Cross-sectional study of dietary patterns around 1990; retrospective cohort study of changes in dietary intake since middle age., Setting: Five cohorts: East and West Finland, Zutphen (Netherlands), Crevalcore (Italy), and Montegiorgo (Italy)., Subjects: Men aged 70-90 years around 1990., Methods: Food intake was estimated using a cross-check dietary history adjusted to the local situation., Results: (i) Cross-sectional: Significant differences were observed between the countries for all food groups, energy and nutrients (P < 0.05). The Finnish diet was characterised by a high consumption of animal products and potatoes, the Italian diet by a high consumption of cereals, vegetables, fruits and alcohol. The Dutch diet was generally intermediate. (ii) Longitudinal: The decrease in energy intake since middle age varied from 4.2 MJ/day in the Finnish cohorts to 2.1 MJ/day in Italy. Also the consumption of most food groups decreased but the consumption of vegetables and fruits increased. Saturated fatty acid intake decreased by 3 E% in the Finnish cohorts and decreased by < 1 E% in Italy. Alcohol intake decreased by approximately 7 E% in Italy while it increased by 2.5 E% in the Netherlands., Conclusions: Although the general patterns of dietary intake of the different cultures still can be recognised at old age, the variation between them has become smaller. Compared to their dietary intake at middle age, however, the dietary pattern of the Finnish and Dutch cohorts has changed slightly in the direction of a healthy diet, while the diet of the Italian men remained Mediterranean, and thus more healthy, at old age.

Cognitive impairment is highly prevalent among the elderly. Subjects with disturbed glucose metabolism may be at risk of impaired cognitive function, as these disturbances can influence cognition through atherosclerosis, thrombosis and hypertension. We therefore studied the cross-sectional association of cognitive function with hyperinsulinaemia, impaired glucose tolerance and diabetes mellitus in a population-based cohort of 462 men aged 69 to 89 years. Cognitive function was measured by the 30-point Mini-Mental State Examination. Results were expressed as the rate ratio (95% confidence interval) of the number of erroneous answers given on the Mini-Mental State Examination by the index compared to the reference group. Compared to subjects with normal glucose tolerance, known diabetic patients had a rate ratio of 1.23 (1.04-1.46), newly-diagnosed diabetic patients of 1.16 (0.91-1.48) and subjects with impaired glucose tolerance of 1.18 (0.98-1.41), after adjustment for confounding due to age, occupation and cigarette smoking (p-trend = 0.01). Non-diabetic subjects in the highest compared to the lowest quartile of the area under the insulin curve had a rate ratio of 1.24 (1.03-1.50), after adjustment for confounding (p-trend = 0.02). The results did not change appreciably when potentially mediating factors, including cardiovascular diseases and risk factors associated with the insulin resistance syndrome, were taken into account. These results suggest that diabetes, as well as impaired glucose tolerance and hyperinsulinaemia in non-diabetic subjects are associated with cognitive impairment.

Background: Increased body iron stores have been suggested as a risk factor for cancer and ischaemic heart disease (IHD). However, all studies carried out to date have focused on relatively young populations although the elderly may also be at increased risk., Methods: We investigated the association between body iron stores and mortality due to cancer and IHD in a 17-year follow-up study of 260 non-institutionalized elderly people aged 64-87 years. Iron status was assessed in 1971 by means of the haemoglobin level, transferrin saturation and total iron binding capacity (TIBC). Information about the vital status and causes of death was obtained in 1988., Results: Among women mortality due to cancer was inversely related to TIBC; the relative risk for the highest tertile of TIBC, adjusted for age, smoking and alcohol intake was 0.05 (95% confidence interval (CI): 0.007-0.39). The risk of mortality due to all-causes was also inversely associated with TIBC. Among men, no association between body iron stores and mortality due to cancer was observed. Mortality due to IHD was not clearly associated with body iron status. Among men, the adjusted relative risk decreased slightly per tertile of transferrin saturation, but this trend was only of borderline significance (P = 0.10)., Conclusions: These results suggest that body iron stores are a risk factor for mortality due to cancer in postmenopausal women. This may be due to accumulation of stored iron among women after menopause. No clear associations with mortality due to IHD were observed in either elderly men or elderly women.

Objective: To investigate the role of diet as a predictor of glucose intolerance and non-insulin-dependent diabetes mellitus (NIDDM)., Research Design and Methods: At the 30-year follow-up survey of the Dutch and Finnish cohorts of the Seven Countries Study, in 1989/1990, men were examined according to a standardized protocol including a 2-h oral glucose tolerance test. Information on habitual food consumption was obtained using the cross-check dietary history method. Those 338 men in whom information on habitual diet was also available 20 years earlier were included in this study. Subjects known as having diabetes in 1989/1990 were excluded from the analyses., Results: Adjusting for age and cohort, the intake of total, saturated, and monounsaturated fatty acids and dietary cholesterol 20 years before diagnosis was higher in men with newly diagnosed diabetes in the survey than in men with normal or impaired glucose tolerance. After adjustment for cohort, age, past body mass index, and past energy intake, the past intake of total fat was positively associated with 2-h postload glucose level (P < 0.05). An independent inverse association with the past intake of vitamin C was observed (P < 0.05). These associations were independent of changes in the intake of fat and vitamin C during the 20-year follow-up. An increase in the consumption of vegetables and legumes, potatoes, and fish during the 20-year follow-up was inversely related with 2-h glucose level (P < 0.05)., Conclusions: Although the regression coefficients were in general not very large, these results indicate that a high intake of fat, especially that of saturated fatty acids, contributes to the risk of glucose intolerance and NIDDM. Foods such as fish, potatoes, vegetables, and legumes may have a protective effect. In addition, the observed inverse association between vitamin C and glucose intolerance suggests that antioxidants may also play a role in the development of derangements in glucose metabolism.

To elucidate the role of hypertension as part of the insulin resistance syndrome, the longitudinal relationships of hypertension and overweight with hyperinsulinaemia and glucose tolerance were examined in the Dutch and Finnish cohorts of the Seven Countries Study (Zutphen, and east and west Finland). Three cohorts of men, born between 1900 and 1919, were first examined in 1959/1960. At the 30-year follow-up survey a 2-h glucose tolerance test was carried out on 619 of the surviving men, and fasting insulin was also measured. Blood pressure and body mass index (BMI) were measured several times during the entire 30-year follow-up period. In cross-sectional analyses, men with diabetes and impaired glucose tolerance at the 30-year follow-up examination had a significantly higher systolic blood pressure and a higher prevalence of hypertension than men with normal glucose tolerance, independent of age, cohort and BMI (p < 0.01). These differences had already been seen 5, 20 and 30 years earlier. Subjects with hyperinsulinaemia (fasting insulin > or = 9.2 mU/l) had a higher BMI and a higher prevalence of hypertension. This cross-sectional association with hypertension was independent of age, cohort and BMI. BMI levels of men with hyperinsulinaemia had been shown to be higher 5, 20 and 30 years earlier, but blood pressure levels had not. These results indicate that hypertension is independently associated with glucose tolerance and insulin resistance in three Caucasian cohorts. Changes in blood pressure precede abnormal glucose tolerance but not hyperinsulinaemia; therefore, glucose tolerance appears to be a stronger correlate of hypertension than hyperinsulinaemia.

Background: We investigated whether dietary patterns were associated with cardiovascular risk factors in 518 elderly men (70-89 years), using data from the 30-year follow-up survey of the Zutphen Study., Methods: Dietary intake was estimated by cross-check dietary history. We used cluster analysis to aggregate individuals into four groups, characterized by high alcohol intake, high meat consumption, healthy dietary pattern, and high intake of refined sugars., Results: In the alcohol cluster socioeconomic status was higher (P < 0.05) than in the meat cluster. High density lipoprotein (HDL)-cholesterol was 0.15-0.23 mmol/l higher (P < 0.05) in the alcohol cluster compared to the other clusters. Furthermore, in the meat cluster HDL-cholesterol was 0.08 mmol/l higher than in the refined sugars cluster (P < 0.05). Total serum cholesterol was 0.26 mmol/l higher in the meat cluster compared to the healthy diet cluster (95% CI: -0.17, 0.69). The prevalence of hypertension was almost 10% higher in alcohol cluster compared to the other three clusters (95% CI: -3, 23). The percentage of non-smokers was highest in the healthy diet cluster. These results were irrespective of potential confounders, such as age, body mass index, socioeconomic status, smoking, and being on a prescribed diet., Conclusions: The effects of moderate alcohol intake on cardiovascular risk factors are confirmed in elderly men. Furthermore, a healthy diet is associated with more favourable levels of cardiovascular risk factors at old age.

Background: A protective effect of a small amount of fish on coronary heart disease (CHD) mortality has been established in observational studies in middle-aged people. In the present study this association was investigated in the elderly., Methods: In 1971 CHD risk factors were measured in 272 people born before 1907. They belonged to a general practice in Rotterdam, the Netherlands and were followed for 17 years. The cross-check dietary history method was used to obtain information on fish consumption., Results: During the follow-up period 58 people died from CHD, 67 from cancer and 187 from all causes. In 1971 about 60% of the elderly ate fish and 40% did not eat fish. Multivariate Cox proportional hazards analyses, taking the confounding effect of major risk factors into account, showed an inverse relation between fish consumption and 17-year CHD mortality. The risk ratio (RR) for fish eaters compared with no-fish eaters was significantly different from unity (RR = 0.51, 95% CI: 0.29-0.89). Cancer and total mortality were not related to fish consumption., Conclusion: The results from the present study suggest that the protective effect of a small amount of fish in relation to CHD observed in middle-aged people seems also to be present in the elderly.

Objectives: To determine whether polymorphism of apolipoprotein E--notably, the e4 allele--predicts cognitive deterioration in the general population., Design: Population based cohort investigated in 1990 and in 1993., Setting: Zutphen, the Netherlands., Subjects: Representative cohort of 538 Dutch men aged 70-89 at baseline., Main Outcome Measures: Cognitive function assessed by mini mental state examination, change in cognitive function and incidence of impaired cognitive function at three years., Results: The baseline prevalence of impaired cognitive function (mini mental state examination score < or = 25) was higher among carriers of the e4 allele compared with men without the allele (41.0% (55) v 31.1% (122) P = 0.03), and this result was still valid after adjustment for age, occupation, smoking, alcohol use, and cardiovascular diseases. The decline in cognitive function at three years was largest in men homozygous for e4 (-2.4 points), intermediate in those heterozygous for e4 (-0.7 points), and lowest in men without e4 (-0.1 points), and it was independent of other risk factors (P = 0.02). The risk of developing impaired cognitive function during follow up was significantly increased in allele carriers compared with non-carriers (27.6% (16/58) v 15.5% (32/207)). The adjusted odds ratio was 2.87 (95% confidence interval 1.29 to 6.42). Twenty two per cent of the risk of developing impaired cognitive function in this population may be attributable to the e4 allele., Conclusions: The apolipoprotein e4 allele predisposes to cognitive decline in a general population of elderly men.

We investigated the association between fasting insulin concentration--an indicator of insulin resistance in nondiabetic individuals--cardiovascular risk factors, and coronary heart disease in a study of 390 men in the town of Zutphen. In 1990, an extensive examination was carried out on the participating men (aged 70 to 89 years). Fasting insulin levels were determined and a number of other risk factors measured. Known and newly diagnosed diabetics were excluded from the data analyses. Fasting insulin concentration was significantly associated with levels of glucose, triglycerides, uric acid, serum albumin, creatinine, and fibrinogen as well as resting heart rate. Inverse associations with high-density lipoprotein cholesterol and factor VII activity were observed. These results were independent of confounding factors such as age, body mass index, ratio of subscapular to triceps skinfold thicknesses, cigarette smoking, physical activity, and alcohol consumption. Men with a fasting insulin level higher than 80 pmol/L (highest quartile of the distribution) had a significantly higher prevalence of coronary heart disease and especially of myocardial infarction. This result was independent of potential confounding variables as well as of possible intermediates (total and high-density lipoprotein cholesterol, hypertension, serum triglycerides, fasting glucose, and other risk factors related to fasting insulin) (odds ratio, 2.2; 95% confidence interval, 1.2-4.0). No association between fasting insulin level and hypertension or blood pressure was observed. These results show that fasting insulin is an important indicator of coronary heart disease in elderly men. Clotting factors, resting heart rate, uric acid, serum albumin, and creatinine may also play a role in this metabolic syndrome.

The relation of dietary factors and physical activity to hyperinsulinemia was examined in 389 men aged 70-89 years who participated in the Zutphen Elderly Study in 1990. Information about the usual diet was obtained using a cross-check dietary history, and habitual physical activity was assessed using a validated questionnaire. Known and newly diagnosed diabetic patients were excluded from this study, since serum insulin and C-peptide levels are indicators of insulin resistance and hyperinsulinemia in non-diabetics only. Insulin levels during the oral glucose tolerance test were lowest in men with the highest physical activity. This inverse association was independent of age, body mass index, the ratio of subscapular to triceps skinfold thickness, cigarette smoking, and energy intake (p < 0.001). In addition, insulin levels were inversely associated with the intake of dietary fiber and polyunsaturated fatty acids, which could not be accounted for by variables such as energy intake, body mass index, physical activity, prescribed diets, or the presence of coronary heart disease. In contrast, insulin levels increased with the increasing intake of saturated fatty acids and alcohol. The fasting C-peptide level was independently associated with the intake of total fat, saturated and monounsaturated fatty acids, and alcohol, whereas an inverse relation with the intake of total carbohydrates and dietary fiber was seen. Besides overweight, physical activity and dietary factors such as the intake of fatty acids, fiber, carbohydrates, and alcohol, were independently associated with hyperinsulinemia and insulin resistance. Therefore, these behavioral factors may partly determine the occurrence of non-insulin-dependent diabetes mellitus and coronary heart disease and play a role in the prevention of these disorders.

Background and Purpose: A low-to-moderate average daily fish consumption has been reported to convey protection against coronary heart disease incidence and mortality. Currently there is no information about its effect on stroke risk., Methods: In 1960, 1965, and 1970 cross-check dietary histories were obtained in 552 men aged 50 to 69 years in 1970 in the town of Zutphen, The Netherlands. The association between fish consumption and stroke incidence in the period 1970 to 1985 was assessed by Cox proportional hazards models. Adjustments were made for confounding by age, systolic blood pressure, cigarette smoking, serum total cholesterol, energy intake, alcohol consumption, and prescribed diet., Results: The mean fish consumption in 1970 was 17.9 g/d. Men who consumed more than 20 g of fish per day in 1970 had a reduced risk of stroke compared with those who consumed less fish. The hazard ratio (HR) amounted to 0.49 (95% confidence interval [CI], 0.24 to 0.99), and did not change after adjustment for potential confounders. Fewer strokes occurred among the 301 men who always reported fish consumption between 1960 and 1970 than among the men who changed fish consumption habits between 1960 and 1970 or did not consume fish at all (HR, 0.63; 95% CI, 0.34 to 1.16)., Conclusions: These results suggest that consumption of at least one portion of fish per week may be associated with a reduced stroke incidence.

Serum total cholesterol (TC) and systolic blood pressure (SBP) were investigated as risk factors for mortality from ischemic heart disease among 272 elderly men and women during 17 years of follow-up. For men, TC was not significantly associated with mortality from ischemic heart disease. Among women, a significant positive association was found (p-trend = 0.03 when adjusted for age, body mass index, SBP, alcohol consumption, smoking, and the prevalence of myocardial infarction, angina pectoris and diabetes mellitus). Among women a significant positive association was also observed for SBP after adjustment for all potential confounders (p-trend = 0.05). Among men, the adjusted association with SBP was not statistically significant. The results suggest that TC and SBP are stronger independent risk factors for mortality from ischemic heart disease among elderly women than among elderly men. These differences between genders may be due to selective mortality among middle-aged men and physiological changes in women during menopause.