The role of HDL cholesterol in metabolic syndrome predicting cardiovascular events. The Gubbio population study.

BACKGROUND AND AIMS: Metabolic syndrome (MS) has recently been claimed to be an important new risk factor for the occurrence of coronary heart disease (CHD) and cardiovascular disease (CVD) events, although it is simply a combination of known risk factors used in a dichotomized fashion. The aims of this analysis were to explore the predictive role of MS for CHD and CVD events in a population study, in comparison with using the same factors in a continuous fashion, with special emphasis on HDL cholesterol. METHODS AND RESULTS: In the second examination of the Gubbio population study from central Italy, 2650 cardiovascular disease-free men and women, aged 35-74 years around 1990, were examined and followed-up for 12 years. The classic risk factors (sex, age, systolic blood pressure, serum cholesterol and smoking habits) were studied as predictors of CHD and CVD events, alone and with the contribution of other factors (HDL cholesterol, blood glucose, serum triglycerides and waist circumference) included in the so-called MS, based on several multivariate models. MS was also tested after adjustment for other risk factors. MS produced a predictive significant relative risk of 1.67 for CHD events and 1.82 for CVD events, but considering its single risk factors, the only ones contributing to prediction were HDL cholesterol and systolic blood pressure. Dedicated analyses showed that MS does not add anything to the power of prediction beyond the role of the single risk factors treated in a continuous fashion, while the best predictive power is obtained using classic risk factors (sex, age, smoking habits, total cholesterol, systolic blood pressure) with the addition of HDL cholesterol. CONCLUSIONS: The predictive power of MS is bound only to the presence of HDL cholesterol and blood pressure and does not add anything to using the same risk factor treated in a continuous fashion.

Impact of the Gubbio population study on community control of blood pressure and hypertension. Gubbio Study Research Group.

BACKGROUND: Awareness and treatment of hypertension have markedly increased in the last 30 years in most parts of the world, but a satisfactory control of blood pressure is still infrequent OBJECTIVES: To describe trends in community control of hypertension and blood pressure levels in the small town of Gubbio, Italy. METHODS: Large samples of the populations (aged 30-79 years) were examined 6 years apart for measurement of blood pressure, other cardiovascular risk factors and knowledge, attitude and practice towards control of hypertension. Data were available from a total of 1125 men and 1445 women with two examinations and 1566 men and 1658 women with at least one examination. Two different definitions of hypertension were used (old definition: systolic blood pressure (SBP) > or = 160 mmHg or diastolic blood pressure (DBP) > or = 95 mmHg or use of antihypertensive drugs; recent definition: SBP > or = 140 mmHg or DBP > or =90 mmHg or use of anti-hypertensive drugs). RESULTS: Awareness, treatment and control of hypertension increased from one survey to the other, whatever definition of hypertension was used. Control rose from 41 to 63% (old definition) and from 12 to 24% (recent definition). In a 6-year period, the average population SBP declined 2-8 mmHg and DBP declined 2-3 mmHg depending on type of analysis, against an expected rise of 9 mmHg for SBP and 2 mmHg for DBP. These trends are partly explained by a marked decline in alcohol consumption and by more common and intensive anti-hypertensive treatment, while change in body mass index, which showed a slight but systematic increase, cannot be considered as a contributor to this trend. CONCLUSIONS: An epidemiological study has motivated a population group and its medical profession towards a better control of hypertension.

Voltage criteria of left ventricular hypertrophy in sudden and nonsudden coronary artery disease mortality: the Italian section of the Seven Countries Study.

It is unclear whether sudden or nonsudden death can be predicted independently from other risk factors for coronary artery disease (CAD). Therefore, this investigation was undertaken to measure 12-lead QRS voltage sum, a recently proposed (Am J Cardiol 1985;55:485-494) index of left ventricular (LV) hypertrophy, and its ability to predict either subsequent sudden (less than 2 hours) or nonsudden CAD death during 20 to 23 years of follow-up in 1,588 middle aged men (40 to 61 years old) from 2 cohorts of the Italian section of the Seven Countries Study who were free of demonstrable CAD (at entry examination in 1962). The Sokolow-Lyon and the modified Sokolow-Lyon indexes, 2 standard electrocardiographic methods to detect LV hypertrophy were also measured and compared. During follow-up, 67 patients died suddenly and 87 died a nonsudden CAD death. In the Cox proportional-hazards model, age, mean blood pressure, heart rate, body mass index, cholesterol, physical activity, smoking habit, ST-T alterations (Minnesota codes 4.1 to 4.3 together with 5.1 to 5.3) and the 3 electrocardiographic indexes, all measured at the time of enrollment into the study, were included. The 12-lead QRS voltage sum retained significant and independent relation to sudden death (t = 2.00); Sokolow-Lyon index entered the Cox solution for nonsudden CAD death but the association was inverse (t = -2.10). ST-T alterations were significantly associated only with nonsudden CAD death (t = 2.19). Thus, in addition to several known risk factors, measurement of 12-lead QRS voltage sum in middle-aged men without clinical evidence of heart disease may help identify subjects at an increased risk of sudden death; nonsudden CAD death is predicted by Sokolow-Lyon index and by ST-T alterations. The usefulness of these indexes needs to be tested in different populations.

Role of body mass index in the prediction of all cause mortality in over 62,000 men and women. The Italian RIFLE Pooling Project. Risk Factor and Life Expectancy.

STUDY OBJECTIVE: To evaluate the relation of body mass index (BMI) to short-term mortality in a large Italian population sample. DESIGN: Within the Italian RIFLE pooling project, BMI was measured in 47 population samples made of 32,741 men and 30,305 women ages 20-69 years (young 20-44, mature 45-69). Data on mortality were collected for the next six years. MAIN OUTCOME MEASURES: Age adjusted death rates in quintile classes of BMI and Cox proportional hazards models with six year all causes mortality as end point, BMI as covariate and age, smoking, systolic blood pressure as possible confounders were computed. Multivariate analysis was tested in all subjects and after the exclusion of smokers, early (first two years) deaths, and both categories. RESULTS: The univariate analysis failed to demonstrate in all cases a U or inverse J shaped relation. The Cox coefficients for the linear and quadratic terms of BMI proved significant for both young and mature women. The minimum of the curve was located at 27.0 (24.0, 30.0, 95% confidence limits, CL) and 31.8 (25.5, 38.2, 95% CL) units of BMI, for young and mature women respectively. Similar findings were obtained even when exclusion were performed. No relation was found for young men while for mature adult men only the model for all subjects retained significant curvilinear relation (minimum 29.3; 22.4, 36.2, 95% CL). CONCLUSION: These uncommon high values of BMI carrying the minimum risk of death seems to be in contrast with weight guidelines. A confirmation of these findings in other population groups might induce the consideration of changes in the suggested healthy values of BMI.

Effects of cicletanine in the left circumflex coronary artery occlusion-reperfusion canine model of sudden death: analysis of 107 experiments using Cox's proportional hazards model.

Multivariate analysis of survival using Cox's proportional hazards model demonstrates that several clinically measurable covariates are determinants of life-threatening arrhythmias following left circumflex coronary artery occlusion-reperfusion in 107 dogs. These are heart rate, ST segment elevation and mean aortic pressure immediately (3 min) following occlusion, and the presence of early (0-10 min) post-occlusion sustained ventricular tachycardia. The risk of occlusion-reperfusion ventricular fibrillation was determined according to Cox's solution based on ST segment elevation, thus enabling quantification of the role of cicletanine. Since cicletanine-treated dogs had reduced mean ST segment elevation at 3 min post-occlusion, lower incidence of early post-occlusion (0-10 min) sustained ventricular tachycardia, and increased endogenous production of prostacyclin, and the latter was inversely correlated with the level of ST segment elevation, it is concluded that such favourable effects on the ischaemic myocardium were contributory to the improved outcome in these experiments. These effects on the ischaemic myocardium obtained in spite of a hypotensive action in the experimental setting might be regarded as desirable and it is therefore suggested that they should be further investigated by pharmacodynamic studies in human subjects.

Long-term time-related predictivity of coronary events as a function of a single measurement of serum cholesterol and systolic blood pressure.

OBJECTIVE: To study the time-related association of a single measurement of serum cholesterol and systolic blood pressure with the occurrence of a first coronary event in a population sample of middle-aged men. METHODS AND RESULTS: A single measurement of serum total cholesterol and systolic blood pressure (along with age, cigarette consumption, physical activity at work and body mass index as possible confounders) was made in 1,605 coronary disease-free men aged 40-59 belonging to the Italian rural cohorts of the Seven Countries Study. During 25 years of follow-up 353 men developed a first event, that is a coronary death (sudden or not), and definite or possible myocardial infarction. Twenty-five partitioned proportional hazards models were solved, one for each independent year of follow-up, to predict the risk of incident events. Single-year hazard functions, separately for serum cholesterol and systolic blood pressure, were cumulated and smoothed. The resulting curves showed a regularly increasing risk for coronary events. They fit straight lines, with large correlation coefficients for both serum total cholesterol (r = 0.99) and systolic blood pressure (r = 0.99). These slopes were similar to the coefficients estimated by a single proportional hazards model solved for all events during 25 years. CONCLUSION: A single measurement of serum total cholesterol and systolic blood pressure in middle aged-men maintains a regular and monotonic relationship with occurrence of a first coronary event during 25 years of follow-up.

Coronary heart disease deaths in 25 years. The experience in the three Serbian cohorts of the Seven Countries Study.

Three cohorts of men aged 40-59 at entry examination were enrolled between 1962 and 1964 in the Serbian section of the Seven Countries Study of Cardiovascular Diseases. They were a sample in the rural village of Velika Krsna (n = 511), the workers in an agro-industrial cooperative in the city of Zrenjanin (n = 516), and the University professors of Belgrade (n = 536). At entry examination and then after 5 and 10 years, some cardiovascular risk factors were measured while the follow-up for mortality and causes of death was continued for 25 years. The 25 year standardized death rates from coronary heart disease (CHD) were higher in Zrenjanin (177 per 1000) and lower in Belgrade (118) and Velika Krsna (122). The multivariate prediction of CHD mortality by the Cox model in the lumped samples showed significant coefficients for age, body mass index, systolic blood pressure and cigarette consumption. The coefficient of serum cholesterol did not reach a statistically significant level. An unknown but significantly protective factor was identified for the Belgrade sample, likely bound to the higher social class of this group. Changes of systolic blood pressure in the first 10 years of follow-up were positively and highly related to the deaths occurred in the subsequent 15 years. The three population groups showed, between year 0 and year 10 follow-up, large increases in mean levels of blood pressure and mainly of serum cholesterol (+30 mg/dl in Velika Krsna; +36 mg/dl in Belgrade and +61 mg/dl in Zrenjanin). The sample in Zrenjanin started from intermediate levels (168.7 mg/dl) but attained the greatest increase and reached the highest CHD death rate in 25 years.

Serum uric acid for short-term prediction of cardiovascular disease incidence in the Gubbio population Study.

OBJECTIVE: The Gubbio Study is an Italian population study measuring risk factors for and incidence of major cardiovascular diseases. This analysis investigates the association of serum uric acid with the incidence of coronary and cardiovascular events. METHODS: A population sample of 2469 men and women aged 35-74 years, free from major cardiovascular diseases and in whom serum uric acid was measured in 1983 along with other standard risk factors, were followed up for 6 years and the incidence of coronary heart disease (CHD) and all cardiovascular atherosclerotic (CVD) events, both fatal and non-fatal, was computed. Proportional hazards models were used for the prediction of these events. RESULTS: In six years 61 CHD hard criteria, 109 CHD any criterion and 149 CVD events were recorded. Age-adjusted rates per 1000 of the 3 event categories were computed in sex-specific quintiles (Q) of serum uric acid with 428 +/- 76 (Q5) and 198 +/- 42 (Q1) micromol/l, respectively. Although higher rates were seen in Q5 as compared to Q1 for all three first event categories considered (relative risks 6.2, 3.6 and 3.7, respectively), a statistically significant trend was seen only for CVD all criteria (t = 3.63, p < 0.036). These trends were borderline significant for CHD any criterion (t = 2.92, p < 0.06) and not significant for CHD hard criteria (t = 2.23, p < 0.11). In multivariate models, adjusted for 8 other risk factors, serum uric acid showed a statistically significant contribution to predict CVD incidence [relative risk (RR) for 92 micromol/l difference of 1.24 with 95% confidence intervals (CI) 1.05-1.45], whereas the statistical contribution to predict CHD any criterion (RR = 1.19 with CI 0.98-1.45) and CHD hard criteria (RR = 1.20 with CI 0.93-1.55) was not significant. Diuretic treatment and blood urea, as further confounders, were positively and significantly related to event incidence (RR ranging from 1.21 to 2.00) but serum uric acid maintained its independent and statistically significant role in the prediction of CVD events (RR = 1.18 with CI 1.00-1.39). Presence of specific treatments to lower serum uric acid levels (in 1.13% of the population), tested as final confounders, was not statistically contributory. CONCLUSIONS: Increased serum uric acid levels are independently and significantly associated with risk of CVD events in the 6-year follow-up of the Gubbio Study. Longer follow-up is needed before the contributory role of serum uric acid can be properly assessed to explain CHD incidence.

Twenty-five-year cardiovascular disease incidence among middle-aged men. Disease burden, time shape, predictors, risk probabilities.

BACKGROUND: This analysis aims at describing the 25-year experience in cardiovascular incidence in a sample of middle-aged men in rural Italy. METHODS: A total of 1712 men aged 40-59 years were examined in 1960 in two rural Italian cohorts belonging to the Seven Countries Study. Major risk factors were measured and a monitoring system for incidence of cardiovascular events was in operation for the next 25 years centered on the first event occurring within each subgroup of cardiovascular diseases. Data were modeled by the Weibull distribution incorporated in the accelerated failure time model. RESULTS: Among 1695 cardiovascular disease-free men at entry, 51.3% experienced at least one cardiovascular event, the first being a coronary heart disease (35.6%), a cerebrovascular disease (17.8%) or a peripheral artery disease (13.0%). Among all first events the most common was intermittent claudication (17.6%), followed by angina pectoris (16.6%). A proportion of 13% of all initial episodes was rapidly fatal, whereas 38 % of subjects developing a cardiovascular event died within the 25-year deadline. Age, cigarette smoking, diabetes, corneal arcus, serum cholesterol, systolic blood pressure, and vital capacity fed into the accelerated failure time model showed a statistically significant association with cardiovascular disease incidence (inverse for vital capacity). The same model provided the shape of hazard during the 25 years with major events continuing to appear in an increasing exponential fashion, while soft criteria events were less likely to appear as a first event in the late phase of follow-up. CONCLUSIONS: In middle-aged men 25-year incidence of cardiovascular diseases is high and more relevant compared to that of traditional hard criteria coronary heart disease that in the past has attracted almost exclusive interest.

First risk functions for prediction of coronary and cardiovascular disease incidence in the Gubbio Population Study.

BACKGROUND: The Gubbio study is an Italian population study which measures the risk factors and incidence of major cardiovascular diseases. This analysis produces multivariate models for the prediction of cardiovascular end-points. METHODS: A population sample of 2,963 men and women aged 35-74, free from major cardiovascular diseases, was examined in 1983 with risk factor measurement, and a 6-year incidence was computed for coronary heart disease and all cardiovascular (atherosclerotic) events. Proportional hazards models were solved for the prediction of these events. RESULTS: Over a 6-year period, 74 hard criteria, and 126 any criterion coronary heart disease and 174 cardiovascular events were recorded. Multivariate models showed the predictive power of sex (relative risk ranging 1.63 to 2.60), age (relative risk for 5-year difference ranging 1.38 to 1.48), systolic blood pressure (relative risk for 20 mmHg difference ranging 1.17 to 1.27), HDL cholesterol (relative risk for a difference of 10 mg/dl ranging 0.73 to 0.81), non-HDL cholesterol (relative risk for 40 mg/dl difference ranging 1.15 to 1.27), cigarette smoking (relative risk for 10 cigarette difference ranging 1.21 to 1.28), and body mass index (relative risk for 3 units ranging 0.99 to 1.02). All coefficients were statistically significant except that for body mass index, they were larger for hard criteria coronary heart disease, and their magnitude was similar to that found in previous Italian population studies. CONCLUSIONS: Traditional cardiovascular risk factors predict coronary and cardiovascular events in another Italian population study confirming previous findings and similar predictive models.

An Italian chart for cardiovascular risk prediction. Its scientific basis.

A risk chart for primary prediction of major coronary and cerebrovascular events based on Italian population data was created. Material from three Italian population studies was available: the Italian Rural Areas of the Seven Countries Study (no. 1712), the Gubbio Study (no. 3061) and the ECCIS Study (no. 4998) for a total of 9771 men and women aged 35 to 74 years and followed-up from 5 to 15 years, for a total of over 55,000 person/years. Sex, age, diabetes, cigarette smoking, systolic blood pressure and serum cholesterol were selected as risk factors, while the endpoint was established as the occurrence of the first major coronary or cerebrovascular event in 10 years. The accelerated failure time model was used as the predictive model. Two models were adopted, i.e., for relatively younger subjects (45-59 years) and for relatively older subjects (60-74 years). Both produced highly significant coefficients for each of the selected risk factors. The two models carried a satisfactory discriminating power, with 40% to more than 50% of all events located in the upper quintile of the estimated risk. Sex, age (6 classes), diabetes, cigarette smoking (4 classes), systolic blood pressure (4 classes) and serum cholesterol (5 classes) were considered for the creation of a risk map derived from multivariate models. A total of 1920 cells were filled with different colors corresponding to 6 classes of absolute risk. A similar set of cells was filled with another color scale for the estimate of the relative risk versus subjects of the same age and sex carrying Italian mean levels of risk factors. The chart is being distributed to the Italian medical profession as a practical tool to select high-risk individuals for the primary prevention of major cardiovascular diseases.

[Notes to the regulatory Appendix 13 of the Italian Committee for Drugs]. / "Not e" alla recente "nota 13" della commissione unica del farmaco.

The Italian Committee for Drugs has recently modified "Appendix 13" to a recent Italian regulation related to reimbursement of hypolipidemic agents for primary or secondary prevention of heart diseases. There is some confusion in concepts, terminology and phrasing, also dealing with disease definition, which need comment. Moreover, "Appendix 13" suggests to estimate risk based on charts derived from the Framingham experience, which are inappropriate when applied to Italy. Finally, "Appendix 13" is not clear as to how categorize high risk individuals. There has been a growing interest in estimating coronary risk since 1994, probably as the result of primary and, secondary intervention trials with statins used to lower blood cholesterol levels. On the other hand, European guidelines have been published, accompanied by risk charts (derived from the Framingham study) helping to index individuals who may benefit from treatment of coronary risk factors. At least thirteen such or similar instruments have been produced worldwide (and three of these in Italy) to estimate coronary risk. In Italy, there are other instruments in preparation. Data are reviewed wherefrom it is possible to conclude that it is inadequate, since substantially erroneous, to use risk functions to estimate absolute coronary risk when these are derived from largely different populations as to those in which practical applications are looked for.

[Obesity and mortality. Italian epidemiologic data]. / Obesità e mortalità. Dati epidemiologici italiani.

The relationship of indicators of obesity, such as the body mass index (BMI) and the skinfold thickness in some areas (SKIN) to all causes mortality have been analyzed in three italian epidemiological studies. They are the Seven Countries Study--italian areas conducted on 2480 men at entry and followed-up for 25 years; the Brisighella study conducted on 1123 men and 1100 women aged 30-69 and followed-up for 15 years; and the NFR study in Rome conducted on 3395 men aged 46-66 and followed-up of 6.5 years. The univariate analysis concerning the BMI for various age groups, the two sexes, and variable periods of follow-up has almost systematically showed a parabolic inverted J shaped relationship with minimal levels of risk for BMI values of 27-29 units. However this was not the case for the women group and for the oldest men where no clear relationship was found. The analysis concerning the SKIN provided similar but less clear-cut results. The multivariate analysis has confirmed the parabolic relationship of BMI to all causes mortality even in the presence of other 4-5 covariates. The left branch of risk is higher than the right one and its slope could be reduced, although not completely, by the exclusion of heavy smokers, of those who died within the first 5 years of follow-up, of those who were carriers of severe diseases at entry examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Normotensive middle-aged men after 5-10 years: normal blood pressure or hypertension?

We evaluated the incidence of hypertension over 5-10 years of follow-up in middle-aged men, 40-59 years at entry, selected from the Italian section of the Seven Countries Study. Out of the 2480 subjects, 852 were normotensive at entry [systolic blood pressure (SBP) less than 140 mmHg and diastolic blood pressure (DBP) less than 90 mmHg)], alive after 10 years and had been evaluated repeatedly after 5 and 10 years. After 5 years, 31.3% had developed borderline hypertension (140 less than or equal to SBP less than 160 and 90 less than or equal to DBP less than or equal to 95 mmHg) and 14.6% had developed definite hypertension (SBP greater than or equal to 160 mmHg or DBP greater than or equal to 95 mmHg). During the next 5 years, out of the 267 borderline hypertensives, 28.5% became definite hypertensives, while 29.6% reverted to normal blood pressure. Out of the 124 definite hypertensives, 46% remained in this category, while 34.7% became borderline hypertensives and 19.4% became normotensive. In men aged 60-69 years, less than 2% of hypertensives were being effectively treated and changes in body weight were closely related to blood pressure. In addition, out of 461 normotensive subjects who remained normotensive at the 5-year examination, 63.6% remained normotensive in the next 5 years also, while 28% developed borderline hypertension and only 8.4% moved into the definite hypertensive class. These data suggest that a normotensive subject aged 40-59 years has a 34.4% probability of remaining normotensive in the next 10 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Lifestyle habits and mortality from all and specific causes of death: 40-year follow-up in the Italian Rural Areas of the Seven Countries Study.

OBJECTIVES: Three lifestyle factors were investigated in a population study to explore their relationships with a long-term mortality. MATERIAL AND METHODS: In a cohort of 1564 men aged 45-64 and examined in 1965 within the Italian Rural Areas of the Seven Countries Study, smoking habits, physical activity at work and eating habits (as derived from factor analysis) were determined. During the follow-up 693 men died in 20 years and 1441 in 40 years. RESULTS: In Cox proportional hazards models men smoking cigarettes (versus never smokers), those having a sedentary activity (versus the very active) and those following the Diet Score 1, indexing an unhealthy Diet (versus men with a Diet close to the healthy Mediterranean style) had highly significant hazards ratios (HR) in relations with 20- and 40-year mortality from all causes, coronary heart disease (CHD), cardiovascular disease (CVD) and cancer. HR for all causes in 40 years were 1.44 (95% confidence intervals, CI, 1.27 and 1.64) for smokers, 1.43 (CI 1.23 and 1.67) for sedentary people, and 1.31 (CI 1.15 and 1.50) for men with unhealthy diet. Larger HR were found for CHD, CVD and cancers deaths. Combination of 3 unhealthy risk factors versus their absence was associated with 4.8-year life loss in the 20-year follow-up and 10.7-year in the 40-year follow-up. CONCLUSIONS: Lifestyle behavior linked to physical activity and smoking and eating habits is strongly associated with mortality and survival in middle aged men during long-term follow-up.

Predicting all causes mortality in the general population as a function of blood pressure and smoking habits measured in population samples: a pilot study. Research Group ATS-RF2.

Nine population samples of mean aged 40-59, for a total of 1777 individuals drawn from nine health units, were examined in 1978-79 for the measurement of some risk factors possibly related to total mortality. The analysis evaluated the possible relationship between blood pressure levels and smoking habits measured in the population samples and the official death rates covering the period 1980-82 in the health units from which the samples were drawn. The analysis was conducted in a direct way but also by the help of a risk function linking blood pressure and smoking habits as obtained from another Italian population sample. The cograduation test between mean blood pressure in the nine areas and total mortality was 0.58 (linear correlation 0.57); the cograduation test was -0.70 for non-smokers, 0.62 for ex-smokers, 0.50 for present smokers (linear correlation of -0.27, 0.29 and 0.14 respectively). The death rates estimated by the risk function (Cox model) tended to overestimate the death rates from 5 to 64% (average 36.3%). The cograduation test between expected and observed death rates was 0.56 (linear correlation coefficient 0.66). Some limitations of this pilot study are largely explained by the small size of the sample and by the need to use a risk function provided by another population sample.

Coronary risk factors predicting early and late coronary deaths.

OBJECTIVE: To study the time related association of a single measurement of coronary risk factors with coronary heart disease (CHD) deaths occurring during a very long follow up period in a population sample of middle aged men. DESIGN, SETTING, AND METHODS: Age, systolic blood pressure, serum total cholesterol, physical activity at work, body mass index, and cigarette smoking were measured once in 1622 CHD-free men aged 40-59 belonging to the Italian rural cohorts of the seven countries study. During 35 years of follow up 214 men died from CHD (sudden death and definite myocardial infarction). Seven partitioned proportional hazards models were solved, one for each independent five year block of follow up, to predict the risk of CHD death. RESULTS: The seven, five year partitioned hazard functions were cumulated and smoothed for each risk factor. The resulting curves showed a regularly increasing time trend in risk for coronary deaths as a function of age, serum cholesterol, systolic blood pressure, and cigarette smoking and a regularly decreasing risk for physical activity. The curves fit straight lines, with large squared correlation coefficients ranging from 0.92-0.97. This suggests a relatively constant strength in the association of risk factor levels with events, which are predicted whatever the length of time after risk factors were measured. These findings were not altered by adding to the models risk factor changes preceding the quinquennium of death. CONCLUSION: A single measurement of some coronary risk factors in middle aged men maintains a regular and almost monotonic relation with the occurrence of CHD deaths during 35 years of follow up.

The duration of the association between serum cholesterol and coronary mortality: a 35-year experience.

OBJECTIVE: Our purpose was to study the time-related association between a single measurement of total serum cholesterol and the occurrence of coronary deaths in a population sample of middle-aged men. DESIGN: This is a longitudinal population study with multiple measurements of serum cholesterol and a 35-year follow-up for coronary mortality in 1622 coronary disease-free men aged 40-59 years belonging to the Italian rural cohorts of the Seven Countries Study. METHOD: A single measurement of serum cholesterol (plus those of five other risk factors as possible confounders) was considered. During 35 years of follow-up, 214 men died from coronary heart disease. Annual partitioned proportional hazards models were solved, one for each independent year of follow-up, to predict the risk of coronary heart disease deaths. Single-year hazard functions were cumulated and smoothed. Similar analyses were made starting from cholesterol measurements taken at years 5, 10 and 20 of follow-up. RESULTS: The resulting hazard curves showed regularly increasing risk for coronary events and fitted straight lines with large correlation coefficients, demonstrating a strong association of serum cholesterol with both early and late events. The slopes were steeper for cholesterol measurements taken at younger ages. The slope for cholesterol measurement taken at year 20 (age 60-84 years) was flat. In slopes starting at an early age, two components could be isolated corresponding to different associations with events (stronger for early events when measurements were taken around the age of 50 years and for late events when measurements were taken around the age of 55 or 60 years). CONCLUSION: A single measurement of total serum cholesterol in middle-aged men maintains a relatively monotone relationship with the occurrence of coronary heart disease deaths over 35 years. In the study population, measurements taken in late adulthood had smaller or null association with coronary disease deaths.

Coronary heart disease incidence in northern and southern European populations: a reanalysis of the seven countries study for a European coronary risk chart.

OBJECTIVE: A systematic reanalysis of 10 year coronary heart disease incidence data from the northern and the southern European cohorts of the seven countries study, to contribute indirectly to the production of a European coronary risk chart. DESIGN AND SETTING: Men aged 40-59 years at entry were studied in three northern European cohorts based in Finland and Netherlands (n = 2213); and in 10 southern European cohorts based in Italy, former Yugoslavia, and Greece (n = 5897). Multiple logistic models for the prediction of coronary deaths, coronary incidence (hard criteria), and coronary incidence (any criterion) were solved for the two geographical groups and their pool. Risk factors fed into the models were age, systolic blood pressure, serum total cholesterol, and cigarette smoking. RESULTS: 10 year coronary heart disease mortality and incidence were higher in northern than in southern Europe, with ratios around 2.65. Ratios among the three coronary heart disease manifestations were identical in the two cultural groupings. Coefficients of the multiple logistic models were similar and not significantly different between the two groupings. When applying the coefficients back to the same or the opposite population, the relative risk was large and similar in the different cultures. Relative risk was larger for more severe coronary heart disease manifestations. The absolute risk was overestimated when applying the northern European model to southern European populations and vice versa, with ratios of about 1.5 and 0.5, respectively. Coronary risk charts created to reproduce the shape of those incorporated in recent European guidelines confirmed the excess of absolute risk in the northern compared with the southern European cohorts, all else being equal. CONCLUSIONS: In theory, a more appropriate European coronary risk chart could be produced by adopting coefficients to correct for different background incidence rates in different cultures. Other coefficients could appropriately be used to transform mortality risk into incidence risk.