Mariapaola Lanti

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.

Evaluation of 10 QT prediction formulas in 881 middle-aged men from the seven countries study: Emphasis on the cubic root Fridericia's equation

In 881 middle-aged men from one Italian cohort of the Seven Countries Study, QT and RR intervals were measured in lead 2 from resting ECGs (25 mm/sec) and fitted separately with 10 mathematically different QT prediction formulas. The relative accuracy of fit to data was assessed from the minimum mean-squared residual and the minimum Akaike Information Criterion values. Using the Minnesota code, 588 men had normal (group 1) and 293 had abnormal (group 2) ECGs. A better fit to QT-RR data by all formulas was observed in group 1, compared with group 2. Among one-parameter equations in both groups, the cubic root Fridericias formula is better suited to fit the data than the Bazetts square root or other formulas. The former compares favorably with multiparameter equations or with the inverse relation and gives the best fit in group 2. Thus the cubic root equation might be more accurate than the square root or several complex formulas for correcting measured QT intervals for cardiac cycle length in middle-aged men.

Inter-cohort differences in coronary heart disease mortality in the 25-year follow-up of the seven countries study

Sixteen cohorts of men aged 40–59 years at entry were examined with the measurement of some risk factors and then followed-up for mortality and causes of death for 25 years. These cohorts were located in the USA (1 cohort), Finland (2), the Netherlands (1), Italy (3), the former Yugoslavia (5), Greece (2), and Japan (2), and included a total of 12,763 subjects.Large differences in age-adjusted coronary heart disease (CHD) death rates were found, with extremes of 45 per 1000 in 25 years in Tanushimaru, Japan, to 288 per 1000 in 25 years in East Finland. In general, higher rates were found in the US and Northern European cohorts as compared to the Southern European and Japanese cohorts. However, during the last 10 years of follow-up large increases of CHD death rates were found in some Yugoslavian areas. Out of 5 measured entry characteristics treated as age-adjusted levels (serum cholesterol, systolic blood pressure, cigarette smoking, body mass index and physical activity at work), only serum cholesterol was significant in explaining cohort differences in CHD death rates.Over 50% of the variance in CHD death rates in 25 years was accounted for by the difference in mean serum cholesterol. This association tended to decline with increasing length of follow-up, but this was due to the great changes in mean serum cholesterol in the two Jugoslavian cohorts of Velika Krsna and Zrenjanin. When these two cohorts were excluded the association increased with time.Changes in mean serum cholesterol between year 0 and 10 helped in explaining differences in CHD death rates from year 10 onward.It can be concluded that this study suggests that mean serum cholesterol is the major risk factor in explaining cross-cultural differences in CHD.

Mediterranean Adequacy Index: correlation with 25-year mortality from coronary heart disease in the Seven Countries Study

BACKGROUND AND AIM The Mediterranean Adequacy Index (MAI) is an overall indicator characterising a diet in comparison with a Reference Mediterranean Diet. We computed the MAI of random samples of men surveyed for their eating habits in the 16 cohorts of the Seven Countries Study, and found that it inversely correlated with the 25-year death rates from coronary heart disease in the 16 cohorts (R = -0.72; p = 0.001). The correlation coefficient was -0.84 (p < 0.001) when the MAI was converted into natural logarithms. CONCLUSIONS These findings once again support the association between typical Mediterranean eating habits and protection against coronary heart disease.

Cardiovascular risk factors as determinants of 25-year all-cause mortality in the seven countries study

This analysis aims at describing all-cause mortality and their determinants in 16 cohorts of middle-aged men of eight nations. A total of 12,763 men aged 40–59 years were enrolled in the late 1950s and early 1960s in 16 cohorts located in the USA, Finland, The Netherlands, Italy, Croatia, Serbia, Greece and Japan. The highest death rates were found in Slavonia–Croatia, due to high rates of infectious diseases and violence (death rate of 610 per 1000), and in East Finland due to high rates from coronary heart disease (death rate of 597 per 1000). The lowest death rates were found in a highly educated group in Belgrade, Serbia (death rate 295 per 1000) and in Crete, Greece (death rate 314 per 1000). The ecological analysis showed no significant relationship between mean risk factor levels and all-cause death rates except for the direct association with systolic blood pressure during the first 15 years follow-up. Individual multivariate analysis on eight national pools showed that age, systolic blood pressure, and smoking habits are direct, significant, and universal long-term predictors of all-cause mortality. Serum cholesterol, physical activity and body mass index were so only in some areas. Multivariate coefficients were similar across nations. Pooled hazards ratios were 1.55 for a difference of 5 years of age (CI: 1.51–1.59); 1.23 for 10 cigarettes smoked per day (CI: 1.20–1.26); 0.91 for one unit (based on three grades) of physical activity score (CI: 0.87–0.95); 1.04 for 1 mmol/l of serum cholesterol (CI: 1.02–1.07); and 0.93 for three units of body mass index (CI: 0.91–0.96). In conclusion some cardiovascular risk factors predict long-term risk of all-cause mortality in different cultures.

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.

Impact of the Gubbio population study on community control of blood pressure and hypertension

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) ⩾ 160 mmHg or diastolic blood pressure (DBP) ⩾ 95 mmHg or use of anti-hypertensive drugs; recent definition: SBP ⩾ 140 mmHg or DBP ⩾ 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.

Prevention of postischemic ventricular fibrillation late after right or left stellate ganglionectomy in dogs.

To gain insight into the differences in antiarrhythmic potential of right vs left stellate ganglionectomy, 72 dogs were randomized to either unilateral stellectomy or second intercostal space thoracotomy and left circumflex coronary arteriovenous pedicle occlusion was performed, without vagotomy, a mean of 8 weeks later under anesthesia. The type and timing of ventricular ectopic beats, including both nonsustained and sustained ventricular tachycardia and ventricular fibrillation, were investigated. Several covariates, including postischemic electrocardiographic changes, were considered. Both right and left stellate ganglionectomy reduced the incidence of early (0 to 10 min) (p = .004 and p = .001, respectively) and total (0 to 60 min) (p = .009 and p = .008, respectively) ischemia-induced ventricular fibrillation, and improved outcome (p = .0013 and p = .0012, respectively). Early sustained ventricular tachycardia was similarly reduced (p = .02) in both stellectomized groups. By contrast, neither the type nor the time distribution of the other forms of ventricular arrhythmias differed significantly among the randomized groups. The multivariate Coxs regression model showed that ST segment elevation at 3 min postocclusion, unilateral stellate ganglionectomy (either right or left), sex, and weight were significant independent predictors of the incidence of ventricular fibrillation during the occlusion period. Lower ST segment elevation and reduced incidence of sustained ventricular tachycardia in the early postischemic period might explain improved outcome in stellectomized dogs by Cox analysis. The side of intervention (either stellectomy or sham operation) did not influence survival; however, left-sided interventions were more effective than right-sided ones. These results confirm the previously reported antifibrillatory effect of left and indicate like effects of right stellate ganglionectomy in a randomized experimental study.

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 (Δ-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 (Δ-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.

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) μmol/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 μmol/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.