G. A Kaplan

Identifying biological and behavioural causes of diseases has been one of the central concerns of epidemiology for the past half century. This has led to the development of increasingly sophisticated conceptual and analytical approaches focused on the isolation of single causes of disease states. However, the growing recognition that (i) factors at multiple levels, including biological, behavioural and group levels may influence health and disease, and (ii) that the interrelation among these factors often includes dynamic feedback and changes over time challenges this dominant epidemiological paradigm. Using obesity as an example, we discuss how the adoption of complex systems dynamic models allows us to take into account the causes of disease at multiple levels, reciprocal relations and interrelation between causes that characterize the causation of obesity. We also discuss some of the key difficulties that the discipline faces in incorporating these methods into non-infectious disease epidemiology. We conclude with a discussion of a potential way forward.

The association between an a priori measure of social connections and five-year mortality from all causes, cardiovascular diseases (International Classification of Diseases, Eighth Revision (ICD-8) codes 390-458), and ischemic heart disease (ICD-8 codes 410-414) was studied in 13,301 men and women from eastern Finland who were first interviewed in 1972 or 1977. For men, there was a graded association between extent of social connections and mortality. In multivariate models with adjustment for age, smoking, serum cholesterol, mean weighted blood pressure, measures of prevalent illness, and other possible confounders, men who were in the two lowest quintiles of the social connections scale were at increased risk compared with those in the highest quintile (odds ratio (OR)all cause = 1.54, 95% confidence interval (CI) = 1.21-1.95; ORcardiovascular disease = 1.54, 95% CI = 1.11-2.13; ORischemic heart disease = 1.34, 95% CI = 0.94-1.90). No strong or consistent association was found for women. The association for men was modified by levels of blood pressure with the effect of low social connections greater at higher levels of blood pressure. In three separate analyses, there was no evidence for confounding or effect modification due to prevalent illness at baseline.

Abstract Objective: To examine the association between beer binging (regular sessions of heavy beer drinking) and mortality. Design: Prospective population based study with the baseline assessment of level of alcohol intake (dose), by type of drink and drinking pattern, previous and existing diseases, socioeconomic background, occupational status, involvement in organisations during leisure time, physical activity in leisure time, body mass index, blood pressure, serum lipids and plasma fibrinogen concentration, during an average of 7.7 years' follow up of mortality. Setting: Finland. Subjects: A population sample of 1641 men who consumed beer who were aged 42, 48, 54, or 60 years at baseline. Main outcome measures: All cause mortality, cardiovascular mortality, death due to external causes, fatal myocardial infarctions. Results: The risk of death was substantially increased in men whose usual dose of beer was 6 or more bottles per session compared with men who usually consumed less than 3 bottles, after adjustment for age and total alcohol consumption (relative risk 3.01 (95% confidence interval 1.54 to 5.90) for all deaths; 7.10 (2.01 to 25.12) for external deaths; and 6.50 (2.05 to 20.61) for fatal myocardial infarction). The association changed only slightly when smoking, occupational status, previous diseases, systolic blood pressure, low density lipoprotein and high density lipoprotein cholesterol concentration, plasma fibrinogen concentration, body mass index, marital status, leisure time physical activity, and involvement in organisations were controlled for. Conclusion: The pattern of beer binging is associated with increased risk of death, independently of the total average consumption of alcoholic drinks. The relation is not explained by known behavioural, psychosocial, or biological risk factors. Death due to injuries and other external causes is overrepresented among beer bingers, but a strong association with fatal myocardial infarction suggests that the pathway may also involve other acute triggers of severe health events. Key messages The effects of drinking pattern on mortality and morbidity are less well known than the effects of total alcohol consumption The binging style of drinking beer was associated with the risk of death from any cause and from cardiovascular and external causes and with fatal myocardial infarctions in middle aged men in Finland The association was not explained by the total amount of alcohol consumption, and it remained after adjustments for several potential confounders Strong association of beer binging with deaths from external causes and fatal myocardial infarction suggests that this type of drinking pattern may involve triggers of severe acute events

Abstract Objective: To examine the combined influence of workplace demands and changes in blood pressure induced by stress on the progression of carotid atherosclerosis. Design: Population based follow up study of unestablished as well as traditional risk factors for carotid atherosclerosis, ischaemic heart disease, and other outcomes. Setting: Eastern Finland. Subjects: 591 men aged 42-60 who were fully employed at baseline and had complete data on the measures of carotid atherosclerosis, job demands, blood pressure reactivity, and covariates. Main outcome measures: Change in ultrasonographically assessed intima-media thickness of the right and left common carotid arteries from baseline to 4 year follow up. Results: Significant interactions between workplace demands and stress induced reactivity were observed for all measures of progression (P<0.04). Men with large changes in systolic blood pressure (20 mm Hg or greater) in anticipation of a maximal exercise test and with high job demands had 10-40% greater progression of mean (0.138 v 0.123 mm) and maximum (0.320 v 0.261 mm) intima-media thickness and plaque height (0.347 v 0.264) than men who were less reactive and had fewer job demands. Similar results were obtained after excluding men with prevalent ischaemic heart disease at baseline. Findings were strongest among men with at least 20% stenosis or non-stenotic plaque at baseline. In this subgroup reactive men with high job demands had more than 46% greater atherosclerotic progression than the others. Adjustment for atherosclerotic risk factors did not alter the results. Conclusions: Men who showed stress induced blood pressure reactivity and who reported high job demands experienced the greatest atherosclerotic progression, showing the association between dispositional risk characteristics and contextual determinants of disease and suggesting that behaviourally evoked cardiovascular reactivity may have a role in atherogenesis. Key messages Psychological stress plays an important part in the illness and premature death associated with cardiovascular disease, but individual susceptibility to disease varies according to biological predispositions, personality, behaviour, and environmental exposures This study found that a demanding work environment in combination with a predisposition to exaggerated blood pressure reactivity to stress was significantly related to progression of carotid atherosclerosis over four years among employed middle aged men and was independent of known atherosclerotic risk factors These findings support the role of stress induced reactivity in human atherogenesis Future research needs to confirm these findings in other populations and to examine the influence of other risk factors and environments on the progression of disease

OBJECTIVE: To investigate whether low vitamin E status is a risk factor for incident non-insulin dependent diabetes mellitus. DESIGN: Population based follow up study with diabetes assessed at baseline and at four years. SETTING: Eastern Finland. SUBJECTS: Random sample of 944 men aged 42-60 who had no diabetes at the baseline examination. INTERVENTION: Oral glucose tolerance test at four year follow up. MAIN OUTCOME MEASURES: A man was defined diabetic if he had either (a) a fasting blood glucose concentration > or = 6.7 mmol/l, or (b) a blood glucose concentration > or = 10.0 mmol/l two hours after a glucose load, or (c) a clinical diagnosis of diabetes with either dietary, oral, or insulin treatment. RESULTS: 45 men developed diabetes during the follow up period. In a multivariate logistic regression model including the strongest predictors of diabetes, a low lipid standardised plasma vitamin E (below median) concentration was associated with a 3.9-fold (95% confidence interval 1.8-fold to 8.6-fold) risk of incident diabetes. A decrement of 1 mumol/l of uncategorised unstandardised vitamin E concentration was associated with an increment of 22% in the risk of diabetes when allowing for the strongest other risk factors as well as serum low density lipoprotein cholesterol and triglyceride concentrations. CONCLUSIONS: There was a strong independent association between low vitamin E status before follow up and an excess risk of diabetes at four years. This supports the theory that free radical stress has a role in the causation of non-insulin dependent diabetes mellitus.