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.

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.

Baseline fatty acids, food groups, a diet score and 50-year all-cause mortality rates. An ecological analysis of the Seven Countries Study.

OBJECTIVES: This analysis deals with the ecologic relationships of dietary fatty acids, food groups and the Mediterranean Adequacy Index (MAI, derived from 15 food groups) with 50-year all-cause mortality rates in 16 cohorts of the Seven Countries Study. MATERIAL AND METHODS: A dietary survey was conducted at baseline in cohorts subsamples including chemical analysis of food samples representing average consumptions. Ecologic correlations of dietary variables were computed across cohorts with 50-year all-cause mortality rates, where 97% of men had died. RESULTS: There was a 12-year average age at death population difference between extreme cohorts. In the 1960s the average population intake of saturated (S) and trans (T) fatty acids and hard fats was high in the northern European cohorts while monounsaturated (M), polyunsaturated (P) fatty acids and vegetable oils were high in the Mediterranean areas and total fat was low in Japan. The 50-year all-cause mortality rates correlated (r= -0.51 to -0.64) ecologically inversely with the ratios M/S, (M + P)/(S + T) and vegetable foods and the ratio hard fats/vegetable oils. Adjustment for high socio-economic status strengthened (r= -0.62 to -0.77) these associations including MAI diet score. CONCLUSION: The protective fatty acids and vegetable oils are indicators of the low risk traditional Mediterranean style diets. KEY MESSAGES We aimed at studying the ecologic relationships of dietary fatty acids, food groups and the Mediterranean Adequacy Index (MAI, derived from 15 food groups) with 50-year all-cause mortality rates in the Seven Countries Study. The 50-year all-cause mortality rates correlated (r = -0.51 to -0.64) ecologically inversely with the ratios M/S [monounsaturated (M) + polyunsaturated (P)]/[saturated (S) + trans (T)] fatty acids and vegetable foods and the ratio hard fats/vegetable oils. After adjustment for high socio-economic status, associations with the ratios strengthened (r = -0.62 to -0.77) including also the MAI diet score. The protective fatty acids and vegetable oils are indicators of the low risk traditional Mediterranean style diets.

Lifetime competing risks between coronary heart disease mortality and other causes of death during 50years of follow-up.

OBJECTIVES: To study coronary heart disease (CHD) death versus 11 other causes of death using the cumulative incidence function (CIF) and the competing risks procedures to disentangle the differential role of risk factors for different end-points. MATERIAL AND METHODS: Standard Cox and Fine-Gray models among 1712 middle-aged men were compared during 50years of follow-up. CHD death was the primary event, while deaths from 11 selected causes, mutually exclusive from the primary end-point, were considered as secondary events. Reverse solutions were also performed. We considered 10 selected risk factors. RESULTS: CHD death risk was the second highest among 12 mostly specific causes of death. Some risk factors were specific: serum cholesterol for CHD death whereas, systolic blood pressure, cigarette smoking and age may have a differential role in other causes of death. Application of the Fine-Gray model based on CIF enabled to dissect, at least in part, the respective role that baseline covariates may have to segregate the probabilities of two types of death in contrast from each other. They also point to the absence of contributing significance for some of the selected risk factors and this calls for a parsimonious approach in predictions. CONCLUSIONS: The relative rarity of competing risk challenges when defining the risk factors role at long-term needs now be corrected since we have clearly shown, with Fine-Gray model, at direct or reverse use, that comparing different end-points heavily influences the risk factor predictive capacity.

Competing risks and lifetime coronary heart disease incidence during 50years of follow-up.

OBJECTIVES: To study coronary heart disease (CHD) incidence versus other cause of death using the cumulative incidence function and the competing risks procedures to disentangle the differential role of risk factors for different end-points. MATERIAL AND METHODS: We compared standard Cox and Fine-Gray models among 1677 middle aged men of an Italian population study of cardiovascular diseases that reached 50years of follow-up with the quasi extinction of the population. The incidence of either fatal or non-fatal cases in 50years was used as primary event, while deaths from any other cause, mutually exclusive from the primary events, were considered as secondary events. We considered 10 selected risk factors. RESULTS: The main result was that cholesterol was significantly and positively related to incidence of CHD contrasted with deaths from any other cause. On the other hand, when the primary events were deaths from any other cause and the competing events were CHD, cholesterol was inversely and age positively related. This outcome did not exclude the predictive role of other risk factors, such as age, cigarettes, arm circumference (protective), systolic blood pressure, vital capacity (protective), cholesterol, corneal arcus and diabetes, documented by the Cox model, that had common roles for both end-points. CONCLUSIONS: Fine-Gray model, initially proposed to handle adequately cumulative incidence function may thus prevent overestimation of risks related to the Kaplan-Meier based methods such as Cox model and identify the specific risk factors for defined end-points.

Cardiovascular and other causes of death as a function of lifestyle habits in a quasi extinct middle-aged male population. A 50-year follow-up study.

OBJECTIVES: To relate major causes of death with lifestyle habits in an almost extinct male middle-aged population. MATERIAL AND METHODS: A 40-59 aged male population of 1712 subjects was examined and followed-up for 50 years. Baseline smoking habits, working physical activity and dietary habits were related to 50 years mortality subdivided into 12 simple and 3 composite causes of death by Cox proportional hazard models. Duration of survival was related to the same characteristics by a multiple linear regression model. RESULTS: Death rate in 50 years was of 97.5%. Out of 12 simple groups of causes of death, 6 were related to smoking habits, 3 to physical activity and 4 to dietary habits. Among composite groups of causes of death, hazard ratios (and their 95% confidence limits) of never smokers versus smokers were 0.68 (0.57-0.81) for major cardiovascular diseases; 0.65 (0.52-0.81) for all cancers; and 0.72 (0.64-0.81) for all-cause deaths. Hazard ratios of vigorous physical activity at work versus sedentary physical activity were 0.63 (0.49-0.80) for major cardiovascular diseases; 1.01 (0.72-1.41) for all cancers; and 0.76 (0.64-0.90) for all-cause deaths. Hazard ratios of Mediterranean Diet versus non-Mediterranean Diet were 0.68 (0.54-0.86) for major cardiovascular diseases; 0.54 (0.40-0.73) for all cancers; and 0.67 (0.57-0.78) for all-cause deaths. Expectancy of life was 12 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.

Lifetime prediction of coronary heart disease and heart disease of uncertain etiology in a 50-year follow-up population study.

OBJECTIVES: The relationships of four basic risk factors with 50-year incidence of coronary heart disease (CHD) and Heart Disease of Uncertain Etiology (HDUE) were investigated in a population study. MATERIAL AND METHODS: There were 1712 men aged 40-59 years in 1960 and 1677, heart disease free, were followed-up for 50 years. Incidence of first event for CHD (sudden death, fatal and non-fatal myocardial infarction, other fatal and non-fatal coronary syndromes) and HDUE (heart failure, chronic arrhythmia, blocks, "chronic CHD", hypertensive heart disease) was estimated and the relationships of four basic risk factors analyzed. RESULTS: In 50 years incidences of CHD and HDUE were respectively 26.9 and 20.6%. Cox proportional hazards models showed serum cholesterol as a strong CHD predictor (hazard ratio, HR, for 1 mmol/l difference 1.22 and confidence intervals, CI, 1.11 to 1.33), irrelevant for HDUE (HR 1.02 and CI 0.87 to 1.18). Age at entry was a stronger predictor for HDUE (HR for 5 year difference 1.65 and CI 1.46 to 1.86) than for CHD (HR 1.26 and CI 1.14 to 1.39). Systolic blood pressure and cigarette smoking had similar predictive power. The diagnosis of angina pectoris (AP) recorded at any time during the study was strongly associated with CHD but not with HDUE. A HDUE subgroup with AP had similar life-expectancy to CHD, suggesting the need to re-classify them as CHD. CONCLUSIONS: Due to important differences in predictors (risk factors) and expectancy of life CHD and HDUE are probably manifestations of different etiologies.