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Background: Risk stratification for cardiovascular outcomes is gaining importance in general population. Prognostic value of natriuretic peptides has been established in patients with heart failure. However, the prognostic significance of natriuretic peptides with respect to stroke is not well known in general populations. Methods: Plasma natriuretic peptides were measured in a representative population-based sample of 958 men (age 46-65 years) from Eastern Finland. There were 46 cases of stroke, 74 of atrial fibrillation and 31 cases of ischaemic strokes during a follow-up of 9.6 years. Results: The multivariable adjusted risk was 1.35-fold (95% CI 1.01 to 1.84, p = 0.049) for any stroke and 1.30-fold (95% CI 0.90 to 1.91, p = 0.0150) for ischaemic stroke for each log-transformed SD (0.240 pmol/l) increment in N-terminal fragment of proA-type natriuretic peptide. The respective risks were 1.36-fold (95% CI 1.05 to 1.76, p = 0.010) and 1.50-fold (95% CI 1.12 to 2.02, p = 0.007) for each log-transformed SD (0.237 pmol/l) increment in N-terminal fragment of proB-type natriuretic peptide. The multivariate adjusted risks for future atrial fibrillation were 1.71 (95% CI 1.32 to 2.22, p<0.001) and 1.68-fold (95% CI 1.38 to 2.07, p<0.001) for each log-transformed SD increment in N-terminal fragments of proA- and proB-type natriuretic peptides, respectively. Conclusions: N-terminal fragments of pro-atrial natriuretic peptide and pro-brain natriuretic peptide are new additional predictors of any stroke and atrial fibrillation. Natriuretic peptides provide prognostic information for stroke and atrial fibrillation and may help in identifying subjects at risk for stroke and atrial fibrillation. [ABSTRACT FROM AUTHOR]

Background. There are no data on directly measured cardiorespiratory fitness combined coronary risk evaluation with respect to death from cardiovascular diseases and all-causes. We investigated the prognostic significance of risk scores and cardiorespiratory fitness with respect to cardiovascular disease and all-cause mortality. Methods. Cardiorespiratory fitness (maximal oxygen uptake, VO2peak) was measured by exercise test with an electrically braked cycle ergometer. The study is based on a random population-based sample of 1639 men (42–60 years) without history of type 2 diabetes or atherosclerotic cardiovascular diseases. Results. During an average follow-up of 16 years, a total of 304 deaths occurred. Independent predictors for all-cause death were European Score (for 1% increment, RR 1.15, 95% CI 1.10–1.20), VO2peak (for 1 MET increment, RR 0.84, 95% CI 0.78–0.89), when adjusted for C-reactive protein, alcohol consumption, serum high-density lipoprotein, waist-to-hip ratio, family history of coronary heart disease, exercise-induced ST changes and the use of medications for hypertension, dyslipidaemia or aspirin. Also, Framingham risk score was related to the risk of death (RR 1.05, 95% CI 1.03–1.07, P < 0.001). Subjects with high European or Framingham score and low VO2peak represent the highest risk group. Conclusion. An important finding is that the risk scores can be used to identify men for whom low cardiorespiratory fitness predicts an especially high risk for death from cardiovascular and any other cause. [ABSTRACT FROM AUTHOR]

Background/Objectives: To assess safety during a diet based on low-fat foods enriched with nonesterified wood-derived plant sterols and mineral nutrients related to serum phytosterol, sex hormone and fat-soluble vitamin metabolism.Subjects/Methods: Seventy-one study participants (52 women, 19 men) with mild-to-moderate hypercholesterolemia completed the double-blind, placebo-controlled feeding trial lasting for 15 weeks. The subjects were randomly allocated to the sterol group receiving food items enriched with mineral nutrients as well as with a total of 1.25, 2.5 and 5.0 g per day of plant sterols during the first, second and third 5-week periods, respectively, or to the placebo group receiving similar food items without plant sterols. This outpatient clinical trial with free-living subjects was carried out at two hospital clinics.Results: Two significant findings were observed. Serum sitosterol concentrations increased from 2.84 to 5.35 mg l−1 (P<0.004 vs placebo) but those of serum total plant sterols did not because of compensatory changes in other phytosterols. The highest plant sterol levels did not exceed 0.6% of total serum sterols. Serum α-tocopherol concentrations decreased in the sterol group by 10% (P<0.0002), but the between-group difference disappeared after adjusting for the change in the carrier (LDL cholesterol).Conclusions: Fifteen-week consumption of natural nonesterified plant sterol-enriched food does not cause any serious adverse effects during such a period. However, serum α-tocopherol levels were somewhat reduced in the sterol group suggesting that long-term effects of plant sterols on serum fat-soluble vitamin concentrations should be further explored, especially in relation to very low-fat diets.European Journal of Clinical Nutrition (2009) 63, 684–691; doi:10.1038/ejcn.2008.11; published online 13 February 2008 [ABSTRACT FROM AUTHOR]

Virtanen JK, Voutilainen S, Alfthan G, Korhonen MJ, Rissanen TH, Mursu J, Kaplan GA, Salonen JT (University of Kuopio, Kuopio; National Public Health Institute, Helsinki, Finland; University of Michigan, Ann Arbor, USA; and Oy Jurilab Ltd, Kuopio, Finland). Homocysteine as a risk factor for CVD mortality in men with other CVD risk factors: the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study.J Intern Med2005;257:255–262.Based on case–control and prospective studies elevated blood total homocysteine (tHcy) has been suggested to be an independent risk factor for cardiovascular diseases (CVD). The purpose of the study was to explore the joint effect of increased serum tHcy concentration and other risk factors on the risk of CVD mortality in middle-aged men without a history of heart disease or stroke.A prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study.Eastern Finland.A total of 802 men aged 46–64 years, examined in 1991–93.CVD mortality event.The mean serum tHcy concentration was 10.8 μmol L−1 (SD 3.3). During the average follow-up time of 10.8 years 50 men experienced a CVD death. The hazard rate ratio for CVD mortality was 1.80 (95% confidence interval: 1.02–3.19) in men in the highest serum tHcy third versus lower thirds after adjustment for cardiovascular risk factors. Furthermore, elevated serum tHcy concentration appeared to increase the risk of CVD death in men who smoke or who have high circulating concentrations of serum total or LDL cholesterol, apo-B apolipoprotein or plasma fibrinogen.We conclude that homocysteine may increase the risk of CVD mortality in middle-aged men from Eastern Finland, and it may especially increase the risk when present with other risk factors for CVD. [ABSTRACT FROM AUTHOR]

Background: Mental depression is an important health problem in many countries. It reduces productivity at work and is the fastest increasing reason for early retirement. Methods: This study followed up a Finnish cohort of 1726 men from 1984 to 2000. Depression was assessed at baseline by HPL depression score. Pension records were obtained from the national pension registers. Cox's regression analysis was used to estimate the associations of depression with the risk of all disability pensions combined, separately for different causes of disability, and non-illness based pension. Results: During the follow up, 839 men (48.6%) received a disability pension. A total of 142 men (16.9% of all disability pensions) retired because of mental disorder and of these, 75 (52.8%) because of depression. After adjustment for the potential confounders, men in the highest third of depression score had an increased risk of non-illness based pension (RR 1.86 95% CI 1.37 to 2.51) and disability pension attributable to mental disorders (RR 2.74, 95% CI 1.68 to 4.46), chronic somatic diseases (RR 1.68, 95% Cl 1.05 to 2.71), cardiovascular diseases (RR 1.61, 95% CI 1.12 to 2.32). The mean age of retirement for men with a high and low depression score was 57.6 years (SD 3.87) and 59.1 years (SD 3.65) (p<0.001) respectively. Conclusions: A high depression score predicted disability attributable to any cause, especially mental disorders, and non-illness based pensions. Depressed people retired on average 1.5 years younger than those without depression. Further studies are needed to elucidate the pathways of how mental depression leads people to seek retirement pension. [ABSTRACT FROM AUTHOR]

Different C18 monohydroxy fatty acids (OHFAs) were evaluated for their usefulness as markers of plasma lipid peroxidation (unsaturated fatty acid oxidation) ex vivo and in vivo . First, plasma samples (n=5) were exposed for 3 h to different radical fluxes ex vivo . The formation of OHFAs was assessed by using varying concentrations of Cu 2+ ions and AAPH (2,2′-azobis(2-amidinopropane) hydrochloride) as radical flux initiators. Secondly, a cross-sectional study was carried out in 47 middle-aged men. In this study, plasma concentrations of different in vivo OHFAs were compared with other indices of lipid peroxidation. Under mild oxidation conditions (heparin plasma containing 4.2 or 8.3 mM AAPH), concentrations of all the measured OHFAs (8, 9, 10, 11, 12, 13, 15 and 16-OH acids) increased in an identical manner, but under highly oxidative conditions (heparin plasma containing 83 mM AAPH or 4.2 to 8.3 mM CuSO 4 ) mainly 9 and 13-OHFAs were formed. In the cross-sectional study, plasma 11 and 13-OHFA levels were associated statistically significantly with plasma free F 2α -isoprostanes, recognized index of in vivo lipid peroxidation (r=0.305, p=0.037 and r=0.308, p=0.035, respectively). In addition, 16-OHFA levels correlated with the ratio of electronegatively charged LDL to total LDL (r=0.335, p=0.021). With respect to the other OHFAs, 15-OHFA had no correlation with either other OHFAs or the reference substances used. In addition, occasionally there were contamination problems in the assessment of 12-OHFA. It is concluded that all of the measured C18 OHFAs can be used as indicators of plasma lipid peroxidation under mild oxidation conditions, though the 12 and 15-OHFAs may need to be used with some caution. Under high oxidation conditions, 9-and 13-OHFAs seem to be the most useful indices because of their high formation capacity. [ABSTRACT FROM AUTHOR]

Abstract Aims Dietary fatty acid intake is reflected in serum fatty acid composition. Studies prospectively investigating serum fatty acids and development of impaired fasting glycaemia (IFG) or diabetes mellitus (DM) are largely lacking. We assessed the association of serum fatty acid composition with development of IFG or DM. Methods Middle-aged normoglycaemic men (n = 895) participating in a prospective cohort study were followed up after 4 years. Results At baseline proportions of serum esterified and non-esterified saturated fatty acids were increased and polyunsaturated fatty acids decreased in men who after 4 years had developed IFG (n = 56) or DM (n = 34). No differences in dietary fatty acid composition as recorded in 4-day dietary records were noted. In logistic regression analyses adjusting for age; obesity; and fasting lipid, glucose and insulin concentrations, men with proportions of non-esterified and esterified linoleate in the upper third had nearly half the risk for IFG or DM compared with the lower third. In covariate analyses, baseline non-esterified linoleate proportions were associated with changes in fasting insulin and glucose concentrations over the 4-year follow-up. Baseline esterified fatty acid composition was also associated with changes in insulin. Conclusions High serum linoleate proportions decreased the risk of developing IFG or DM in middle-aged men over a 4-year follow-up, possibly mediated in part by insulin resistance. These findings support recommendations to substitute vegetable fat for animal and dairy fat in the prevention of disturbances of glucose and lipid metabolism. [ABSTRACT FROM AUTHOR]

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]

Objectives: The purpose of the study was to test whether the pentanucleotide insertion/deletion polymorphism in the 3'-untranslated region (3'-UTR) of the leptin receptor gene, which has previously been associated with serum insulin levels in obese subjects, is associated with insulin levels and the risk of type 2 diabetes in non-diabetic middle-aged men.Subjects and Design: We studied these associations in a prospective population-based nested case-control study in 41 men who developed type 2 diabetes during 4-year follow-up and 81 controls who were matched for age, obesity, baseline glucose and insulin and other strongest risk factors. Both the cases and the controls came from a cohort of 985 men who had no diabetes at baseline.Results: There was one homozygote and 22 heterozygotes for the 3'-UTR insertion allele amongst all 122 men. The carrier frequency of this allele was 9.8% amongst the cases and 23.5% amongst the controls. At baseline, the mean fasting serum insulin was 12.2 mU L-1 in the 23 men who were heterozygous or homozygous for the insertion allele and 17.1 mU L-1 in the 99 men who were homozygous for the deletion allele (P = 0.005). In a logistic regression model adjusting for four strongest non-matched predictors of type 2 diabetes, the carriers of the insertion allele had a 79% reduced risk of diabetes (OR = 0.21; 95% CI = 0.06-0.77, P = 0.019), compared with non-carriers.Conclusion: Our findings support the hypothesis that alterations in the leptin signalling system could contribute to serum insulin levels and the development of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Insulin resistance or compensatory hyperinsulinemia has been associated with hypertension and dyslipidemia in cross-sectional studies. In contrast, evidence from prospective population-based studies, which could establish the time order of the relationship, is sparse and inconsistent. Therefore, we investigated the associations of hyperinsulinemia with the incidence of hypertension and dyslipidemia in the Kuopio Ischemic Heart Disease Risk Factor Study, a population-based 4-year follow-up study of middle-aged men from eastern Finland. Out of 975 men who had no diabetes, 543 had resting systolic blood pressure (sBP) of < 165 mmHg and resting diastolic blood pressure (dBP) of < 95 mmHg at baseline and were not taking antihypertensive medication, and 764 had serum triglycerides of < 2.3 mmol/l and HDL cholesterol of > or =1.0 mmol/l at baseline. In logistic regression models adjusted for age, baseline resting blood pressure, baseline lipids, obesity, weight change, and other risk factors, men with hyperinsulinemia (fasting insulin in the highest quintile, > or =12.0 mU/l) at baseline had a 2.0-fold (95% CI 1.1-3.5, P = 0.025) incidence of hypertension (sBP of > or =165 or dBP of > or =95 mmHg), a 2.1-fold (95% CI 1.3-3.4, P = 0.002) incidence of dyslipidemia (serum HDL cholesterol of < 1.0 mmol/l or serum triglycerides of > or =2.3 mmol/l), and a 2.6-fold (95% CI 1.1-6.3, P = 0.028) incidence of the combination of these disorders in 4 years, compared with normoinsulinemic men. These findings demonstrate the role of hyperinsulinemia in incident hypertension and dyslipidemia and suggest that both hypertension and dyslipidemia are associated with insulin metabolism disturbance, independently of obesity and body weight. [ABSTRACT FROM AUTHOR]

Cardiovascular responses to psychological events may mediate the influence of stress on cardiovascular disease. In this study the authors asked whether cardiovascular responses to psychological challenge changed with age and whether such changes were intrinsic to aging or could be attributed to the influence of disease and medications. Cardiovascular reactivity to mental challenge was examined in 902 men ranging in age from 46 to 64 years who participated in the Kuopio Ischemic Heart Disease Risk Factor Study. A battery of 4 tasks was used to induce cardiovascular responses. Current disease status, age, and medication use were entered into hierarchical regression analyses to assess their relation with measures of cardiovascular reactivity. Age and hypertension contributed independent, approximately equal, but small amounts of variance in the cardiac and vascular reactivity indexes. Medications also influenced reactivity independently of age and disease. Performance on the tasks was more consistently altered by age than by disease or medication. Cardiac and vascular reactivity increased with increasing age and the presence of hypertension. The authors conclude that both age and disease state must be considered when examining cardiovascular reactivity as a risk factor for disease. [ABSTRACT FROM AUTHOR]

Low plasma levels of high density lipoprotein (HDL) and high levels of low density lipoprotein (LDL) as well as smoking are known risk factors in coronary heart disease. It has been suggested that oxidative modification renders LDL atherogenic. We investigated the influence of smoking cessation on plasma lipid and lipoprotein levels and on the ability of lipoproteins to resist oxidation in vitro (lag time). A total of 182 healthy smokers who smoked more than 15 cigarettes per day were randomized to stop smoking (smoking cessation group, n = 100) or to continue smoking for 4 weeks (control group, n = 82). The smoking cessation group was followed up after 26 weeks. After 4 weeks, the HDL level had increased from mean ± SD 1.36 ± 0.34 to 1.48 ± 0.40 mmol l (p<0.001) in 62 successful quitters, while levels were unchanged in the control group (72 subjects in per-protocol analysis). However, after 26 weeks there was no change in HDL (1.34 ± 0.36 vs. 1.36 ± 0.35 mmol l) in 29 subjects from the smoking cessation group who fulfilled the study. Plasma levels of very low density lipoprotein (VLDL), LDL, total cholesterol, triglycerides and oxidation resistance of VLDL + LDL did not show significant changes any time during the study for either group. Thus, plasma levels of lipids and lipoproteins as well as oxidation resistance of lipoproteins seem unaffected by smoking cessation for 26 weeks. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The aim of this work was to investigate whether measurement of the mean common carotid intima-media thickness (CIMT) improves cardiovascular risk prediction in individuals with diabetes., Methods: We performed a subanalysis among 4,220 individuals with diabetes in a large ongoing individual participant data meta-analysis involving 56,194 subjects from 17 population-based cohorts worldwide. We first refitted the risk factors of the Framingham heart risk score on the individuals without previous cardiovascular disease (baseline model) and then expanded this model with the mean common CIMT (CIMT model). The absolute 10 year risk for developing a myocardial infarction or stroke was estimated from both models. In individuals with diabetes we compared discrimination and calibration of the two models. Reclassification of individuals with diabetes was based on allocation to another cardiovascular risk category when mean common CIMT was added., Results: During a median follow-up of 8.7 years, 684 first-time cardiovascular events occurred among the population with diabetes. The C statistic was 0.67 for the Framingham model and 0.68 for the CIMT model. The absolute 10 year risk for developing a myocardial infarction or stroke was 16% in both models. There was no net reclassification improvement with the addition of mean common CIMT (1.7%; 95% CI -1.8, 3.8). There were no differences in the results between men and women., Conclusions/interpretation: There is no improvement in risk prediction in individuals with diabetes when measurement of the mean common CIMT is added to the Framingham risk score. Therefore, this measurement is not recommended for improving individual cardiovascular risk stratification in individuals with diabetes.

Background: Risk stratification for cardiovascular outcomes is gaining importance in general population. Prognostic value of natriuretic peptides has been established in patients with heart failure. However, the prognostic significance of natriuretic peptides with respect to stroke is not well known in general populations., Methods: Plasma natriuretic peptides were measured in a representative population-based sample of 958 men (age 46-65 years) from Eastern Finland. There were 46 cases of stroke, 74 of atrial fibrillation and 31 cases of ischaemic strokes during a follow-up of 9.6 years., Results: The multivariable adjusted risk was 1.35-fold (95% CI 1.01 to 1.84, p = 0.049) for any stroke and 1.30-fold (95% CI 0.90 to 1.91, p = 0.0150) for ischaemic stroke for each log-transformed SD (0.240 pmol/l) increment in N-terminal fragment of proA-type natriuretic peptide. The respective risks were 1.36-fold (95% CI 1.05 to 1.76, p = 0.010) and 1.50-fold (95% CI 1.12 to 2.02, p = 0.007) for each log-transformed SD (0.237 pmol/l) increment in N-terminal fragment of proB-type natriuretic peptide. The multivariate adjusted risks for future atrial fibrillation were 1.71 (95% CI 1.32 to 2.22, p<0.001) and 1.68-fold (95% CI 1.38 to 2.07, p<0.001) for each log-transformed SD increment in N-terminal fragments of proA- and proB-type natriuretic peptides, respectively., Conclusions: N-terminal fragments of pro-atrial natriuretic peptide and pro-brain natriuretic peptide are new additional predictors of any stroke and atrial fibrillation. Natriuretic peptides provide prognostic information for stroke and atrial fibrillation and may help in identifying subjects at risk for stroke and atrial fibrillation.

One difficulty in performing meta-analyses of observational cohort studies is that the availability of confounders may vary between cohorts, so that some cohorts provide fully adjusted analyses while others only provide partially adjusted analyses. Commonly, analyses of the association between an exposure and disease either are restricted to cohorts with full confounder information, or use all cohorts but do not fully adjust for confounding. We propose using a bivariate random-effects meta-analysis model to use information from all available cohorts while still adjusting for all the potential confounders. Our method uses both the fully adjusted and the partially adjusted estimated effects in the cohorts with full confounder information, together with an estimate of their within-cohort correlation. The method is applied to estimate the association between fibrinogen level and coronary heart disease incidence using data from 154,012 participants in 31 cohorts

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.

Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.

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.

A low level of physical activity has been associated with depression, and increased physical activity has been found to have a positive effect on mood. However, the association between maximal oxygen uptake (VO(2max)) and mood has been poorly studied. In this study VO(2max) (ml/kg per min) was measured in a sample of 1,519 men aged 46-61 years during a cycle ergometer test by using respiratory gas exchange. Men with a history of psychiatric disorder or serious physical illness were excluded. Depressive symptoms were assessed using the 18-item Human Population Laboratory Depression Scale (HPL). Those who scored 5 or more in the HPL were considered to have elevated depressive symptoms. The participants were classified into quartiles according to the VO(2max). Those in the lowest quartile had a more than 3-fold (OR: 3.42; 95% CI: 1.65-7.09; p < 0.001) higher risk of having elevated depressive symptoms compared with those in the highest quartile, even after adjusting for several confounders (OR: 3.38; 95% CI: 1.60-7.14; p < 0.001). In conclusion, low VO(2max) is associated with having elevated depressive symptoms in middle-aged men.

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/hypothesis: Type 2 diabetes is associated with a two- to seven-fold increase in cardiovascular morbidity and mortality. The aim of this study was to determine the relationships between intima-media thickness (IMT), an established marker of atherosclerosis, large artery function and other determinants of cardiovascular risk in type 2 diabetic patients., Methods: We studied 228 type 2 diabetic patients (75 women, aged 62+/-2 years [mean+/-SEM]). Carotid IMT was bilaterally measured using ultrasound technology. Applanation tonometry and pulse wave analysis were used to measure aortic systolic and diastolic blood pressures, central pressure augmentation (AG) and the augmentation index (AIx), a measure of systemic arterial stiffness. Conventional cardiovascular risk factors (lipids, HbA(1)c, smoking and diabetes duration) were also assessed., Results: Women had higher AG and AIx (p<0.0001), despite comparable systolic BP and heart rate in women and men. In women, AG (r=0.39, p<0.001), age (r=0.32, p<0.01), brachial systolic BP (r=0.34, p<0.01) and aortic systolic BP (r=0.34, p<0.01) correlated with IMT. In men, age (r=0.41, p<0.001), diabetes duration (r=0.25, p<0.01), AG (r=0.22, p<0.01), aortic systolic BP (r=0.21, p<0.01), brachial systolic BP (r=0.21, p<0.01) and body weight (r=0.16, p<0.05) correlated with IMT. In multiple linear regression analyses, AG and aortic systolic BP, but not brachial systolic BP, were age-independent determinants of IMT in men and women. In all patients, increased AG (adjusted for sex, age and heart rate) correlated with longer duration of diabetes, urinary albumin excretion and IMT., Conclusions/interpretation: Measures of central systolic pressure correlate with carotid IMT, independently of age and other risk markers.

Background and Purpose: Low maximal oxygen uptake (VO2max) has been shown to predict the risk of stroke. However, VO2max does not take into account the differences in cardiac afterload between subjects. The aim of this study was to examine the relationship of exercise cardiac power (ECP), defined as a ratio of VO2max with peak systolic blood pressure (SBP) during exercise, with the risk for stroke., Methods: Population-based cohort study with an average follow-up of 12 years from eastern Finland. A total of 1761 men with no history of stroke or coronary heart disease at baseline participated. Among these men, 91 strokes occurred, of which 69 were attributable to ischemic causes., Results: The relative risk of any stroke in men with low ECP (<10.3 mL/mm Hg) was 2.7 (95% CI, 1.2 to 6.0; P=0.01; P=0.02 for the trend across the quartiles), and the relative risk for ischemic stroke was 2.7 (95% CI, 1.1 to 7.0; P=0.03; P=0.04 for trend across the quartiles) compared with men having high ECP (>14.3 mL/mm Hg) during exercise after adjusting for age, examination year, cigarette smoking, alcohol consumption, body mass index, diabetes, serum total cholesterol level, energy expenditure of physical activity, exercise-induced myocardial ischemia, and the use of antihypertensive medication. After further adjustment for resting SBP, results were statistically nonsignificant., Conclusions: Low ECP provides noninvasive and easily available measure for stroke risk. One of the most potential explanations for the association between ECP and the increased risk of stroke is an elevated afterload and peripheral resistance indicated by elevated SBP.

Objectives: The objective of this study was to assess the relationship between inflammation, endothelial activation and incipient atherosclerosis in type 2 diabetes., Design: Cross-sectional study. Setting and subjects. We studied 239 type 2 diabetic patients [71 with clinical cardiovascular disease (CVD)] and 78 healthy control subjects, aged 50-75 in a single research centre., Methods: Carotid intima-media thickness (IMT) was determined by ultrasound. Circulating intracellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, ultra-sensitive C-reactive protein, human serum amyloid A, interleukin-6, monocyte colony-stimulating factor, secretory nonpancreatic phospholipase A(2) type IIA, glucose, HbA1c, and lipid/lipoprotein variables were measured., Results: Carotid IMT was significantly thicker in diabetic patients than healthy controls across the whole age range. IMT was also thicker in diabetic patients with, than without, CVD, but this difference disappeared after controlling for confounding factors. Concentrations of the inflammatory and endothelial markers except IL-6 were significantly higher in the diabetic patients than in healthy controls, but comparable in diabetic patients with and without CVD. The main determinants of IMT in the diabetic patients were blood pressure, age and diabetes duration., Conclusions: Low-grade inflammation and endothelial activation are increased in diabetic patients but do not associate with IMT or clinical CVD. The inflammatory reaction seems to be rather a feature of the metabolic syndrome than a direct determinant of atherosclerosis.

Aims/hypothesis: Low-grade inflammation has been implicated in the development of Type 2 diabetes and cardiovascular disease, but its role in the pathogenesis of the metabolic syndrome is unclear. We investigated the association between C-reactive protein (CRP) levels and the development of the metabolic syndrome and diabetes in men., Methods: Serum CRP concentrations and factors related to insulin resistance were determined in middle-aged Finnish men who participated in a population-based cohort study and were free of diabetes at baseline., Results: At the 11-year follow-up, 143 of 680 men had developed the metabolic syndrome as defined by the National Cholesterol Education Program (NCEP) and 103 of 598 men had developed the metabolic syndrome as defined by the World Health Organization (WHO). Our analyses excluded men with the metabolic syndrome by the respective definition at baseline. In all, 78 of 762 men developed diabetes over the same period. Men with CRP concentrations > or =3 mg/l had a several-fold higher age-adjusted risk of developing the metabolic syndrome (NCEP definition: odds ratio [OR]=3.2, 95% CI 1.9-5.5; WHO definition: OR=3.4, 95% CI 2.0-6.1) or diabetes (OR=4.1, 95% CI 2.1-8.0) than men whose CRP levels were <1.0 mg/l. Even after further adjustment for potentially confounding lifestyle factors and factors related to insulin resistance, the risk of diabetes (OR=2.3, 95% CI 1.0-5.1) was still increased in men with CRP concentrations > or =3 mg/l, but the association with the metabolic syndrome was no longer significant., Conclusions/interpretation: Low-grade inflammation may increase the risk of the metabolic syndrome and diabetes in middle-aged men, but some of the risk is mediated through obesity and factors related to insulin resistance.

Background: Early retiring is a major social problem in many western countries., Aim: To investigate whether good cardiorespiratory fitness prevents disability pensioning in Finnish middle-aged men., Methods: Subjects were a random population based sample of 1307 men who were 42-60 years old at baseline, had not retired before baseline or died during follow up, and had undergone a cycle ergometer test at baseline. Cardiorespiratory fitness was assessed at baseline with a maximal but symptom limited exercise test on an electrically braked cycle ergometer., Results: During a follow up of 11 years on average, 790 (60.4%) men were awarded a disability pension, only 254 (19.4%) men reached the old-age pension without previous early pension, and 263 (20.1%) men were still working at the end of follow up. After adjustment for age, body mass index, alcohol consumption, smoking, education, occupation, and baseline chronic diseases, an inverse association was observed between cardiorespiratory fitness and the risk of disability pension. Men with VO2max <25.98 ml/kg/min (lowest fifth) had a 3.28-fold (95% CI 1.70 to 6.32) and men with the duration of exercise test <9.54 minutes (lowest fifth) had a 4.66-fold (95% CI 2.43 to 8.92) risk of disability pension due to cardiovascular diseases compared with men in the highest fifths. Men with lowest fitness level also had an increased risk of disability pension due to musculoskeletal disorders, or all reasons combined., Conclusions: Physical fitness is inversely associated with the risk of disability pension and especially with the risk of disability due to cardiovascular diseases.

Background and Purpose: There are few if any data on the prognostic importance of silent myocardial ischemia during exercise with regard to the risk of stroke and cardiovascular diseases (CVDs) among asymptomatic men. In this prospective study, we investigated the relation of silent myocardial ischemia and the risk of stroke and CVD death in men with and without conventional risk factors., Methods: The study sample included 1726 middle-aged men with no history of stroke, coronary heart disease, or atrial fibrillation at baseline. Silent myocardial ischemia was defined as a horizontal or downsloping ST-segment depression (>or=1 mm) during exercise electrocardiography. A total of 86 CVD-related deaths and 78 strokes occurred during an average follow-up of 10 years., Results: Men with silent ischemia during exercise had a 3.5-fold increased risk of CVD death and a 2.2-fold increased risk of stroke compared with men without silent ischemia, after adjusting for conventional risk factors. Silent ischemia during exercise was associated with a 3.8-fold (95% confidence interval [CI], 1.5 to 9.5) increased risk for CVD in smokers, a 3.9-fold (95% CI, 2.1 to 7.3) increased risk in hypercholesterolemic subjects, a 3.6-fold (95% CI, 1.9 to 6.8) increased risk in the hypertensives, and 3.8-fold (95% CI, 2.0 to 7.1) increased risk in overweight men. The respective relative risks for stroke were 3.8 (95% CI, 1.1 to 12.5), 3.5 (95% CI, 1.7 to 7.4), 3.4 (95% CI, 1.6 to 7.1), and 2.9 (95% CI, 1.4 to 6.1)., Conclusions: Exercise-induced silent myocardial ischemia is an important indicator of increased risk of stroke and CVD in men with other risk factors, such as smoking, hypercholesterolemia, hypertension, and being overweight.

Background: Low high-density lipoprotein cholesterol (HDL-C) is associated with increased risk for developing coronary artery disease. Cardiovascular disease is characterized by increased intima-media thickness (IMT) and arterial stiffness, but the effect of low HDL on these measurements has not been reported., Materials and Methods: We studied 18 apparently healthy subjects from families with low HDL-C and 18 control subjects, which were pair-matched to maximize statistical power. Intima-media thickness was assessed using ultrasound examination of the carotid arteries. Arterial stiffness was measured using applanation tonometry on the radial artery and pulse-wave analysis to obtain central aortic pulse-pressure waveform, from which the augmentation index, a measure of global large artery stiffness, was calculated., Results: Low HDL subjects (age 41 +/- 3 years, BMI 26.6 +/- 1.0 kg m(-2) had significantly lower HDL-C than the control subjects (age 41 +/- 3 years, BMI 26.5 +/- 1.0 kg m-2; 1.00 +/- 0.05 vs. 1.49 +/- 0.09 mmol L-1, low HDL vs. control subjects, P < 0.0001). Subjects with low HDL-C had significantly thicker mean IMTs than the control subjects (0.77 +/- 0.03 vs. 0.70 +/- 0.02 mm, low HDL vs. control subjects, P < 0.01). The maximal (0.99 +/- 0.04 vs. 0.89 +/- 0.03 mm, P < 0.01), far wall (0.76 +/- 0.04 vs. 0.69 +/- 0.02 mm, P < 0.05) and carotid bulb (1.11 +/- 0.06 vs. 0.97 +/- 0.04 mm) IMTs were also significantly increased, whereas the mean common carotid and the internal artery IMT were not. The age-related increase in mean IMT was more pronounced in the low HDL subjects than the control subjects (P < 0.01 for difference between elevations of age vs. IMT slopes). There were no differences in central pressure augmentation, the augmentation index, peripheral or central blood pressures between the groups., Conclusions: A low HDL-C concentration is associated with thickening of carotid IMT independent of other risk factors in healthy affected members of low HDL families.

The dopaminergic system in the human brain is thought to play a major role in the development of alcohol consumption habits and alcoholism. It has been reported that homozygous D2-/- knock-out mice lacking D2 receptors consume about 50% to 60% less ethanol than wild-type D2+/+ mice, and heterozygous mice have an intermediate level of alcohol consumption. The DRD2 gene TaqI A polymorphism has been suggested to associate with a low D2 receptor density in post mortem and in vivo measurements. Numerous association studies on this polymorphism and alcoholism have shown most controversial results. We studied whether DRD2 TaqI A genotype affects alcohol consumption in an ethnically homogeneous, representative sample of 1,019 Finnish Caucasian males. After excluding the abstainers from the study, the self-reported alcohol consumption among the remaining 884 non-abstainers was compared in the TaqI A genotype groups (A1/A1, A1/A2, A2/A2). The alcohol consumption of the homozygous A1/A1 group was about 30% lower than in A1/A2 group, and 40% lower than in A2/A2 group (P = 0.042 and 0.041 in a sociodemographic variable-adjusted multivariate model). The results indicate an association between DRD2 genotype and alcohol consumption habits in humans. These results in the large sample of non-alcoholic males are also opposite to some previous findings on the higher A1 allele frequency among alcoholic populations., (Copyright 2003 Wiley-Liss, Inc.)

Objective: To analyse the lignan content of phloem powder enriched rye bread and to study the dose-response relationship of the effect of dietary plant lignans derived from phloem on intestinal production of enterolactone by measuring enterolactone concentration in serum., Design: A randomized double-blind supplementation trial., Subjects: Seventy-five non-smoking men recruited by newspaper advertisements., Intervention: Subjects were randomized to three study groups receiving either rye bread high in phloem (HP, 14% of rye flour substituted with phloem powder), rye bread low in phloem (LP, 7% of rye flour substituted with phloem powder) or placebo rye bread. Participants consumed 70 g of study bread daily for 4 weeks and provided serum samples for enterolactone analysis at baseline and at the end of the intervention., Results: There was a significant increase in serum enterolactone concentration in the LP and HP groups compared with the placebo group (P=0.009 and P=0.003, respectively). Considerable interindividual differences were observed in the response to dietary lignans within the study groups., Conclusions: Our results indicate that plant lignans attached to insoluble fibre layer in phloem can be further metabolized and converted to enterolactone presumably by the bacteria present in the colon. Phloem powder is useful source of lignans for functional foods aimed to elevate serum enterolactone levels., Sponsorship: Phloem powder and the study breads were provided by Finnpettu Oy and Linkosuo Oy, respectively. The clinical study work was sponsored in part by Oy Jurilab Ltd.

We investigated the temporal relationships between obesity, weight change and hyperinsulinemia in a population-based 4-year follow-up study of 695 middle-aged, non-diabetic, and normoinsulinemic men. Thirty-eight men developed hyperinsulinemia during the follow-up (fasting serum insulin > or = 12.0 mU/l). In logistic regression analysis adjusting for other risk factors, men with body mass index of > or = 26.7 kg/m2 (highest third) had a 6.6-fold (p = 0.001) risk of developing hyperinsulinemia, compared with men with body mass index of < 24.4 kg/m2 (lowest third). Correspondingly, men with waist-to-hip ratio of > or = 0.95 (highest third) had a 3.5-fold (p = 0.028) incidence of hyperinsulinemia compared with men with waist-to-hip ratio of < 0.90 (lowest third). Weight gain in middle age and weight gain from the age of 20 years to middle age were also associated with increased risk of hyperinsulinemia. Hyperinsulinemia at baseline was not associated with weight gain during the follow-up. This prospective population-based study emphasizes the importance of avoiding obesity and weight gain during adulthood in preventing hyperinsulinemia.