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Heart tissue engineering is critical in the treatment of myocardial infarction, which may benefit from drug-releasing smart materials. In this study, we load a small molecule (3i-1000) in new biodegradable and conductive patches for application in infarcted myocardium. The composite patches consist of a biocompatible elastomer, poly(glycerol sebacate) (PGS), coupled with collagen type I, used to promote cell attachment. In addition, polypyrrole is incorporated because of its electrical conductivity and to induce cell signaling. Results from the in vitro experiments indicate a high density of cardiac myoblast cells attached on the patches, which stay viable for at least 1 month. The degradation of the patches does not show any cytotoxic effect, while 3i-1000 delivery induces cell proliferation. Conductive patches show high blood wettability and drug release, correlating with the rate of degradation of the PGS matrix. Together with the electrical conductivity and elongation characteristics, the developed biomaterial fits the mechanical, conductive, and biological demands required for cardiac treatment.

Transcription factors are fundamental regulators of gene transcription, and many diseases, such as heart diseases, are associated with deregulation of transcriptional networks. In the adult heart, zinc-finger transcription factor GATA4 is a critical regulator of cardiac repair and remodelling. Previous studies also suggest that NKX2-5 plays function role as a cofactor of GATA4. We have recently reported the identification of small molecules that either inhibit or enhance the GATA4-NKX2-5 transcriptional synergy. Here, we examined the cardiac actions of a potent inhibitor (3i-1000) of GATA4-NKX2-5 interaction in experimental models of myocardial ischemic injury and pressure overload. In mice after myocardial infarction, 3i-1000 significantly improved left ventricular ejection fraction and fractional shortening, and attenuated myocardial structural changes. The compound also improved cardiac function in an experimental model of angiotensin II -mediated hypertension in rats. Furthermore, the up-regulation of cardiac gene expression induced by myocardial infarction and ischemia reduced with treatment of 3i-1000 or when micro- and nanoparticles loaded with 3i-1000 were injected intramyocardially or intravenously, respectively. The compound inhibited stretch- and phenylephrine-induced hypertrophic response in neonatal rat cardiomyocytes. These results indicate significant potential for small molecules targeting GATA4-NKX2-5 interaction to promote myocardial repair after myocardial infarction and other cardiac injuries.

Background-Homozygosity for a relatively common Cys282Tyr mutation of the human hemochromatosis-associated (HFE) gene was recently found to account for most cases of hereditary hemochromatosis. Because excess iron has been postulated to enhance risk of vascular disease, we studied whether occurrence of this mutation was associated with increased risk of first acute myocardial infarction in healthy middle-aged men in a prospective cohort study. Methods and Results-Study subjects were the 1150 participants in the population-based Kuopio Ischemic Heart Disease Risk Factor Study (KIHD), aged 42, 48, 54, or 60 years at baseline, who had no coronary heart disease at baseline and for whom a DNA sample was available. Information about myocardial infarctions was collected prospectively by use of FINMONICA (FINnish MONItoring of trends and determinants in CArdiovascular disease study) and hospital data. Events were classified by MONICA (MONItoring of trends and determinants in CArdiovascular disease study) diagnostic criteria. The HFE Cys282Tyr mutation was assayed by a solid-phase minisequencing technique. One subject was homozygous and 76 individuals were heterozygous for the HFE Cys282Tyr mutation (6.7%). During a mean follow-up of 9 years, 8 (10.4%) of 77 carriers and 60 (5.6%) of 1073 noncarriers experienced an acute myocardial infarction. In a Cox proportional hazards model allowing for the other strongest risk factors, the carriers had a 2.3-fold (95% CI 1. 1 to 4.8; P=0.03) risk of acute myocardial infarction compared with noncarriers. Conclusions-Male carriers of the common hemochromatosis gene mutation are at 2-fold risk for first acute myocardial infarction compared with noncarriers.

Because high body iron stores have been suggested as a risk factor for acute myocardial infarction, donation of blood could theoretically reduce the risk by lowering body iron stores. For this reason, the authors tested the hypothesis that voluntary blood donation is associated with reduced risk of acute myocardial infarction in a prospective epidemiologic follow-up study in men from eastern Finland. The subjects are all participants of the Kuopio Ischaemic Heart Disease Risk Factor Study. A cohort of 2,862 men aged 42-60 years were followed for an average of almost 9 years. One man (0.7%) out of 153 men who had donated blood in 24 months preceding the baseline examination experienced an acute myocardial infarction during 1984 to 1995, whereas 316 men (12.5%) of 2,529 non-blood donors had an acute myocardial infarction (p < 0.0001 for difference between proportions). In a Cox proportional hazards model adjusting for age, examination years and all other predictive coronary disease risk factors, blood donors had a 88% reduced risk (relative hazard = 0.12, 95% confidence interval 0.02-0.86, p = 0.035) of acute myocardial infarction, compared with non-blood donors. These findings suggest that frequent blood loss through voluntary blood donations may be associated with a reduced risk of acute myocardial infarction in middle-aged men.

Background: Epidemiological evidence concerning the role of iron, a lipid peroxidation catalyst, in coronary heart disease (CHD) is inconsistent. We investigated the association of the concentration ratio of serum transferrin receptor to serum ferritin (TfR/ferritin), a state-of-the-art measurement of body iron stores, with the risk of acute myocardial infarction (AMI) in a prospective nested case-control study in men from eastern Finland., Methods and Results: Transferrin receptor assays were carried out for 99 men who had an AMI during an average 6.4 years of follow-up and 98 control men. Both the cases and the controls were nested from the Kuopio Ischemic Heart Disease Risk Factor Study (KIHD) cohort of 1931 men who had no clinical CHD at the baseline study. The controls were matched for age, examination year, and residence. AMIs were registered prospectively. Soluble transferrin receptors were measured by immunoenzymometric assay and ferritin concentration by radioimmunoassay from frozen baseline serum samples. The mean TfR/ferritin ratio was 15.1 (SE, 2.0) among cases and 21.3 (SE, 2.2) among controls (P=.035 for difference). In logistic regression models adjusting for other strongest risk factors for AMI and indicators of inflammation and alcohol intake, men in the lowest and second lowest thirds of the TfR/ferritin ratio had a 2.9-fold (95% CI, 1.3 to 6.6, P=.011) and 2.0-fold (0.9 to 4.2, P=.081) risk of AMI compared with men in the highest third (P=.010 for trend)., Conclusions: These data show an association between increased body iron stores and excess risk of AMI, confirming previous epidemiological findings.

Cynical hostility has been associated with increased cardiovascular morbidity and mortality; yet few studies have investigated this relation in population-based samples, and little is known about underlying mechanisms. This study examined the association between hostility, measured by the eight-item Cynical Distrust Scale, and risk for all-cause and cardiovascular mortality and incident myocardial infarction. Subjects were 2,125 men, ages 42-60 years, from the Kuopio Ischemic Heart Disease Risk Factor Study, a longitudinal study of unestablished and traditional risk factors for ischemic heart disease, mortality, and other outcomes. There were 177 deaths (73 cardiovascular) in 9 years of follow-up. Men with hostility scores in the top quartile were at more than twice the risk of all-cause mortality (relative hazards (RH) 2.30, 95% confidence interval (CI) 1.47-3.59) and cardiovascular mortality (RH 2.70, 95% CI 1.27-5.76), relative to men with scores in the lowest quartile. Among 1,599 men without previous myocardial infarction or angina, high scorers also had an increased risk of myocardial infarction (RH 2.18, 95% CI 1.01-4.70). Biologic and socioeconomic risk factors, social support, and prevalent diseases had minimal impact on these associations, whereas adjustments for the behavioral risk factors of smoking, alcohol consumption, physical activity, and body mass index substantially weakened the relations. Simultaneous risk factor adjustment eliminated the observed associations. Results show that high levels of hostility are associated with increased risk of all-cause and cause-specific mortality and incident myocardial infarction and that these effects are mediated primarily through behavioral risk factors.

Objectives: This study investigated whether the association between workplace conditions and the risk of all-cause and cardiovascular mortality and acute myocardial infarction differed by socioeconomic status., Methods: Prospective data were used to examine these associations in 2297 Finnish men, with adjustment for prevalent diseases and biological, behavioral, and psychosocial covariates, and stratified by employment status and workplace social support., Results: Elevated age-adjusted relative hazards for all-cause mortality were found for men who reported high demands, low resources, and low income; high demands, high resources, and low income; and low demands, high resources, and low income. Similar patterns were found for cardiovascular mortality. In contrast, elevated age-adjusted relative hazards for acute myocardial infarction were observed only in men who reported high demands, low resources, and low income. These results did not differ by level of workplace social support or employment status., Conclusions: The negative effects of workplace conditions on mortality and of myocardial infarction risk depended on income level and were largely mediated by known risk factors.

Objective: To examine the association between plasma vitamin C concentrations and the risk of acute myocardial infarction., Design: Prospective population study., Setting: Eastern Finland., Subjects: 1605 randomly selected men aged 42, 48, 54, or 60 who did not have either symptomatic coronary heart disease or ischaemia on exercise testing at entry to the Kuopio ischaemic heart disease risk factor study in between 1984 and 1989., Main Outcome Measures: Number of acute myocardial infarctions; fasting plasma vitamin C concentrations at baseline., Results: 70 of the men had a fatal or non-fatal myocardial infarction between March 1984 and December 1992.91 men had vitamin C deficiency (plasma ascorbate < 11.4 mumol/l, or 2.0 mg/l), of whom 12 (13.2%) had a myocardial infarction; 1514 men were not deficient in vitamin C, of whom 58 (3.8%) had a myocardial infarction. In a Cox proportional hazards model adjusted for age, year of examination, and season of the year examined (August to October v rest of the year) men who had vitamin C deficiency had a relative risk of acute myocardial infarction of 3.5 (95% confidence interval 1.8 to 6.7, P = 0.0002) compared with those who were not deficient. In another model adjusted additionally for the strongest risk factors for myocardial infarction and for dietary intakes of tea fibre, carotene, and saturated fats men with a plasma ascorbate concentration < 11.4 mumol/l had a relative risk of 2.5 (1.3 to 5.2, P = 0.0095) compared with men with higher plasma vitamin C concentrations., Conclusions: Vitamin C deficiency, as assessed by low plasma ascorbate concentration, is a risk factor for coronary heart disease.

Much remains to be understood about how low socioeconomic status (SES) increases cardiovascular disease and mortality risk. Data from the Kuopio Ischemic Heart Disease Risk Factor Study (1984-1993) were used to estimate the associations between acute myocardial infarction and income, all-cause mortality, and cardiovascular mortality in a population-based sample of 2,272 Finnish men, with adjustment for 23 biologic, behavioral, psychologic, and social risk factors. Compared with the highest income quintile, those in the bottom quintile had age-adjusted relative hazards of 3.14 (95% confidence interval (CI) 1.77-5.56), 2.66 (95% CI 1.25-5.66), and 4.34 (95% CI 1.95-9.66) for all-cause mortality, cardiovascular mortality, and AMI, respectively. After adjustment for risk factors, the relative hazards for the same comparisons were 1.32 (95% CI 0.70-2.49), 0.70 (95% CI 0.29-1.69), and 2.83 (95% CI 1.14-7.00). In the lowest income quintile, adjustment for risk factors reduced the excess relative risk of all-cause mortality by 85%, that of cardiovascular mortality by 118%, and that of acute myocardial infarction by 45%. These data show how the association between SES and cardiovascular mortality and all-cause mortality is mediated by known risk factor pathways, but full "explanations" for these associations will need to encompass why these biologic, behavioral, psychologic, and social risk factors are differentially distributed by SES.

Background: It has been documented that the HMG coenzyme A reductase inhibitors, or statins, can decrease cardiovascular events and mortality in patients with clinical coronary disease and moderately to severely elevated lipid levels. Additional data are required to demonstrate a reduction of vascular events in coronary patients with less than severely elevated lipid levels and in subgroups of this population., Methods and Results: Clinical data from four atherosclerosis regression trials that evaluated pravastatin were pooled for a predetermined analysis of the effect of that agent on the risk of coronary events. All trials were double-masked, placebo-controlled designs that used pravastatin as monotherapy for 2 to 3 years. The 1891 participants in the trials had evidence of atherosclerosis and mildly to moderately elevated lipid levels. For fatal or nonfatal myocardial infarction, there was a 62% reduction in events attributable to pravastatin (p = .001). This effect was evident in younger and older patients, men and women, and patients with and without histories of hypertension and prior infarction. There was a 46% reduction in all-cause mortality (p = 17), which, although not statistically significant, is consistent with the results of other statin trials. There also was a 62% reduction in the risk of fatal or nonfatal stroke (p = .054)., Conclusions: These pooled results provide strong evidence that pravastatin reduces the risk of cardiovascular events in patients with atherosclerotic disease and mildly to moderately elevated lipid levels. The benefit for reducing myocardial infarction is evident in older and younger patients, men and women, and patients with and without histories of hypertension and prior infarction.

We examined the relationship among low, moderate, and high levels of hopelessness, all-cause and cause-specific mortality, and incidence of myocardial infarction (MI) and cancer in a population-based sample of middle-aged men. Participants were 2428 men, ages 42 to 60, from the Kuopio Ischemic Heart Disease study, an ongoing longitudinal study of unestablished psychosocial risk factors for ischemic heart disease and other outcomes. In 6 years of follow-up, 174 deaths (87 cardiovascular and 87 noncardiovascular, including 40 cancer deaths and 29 deaths due to violence or injury), 73 incident cancer cases, and 95 incident MI had occurred. Men were rated low, moderate, or high in hopelessness if they scored in the lower, middle, or upper one-third of scores on a 2-item hopelessness scale. Age-adjusted Cox proportional hazards models identified a dose-response relationship such that moderately and highly hopeless men were at significantly increased risk of all-cause and cause-specific mortality relative to men with low hopelessness scores. Indeed, highly hopeless men were at more than three-fold increased risk of death from violence or injury compared with the reference group. These relationships were maintained after adjusting for biological, socioeconomic, or behavioral risk factors, perceived health, depression, prevalent disease, or social support. High hopelessness also predicted incident MI, and moderate hopelessness was associated with incident cancer. Our findings indicate that hopelessness is a strong predictor of adverse health outcomes, independent of depression and traditional risk factors. Additional research is needed to examine phenomena that lead to hopelessness.

Background: It has been documented that the HMG coenzyme A reductase inhibitors, or statins, can decrease cardiovascular events and mortality in patients with clinical coronary disease and moderately to severely elevated lipid levels. Additional data are required to demonstrate a reduction of vascular events in coronary patients with less than severely elevated lipid levels and in subgroups of this population., Methods and Results: Clinical data from four atherosclerosis regression trials that evaluated pravastatin were pooled for a predetermined analysis of the effect of that agent on the risk of coronary events. All trials were double-masked, placebo-controlled designs that used pravastatin as monotherapy for 2 to 3 years. The 1981 participants in the trials had evidence of atherosclerosis and mildly to moderately elevated lipid levels. For fatal or nonfatal myocardial infarction, there was a 62% reduction in events attributable to pravastatin (P = .001). This effect was evident in younger and older patients, men and women, and patients with and without histories of hypertension and prior infarction. There was a 46% reduction in all-cause mortality (P = .17), which, although not statistically significant, is consistent with the results of other statin trials. There also was a 62% reduction in the risk of fatal or nonfatal stroke (P = .054)., Conclusions: These pooled results provide strong evidence that pravastatin reduces the risk of cardiovascular events in patients with atherosclerotic disease and mildly to moderately elevated lipid levels. The benefit for reducing myocardial infarction is evident in older and younger patients, men and women, and patients with and without histories of hypertension and prior infarction.

Background: Even though previous studies have suggested an association between high fish intake and reduced coronary heart disease (CHD) mortality, men in Eastern Finland, who have a high fish intake, have an exceptionally high CHD mortality. We hypothesized that this paradox could be in part explained by high mercury content in fish., Methods and Results: We studied the relation of the dietary intake of fish and mercury, as well as hair content and urinary excretion of mercury, to the risk of acute myocardial infarction (AMI) and death from CHD, cardiovascular disease (CVD), and any cause in 1833 men aged 42 to 60 years who were free of clinical CHD, stroke, claudication, and cancer. Of these, 73 experienced an AMI in 2 to 7 years. Of the 78 decreased men, 18 died of CHD and 24 died of CVD. Men who had consumed local nonfatty fish species had elevated hair mercury contents. In Cox models with the major cardiovascular risk factors as covariates, dietary intakes of fish and mercury were associated with significantly increased risk of AMI and death from CHD, CVD, and any death. Men in the highest tertile (> or = 2.0 micrograms/g) of hair mercury content had a 2.0-fold (95% confidence interval, 1.2 to 3.1; P = .005) age- and CHD-adjusted risk of AMI and a 2.9-fold (95% CI, 1.2 to 6.6; P = .014) adjusted risk of cardiovascular death compared with those with a lower hair mercury content. In a nested case-control subsample, the 24-hour urinary mercury excretion had a significant (P = .042) independent association with the risk of AMI. Both the hair and urinary mercury associated significantly with titers of immune complexes containing oxidized LDL., Conclusions: These data suggest that a high intake of mercury from nonfatty freshwater fish and the consequent accumulation of mercury in the body are associated with an excess risk of AMI as well as death from CHD, CVD, and any cause in Eastern Finnish men and this increased risk may be due to the promotion of lipid peroxidation by mercury.

Background: Previous studies have suggested that higher levels of regular physical activity and cardiorespiratory fitness are associated with a reduced risk of coronary heart disease. We investigated the independent associations of physical activity during leisure time and maximal oxygen uptake (a measure of cardiorespiratory fitness) with the risk of acute myocardial infarction., Methods: During the period 1984 to 1989, we performed base-line examinations in 1453 men 42 to 60 years old who did not report having cardiovascular disease or cancer. Physical activity was assessed quantitatively with a detailed questionnaire, and maximal oxygen uptake was measured directly by exercise testing. During an average follow-up of 4.9 years, 42 of the 1166 men with normal electrocardiograms at base line had a first acute myocardial infarction., Results: After adjustment for age and the year of examination, the relative hazard (risk) of myocardial infarction in the third of subjects with the highest level of physical activity (> 2.2 hours per week) was 0.31 (95 percent confidence interval, 0.12 to 0.85; P = 0.02), as compared with the third with the lowest level (P = 0.04 for linear trend over all three groups). The relative hazard in the third with the highest maximal oxygen uptake (> 2.7 liters per minute) was 0.26 (95 percent confidence interval, 0.10 to 0.68; P = 0.006) (P = 0.006 for linear trend), after adjustment for age, the year and season when the examination was performed, weight, height, and the type of respiratory-gas analyzer used. After up to 17 confounding variables were controlled for, the relative hazards for the third of subjects with the highest level of physical activity (0.34; 95 percent confidence interval, 0.12 to 0.94; P = 0.04) and maximal oxygen uptake (0.35; 95 percent confidence interval, 0.13 to 0.92; P = 0.03), as compared with the values in the lowest third, were significantly (P < 0.05) less than 1.0., Conclusions: Higher levels of both leisure-time physical activity and cardiorespiratory fitness had a strong, graded, inverse association with the risk of acute myocardial infarction, supporting the idea that lower levels of physical activity and cardiorespiratory fitness are independent risk factors for coronary heart disease.

Background: Iron can induce lipid peroxidation in vitro and in vivo in humans and has promoted ischemic myocardial injury in experimental animals. We tested the hypothesis that high serum ferritin concentration and high dietary iron intake are associated with an excess risk of acute myocardial infarction., Methods and Results: Randomly selected men (n = 1,931), aged 42, 48, 54, or 60 years, who had no symptomatic coronary heart disease at entry, were examined in the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) in Eastern Finland between 1984 and 1989. Fifty-one of these men experienced an acute myocardial infarction during an average follow-up of 3 years. On the basis of a Cox proportional hazards model adjusting for age, examination year, cigarette pack-years, ischemic ECG in exercise test, maximal oxygen uptake, systolic blood pressure, blood glucose, serum copper, blood leukocyte count, and serum high density lipoprotein cholesterol, apolipoprotein B, and triglyceride concentrations, men with serum ferritin greater than or equal to 200 micrograms/l had a 2.2-fold (95% CI, 1.2-4.0; p less than 0.01) risk factor-adjusted risk of acute myocardial infarction compared with men with a lower serum ferritin. An elevated serum ferritin was a strong risk factor for acute myocardial infarction in all multivariate models. This association was stronger in men with serum low density lipoprotein cholesterol concentration of 5.0 mmol/l (193 mg/dl) or more than in others. Also, dietary iron intake had a significant association with the disease risk in a Cox model with the same covariates., Conclusions: Our data suggest that a high stored iron level, as assessed by elevated serum ferritin concentration, is a risk factor for coronary heart disease.

The authors investigated the association of serum copper concentration with the risk of acute myocardial infarction in 1,666 randomly selected men aged 42, 48, 54, or 60 years who had no symptomatic ischemic heart disease at entry. Baseline examinations in the Kuopio Ischaemic Heart Disease Risk Factor Study in Eastern Finland were done during 1984 to 1988. In Cox multivariate survival models adjusting for age, examination year, ischemic electrocardiogram in exercise, maximal oxygen uptake, diabetes, family history of ischemic heart disease, cigarette-years, mean systolic blood pressure, serum high density lipoprotein (HDL) cholesterol subfraction HDL2 and low density lipoprotein (LDL) cholesterol concentrations and blood leukocyte count, serum copper concentration in the two highest tertiles (1.02-1.16 mg/liter and 1.17 mg/liter or more) associated with 3.5-fold (95% confidence interval (Cl) 1.3-9.4, p less than 0.05) and 4.0-fold (95 percent Cl 1.5-10.8, p less than 0.01) risk of acute myocardial infarction. These data indicate that high copper status, reflected by elevated serum copper concentration, is an independent risk factor for ischemic heart disease.

Background: We investigated the association of cholesterol concentrations in serum high density lipoprotein (HDL) and its subfractions HDL2 and HDL3 with the risk of acute myocardial infarction in 1,799 randomly selected men 42, 48, 54, or 60 years old., Methods and Results: Baseline examinations in the Kuopio Ischaemic Heart Disease Risk Factor Study were done during 1984-1987. In Cox multivariate survival models adjusted for age and examination year, serum HDL cholesterol of less than 1.09 mmol/l (42 mg/dl) was associated with a 3.3-fold risk of acute myocardial infarction (95% confidence intervals [CI], 1.7-6.4), serum HDL2, cholesterol of less than 0.65 mmol/l (25 mg/dl) was associated with a 4.0-fold risk of acute myocardial infarction (95% CI, 1.9-8.3), and serum HDL3 cholesterol of less than 0.40 mmol/l (15 mg/dl) was associated with a 2.0-fold (95% CI, 1.1-4.0) risk of acute myocardial infarction. Adjustments for obesity, ischemic heart disease, other cardiovascular disease, maximal oxygen uptake, systolic blood pressure, antihypertensive medication, serum low density lipoprotein cholesterol, and triglyceride concentrations reduced the excess risks associated with serum HDL, HDL2, and HDL3 cholesterol in the lowest quartiles by 52%, 48%, and 41%, respectively. Additional adjustments for alcohol consumption, cigarettes smoked daily, smoking years, and leisure time energy expenditure reduced these excess risks associated with low HDL, HDL2, and HDL3 cholesterol levels by another 26%, 24% and 21%, respectively., Conclusions: Our data confirm that both total HDL and HDL2 levels have inverse associations with the risk of acute myocardial infarction and may thus be protective factors in ischemic heart disease, whereas the role of HDL3 remains equivocal.

A prospective follow-up study was carried out to investigate the relation between smoking and risk of death after an acute myocardial infarction. The study consisted of male patients under the age of 65 years, who had had an acute myocardial infarction between 1972 and 1975 in North Karelia, Finland. Of these patients, 888 survived the first six months after the acute infarction and were followed-up for three years after the infarction with regard to their deaths. The cumulative all-causes mortality rate of the patients who were still smoking six months after the acute myocardial infarction was 1.7 times that of the patients who had stopped smoking within the first six months. There was a dose-response relation between the number of cigarettes smoked daily and the mortality. The impact of smoking was greatest in the subgroups of patients with an otherwise good prognosis. We estimated that 28 per cent of the deaths in the whole group of initial smokers was attributable to continuing smoking after the infarction. On the basis of these findings we suggest that the anti-smoking advice should be an important part of the modern comprehensive care of patients with an acute myocardial infarction.

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.

A random population sample from two countries of eastern Finland was studied in 1972, measuring eg the serum total cholesterol and triglycerides, blood pressure, and smoking. The participation rate among men aged 30 to 59 was 92%. Men who had had a myocardial infarction, angina or cerebral stroke in the preceding 12 months were excluded. During the seven-year follow-up 211 men had an acute myocardial infarction (AMI), 59 men had a cerebral stroke and 185 men died of any disease. The serum total cholesterol (greater than or equal to 8.0 mmol/l) had a positive association with the risk of AMI (relative risk RR = 2.8, 95% Cl = 1.8-4.3) and the risk of death (RR = 2.2, 95% Cl = 1.3-3.7) among men aged 30-49 but only with the risk of AMI (RR = 2.0, 95% Cl = 1.3-3.1) among those aged 50-59 based on multiple logistic models including also age, serum triglycerides, diastolic blood pressure, smoking and obesity. Serum triglycerides (greater than or equal to 2.8 mmol/l) had a positive risk factor-adjusted association with the risk of cerebral stroke (RR = 2.7, 95% Cl = 1.0-7.1) among men aged 30-49, but no independent association with the risk of AMI or death.

Physical activity at work and in leisure time was studied by using a questionnaire in a random population sample from two counties of Eastern Finland in 1972. Data on age, serum cholesterol, diastolic blood pressure, height, weight and smoking were recorded in a field examination. The study population consisted of 3978 men aged 30-59 years and 3688 women aged 35-59 years. The participation rate was 92% in men and 94% in women in these age groups. During the approximately seven-year follow-up until December 31, 1978, 210 men and 63 women had an acute myocardial infarction (AMI), 89 men and 14 women died of acute ischemic heart disease, 71 men and 56 women had a cerebral stroke and 172 men and 75 women died of any disease. The subjects with a history of myocardial infarction, angina or cerebral stroke in the 12 months preceding the baseline survey were excluded in the respective analysis. Low physical activity at work was associated with an increased risk of AMI, cerebral stroke and death due to any disease in both men and women, even when controlling for age, serum total cholesterol, diastolic blood pressure, height, weight and smoking in a multiple logistic model. The relative risk of AMI was 1.5 (90% confidence interval (CI) = 1.2-2.0) in men and 2.4 (90% CI = 1.5-3.7) in women. Low physical activity in leisure time had a significant association with an increased risk of death, but not with an increased risk of AMI or stroke in the multivariate analysis.

Intake of spirits and beer as well as smoking was measured by questionnaire in a random population sample from two counties of Eastern Finland in 1972. At the same time serum cholesterol, triglycerides and blood pressure were measured in a field examination. The study material consists of 4063 men aged 30-59 years (participation rate 92%). During a 7-yr follow-up 209 of these men had developed an acute myocardial infarction (AMI) and 223 men had died. Reported spirits and beer intake had both a strong positive association with smoking and serum triglycerides, a weak positive association with diastolic blood pressure, but no relationship to serum total cholesterol. Use of spirits at least once a week was associated with a reduced risk of AMI. The relative risk (RR), adjusted for age and conventional coronary risk factors was 0.5 (95% confidence interval (CI), 0.3-0.9). Consumption of beer had no significant relationship to the risk of AMI. Consumption of at least five bottles of beer a week was related to a slightly excessive risk of death from any cause (adjusted RR = 1.5, 95% CI = 1.0-2.1). Spirits intake had no significant association with the risk of death.

The prevalence of hypertension in general and of those complications associated with isolated systolic hypertension (at least 165 mmHg systolic and less than 95 mmHg diastolic pressure) were assessed in a random sample of 3888 men and 4336 women aged 30-59 years at the beginning of the study. The prevalence of isolated systolic hypertension was about 5% both in men and women aged 30 to 49 years; in those aged 50 to 59 years the prevalence was 7% in men and 13% in women. Systolic hypertension was associated with an increased risk of acute myocardial infarction (AMI), cerebrovascular stroke and death both in men and women in the seven-year follow-up period. The relative risk of AMI in men and women with isolated systolic hypertension was 1.65 (P less than 0.05) and 0.87, respectively, and the relative risk of stroke 0.57 and 1.29, respectively. Isolated systolic hypertension is not uncommon in the middle-aged population and its impact on cardiovascular complications seems to be significant not only on the elderly but also in the middle-aged.

A prospective follow-up study was carried out to investigate the impact of a health education program and other factors related to patient's social background and severity of heart attack on stopping smoking after heart attack. The study consisted of male patients below the age of 65 years, who had suffered a heart attack between April 1 and September 30, 1977, living in two provinces of eastern Finland, North Karelia and Kuopio. Of the patients who smoked before the heart attack, 102 responded to both the 6- and the 12-month follow-up postal survey. Of these 102 patients, 25 stopped smoking within 12 months after the heart attack, while 77 continued to smoke. Continuing smoking was most strongly associated with working and unemployment before heart attack, maximum serum aspartate aminotransferase (GOT) concentration and subjective recovery after the heart attack. The quitting rate among men in the program area was 1.2-fold (p = 0.012) compared with the reference area men, after making allowance for the seven most confounding factors in the multivariate analysis. This observation indicates that either the community-based primary program or the secondary prevention program in North Karelia succeeded in dissuading patients from smoking after heart attack.

The comprehensive community programme for the control of cardiovascular diseases in North Karelia includes a special subprogramme for the rehabilitation and secondary prevention among patients with an acute myocardial infarction (AMI). The target group of the programme were persons under the age of 65 who had an AMI according to the community-based AMI register and had survived the acute phase of the disease. The programme consisted of systematic long-term medical follow-up at an outpatient MI clinic and of decentralized local group-rehabilitation with special emphasis on secondary prevention. The main component of the programme were health education and submaximal physical exercise, aiming at the reduction of the known secondary risk factors and the improvement of the general well-being of the patients. The feasibility of this programme was good. During the five-year period from 1973 to 1977 a total of 1308 persons under the age of 65 survived an AMI. Out of these patients 515 visited the outpatient MI clinic and 575 took part in the rehabilitation groups. The participation rate in the rehabilitation groups in the whole community increased during the period from 24% to 63%. During the programme period there was a reduction in incidence of recurrent infarctions and new vocational invalidity pensions among the patients with AMI.

The use of oral contraceptives (OC) and smoking habits were studied by using a questionnaire in a random population sample of women from two counties of Eastern Finland in 1972. The participation rate was 95%. Data on use of OC and smoking were collected for 2,653 women aged 35-49 years. During the next seven years, 27 of them had developed an acute myocardial infarction (AMI). Smokers had a 2.6-fold (95% confidence interval (CI)=1.2-6.0) crude risk of developing AMI compared with non-smokers. Women taking OC had a 1.3-fold (95% CI = 0.4-6.9) risk of developing AMI compared with those who did not. Women who both smoked and used OC had a 7.2-fold (95% CI = 2.1-24.7) risk of AMI compared with non-smokers and non-users of OC. The results indicate that use of OC is associated with an excessive risk of AMI among female smokers.

The contribution of electrocardiograms, serum enzymes and history of chest pain to the diagnosis of acute myocardial infarction (AMI) was examined in a series of 3123 persons with a definite acute myocardial infarction registered in a community-based myocardial infarction register study in North Karelia, eastern Finland in 1972-1981. Criteria for chest pain history, serum enzyme and electrocardiographic findings were those used in the WHO co-ordinated myocardial infarction register studies. The history of chest pain typical of AMI was obtained in approximately 90% of both men and women in all age groups. Among persons with first AMI, the proportion of unequivocal ECG changes was higher among men than in women and declined with age in both sexes (81.8% in men 20-44 years of age, 47.8% in men 75 years of age or more; 61.7% in women 20-54 years of age and 45-6% in women 75 years of age or more) and lower among persons with recurrent AMI, but even among them it decreased with age. The proportion of serum enzyme elevations was approximately 90% in all subgroups. The results of the present study reconfirm that the contribution of elevated serum enzymes is particularly important in patients with recurrent acute myocardial infarction and old age. Elevated serum enzymes should receive greater attention in surveillance studies aiming to detect trends in AMI incidence in populations.

Body mass index (weight (kg) divided by height squared (m2] and its association with the risk of myocardial infarction and death from all causes were studied prospectively in a randomly selected population sample in eastern Finland aged 30-59 at outset in 1972. The study population consisted of 3786 men and 4120 women. The participation rate in the survey in 1972 was over 90%. All deaths and admissions to hospital in the sample were obtained from the National Death Certificate and Hospital Discharge Registers. During the seven years of follow up until 1978, 170 men and 52 women had acute myocardial infarction, and during the nine years up to 1980, 223 men and 92 women died. Independent of age, men with a body mass index of 28.5 or more had a significantly higher incidence of acute myocardial infarction. This effect was also independent of smoking but not independent of biological coronary risk factors--that is, serum cholesterol concentration and blood pressure. In the analysis stratified for smoking in men the body mass index total mortality curve was J shaped among non-smokers, whereas smoking entirely outweighed body mass index as a predictor of death. Body mass index did not contribute significantly to the risk of either acute myocardial infarction or death in women. It is concluded that a body mass index of around 29.0-31.0 or more is not only a marker for coronary risk factors but is also a predictor of acute myocardial infarction in men.

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. [ABSTRACT FROM AUTHOR]