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.

Homogeneity in the relationship of serum cholesterol to coronary deaths across different cultures: 40-year follow-up of the Seven Countries Study.

BACKGROUND: The aim was to investigate whether multivariate coefficients of serum cholesterol in the prediction of coronary heart disease (CHD) deaths were similar across different cultures in a long-term follow-up. DESIGN: Thirteen cohorts for a total of 10,157 men aged 40-59 years at entry, enrolled in seven countries (USA, Finland, the Netherlands, Italy, Serbia, Greece, Japan) were repeatedly examined and followed up for 40 years. METHODS: Serum cholesterol measured at baseline, and then on repeated occasions, was studied, using multivariate models, in relation with the occurrence of CHD deaths during a 40-year follow-up. RESULTS: Homogeneity of multivariate serum cholesterol coefficients was found considering cholesterol levels at baseline, as average of up to three measurements during the first 10 years, as average of up to six measurements in 35 years, using the time-dependent technique with up to three measurements in 10 years, and with up to six measurement in 35 years. CONCLUSION: The strength of the association between serum cholesterol and CHD death seems homogeneous across different cultures characterized by different levels of serum cholesterol and different absolute risk of CHD death.

Type 2 diabetes and its correlates in a first nationwide study among Cypriot adults.

Obesity rates in Cyprus are very high and epidemiological information on type 2 diabetes mellitus is limited. The correlates of type 2 diabetes among adults remain unknown in the Cypriot population. Thus, the purpose of this study is to provide the first national estimate of the prevalence of type 2 diabetes and investigate its correlates. A randomly stratified nationally sample of 1001 adults aged 18-80 participated in the study. Only 950 subjects completed the study. All subjects were free of any diseases (known diabetes, kidney, liver), medication and supplementation. The overall prevalence of diabetes and pre-diabetes based on WHO criteria was 9.2% and 16.3%, respectively. After adjusting for age, energy intake, smoking and physical activity participants with obesity (BMI) (OR=2.00, P<0.001), waist circumference (WC) (OR=2.08, P<0.001), hypertension (HT) (OR=1.99, P<0.001) and hypercholesterolemia (HC) (OR=2.07, P<0.007) were most likely to develop T2DM compared with the normal ones. The odds of having diabetes were also found significant between subjects with high levels of triglycerides (TG) (OR=1.49, P<0.007), compared with the normal ones and between subjects with low levels of HDL (OR=1.44, P<0.008) compared with the ones with high levels of HDL. The prevalence of type 2 diabetes in Cyprus is relatively medium-high. However, the pre-diabetes rates are very high showing a promising increase toward total rates of type 2 diabetes. Obesity, HT, WC, TG, HC and low HDL are all strong correlates of type 2 diabetes. Healthy education programs should be initiated for young and older-aged people and those with described abnormal risk factors.

Impact of physical activity and cardiovascular fitness on total homocysteine concentrations in European adolescents: The HELENA study.

We examined the association of physical activity (PA), cardiovascular fitness (CVF) and fatness with total homocysteine (tHcy) concentrations in European adolescents. The present study comprised 713 European adolescents aged 14.8 ± 1.2 y (females 55.3%) from the multicenter HELENA cross-sectional study. PA was assessed through accelerometry, CVF by the 20-m shuttle run test, and body fat by skinfold thicknesses with the Slaughter equation. Plasma folate, cobalamin, and tHcy concentrations were measured. To examine the association of tHcy with PA, CVF, and fatness after controlling for a set of confounders including age, maturity, folate, cobalamin, creatinine, smoking, supplement use, and methylenetetrahydrofolate reductase 677 genotype (CC 47%, CT 43%, TT 10%), bivariate correlations followed by multiple regression models were performed. In the bivariate correlation analysis, tHcy concentrations were slightly negatively correlated (p<0.05) with CVF in females (measured both by stages: r=-0.118 and by VO2max: r=-0.102) and positively with body mass index (r=0.100). However, daily time spent with moderate and vigorous PA showed a weak positive association with tHcy in females (p<0.05). tHcy concentrations showed a tendency to decrease with increasing CVF and increase with increasing BMI in female European adolescents. However, tHcy concentrations were positively associated with moderate and vigorous PA in female European adolescents.

The role of a baseline casual blood pressure measurement and of blood pressure changes in middle age in prediction of cardiovascular and all-cause mortality occurring late in life: a cross-cultural comparison among the European cohorts of the Seven Countries Study.

OBJECTIVE: The first objective was to study the long-term association of a casual measurement of systolic blood pressure (SBP) with cardiovascular deaths (CVD) and all causes of death (ALL) occurring during 35 years of follow-up in different population samples of men aged 40-59 years in five European countries. The second objective was to study the predictive power of early change in SBP levels (years 0-10) in relation to late fatal events (years 10-35). DESIGN, SETTING AND PARTICIPANTS: A single measurement of SBP was considered in cohorts in Finland, The Netherlands, Italy, Serbia and Greece for a total of 6507 men. Three partitioned proportional hazards models were solved, one for each independent and subsequent time block of 10 years, after excluding data from the first 5 years, to predict the risk of cardiovascular disease deaths of atherosclerotic origin (CVD) and all cause mortality (ALL). Independently, the predictive power of SBP changes (Delta-SBP) occurred during the first 10 years of follow-up was explored as a possible additional risk factor in relation to CVD and ALL deaths occurring between year 10 and year 35 of follow-up. RESULTS: Partitioned hazard scores derived from the three partitioned functions were cumulated. The resulting curves showed a continuous and significant association of baseline SBP with CVD and ALL deaths during three decades, although the strength of association declined significantly from the first to the third decade. The relative risk for 20 mmHg of SBP (and its 95% confidence intervals) in predicting CVD deaths was 1.65 (1.54-1.77) for the first 10-year block; 1.33 (1.24-1.42) for the second block; and 1.22 (1.13-1.31) for the last 10-year block. The corresponding levels of ALL deaths were 1.41 (1.34-1.49), 1.26 (1.19-1.32) and 1.11 (1.05-1.17). Changes in SBP during 10 years (Delta-SBP) added predictive power to baseline measurements in a direct and significant way, with a relative risk for a change of 10 mmHg of 1.14 (1.10-1.17) for CVD deaths and 1.11 (1.09-1.13) for ALL deaths. CONCLUSION: A single measurement of systolic blood pressure in middle-aged men maintains a strong relationship with fatal CVD and ALL deaths during the next 35 years, although for late events the strength of the association definitely declines. Changes in systolic blood pressure levels during the first 10 years of follow-up add predictive power, while baseline measurements retain their predictive power.

Epidemiology of typical coronary heart disease versus heart disease of uncertain etiology (atypical) fatalities and their relationships with classic coronary risk factors.

OBJECTIVES: The relationships were explored of some cardiovascular risk factors to typical (TYP) and atypical (ATYP) fatal coronary events (CHD). MATERIAL AND METHODS: Thirteen cohorts of 40-59 year-old men of the Seven Countries Study were followed-up for 40 years (N = 9704 heart disease free subjects). Fatal TYP-CHD were classified when manifested as myocardial infarction, other acute coronary syndromes, angina pectoris and sudden death; and as ATYP-CHD when manifested only as heart failure or arrhythmia in the absence of other clear etiologies. Death rates were computed for single countries separately for TYP and ATYP and for different lengths of follow-up. Cox models included: age, smoking habits, systolic blood pressure (SBP), serum cholesterol (CHOL), forced expiratory volume in ¾ sec (FEV) and diabetes. RESULTS: TYP-CHD was more common in North American and Northern European countries, while ATYP-CHD were more common in Southern and Eastern Europe. Age at death was 5 years greater for ATYP-CHD than for TYP-CHD. Cox models in the pool of 13 cohorts showed that coefficient for age was significantly larger for ATYP-CHD (hazard ratio, HR: 2.36; confidence intervals CI: 2.18 - 2.26) versus TYP-CHD (HR 1.50, CI 1.43-1.58) while coefficients for CHOL was larger and significant for TYP-CHD (HR 1.29, CI 1.22-1.35) but not for ATYP-CHD (HR 0.93, CI 0.85-1.03). SBP, smoking habits, FEV and diabetes all predicted both conditions almost equally. CONCLUSION: The different relationships of CHOL and age with the two types of fatal CHD suggest that the two groups of manifestations may belong to different diseases.

Respiratory function and other biological risk factors for completed suicide: 40 years of follow-up of European cohorts of the Seven Countries Study.

BACKGROUND: Prospective cohort studies on biological risk factors of completed suicide are scarce. We aimed to test which biological risk factors independently identify subjects at increased risk of suicidal death. METHODS: In the prospective cohort of the Seven Countries Study, 5,321 middle-aged men from Finland, Serbia, Italy, and Greece were included. Completed suicide (ICD-8 codes E950-959) was assessed during 40 years of follow-up. Biological cardiovascular risk factors (including forced vital capacity [FVC] and height) were tested for their role as predictors in multivariable Cox models stratified by country. RESULTS: There were 4518 deaths during follow-up, with 64 from suicide (1.4%). In univariable models, only FVC and height were strongly inversely related with suicide. Socio-economic status and being unmarried were potential confounders. In multivariable models taking these confounders into account, both a low FVC (0.30 for top vs. lowest quartile; 95% CI: 0.12-0.76; P=0.006 for trend) and a low FVC/height ratio (0.37 for top vs. lowest quartile; 95% CI: 0.17-0.82; P=0.004 for trend) were strongly inversely related with completed suicide. LIMITATIONS: Information on proximal causes, such as prior suicidal ideation, emotional distress and depression, was lacking at baseline. CONCLUSIONS: Poor respiratory function in middle-aged men was an independent risk factor for completed suicide.

Forty-year coronary mortality trends and changes in major risk factors in the first 10 years of follow-up in the seven countries study.

Time trends in coronary heart disease (CHD) mortality during a 40-year follow-up were studied in the Seven Countries Study. Thirteen cohorts of men aged 40-59 at entry were enrolled in seven countries (USA, Finland, the Netherlands, Italy, Serbia, Greece and Japan) for a total of 10,628 subjects. Cardiovascular risk factors were measured at entry and at the 10-year follow-up examination and coronary heart disease mortality data collected during 40 years. During the 40-year follow-up, the hazard rate of the Weibull parametric distribution (annual conditional risk of death) for CHD mortality tended to slightly decline in the US, Finnish, Dutch and Japanese cohorts, moderately increased in Italy and exponentially increased in cohorts of Serbia and Greece. A strong positive association was found between the shape of the hazard curve, describing the acceleration of the hazard, and a score of population mean risk factor changes (serum cholesterol, systolic blood pressure and smoking prevalence) observed during the first 10 years of follow-up, with a correlation coefficient of 0.91 between the two indicators. The countries with a relative decline in the annual hazard function were the same where, during the same historical period, large decreases in official death rate from CHD were recorded, and viceversa. The acceleration in mortality risk for CHD mortality in different countries, described by the shape of the Weibull distribution, is related to changes in mean levels of major coronary risk factors.