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Background and Aims: Cardiovascular health scores have emerged as a simple way to assess the risk to suffer from a cardiovascular disease. The American Heart Association's Life's Simple 7 constitutes of modifiable lifestyle factors to reduce cardiovascular risk. Its association with carotid properties is yet inconclusive. The aim of this study is to determine the association between the adherence to Life's Simple 7 and carotid properties in middle-aged to elderly Finns., Methods: A representative sample of Finnish men and women aged 55-74 years was included in the present study. Carotid intima-media thickness (cIMT), lumen diameter (cLD), and carotid distensibility were measured by transcutaneous ultrasound using state-of-the-art wall contour detection techniques. The Life's Simple 7 cardiovascular health score was calculated using seven categories (body mass index, cholesterol, systolic blood pressure, fasting plasma glucose, smoking status, physical activity, and diet). In accordance to the American Heart Association, for each category, an ideal score was given 2 points, intermediate scores 1 point, and poor scores 0 points., Results: In total, 1400 (49.4% male) subjects were included in the analyses. After adjusting for age and sex, we found that subjects with a an ideal cardiovascular health score had lower cLD than those with an intermediate score (-0.21 mm, 95% CI: 0.37 to -0.05 mm, p=0.005) and a poor score (-0.39 mm, 95% CI: 0.65 to -0.12 mm, p=0.001). Similarly, subjects with an ideal health score had higher carotid distensibility than those with an intermediate score (0.0032 1/kPa, 95% CI: 0.009-0.0055 1/kPa, p=0.002) and a poor score (0.0018 1/kPa, 95% CI: 0.0005-0.0032 1/kPa, p=0.004). We found no differences regarding cIMT., Conclusions: In middle-aged to elderly Finns, higher adherence to the Life's Simple 7 is associated with lower cLD and higher distensibility, but not with cIMT. Adherence to healthy lifestyle habits is therefore associated with better carotid structure and carotid function in middle-aged to elderly Finns., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Background: The Mediterranean Diet (MD) is a model of healthy eating contributing to a favorable health status, but its clinical usefulness is still debated. The aim of this study was to relate the adherence to MD with the incidence of cardio/cerebro-vascular events (VEs) in north and south European participants of the IMPROVE study., Methods: IMPROVE is an observational, longitudinal, prospective cohort study involving 3703 individuals from five European countries (Finland, Sweden, Netherlands, France and Italy). The study end-point was the incidence of the first combined cardio/cerebro-vascular event occurring during 36-months follow-up. At baseline, a dietary questionnaire about the usual intake during the year preceding enrollment was administered. Based on 7 nutritional items, a MD Score was constructed in which minimal adherence was 0 and maximal adherence was 7., Results: Latitude was the strongest determinant of MD score (p < 0.001). VEs occurred in 215 participants. The incidence of VEs was the highest in subjects with MD score 0-1, lower in those with score 2-3 and the lowest in those with score ≥ 4. MD score remained significantly associated with subsequent VEs after adjustment for confounders (hazard ratio for one-point increment of the score = 0.75, p < 0.001) and the association was stronger in northern than in southern countries (p = 0.04 for MD Score × latitude interaction)., Conclusions: The MD adherence score based on a simple dietary questionnaire detects changes of risk of VEs. According to our findings north Europeans appear to benefit most from VE-prevention when their diet is altered to the MD diet., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide, particularly in individuals with diabetes. The current study objective was to determine the circulating metabolite profiles associated with the risk of future cardiovascular events, with emphasis on diabetes status. Nontargeted metabolomics analysis was performed by LC-HRMS in combination with targeted quantification of eicosanoids and endocannabinoids. Plasma from 375 individuals from the IMPROVE pan-European cohort was included in a case-control study design. Following data processing, the three metabolite data sets were concatenated to produce a single data set of 267 identified metabolites. Factor analysis identified six factors that described 26.6% of the variability in the given set of predictors. An association with cardiovascular events was only observed for one factor following adjustment (p = 0.026). From this factor, we identified a free fatty acid signature (n = 10 lipids, including saturated, monounsaturated, and polyunsaturated fatty acids) that was associated with lower risk of future cardiovascular events in nondiabetics only (OR = 0.65, 0.27-0.80 95% CI, p = 0.030), whereas no association was observed among diabetic individuals. These observations support the hypothesis that increased levels of circulating omega-6 and omega-3 fatty acids are associated with protective effects against future cardiovascular events. However, these effects were only observed in the nondiabetic population, further highlighting the need for patient stratification in clinical investigations.

Purpose: We aimed to assess the associations of oxygen uptake at aerobic threshold (VO 2 at AT) with cardiovascular and all-cause mortality., Design: VO 2 at AT was assessed in 1663 middle-aged men in a cohort study. Hazard ratios (HRs) were calculated for sudden cardiac death (SCD), fatal coronary heart disease (CHD) and cardiovascular disease (CVD) and all-cause mortality., Results: During a median follow-up of 25.6 years, 138 SCDs, 209 fatal CHDs, 333 fatal CVDs and 719 all-cause mortality events occurred. On adjustment for established risk factors, the HRs (95% CIs) for SCD, fatal CHD, fatal CVD and all-cause mortality were 0.48 (0.28-0.82), 0.48 (0.31-0.74), 0.57 (0.41-0.79) and 0.66 (0.53-0.82), respectively comparing extreme quartiles of VO 2 at AT. On further adjustment for peak VO 2 , the HRs were 0.87 (0.48-1.56), 0.83 (0.52-1.34), 0.91 (0.63-1.30) and 0.88 (0.69-1.12), respectively. Addition of VO 2 at AT to a standard CVD mortality risk prediction model was associated with a C-index change of 0.0085 (95% CI: -0.0002-0.0172; p = .05) at 25 years., Conclusions: VO 2 at AT is inversely associated with cardiovascular and all-cause mortality events, but the associations are partly dependent on peak VO 2 . VO 2 at AT may improve the prediction of the long-term risk for CVD mortality. KEY MESSAGES Oxygen uptake at aerobic threshold (VO 2 at AT), a cardiopulmonary exercise testing parameter, may be a useful prognostic tool for adverse clinical outcomes in the general population. In a population-based prospective cohort study of men, VO 2 at AT was inversely associated with cardiovascular and all-cause mortality events and improved the prediction of cardiovascular mortality. In populations who cannot achieve maximal VO 2 , VO 2 at AT may serve as a useful prognostic tool; however, further studies are warranted.

Recent advances in highly multiplexed immunoassays have allowed systematic large-scale measurement of hundreds of plasma proteins in large cohort studies. In combination with genotyping, such studies offer the prospect to 1) identify mechanisms involved with regulation of protein expression in plasma, and 2) determine whether the plasma proteins are likely to be causally implicated in disease. We report here the results of genome-wide association (GWA) studies of 83 proteins considered relevant to cardiovascular disease (CVD), measured in 3,394 individuals with multiple CVD risk factors. We identified 79 genome-wide significant (p<5e-8) association signals, 55 of which replicated at P<0.0007 in separate validation studies (n = 2,639 individuals). Using automated text mining, manual curation, and network-based methods incorporating information on expression quantitative trait loci (eQTL), we propose plausible causal mechanisms for 25 trans-acting loci, including a potential post-translational regulation of stem cell factor by matrix metalloproteinase 9 and receptor-ligand pairs such as RANK-RANK ligand. Using public GWA study data, we further evaluate all 79 loci for their causal effect on coronary artery disease, and highlight several potentially causal associations. Overall, a majority of the plasma proteins studied showed evidence of regulation at the genetic level. Our results enable future studies of the causal architecture of human disease, which in turn should aid discovery of new drug targets.

Few studies have investigated long-term changes in cardiorespiratory fitness (CRF), defined by indirect measures of CRF, and all-cause mortality. We aimed to investigate whether long-term change in CRF, as assessed by the gold standard method of respiratory gas exchange during exercise, is associated with all-cause mortality. A population-based sample of 579 men aged 42 to 60 years with no missing data at baseline examination (V1) and at reexamination at 11 years (V2) were included. Maximal oxygen uptake (VO2max) was measured at both visits using respiratory gas exchange during maximal exercise testing, and the difference (ΔVO2max) was calculated as VO2max (V2) - VO2max (V1). Deaths were ascertained annually using national death certificates during 15 years of follow-up after V2. The mean ΔVO2max was -5.2 mL/min*kg. During median follow-up of 13.3 years (interquartile range, 12.5-14.0 years), 123 deaths (21.2%) were recorded. In a multivariate analysis adjusted for baseline age, VO2max, systolic blood pressure, smoking status, low- and high-density lipoprotein cholesterol and triglyceride levels, C-reactive protein level, body mass index, alcohol consumption, physical activity, socioeconomic status, and history of type 2 diabetes mellitus and ischemic heart disease, a 1 mL/min*kg higher ΔVO2max was associated with a 9% relative risk reduction of all-cause mortality (hazard ratio, 0.91; 95% CI, 0.87-0.95). This study suggested that in this population, long-term CRF reduction was associated with an increased risk of mortality, emphasizing the importance of maintaining good CRF over the decades., (Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Little is known about the joint impact of C-reactive protein (CRP) and cardiorespiratory fitness (CRF) in lung cancer risk. The aim of this study is to examine the joint impact of CRF and CRP in predicting lung cancer risk., Methods: A population-based cohort study of 2276 men with no history of cancer was carried out. Baseline measures of CRP and CRF were divided into median values and categorised. During an average follow-up of 21-years, 73 cases of lung cancer occurred., Results: In a multivariate model, men with the combination of high CRP (>50% 1.24 mg/l) and low CRF (maximal oxygen uptake (VO2max) < 50% 30.08 ml/kg/min) had a fourfold (relative risk (RR) 4.19 95% confidence interval (CI) 1.66-10.57, p < 0.01) risk of lung cancer as compared to the reference group of low CRP (<50% 1.24 mg/l) and high CRF (VO2max>50% 30.08 ml/kg/min). Furthermore, men categorised in high CRP and combined with either low/high CRF, had an increased risk for lung cancer as compared to reference group. In further separate independent analysis for CRP and CRF, lung cancer risk was threefold for high CRP (RR 3.22, 95% CI 1.44-7.20, p < 0.01) and low CRF (RR 3.15, 95% CI 1.27-7.78, p = 0.01) as compared to reference CRP (>2.38 mg/l) and CRF (>35.15 ml/kg/min)., Conclusions: In this study, the joint impact of CRP and CRF is a strong risk marker for lung cancer. Furthermore, men with an increase in CRP were at higher risk for lung cancer than men with low CRP and high CRF may reduce the risk., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Recognizing correlates of low physical activity (PA) can help in targeting PA interventions for individuals who would benefit most from increasing their PA. We studied the associations of demographic, social, health, and lifestyle factors with low PA by sex in a population sample of 1,303 Finnish individuals aged 57-78 years. We defined low PA as no moderate or vigorous leisure-time PA reported in an interview. Altogether, 39% of men and 48% of women reported low PA. Satisfactory or poor perceived health and high BMI were independently associated with low PA in both sexes. In men, factors such as age, being divorced or separated, still working, having a weak social network, poor diet, and a health professional's suggestion to increase PA were associated with low PA. In women, cardiovascular disease and depressive symptoms were associated with low PA. These results can be applied in targeting PA interventions.

Objective: Low levels of IgM anti-phosphorylcholine (anti-PC) increase the risk of cardiovascular events (CVE). Here we investigate the association of low anti-PC with the progression of carotid intima media thickness (C-IMT) and incidence of CVE in a large cohort of individuals at high risk of CVE, the IMPROVE, a prospective multicenter European study., Methods: 3711 subjects (54-79 years) with at least three established cardiovascular risk factors were enrolled. Baseline serum levels of IgM anti-PC were measured by ELISA. Carotid ultrasound investigations were performed at baseline and after 15 and 30 months of follow-up. The risk of C-IMT progression and ischemic CVE associated with low anti-PC levels was tested by logistic regression and Cox regression analysis, respectively. Risk estimates were adjusted by center and conventional cardiovascular risk factors., Results: 3670 study participants were included in the present analysis and 213 CVE were recorded during a 3 year follow up. Anti-PC levels (U/ml) were classified into quartiles [Q1≤ 40, Q2 >40-≤64, Q3 >64-≤102, Q4 >102]. In men, low levels of anti-PC (Q1) were associated with the highest (>90th) percentile of the fastest C-IMT progression, i.e. the segment showing the fastest progression over 30 months in the whole carotid tree, with an OR of 1.41 (95%CI, 1.02-1.9) and with an increased risk of CVE with a multivariable adjusted HR of 1.85 (95%CI, 1.1-3.1). No significant associations were found in women., Conclusions: Low anti-PC levels increase the risk of CVE in men. This effect may be partly mediated by a fast C-IMT progression., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Aims/hypothesis: We validated the metabolic syndrome (MetS) score by confirmatory factor analysis (CFA) in children, middle-aged men, and older women and men and by investigating the relationships of the MetS score to incident type 2 diabetes, myocardial infarction, and cardiovascular and overall death in middle-aged men., Methods: We assessed the core features of MetS, calculated the MetS score using z scores for waist circumference, insulin, glucose, triacylglycerols, HDL-cholesterol and blood pressure, and carried out CFA to investigate whether MetS represents a single entity in population samples of 491 children, 1,900 middle-aged men, 614 older women and 555 older men from Finland. We also followed-up incident type 2 diabetes for 11 years and other outcomes for 17-18 years in middle-aged men., Results: We carried out second-order CFAs in which the MetS was represented by a second-order latent variable underlying four latent variables characterised by abdominal obesity, insulin resistance, dyslipidaemia and raised blood pressure in different age groups. These second-order factors and factors derived from first-order CFA using previously proposed models were strongly associated with a composite MetS score in all age groups (r = 0.84-0.94) and similarly predicted type 2 diabetes, cardiovascular outcomes and mortality in middle-aged men. The risk of type 2 diabetes, myocardial infarction, cardiovascular death and overall death increased 3.67-, 1.38-, 1.56- and 1.44-fold, respectively, for a 1 SD increase in the MetS score., Conclusions: The MetS can be described as a single entity in all age groups. The MetS score is a valid tool for research evaluating cardiometabolic risk in different age groups. Further research is needed to define cut-off points for risk estimation in clinical practice.

Background: A slow heart rate recovery (HRR) after an exercise test is associated with an increased risk of all-cause mortality in asymptomatic individuals, but the data regarding additional prognostic information provided by HRR beyond other exercise test variables are inconsistent. We investigated the prognostic significance of HRR for premature death, particularly in relation to other exercise test variables., Methods: The study subjects were a representative population-based sample of 1102 men (42-61 years of age) without cardiovascular disease, cancer or diabetes. HRR was defined as the difference between maximal HR and HR 2 min after a maximal symptom-limited exercise test using a cycle ergometer. The association between HRR and premature mortality was examined with Cox regression models., Results: During an average follow-up of 18 years, 238 deaths occurred. HRR was an independent predictor of death [for a decrease of 12 beats min(-1) , relative risk (RR) 1.16, 95% CI 1.02-1.33, P = 0.02] after adjustment for age and established risk factors. When added in a Cox model with chronotropic response (decrease of 12 beats min(-1) , RR 1.09, 95% CI 0.93-1.27, P = 0.26) or cardiorespiratory fitness (decrease of 12 beats min(-1) , RR 1.12, 95% CI 0.98-1.30, P = 0.08), the association between a slow HRR and an increased risk of death was clearly weaker., Conclusion: A slow 2-min HRR after a cycle ergometer exercise test was an independent predictor of death in healthy middle-aged men after accounting for demographic and clinical characteristics. However, it was no longer predictive after accounting for chronotropic response and exercise capacity., (2011 The Association for the Publication of the Journal of Internal Medicine.)

Objectives: Our aim was to examine the relation of cardiorespiratory fitness with sudden cardiac death (SCD) in a population-based sample of men., Background: Very limited information is available about the role of cardiorespiratory fitness in the prediction of SCD., Methods: This population study was based on 2,368 men 42 to 60 years of age. Cardiorespiratory fitness was defined by using respiratory gas exchange analyzer and maximal workload during cycle ergometer exercise test., Results: During the 17-year follow-up, there were 146 SCDs. As a continuous variable, 1 metabolic equivalent (MET) increment in cardiorespiratory fitness was related to a decrease of 22% in the risk of SCD (relative risk: 0.78, 95% confidence interval: 0.71 to 0.84, p<0.001). In addition to cardiorespiratory fitness, ischemic ST-segment depression during exercise testing, smoking, systolic blood pressure, prevalent coronary heart disease, family history of coronary heart disease, and type 2 diabetes mellitus were related to the risk of SCD. The Harrell C-index for the total model discrimination was 0.767, while cardiorespiratory fitness provides modest improvement (from 0.760 to 0.767) in the risk prediction when added with all other risk factors. The integrated discrimination improvement was 0.0087 (p=0.018, relative integrated discrimination improvement 0.11) when cardiorespiratory fitness was added in the model. However, the net reclassification index (-0.018) was not statistically significantly improved (p=0.703)., Conclusions: Cardiorespiratory fitness is a predictor of SCD in addition to that predicted by conventional risk factors. There was a slight improvement in the level of discrimination, although the net reclassification index did not change while using cardiorespiratory fitness with conventional risk factors., (Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: No data exist on exercise workload combined with European Systematic Coronary Risk Evaluation (SCORE) with respect to death from cardiovascular diseases and other causes. We therefore investigated the prognostic significance of risk scores and exercise capacity with respect to cardiovascular diseases., Design: A population-based follow-up study., Methods: Exercise workload 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 II diabetes or atherosclerotic cardiovascular disease including coronary heart disease, stroke or claudication., Results: During an average follow-up of 16 years, a total of 304 overall deaths and 116 cardiovascular deaths occurred. Relative risk (RR) was 2.50 [95% confidence intervals (CI): 1.71-3.68, P<0.001] for all-cause death and 2.04 (95% CI: 1.14-3.65, P=0.016) for cardiovascular death among men with exercise capacity less than 162 W as compared with those with exercise capacity over 230 W, after adjustment for risk factors. Independent predictors for all-cause death were European SCORE (for 1% increment, RR: 1.15, 95% CI: 1.10-1.20, P<0.001), exercise workload (for 20 W increment, RR: 0.86, 95% CI: 0.82-0.91, P<0.001), C-reactive protein and alcohol consumption, when adjusted for serum high-density lipoprotein, body mass index, family history of coronary heart disease, exercise-induced ST changes and the use of medications for hypertension, dyslipidemia or aspirin., Conclusion: Low exercise workload predicts an especially high risk for death from cardiovascular and any other cause when combined with high risk SCORE.

The magnitude of work an individual is able to perform at the heart rate (HR) of 100 beats/min (WL(100)) is a simple, integrated measure of HR at rest, HR response to light dynamic exercise, as well as cardiorespiratory performance. Because a high HR at rest and a low cardiorespiratory performance are previously established risk factors for cardiovascular disease (CVD) mortality, it can be deduced that WL(100) is a potential predictor of CVD and coronary heart disease (CHD) mortality. The aim of the present study was to investigate whether WL(100) independently predicts CVD and CHD mortality in middle-aged men. The subjects were a representative sample of 1,314 middle-aged men who did not have CHD and did not use HR-lowering medication at baseline. The association of WL(100) with CVD and CHD mortality was examined by Cox regression models with backward stepwise selection, including numerous known risk factors for CVD death. During an average follow-up of 11.5 years, there were 51 CVD deaths, of which 35 were due to CHD. In Cox multivariable models, CVD mortality increased by 72% (95% confidence interval 27% to 138%, p = 0.001) and CHD mortality by 89% (95% confidence interval 28% to 178%, p = 0.001) with 1 SD (31 W) decrement in WL(100). WL(100) improved the predictive power of the adjusted Cox models, including other HR-derived and exercise test variables. In conclusion, WL(100) predicts CVD and CHD mortality in men without previous CHD. The association of WL(100) with CVD and CHD mortality is not explained by maximal cardiorespiratory performance.

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.

Aims: The objective is to study whether a heart rate (HR) response during exercise test independently predicts cardiovascular disease (CVD) mortality., Methods and Results: The subjects were a representative sample of 1378 men, 42-61 years of age, from eastern Finland with neither prior coronary heart disease (CHD) nor use of beta-blockers at baseline. HR was measured at rest and during a maximal, symptom-limited exercise test at 20, 40, 60, 80, and 100% of maximal workload. During an average follow-up of 11.4 years, there were 56 deaths due to CVD. The slope of HR increase during exercise test was steeper in survivors when compared with those who died due to CVD during follow-up (P<0.001), and the difference in the steepness of HR slope between the groups was the strongest at interval 40-100% (P<0.001). In Cox-multivariable models, maximal HR-HR at 40% workload as a continuous variable was inversely associated with CVD (P=0.04), CHD (P=0.004), and all-cause (P=0.002) mortality after adjustment for known risk factors for CVD death., Conclusion: By considering an HR response throughout an exercise test, we found that a blunted HR increase at 40-100% of maximal workload was associated with increased CVD mortality.

Aims: Few data exist to show if the prognostic value of peak exercise oxygen consumption (VO2peak) for fatal and non-fatal coronary events is different among men with low and high pre-test probability for cardiovascular disease (CVD). Our objective was to determine whether VO2peak could predict fatal and non-fatal cardiac events in 2361 men aged 42-60 years with and without conventional risk predictors of CVD or with documented CVD during a 13-year follow-up., Methods and Results: Maximal oxygen consumption (ml/kg/min) was measured directly by using respiratory gas exchange in a cycle ergometer exercise test. Of 204 CVD deaths, 153 were due to coronary disease and 51 were due to other CVDs. A total of 323 non-fatal coronary events occurred during the follow-up. One metabolic equivalent (MET) increment in VO2peak was related to a decreased risk of coronary death in both healthy (RR=0.82, 95% CI 0.66-0.99) and unhealthy (RR=0.72, 95% CI 0.63-0.82) men. VO2peak was predictive of non-fatal and fatal cardiac events among men with or without known risk factors. In subjects with or without common risk factors, one MET increment amounted to an average decrease of 17-29% in non-fatal and 28-51% in fatal cardiac events, after adjustment for age. VO2peak and smoking represented two strongest independent and consistent risk predictors., Conclusions: VO2peak can be used as a very powerful predictor of future fatal cardiac events beyond that predicted by many conventional risk factors. On the prognostic consideration, unfit men with unfavourable risk profiles or underlying chronic disease are the risk groups that will benefit most from preventive measures.

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.

Objective: To examine the relations of cardiorespiratory fitness, as measured by maximal oxygen uptake and exercise test duration at the initiation of the study, with overall, cardiovascular disease (CVD)-related, and non-CVD-related mortality., Methods: A population-based cohort study of 1294 men with no CVD, pulmonary disease, or cancer at baseline in Kuopio and surrounding communities in eastern Finland. During an average follow-up of 10.7 years, there were 124 overall, 42 CVD-related, and 82 non-CVD-related deaths., Results: The relative risk of overall death in unfit men (maximal oxygen uptake <27.6 mL/kg per minute) was 2.76 (95% confidence interval, 1.43-5.33) (P =.002), and the relative risk of CVD-related death was 3.09 (95% confidence interval, 1.10-9.56) (P =.05), compared with fit men (maximal oxygen uptake >37.1 mL/kg per minute) after adjusting for age, examination years, smoking, and alcohol consumption. The relative risk of non-CVD-related death in unfit men was almost the same magnitude as for overall death. Furthermore, adjustment for serum lipid levels, blood pressure, plasma fibrinogen level, diabetes, and fasting serum insulin level did not weaken these associations significantly. Exercise test duration also had a strong inverse relation to overall, CVD-related, and non-CVD-related mortality. Poor cardiorespiratory fitness was comparable with elevated systolic blood pressure, smoking, obesity, and diabetes in importance as a risk factor for mortality., Conclusions: Cardiorespiratory fitness had a strong, graded, inverse association with overall, CVD-related, and non-CVD-related mortality. Maximal oxygen uptake and exercise test duration represent the strongest predictors of mortality.

Consistent findings about the inverse association of social network level with coronary heart disease mortality and morbidity suggest the importance of investigating biological pathways of association. Differences in plasma fibrinogen level were investigated among middle-aged men with weak and strong structural and functional social network ties. Men with low scores in the adequacy of social participation variable (structural) had higher mean values of plasma fibrinogen than those with high scores. The difference remained after adjustment for age, smoking and cardiovascular health status and after possible modifying factors were taken into account, but did not remain significant after allowing for physical fitness. Men with high scores in overall support (functional) had higher plasma fibrinogen levels compared to the men with low scores. This difference persisted after age and cardiovascular health status were taken into account but was explained by smoking. The data suggest that smoking and cardiorespiratory fitness are important mediating or modifying factors between structural and functional aspects of social network ties and plasma fibrinogen.