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Objective: To investigate whether a workload which an individual is able to perform at the heart rate (HR) of 100 beats/min (WL(100)) independently predicts mortality in middle-aged men with known or suspected coronary heart disease (CHD)., Design: Prospective population-based study based on 365 middle-aged men with known or suspected CHD at baseline., Results: During an average follow-up of 11.1 years, there were 75 deaths (20.5%). In Cox multivariable models mortality increased by 72% (95% CI 32% to 122%, p<0.001) with 1 SD (34 Watts) decrement in WL(100) after adjustment for age, examination year, alcohol consumption, body mass index, cigarette smoking, cardiac insufficiency, history of myocardial infarction, diabetes, myocardial ischaemia during exercise test, serum low-density lipoprotein and high-density lipoprotein cholesterol, systolic and diastolic blood pressure at rest, testing protocol, and use of HR-lowering medication. The risk of death was 2.4 (95% CI 1.5 to 4.0, p<0.001) times higher in 130 men with WL(100) <55 W than in 235 men with WL(100) >or=55 W. In men using and not using HR-lowering medication the risk of death increased 72% (95% CI 14% to 163%, p = 0.01), and 54% (95% CI 14% to 108%, p = 0.005) with 1 SD decrement in WL(100), respectively. WL(100 )improved the predictive power of the adjusted Cox models including other HR and exercise test variables., Conclusions: WL(100) predicts mortality in men with known or suspected CHD. The association of WL(100) with mortality was not explained by other well-established HR and exercise test variables. WL(100) is derived from a submaximal test which avoids the cardiovascular risks associated with a high-intensity exertion.

Objective: To investigate the prognostic value of peak oxygen pulse, which is the amount of oxygen consumed per heart beat during exercise, and to compare the prognostic value of peak oxygen pulse and maximum oxygen uptake (Vo(2max)) with respect to coronary heart disease (CHD) and overall death., Design: Prospective population-based study based on 1596 men without CHD or the use of beta blockers at baseline., Results: The risk of CHD was 2.45 (95% CI 1.10 to 5.45) times higher in men with low peak oxygen pulse (< 13.5 ml/beat) than in those with high peak oxygen pulse (> 17.8 ml/beat) after adjustment for age, alcohol consumption, smoking, body mass index, blood pressure, serum lipids, diabetes, family history of CHD and ischaemic ST changes during exercise. During an average follow up of 14 years, 267 men died, 67 of them due to CHD. The respective risk for overall death was 1.79 (95% CI 1.21 to 2.65). The continuous variable Vo(2max) was a stronger risk predictor than peak oxygen pulse for CHD and overall death., Conclusions: Assessment of oxygen pulse provides no complementary information to Vo(2max) about cardiorespiratory fitness and prognosis for CHD. The analysis of respiratory gas exchange including the assessment of oxygen pulse during exercise does, however, provide an additional means for defining prognosis for patients with CHD.

Context: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke., Objective: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data., Data Sources: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators., Study Selection: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded., Data Extraction: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias., Data Synthesis: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design., Conclusions: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.

Aims: The purpose of the study was to investigate the associations of abdominal obesity and overall obesity with the risk of acute coronary events., Methods and Results: Body mass index indicating overall obesity and waist-to-hip ratio and waist circumference indicating abdominal obesity were measured for 1346 Finnish men aged 42-60 years who had neither cardiovascular disease nor cancer at baseline. There were 123 acute coronary events during an average follow-up of 10.6 years. In Cox regression analyses adjusted for confounding factors, waist-to-hip ratio (P=0.009), waist circumference (P=0.010) and body mass index (P=0.013) as continuous variables were associated directly with the risk of coronary events. These associations were in part explained by blood pressure, diabetes, fasting serum insulin, serum lipids, plasma fibrinogen, and serum uric acid. Waist-to-hip ratio of > or =0.91 was associated with a nearly threefold risk of coronary events. Waist-to-hip ratio provided additional information beyond body mass index in predicting coronary heart disease, whereas body mass index did not add to the predictive value of waist-to-hip ratio. Abdominal obesity combined with smoking and poor cardiorespiratory fitness increased the risk of coronary events 5.5 and 5.1 times, respectively., Conclusions: Abdominal obesity is an independent risk factor for coronary heart disease in middle-aged men and even more important than overall obesity. Since the effect of abdominal obesity was strongest in smoking and unfit men, the strategy for lifestyle modification to prevent coronary heart disease should address these issues jointly., (Copyright 2001 The European Society of Cardiology.)

Objectives: We investigated the prognostic significance of exercise-induced silent myocardial ischemia in both high and low risk men with no prior coronary heart disease (CHD)., Background: Silent ischemia predicts future coronary events in patients with CHD, but there is little evidence of its prognostic significance in subjects free of CHD., Methods: We investigated the association of silent ischemia, as defined by ST depression during and after maximal symptom-limited exercise test, with coronary risk in a population-based sample of men with no prior CHD followed for 10 years on average., Results: Silent ischemia during exercise was associated with a 5.9-fold (95% CI 2.3 to 11.8) CHD mortality in smokers, 3.8-fold (95% CI 1.9 to 7.9) in hypercholesterolemic men and 4.7-fold (95% CI 2.4 to 9.1) in hypertensive men adjusting for other risk factors. The respective relative risks (RRs) of any acute coronary event were 3.0 (95% CI 1.7 to 5.1), 1.9 (95% CI 1.2 to 3.1) and 2.2 (95% CI 1.4 to 3.5). These associations were weaker in men without these risk factors. Furthermore, silent ischemia after exercise was a stronger predictor for the risk of acute coronary events and CHD death in smokers and in hypercholesterolemic and hypertensive men than in men without risk factors., Conclusions: Exercise-induced silent myocardial ischemia was a strong predictor of CHD in men with any conventional risk factor, emphasizing the importance of exercise testing to identify asymptomatic high risk men who could benefit from risk reduction and preventive measures.

Background: Although several prospective studies have shown that low folate intake and low circulating folate are associated with increased risk of coronary heart disease (CHD), the findings are inconsistent., Methods and Results: We studied the associations of dietary intake of folate, vitamin B(6), and vitamin B(12) with the risk of acute coronary events in a prospective cohort study of 1980 Finnish men 42 to 60 years old examined in 1984 to 1989 in the Kuopio Ischemic Heart Disease Risk Factor Study. Nutrient intakes were assessed by 4-day food record. During an average follow-up time of 10 years, 199 acute coronary events occurred. In a Cox proportional hazards model adjusted for 21 conventional and nutritional CHD risk factors, men in the highest fifth of folate intake had a relative risk of acute coronary events of 0.45 (95% CI 0.25 to 0.81, P=0.008) compared with men in the lowest fifth. This association was stronger in nonsmokers and light alcohol users than in smokers and alcohol users. A high dietary intake of vitamin B(6) had no significant association and that of vitamin B(12) a weak association with a reduced risk of acute coronary events., Conclusions: The present work in CHD-free middle-aged men is the first prospective cohort study to observe a significant inverse association between quantitatively assessed moderate-to-high folate intakes and incidence of acute coronary events in men. Our findings provide further support in favor of a role of folate in the promotion of good cardiovascular health.

A number of epidemiological studies have shown an association between beta-carotene and the risk of cardiovascular diseases, whereas only a few studies are available concerning the association of lycopene with the risk of coronary events, and no studies have been undertaken concerning lycopene and stroke. Thus, we tested the hypothesis that low serum levels of lycopene are associated with increased risk of acute coronary events and stroke in middle-aged men previously free of CHD and stroke. The subjects were 725 men aged 46-64 years examined in 1991-3 in the Kuopio Ischaemic Heart Disease Risk Factor Study. Forty-one men had either a fatal or a non-fatal acute coronary event or a stroke by December 1997. In a Cox' proportional hazard's model adjusting for examination years, age, systolic blood pressure and three nutritional factors (serum folate, beta-carotene and plasma vitamin C), men in the lowest quarter of serum lycopene levels (< or =0.07 micromol/l) had a 3.3-fold (95 % CI 1.7, 6.4, risk of acute coronary events or stroke compared with the others. Our study suggests that a low serum level of lycopene is associated with an increased risk of atherosclerotic vascular events in middle-aged men previously free of CHD and stroke.

Objectives: Our aim was to study whether an insertion/deletion (I/D) polymorphism in the alpha2B-adrenoceptor gene is associated with the risk for cardiovascular diseases., Background: alpha2-adrenoceptors mediate contraction of vascular smooth muscle and induce coronary vasoconstriction in humans. The alpha2-adrenoceptor subtype B mediates vasoconstriction in mice. A variant of the human alpha2B-adrenoceptor gene that encodes a D of three residues in an intracellular acidic motif has been shown to confer decreased receptor desensitization. This receptor variant could, therefore, be involved in diseases associated with enhanced vasoconstriction., Methods: This study was part of a prospective population-based study investigating risk factors for cardiovascular diseases in a cohort of middle-aged men from eastern Finland. Nine hundred twelve men aged 46 to 64 years were followed for an average time of 4.5 years., Results: In this study population, 192 men (21%) had the D/D genotype; 256 (28%) had the I/I genotype, and 464 (51%) had a heterozygous genotype. In a Cox model adjusting for other coronary risk factors, men with the D/D genotype had 2.2 times (95% confidence interval: 1.1 to 4.4, p = 0.02) the risk to experience an acute coronary event (n = 15 for D/D, 10 for I/I and 12 for I/D) compared with men carrying either of the other two genotypes. The alpha2B-adrenoceptor genotype was not associated with hypertension in this study population., Conclusions: The D/D genotype of the alpha2B-adrenoceptor is a novel genetic risk factor for acute coronary events, but not for hypertension.

Background: Previous findings concerning the serum levels of fish-derived (n-3) fatty acids and coronary heart disease are inconsistent. The purpose of this study was to investigate the association between the serum n-3 end-product fatty acids docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and eicosapentaenoic acid and the risk of acute coronary events in middle-aged men., Methods and Results: We studied this association in the Kuopio Ischaemic Heart Disease Risk Factor Study, a prospective population study in Eastern Finland. Subjects were randomly selected and included 1871 men aged 42 to 60 years who had no clinical coronary heart disease at baseline examination. A total of 194 men had a fatal or nonfatal acute coronary event during follow-up. In a Cox proportional hazards' model adjusting for other risk factors, men in the highest fifth of the proportion of serum DHA+DPA in all fatty acids had a 44% reduced risk (P=0.014) of acute coronary events compared with men in the lowest fifth. Men in the highest fifth of DHA+DPA who had a low hair content of mercury (2.0 microgram/g). There was no association between proportion of eicosapentaenoic acid and the risk of acute coronary events., Conclusions: Our data provide further confirmation for the concept that fish oil-derived fatty acids reduce the risk of acute coronary events. However, a high mercury content in fish could attenuate this protective effect.

Objectives: Results from prospective studies concerning the association between plasma total homocysteine (tHcy) concentration and coronary heart disease (CHD) are conflicting. The purpose of this study was to test the hypothesis that plasma tHcy is associated with an increased risk of acute coronary events in middle-aged men., Design and Subjects: We investigated this association in a prospective nested case-control study among Eastern Finnish men aged 42-60 years. Plasma tHcy measurements were carried out for 163 men who had an acute coronary event during an average 8 years and 11 months follow-up of the whole cohort and for 163 control subjects. Both the cases and the controls were from a cohort of 2005 men who had no clinical CHD at the Kuopio Ischaemic Heart Disease (KIHD) baseline., Results: Men in the highest plasma tHcy concentration quarter had no increase in the risk of coronary events compared with men with lower tHcy concentrations (odds ratio = 0.88, 95% confidence interval 0.44-1.76). Average follow-up time before the first coronary event was 4.9 years (SD 3.2) in men in the highest plasma tHcy quarter and 5.5 years (SD 3.1) in men in the three lowest quarters (P = 0.368)., Conclusion: We conclude that plasma tHcy is not associated with an increased risk of coronary events in the middle-aged male population in eastern Finland.

Objective: To test the hypothesis that low serum folate concentrations are associated with an increased risk of acute coronary events in men free of prior coronary heart disease., Setting: Research Institute of Public Health, University of Kuopio, Kuopio, Finland., Design: Prospective study in a cohort of 734 men aged 46-64 y examined in 1991-1993 as part of the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) and followed for 5 y and 3 months., Intervention: Acute coronary events during the follow-up period were obtained by national hospital discharge registry. Baseline serum folate concentrations were measured by radioimmunoassay., Results: During the follow-up, six (2.5%) men with higher serum folate concentrations (highest third>11.3 nmol/1) and 28 (5.7%) men with lower serum folate (two lowest thirds) developed an acute coronary event (P=0.008). In a Cox model adjusting for age, examination years, and plasma lycopene concentration, in men with higher serum folate concentrations the relative risk for an acute coronary event was 0.31 (95% CI 0.11-0.90, P=0.031) when compared with men with lower serum folates., Conclusion: This prospective cohort study in middle-aged men from eastern Finland indicates that moderate-to-high levels of serum folate are associated with a greatly reduced incidence of acute coronary events.

Background: The role of hyperinsulinemia as a cardiovascular risk factor is controversial. We studied whether hyperinsulinemia is independently associated with increased cardiovascular morbidity and mortality., Methods: Fasting serum insulin level and other cardiovascular risk factors were determined in 1521 men in eastern Finland aged 42 to 60 years with neither cardiovascular disease nor diabetes at baseline. Forty-five cardiovascular deaths, 110 acute coronary events, 48 strokes, and 163 any cardiovascular events occurred during an average follow-up of 9.5 years. A total of 163 cardiovascular events (45 cardiovascular deaths, 110 acute coronary events, and 48 strokes) occurred during an average follow-up of 9.5 years., Results: In Cox regression analysis adjusting for age and examination years, fasting serum insulin level as a continuous variable was directly associated with the risk of cardiovascular death (P = .006), acute coronary events (P = .04), and stroke (P = .02). Men with insulin levels of 52 to 66 pmol/L, 67 to 89 pmol/L, and 90 pmol/L or more (3 highest quartiles) had 1.4-fold (95% confidence interval, 0.5-3.7), 1.4-fold (95% confidence interval, 0.5-3.7), and 2.5-fold (95% confidence interval, 1.0-5.9; P = .05) cardiovascular mortality, respectively, compared with men with insulin levels of less than 52 pmol/L (lowest quartile) (P = .04 for linear trend). Adjustment for serum lipid levels, blood pressure, and obesity reduced the excess cardiovascular mortality in the highest insulin quartile by 7%, 33%, and 67%, respectively. There were no statistically significant differences in the incidence of acute coronary events and stroke between the insulin quartiles., Conclusions: Hyperinsulinemia had a modest association with increased cardiovascular mortality in middle-aged men. This relationship was largely explained by obesity, hypertension, and dyslipidemia. Hyperinsulinemia had even weaker associations with the risk of acute coronary event and stroke.

Background: The lignan enterolactone, produced by the intestinal microflora from dietary precursors, has been implicated in protection against cancer. We investigated the association of serum enterolactone concentration with the risk of acute coronary events in a prospective nested case-control study in middle-aged men from eastern Finland., Methods: Enterolactone was measured by time-resolved fluoroimmunoassay in serum from 167 men who had an average 7.7 years of follow-up to an acute coronary event and from 167 control men. Both cases and controls were from a cohort of 2005 men who had no clinical coronary heart disease (CHD) at baseline. The controls were matched for age, examination year, and residence. Acute coronary events were registered prospectively., Findings: The mean baseline serum enterolactone concentration was lower among the cases than the controls (18.2 [SD 21.1] vs 23.5 [18.2] nmol/L, p=0.001). The men in the highest quarter of the enterolactone distribution (>30.1 nmol/L) had a 58.8% (95% CI 24.1-77.6, p=0.005) lower risk of acute coronary events than men in the lowest quarter. After adjustment for the nine most strongly predictive risk factors, men in the highest enterolactone quarter had a 65.3% (11.9-86.3, p=0.03) lower risk than men in the lowest quarter., Interpretation: Healthy men with high serum concentrations of enterolactone had a lower risk of acute coronary events than men with lower concentrations. These findings support the hypothesis that plant-dominated fibre-rich food lowers the risk of CHD.

A number of psychosomatic studies have suggested that alexithymia, impairment in identifying and expressing inner feelings, might somehow affect the course of various illnesses. However, none of these studies have distinguished between an impact of alexithymia on actual pathophysiological change versus an impact only on illness behavior. In the present study, a population-based random sample of 2297 middle-aged men from Eastern Finland was evaluated for alexithymia using the Finnish version of the self-report Toronto Alexithymia Scale (TAS). Although high TAS scores were associated with prior diagnosis of coronary heart disease (CHD), they were not associated with greater prevalence of ischemia on an exercise tolerance test. The results of B-mode ultrasonography of the carotid artery for those who had a CHD diagnosis showed that carotid atherosclerosis actually decreased significantly as alexithymia increased. An interaction analysis indicated that alexithymia was related to increased probability of being diagnosed with CHD only among those who had mildly or moderately progressed carotid atherosclerosis, and not among those with the most severe progression. Alexithymia was associated with higher perceived exertion, and to some extent, with more self-reported symptoms during the exercise tolerance test. The findings support the hypothesis that alexithymia relates to increased symptom reporting rather than pathophysiological changes in CHD. The results also suggest that alexithymic men may get diagnosed earlier, perhaps because of their different illness behavior.

A reduction of plasma fibrinogen has been suggested as one mechanism through which physical activity would protect against coronary heart disease (CHD). Therefore, we investigated the association of conditioning leisure time physical activity (CLTPA), assessed quantitatively by a 12-month history, and maximal oxygen uptake (VO2max) with plasma fibrinogen concentration in eastern Finnish men aged 42-60 years. A high mean intensity of CLTPA (standardized multivariate regression coefficient beta -0.059, p = 0.020) and a high maximal oxygen uptake (beta -0.163, p < 0.001) were associated with reduced plasma fibrinogen when adjusting for the strongest covariates. The adjusted relative difference in plasma fibrinogen concentration was 6.6% between men with a mean CLTPA intensity of < 4 and > 8 METs and 9.1% between the extreme quartiles of VO2max (< 2.21 vs > 2.961/min). The association between the mean intensity of CLTPA (p = 0.030 for interaction) and VO2max (p = 0.033) and plasma fibrinogen was stronger for smokers than for non-smokers. These data indicate that a reduction of plasma fibrinogen concentration may be one mechanism through which moderate to high intensity CLTPA and high cardiorespiratory fitness reduce the risk of CHD.

In a 30-year follow-up survey of the Finnish cohorts of the Seven Countries Study in 1989, 470 men aged 70-89 years were examined in two rural areas of Finland, in the East and in the West. Life-style-related coronary heart disease risk factors were at high levels in both groups, but the difference between areas found in the same cohort in middle age had mostly disappeared or partially reversed. Mean levels of systolic/diastolic blood pressure, body mass index, fasting blood glucose, blood glucose after 2-hour oral glucose tolerance test, and plasma fibrinogen were higher in the West than in the East (p < or = 0.05), but serum thiocyanate which reflects smoking habits was higher in the East (p < 0.001). No significant differences between areas were found in mean levels of serum total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, apolipoprotein A-I, apolipoprotein B, lipoprotein (a), plasma coagulation factor VIIc, and prevalence of current smoking.

We investigated the 12-month intra-person variability of various physical activity assessments used in the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) in 51 men aged 54 years. The methods were a 24-hour total activity recording, a 12-month leisure time activity history, a 7-day leisure time activity recall and a habitual occupational activity interview. More leisure time activity was reported in the retest. Intra-person variability was high for all physical activity indices. The proportion of the mean absolute test-retest difference out of the test-retest mean was 18% for the 24-hour total activity recording, 45% for the 12-month leisure time activity history, 86% for the 7-day leisure time activity recall, 70% for kilometres of conditioning activity per week (No. = 51) and 22% for the occupational activity interview (No. = 39). However, respective intraclass correlations for these indices were 0.43, 0.58, 0.35, 0.71 and 0.69. The physical activity assessments differ in observed intra-person variability in accordance with the type of activity, time frame and the method of recall. Owing to its representative time frame and relatively small intra-person variability the 12-month history may be recommended for a standard instrument for population studies concerning leisure time activity.

The North Karelia Project was the first population-based cardiovascular disease prevention programme. Even though it achieved, as compared to the reference population, a sizeable reduction in smoking and small effect in blood pressure and serum cholesterol levels, the effect on coronary and cardiovascular mortality of the programme remains equivocal. This is mainly due to shortcomings in the original study design and unanticipated start of the national decline in coronary mortality at the same time with the programme. North Karelia Project contributed, however, to the initiation of national activities in the prevention of cardiovascular disease. These have produced a favourable trend in lipids in the whole Finnish population. The recommendations and activities by national authorities and organizations have suffered, until recently, from orientation towards screening and individual risk factors. The success in North Karelia in early 1970's in the reduction of smoking has still not occurred nationally. Further emphasis is needed in the population approach and in the integration of preventive activities into the community and legislation.

As ultrasonographically assessed carotid arteriosclerosis is being used as a surrogate measure for coronary arteriosclerosis, we performed a prospective longitudinal study of the association of our high-resolution ultrasound assessment of extracranial carotid morphology with the risk of acute coronary events in 1,288 eastern Finnish men. The presence of any structural changes in the common carotid arteries or carotid bulbs was associated with a 3.29-fold (95% confidence interval, 1.31-8.29; p = 0.0074), intimal-medial thickening with a 2.17-fold (95% confidence interval, 0.70-6.74; p = NS), small carotid plaques with a 4.15-fold (95% confidence interval, 1.51-11.47; p less than 0.01), and large ("stenotic") plaques with a 6.71-fold (95% confidence interval, 1.33-33.91; p less than 0.01) risk of acute myocardial infarction compared with men free of any structural changes in the carotid artery wall at baseline. These data confirm the close relation between carotid artery wall morphology and coronary heart disease.

Objective: To examine the association between socioeconomic conditions in childhood and ischaemic heart disease in middle aged men, including the role of physiological and behavioural risk factors., Design: Prevalence study with extensive examination and testing and with recall of childhood conditions., Setting: Population based study in Kuopio, Finland., Subjects: Representative sample of 2679 men aged 42, 48, 54, and 60., Main Outcome Measures: Ischaemic findings on progressive maximal exercise test., Results: Low socioeconomic style in childhood was associated with significantly higher prevalence of findings indicating ischaemias. Compared with those in the highest tertile of childhood socioeconomic conditions, the age adjusted odds ratio for subjects in the lowest tertile was 1.44 and for those in the middle tertile 1.35. Adjustment for years of cigarette smoking times the average number of cigarettes smoked, ratio of high density lipoprotein to low density lipoprotein cholesterol, fibrinogen and serum selenium concentrations, and adult height did not appreciably weaken the association. Adjustment for adult socioeconomic state resulted in a 16% decline in the association. The association was reduced to non-significance by adjustment for measures of prevalent cardiovascular illness., Conclusions: Socioeconomic state in childhood was significantly associated with ischaemic heart disease in middle aged men. Levels of risk factors measured at middle age did not account for this association, nor did adult height. Because childhood socioeconomic conditions precede the development of ischaemic heart disease the substantial impact of prevalent illness on the observed association suggests that ischaemic heart disease develops earlier in those with lower socioeconomic state during childhood.

A case-control study was conducted to investigate the association between serum selenium and risk of death from acute coronary heart disease (CHD) as well as risk of fetal and non-fetal myocardial infarction (MI). Case-control pairs came from a population of 11,000 persons examined in 1972 from two counties in eastern Finland, an area with an exceptionally high mortality from cardiovascular diseases. Cases were aged 35-59 years and had died of CHD or other CVD or had a non-fetal MI during a seven-year follow-up. Controls were matched for sex, age, daily tobacco consumption, serum cholesterol, diastolic blood pressure, and history of angina pectoris. The mean serum selenium concentration for all cases was 51.8 micrograms/l and for all controls 55.3 micrograms/l (p less than 0.01). Serum selenium of less than 45 micrograms/l was associated with an adjusted relative risk of CHD death of 2.9 (p less than 0.01, 95% CI, 1.4-6.0), a relative risk of CVD death of 2.2 (p less than 0.01, 95% CI, 1.2-4.0), and a relative risk of fatal and nonfatal MI of 2.1 (p less than 0.001, 95% Ci, 1.4-3.1). 22% (95% CI, 8-35%) of contrary deaths were attributable to serum selenium in the whole study population.

The association of socioeconomic status with the risk of death from ischaemic heart disease and any disease as well as the risk of cerebral stroke and any cancer was studied in 3644 men aged 30-59, based on a random sample from the population of eastern Finland. Age, smoking, blood pressure, and serum cholesterol concentration were allowed for in multiple logistic models. On the basis of these data, not being married, short education, and low income are associated with an excessive risk of death from ischaemic heart disease and any disease. The data also indicated that men who were not married and who lived in urban areas might have an increased risk of cerebral stroke and those with a short education an increased risk of cancer.

The relationship between change in one coronary heart disease risk factor and levels of other risk factors was investigated in independent pre-and post-intervention samples and in a cohort surveyed both before and after a community-based cardiovascular disease prevention programme. A risk score that did not include the factor being analysed for change was developed and used to estimate risk. In the independent samples generally neither change in smoking nor change in saturated fat intake was related to coronary heart disease risk estimated from other factors in either men or women. Only the intake of saturated fats reduced slightly more among the hypertensive than other men (p less than 0.05). In the cohort, only change in smoking by women was related to initial risk estimated from other factors (p less than 0.05). Since change in behaviour had no consistent relation to the preprogramme risk level, it was concluded that health behaviour change in the population was based on common lifestyle changes in th intervention community, and that either face-to-face counselling or new techniques of mass communication are needed to induce high-risk individuals to do more to change their risk-inducing behaviours.

The serum high density lipoprotein (HDL) and total cholesterol levels and their determinants were explored in a random population sample from eastern Finland, an area with an exceptionally high mortality and morbidity from coronary heart disease (CHD). A total of 1792 persons aged 14-65 years were studied. Serum HDL cholesterol was determined in one series by using an enzymatic method after precipitation by dextran-magnesium chloride. The mean serum HDL cholesterol was 1.41 mmol/l in men and 1.62 mmol/l in women. Although a multivariate linear regression model explained 21% (for men) and 28% (for women) of the variation in serum total cholesterol, the same variables were able to account for only 9 and 4%, respectively, of the variation in serum HDL cholesterol. Among men, obesity and the daily consumption of tobacco products were inversely associated and the weekly consumption of beer and age were directly associated with serum HDL cholesterol and the serum HDL cholesterol/total cholesterol ratio.

The relation of leisure time and occupational physical activity to the risk of death from ischemic heart disease was investigated in a cohort of 15,088 persons aged 30-59 years who had no history of cardiovascular disease or other condition which hindered physical activity. Two population samples were randomly chosen from eastern Finland. During a six-year follow-up, persons who were sedentary in leisure time (relative risk = 1.3, 95% confidence interval (CI) = 1.1-1.6) or at work (relative risk = 1.3, 95% CI = 1.1-1.6) had an excess risk of ischemic heart disease death when adjusted for age, health status, family history, and body mass index in multivariate logistic models. Adjustment for years of education, social network participation, cigarette consumption, serum cholesterol level, and blood pressure level weakened the residual association of low leisure time physical activity with the risk of ischemic heart disease death (relative risk = 1.2, 95% CI = 1.0-1.5), whereas the association for low occupational physical activity remained unchanged. The lack of leisure time physical activity and a sedentary occupation are associated with an increased risk of ischemic heart disease death, and the excess risk due to lack of leisure time physical activity is, in part, accounted for by other ischemic heart disease risk factors.

In this study an attempt was made to investigate the application of epidemiological methodology in a cross-national context of studying the variation of coronary mortality. The data on the exposing factors of coronary mortality, the consumption of cigarettes and dairy products, were obtained from OECD statistics, and the data concerning the mortality of coronary heart disease were obtained from World Health Organization statistics. From the correlation and regression analyses performed on the basis of data from 14 countries it appeared that the cross-sectional exposure measurements strongly correlate over decades. For the consumption of cigarettes the time-lag found was from one to two years, while for the consumption of dairy products the respective time-lag was about six to eight years with respect to the effects on the coronary mortality. Because of the small number of observations available the statistical results should not be examined in terms of precise estimates of magnitude but rather in terms of the existence and the direction of relationship between the changes in coronary mortality and the consumption of cigarettes and dairy products. Although the data were insufficient to examine the confounding between the grouping of observations, and length of exposure, they did provide enough information to illustrate the importance of these two methodological aspects in analyses of populations.

We investigated the contribution of risk factor changes to the decline in incidence of ischaemic heart disease between three five-year periods (1972-76, 1977-81, 1982-86) in a community-based cardiovascular disease (CVD) control programme, the nOrth Karelia project. Random population samples of over 10,000 people were examined in 1972, 1977 and 1982 and followed for five years. Population attributable benefits were estimated for each time period from reductions in excess risk associated with S-cholesterol, tobacco products per day and the mean of systolic and diastolic blood pressure which were entered in logistic models with age and sex. Changes in risk factors accounted in North Karelia for 89% and in the reference population for 20% of the decline in ischaemic heart disease from 1972-6 to 1977-81. In healthy people, risk factor reductions accounted in North Karelia for 100%, but in the reference population only for 23% of the decline. The decline was non-significant in both areas from 1977-81 to 1982-86. In subjects with either CVD or diabetes, there was no decline in North Karelia in either period, whereas 30% and 64% of the decline (ns) in the reference population in the two periods, respectively, was attributable to risk factor changes. These data suggest that although the decline in the incidence of ischaemic heart disease in North Karelia did not differ from that in the reference population it was largely attributable to risk factor reductions in the healthy population. The decline in the reference population appears to be associated with changes in lifestyle, secondary prevention activities and medical care.

The trends in mortality from coronary heart disease in the 1970s and the differences in trends between counties within Finland were calculated from official mortality statistics among the population aged 35 to 64 years. During this period coronary mortality declined by a mean of 1.1% for men and 2.3% for women annually in the whole of Finland. A community based cardiovascular control programme was started in 1972 in North Karelia, a county in the east of Finland. The decline in coronary mortality in this county between 1969 and 1979 was 24% in men and 51% in women. The decline in the rest of Finland over the same period was 12% in men and 24% in women. The decline in North Karelia was greater than that in other counties of Finland for both men and women and that difference exceeded random variation, with over 95% likelihood for both sexes. Even with adjustment for rates before 1974 with cross-county multiple regression analyses the difference persisted. Although further studies are needed, the changes in coronary mortality in North Karelia suggest that the preventive programme has been effective.

The North Karelia Project - a community-wide health intervention programme - was launched in 1972 as response to the local petition to reduce the heavy toll of heart disease in North Karelia. The strategy of community-based prevention was based on the previous pioneering international work on epidemiology of cardiovascular diseases and prevention in which Finland had in many ways participated. Comprehensive scientific evaluation of the programme was carefully designed. The effects of the programme on risk factor reduction and on prevention of cardiovascular diseases are assessed by large population surveys every five years and by data on incidence of cardiovascular diseases and mortality rates. The authors present the 15 years' results and some of the most recent findings of the North Karelia Project, and discuss the overall experience and its national an international implications.

The North Karelia Project was a community-based pilot programme in an Eastern Finnish community of 180,000 adults. During the intervention period from 1972 to 1977, the project successfully demonstrated that changing risk factors at the community level was feasible and could result in a significant reduction in disease rates. The North Karelia Project used mass media for dissemination of the message, but relied on face-to-face contact to persuade people to adopt the new lifestyles. Training seminars for professionals were a key programme component. On average, one seminar was conducted every two and a half weeks. Total project costs were only one per cent of the total health services costs for the county during the project. These findings suggest that community programmes can improve both subjective and objective cardiovascular health, and that the strategy of integrating funding into the project recruitment and commitment process is appropriate and may even be necessary for a successful community based heart disease prevention programme.

It has been postulated that platelet function plays an important role in the initiation of atherosclerosis. Currently there are no definitive data on the longer-term effects of regular physical exercise on platelet function in humans. We assessed the influence of regular moderate-intensity physical exercise (brisk walking to slow jogging) on platelet aggregation in a population-based sample of middle-aged, overweight, mildly hypertensive men in eastern Finland. In this controlled study, we evaluated the net effect of exercise on platelet aggregation by studying changes in optical density and ATP release in platelet-rich plasma. A significant inhibition of secondary platelet aggregation from 27% to 36% was observed in the men taking regular exercise. These findings give new insight into the possible protective effects of exercise against the risk of ischemic heart disease.

A comprehensive community based programme to control cardiovascular diseases was started in North Karelia, Finland, in 1972. Reductions in smoking, serum cholesterol concentrations, and blood pressure were among the central intermediate objectives. The effect of the programme during the 10 year period 1972-82 was evaluated by examining independent random population samples at the outset (1972) and five (1977) and 10 (1982) years later both in the programme and in a matched reference area. Over 10 000 subjects were studied in 1972 and 1977 (participation rate about 90%) and roughly 8000 subjects in 1982 (participation rate about 80%). Analyses were conducted of the estimated effect of the programme on the risk factor population means by comparing the baseline and five year and 10 year follow up results in the age range 30-59 years. The effect of the programme (net reduction in North Karelia) at 10 years among the middle aged male population was estimated to be a 28% reduction in smoking (p less than 0.001), a 3% reduction in mean serum cholesterol concentration (p less than 0.001), a 3% fall in mean systolic blood pressure (p less than 0.001), and a 1% fall in mean diastolic blood pressure (p less than 0.05). Among the female population the reductions were respectively, 14% (NS), 1% (NS), 5% (p less than 0.001), and 2% (p less than 0.05). During the first five years of the project (1972-7) the programme effectively reduced the population mean values of the major coronary risk factors. At 10 years the effects had persisted for serum cholesterol concentrations and blood pressure and were increased for smoking.

In a cross-sectional population study of 1132 unselected Eastern Finnish men aged 54 years, serum selenium concentration had a weak positive association with plasma HDL cholesterol (standardised partial regression coefficient, beta = 0.061, P = 0.019) and a fairly strong inverse relationship (beta = -0.223, P less than 0.001) with the extent of ADP-induced platelet aggregation. Neither plasma ascorbate concentration nor alpha-tocopherol to total cholesterol ratio had any association with plasma lipoproteins, platelet aggregability or prevalent ischaemic heart disease (IHD). When a covariance-correction was applied, men with ischaemic ECG findings at exercise had a lower mean serum selenium than others (81.5 micrograms/l vs. 85.9 micrograms/l, P less than 0.01 for difference). This difference was equally large for men with neither symptoms nor previous diagnosis of IHD.

The independent association of serum concentrations of saturated and polyunsaturated fatty acids, apolipoproteins AI and B, selenium and vitamins A and E with the risk of death from coronary artery disease (CAD) was studied in 92 persons with no previous myocardial infarction, who died from CAD during a 5-year follow-up, and their 92 1-to-1 matched controls. Case-control pairs came from a randomly drawn population sample of approximately 12,000 persons aged 30 to 64 years from 2 provinces of eastern Finland, an area with exceptionally high CAD mortality. Control subjects were matched for sex, age, serum cholesterol, mean arterial pressure, tobacco consumption and history of cardiovascular diseases. The persons who died of CAD had lower serum esterified arachidonic acid concentrations before follow-up than the control subjects (41 vs 48 mg/liter, p = 0.05), and this difference was greater for pairs with no chest pain on effort (36 vs 50 mg/liter, p less than 0.05). The adjusted risk of CAD death in persons with a serum polyunsaturated to saturated (P/S) fatty acid ratio of 0.28 or less (in the lowest tertile) was 3.5-fold (95% confidence interval [CI], 1.5 to 8.2) compared with those with higher serum P/s ratios in a multivariate logistic model and 5.6-fold (95% CI 1.6 to 19.8) for pairs with no chest pain on effort. A low serum apolipoprotein AI concentration (1.25 g/liter or less, in the lowest tertile) was associated with a 2.5-fold (95% CI 1.1 to 5.7) adjusted risk of CAD death among the chest pain-free persons.(ABSTRACT TRUNCATED AT 250 WORDS)

A random population sample from Eastern Finland was studied. Altogether approximately 12 000 persons aged 25 to 59 years were examined with participation rate of 92%. Smoking, high saturated fat diet, increased serum cholesterol and elevated blood pressure showed clustering among men but not among women. Smoking tended to cluster in men with high saturated fat intake and hypercholesterolaemia. Increased serum cholesterol clustered with high blood pressure among both men and women. This risk factor clustering may contribute to the exceptionally high coronary heart disease incidence among men in the area. The reverse was true for women: smoking was less prevalent among women with elevated blood pressure or high saturated fat intake and did not differ by serum cholesterol.

The association between oral analgesics and the risk of death from ischaemic heart disease (IHD), cardiovascular disease, disease other than IHD, and any disease was studied in a cohort of 3551 men aged 30-59 years, based on a random sample from the population of eastern Finland. A number of potential coronary risk factors were allowed for in multiple logistic models. On the basis of these data, a regular use of oral analgesics is associated with a decreased risk of death from IHD. The relative risk was 0.6 with 95% confidence interval (CI) of 0.2-0.9 for IHD death and 0.6 (95% CI = 0.4-0.9) for cardiovascular death. No significant association was found between oral analgesics and the risk of death from diseases other than IHD.

Ecological between-area comparisons, hospital-based case-control studies and cross-sectional angiography studies have provided data on the role of selenium (Se) deficiency in the aetiology of ischaemic heart disease (IHD), but this evidence is, at best, suggestive because of the potential selection biases and the lack of certainty of the temporal direction of the observed associations. Out of the four cohort-based population studies published so far, one observed a moderate association between a reduced serum Se and an increased risk of IHD and all cardiovascular (CVD) deaths, one was equivocal and two did not find any association between serum Se and IHD. There are, however, several potential sources of biases acting towards the null hypothesis in these studies. In the pooled data of the two separate cohorts from eastern Finland including 377 people who experienced a CVD death or a non-fatal myocardial infarction and equally many event-free risk-factor matched controls, people with serum Se of less than 45 micrograms/l had a 1.7-fold (95% confidence interval 1.2-2.7) risk of an CVD event compared to those with higher serum Se. This association could, however, be explained by the covariation of Se with other nutrients, as for example n-3 polyunsaturated fatty acids. As the evidence concerning the role of serum Se in IHD is inconclusive, we need new epidemiological studies to test the association and experiments exploring the possible mechanisms.

Coronary risk factors and levels of physical activity at leisure were measured in a random sample of 3975 men 25-64 years of age residing in four areas of Finland. An index of leisure-time physical activity (LTPA) as the product of weekly exercise sessions times their usual intensity (expressed as metabolic equivalents) was computed. It showed a graded, inverse association with mean arterial blood pressure, smoking and serum thiocyanate, coronary heart disease risk estimate (combining blood pressure, total cholesterol and smoking), and a nonlinear favorable association with serum lipoproteins. In multiple regression analysis, LTPA contributed significantly and independently to the variation in mean arterial pressure; the standardized regression coefficients were -0.06 for LTPA, 0.09 for weekly alcohol consumption, 0.25 for body mass index, 0.25 for age. In the regression of coronary risk estimate, the standardized regression coefficients were -0.19 for LTPA, 0.22 for weekly alcohol consumption, 0.09 for body mass index, 0.15 for age. There was no evidence that LTPA above 2000 kcal of weekly energy expenditure was associated with further reduced coronary risk factor levels. These findings thus support the inverse direction of the association between exercise and coronary risk factors but they also point towards an independent, but modest, role of leisure-time physical activity as a determinant of coronary risk estimate and blood pressure.

The potential benefits of a high-risk and a population strategy to prevent cardiovascular disease deaths by lowering total serum cholesterol and diastolic blood pressure were estimated. The first strategy concentrates on the top 10% of the risk distribution, and the second strategy changes risk factor distributions of the entire population. With the high-risk strategy, lowering total serum cholesterol 20% and diastolic blood pressure to 90 mmHg would result in a 28% reduction in death from cardiovascular disease. Lowering total serum cholesterol to 190 mg/dl and diastolic blood pressure to 80 mmHg with this strategy would result in a 33 per cent reduction in death from cardiovascular disease. These expected changes approximate those expected by lowering total serum cholesterol by 10% and diastolic blood pressure by 5% with the population strategy. Changes in total serum cholesterol (20% lowering) and diastolic blood pressure (10% lowering) that have been achieved in nutrition intervention trials would result in a 50% decline in cardiovascular disease death rates if applied to the whole population. If population mean total serum cholesterol could be lowered to 190 mg/dl and population mean diastolic blood pressure could be lowered to 80 mmHg, a 70% reduction in cardiovascular disease death rates would be expected. This suggests that only a population approach can prevent the majority of deaths from cardiovascular disease in a community.