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.

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.

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.

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.

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.

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.

Age at death in elderly cohorts of four European countries of the Seven Countries Study: the role of comorbidities.

PURPOSE: To study age at death (AD) in elderly men as a function of risk factors and morbid conditions in a 25-year follow-up. MATERIALS AND METHODS: Men enrolled in the Seven Countries Study belonging to 8 cohorts in 4 European countries (Finland, The Netherlands, Italy and Serbia) were examined between 1984 and 1989 (aged 65-84 years) with measurement of some cardiovascular risk factors and recording of a few major morbid conditions. AD was measured after 25-year follow-up and used in multiple linear regression (MLR) models as dependent variable; while, risk factors and morbid conditions had the role of independent variables. RESULTS: Out of 2457 men, 2290 died during 25-year follow-up. Overall mean AD was of 82.0 years and slightly different across cohorts, the lowest being recorded in Finland. Age at entry examination and HDL cholesterol were directly associated with AD; while, blood pressure, heart rate, smoking habits and morbid conditions (major cardiovascular diseases, either independently or combined together with diabetes, chronic bronchitis, cancer and silent ECG abnormalities) were inversely related to AD. Body mass index had a parabolic relation with AD with longer survival for levels around 24 units; while, total serum cholesterol was not related to AD. However, only three independent variables were statistically significant when tested in each individual country (age, heart rate and stroke). In a MLR model, where a comorbidity score was entered as independent variable (everything else being equal), the presence of 1 morbid condition was associated with a reduced AD by 1.87 years that increased up to 6.39 years when 4 morbid conditions were present. CONCLUSION: AD seems a valuable indicator of all-cause mortality when the study population has reached or approached the extinction.

Lifestyle as determinant of all-cause mortality and age at death. A middle-aged male population followed-up 60 years until the survivors were aged 100 years.

OBJECTIVES: To relate major lifestyle habits with all-cause mortality in an almost extinct male middle-aged population. MATERIAL AND METHODS: A 40-59 aged male population of 1712 subjects was enrolled and examined in 1960 and then followed-up for 60 years. Baseline smoking habits, working physical activity and dietary habits, each subdivided into 3 classes, were related to 60-year mortality, by Kaplan-Meier survival curves, Cox proportional hazards model and to age at death during 60 years by multiple linear regression. RESULTS: Death rate in 60 years was of 99.7% with only 5 survivors and 2 lost to follow-up after 50 years. Two out of three classes of each behavior were significantly protective versus the third class in all the statistical approaches. Cox hazard ratios (and their 95% confidence limits) of never smokers versus smokers was 0.71 (0.63-0.79); that of vigorous physical activity versus sedentary activity was 0.75 (0.64-0.89); that of Mediterranean diet versus Not Mediterranean diet was 0.74 (0.66-0.84). The gain of age at death for never smokers versus smokers was 3.32 years (2.05-4.54); of vigorous physical activity versus sedentary activity was 3.53 years (1.68-5.37); that of Mediterranean diet versus Not Mediterranean diet was 3.67 years (2.32-5.02). Age at death was more than 10 years longer for men with the 3 best behaviors than for those with the 3 worst behaviors. CONCLUSIONS: Some lifestyle habits are strongly related to lifetime mortality and longevity.

How the Seven Countries Study contributed to the launch and development of cardiovascular epidemiology in Italy. A historical perspective.

The Italian research group of the Seven Countries Study of Cardiovascular Diseases (SCS), through the independent use of the national cohorts and data, had the lucky opportunity, starting in the early 1960, to launch the Italian research in epidemiology of cardiovascular diseases (CVD). In this way, the Italian Section of that international study became the first investigation with baseline measurements in various cohorts, subsequent re-examinations, systematic search for morbid events, and follow-up for mortality up to 50 years. A large number of scientific aspects has been tackled including estimates of morbidity and mortality rates, the association of risk factors with cardiovascular events and total mortality, the role of risk factor changes, the use of multivariable models, the role of lifestyle behavior, the determinants of all-cause mortality including risk factors rarely measured in other studies, the identification of characteristics of a condition called Heart Disease of Uncertain Etiology (HDUE), the production of predictive tools for practical use and several other issues. All this has been enhanced by the availability of extremely long follow-up data rarely found in other studies. Field work organization, measurement techniques, diagnostic criteria, data handling and computing had the limitations and difficulties typical of those times, the mid of last century, when CVD epidemiology was at its beginning. All this represented anyhow the start of CVD epidemiology research in the country and was the stimulus to the start of other studies and a valuable collaboration with some of them.

Association of serum cholesterol with coronary heart disease mortality during 50-year follow-up in ten cohorts of the seven countries study.

BACKGROUND AND AIM: The association of serum cholesterol levels with the occurrence of coronary heart disease (CHD) mortality during a follow-up of 50 years was rarely investigated previously. Thus, we took advantage of results at hand in 10 pooled cohorts of men aged 40-59 years from the Seven Countries Study (9063 individuals and 2057 CHD fatal events) and we assessed this. METHODS AND RESULTS: Cox proportional hazards models were run with CHD fatal events (as dependent variable) and cholesterol levels (as independent variables) at years 0, 10, and 25 (in 5 cohorts). Cumulative events during subsequent decades (cumulative approach: CA) and separately in each subsequent decade (partitioned approach: PA) were analyzed. The ecological correlation of average baseline serum cholesterol levels with CHD mortality was very high (R = 0.97). Serum cholesterol and CHD mortality for 50 years were associated at the individual level, and the association estimated by the Cox's coefficients (and related hazards ratios) was initially strong in both CA and PA, but slightly declined during later decades. Hazards ratios (for a difference of 40 mg/dl) ranged from 1.39 to 1.20 for CA and from 1.39 to 0.80 for PA. Coefficients were larger for CA than for PA and the decline was more evident for the latter. Partitioned coefficient became negative and significant in the last decade (from year 40-50). Coefficients derived from cholesterol levels measured at year 10 of follow-up showed similar trends but their magnitude was smaller. CONCLUSION: Thus, the relationship of serum cholesterol levels with CHD mortality remained relatively stable during at least 40 years after a single cholesterol measurement at baseline in middle-aged men.

Age at death of major cardiovascular diseases in 13 cohorts. The seven countries study of cardiovascular diseases 45-year follow-up.

OBJECTIVES: To explore age at death (AD) for major cardiovascular diseases (CVD) and their risk factors in originally middle-aged men followed nearly to extinction in the Seven Countries Study. MATERIALS AND METHODS: Thirteen cohorts of men aged 40-59 years (N = 10,628) in seven countries (USA, Finland, the Netherlands, Italy, Serbia, Greece, Japan) were enrolled in late 1950s and early 1960s and were followed 45 years for mortality. AD was computed for coronary heart disease (CHD), stroke (STR), heart disease of uncertain aetiology (HDUE) and for all-causes. AD was compared across CHD-HDUE-STR. Cox models were computed for each end-point using baseline age, cigarettes smoking, systolic blood pressure and serum cholesterol. RESULTS: After 45 years 92.9% of men had died. The most common CVD death was CHD in most cohorts except some Mediterranean and Japanese cohorts where STR or HDUE were most prevalent. In 13 cohorts mean AD was 74.5, 73.5, 75.7 and 79.1 years, respectively, for all-cause, CHD, STR and HDUE mortality (all possible differences were significant). The difference, across cohorts, between the highest and the lowest mean AD was 12.9, 9.0 and 4.7 years for CHD, HDUE and STR mortality, respectively. Risk factors explored were significant predictors of all three CVD end-points, except serum cholesterol, specific to CHD mortality. CONCLUSIONS: AD is a useful indicator of previous health and aging populations. STR and HDUE are diseases appearing later in life, thus being associated with a higher AD compared with CHD mortality.

Epidemiology of Heart Disease of Uncertain Etiology: A Population Study and Review of the Problem.

Background and objectives: Previous epidemiological studies have identified a group of heart diseases (here called heart diseases of uncertain etiology-HDUE) whose characteristics were rather different from cases classified as coronary heart disease (CHD), but frequently confused with them. This analysis had the purpose of adding further evidence on this issue based on a large population study. Materials and Methods: Forty-five Italian population samples for a total of 25,272 men and 21,895 women, free from cardiovascular diseases, were examined with measurement of some risk factors. During follow-up, CHD deaths were those manifested as myocardial infarction, other acute ischemic attacks, and sudden death of probable coronary origin, after reasonable exclusion of other causes. Cases of HDUE were those manifested only as heart failure, chronic arrhythmia, and blocks in the absence of typical coronary syndromes. Cox proportional hazards models were computed separately for CHD and HDUE, with 11 risk factors as possible predictors. Results: During an average of 7.4 years (extremes 1-16) there were 223 CHD and 150 HDUE fatal events. Male sex, age, smoking habits, systolic blood pressure, serum cholesterol, and plasma glucose were significantly and directly related to CHD events, while high density lipoprotein (HDL) cholesterol was so in an inverse way. The same risk factors were predictive of HDUE events except serum cholesterol and HDL cholesterol. Multivariable hazards ratio of serum cholesterol (delta = 1 mmol/L) was higher in the CHD model (1.24, 95% CI 1.11-1.39) than in the HDUE model (1.03, 0.5% C.I. 0.89-1.19) and the difference between the respective coefficients was statistically significant (p = 0.0444). Age at death was not different between the two end-points. Conclusions: CHD and HDUE are probably two different morbid conditions, only the first one is likely bound to gross atherosclerotic lesions of coronary arteries and linked to blood lipid levels. We reviewed the problem in epidemiological investigations and addressed inflammation as a potential cofactor to differentiate between CHD and HDUE.

Can we still learn from the Seven Countries Study?

PURPOSE OF REVIEW: The Seven Countries Study (SCS) of Cardiovascular Diseases started midway last century and was the pioneer investigation of coronary heart disease (CHD) at international level. The 16 cohorts of middle-aged men enrolled in eight nations of seven countries allowed to show large differences of CHD incidence and mortality across different cultures, partly explained by average levels of serum cholesterol and dietary habits, that is, Western type patterns in the high-risk populations, and Mediterranean or Oriental type in Southern Europe and Japan. Later, critics to the validity of the study were largely based on fake news, wrong or distorted information uncritically transmitted in a cascade of media. RECENT FINDINGS: Recent analyses based on 45-50 years of follow-up showed and confirmed that diet patterns were associated with all-cause mortality and age at death; that multivariate coefficients of major risk factors of CHD were not heterogeneous across different populations and cultures; that analysis of competing risks of CHD versus other conditions identified serum cholesterol as the critical determinant; that true CHD manifestations had different determinants compared with Heart Diseases of Uncertain Etiology frequently confused with CHD. SUMMARY: The SCS can still teach investigators and scholars of cardiovascular epidemiology, if old contributions are carefully read and interpreted; it is still recognized as the seminal study in this area at international level although it had limits as any other study but represented the first step into the identification of the relationship of diet with CHD and mortality across populations, and of the Mediterranean diet.

Age at death as a useful indicator of healthy aging at population level: a 50-year follow-up of the Italian Rural Areas of the Seven Countries Study.

OBJECTIVES: To explore age at death (AD), overall and for different causes of death, in a cohort followed up to quasi-extinction. MATERIALS AND METHODS: In 1960, in the Italian Rural Areas of the Seven Countries Study, 1712 men aged 40-59 years were enrolled, examined and then followed up for 50 years. AD was computed for all fatal events and compared across 12 groups of causes of death. Multiple linear regression model was used to estimate AD and Cox model to predict each of the 12 causes of death, as a function of 28 selected baseline risk factors. RESULTS: After 50 years, 97.5% of men had died. Mean AD was 75.0 years (median 76), while large variation was found across the 12 causes of death, with the highest levels for Heart Disease of Uncertain Etiology (HDUE) and Senility plus Causes Unknown (SNUNK), having means of 79.2 and 84.5 (median of 80 and 86) years, respectively. Many risk factors were directly associated with overall AD, the most significant being subscapular skinfold, arm circumference, Mediterranean diet, age at baseline examination, never smokers and vigorous physical activity. Systolic blood pressure (SBP) was inversely related. The relevant modifiable risk factors predicting single causes of death were SBP and the lifestyle behaviors of dietary, motion and smoking habits. CONCLUSIONS: AD proved to be a useful indicator of previous health and aging of populations. HDUE and SNUNK seem the most "physiological" causes of death. SBP and lifestyle risk factors are the most relevant characteristics associated with AD.

The strength of the multivariable associations of major risk factors predicting coronary heart disease mortality is homogeneous across different areas of the Seven Countries Study during 50-year follow-up.

OBJECTIVES: To compare the magnitude of multivariable coefficients and hazard ratios of four cardiovascular risk factors across five worldwide regions of the Seven Countries Study in predicting 50-year coronary deaths. MATERIAL AND METHODS: A total of 13 cohorts of middle-aged men at entry (40-59 years old) were enrolled in the mid-1900s from five relatively homogeneous groups of cohorts (areas): USA, Finland and Zutphen - the Netherlands, Italy and Greece, Serbia, Japan for a total of 10,368 middle-aged men. The major risk factors measured at baseline were age, number of cigarettes smoked, systolic blood pressure and serum cholesterol. Cox proportional hazards models were solved for 50-year (45 years for Serbia) deaths from coronary heart disease (CHD), and the multivariable coefficients were compared for heterogeneity. RESULTS: The highest levels of risk factors and CHD death rates were found in Finland and Zutphen - the Netherlands and the lowest in Japan. All four risk factors were predictive for long-term CHD mortality in all regions, except serum cholesterol in Japan where the mean levels and CHD events were lowest. Tests of heterogeneity of coefficients for single risk factors in predicting CHD mortality were non-significant across the five areas. The same analyses for the first 25 years of follow-up produced similar findings. CONCLUSIONS: The strength of the multivariable associations of four major traditional CHD risk factors with long-term CHD mortality appears to be relatively homogeneous across areas, pending needed further evidence.

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.

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.