Martti J. Karvonen

Probability of Middle-Aged Men Developing Coronary Heart Disease in Five Years

Characteristics of 11,132 men aged 40-59 years and free from coronary heart disease (CHD) at entry were related to follow-up experience, using multivariate analysis. In 5 years among 2,404 U. S. railroad men and 8,728 European men there were 615 cases of CHD, 214 of whom died from CHD or suffered definite nonfatal infarction.With five entry characteristics (age, systolic blood pressure, serum cholesterol, smoking habit, and body mass index), multiple logistic solutions for Europeans and Americans, separately, gave estimates of the individual probability of CHD. Classified by deciled scores for these probabilities, the expected and observed CHD cases were highly correlated (r = 0.930-0.981). Predictions based on European data applied to Americans, and vice versa, gave similar high correlations but American incidence was excessive compared with European experience.Application of the analysis coefficients obtained from data in Europe and in the U. S. railroad to 6,221 other U. S. men 40-59 years of age, CHD-free at entry, gave good prediction of relative risk (r = 0.94) for observed versus predicted cases in deciles of risk score; however, the actual numbers of cases were underpredicted.From single measurements of a few characteristics the multiple logistic solution usefully estimates the relative risk of CHD for individuals. Age, systolic pressure, and serum cholesterol are universally powerful predictors of risk. Variables not measured in this study or not yet identified contribute to the risk of CHD among American men.

Coronary heart disease: overweight and obesity as risk factors.

Abstract The relationship of relative weight and of skinfold thickness to the 5-year incidence (632 cases) of coronary heart disease was examined in men aged 40 through 59 years at entry to the stu...

Comparison of Multivariate Predictive Power of Major Risk Factors for Coronary Heart Diseases in Different Countries: Results from Eight Nations of the Seven Countries Study, 25-Year Follow-up

BACKGROUND It was hypothesized that among eight national groups of men aged 40-59 years enrolled in the Seven Countries Study, the multivariate coefficients of major risk factors predicting coronary heart disease mortality over 25 years would be relatively similar. MATERIALS AND METHODS Sixteen cohorts were located in eight nations and pooled, comprising one cohort in the USA, two in Finland, one in the Netherlands, three in Italy, two in Croatia (former Yugoslavia), three in Serbia (Yugoslavia), two in Greece and two in Japan, for a total of over 12000 subjects at entry. Coronary heart disease (CHD) mortality was defined as fatal myocardial infarction or sudden coronary death, and proportional hazard models were solved, for each country, with age, serum cholesterol level, systolic blood pressure and cigarette consumption as covariates. RESULTS The relationships between risk factors and CHD mortality were statistically significant for all risk factors and for all countries, except for age in Croatia and Japan, cholesterol in Croatia and Japan, systolic blood pressure in Serbia and Greece, and cigarette-smoking in the Netherlands, Croatia, Serbia and Greece. When comparing all pairs of coefficients (28 comparisons for each factor) significant differences were found on four occasions for age, on six occasions for cholesterol, on no occasion for blood pressure and on four occasions for cigarette-smoking. Other tests suggested a substantial homogeneity among multivariate coefficients. Estimates for pooled coefficients were: age, in years, 0.0570 (95% confidence limits 0.0465 and 0.0673); relative risk for 5 years 1.33 (95% confidence limits 1.26 and 1.40); serum cholesterol level in mg/dl, 0.0057 (95% confidence limits 0.0045 and 0.0069); relative risk for 40 mg/dl 1.31 (95% confidence limits 1.20 and 1.31); systolic blood pressure in mmHg, 0.0160, (95% confidence limits 0.0134 and 0.0185), relative risk for 20 mmHg 1.38 (95% confidence limits 1.31 and 1.45); cigarettes per day, 0.0220 (95% confidence limits 0.0170 and 0.0272); relative risk for 10 cigarettes per day 1.25 (95% confidence limits 1.18 and 1.31). CONCLUSIONS Great similarities were found in the multivariate coefficients of major coronary risk factors to CHD risk derived from population samples varying in CHD frequency.

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.

Seven Countries Study. First 20-Year Mortality Data in 12 Cohorts of Six Countries

Out of the original 16 cohorts in the Seven Countries Study on Cardiovascular Diseases, 12 population samples in six countries have reached the 20 year follow-up deadline. Data on mortality became fully available for a total of 8287 men aged 40-59 at entry examination (two cohorts in Finland, one in the Netherlands, three in Italy, two in Yugoslavia, two in Greece, and two in Japan). Death rates from CHD as well as from all causes follow the traditional falling north to south trend (18 fold between the extremes for CHD; 2.7 fold for total mortality). The differences in all causes mortality are, however, largely accounted for by the variation in CHD mortality. The mean entry levels of serum cholesterol and representative levels of the consumption of saturated fats, mono-unsaturated fats, poly-unsaturated fats and carbohydrates explain a large proportion of inter-cohort difference in CHD mortality (81% for saturated fats). By applying the proportional hazards model to the pools of national cohorts, with CHD deaths as end-point and five risk factors as covariates, only age and mean blood pressure are universally significant predictors of fatal events. Cholesterol, smoking habits, body mass index and physical activity play some part but not in all the pools. Age and mean blood pressure are also the only universal risk factors for all causes of death.

Serum selenium and risk of cancer: a prospective follow-up of nine years

The association between serum selenium concentration and the risk of cancer was studied in 1110 men aged 55 to 74 years in two rural areas of Finland. The men were followed‐up prospectively for 9 years and there were 109 new cases of cancer, with the cases of the first follow‐up year excluded. The serum selenium concentrations were adjusted for age, area, smoking, serum cholesterol, and alcohol intake. The patients had a slightly lower adjusted mean serum selenium than the subjects without cancer at the end of the follow‐up (±standard error of mean) 53.9 ± 1.5 and 55.3 ± 0.5 μg/1, respectively. The relative risks of cancer were essentially the same when these were calculated in the tertiles of the serum selenium distribution. Thirty‐seven men had a history of cancer at baseline or had cancer diagnosed during the first follow‐up year and their adjusted mean serum selenium was 49.4 ± 2.6 μg/1, which was significantly lower (P<0.05) than that of the subjects without cancer during the follow‐up.

Indices of relative weight and obesity

Analyses are reported on the correlation with height and with subcutaneous fat thickness of relative weight expressed as per cent of average weight at given height, and of the ratios weight/height, weight/height squared, and the ponderal index (cube root of weight divided by height) in 7424 ‘healthy’ men in 12 cohorts in five countries. Analyses are also reported on the relationship of those indicators of relative weight to body density in 180 young men and in 248 men aged 49–59. Judged by the criteria of correlation with height (lowest is best) and to measures of body fatness (highest is best), the ponderal index is the poorest of the relative weight indices studied. The ratio of weight to height squared, here termed the body mass index, is slightly better in these respects than the simple ratio of weight to height. The body mass index seems preferable over other indices of relative weight on these grounds as well as on the simplicity of the calculation and, in contrast to percentage of average weight, the applicability to all populations at all times.

Coronary heart disease and drinking water: A search in two Finnish male cohorts for epidemiologic evidence of a water factor☆

A search for the hypothetical factor in drinking water that might influence the mortality from C.H.D. was made in two rural areas in western and eastern Finland. A 10-yr follow-up of the resident males had shown a higher death rate from C.H.D. in the eastern area. The difference is only partly explained by the currently known risk factors of C.H.D. The levels of 22 water characteristics were investigated in 327 wells and six tap-water samples. In both areas the water used for drinking is soft but the mean concentrations of several components differ. In general, the concentrations are lower in the eastern area. The difference is significant for pH, F, Ca, Mg, Na, and Cr. The concentrations of NO3, K, Cu, Co, Ni, and Ba are significantly higher in the eastern area. In both populations there were indications that death from, or the development of, C.H.D. was connected with the quality of the water, particularly with low concentrations of constituents. Assuming that a single water constituent is responsible for the difference in mortality from C.H.D. between the cohorts, the elements most suspect were chromium and, to a lesser degree, copper. C.H.D. was associated with low concentrations of chromium and high concentrations of copper in drinking water. Findings on magnesium were equivocal, and no association was observed with calcium. The relationships of the components of drinking water to the following risk factors of death from C.H.D. were also investigated: systolic blood pressure, serum cholesterol, extrasystoles in ECG, and cigarette smoking. In the eastern area the concentration of serum cholesterol correlated negatively with the concentration of chromium in drinking water.

Smoking, carbon monoxide, and atherosclerotic diseases.

Smoking habits and random measurements of the proportion of haemoglobin bound to carbon monoxide (COHb%) were examined for their association with atherosclerotic diseases in 1068 men aged 55 to 74 years from rural areas of Finland. COHb% and smoking history were similarly associated with claudication and coronary heart disease. Random measurements of COHb% did not show a better overall relation to the prevalence of atherosclerotic diseases than smoking history, though COHb% showed a stronger association with a probable previous myocardial infarction. Further studies are needed to clarify the role of carbon monoxide in atherosclerosis.

Does the Predictive Value of Baseline Coronary Risk Factors Change over a 30-Year Follow-Up?

The association of baseline serum total cholesterol, systolic blood pressure, smoking and body mass index with coronary heart disease (CHD) mortality was analyzed among 1,619 men aged 40-59 at baseline. Analyses were made separately for the first, second and third decade of follow-up. Serum cholesterol and smoking more than 9 cigarettes daily were strong predictors of risk of CHD death (n = 450) occurring early and late during the 30-year follow-up. After 20 years of follow-up, systolic blood pressure was no longer associated with CHD risk. In contrast, highest tertile of body mass index (over 24.7 kg/m2) was only then associated with increased CHD risk. The correlations between the baseline and the 30-year risk factor values were 0.42 for serum cholesterol (n = 444), 0.28 for systolic blood pressure (n = 444) and 0.57 for body mass index (n = 429). Our results showed large differences in the long-term predictive power of the classical coronary risk factors. The reasons for these differences are discussed.