Zutphen Study Research Articles

Loneliness and All-Cause, Cardiovascular, and Noncardiovascular Mortality in Older Men: The Zutphen Elderly Study

Loneliness, defined as the discrepancy between one's desired and actual relationships, is prevalent in the elderly and can be both emotional and social loneliness. We aimed to determine whether loneliness is independently related to higher all-cause, cardiovascular, and noncardiovascular mortality in elderly men. Using a population-based cohort study with 25 years of follow-up from 1985, the Zutphen Study, 719 of 939 men (76.2%; age range: 64-84 years) who had complete data on loneliness at baseline and at least 2 years of survival were studied. Loneliness was assessed using a validated 11-item questionnaire in 1985, 1990, 1995, and 2000. Time-dependent Cox proportional hazards models were adjusted for sociodemographic characteristics and cardiovascular risk factors. At baseline, point prevalence of moderate and severe loneliness was, respectively, 38.8% (N = 279) and 3.2% (N = 23). Loneliness, especially emotional loneliness, did significantly increase over 15 years with an overall reliability coefficient of 0.50. All-cause, cardiovascular, and noncardiovascular mortality were not higher among moderately lonely participants (hazard ratio [HR]: 1.00; 95% confidence interval [CI]: 0.84-1.17; HR: 0.99; 95% CI: 0.78-1.25; and HR: 0.99; 95% CI: 0.79-1.24, respectively) and severely lonely participants (HR: 1.40; 95% CI: 0.85-2.31; HR: 1.18; 95% CI: 0.58-2.39; and HR: 1.63; 95% CIH 0.80-3.31, respectively). Loneliness is common and increases during aging, due to the increase in its component emotional loneliness over time. No independent associations with risks of all-cause, cardiovascular, and noncardiovascular death were found.

Pulse pressure trajectories in relation to cardiovascular mortality and dietary protein intake: the Zutphen Study

Pulse pressure trajectories in relation to cardiovascular mortality and dietary protein intake: the Zutphen Study

Effects of early reperfusion on creatine kinase release in patients with acute myocardial infarction: Implications for reperfusion injury

[1] Dekker JM, Schouten EG, Klootwijk P, Pool J, Swenne CA, Kromhout D. Heart rate variability from short electrocardiographic recordings predicts mortality from all causes in middle-aged and elderly men. The Zutphen Study. Am J Epidemiol 1997;145:899–908. [2] Pikkujamsa SM, Huikuri HV, Airaksinen KE, Rantala AO, Kauma H, Lilja M, et al. Heart rate variability and baroreflex sensitivity in hypertensive subjects with and without metabolic features of insulin resistance syndrome. Am J Hypertens 1998;11:523–31. [3] Beske SD, Alvarez GE, Ballard TP, Davy KP. Reduced cardiovagal baroreflex gain in visceral obesity: implications for the metabolic syndrome. Am J Physiol Heart Circ Physiol 2002;282:H630–5. [4] LindgrenK, Hagelin E, HansenN, Lind L. Baroreceptor sensitivity is impaired in elderly subjects with metabolic syndrome and insulin resistance. J Hypertens 2006;24: 143–50. [5] Lucini D, Cusumano G, Bellia A, Kozakova M, Difede G, Lauro R, et al. Is reduced baroreflex gain a component of the metabolic syndrome? Insights from the LINOSA study. J Hypertens 2006;24:361–70. [6] Barthelemy JC, Pichot V, Dauphinot V, Celle S, Laurent B, Garcin A, et al. Autonomic nervous system activity and decline as prognostic indicators of cardiovascular and cerebrovascular events: the ‘PROOF’ Study. Study design and population sample. Associations with sleep-related breathing disorders: the ‘SYNAPSE’ Study. Neuroepidemiology 2007;29:18–28. [7] Parlow J, Viale JP, Annat G, Hughson R, Quintin L. Spontaneous cardiac baroreflex in humans. Comparison with drug-induced responses. Hypertension 1995;25: 1058–68. [8] Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment Panel III). JAMA 2001;285:2486–97. [9] Erdogan D, Gonul E, Icli A, Yucel H, Arslan A, Akcay S, et al. Effects of normal blood pressure, prehypertension, and hypertension on autonomic nervous system function. Int J Cardiol 2011;151:50–3. [10] Arrone LJ, Mackintosh R, Rosenbaum M, Leibel RL, Hirsch J. Cardiac autonomic nervous system activity in obese and never-obese young men. Obes Res 1997;5: 354–9.

Long-term wine consumption is related to cardiovascular mortality and life expectancy independently of moderate alcohol intake: the Zutphen Study

Background:Light to moderate alcohol intake lowers the risk of cardiovascular mortality, but whether this protective effect can be attributed to a specific type of beverage remains unclear. Moreover, little is...

Dietary fiber intake in relation to coronary heart disease and all-cause mortality over 40 y: the Zutphen Study

Background: Little is known about the effects of dietary fiber intake on long-term mortality.Objective: We aimed to study recent and long-term dietary fiber intake in relation to coronary heart disease and all-cause mortality.Design: The effects of recent and long-term dietary fiber intakes on mortality were investigated in the Zutphen Study, a cohort of 1373 men born between 1900 and 1920 and examined repeatedly between 1960 and 2000. During that period, 1130 men died, 348 as a result of coronary heart disease. Hazard ratios were obtained from time-dependent Cox regression models.Results: Every additional 10 g of recent dietary fiber intake per day reduced coronary heart disease mortality by 17% (95% CI: 2%, 30%) and all-cause mortality by 9% (0%, 18%). The strength of the association between long-term dietary fiber intake and all-cause mortality decreased from age 50 y (hazard ratio: 0.71; 95% CI: 0.55, 0.93) until age 80 y (0.99; 0.87, 1.12). We observed no clear associations for different types of dietary fiber.Conclusions: A higher recent dietary fiber intake was associated with a lower risk of both coronary heart disease and all-cause mortality. For long-term intake, the strength of the association between dietary fiber and all-cause mortality decreased with increasing age.

Long-term fish consumption and n-3 fatty acid intake in relation to (sudden) coronary heart disease death: the Zutphen study

To assess the relationship between fish consumption or eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA) intake from fish, and (sudden) coronary death. The impact of recent and long-term fish consumption and EPA+DHA intake on (sudden) coronary death was investigated in the Zutphen Study, a cohort of 1373 men born between 1900 and 1920, and examined repeatedly between 1960 and 2000. Hazard ratios were obtained from time-dependent Cox regression models. The associations between long-term fish consumption, EPA+DHA intake, and (sudden) coronary death were stronger than those of recent consumption. Long-term fish consumption was inversely associated (borderline significant) with coronary heart disease (CHD) death; however, the strength of the association decreased from age 50 [HR: 0.32 (95% CI: 0.13-0.80)] until age 80 [HR: 1.34 (0.58-3.12)]. For men with a daily EPA+DHA intake from fish below 250 mg compared with no intake, CHD death risk was reduced to the same extent as for men with a daily intake above 250 mg (P-value for trend: 0.27). Moreover, long-term fatty-fish consumption lowered the risk of sudden coronary death [HR: 0.46 (0.27-0.78)]. The strength of the association between long-term fish consumption and CHD death decreased with increasing age. Fatty-fish consumption lowered sudden coronary death risk. There was no clear dose-response relationship between EPA+DHA intake and (sudden) coronary death.

A new predictor for the onset of atrial fibrillation?

In this issue of the Netherlands Heart Journal, the results of a substudy of the PREVEND trial are published.1 This prospective registry of presumably healthy citizens of Groningen aims to establish the association between microalbuminuria and the emergence of renal and cardiovascular diseases.2 This general population based long-term study extends the series of previous large-scale epidemiological trials conducted in the Netherlands. We recall among them the 1970 Vlagtwedde study for epidemiological cardiology and ischaemic heart disease, the 1982 Zutphen study of diet and cardiovascular diseases, the 1997 Maastricht study of circulatory arrest and sudden death, the 1998 Amsterdam study of out-of-hospital cardiac arrest and the 1999 Rotterdam study of prolonged QT interval and mortality.

Mortality and life expectancy in relation to long-term cigarette, cigar and pipe smoking: The Zutphen Study

Study objective: To study the effect of long-term smoking on all-cause and cause-specific mortality, and to estimate the effects of cigarette and cigar or pipe smoking on life expectancy. Design:...

AHA Science Advisory. Monounsaturated fatty acids and risk of cardiovascular disease. American Heart Association. Nutrition Committee.

This report summarizes our current understanding of how monounsaturated fatty acids (MUFAs) affect risk for cardiovascular disease (CVD). This is a topic that has attracted considerable scientific interest,1 2 3 in large part because of uncertainty regarding whether MUFA or carbohydrate should be substituted for saturated fatty acids (SFAs) and the desirable quantity of MUFA to include in the diet. MUFAs are distinguished from the other fatty acid classes on the basis of having only 1 double bond. In contrast, polyunsaturated fatty acids (PUFAs) have 2 or more double bonds, and SFAs have none. The position of the hydrogen atoms around the double bond determines the geometric configuration of the MUFA and hence whether it is a cis or trans isomer. In a cis MUFA, the hydrogen atoms are present on the same side of the double bond, whereas in the trans configuration, they are on opposite sides. The American Heart Association Nutrition Committee recently published a scientific statement regarding the relationship of trans MUFA to CVD risk,4 and the present statement, therefore, will be limited to a discussion of dietary cis MUFAs, of which oleic acid ( cis C18:1) comprises ≈92% of cis MUFAs. In the United States, average total MUFA intake is 13% to 14% of total energy intake, an amount that is comparable to (or slightly greater than) SFA intake. In contrast, PUFAs contribute less (ie, 7% of energy). The major emphasis of current dietary guidelines involves replacing SFAs with complex carbohydrates to achieve a total fat intake of ≤30% of calories. There is evidence suggesting that the substitution of MUFA instead of carbohydrate for SFA calories may favorably affect CVD risk.5 6 7 The American Heart Association dietary guidelines for healthy American adults recommend a diet that provides <10% of calories from SFA, up …

Anti-oxidants and cognitive function: a review of clinical and epidemiologic studies.

While the role of diet in heart disease and cancer has received much attention, a possible role for diet in the development of cognitive impairment and dementia is just now being investigated. In this presentation, the putative mechanisms through which anti-oxidants could modulate cellular life in the brain will be briefly discussed. Epidemiologic studies that describe the relation of selected dietary nutrients to cognitive impairment and dementia will be reviewed. In particular, recent results from the analyses of community based follow-up studies, including the Rotterdam Study and the Zutphen Study will be presented. Briefly, these studies provide a mixed picture concerning the relation of anti-oxidants to cognitive impairment or dementia.

Heart rate variability from short electrocardiographic recordings predicts mortality from all causes in middle-aged and elderly men. The Zutphen Study.

Low heart rate variability is associated with high risk of sudden death in myocardial infarction patients. This has been attributed to unfavorable autonomic cardiac control. In the present study, the predictive value of heart rate variability for sudden death, mortality from coronary heart disease, and from all causes was investigated in the general population, using brief electrocardiographic recordings. From 1960 to 1985, 878 middle-aged Dutch men, aged 40-60 years, were followed and repeatedly examined as part of the Zutphen Study. In 1985 the remaining cohort was extended to 885 elderly men, aged 65-85 years, and followed until 1990. Heart rate variability (standard deviation of duration of normal RR intervals) was determined from the resting 12-lead electrocardiogram. The 5-year age-adjusted relative rate of total mortality of men with heart rate variability of < 20 milliseconds (msec) compared with men with heart rate variability of 20-39 msec was 2.1 (95 percent confidence interval 1.4-3.0) in middle-aged men and 1.4 (95% confidence interval 0.9-2.2) in elderly men. Death from noncoronary causes, especially cancer, contributed significantly to this elevated risk. The association of low heart rate variability with sudden death or coronary heart disease mortality was less consistent. In conclusion, in middle-aged men and probably in elderly men, low heart rate variability is predictive of mortality from all causes. This suggests that low heart rate variability is an indicator of compromised health in the general population.

Repeated measurements of vegetables, fruits, beta-carotene, and vitamins C and E in relation to lung cancer. The Zutphen Study.

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.

Dietary flavonoids, antioxidant vitamins, and incidence of stroke: the Zutphen study

Dietary flavonoids, antioxidant vitamins, and incidence of stroke: the Zutphen study

The Cardiac Infarction Injury Score and coronary heart disease in middle-aged and elderly men: The Zutphen study

The Cardiac Infarction Injury Score (CIIS), based on electrocardiographic characteristics, was developed as a measure to determine the presence of myocardial infarctions. In the present study the association of the CIIS with coronary morbidity and mortality was investigated among middle-aged and elderly men. A cohort of 877 men, born between 1900 and 1919, was followed and repeatedly examined from 1960 onwards. In 1985 the remaining cohort was extended to 836 elderly men from the same birth cohort, and followed until 1990. In both middle-aged and elderly men with high CIIS the prevalence of (silent) previous myocardial infarction and the occurrence of ST-T abnormalities were increased. Five-year relative risks of men with CIIS 20 or more relative to men with CIIS < 5 were 2.2 (95% confidence interval: 1.2–4.1) for angina pectoris, 2.4 (1.4–4.0) for myocardial infarction and 5.8 (3.4–9.9) for coronary heart disease death. Thus, the CIIS is associated with risk of coronary heart disease in apparently healthy middle-aged as well as elderly men.

ST segment and T wave characteristics as indicators of coronary heart disease risk: The Zutphen study

This study evaluated the predictive value of T wave amplitude and ST segment level on lead I for angina pectoris, a first myocardial infarction, sudden death and coronary heart disease death in middle-aged and elderly men. Certain ST-T wave characteristics may reflect favorable autonomic cardiac control. Slight ST segment elevation has been reported to indicate a low risk of coronary heart disease mortality. A total of 876 men, born between 1900 and 1920, participated in periodic medical examinations and were followed up with respect to morbidity and mortality from 1960 to 1985. In 1985, the remaining cohort was extended to 836 elderly men from the same birth cohort who were followed up until 1990. Relative risks in categories of T wave amplitude and ST segment level were estimated by survival analysis. Both middle-aged and elderly men with T wave amplitudes > or = 0.15 mV had a lower risk of myocardial infarction, coronary heart disease death and sudden death than men with T wave amplitudes 0.05 to 0.15 mV. The adjusted relative risk of coronary heart disease death was 0.5 (95% confidence interval [CI] 0.2 to 1.0); in men with T wave amplitude < or = 0.05 mV, relative risk was 2.0 (95% CI 1.3 to 3.1). Slight ST segment elevation was also associated with decreased risk: relative risk 0.5 (95% CI 0.3 to 1.0) compared with the isoelectric ST segment level. In men with ST segment depression, relative risk was 2.2 (95% CI 1.4 to 3.4). The association of T wave amplitude and ST segment level were independent of each other. In addition to the elevated risk of coronary heart disease that is associated with ST-T wave abnormalities, we observed that normal variations in repolarization characteristics are predictive of future heart disease.

Association between QT interval and coronary heart disease in middle-aged and elderly men. The Zutphen Study.

Heart-rate-adjusted QT-interval (QTc) is prognostic of sudden death in myocardial infarction patients. So far, population studies have yielded conflicting results on the predictive value of QTc for coronary heart disease morbidity and mortality. Therefore, we investigated this in a longitudinal study of middle-aged and elderly men. From 1960 to 1985, 877 middle-aged men were followed and repeatedly examined in the Zutphen Study. In 1985 the remaining cohort was extended to 835 elderly men from the same birth cohort and followed until 1990. Men with prolonged QTc (420 ms1/2 or more) had a higher risk of myocardial infarction and coronary heart disease death relative to men with QTc less than 385 ms1/2. Age-adjusted coronary heart disease mortality rate ratios were 4.3 (95% confidence interval, 1.3 to 13.8) in middle-aged men and 3.3 (95% confidence interval, 1.0 to 11.6) in elderly men. These associations could not be attributed to prevalent heart disease and were independent of other cardiovascular risk factors. These results indicate that within the normal range of QTc in the general population, men with long QTc are at higher risk for coronary heart disease. Because QTc is easily determined, it may provide a valuable contribution to risk stratification.

Occupation and chronic obstructive pulmonary disease (COPD)

Chronic bronchitis, defined as increased cough and sputum production, is well established as an occupational disease independent of cigarette smoking, which is a major confounding factor. The relevance of industrial exposure to the development of airflow obstruction (chronic obstructive pulmonary disease (COPD)) is more controversial. Good data exist linking the inhalation of cadmium fume to the development of emphysema. The pathology of airflow obstruction due to other occupational exposures is less clear. The principal measure of occupational bronchitis with airflow obstruction is accelerated loss of forced expiratory volume in one second (FEV1); and epidemiology is the principal tool for investigation. Using these methods, many workers have established links between occupational exposure and disease, which will be reviewed. From an occupational standpoint tobacco smoking is unique, in that the pollutant is put into the mouth and deliberately inhaled in concentrations far exceeding occupational exposures. Despite this, less than 20% of smokers develop significant airflow obstruction. The factors which determine whether an individual smoker develops airflow obstruction are usually unknown. There are two ways in which an occupational agent may act: 1) by promoting the deleterious effects of smoking; or 2) by acting in a manner similar to tobacco smoking, requiring other promoting factors before an effect is seen. Examples will be given of both of these mechanisms. From a pragmatic point of view, it is highly unlikely that the mixed agents in tobacco smoke are the only cause of significant COPD. The widespread habit of tobacco smoking in industrial populations has delayed the recognition of other factors contributing to disease, as it is only possible to examine the independent risks of smoking and occupational exposures when a reasonable proportion of those occupationally exposed are lifelong nonsmokers. The studies of specific workforces are often difficult to interpret, as workers commencing exposure in jobs with a high risk of lung disease have even better lung function than the normal worker, and losses from a cohort are higher in those with disease, leading to lower estimates of risk as an increasingly smaller proportion of survivors are followed-up. These problems have been overcome by sampling the general population away from the workplace. Such studies suffer from less selection bias (but exclude those who have died prematurely), and have less satisfactory estimates of occupational exposure, usually including a greater proportion of those with low exposure and, thus, reducing the relative risks of exposure. Such studies have included a general older working population in Beijing (China) [1], an urban and rural population in Norway [2], a rural population in Northern Italy [3], and two studies of city dwellers designed to investigate air pollution in France [4] and the USA [5]. Different outcome measures have been used, but all show significant excess risks with occupation. In general, dust exposure is associated with higher risks of reduced lung function than gas or fume exposure [1, 5], with relative risks of around 1.5. General population samples have been studied longitudinally in Paris [6], Cracow (Poland) [7], Zutphen (Holland) [8] and Bergen (Norway) [9]. The Zutphen study again started with a community sample, using a job matrix to link symptoms and diagnoses with the occupation. The study has been analyzed longitudinally, initially using the time, intensity and duration of exposure. The longitudinal analysis found a cumulative 25 yr incidence of chronic nonspecific lung disease of 27.9%. Incidence density ratios were calculated, and ratios for smoking increased from 1.5 for light smokers to 4.5 for those smoking more than 20 cigarettes daily. Increased risks of chronic nonspecific lung disease (which includes asthma), were found in a number of occupations which are shown in table 1. A further analysis of this study, by the same group, appears in this issue of the Journal [10], using a different job exposure matrix generated from the sample itself. It is disappointing that the results of the reanalysis are less clear than the original analysis, perhaps because of the lack of differentiation between the proportion of the workforce exposed to a particular agent, and its intensity. The mortality analysis was limited by the small number of deaths (33 out of 799) due to chronic nonspecific lung disease. Nevertheless, for occupational groups where at

Occupational exposures estimated by a population specific job exposure matrix and 25 year incidence rate of chronic nonspecific lung disease (CNSLD): the Zutphen Study

The influence of occupational exposures on total mortality and respiratory mortality and morbidity was examined, employing a population specific Job Exposure Matrix (JEM). Moreover, the relationship between time-related variables of exposure to dust and chronic nonspecific lung disease (CNSLD) incidence was analysed, using time since first exposure and duration of exposure. Occupational exposures in the Zutphen cohort were assessed by application of a JEM, arbitrarily considering jobs as exposed when at least 10% of men who had held the job of interest reported an exposure to one or more from a list of 27 chemical agents. None of the exposures was related to mortality due to CNSLD, although results were influenced by the healthy-worker effect and low mortality rates. Exposure to wood dust and a high probability of exposure to dust were associated with total mortality. Exposures to dust and solvents were statistically significantly related to CNSLD incidence. An exposure-response relationship was found for the probability of exposure to dust with CNSLD incidence. Time-related estimates of exposure to dust based on work history were negatively related to CNSLD incidence. The results suggest the presence of a healthy-worker effect, in a general population study, resulting in an underestimation of the relationship between occupational exposures and respiratory diseases based on the evidence published so far. The use of the full work history to determine exposure to dust leads to stronger relationships with CNSLD incidence, compared to conventional analyses using exposure at the start of follow-up.

Dietary risk factors for clinically diagnosed gallstones in middle-aged men. A 25-year follow-up study (the Zutphen Study).

In a long-term follow-up study of middle-aged men, the relation between the intake of energy, nutrients, and foods and the 25-year incidence of clinically diagnosed gallstones was studied. Information on the presence of gallstones was obtained by self-report and verified through medical records after death. Of 860 men, 54 developed symptomatic gallstones, yielding an incidence rate of 3.1/1000 person-years. The present study provides a comprehensive picture of dietary risk factors for clinically diagnosed gallstones based on a long-term follow-up. Calcium intake was inversely associated with gallstone incidence in the univariate and multivariate Cox proportional hazards analyses (hazard ratio (HR) upper tertile: 0.3; 95% CI: 0.1 to 0.7). A positive association with sugars (monosaccharides and disaccharides) appeared after the introduction of age, body mass index, calcium intake, and the intake of energy from nutrients other than sugars into the model (HR upper tertile: 2.3; 95% CI: 1.0 to 4.8). Calcium may alter the composition of bile by preventing the reabsorption of secondary bile acids in the colon, whereas sugars may influence bile composition through lipoprotein metabolism.

The assessment of oily fish intake in two clinic populations

A dietary intake assessment by questionnaire was carried out on 96 patients attending dietetic clinics in Wolverhampton and West Birmingham to ascertain the oily fish consumption in the local population. Only 37.5% of the people questioned ate oily fish more than twice a week. This is the intake recommended by the Zutphen study to be protective against heart disease. The main reasons for the unpopularity of oily fish were: dislike taste/repeats, don't think about it, bones, smell, too oily, don't know how to use it, thought it was fattening. Seventy‐nine per cent of the sample said they would eat more oily fish if recommended by a health professional. Sardines, tuna, kippers and salmon respectively were the most commonly eaten oily fish.