Change in Body Weight and Long-Term Risk of Stroke and Death in Healthy Men.

Background and Purpose- The importance of weight change for the risk of stroke is not well known. We examined the associations between early- and mid-life weight change and risks of stroke and death during long-term follow-up of healthy men. Methods- We recruited healthy men aged between 40 and 59 years and performed a cardiovascular examination at baseline and again at 7 years. We collected data on weight change since the age of 25 (early-life weight change) and measured weight change from baseline to the visit at 7 years (mid-life weight change). For both weight change periods, participants were divided into the following categories: weight loss, weight gain 0 to 4.9 kg, weight gain 5 to 9.9 kg, and weight gain ≥10 kg. Data on stroke and death were collected up to 35 years, from study visits, hospital records, and the National Cause of Death Registry. We used Cox regression to analyze the associations between weight change during early-life and mid-life and risks of stroke and death. Results- Of the 2014 participants, 2014 (100%) had data on early-life weight change and were followed for a median of 30.1 years, while 1403 had data on mid-life weight change and were followed for a median of 24.6 years. During early-life, compared with those who had weight gain 0 to 4.9 kg, hazard ratio for stroke was 1.46 (95% CI, 1.09-1.95) among those with weight gain 5 to 9.9 kg, 1.39 (95% CI, 1.03-1.87) for those with weight gain ≥10 kg, and 1.46 (95% CI, 0.99-2.11) among those with weight loss. For all-cause death, the hazard ratios were 1.08 (95% CI, 0.92-1.23), 1.14 (95% CI, 0.98-1.33), and 1.29 (95% CI, 1.06-1.56), respectively. During mid-life, there were no significant differences in risk of stroke or death between the groups. Conclusions- Weight increase during early-life, but not mid-life, seems to be associated with increased long-term risk of stroke in healthy men. If these findings can be confirmed, efforts to prevent weight increase should target the younger population.

Ten-year prediction of cardiovascular disease in healthy Norwegian men, based on NORRISK-2. / Tiårsprediksjon av hjerte- og karsykdom hos friske norske menn basert på NORRISK-2.

BACKGROUND: Norwegian guidelines for primary prevention of cardiovascular disease recommend the use of the NORRISK-2 risk model, with some additions. We wished to investigate whether NORRISK-2 could predict cardiovascular disease in healthy Norwegian men who took part in the Oslo Ischaemia Study. MATERIAL: NORRISK-2 scores were calculated for 2 014 men in the age group 40-60 years who were included in the Oslo Ischaemia Study in 1972-75. Cox regression analyses were used to calculate the hazard ratio for death and cardiovascular disease within ten years of the participants' initial assessment. RESULTS: No participant was lost to follow-up of the 2 014 men, 125 died in the first ten years after inclusion, 61 of whom died from cardiovascular disease. Those who died were older than those who survived, with a larger proportion of daily smokers, and they had higher systolic blood pressure and resting pulse, increased total cholesterol and lower physical fitness. The majority of those who died from acute myocardial infarction and ischaemic stroke within ten years were classified in the high-risk group in NORRISK-2. INTERPRETATION: NORRISK-2 satisfactorily identified the high-risk persons in this cohort of healthy, middle-aged Norwegian men. This supports use of the Norwegian guidelines in the decision on possible primary protection against cardiovascular disease.

Change in Cardiorespiratory Fitness and Risk of Stroke and Death: Long-Term Follow-Up of Healthy Middle-Aged Men.

Background and Purpose- Low cardiorespiratory fitness is associated with increased risk of cardiovascular disease. The present study aims to assess whether change of fitness over time has any impact on long-term risk of stroke and death. Methods- We recruited healthy men aged 40 to 59 years in 1972 to 1975, and followed them until 2007. Physical fitness was assessed with a bicycle ECG test at baseline and again at 7 years, by dividing the total exercise work by body weight. Participants were categorized as remained fit, became unfit, remained unfit, or became fit, depending on whether fitness remained or crossed the median values from baseline to the 7-year visit. Outcome data were collected up to 35 years, from study visits, hospital records, and the National Cause of Death Registry. Risks of stroke and death were estimated by Cox regression analyses and expressed as hazard ratios (HRs) with 95% CIs. Results- Of 2014 participants, 1403 were assessed both at baseline and again at 7 years, and were followed for a mean of 23.6 years. Compared with the became unfit group, risk of stroke was 0.85 (0.54-1.36) for the remained unfit, 0.43 (0.28-0.67) for the remained fit, and 0.34 (0.17-0.67) for the became fit group. For all-cause death, risks were 0.99 (0.76-1.29), 0.57 (0.45-0.74), and 0.65 (0.46-0.90), respectively. Among those with high fitness at baseline, the became unfit group had a significantly higher risk of stroke (HR, 2.35; CI, 1.49-3.63) and death (HR, 1.74; CI, 1.35-2.23) than those who remained fit. Among those who had low fitness at baseline, the became fit group had a significantly lower risk of stroke (HR, 0.40; CI, 0.21-0.72) and death (HR, 0.66; CI, 0.50-0.85) than participants in the remained unfit group. Conclusions- Cardiorespiratory fitness at baseline and change in fitness was associated with large changes in long-term risk of stroke and death. These findings support the encouragement of regular exercise as a stroke prevention strategy.

Cross-sectional and longitudinal analyses of the association between lung function and exercise capacity in healthy Norwegian men.

BACKGROUND: It is widely accepted that exercise capacity in healthy individuals is limited by the cardiac function, while the respiratory system is considered oversized. Although there is physiological, age-related decline in both lung function and physical capacity, the association between decline in lung function and decline in exercise capacity is little studied. Therefore, we examined the longitudinal association between lung function indices and exercise capacity, assessed by the total amount of work performed on a standardized incremental test, in a cohort of middle-aged men. METHODS: A total of 745 men between 40 and 59 years were examined using spirometry and standardized bicycle exercise ECG test within "The Oslo Ischemia Study," at two time points: once during 1972-1975, and again, approximately 16 years later, during 1989-1990. The subjects exercise capacity was assessed as physical fitness i.e. the total bicycle work (in Joules) at all workloads divided by bodyweight (in kg). RESULTS: Higher FEV1, FVC and PEF values related to higher physical fitness at both baseline and follow-up (all p values < 0.05). Higher explanatory values were found at follow-up than baseline for FEV1 (r2 = 0.16 vs. r2 = 0.03), FVC (r2 = 0.14 vs. r2 = 0.03) and PEF (r2 = 0.13 vs. r2 = 0.02). No significant correlations were found between decline in physical fitness and declines in FEV1, FVC or PEF. CONCLUSIONS: A weak association between lung function indices and exercise capacity, assessed through physical fitness, was found in middle-aged, healthy men. This association was strengthened with increasing age, suggesting a larger role for lung function in limiting exercise capacity among elderly subjects. However, decline in physical fitness over time was not related to decline in lung function.

Exercise systolic blood pressure at moderate workload predicts cardiovascular disease and mortality through 35 years of follow-up in healthy, middle-aged men.

OBJECTIVE: There is an association between exercise systolic blood pressure (SBP) and cardiovascular disease and mortality. The aim of this study was to investigate this association, with 35 years of follow-up. METHODS: Through 1972-75, 2014 healthy, middle-aged men underwent thorough medical examination and a bicycle exercise test. 1999 participants completed six minutes at 100 W. SBP was measured manually, both before the test and every two minutes during the test. Highest SBP measured during the first six minutes (SBP100W) was used in further analyses. RESULTS: Participants were divided into quartiles (Q) based on their SBP100W; Q1: 100-160 mm Hg (n = 457), Q2: 165-175 mm Hg (n = 508), Q3: 180-195 mm Hg (n = 545) and Q4: 200-275 mm Hg (n = 489). After 35-years follow-up, there was a significant association between exercise SBP at baseline and cardiovascular disease and mortality. In the multivariate analysis adjusting for resting SBP, age, smoking status, total serum cholesterol and family history of coronary heart disease, as well as physical fitness, there is a 1.39-fold (CI: 1.00-1.93, p = 0.05) increased risk of cardiovascular mortality in Q4 compared to Q1. When not adjusting for physical fitness, there is a 1.29-fold (CI: 1.03-1.61, p = 0.02) increase in risk of cardiovascular disease between Q1 and Q4. CONCLUSIONS: The results of this study suggest that the association between exercise SBP at moderate workload and cardiovascular disease and mortality in middle-aged men extends through as long as 35 years and into old ages.

Cholesterol and prostate cancer risk: a long-term prospective cohort study.

BACKGROUND: Few studies have taken risk of competing events into account when examining the relationship between cholesterol and prostate cancer incidence, and few studies have a follow-up over several decades. We aimed to use these approaches to examine the relationship between cholesterol and prostate cancer. METHODS: A cohort of 1997 healthy Norwegian men aged 40-59 years in 1972-75 was followed throughout 2012. Cancer data were extracted from the Cancer Registry of Norway. The association between cholesterol and prostate cancer incidence was assessed using competing risk regression analysis, with adjustment for potential confounders. Date and cause of death was obtained from the Cause of Death Registry of Norway. RESULTS: The study cohort had a cancer risk similar to the general Norwegian population. Prostate cancer was registered in 213 men (11 %), including 62 (3 %) with advanced stage at diagnosis. For overall and advanced stage prostate cancer, the incidence was twice as high in the lowest quartile of cholesterol compared to the highest quartile. These associations remained significant after adjustment for age, smoking, physical fitness, BMI, and systolic blood pressure. Furthermore, high physical fitness and low BMI were associated with increased prostate cancer incidence. Sensitivity analyses excluding events during the first 20 years of observation revealed similar results. CONCLUSION: Low cholesterol, as well as high physical fitness and low BMI, may be associated with increased risk of prostate cancer. These findings conflict with current prostate cancer prevention recommendations.

[Deaths in Norwegian police cells from 2003 to 2012]. / Dødsfall i norske politiarrester 2003-12.

BACKGROUND: In 2002 the Politiarrestprosjektet (a police custody project in Norway) examined deaths in Norwegian police cells during the period from 1993 to 2001. They found a total of 36 deaths, 16 of which were due either to acute alcohol poisoning or to head injuries suffered by people who had been detained for intoxication. A range of preventive measures were proposed. We have now reviewed deaths in the period from 2003 to 2012 and compared them with the first study. MATERIAL AND METHOD: We asked all police districts in Norway to submit information about deaths in police cells from 2003 up to and including 2012. Autopsy reports, police reports and reports from the Norwegian Bureau for the Investigation of Police Affairs were requested. RESULTS: Altogether 11 deaths were reported, i.e. an average of 1.1 deaths per year. The most usual cause of death with six fatalities was a combination of toxic substances. Three deaths were due to suicide, one was a natural death, and one was due to acute alcohol poisoning. There were no deaths due to head injuries related to intoxication. INTERPRETATION: The number of deaths in Norwegian police cells has declined considerably. It is primarily the number of alcohol-related deaths that has fallen.

Life style and longevity among initially healthy middle-aged men: prospective cohort study.

BACKGROUND: Few studies have examined how various lifestyle factors in midlife predict longevity, and none of these studies have examined the impact of physical fitness. The present study aimed to examine longevity in relation to smoking, overweight and physical fitness. METHODS: We prospectively studied longevity (defined as reaching at least 85 years of age) in relation to smoking status, body mass index and physical fitness in 821 healthy men between 51 and 59 years of age. Of these, 369 were smokers, 320 were overweight, and 31 were obese. The associations were adjusted for age, systolic blood pressure and cholesterol level, using multivariate logistic regression analysis. Deaths were registered until the 31st of December, 2006. Physical fitness was measured as the total work performed in a maximal exercise tolerance bicycle test. RESULTS: 252 men survived to the age of 85 years (30.7%). Smoking status was significantly and independently related to longevity; 37.2% of the non-smokers survived to the age of 85, and 22.8% of the smokers. Among non-smokers, overweight and physical fitness were significantly and independently related to longevity after adjustment for age, blood pressure and cholesterol level, but not among smokers. Among non-smokers with high physical fitness, 48.8% reached the age of 85 years, compared to 27.9% among non-smokers with low physical fitness. CONCLUSION: Lifestyle variables appear to be strong and independent predictors of longevity in initially healthy middle-aged men. The probability of longevity may be a useful concept when informing the general public about the benefits of a healthy lifestyle.

Novel insights into stroke risk beyond resting and maximal bicycle exercise systolic blood pressure.

OBJECTIVE: Previous research has shown an association between moderate workload exercise blood pressure (BP) and coronary disease, whereas maximal exercise BP is associated with stroke. We aimed to investigate the association between the increase in BP during maximal exercise and the long-term risk of stroke in healthy, middle-aged men. METHODS: Two thousand and fourteen men were included in the Oslo Ischemia Study in the 1970s. In the present study, we examined baseline data of the 1392 participants who remained healthy and performed bicycle exercise tests both at baseline and 7 years later. Cox proportional hazard was used to assess the risk of stroke in participants divided into quartiles based on the difference between resting and maximal workload SBP (ΔSBP) at baseline, adjusting for resting BP, age, smoking, serum cholesterol and physical fitness. Follow-up was until the first ischemic or hemorrhagic stroke through 35 years. RESULTS: There were 195 incident strokes; 174 (89%) were ischemic. In univariate analyses, there were significant positive correlations between age, resting SBP, resting DBP and SBP at moderate and maximal workload, and risk of stroke. In the multivariate analysis, there was a 2.6-fold (P < 0.0001) increase in risk of stroke in ΔSBP quartile 4 (ΔSBP > 99 mmHg) compared with ΔSBP quartile 2 (ΔSBP 73-85 mmHg), which had the lowest risk of stroke. ΔSBP quartile 1 had a 1.7-fold (P = 0.02) increased risk compared with quartile 2, suggesting a J-shaped association to stroke risk. CONCLUSION: Stroke risk increased with increasing difference between resting and maximal exercise SBP, independent of BP at rest, suggesting that an exaggerated BP response to physical exercise may be an independent predictor of stroke.

The Oslo Ischaemia Study: cohort profile.

PURPOSE: The Oslo Ischaemia Study was designed to investigate the prevalence and predictors of silent coronary disease in Norwegian middle-aged men, specifically validating exercise electrocardiography (ECG) findings compared with angiography. The study has been important in investigating long-term predictors of cardiovascular morbidity and mortality, as well as investigating a broad spectrum of epidemiological and public health perspectives. PARTICIPANTS: In 1972-1975, 2014 healthy men, 40-59 years old, were enrolled in the study. Comprehensive clinical examination included an ECG-monitored exercise test at baseline and follow-ups. The cohort has been re-examined four times during 20 years. Linkage to health records and national health registries has ensured complete endpoint registration of morbidity until the end of 2006, and cancer and mortality until the end of 2017. FINDINGS TO DATE: The early study results provided new evidence, as many participants with a positive exercise ECG, but no chest pain ('silent ischaemia'), did not have significant coronary artery stenosis after all. Still, they were over-represented with coronary disease after years of follow-up. Furthermore, participants with the highest physical fitness had lower risk of cardiovascular disease, and the magnitude of blood pressure responses to moderate exercise was shown to influence the risk of cardiovascular disease and mortality. With time, follow-up data allowed the scope of research to expand into other fields of medicine, with the aim of investigating predictors and the importance of lifestyle and risk factors. FUTURE PLANS: Recently, the Oslo Ischaemia Study has been found worthy, as the first scientific study, to be preserved by The National Archives of Norway. All the study material will be digitised, free to use and accessible for all. In 2030, the Oslo Ischaemia Study will be linked to the Norwegian Cause of Death Registry to obtain complete follow-up to death. Thus, a broad spectrum of additional opportunities opens.

Interaction between inflammation and blood viscosity predicts cardiovascular mortality.

OBJECTIVES: Inflammation and increased blood viscosity are associated with increased risk of cardiovascular mortality. Erythrocyte sedimentation rate (ESR) and hematocrit both influence blood viscosity whereas the first also is a marker of inflammation. We aimed to investigate ESR, hematocrit and the interaction between them as predictors of cardiovascular mortality during 26 years follow-up among healthy middle aged men. DESIGN: Four hundred and eighty eight men aged 40-59 were extensively examined in 1972-1975 and followed over a period of 26 years. Risk estimation was made in Cox proportional hazards and adjusted for age, smoking, systolic blood pressure, total serum cholesterol, and physical fitness. RESULTS: A 2.44-fold (95% CI 1.37-4.35) adjusted risk of cardiovascular mortality was found in the highest quartile of hematocrit compared to the lowest. Among the 265 men who had an ESR <6 mm/h (median), the adjusted risk of cardiovascular mortality was 3.05-fold (95% CI 1.49-6.23) in the highest quartile of hematocrit compared to the lowest. This association was not observed among the 223 men with ESR <6 mm/h. CONCLUSION: Elevated hematocrit is independently associated with increased long-term risk of cardiovascular mortality in men with high ESR. Our data suggest that the combination of inflammation and blood viscosity may improve the prediction of cardiovascular risk.

Fasting Serum Levels of Potassium and Sodium in Relation to Long-Term Risk of Cancer in Healthy Men.

PURPOSE: To examine whether serum levels of potassium and sodium were associated with long-term cancer risk in initially healthy men. PATIENTS AND METHODS: A cohort of 1994 initially healthy men with no use of medication, aged 40-59 years, was followed for cancer during 40 years of follow-up. Associations between fasting electrolyte levels and cancer risk were assessed with incidence rates and Cox proportional hazards models. RESULTS: Potassium, but not sodium, was linearly associated with cancer risk. This association remained significant after adjustment of several potential confounding factors, and also after excluding the first 10 years of follow-up. The age-adjusted risk of all-site cancer increased with 16% for each SD increase in potassium level. Men with hyperkalemia showed an incidence rate that was 40% higher than for men with normal potassium levels. CONCLUSION: Fasting serum potassium level in healthy men was positively associated with long-term cancer risk. Potassium or potassium ion channels may have a role in cell proliferation or differentiation. These findings might imply future cancer strategies for targeting individuals with high serum potassium levels.

Exercise Systolic Blood Pressure at Moderate Workload Is Linearly Associated With Coronary Disease Risk in Healthy Men.

There is no consensus on the definition of an exaggerated increase in systolic blood pressure (SBP) during exercise. The aim was to explore a potential threshold for exercise SBP associated with increased risk of coronary heart disease in healthy men using repeated exercise testing. Two thousand fourteen healthy white male employees were recruited into the Oslo Ischemia Study during early 1970s. At follow-up 7 years later, 1392 men were still considered healthy. A bicycle exercise test at 100 W workload was performed at both visits. Cox regression analyses were performed with increasing cutoff levels of peak exercise SBP at 100 W workload (SBP100W) from 160 mm Hg to 200 mm Hg, adjusted for cardiovascular risk factors and physical fitness. Participants with SBP100W below cutoff level at both baseline and first follow-up were compared with participants with SBP100W equal to or above cutoff level at both visits. Compared with participants with SBP100W below all cutoff levels between 165 and 195 mm Hg, coronary heart disease risk was increased among participants with SBP100W equal to or above cutoff at all levels. There was no evidence of a distinct threshold level for coronary heart disease risk, and the relation between SBP100W and coronary heart disease appears linear. When investigating exercise SBP at moderate workload measured at 2 exercise tests in healthy middle-aged white men, there is increasing risk of coronary heart disease with increasing exercise SBP independent of SBP at rest. The association is linear from the low range of exercise SBP, and there is no sign of a distinct threshold level for increased coronary disease risk.

Changes in midlife fitness, body mass index, and smoking influence cancer incidence and mortality: A prospective cohort study in men.

Cancer prevention efforts include modification of unhealthy lifestyle, such as smoking cessation and resisting gain in body weight. Although physical activity is inversely related to risk of several cancers, it is poorly studied whether changes in physical activity or fitness influence future cancer risk. Thus, we aimed to investigate whether changes in midlife cardiorespiratory fitness (CRF), body mass index (BMI), and smoking habits influence cancer incidence and mortality. The study cohort includes 1689 initially healthy men, aged 40-59 years. Measurements of CRF, BMI and information on smoking habits were collected in two repeated waves, 7 years apart. Cox regression models estimated associations as hazard rates (HR) with 95% confidence intervals (CI), between midlife changes in the modifiable lifestyle factors and cancer incidence and mortality. The men were followed prospectively for more than 30 years. Compared to CRF loss (>5%), improved CRF (>5%) was associated with lower cancer incidence (HR 0.81, 95% CI 0.67-0.98) and mortality (HR 0.70, 95% CI 0.54-0.92), and maintaining the CRF stable yielded lower cancer incidence (HR 0.76, 95% CI 0.61-0.95). No association was seen for BMI gain, but maintaining the BMI stable was related to lower cancer incidence (HR 0.77, 95% CI 0.60-0.98), compared to BMI loss. Continue smoking was associated with higher cancer incidence and mortality, compared to men who stopped smoking. In particular, this study adds new knowledge about the potential preventive role of CRF in cancer development and emphasizes lifestyle modification as a highly important effort in cancer prevention.

SBP above 180 mmHg at moderate exercise workload increases coronary heart disease risk in healthy men during 28-year follow-up.

OBJECTIVE: We investigated the association between exercise SBP at a moderate workload and long-term risk of coronary heart disease (CHD) in men who were healthy when assessed by two bicycle exercise tests 7 years apart. METHODS: During 1972-1975, apparently healthy men (n = 1999) were initially enrolled following thorough medical examination and ECG-monitored bicycle exercise test. Participants (n = 1392) who were healthy also at a second exercise test 7 years later were included in the present study. They were divided into quartiles, Q1-Q4, according to the highest SBP during the initial 6 min of the exercise test on a moderate workload of 100 W (SBP100W) at 7 years and followed for up to 28 years. Adjusted Cox regression was used to estimate CHD risk defined as first occurrence of angina pectoris, nonfatal myocardial infarction or CHD mortality. RESULTS: During follow-up, 452 of the 1392 men suffered incident CHD, and unadjusted, there was increased risk of CHD with increasing SBP100 W, with significant differences between Q1-Q4. In the multivariate analysis adjusting for classical coronary risk factors, including SBP at rest, there was increased risk of CHD in Q3 (SBP100 W above 180 mmHg) and Q4 (SBP100 W above 200 mmHg) compared with Q1 (≤160 mmHg, lowest SBP100 W), hazard ratios 1.42 (CI 1.07-1.90) and 1.93 (CI 1.38-2.70), respectively. CONCLUSION: Healthy middle-aged men had increased long-term risk of CHD with exercise SBP above 180 mmHg at moderate workload. The prognostic impact of SBP above 180 mmHg at exercise is independent of classical coronary risk factors and blood pressure at rest.

Physical fitness is a modifiable predictor of early cardiovascular death: A 35-year follow-up study of 2014 healthy middle-aged men.

Background Physical fitness has been shown to predict cardiovascular death during long-term follow-up. In the present study we aimed to investigate how physical fitness and other cardiovascular risk factors at middle-age influenced the risk of cardiovascular death during the early (0-11 years), intermediate (12-23 years) and late (24-35 years) parts of a 35-year observation period. Methods and results Age-adjusted physical fitness was calculated in 2014 apparently healthy, middle-aged men after maximal bicycle electrocardiogram-tests in 1972-1975 (Survey 1) and 1979-1982 (Survey 2). The men were assessed through 35 years after Survey 1, and 28 years after Survey 2 by Cox proportional hazards models. Low Survey 1 physical fitness was independently associated with increased risks of early and intermediate, but not late, cardiovascular death. Survey 1 to Survey 2 change in physical fitness, age, smoking status, systolic blood pressure and cholesterol impacted cardiovascular death risks in all periods. Family history of coronary heart disease impacted early and intermediate, but not late, cardiovascular death. Conclusions Most classical cardiovascular risk factors were strong predictors of early, intermediate and late cardiovascular death. Physical fitness measured at median age 50 years was independently associated with risk of early cardiovascular death, but the association weakened as time progressed. Change in physical fitness during middle-age impacted cardiovascular death risk in a full lifetime perspective. Thus, our data suggest that physical fitness is a modifiable cardiovascular risk factor with limited duration in contrast to the sustained impact of smoking, blood pressure and cholesterol on cardiovascular mortality.

Long-term predictors of stroke in healthy middle-aged men.

Background There are few data on risk factors for stroke during long-term follow-up of healthy individuals. Aims We aimed to investigate the long-term predictive impact on stroke risk of baseline variables including hemodynamic variables measured at rest and during exercise in middle-aged, healthy men. Methods We performed a prospective cohort study of 2014 healthy Norwegian men aged 40-59 years, recruited during the period 1972-1975 and followed until 2007. Participants underwent a comprehensive clinical assessment at baseline, including a bicycle exercise test. Data on stroke, transient ischemic attack, and death were collected on all participants from follow-up visits, medical records, and the National Cause of Death Registry. We used Cox regression for analysis and estimated hazard ratios with 95% confidence intervals, adjusting for traditional risk factors and hemodynamic variables measured at rest and during exercise. Results During 35 years' follow-up, 316 participants (16%) had stroke, of which 287 (91%) were ischemic and 29 (9%) were hemorrhagic. Age (hazard ratio 2.70 per increase in one standard deviation, 95% confidence interval 2.13-3.43), resting systolic blood pressure (hazard ratio 1.24, 95% confidence interval 1.11-1.39), body mass index (hazard ratio 1.14, 95% confidence interval 1.02-1.29), and atrioventricular conduction time (hazard ratio 1.11, 95% confidence interval 1.03-1.19) were significantly associated with long-term risk of stroke, as were maximal systolic blood pressure and heart rate during exercise (hazard ratio 1.28, 95% confidence interval 1.13-1.46, and hazard ratio 0.86, 95% confidence interval 0.74-0.99, respectively). Conclusions Hemodynamic variables at rest and during exercise testing add to the predictive value of clinical variables in healthy, middle-aged men, and should be included in the assessment of long-term risk of stroke, when available.

Warfarin, aspirin, or both after myocardial infarction.

BACKGROUND: The role of antithrombotic therapy in secondary prevention after myocardial infarction is well established. Although the available literature suggests that warfarin is superior to aspirin, aspirin is currently the more widely used drug. We studied the efficacy and safety of warfarin, aspirin, or both after myocardial infarction. METHODS: In a randomized, multicenter trial in 3630 patients, 1216 received warfarin (in a dose intended to achieve an international normalized ratio [INR] of 2.8 to 4.2), 1206 received aspirin (160 mg daily), and 1208 received aspirin (75 mg daily) combined with warfarin (in a dose intended to achieve an INR of 2.0 to 2.5). The mean duration of observation was four years. RESULTS: The primary outcome, a composite of death, nonfatal reinfarction, or thromboembolic cerebral stroke, occurred in 241 of 1206 patients receiving aspirin (20.0 percent), 203 of 1216 receiving warfarin (16.7 percent; rate ratio as compared with aspirin, 0.81; 95 percent confidence interval, 0.69 to 0.95; P=0.03), and 181 of 1208 receiving warfarin and aspirin (15.0 percent; rate ratio as compared with aspirin, 0.71; 95 percent confidence interval, 0.60 to 0.83; P=0.001). The difference between the two groups receiving warfarin was not statistically significant. Episodes of major, nonfatal bleeding were observed in 0.62 percent of patients per treatment-year in both groups receiving warfarin and in 0.17 percent of patients receiving aspirin (P<0.001). CONCLUSIONS: Warfarin, in combination with aspirin or given alone, was superior to aspirin alone in reducing the incidence of composite events after an acute myocardial infarction but was associated with a higher risk of bleeding.

Respiratory rate at rest was not associated with long-term mortality in healthy males.

OBJECTIVE: In various diseases, resting respiratory rate (RR) is associated with mortality. We hypothesized that RR could be an early marker of low-grade disease and hence be associated with mortality also in healthy individuals. The objective of the study was to assess if resting RR was associated with long-term mortality in healthy males. STUDY DESIGN AND SETTING: In a cohort of healthy men aged 40-59, we studied the relation of RR in 1972-1975 with all-cause and respiratory mortality until 2000. We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Among 1,623 men, 615 died during follow-up, 96 from respiratory causes. Men in the upper RR quartile (>16 breaths/min) had higher all-cause mortality than in the lowest quartile (<13 breaths/min), HR 1.29 (95% CI 1.04-1.60, P=0.02), though this was not statistically significant in multivariable models. Resting RR was not associated with respiratory mortality. CONCLUSION: RR at rest was not independently associated with long-term all-cause or respiratory mortality in this cohort of healthy men.

Cardiorespiratory fitness and risk of site-specific cancers: a long-term prospective cohort study.

Based on self-reported physical activity, there is epidemiologic evidence for a beneficial relation between physical activity and colon cancer in men, but findings for other cancers are inconclusive. Measured cardiorespiratory fitness (CRF) can provide knowledge about the cancer-preventive value of physical activity. We aimed to assess relationships between CRF and risk of site-specific cancers. A cohort of 1997 healthy Norwegian men, aged 40-59 years at inclusion in 1972-1975, was followed for cancer throughout 2012 using data from the Cancer Registry of Norway. CRF was measured by a maximal exercise bicycle test at inclusion. Relationships between CRF and site-specific cancers were estimated using Cox regression, adjusted for age, body mass index, and smoking. During follow-up, 898 cancer cases were diagnosed in 758 men. When comparing men in CRF tertile 1 with men in tertiles 2 and 3, respectively, we found decreased risk of proximal colon cancer in tertile 2 (HR: 0.30, 95% CI: 0.13-0.73) and decreased risk of cancers of lung (0.39 95% CI: 0.22-0.66), pancreas (0.32 95% CI: 0.10-1.00), and bladder (HR: 0.40 95% CI: 0.21-0.74) in tertile 3. Furthermore, a significant trend for lower risk by increasing CRF tertile was found for cancers of proximal colon, lung, and bladder (P-value for trend <0.05). For other cancer sites, no significant association was found. Our results indicate that high midlife CRF may have cancer-preventive value.