Excess weight, weight gain, and prostate cancer risk and prognosis: the PROCA-life study.

BACKGROUND: Studies of excess weight and weight changes throughout adult life for prostate cancer (PCa) risk and prognosis have shown inconsistent results. METHODS: In a population-based cohort, the Prostate Cancer Study throughout life (PROCA-life), 16,960 healthy men from the prospective cohort Tromsø Study (1994-2016) were included. Body mass index (BMI) and weight were measured at all four attendings, and weight change was calculated as the difference between the first and last of either Tromsø4, Tromsø5 or Tromsø6. Overall, 904 men developed PCa during 16 years of follow-up, and Poisson regression with fractional polynomials was used to investigate trends in incidence. Cox proportional hazard and logistic regression models were used to study associations between measurements of BMI and weight change and PCa risk, severity, and mortality. RESULTS: At study entry, 46% of the participants (median age 44 years) were overweight, and 14% were obese (BMI > 30 kg/m2). We observed a 127% increase in overall age adjusted PCa incidence in the cohort during 1995 through 2019. No overall associations between BMI or weight change and PCa risk were observed. However, in sub-group analysis, weight gain among obese men was associated with a three-fold higher PCa risk (HR 3.03, 95% CI 1.39-6.58) compared with obese men with stable weight. Overweight was associated with lower risk of metastatic cancer (OR 0.48, 95% CI 0.30-0.75) at diagnosis. Men with obesity had higher risk of PCa-specific death (HR 1.72, 95% CI 1.03-2.88), while nonsmoking obese PCa cases had two times higher PCa-specific mortality compared with normal weighted PCa cases (HR 2.10, 95% CI 1.11-3.70). INTERPRETATION: In our cohort, weight gain among obese men was associated with higher risk of PCa, and obesity was associated with higher PCa-specific mortality, especially among nonsmokers. The relationship between weight and risk for PCa remains complicated, and future studies are needed to determine clinical implications.

Social inequality in prevalence of NCD risk factors: a cross-sectional analysis from the population-based Tromsø Study 2015-2016.

OBJECTIVE: We aimed to examine associations between educational level, serving as an indicator of socioeconomic position, and prevalence of WHO-established leading behavioural and biological risk factors for non-communicable diseases (NCDs), in middle-aged to older women and men. DESIGN: Population-based cross-sectional study. SETTING: All inhabitants of the municipality of Tromsø, Norway, aged ≥40 years, were invited to the seventh survey (2015-2016) of the Tromsø Study; an ongoing population-based cohort study. PARTICIPANTS: Of the 32 591 invited; 65% attended, and a total of 21 069 women (53%) and men aged 40-99 years were included in our study. OUTCOME MEASURES: We assessed associations between educational level and NCD behavioural and biological risk factors: daily smoking, physical inactivity (sedentary in leisure time), insufficient fruit/vegetable intake (<5 units/day), harmful alcohol use (>10 g/day in women, >20 g/day in men), hypertension, obesity, intermediate hyperglycaemia and hypercholesterolaemia. These were expressed as odds ratios (OR) per unit decrease in educational level, with 95% CIs, in women and men. RESULTS: In women (results were not significantly different in men), we observed statistically significant associations between lower educational levels and higher odds of daily smoking (OR 1.69; 95% CI 1.60 to 1.78), physical inactivity (OR 1.38; 95% CI 1.31 to 1.46), insufficient fruit/vegetable intake (OR 1.54, 95% CI 1.43 to 1.66), hypertension (OR 1.25; 95% CI 1.20 to 1.30), obesity (OR 1.23; 95% CI 1.18 to 1.29), intermediate hyperglycaemia (OR 1.12; 95% CI 1.06 to 1.19), and hypercholesterolaemia (OR 1.07; 95% CI 1.03 to 1.12), and lower odds of harmful alcohol use (OR 0.75; 95% CI 0.72 to 0.78). CONCLUSION: We found statistically significant educational gradients in women and men for all WHO-established leading NCD risk factors within a Nordic middle-aged to older general population. The prevalence of all risk factors increased at lower educational levels, except for harmful alcohol use, which increased at higher educational levels.

Females Display Lower Risk of Myocardial Infarction From Higher Estimated Cardiorespiratory Fitness Than Males: The Tromsø Study 1994-2014.

Objective: To examine the dose-response association between estimated cardiorespiratory fitness (eCRF) and risk of myocardial infarction (MI). Patients and Methods: Adults who attended Tromsø Study surveys 4-6 (Janurary 1,1994-December 20, 2008) with no previous cardiovascular disease were followed up through December 31, 2014 for incident MI. Associations were examined using restricted cubic splines Fine and Gray regressions, adjusted for education, smoking, alcohol, diet, sex, adiposity, physical activity, study survey, and age (timescale) in the total cohort and subsamples with hyperlipidemia (n=2956), hypertension (n=8290), obesity (n=5784), metabolic syndrome (n=1410), smokers (n=3823), and poor diet (n=3463) and in those who were physically inactive (n=6255). Results: Of 14,285 participants (mean age ± SD, 53.7±11.4 years), 979 (6.9%) experienced MI during follow-up (median, 7.2 years; 25th-75th, 5.3-14.6 years). Females with median eCRF (32 mL/kg/min) had 43% lower MI risk (subdistributed hazard ratio [SHR], 0.57; 95% CI, 0.48-0.68) than those at the 10th percentile (25 mL/kg/min) as reference. The lowest MI risk was observed at 47 mL/kg/min (SHR, 0.02; 95% CI, 0.01-0.11). Males had 26% lower MI risk at median eCRF (40 mL/kg/min; SHR, 0.74; 95% CI, 0.63-0.86) than those at the 10th percentile (32 mL/kg/min), and the lowest risk was 69% (SHR, 0.31; 95% CI, 0.14-0.71) at 60 mL/kg/min. The associations were similar in subsamples with cardiovascular disease risk factors. Conclusion: Higher eCRF associated with lower MI risk in females and males, but associations were more pronounced among females than those in males. This suggest eCRF as a vital estimate to implement in medical care to identify individuals at high risk of future MI, especially for females.

Occupational physical activity and risk of mortality in women and men: the Tromsø Study 1986-2021.

OBJECTIVE: Associations between occupational physical activity (OPA) and mortality risks are inconclusive. We aimed to examine associations between (1) OPA separately and (2) jointly with leisure time physical activity (LTPA), and risk of all-cause, cardiovascular disease (CVD) and cancer mortality, over four decades with updated exposure and covariates every 6-8 years. METHODS: Adults aged 20-65 years from the Tromsø Study surveys Tromsø3-Tromsø7 (1986-2016) were included. We categorised OPA as low (sedentary), moderate (walking work), high (walking+lifting work) or very high (heavy manual labour) and LTPA as inactive, moderate and vigorous. We used Cox/Fine and Gray regressions to examine associations, adjusted for age, body mass index, smoking, education, diet, alcohol and LTPA (aim 1 only). RESULTS: Of 29 605 participants with 44 140 total observations, 4131 (14.0%) died, 1057 (25.6%) from CVD and 1660 (40.4%) from cancer, during follow-up (median: 29.1 years, 25th-75th: 16.5.1-35.3). In men, compared with low OPA, high OPA was associated with lower all-cause (HR 0.83, 95% CI 0.74 to 0.92) and CVD (subdistributed HR (SHR) 0.68, 95% CI 0.54 to 0.84) but not cancer mortality (SHR 0.99, 95% CI 0.84 to 1.19), while no association was observed for moderate or very high OPA. In joint analyses using inactive LTPA and low OPA as reference, vigorous LTPA was associated with lower all-cause mortality combined with low (HR 0.75, 95% CI 0.64 to 0.89), high (HR 0.67, 95% CI 0.54 to 0.82) and very high OPA (HR 0.74, 95% CI 0.58 to 0.94), but not with moderate OPA. In women, there were no associations between OPA, or combined OPA and LTPA, with mortality. CONCLUSION: High OPA, but not moderate and very high OPA, was associated with lower all-cause and CVD mortality risk in men but not in women. Vigorous LTPA was associated with lower mortality risk in men with low, high and very high OPA, but not moderate OPA.

Lifestyle factors as mediators of area-level socioeconomic differentials in mental health and cognitive function: the Tromsø Study.

INTRODUCTION: Low socioeconomic status (SES) is associated with poor mental health and cognitive function. Individual-level SES and area-level SES (ASES) may affect mental health and cognitive function through lifestyle. We aimed to quantify the associations of ASES with mental health and cognitive function and examine the mediating role of lifestyle behaviours independent of individual-level SES in a Norwegian population. METHODS: In this cross-sectional study, we included 7211 participants (54% women) from the seventh survey of the Tromsø Study (2015-2016) (Tromsø7). The exposure variable ASES was created by aggregating individual-level SES variables (education, income, housing ownership) from Statistics Norway at the geographical subdivision level. Tromsø7 data were used as mediators (smoking, snuff, alcohol, physical activity, diet) and outcomes (cognitive function, anxiety, depression, insomnia). Mediation and mediated moderation analysis were performed with age as a moderator, stratified by sex. RESULTS: Higher ASES was associated with better cognitive function and fewer depression and insomnia symptoms, independent of individual-level SES. These associations were mediated by smoking and physical activity. Alcohol was a mediator for depression and cognitive function in women. Age was a significant moderator of the association between ASES and global cognitive function in women. The largest total indirect effect of ASES was found for depression, with the joint effect of the mediators accounting for 36% of the total effect. CONCLUSIONS: People living in areas with lower ASES are at higher risk of poor mental health, such as depression and insomnia, and have lower cognitive function possibly due to unhealthy lifestyle (smoking, alcohol and physical inactivity).

Device-measured physical activity, sedentary time, and risk of all-cause mortality: an individual participant data analysis of four prospective cohort studies.

OBJECTIVES: To examine whether moderate-to-vigorous physical activity (MVPA) modifies the association between sedentary time and mortality and vice versa, and estimate the joint associations of MVPA and sedentary time on mortality risk. METHODS: This study involved individual participant data analysis of four prospective cohort studies (Norway, Sweden, USA, baseline: 2003-2016, 11 989 participants ≥50 years, 50.5% women) with hip-accelerometry-measured physical activity and sedentary time. Associations were examined using restricted cubic splines and fractional polynomials in Cox regressions adjusted for sex, education, body mass index, smoking, alcohol, study cohort, cardiovascular disease, cancer, and/or diabetes, accelerometry wear time and age. RESULTS: 6.7% (n=805) died during follow-up (median 5.2 years, IQR 4.2 years). More than 12 daily sedentary hours (reference 8 hours) was associated with mortality risk only among those accumulating <22 min of MVPA per day (HR 1.38, 95% CI 1.10 to 1.74). Higher MVPA levels were associated with lower mortality risk irrespective of sedentary time, for example, HR for 10 versus 0 daily min of MVPA was 0.85 (95% CI 0.74 to 0.96) in those accumulating <10.5 daily sedentary hours and 0.65 (95% CI 0.53 to 0.79) in those accumulating ≥10.5 daily sedentary hours. Joint association analyses confirmed that higher MVPA was superior to lower sedentary time in lowering mortality risk, for example, 10 versus 0 daily min of MVPA was associated with 28-55% lower mortality risk across the sedentary time spectrum (lowest risk, 10 daily sedentary hours: HR 0.45, 95% CI 0.31 to 0.65). CONCLUSIONS: Sedentary time was associated with higher mortality risk but only in individuals accumulating less than 22 min of MVPA per day. Higher MVPA levels were associated with lower mortality risk irrespective of the amount of sedentary time.

Trajectories of body mass index in adulthood and risk of subtypes of postmenopausal breast cancer.

BACKGROUND: Body fatness is a dynamic exposure throughout life. To provide more insight into the association between body mass index (BMI) and postmenopausal breast cancer, we aimed to examine the age at onset, duration, intensity, and trajectories of body fatness in adulthood in relation to risk of breast cancer subtypes. METHODS: Based on self-reported anthropometry in the prospective Norwegian Women and Cancer Study, we calculated the age at onset, duration, and intensity of overweight and obesity using linear mixed-effects models. BMI trajectories in adulthood were modeled using group-based trajectory modeling. We used Cox proportional hazards models to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the associations between BMI exposures and breast cancer subtypes in 148,866 postmenopausal women. RESULTS: A total of 7223 incident invasive postmenopausal breast cancer cases occurred during follow-up. Increased overweight duration and age at the onset of overweight or obesity were associated with luminal A-like breast cancer. Significant heterogeneity was observed in the association between age at overweight and overweight duration and the intrinsic-like subtypes (pheterogeneity 0.03). Compared with women who remained at normal weight throughout adulthood, women with a descending BMI trajectory had a reduced risk of luminal A-like breast cancer (HR 0.54, 95% CI 0.33-0.90), whereas women with ascending BMI trajectories were at increased risk (HR 1.09; 95% CI 1.01-1.17 for "Normal-overweight"; HR 1.20; 95% CI 1.07-1.33 for "Normal-obesity"). Overweight duration and weighted cumulative years of overweight and obesity were inversely associated with luminal B-like breast cancer. CONCLUSIONS: In this exploratory analysis, decreasing body fatness from obesity in adulthood was inversely associated with overall, hormone receptor-positive and luminal A-like breast cancer in postmenopausal women. This study highlights the potential health benefits of reducing weight in adulthood and the health risks associated with increasing weight throughout adult life. Moreover, our data provide evidence of intrinsic-like tumor heterogeneity with regard to age at onset and duration of overweight.

The Longitudinal Course of Prospectively Recorded Patient-reported Outcomes in Prostate Cancer Patients Treated with Surgery and Salvage Radiotherapy.

Background: Patient-reported outcome measures (PROMs) after prostate cancer (PC) treatment, including both radical prostatectomy (RP) and salvage radiation therapy (SRT), are under-reported. Objective: To investigate PROMs longitudinally from before SRT until 18 mo after SRT for men treated with contemporary treatment modalities. Design setting and participants: This prospective, longitudinal cohort study included 120 men (whole cohort) treated with SRT administered with volumetric modulated arc radiotherapy from 2016 to 2021 at the University Hospital of North Norway. The whole cohort was followed from before SRT until 18 mo after SRT. A subcohort of 48 men was followed from before RP until 18 mo after SRT. Outcome measurements and statistical analysis: PROMs were collected with the Expanded Prostate Cancer Index-26 (EPIC-26), covering symptoms of urinary incontinence, urinary irritative, bowel, sexual, and hormonal domains. The domain scores were inquired before RP, 3 mo after RP, before SRT, at SRT termination, and 3 and 18 mo after SRT. We used linear mixed models with repeated measurements design to assess changes in PROMs throughout the treatment period. Results and limitations: The median age before SRT was 63 yr. For the whole cohort, all five domains worsened at 3 and 18 mo after SRT compared with those before SRT. The estimated mean changes from before SRT to 18 mo after SRT are as follows: urinary incontinence -13.1, urinary irritative function -10.4, bowel -16.8, sexual function -9.1, and hormonal function -20.2 (at clinically important levels for all domains but sexual). For the subcohort, the mean urinary incontinence, bowel, sexual, and hormonal functions were significantly worsened 3 and 18 mo after SRT compared with those before RP at clinically important levels. Conclusions: Men treated for PC report particular increased severity of urinary, bowel, sexual, and hormonal symptoms after SRT compared with baseline status. Patient summary: For men with prostate cancer, the treatment combination of surgery and salvage radiotherapy worsens urinary incontinence and bowel, sexual, and hormonal functions.

Hypothetical interventions and risk of atrial fibrillation by sex and education: application of the parametric g-formula in the Tromsø Study.

AIMS: To use the parametric g-formula to estimate the long-term risk of atrial fibrillation (AF) by sex and education under hypothetical interventions on six modifiable risk factors. METHODS AND RESULTS: We estimated the risk reduction under hypothetical risk reduction strategies for smoking, physical activity, alcohol intake, body mass index, systolic, and diastolic blood pressure in 14 923 women and men (baseline mean age 45.8 years in women and 47.8 years in men) from the population-based Tromsø Study with a maximum of 22 years of follow-up (1994-2016). The estimated risk of AF under no intervention was 6.15% in women and 13.0% in men. This cumulative risk was reduced by 41% (95% confidence interval 17%, 61%) in women and 14% (-7%, 30%) in men under joint interventions on all risk factors. The most effective intervention was lowering body mass index to ≤ 25 kg/m2, leading to a 16% (4%, 25%) lower risk in women and a 14% (6%, 23%) lower risk in men. We found significant sex-differences in the relative risk reduction by sufficient physical activity, leading to a 7% (-4%, 18%) lower risk in women and an 8% (-2%, -13%) increased risk in men. We found no association between the level of education and differences in risk reduction by any of the interventions. CONCLUSION: The population burden of AF could be reduced by modifying lifestyle risk factors. Namely, these modifications could have prevented 41% of AF cases in women and 14% of AF cases in men in the municipality of Tromsø, Norway during a maximum 22-year follow-up period.

The heart normally has a regular rhythm. However, in an increasing number of adults worldwide, the rhythm is irregular, which is known as arrhythmia. Atrial fibrillation, or AF, is the most common type of arrhythmia. We know that the risk of AF may be related to lifestyle. In this project, we investigated how much the risk of AF in the population could have been reduced by improvements in smoking habits, physical activity level, alcohol intake, body mass index (BMI), and blood pressure. We found that the risk could have been reduced by 41% in women and 14% in men if everyone quit smoking, was sufficiently physically active, limited their alcohol intake to two units per week, lowered their BMI to 25 kg/m2, and lowered their blood pressure to 130/80 mm Hg. Reducing BMI was the most effective intervention to prevent AF.

Sex-specific time trends in incident atrial fibrillation and the contribution of risk factors: the Tromsø Study 1994-2016.

AIMS: To explore sex-specific time trends in atrial fibrillation (AF) incidence and to estimate the impact of changes in risk factor levels using individual participant-level data from the population-based Tromsø Study 1994-2016. METHODS AND RESULTS: A total of 14 818 women and 13 225 men aged 25 years or older without AF were enrolled in the Tromsø Study between 1994 and 2008 and followed up for incident AF throughout 2016. Poisson regression was used for statistical analyses. During follow-up, age-adjusted AF incidence rates in women decreased from 1.19 to 0.71 per 1000 person-years. In men, AF incidence increased from 1.18 to 2.82 per 1000 person-years in 2004, and then declined to 1.94 per 1000 person-years in 2016. Changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP), body mass index (BMI), physical activity, smoking and alcohol consumption together accounted for 10.9% [95% confidence interval (CI): -2.4 to 28.6] of the AF incidence decline in women and for 44.7% (95% CI: 19.2; 100.0) of the AF incidence increase in men. Reduction in SBP and DBP had the largest contribution to the decrease in AF incidence in women. Increase in BMI had the largest contribution to the increase in AF incidence in men. CONCLUSION: In the population-based Tromsø Study 1994-2016, AF incidence decreased in women and increased following a reverse U-shape in men. Individual changes in SBP and DBP in women and individual changes in BMI in men were the most important risk factors contributing to the AF incidence trends.

Lifestyle factors as mediators of area-level socio-economic differentials in cardiovascular disease risk factors. The Tromsø Study.

Introduction: Cardiovascular disease (CVD) is a leading cause of death and disability and living in areas with low socio-economic status (SES) is associated with increased risk of CVD. Lifestyle factors such as smoking, physical inactivity, an unhealthy diet and harmful alcohol use are main risk factors that contribute to other modifiable risk factors, such as hypertension, raised blood cholesterol, obesity, and diabetes. The potential impact of area-level socio-economic status (ASES) on metabolic CVD risk factors via lifestyle behaviors independent of individual SES has not been investigated previously. Aims: To estimate associations of ASES with CVD risk factors and the mediating role of lifestyle behaviors independent of individual-level SES. Methods: In this cross-sectional study, we included 19,415 participants (52% women) from the seventh survey of the Tromsø Study (2015-2016) (Tromsø7). The exposure variable ASES was created by aggregating individual-level SES variables (education, income, housing ownership) at the geographical subdivision level. Individual-level SES data and geographical subdivision of Tromsø municipality (36 areas) were obtained from Statistics Norway. Variables from questionnaires and clinical examinations obtained from Tromsø7 were used as mediators (smoking, snuff, alcohol, and physical activity), while the outcome variables were body mass index (BMI), total/high-density lipoprotein (HDL) cholesterol ratio, waist circumference, hypertension, diabetes. Mediation and mediated moderation analysis were performed with age as a moderator, stratified by sex. Results: ASES was significantly associated with all outcome variables. CVD risk factor level declined with an increase in ASES. These associations were mediated by differences in smoking habits, alcohol use and physical activity. The associations of ASES with total/HDL cholesterol ratio and waist circumference (women) were moderated by age, and the moderating effects were mediated by smoking and physical activity in both sexes. The largest mediated effects were seen in the associations of ASES with total/HDL cholesterol ratio, with the mediators accounting for 43% of the observed effects. Conclusions: Living in lower SES areas is associated with increased CVD risk due to unhealthy lifestyle behaviors, such as smoking, alcohol use and physical inactivity. These associations were stronger in women and among older participants.

Achievements of primary prevention targets in individuals with high risk of cardiovascular disease: an 8-year follow-up of the Tromsø study.

Aims: To study change over 8 years in cardiovascular risk, achievement of national guideline-based treatment targets of lipids, blood pressure (BP) and smoking in primary prevention of cardiovascular disease (CVD), medication use, and characteristics associated with target achievement among individuals with high CVD risk in a general population. Methods and results: We followed 2524 women and men aged 40-79 years with high risk of CVD attending the population-based Tromsø study in 2007-08 (Tromsø6) to their participation in the next survey in 2015-16 (Tromsø7). We used descriptive statistics and regression models to study change in CVD risk and medication use, and characteristics associated with treatment target achievement. In total, 71.4% reported use of BP- and/or lipid-lowering medication at second screening. Overall, CVD risk decreased during follow-up, with a larger decrease among medication users compared with non-users. Treatment target achievement was 31.0% for total cholesterol <5 mmol/L, 27.3% for LDL cholesterol <3 mmol/L, 43.4% for BP <140/90 (<135/85 if diabetes) mmHg, and 85.4% for non-smoking. A total of 9.8% reached all treatment targets combined. Baseline risk factor levels and current medication use had the strongest associations with treatment target achievement. Conclusion: We found an overall improvement in CVD risk factors among high-risk individuals over 8 years. However, guideline-based treatment target achievement was relatively low for all risk factors except smoking. Medication use was the strongest characteristic associated with achieving treatment targets. This study has demonstrated that primary prevention of CVD continues to remain a major challenge.

Expression of miR-24-1-5p in Tumor Tissue Influences Prostate Cancer Recurrence: The PROCA-life Study.

The role of miR-24-1-5p and its prognostic implications associated with prostate cancer are mainly unknown. In a population-based cohort, the Prostate Cancer Study throughout life (PROCA-life), all men had a general health examination at study entry and were followed between 1994 and 2016. Patients with available tissue samples after a prostatectomy with curative intent were identified (n = 189). The tissue expression of miR-24-1-5p in prostate cancer was examined by in situ hybridization (ISH) in tissue microarray (TMA) blocks by semi-quantitative scoring by two independent investigators. Multivariable Cox regression models were used to study the associations between miR-24-1-5p expression and prostate cancer recurrence. The prostate cancer patients had a median age of 65.0 years (range 47−75 years). The Cancer of the Prostate Risk Assessment Postsurgical Score, International Society of Urological Pathology grade group, and European Association of Urology Risk group were all significant prognostic factors for five-year recurrence-free survival (p < 0.001). Prostate cancer patients with a high miR-24-1-5p expression (≥1.57) in the tissue had a doubled risk of recurrence compared to patients with low expression (HR 1.99, 95% CI 1.13−3.51). Our study suggests that a high expression of miR-24-1-5p is associated with an increased risk of recurrence of prostate cancer after radical prostatectomy, which points to the potential diagnostic and therapeutic value of detecting miR-24-1-5p in prostate cancer cases.

Obesity Does Not Protect From Subarachnoid Hemorrhage: Pooled Analyses of 3 Large Prospective Nordic Cohorts.

BACKGROUND: Several population-based cohort studies have related higher body mass index (BMI) to a decreased risk of subarachnoid hemorrhage (SAH). The main objective of our study was to investigate whether the previously reported inverse association can be explained by modifying effects of the most important risk factors of SAH-smoking and hypertension. METHODS: We conducted a collaborative study of three prospective population-based Nordic cohorts by combining comprehensive baseline data from 211 972 adult participants collected between 1972 and 2012, with follow-up until the end of 2018. Primarily, we compared the risk of SAH between three BMI categories: (1) low (BMI<22.5), (2) moderate (BMI: 22.5-29.9), and (3) high (BMI≥30) BMI and evaluated the modifying effects of smoking and hypertension on the associations. RESULTS: We identified 831 SAH events (mean age 62 years, 55% women) during the total follow-up of 4.7 million person-years. Compared with the moderate BMI category, persons with low BMI had an elevated risk for SAH (adjusted hazard ratio [HR], 1.30 [1.09-1.55]), whereas no significant risk difference was found in high BMI category (HR, 0.91 [0.73-1.13]). However, we only found the increased risk of low BMI in smokers (HR, 1.49 [1.19-1.88]) and in hypertensive men (HR, 1.72 [1.18-2.50]), but not in nonsmokers (HR, 1.02 [0.76-1.37]) or in men with normal blood pressure values (HR, 0.98 [0.63-1.54]; interaction HRs, 1.68 [1.18-2.41], P=0.004 between low BMI and smoking and 1.76 [0.98-3.13], P=0.06 between low BMI and hypertension in men). CONCLUSIONS: Smoking and hypertension appear to explain, at least partly, the previously reported inverse association between BMI and the risk of SAH. Therefore, the independent role of BMI in the risk of SAH is likely modest.

Systolic and diastolic blood pressure, prostate cancer risk, treatment, and survival. The PROCA-life study.

BACKGROUND: Inflammation has been linked to prostate cancer and hypertension, but it remains equivocal whether elevated blood pressure (BP) influence prostate cancer risk and survival. METHOD: Using Cox regression models, we examined the association between prediagnostic BP and prostate cancer risk among 12,271 men participating in the Prostate Cancer throughout life (PROCA-life) study. Systolic and diastolic BP were measured. A total of 811 men developed prostate cancer, and followed for additional 7.1 years, and we studied the association between prediagnostic BP and overall mortality among patients with prostate cancer. RESULTS: Men (>45 years) with a systolic BP >150 mmHg had a 35% increased risk of prostate cancer compared with men with a normal systolic BP (<130 mmHg) (HR 1.35, 95% CI 1.08-1.69). Among patients with prostate cancer, men with systolic BP >150 mmHg had a 49% increased overall mortality compared with men with a normal systolic BP (HR 1.49, 1.06-2.01). Among patients with prostate cancer treated with curative intent, those with a high diastolic BP (>90 mmHg) had a threefold increase in overall mortality risk (HR 3.01, 95% CI 1.40-6.46) compared with patients with a normal diastolic BP (<80 mmHg). CONCLUSION: Our results support that systolic and diastolic BP are important factors when balancing disease management in patients with prostate cancer.

Thromboembolic Events During Treatment with Cisplatin-based Chemotherapy in Metastatic Testicular Germ-cell Cancer 2000-2014: A Population-based Cohort Study.

BACKGROUND: Cisplatin-based chemotherapy (CBCT) in testicular cancer (TC) is associated with elevated venous thromboembolism (VTE) risk, but trials evaluating the safety and efficacy of thromboprophylaxis are lacking. OBJECTIVE: To evaluate the arterial thromboembolism (ATE) and VTE incidence and risk factors during first-line CBCT for metastatic TC, and the effect of thromboprophylaxis on VTE and bleeding. DESIGN SETTING AND PARTICIPANTS: In a population-based study, 506 men administered first-line CBCT during 2000-2014 at three university hospitals in Norway were included. Clinical variables were retrieved from medical records. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients with ATE and VTE diagnosed at initiation of or during CBCT until 3 mo after completion were registered. Age-adjusted logistic regression was performed to identify possible VTE risk factors. RESULTS AND LIMITATIONS: Overall, 69 men (13.6%) were diagnosed with 70 thromboembolic events. Twelve men (2.4%) experienced ATE. Overall, 58 men (11.5%) experienced VTE, of whom 13 (2.6%) were prevalent at CBCT initiation, while 45 (8.9%) were diagnosed with incident VTE. Age-adjusted logistic regression identified retroperitoneal lymph node metastasis >5 cm (odds ratio [OR] 1.99, 95% confidence interval [CI] 1.01-3.91), central venous access (OR 2.84, 95% CI 1.46-5.50), and elevated C-reactive protein (>5 mg/l; OR 2.38, 95% CI 1.12-5.07) as incident VTE risk factors. Thromboprophylaxis (n = 84) did not influence the risk of VTE (VTE incidence with or without prophylaxis 13% vs 8%, p = 0.16). The incidence of bleeding events was significantly higher among those who received thromboprophylaxis than among those without thromboprophylaxis (14.5% vs 1.1%, p < 0.001). CONCLUSIONS: We found a high rate of thromboembolism incidence of 13.6%. Thromboprophylaxis did not decrease the risk of VTE but was associated with an increased risk of bleeding. PATIENT SUMMARY: We found a high rate of thromboembolism (13.6%) during cisplatin-based chemotherapy for metastatic testicular cancer. Prophylactic treatment against thromboses did not reduce the thrombosis frequency, but it resulted in a high incidence of bleeding events.

Long-Term Survival, Causes of Death, and Trends in 5-Year Mortality After Intracerebral Hemorrhage: The Tromsø Study.

BACKGROUND AND PURPOSE: Data on long-term survival after intracerebral hemorrhage (ICH) are scarce. In a population-based nested case-control study, we compared long-term survival and causes of death within 5 years in 30-day survivors of first-ever ICH and controls, assessed the impact of cardiovascular risk factors on 5-year mortality, and analyzed time trend in 5-year mortality in ICH patients over 2 decades. METHODS: We included 219 participants from the population-based Tromsø Study, who after the baseline participation had a first-ever ICH between 1994 to 2013 and 1095 age- and sex-matched participants without ICH. Cumulative survival was presented using the Kaplan-Meier method. Hazard ratios (HRs) for mortality and for the association between cardiovascular risk factors and 5-year mortality in 30-day survivors were estimated by stratified Cox proportional hazards models. Trend in 5-year mortality was assessed by logistic regression. RESULTS: Risk of death during follow-up (median time, 4.8 years) was increased in the ICH group compared with controls (HR, 1.62 [95% CI, 1.27-2.06]). Cardiovascular disease was the leading cause of death, with a higher proportion in ICH patients (22.9% versus 9.0%; P<0.001). Smoking increased the risk of 5-year mortality in cases and controls (HR, 1.59 [95% CI, 1.15-2.19]), whereas serum cholesterol was associated with 5-year mortality in cases only (HR, 1.39 [95% CI, 1.04-1.86]). Use of anticoagulants at ICH onset increased the risk of death (HR, 2.09 [95% CI, 1.09-4.00]). There was no difference according to ICH location (HR, 1.15 [95% CI, 0.56-2.37]). Five-year mortality did not change during the study period (odds ratio per calendar year, 1.01 [95% CI, 0.93-1.09]). CONCLUSIONS: Survival rates were significantly lower in cases than in controls, driven by a 2-fold increased risk of cardiovascular death. Smoking, serum cholesterol, and use of anticoagulant drugs were associated with increased risk of death in ICH patients. Five-year mortality rates in ICH patients remained stable over time.

Testicular Cancer in the Cisplatin Era: Causes of Death and Mortality Rates in a Population-Based Cohort.

PURPOSE: Using complete information regarding testicular cancer (TC) treatment burden, this study aimed to investigate cause-specific non-TC mortality with impact on previous treatment with platinum-based chemotherapy (PBCT) or radiotherapy (RT). METHODS: Overall, 5,707 men identified by the Cancer Registry of Norway diagnosed with TC from 1980 to 2009 were included in this population-based cohort study. By linking data with the Norwegian Cause of Death Registry, standardized mortality ratios (SMRs), absolute excess risks (AERs; [(observed number of deaths - expected number of deaths)/person-years of observation] ×10,000), and adjusted hazard ratios (HRs) were calculated. RESULTS: Median follow-up was 18.7 years, during which non-TC death was registered for 665 (12%) men. Overall excess non-TC mortality was 23% (SMR, 1.23; 95% CI, 1.14 to 1.33; AER, 11.14) compared with the general population, with increased risks after PBCT (SMR, 1.23; 95% CI, 1.07 to 1.43; AER, 7.68) and RT (SMR, 1.28; 95% CI, 1.15 to 1.43; AER, 19.55). The highest non-TC mortality was observed in those < 20 years at TC diagnosis (SMR, 2.27; 95% CI, 1.32 to 3.90; AER, 14.42). The most important cause of death was non-TC second cancer with an overall SMR of 1.53 (95% CI, 1.35 to 1.73; AER, 7.94), with increased risks after PBCT and RT. Overall noncancer mortality was increased by 15% (SMR, 1.15; 95% CI, 1.04 to 1.27; AER, 4.71). Excess suicides appeared after PBCT (SMR, 1.65; 95% CI, 1.01 to 2.69; AER, 1.39). Compared with surgery, increased non-TC mortality appeared after 3 (HR, 1.47; 95% CI, 0.91 to 2.39), 4 (HR, 1.41; 95% CI, 1.01 to 1.99), and more than four (HR, 2.04; 95% CI, 1.25 to 3.35) cisplatin-based chemotherapy cycles after > 10 years of follow-up. CONCLUSION: TC treatment with PBCT or RT is associated with a significant excess risk of non-TC mortality, and increased risks emerged after more than two cisplatin-based chemotherapy cycles after > 10 years of follow-up.

Age-specific atrial fibrillation incidence, attributable risk factors and risk of stroke and mortality: results from the MORGAM Consortium.

BACKGROUND: The main aim was to examine age-specific risk factor associations with incident atrial fibrillation (AF) and their attributable fraction in a large European cohort. Additionally, we aimed to examine risk of stroke and mortality in relation to new-onset AF across age. METHODS: We used individual-level data (n=66 951, 49.1% men, age range 40-98 years at baseline) from five European cohorts of the MOnica Risk, Genetics, Archiving and Monograph Consortium. The participants were followed for incident AF for up to 10 years and the association with modifiable risk factors from the baseline examinations (body mass index (BMI), hypertension, diabetes, daily smoking, alcohol consumption and history of stroke and myocardial infarction (MI)) was examined. Additionally, the participants were followed up for incident stroke and all-cause mortality after new-onset AF. RESULTS: AF incidence increased from 0.9 per 1000 person-years at baseline age 40-49 years, to 17.7 at baseline age ≥70 years. Multivariable-adjusted Cox models showed that higher BMI, hypertension, high alcohol consumption and a history of stroke or MI were associated with increased risk of AF across age groups (p<0.05). Between 30% and 40% of the AF risk could be attributed to BMI, hypertension and a history of stroke or MI. New-onset AF was associated with a twofold increase in risk of stroke and death at ages≥70 years (p≤0.001). CONCLUSION: In this large European cohort aged 40 years and above, risk of AF was largely attributed to BMI, high alcohol consumption and a history MI or stroke from middle age. Thus, preventive measures for AF should target risk factors such as obesity and hypertension from early age and continue throughout life.

Heavy alcohol drinking and subclinical echocardiographic abnormalities of structure and function.

OBJECTIVE: The aim of the study is to assess changes in heart structure and function associated with heavy alcohol use by comparing echocardiographic indices in a population-based sample to those in patients admitted to an inpatient facility with severe alcohol problems. METHODS AND RESULTS: We used data from the Know Your Heart study (2015-2017) which is a cross-sectional study that recruited 2479 participants aged 35-69 years from the general population of the city of Arkhangelsk in Northwest Russia and 278 patients from the Arkhangelsk Regional Psychiatric Hospital with a primary diagnosis related to chronic alcohol use (narcology clinic subsample). The drinking patterns of the population-based sample were characterised in detail. We used regression models controlling for age, sex, smoking, education and waist to hip ratio to evaluate the differences in echocardiographic indices in participants with different drinking patterns. The means of left ventricular end-diastolic diameter and indexed left atrial systolic diameter were increased among heavy drinkers (narcology clinic subsample), while mean left ventricular ejection fraction was decreased in this group compared with the population-based sample. In contrast, the harmful and hazardous drinkers in the population-based sample did not differ from non-problem drinkers with respect to echocardiographic indices of systolic and diastolic function. CONCLUSIONS: Extremely heavy drinking is associated with a specific set of structural and functional abnormalities of the heart that may be regarded as precursors of alcohol-related dilated cardiomyopathy.