Dietary atherogenicity and thrombogenicity indexes predicting cardiovascular mortality: 50-year follow-up of the Seven Countries Study.

BACKGROUND AND AIM: To study the relationships of an Atherogenicity Index (ATI) and a Thrombogenicity Index (THI), with 50-year mortality from coronary heart disease (CHD), other heart diseases of uncertain etiology (HDUE) and cerebrovascular disease or stroke (STR), in 16 international cohorts of middle-aged men. METHODS AND RESULTS: Foods from a dietary survey in subsamples of men in each cohort of the Seven Countries Study (SCS) were chemically analyzed for several types of fatty acids that were converted into ATI and THI identifying each of 16 cohorts. Ecological correlations of the ATI and THI were calculated with the three fatal CVD conditions and with all-cause mortality at 25 and 50 years. Correlation coefficients (Rs) were positive and highly significant between ATI and THI versus CHD mortality, with levels ranging from 0.79 to 0.97, depending on the duration of follow-up and the choice of 10 or of 16 cohorts. This was not the case for HDUE and STR mortality for which Rs were variable and not significant. A strong direct association was also found with all-causes deaths at 25 and 50-years. ATI and THI were also directly related with dietary saturated fat and cholesterol levels and inversely with the Mediterranean Adequacy Index (a score identifying the Mediterranean diet). CONCLUSION: These findings indicate that CHD has a different relationship with dietary lipids intake than HDUE and STR. This suggests that HDUE and STR have different underlying pathways or are different diseases.

Mortality Time-Trends of Different Cardiovascular Diseases in a Practically Extinct Cohort of Italian Middle-Aged Men Followed-Up for 61 Years: A Possible Etiological Explanation?

PURPOSE: To study a male Italian cohort (initially aged 40-59, n = 1712) during 61 years and the natural history of major CVD mortality categories including coronary heart disease (CHD), stroke and other heart diseases of uncertain etiology (HDUE), including congestive heart failure) along with their risk factor relationships. METHODS AND RESULTS: Cox models were run with 12 covariates as possible predictors measured at entry to the study. About 93% of all CVD deaths were covered by the three major groups selected here (N = 751): 37.4% of them were diagnosed as CHD, 30.6% as stroke and 28.5% as HDUE. CHD declined in the last 20 years of follow-up, while a sharp increase in HDUE mortality was seen. Baseline mean levels of serum cholesterol were 209.6, 204.2 and 198.0 mg/dL, respectively, for CHD, stroke and HDUE deaths: the multivariable coefficients of serum cholesterol were positive and significant for CHD (p < 0.0001), and stroke (p = 0.0203) and not significant for HDUE (p = 0.3467). In Fine-Gray models, the algebraic signs of cholesterol coefficients were opposite for CHD versus the other mortality categories (t = 3.13). The predictive performances of remaining risk factors were varied whereas that of Cox models was not very good, probably due to the attrition phenomenon and possible competing risks. CONCLUSION: Large differences in natural history and risk factors were found comparing the three CVD conditions, potentially indicating different etiologies and pointing to the need of not mixing them up in a grouped CVD category.

Physical activity and Physical fitness in Prediction of all-cause Mortality and Age at Death in European Extinct Cohorts of middle-aged men followed for 60 Years.

BACKGROUND: A study of the power of physical activity (Phyac) and physical fitness (Fitscore) in predicting very long-term all-cause mortality and age at death (AD) is missing. METHODS: A total of 5,482 middle-aged men were examined with measurement of several risk factors and followed for 60 years until virtual extinction of cohorts. Phyac in 3 classes was estimated from their type of work while Fitscore was derived from the linear combinations of levels of arm circumference, heart rate and vital capacity computed as a factor score by principal components analysis. Predictive power of these characteristics (adjusted for 5 traditional cardiovascular risk factors) was made by Cox models (for all-cause mortality) and multiple linear regression models (for AD). RESULTS: Single levels of the 3 indicators of fitness were highly related to the 3 levels of Phyac and of Fitscore. High levels of both Phyac and of Fitscore forced into the same models were associated with lower all-cause mortality and higher AD. Predictive power of Fitscore was systematically better than that of Phyac. Hazard ratios (high versus low) for all-cause mortality were 0.85 (Phyac) and 0.70 (Fitscore). Coefficients (all significant) were 2.25 years (Phyac) and 3.79 of AD by Fitscore. Fitscore was independently and significantly predictive of all-cause mortality for both first and second 30-year follow-up periods. CONCLUSIONS: Phyac and Fitscore are related and both showed important predictive power for all-cause mortality and AD. The role of Fitscore was more powerful and both characteristics seem to be expressions of health status.

Objectively measured physical fitness derived from linearly combined arm circumference, heart rate and vital capacity (Fitscore) may represent an improvement over classes of physical activity (Phyac) estimated from the type of work performed. What was comparatively assessed among 5,482 middle-aged men examined with measurement of several risk factors and followed for 60 years until virtual extinction of cohorts. Arm circumference, heart rate and vital capacity were highly related to the 3 levels of Phyac and of Fitscore. High levels of both Phyac and of Fitscore were associated with lower all-cause mortality and higher age at death (AD). The predictive power of Fitscore was systematically better than that of Phyac and comparing high versus low Phyac and Fitscore there was a statistically significant difference in all-cause mortality risk and AD, respectively 0.85 of hazard and 2.25 years (for Phyac) and 0.70 of hazard and 3.79 years (for Fitscore). Physical fitness is reportedly defined as the ability to carry out daily tasks with vigor and alertness, without undue fatigue and with ample energy to enjoy leisure-time pursuits and to meet unforeseen emergencies and might thus help to better assess long-term risk of all-cause mortality and higher AD when Fitscore based on arm circumference, heart rate and vital capacity are in the upper tertile. This is an improvement over Phyac that is reportedly defined as any bodily movement produced by skeletal muscles that results in energy expenditure. This study shows that Fitscore should be applied in day-to-day clinical/preventive cardiology practice.

In Search of Risk Factors: The Origin and Early Stages of Cardiovascular Epidemiology.

Based mainly on their personal experience, the authors try to describe the origin of cardiovascular disease (CVD) epidemiology and the problems and difficulties practitioners attempted to tackle and solve during the first few decades of this discipline, which started around the middle of the last century. Beyond identifying the characteristics of those who became CVD epidemiologists, a description is given of the initial structures of the involved studies, participation rates, risk factors measurements and standardization, clinical measurements and diagnostic criteria, mortality data collection and coding, data loading and analysis, plus a number of problems still unsolved at the beginning of the 2000s. Despite many obstacles, and the initial hostility of the medical-scientific establishment, CVD epidemiology represented a revolution in researching in the bio-medical field. In the end, it also affected clinical research introducing the use of the quantitative approach bound to mathematical-statistical procedures. After decades of hard work and the development of a number of innovative tools, CVD epidemiology received its deserved recognition, eventually being accepted as a reputable and independent scientific discipline. Yet, in several countries, especially those from Southern Europe, an academic recognition of CVD epidemiology is still lacking.

Competing Risks of Coronary Heart Disease Mortality versus Other Causes of Death in 10 Cohorts of Middle-Aged Men of the Seven Countries Study Followed for 60 Years to Extinction.

OBJECTIVES: To assess whether competing risks help explain why regions with initially high serum cholesterol have higher mortality from coronary heart disease (CHD) and lower mortality from stroke and other major heart diseases, while the reverse is found for those with initially lower serum cholesterol. MATERIAL AND METHODS: Ten cohorts of men (N = 9063) initially aged 40-59 in six countries were examined and followed for fatal outcomes for 60 years. Major cardiovascular disease (CVD) groups were CHD, stroke, and other Heart Diseases of Uncertain Etiology (HDUE), or the combination of stroke and HDUE (STHD), along with all other causes of death. Fine-Gray competing risk analysis was applied with CHD versus all other causes of death or STHD (direct mode) and all other causes of death or STHD versus CHD (inverse mode), and the effects of 19 covariates (of which 3 references) on the cause-specific hazard of the outcomes were assessed, thus investigating potential etiologic roles. A systematic comparison with results obtained by running the Cox model in direct and inverse modes with the same end-point results was also performed and illustrated graphically. RESULTS: CHD mortality is bound to different risk factor relationships when compared with all other causes of death and with STHD. The role of serum cholesterol is crucial since, in both comparisons, by Fine-Gray, its coefficients are positive and significant for CHD and negative and significant for all other causes of death and STHD. Risk factor capabilities in specific outcome types of the CVD domain (CHD versus STHD) are different depending on the outcome types considered. Risk factor coefficients are smaller in Fine-Gray modelling and larger in the Cox model. Fine-Gray detects different risk factors whose coefficients may have opposite algebraic signs. CONCLUSIONS: This is the first report whereby a large group of risk factors are investigated in connection with life-long CVD outcomes by Fine-Gray competing risk analysis, and a systematic comparison is performed with results obtained by Cox models in both direct and inverse modes. Subtypes of CVD mortality should be summed with full awareness that some risk factors vary by pathology, and they should at least be disentangled into CHD and STHD.

Cardiovascular Mortality in 10 Cohorts of Middle-Aged Men Followed-Up 60 Years until Extinction: The Seven Countries Study.

OBJECTIVES: To investigate mortalities from three major groups of cardiovascular diseases (CVDs) in a pooled cohort and followed up until extinction. MATERIALS AND METHODS: Ten cohorts of men (N = 9063) initially aged 40-59, in six countries, were examined and followed-up for 60 years. The major CVD groups were coronary heart disease (CHD), cerebrovascular diseases (STROKE) and other heart diseases of uncertain etiology (HDUE). RESULTS: Death rates from CHD were higher in countries with high serum cholesterol levels (USA, Finland and The Netherlands) and lower in countries with low cholesterol levels (Italy, Greece and Japan), but the opposite was observed for STROKE and HDUE, which became the most common CVD mortalities in all countries during the last 20 years of follow-up. Systolic blood pressure and smoking habits were, at an individual level, the common risk factors for the three groups of CVD conditions, while serum cholesterol level was the most common risk factor only for CHD. Overall, death rates for the pooled CVDs were 18% higher in North American and Northern European countries, while CHD rates were 57% higher in the same countries. CONCLUSIONS: Differences in lifelong CVD mortalities across different countries were smaller than expected due to the different rates of the three groups of CVD, and the indirect determinant of this seemed to be baseline serum cholesterol levels.

Focus on age at death in field epidemiology.

Age at death (AD) is an old metric recently re-evaluated for the study of longevity and mainly used in demography. Developed experience using AD in field epidemiology is summarized with cohorts followed-up for variable periods of time, frequently until extinction or close to extinction, a must to correctly adopt this metric. For practical purposes, a small number of examples is reported condensing previously published results to highlight various aspects of the problem. AD became the alternative of overall death rates when comparing cohorts reaching extinction or near extinction. AD was useful to characterize different causes of death in order to describe their natural history and possible etiology. With the use of multiple linear regression, a large number of possible determinants of AD were identified and some combinations of them resulted in large estimated differences in AD of 10 years or more across individuals. AD is a powerful tool to study population samples followed-up until extinction or near extinction. It allows to compare the life-long experience of different populations, to compare the role of different causes of death and to study the determinants of AD that are conditioning longevity.

Marital status and long-term cardiovascular risk in general population (Gubbio, Italy).

To investigate whether marital status is associated to long-term major fatal and non-fatal cardiovascular events in men and women from the Gubbio Population Study. The incidence of cardiovascular disease (CVD), including stroke and coronary heart disease (CHD) and CVD death together with all-cause mortality were analyzed. The analysis included 2832 persons (44% men, 54 ± 11 years old). Marital status was defined at entry as married (married or living conjugally) versus unmarried subjects (widowed, separated, divorced or single). Married and unmarried subjects did not differ concerning socio-demographic, anthropometric and biological variables at baseline. Over 191 months median follow-up, the incidence of CHD was lower among married versus unmarried women [HR: 0.63 (95% CI 0.41-0.96)] only; the same was true for CHD mortality [HR: 0.43 (95% CI 0.22-0.84)] and all-cause mortality [HR: 0.75 (95% CI 0.59-0.96)] independently of traditional risk factors (age, SBP, total and HDL cholesterol, cigarette smoke and BMI). In men, marital status was not associated to any of the investigated outcomes. In primary care, marital status should be investigated as it can be associated with long-term CHD and all-cause incidence and mortality risks among women.

Heart Diseases of Uncertain Etiology: A New Definition of Heart Failure for Epidemiological Studies.

It has been a long time since, in the spectrum of ischemic (IHD) or coronary (CHD) heart diseases, a differentiation was performed between the forms presenting with and those without pain [...].

Relationship between lifestyle factors and hypertension: a cross-sectional analysis from the Gubbio study.

BACKGROUND: Hypertension (HTN) is a well-established and a major risk factor for cardiovascular disease. Lifestyle behaviours for its prevention and control are recommended within worldwide guidelines. Their relationship with HTN need more investigations. AIM: We aimed to investigate the associations between lifestyle, anthropometric and biological measurements and BP in the Gubbio residential study. METHODS: Cross-sectional analyses were performed using data from Gubbio study. Information concerning lifestyle factors were collected using self-reported questionnaire and were further completed with a baseline clinical examination and blood exams. Three BP measurements were performed following a standard protocol. Age-adjusted and multivariable logistic regressions were used to examine the relationships between lifestyle parameters and HTN separately for each sex. We used heterogeneity test to observe sex differences. RESULTS: There were 3,183 persons included (48% men, 43 ± 17 years old). Mean systolic BP (SBP) was 119 ± 16 mmHg and 10.6% were hypertensives. Age [OR: 129.70 (95%CI: 18.57-905.79) in women and OR: 8.37 (95%CI: 4.01-17.48) (p < 0.0001) in men] and BMI [OR: 2.14 (95%CI: 1.32-3.46) (p = 0.006) in women and OR: 1.81 (95%CI: 1.05-3.12), p = 0.03 in men], were positively associated with SBP in both sexes. Serum uric acid [OR: 3.86 (95%CI: 2.03-7.26), p = 0.04] was positively associated with HTN in women while fasting blood glucose [OR: 3.04 (95%CI: 1.55-5.97), p < 0.001] were associated to HTN only in men. DISCUSSION: In addition to age, BMI is associated with HTN in both sexes while sex differences were observed in the associations between serum uric acid, fasting blood glucose and HTN.

Cardiovascular mortality in Northern and Southern European cohorts of the Seven Countries Study at 60-year follow-up.

OBJECTIVES: The aim of this study was to describe and interpret differences in major cardiovascular disease (CVD) mortality during 60 years between Northern European and Southern European cohorts of the Seven Countries Study of Cardiovascular Diseases. MATERIAL AND METHODS: Northern Europe included two cohorts from Finland and one from the Netherlands, and Southern Europe included two cohorts from Italy and two from Greece, for a total of 2360 and 2792 CVD-free men, respectively, at entry examination. Coronary heart disease (CHD), STROKE and other Heart Diseases of Uncertain Etiology (HDUE) deaths were the outcomes and Cox models were solved separately based on 12 risk factors. RESULTS: In 60 years, overall death rates were 99.8% in both Northern and Southern Europe and the pooled CVD rates were 46.9% (significantly higher) and 42.2%, respectively: CHD mortality was higher in Northern Europe, whereas STROKE and HDUE mortality were higher in Southern Europe. Significant Cox coefficients for both areas (but not significantly different between areas) were age, smoking habits, SBP and serum cholesterol for CHD, and only age and SBP did so for STROKE and HDUE. Age at death was lower for CHD, intermediate for STROKE and higher for HDUE in both areas. CONCLUSION: The advantage for Southern Europe was small in terms of overall CVD death rates, but definitely larger in terms of expectancy of life due to the differences in age at death in the three types of CVD mortality. Mean entry levels of serum cholesterol, 50 mg/dl higher in Northern Europe than in Southern Europe are a major culprit of these outcomes.

Cardiovascular risk factors predict age at death in 60-year follow-up of the Seven Countries Study.

OBJECTIVES: To study age at death (AD) and its determinants in cohorts of middle-aged men followed-up until extinction. MATERIAL AND METHODS: A total of 9063 middle-aged men enrolled in 10 cohorts of 6 countries (USA, Finland, the Netherlands, Italy, Greece and Japan) within the Seven Countries Study were examined and then followed up for 60 years until extinction. AD was computed and a small number of risk factors were tested through multiple linear regression as possibly related to attained AD. RESULTS: AD ranged across cohorts from 71.8 years in East Finland and 80.5 years in Crete with levels roughly lower in the USA and Northern Europe and higher elsewhere. Across cohorts, the correlation coefficients of systolic blood pressure (R = -0.58) and of CVD prevalence (R = -0.65) versus average AD were the only significant ones. At the individual level in the pool of all cohorts, a multiple linear regression model showed that age, vigorous physical activity, never and ex-smokers were favorably related to AD, while the reverse was true for systolic blood pressure, heart rate, serum cholesterol, CVD prevalence and silent ECG abnormalities. BMI had a parabolic relationship with AD. The predicting power of single risk factors, expressed in years gained or lost, was relatively small, but arbitrary combinations of several of them produced large differences in AD. CONCLUSIONS: A small number of CVD risk factors were strongly associated with AD in a life-long follow-up.

Lifestyle behaviours predicting major cardiovascular diseases mortality in a practically extinct cohort of middle-aged men followed-up for 61 years.

To study lifetime relationships of three major lifestyle behaviours with cardiovascular mortality in a cohort of middle-aged men that reached practical extinction. In the Italian Areas of the Seven Countries Study of Cardiovascular Diseases (SCS), 1712 men were enrolled and examined in 1960, and behavioural habits were measured: smoking habits, physical activity and diet each divided into three classes. Follow-up for mortality was extended for 61 years. Three groups of major cardiovascular diseases (CVD) were used for analysis, coronary heart disease (CHD), STROKE and other Heart Diseases of Uncertain Aetiology (HDUE). Kaplan-Meier curves, death rates in classes of behaviours and Cox proportional hazard models were computed, the last ones adjusted for other major risk factors.In 61 years of follow-up, 1708 men died and 727 were cases of CVD as defined above. Clear separation of classes in Kaplan-Meier survival curves were seen only for physical activity and diet in CHD, and physical activity for STROKE. Cox proportional hazard ratios (HR, adjusted for age, blood pressure and serum cholesterol) showed the significant protective effect on CHD of Mediterranean diet (HR = 0.72), vigorous physical activity (0.55), never smoking (0.73); on STROKE of vigorous physical activity (0.67); on HDUE of never smoking (0.57). Combination of three healthy versus three unhealthy behaviours was associated for CHD to a lower mortality of 39%. This comparison was not coherent for STROKE and HDUE.Lifetime healthy behaviours are clearly beneficial versus CHD mortality but not necessarily for mortality from HDUE and STROKE that probably represent different morbid conditions.

High R wave as a risk factor for cardivoascular and all-cause mortality. A 45-year follow-up of 13 cohorts of the Seven Countries Study.

OBJECTIVES: To study the role of high R waves predicting cardiovascular (CVD) and all-cause mortality in a male middle-aged population followed-up 45 years. MATERIAL AND METHODS: A total of 7985 CVD-free men aged 40-59 years were enrolled in 13 cohorts in seven countries (USA, Finland, the Netherlands, Italy, Serbia, Greece, Japan) and high R waves were classified by Minnesota Code 3.1 (as a dichotomous variable) from baseline resting otherwise normal ECG at entry examination together with other personal characteristics. Cox models were solved to detect the possible predictive role of high R waves for CVD and all-cause mortality. RESULTS: In Cox models high R waves were predictive of 45-year major CVD deaths with a hazard ratio of 1.17 (95% confidence intervals of 1.03-1.33) after adjustment for 6 major CVD risk factors (age, systolic blood pressure, serum cholesterol, cigarette smoking, physical activity and body mass index). The predictive role of high R wave was less evident for 45-year all-cause mortality and after adjustment for the 6 covariates the HR of high R wave lost its significance. A multiple logistic model indicated that body mass index, serum cholesterol, systolic blood pressure and mainly vigorous physical activity were directly related to high R wave prevalence while heart rate, subscapular skinfold, laterality index and shoulder pelvis shape did so in an inverse way. CONCLUSION: High R waves seem associated with an excess CVD mortality in a 45-year follow-up of middle-aged men, while their role is diluted when the end-point is all-cause mortality.

Dietary habits, cardiovascular and other causes of death in a practically extinct cohort of middle-aged men followed-up for 61 years.

BACKGROUND AND AIM: To test a dietary score produced from individual data of middle-aged-men enrolled in 1960 based on an a-posteriori approach and to study its association with some specific causes of death during 61 years until their practical extinction. METHODS AND RESULTS: In 1960 the Italian Rural Areas of the Seven Countries of Cardiovascular Diseases were enrolled and 1712 men aged 40-59 were examined with measurement of several risk factors and the collection of dietary history. Using 18 food groups a factor score was obtained from a Principal Component Analysis, that was divided into three classes, arbitrarily called non-Mediterranean, Intermediate and Mediterranean diets. Follow-up for mortality was extended for 61 years and dietary habits were related to several causes of death. There were 1708 deaths (99.8%) and Cox proportional hazards models, adjusted for five major risk factors, showed a significant protective effect of Mediterranean diet for coronary heart disease [Hazard Ratio (HR) = 0.67], cancer other than lung (0.74) and other causes, as from an operational definition (0.71), covering overall about 60% of all deaths. HR for all-cause mortality was of 0.85. In parallel, Kaplan-Meier curves provided significant p of log rank test for the same end-points (<0.0001, 0.0002, 0.0002 and < 0.0001, respectively). On the other hand, stroke, heart diseases of uncertain etiology, lung cancer, chronic bronchitis, unknown causes were not associated to dietary habits. CONCLUSION: In a 61-year follow-up of middle-aged men, the Mediterranean diet was beneficial for a large part of the causes of death and for total mortality.

Determinants of longevity and age at death in a practically extinct cohort of middle-aged men followed-up for 61 years.

OBJECTIVES: To explore possible determinants of longevity as a function of many personal characteristics in a cohort of middle-aged men followed-up until practical extinction. MATERIALS AND METHODS: In the Italian Rural Area of the Seven Countries Study, 1712 men aged 40-59 were examined in 1960 and 35 personal characteristics were measured. The subsequent follow-up for life status was of 61 years when only 3 men survived. A Kaplan-Meier curve was computed. A Cox model was solved with all-cause mortality as end-point and 35 potential determinants as covariates. A Multiple Linear Regression (MLR) model was also solved with the same covariates and age at death (AD) as end-point. RESULTS: After 61 years, 99.8% of men had died and median age at death was 75. Beneficial risk factors for both models (p < 0.05) were: never smoker, vigorous physical activity, prudent and Mediterranean diets, arm circumference, subscapular skinfold, and vital capacity. Adverse risk factors (p < 0.05) were: mother early death, laterality/linearity index, systolic blood pressure, serum cholesterol, corneal arcus, xanthelasma, cardiovascular diseases, cancer, diabetes, and chronic bronchitis. Some arbitrary combinations of selected risk factors were used to estimate AD as a function of coefficients of the MLR, showing large differences up to 10 years or more. CONCLUSIONS: Several personal characteristics of anthropometric, behavioral, biophysical, biochemical, and clinical nature are strongly associated with longevity when measured in middle-aged men and then followed up until extinction.

Simple versus complex carbohydrates and health: A frequently neglected problem.

AIMS: For several decades, there has been a notion that dietary fat is made of different components (at least SAFA, MUFA, and PUFA) that exhibit different and sometimes contrasting effects when associated with health and diseases: coronary heart disease (CHD) and cardiovascular diseases (CVD) in general. A similar fact is not noticed in carbohydrates and their components considering that even some major recent studies on the issue did not segregate simple carbohydrates from complex carbohydrates. In this study, we aimed to stress this need. DATA SYNTHESIS: A small number of selected studies are presented and commented where segregation of simple from complex carbohydrates was either performed or disregarded to address the inconsistency of not disentangling them. CONCLUSIONS: If only total fats were considered in investigations where fat was studied, the present notion and attitude toward different roles of the various classes of fats, at least SAFA versus unsaturated (MUFA and PUFA) would be missing. Therefore, there is a need to disentangle simple from complex carbohydrates, and this should be systematically applied when addressing CHD or CVD mortality risks and their preventive measures.

Chronic bronchitis in the 50-year follow-up of the European cohorts of the Seven Countries Study: prevalence, mortality and association with cardiovascular diseases.

OBJECTIVES: To study prevalence of chronic bronchitis (CB) in residential populations and its relationship with mortality in a 50-year follow-up. MATERIAL AND METHODS: In the late 1950's-early 1960's, 7047 men aged 40-59 years were enrolled in 10 European cohorts of the Seven Countries Study (in Finland, the Netherlands, Italy, Serbia and Greece). After baseline examination, follow-up for mortality was extended during 50 years (45 year in the Serbian cohorts). Prevalence of CB, and 50-year mortality from CB and other major causes of death were used as end-points to identify their determinants using multivariate models. RESULTS: Prevalence of CB was directly associated with smoking habits and inversely associated with high socio-economic status (SES), forced expiratory volume in ¾ sec (FEV) and the ratio FEV/vital capacity (VC). Fifty-year mortality from CB was directly predicted by CB prevalence (from a minimum hazard ratio [HR] 2.35, 95% confidence limits [CI] 1.70-3.24, to a maximum HR 3.01, CI 2.18-5.20, depending on diagnostic criteria and different models) and age, and inversely by high SES, FEV and FEV/VC. The same applied in models predicting mortality from coronary heart disease (HR for prevalent CB: 1.53, CI 1.24-1.88), major cardiovascular diseases (HR 1.43, CI 1.23-1.67) and all-cause mortality (HR 1.48, CI 1.34-1.64) all adjusted for age, high SES, smoking habits and FEV. CONCLUSIONS: CB is strongly associated with major cardiovascular disease and all-cause mortality while FEV and FEV/VC seem to carry at least partly an independent role from CB in predicting long-term mortality.