Warfarin intake in relation to diagnosis reduces mortality in patients with colorectal cancer - a register-based study.

BACKGROUND: Several studies have analyzed the effect of anticoagulants on cancer survival, with varying results. This study aimed to assess the effect of warfarin on survival in patients with colorectal cancer (CRC) in relation to timing of warfarin initiation. METHODS: Data on 10,051 individuals aged ≥45 years in the Västra Götaland Region of Sweden, and diagnosed with CRC between 2000 and 2009, were obtained from the Swedish National Cancer Register. Those who received warfarin treatment (n= 1,216) during the study period were labeled cases and those who did not (n= 8,873) were labeled controls. For statistical analysis, National Cancer Register data were merged with mortality data from the Swedish National Cause of Death register and data from the regional warfarin treatment register. RESULTS: Hazard rates for CRC-specific mortality were lower in cases than in controls. When warfarin was used for any reason at any time, cases had a significantly lower CRC-specific mortality than controls among both women (hazard ratio [HR] 0.71; 95 % confidence interval [CI] 0.59-0.85; p= 0.0002) and men (HR 0.61; 95 % CI 0.52-0.72; p < 0001). Warfarin treatment after CRC diagnosis reduced CRC-specific mortality by 80 %; however, when warfarin was given before or ≥5 years after diagnosis, CRC-specific mortality did not significantly decrease. The number needed to treat to avoid one death was four. CONCLUSION: Use of warfarin early after diagnosis in patients with CRC was associated with improved survival.

The risk of recurrent venous thromboembolism after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis: a systematic review and meta-analysis.

Background: The optimal duration of anticoagulation in patients with active cancer and venous thromboembolism (VTE) is unknown. Current clinical guidelines advocate anticoagulant therapy for 3-6 months and to continue anticoagulant therapy for as long as the cancer is active. However, an adequate systematic review on the rate of recurrent VTE after discontinuation of anticoagulant therapy has not been performed. Methods: For this systemic review and meta-analysis, we searched Embase.com, Medline (Ovid), Web of Science, Cochrane Library, and Google Scholar, from database inception to February 16, 2023, for studies on anticoagulant therapy in patients with cancer and the recurrence of venous thromboembolism after discontinuation of this therapy. We included randomised controlled trials and cohort studies published in English that reported on patients who met the following: cancer and a first VTE, completed at least 3 months of anticoagulant therapy, were followed after discontinuation of anticoagulant therapy, and with symptomatic recurrent VTE as an outcome during follow-up. Study-level data were requested from study authors. The primary outcome was the rate of recurrent VTE after discontinuation of anticoagulant therapy. A Bayesian random-effects meta-analysis was used to estimate the rate of recurrent VTE per 100 person-years for the pooled studies at different time intervals after discontinuation of anticoagulation therapy. We also calculated the cumulative VTE recurrence rate at different time intervals. Forest plots were mapped and the results were summarized by the median and 95% credible interval (CIs). This study was registered with PROSPERO, CRD42021249060. Findings: Of 3856 studies identified in our search, 33 studies were identified for inclusion. After requesting study-level data, 14 studies involving 1922 patients with cancer-associated thrombosis were included. The pooled rate of recurrent VTE per 100 person-years after discontinuation of anticoagulant therapy was 14.6 events (95% credible interval 6.5-22.8) in the first three months, decreasing to 1.1 events (95% CI 0.3-2.1) in year 2-3, and 2.2 events (95% CI 0.0-4.4) in year 3-5 after discontinuation of anticoagulant therapy. The cumulative VTE recurrence rate was 28.3% (95% CI 15.6-39.6%) at 1 year; 31.1% (95% CI 16.5-43.8%) at 2 years; 31.9% (95% CI 16.8-45.0%) at 3 years; and 35.0% (95% CI 16.8-47.4%) at 5 years after discontinuation of anticoagulant therapy. Interpretation: This meta-analysis demonstrates a high rate of recurrent VTE over time after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis. Our results support the current clinical guidelines to continue anticoagulant therapy in patients with active cancer. Funding: Erasmus MC.

Cumulative incidence and risk factors of myocardial infarction during 20 years of follow-up: comparing two cohorts of middle-aged men born 30 years apart.

OBJECTIVE: To study cumulative incidence and predictors of myocardial infarction (MI) in two random general population samples consisting of middle-aged Swedish men born 30 years apart. METHOD: Results from the "Study of Men Born In 1913" and the "Study of Men Born In 1943", two longitudinal cohort studies performed in the same geographic area and using the same methodology were compared. Both cohorts were followed prospectively from 50 to 70 years of age. MI was defined as first myocardial infarction, fatal or non-fatal. RESULTS: Men born in 1943 had a 34% lower cumulative risk of first MI [HR 0.66 (0.50-0.88), p = 0.0051] during follow-up as compared to men born in 1913. Interaction analysis showed that hypertension had a significantly higher impact on risk of MI in cohort 1943 than in cohort 1913 [HR 2.33 (95% CI 1.41-3.83)] and [HR 1.10 (0.74-1.62)], p = 0.0009 respectively. The population attributable risk for hypertension was 2.5-fold higher in the cohort of men born in 1943 as compared to men born in 1913, and diabetes mellitus and sedentary lifestyle attributed more to MI risk in cohort 1943 than in cohort 1913. On the contrary, smoking and total cholesterol have less attributable risk to MI in cohort 1943 than in cohort 1913. CONCLUSION: Despite declining incident MI and improved cardiovascular prevention in general, hypertension remains an increasingly important attributable risk factor to MI together with diabetes mellitus and sedentary lifestyle over time.

Association of type of oral anticoagulation with risk of bleeding in 45,114 patients with venous thromboembolism during initial and extended treatment-A nationwide register-based study.

BACKGROUND: Safety data for different anticoagulant medications in venous thromboembolism (VTE) are scarce, in particular for extended treatment. OBJECTIVES: To compare major bleeding rates depending on the choice of anticoagulation during initial (first 6 months) and extended treatment (6 months up to 5 years). METHODS: A nationwide register-based study including cancer-free patients with a first-time VTE between 2014 and 2020. Cox proportional hazards models were used to compare bleeding rates. RESULTS: We included 6558 patients on warfarin, 18,196 on rivaroxaban, and 19,498 on apixaban. At 6 months, 4750 (72.4%) remained on warfarin, 11,366 (62.5%) on rivaroxaban, and 11,940 (61.2%) on apixaban. During initial treatment, major bleeding rates were 3.86 (95% CI 3.14-4.58), 2.93 (2.55-3.31), and 1.95 (1.65-2.25) per 100 patient-years for warfarin, rivaroxaban, and apixaban, respectively, yielding adjusted hazard ratios (aHRs) of 0.89 (95% CI 0.71-1.12) for rivaroxaban versus warfarin, 0.55 (0.43-0.71) for apixaban versus warfarin, and 0.62 (0.50-0.76) for apixaban versus rivaroxaban. During extended treatment, major bleeding rates were 1.55 (1.19-1.91), 1.05 (0.85-1.26), and 0.96 (0.78-1.15) per 100 patient-years for warfarin, rivaroxaban, and apixaban, respectively, with aHRs of 0.72 (0.53-0.99) for rivaroxaban versus warfarin, 0.60 (0.44-0.82) for apixaban versus warfarin, and 0.85 (0.64-1.12) for apixaban versus rivaroxaban. Previous bleeding and increasing age were risk factors for bleeding both during initial and extended treatment. CONCLUSION: Apixaban had a lower bleeding risk than warfarin or rivaroxaban during initial treatment. During extended treatment, bleeding risk was similar for apixaban and rivaroxaban, and higher with warfarin.

Prevalence of Cancer in Patients with Venous Thromboembolism: A Retrospective Nationwide Case-Control Study in Sweden.

Cancer is a risk factor for venous thromboembolism (VTE). We aimed to define sex-specific risk of preceding cancer in patients with a first-time VTE by conducting a nationwide Swedish registry-based study including 298 172 patients with VTE and 1 185 079 matched controls. This included 44 685 patients with a diagnosis of cancer at/or within 1 year before a VTE diagnosis. Female patients with VTE had a higher multivariable adjusted odds ratios of preceding cancer than male patients with VTE (5.5 [99% confidence interval 5.4-5.7] vs 3.9 [3.8-4.0]). The highest risk of cancer in patients with VTE were found for pancreatic cancer (women: 19.6 [15.8-24.4]; men: 17.2 [13.7-21.6]) and brain cancer (women: 17.4 [12.9-23.4]; men: 17.5 [13.8-22.2]). Weak associations were seen between VTE and bladder/urothelial cancer (women: 1.31 [1.12-1.53]; men: 1.34 [1.23-1.47]), prostate cancer (men: 2.17 [2.07-2.27]), malignant melanoma (women: 2.51 [2.07-3.05]; men: 2.67 [2.23-3.18]), and kidney cancer (women: 3.20 [2.49-4.11]; men: 3.33 [2.79-4.07]). In conclusion, associations with VTE were weak for bladder/urothelial cancer and kidney cancer, and strong for pancreatic, brain, and biliary cancers.

Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses.

BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

Pulmonary embolism and deep vein thrombosis-comorbidities and temporary provoking factors in a register-based study of 1.48 million people.

Background: Knowledge on differences in patients who present with deep vein thrombosis (DVT) and those with pulmonary embolism (PE) is incomplete. Objective: To determine comorbidities and temporary provoking factors in patients with a first-time PE or DVT. Methods: This was a nationwide Swedish registry-based, retrospective, case-control study including 298 172 patients with first-time venous thromboembolism (VTE) and 1 185 079 controls matched for age, sex, and county of residence, free of VTE at the time of matching. Results: Patients with PE were older than those with DVT (mean age, 69 vs 66 years) and included slightly more women (PE, 53.4% vs DVT, 52.1%). After multivariable adjustment for comorbidities (within 7 years) and temporary provoking factors (within 3 months), heart failure (PE: adjusted odds ratio [aOR], 2.64 [99% confidence interval [CI], 2.55-2.73]; DVT: aOR, 1.66 [99% CI, 1.60-1.72]), ischemic heart disease (PE: aOR, 1.51 [99% CI, 1.47-1.56]; DVT: aOR, 1.01 [99% CI, 0.98-1.04]), and chronic obstructive pulmonary disease (PE: aOR, 2.51 [99% CI, 2.40-2.63]; DVT, 1.54 [99% CI, 1.47-1.62]) were among diseases that showed higher odds ratios in patients with PE than in those with DVT, compared with controls. Comorbidities registered within 6 months were associated with higher aORs than those within 7 years. The highest population attributable risks for PE were for cancer (13.0%) and heart failure (11.7%). Conclusion: Cardiopulmonary diseases, particularly with recent onset, imply a higher risk for PE, whereas orthopedic surgery and lower-extremity fractures carry a higher risk of DVT.

Body iron stores had no impact on coronary heart disease outcomes: a middle-aged male cohort from the general population with 21-year follow-up.

BACKGROUND: Body iron stores (BISs) have been proposed to be related to the development of cardiovascular diseases. However, results from epidemiological studies are conflicting. Knowledge on the long-term impact of BIS on cardiovascular outcomes in the general population is lacking. PURPOSE: The aim of this study was to explore the relationship between BIS and coronary heart disease (CHD) including death due to CHD. METHODS: This investigation is part of 'The Study of Men Born in 1943', a longitudinal prospective study of men living in the city of Gothenburg, Sweden. This random population sample was examined in 1993 (all at 50 years of age at baseline). A medical examination was performed, and questionnaires were used to evaluate lifestyle factors. Biomarkers for iron stores (serum ferritin and serum transferrin receptor) was analysed from frozen blood samples in 2014. All hospital admissions were registered through national registers during the entire follow-up from 1993 to 2014. HRs were estimated by Cox proportional-hazard regression analyses. RESULTS: During the 21 years follow-up period, 120 participants (15.2%) developed CHD and 16 patients (2%) died due to CHD. The all-cause mortality was 15.2% (n=120) including 40 cardiovascular deaths (5.1%). In a multivariable Cox regression analysis, the daily smoking, hypertension and the increased resting heart rate was independent predictors of CHD, while no significant association was found between BIS and risk of CHD. CONCLUSIONS: In a cohort of middle-aged men from the general population with well validated and prospectively collected data, we did not find any association between serum ferritin or serum transferrin receptor as markers of BIS and CHD events after 21 years of follow-up. TRAIL REGISTRATION NUMBER: NCT03138122.

Mid-life extrapyramidal symptoms predict cognitive impairment 23 years later.

OBJECTIVES: The prevalence of dementia is growing rapidly worldwide. The early identification and treatment of cognitive decline could reduce the burden on the health care system. Our objective was to investigate whether factors measured at an examination at age 50 predict cognitive impairment (CI) 23 years later. MATERIALS & METHODS: In 1993 we enrolled a randomly selected sample of 798 men, 50 years of age, from the general population. They all underwent a physical examination, provided blood samples and filled out questionnaires addressing lifestyle and psychosocial factors. Cognitive testing was offered to all participants still alive in 2016, at age 73. RESULTS: A total of 333 men participated in the cognitive study, of which 80 (24.0%) performed at a level corresponding to mild cognitive impairment, and four (1.2%) at a level consistent with severe cognitive impairment. After the first step in the multivariable analysis, hypertension, heavy smoking, high intake of alcohol, financial stress, difficulty falling asleep, and cogwheel rigidity were associated with cognitive impairment. After further adjustment, only wide waist circumference measured in cm (OR 1.04, 95% CI 1.00-1.08, p = .04), leg pendulousness (OR 41.97, 95% CI 3.27-538.62, p = .004) and self-assessed hidden irritability (OR 2.18, 95% CI 1.10-4.32, p = .03) at baseline, remained as being associated with cognitive impairment 23 years later. CONCLUSIONS: Extrapyramidal symptoms such as leg pendulousness, at the age of 50, may be an indicator for very early identification of future cognitive decline.

Determinants of falls after stroke based on data on 5065 patients from the Swedish Väststroke and Riksstroke Registers.

We aimed to identify determinants in acute stroke that are associated with falls during the stroke unit stay. In order to enable individualized preventive actions, this knowledge is fundamental. Based on local and national quality register data on an unselected sample of 5065 stroke patients admitted to a stroke unit at a Swedish university hospital, univariable and multivariable logistic regression analyses were performed. The dependent variable was any fall during stroke unit stay. The independent variables related to function, activity, personal factors, time to assessment, comorbidities and treatments. Determinants of falls were: being male (odds ratio (OR) 2.25, 95% confidence interval (95% CI) 1.79-2.84), haemorrhagic stroke (OR 1.39, 95% CI 1.05-1.86), moderate stroke symptoms according to the National Institutes of Health Stroke Scale (NIHSS score 2-5 vs. NIHSS score 0-1) (OR 1.43, 95% CI 1.08-1.90), smoking (OR 1.70, 95% CI 1.29-2.25), impaired postural control in walking (OR 4.61, 95% CI 3.29-6.46), impaired postural control in standing (OR 1.60, 95% CI 1.25-2.05), stroke-related arm- and hand problems, OR 1.45, 95% CI 1.11-1.91), impaired cognition (OR 1.43, 95% CI 1.04-1.95), and urinary tract infection (OR 1.91, 95% CI 1.43-2.56). The findings from this study are useful in clinical practice and might help to improve patient safety after stroke.

Incremental changes in QRS duration as predictor for cardiovascular disease: a 21-year follow-up of a randomly selected general population.

The QRS complex has been shown to be a prognostic marker in coronary artery disease. However, the changes in QRS duration over time, and its predictive value for cardiovascular disease in the general population is poorly studied. So we aimed to explore if increased QRS duration from the age of 50-60 is associated with increased risk of major cardiovascular events during a further follow-up to age 71. A random population sample of 798 men born in 1943 were examined in 1993 at 50 years of age, and re-examined in 2003 at age 60 and 2014 at age 71. Participants who developed cardiovascular disease before the re-examination in 2003 (n = 86) or missing value of QRS duration in 2003 (n = 127) were excluded. ΔQRS was defined as increase in QRS duration from age 50 to 60. Participants were divided into three groups: group 1: ΔQRS < 4 ms, group 2: 4 ms ≤ ΔQRS < 8 ms, group 3: ΔQRS ≥ 8 ms. Endpoints were major cardiovascular events. And we found compared with men in group 1 (ΔQRS < 4 ms), men with ΔQRS ≥ 8 ms had a 56% increased risk of MACE during follow-up to 71 years of age after adjusted for BMI, systolic blood pressure, smoking, hyperlipidemia, diabetes and heart rate in a multivariable Cox regression analysis (HR 1.56, 95% CI:1.07-2.27, P = 0.022). In conclusion, in this longitudinal follow-up over a decade QRS duration increased in almost two out of three men between age 50 and 60 and the increased QRS duration in middle age is an independent predictor of major cardiovascular events.

Multi-modality biomarkers in the early prediction of ischaemic heart disease in middle-aged men during a 21-year follow-up.

BACKGROUND: Ischaemic heart disease (IHD) often develops after decades of preceding subclinical coronary atherosclerosis. Biomarkers are useful prognostic predictors of IHD, but their long-term predictive value in a general population has not been adequately studied. PURPOSE: To investigate the early predictive value of multi-modality biomarkers in addition to clinical risk factors in incident IHD in a random male general population sample followed from 50 to 71 years of age. METHOD: "The Study of Men Born in 1943" is a longitudinal cohort study during follow-up. All the men underwent a baseline examination in 1993, where a panel of biomarkers were analysed and incident IHD was registered during 21-year follow-ups. RESULTS: Of 739 participants, 97 men (13.1%) developed an IHD event. For time to first occurrence of IHD, univariable analyses showed that elevated levels of high sensitivity troponin T (hs-TNT), high sensitivity-C reactive protein (hs-CRP) and interleukin-6 (IL-6) were significant predictors of IHD. In addition, a high number of biomarkers with elevated levels (hs-TNT > 10 ng/L, hs-CRP > 1 mg/L, IL-6 > 8 ng/L and N-terminal pro b-type natriuretic peptide (NT-proBNP) > 100 pg/mL) increased predictive ability. In univariable and multivariable analysis high-density lipoprotein-cholesterol (HDL-C) had the highest predictive ability. Hs-TNT provided better predictive ability than smoking, body mass index and glucose, and was an independent significant predictor when adjusted for HDL-C, total cholesterol and hypertension. Addition of biomarkers on top of clinical risk factors provided significantly better prediction as tested by likelihood ratio test (p = 0.033), but did not significantly enhance the model's discriminative ability However, it appeared contributing to higher sensitivity in the late phase of follow-up. CONCLUSION: In this random, middle-aged male population sample, the addition of biomarker hs-TNT was an independent significant predictor of IHD and significantly improved prediction, indicating the probability of a better prediction of long-term risk of IHD in a low-risk population. TRIAL REGISTRATION: The study is registered at Clinical Trials.gov Identifier number: NCT03138122.

Long-term risk of stroke and myocardial infarction in middle-aged men with a hypertensive response to exercise: a 44-year follow-up study.

INTRODUCTION: Data on the prognostic value of hypertensive response to exercise in cardiovascular disease are limited. The aim was to determine whether SBP reactions during exercise have any prognostic value in relation to the long-term risk of stroke and myocardial infarction (MI). PATIENTS AND METHODS: A representative cohort of men from Gothenburg, Sweden, born in 1913, who performed a maximum exercise test at age 54 years, (n = 604), was followed-up for a maximum of 44 years with regard to stroke and MI. RESULTS: Among the 604 men, the mean resting and maximum SBP was 141.5 (SD 18.8) and 212.1 (SD 24.6) mmHg, respectively. For maximum SBP, the risk of stroke increased by 34% (hazard ratio 1.34, 95% confidence interval 1.11-1.61) per 1-SD increase, while no risk increase was observed for MI. The highest risk of stroke among blood pressure groups was observed among men with a resting SBP of at least 140 mmHg and a maximum SBP of at least 210 mmHg with an hazard ratio of 2.09 (95% confidence interval 1.29-3.40), compared with men with a resting SBP of less than 140 mmHg and a maximum SBP of less than 210 mmHg, independent of smoking, blood glucose, cholesterol and BMI. CONCLUSION: Among middle-aged men with high resting and maximum blood pressure during maximum exercise workload, an increased risk of stroke was observed but not for MI. Further studies with larger sample sizes are needed to investigate the underlying mechanisms of the increased risk of stroke among individuals with hypertensive response to exercise.

Secular trends in cardiovascular risk factors among women aged 45-54 years in Gothenburg, Sweden, from 1980 to 2014.

BACKGROUND: A declining trend in mean cholesterol levels and smoking has been observed in high-income western countries during the last few decades, whereas obesity rates have increased. Simultaneously, mortality from coronary heart disease has decreased. The aim of the present study was to determine whether the trends in cardiovascular risk factors have continued in successive cohorts of middle-aged women over a period of 34 years. METHODS: Six population-based, cross-sectional samples of women (n = 2294) mean age: 49.8 years (range: 45-54), living in Gothenburg, Sweden, were investigated between 1980 and 2014. RESULTS: Body mass index (BMI) increased over time, with a mean BMI of 24.7 kg/m2 in 1980 to 25.7 kg/m2 in 2013-2014, corresponding to a weight gain of 4.5 kg, together with an increase in the proportion of obese individuals (BMI ≥ 30 kg/m2) from 10.4 to 16.6% (p = 0.0012). The proportion of smokers and women with hypertension decreased from 34.5 to 12.8% (p = 0.0006) and from 37.7 to 24.5% (p < 0.0001) respectively. Mean total serum cholesterol levels decreased from 6.23 (SD 1.09) mmol/L in 1980 to 5.43 (SD 0.98) mmol/L in 2013-2014 (p < 0.0001). Self-reported leisure time regular exercise increased from 7.8% in 1980 to 35.6% in 2013-2014 (p < 0.0001). For women born in 1963, the prevalence ratio of not having any of five major cardiovascular risk factors was 1.82 (95% confidence interval (CI) 1.38-2.41), compared with women born in 1925-1934. CONCLUSION: The trend towards increasing obesity, more leisure-time physical activity and less smoking remains, while the decrease in serum cholesterol appears to have abated.

Comparison of incidence rates and risk factors of heart failure between two male cohorts born 30 years apart.

OBJECTIVE: To compare two cohorts of middle-aged men from the general population born 30 years apart for incidence and predictors of heart failure (HF). METHODS: Two population samples of men, born in 1913 (n=855) and in 1943 (n=797), were examined at 50 years of age and followed up for 21 years (1963-1994 and 1993-2014). Cox regression analysis was used to examine the impact of different factors on the risk of developing HF. RESULTS: Eighty men born in 1913 (9.4%) and 42 men born in 1943 (5.3%) developed HF during follow-up; adjusted HRs comparing the two cohorts (born 1943 vs 1913) were: 0.46 (95% CI 0.28 to 0.74, p=0.002). In both cohorts, higher body mass index, higher diastolic blood pressure, treatment for hypertension, onset of either atrial fibrillation (AF), ischaemic heart disease and diabetes mellitus were associated with higher risk of HF. Higher heart rate was associated with an increased risk only in men born in 1913, whereas higher systolic blood pressure (SBP), smoking, higher glucose, higher cholesterol and physical inactivity were associated with an increased risk in men born in 1943. AF contributed higher risk of incident HF, whereas SBP and physical inactivity contributed lower risk in men born in 1943 compared with men born in 1913. CONCLUSIONS: Men born in 1943 had half the risk of HF after their 50s than those born 30 years earlier. AF, obesity, ischaemic heart disease, diabetes and hypertension remain important precursors of HF.

High prevalence of cardiac dysfunction or overt heart failure in 71-year-old men: A 21-year follow-up of "The Study of men born in 1943".

BACKGROUND: Knowledge about long-term risk factors and the prevalence of heart failure stages in general population is limited. We aimed to study the prevalence of cardiac dysfunction and heart failure in 71-year-old men and potential risk factors in the past two decades. DESIGN: This research was based on a randomized selected population study with longitudinal follow-up. METHODS: A random sample of men born in 1943 in Gothenburg, Sweden were examined in 1993 (at 50 years of age) and re-examined 21 years later in 2014 (at 71 years of age). Cardiac dysfunction or heart failure was classified into four stages (A-D) according to American Heart Association/American College of Cardiology guidelines on heart failure. RESULTS: Of the 798 men examined in 1993 (overall cohort), 535 (67%) were re-examined in 2014 (echo cohort). In the echo cohort 122 (23%) men had normal cardiac function, 135 (25%) were at stage A, 207 (39%) men were at stage B, 66 (12%) men were at stage C, and five (1%) men were at stage D. Multivariable logistic regression demonstrated that elevated body mass index at 50 years old was the only independent risk factor for developing heart failure/cardiac dysfunction during the subsequent 21 years. For each unit (1 kg/m2) of increased body mass index, the odds ratio for stages C/D heart failure vs no heart failure/stage A increased by 1.20 (95% confidence interval, 1.11-1.31, p < 0.001), after adjustment for smoking, sedentary life style, systolic blood pressure, diabetes, and hyperlipidemia. CONCLUSION: In a random sample of men at 71 years of age, half presented with either cardiac dysfunction or clinical heart failure. High body mass index was associated with an increased risk for developing cardiac dysfunction or heart failure over a 21-year period.

Hyperparathyroidism in men - morbidity and mortality during 21 years' follow-up.

Hyperparathyroidism (HPT), including normocalcaemic, vitamin D sufficient (Serum (S)-25(OH)D ≥ 50 nmol/L) hyperparathyroidism (nHPT), has increasingly been diagnosed in the last few decades due to the more common use of the serum parathyroid hormone (S-PTH) assay. We investigated if men with HPT had higher morbidity and mortality than men without HPT during 21 years' follow-up.A random population sample of 750 men, all 50 years of age, was examined in 1993. Endpoints were retrieved 21 years later at 71 years of age.Albumin-corrected serum (S) calcium, S-25-hydroxyvitamin D and S-PTH were assessed along with data on cardiovascular risk factors and medication. Outcome data on fractures, stroke, myocardial infarction, cancer and death were retrieved in 2014; 21 years after primary assessment. The prevalence of HPT at 50 years of age was 9.3%; nHPT 2.8%, primary HPT 0.4%, secondary HPT 0.4%, and HPT with vitamin D insufficiency 6%. Fracture rate, myocardial infarction, stroke, cancer and death occurred similarly in men with or without HPT, as well as in men with nHPT as compared with men without calcium/PTH aberrations during 21 years' follow-up. S-PTH was evenly distributed in the univariable analyses for each outcome. Cox regression analyses showed no increase in serious morbidity or in mortality in men with HPT, irrespective of cause, compared with men with normal S-PTH over a 21-year period. None had HPT at a S-25(OH)D level of 100 nmol/L.

Risk factors for subarachnoid haemorrhage: a nationwide cohort of 950 000 adults.

BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium. METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries. RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH. CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.

Determinants of Stroke in a General Male Population.

Background and Purpose- To further improve preventive strategies against stroke, there is a need for epidemiological long-term studies. The study aimed at a prospective investigation of stroke determinants in the general male population. Methods- During a period of 48 years, from 50 to 98 years of age, a population-based sample of 854 men was followed using repeated medical examinations, lifestyle questionnaires, data from hospital records and the National Cause of Death Register. Results- Determinants of ischemic stroke were atrial fibrillation (hazard ratio [HR], 6.61; 95% CI, 4.47-9.77); mother dead from cardiovascular disease (HR, 1.53; 1.09-2.17); high education (HR, 0.81; 0.69-0.96); and high physical activity level during leisure time (HR, 0.68; 0.50-0.93). For hemorrhagic stroke heart rate (HR, 1.04; 1.01-1.06) and mother dead from stroke (HR, 3.56; 1.43-8.87) constituted an increased risk. Statistically significant determinants for all stroke were atrial fibrillation (HR, 5.34; 3.68-7.75); high diastolic blood pressure (HR, 1.02; 1.01-1.03); high body weight (HR, 0.96; 0.94-0.99); high educational level (HR, 0.79; 0.68-0.92); wide waist circumference (HR, 1.04; 1.01-1.07); smoking (HR, 1.25; 1.06-1.48); mother dead from cerebrovascular disease (HR, 1.43; 1.05-1.94); and diabetes mellitus (HR, 1.65; 1.02-2.68). Of all men diagnosed with atrial fibrillation, 88% had a stroke during follow-up. Conclusions- Atrial fibrillation was by far the strongest determinant of stroke during 48 years of follow-up in a male population sample followed until the age of 98 years. The results warrant improved prophylaxis through intense treatment of modifiable determinants.

Natriuretic and Inflammatory Biomarkers as Risk Predictors of Heart Failure in Middle-Aged Men From the General Population: A 21-Year Follow-Up.

BACKGROUND: Although several biomarkers, including natriuretic peptides and inflammatory biomarkers, have proven to be useful prognostic predictors in patients with heart failure (HF), their predictive value for incident HF has not been extensively studied. METHODS AND RESULTS: The "Study of Men Born in 1943" is a longitudinal, prospective study of men living in the city of Gothenburg, Sweden. A panel of biomarkers consisting of interleukin-6 (IL-6), cystatin C, high-sensitivity C-reactive protein (hs-CRP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) was analyzed from blood samples collected in 1993 in men aged 50 years. Incident HF was recorded from multiple sources, including an echocardiographic assessment in 2014. A total of 747 (94%) of the 798 participants with no previous history of HF were included. Of these 747 participants, 85 (11.4%) developed HF over a 21-year follow-up. After adjustment for body mass index (BMI) and hypertension at baseline, NT-proBNP ≥25 ng/L was associated with a higher risk of HF (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.30-3.36; P = .0024), as was hs-CRP >3 mg/L (OR 2.61, 95% CI 1.59-4.29; P = .0002). In a multivariable model, the expected probability of HF was 0.33 (95% CI 0.23-0.45) in hypertensive patients with hs-CRP >3 mg/L, NT-proBNP ≥25 ng/L, and BMI ≥25 kg/m2, compared with a probability of 0.04 (95% CI 0.02-0.07) in nonhypertensive patients with hs-CRP ≤3 mg/L, NT-proBNP <25 ng/L, and BMI <25 kg/m.2 CONCLUSIONS: NT-proBNP ≥25 ng/L and elevated hs-CRP levels in men aged 50 years were predictive biomarkers for HF over a 2one year follow-up.