Publications by authors named "Tom Wilsgaard"

281 Publications

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

Cancer Med 2021 Dec 22. Epub 2021 Dec 22.

Department of Clinical Medicine, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromsø, Norway.

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.
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http://dx.doi.org/10.1002/cam4.4523DOI Listing
December 2021

Associations Between Intake of Fermented Dairy Products and Blood Lipid Concentrations Are Affected by Fat Content and Dairy Matrix - The Tromsø Study: Tromsø7.

Front Nutr 2021 22;8:773468. Epub 2021 Nov 22.

Department of Clinical Medicine, UiT the Arctic University of Norway, Tromsø, Norway.

Dairy fat is rich in saturated fatty acids known to increase serum low-density lipoprotein cholesterol (LDL-C) concentration, an important risk factor for cardiovascular disease (CVD). However, intake of fermented dairy products has been associated with reduced CVD risk in observational studies. How intakes of different fermented dairy products are associated with blood lipid concentrations may provide a possible explanation for the suggested reduced CVD risk. To examine the associations between different types of fermented dairy products, with various fat contents and dairy matrix structures, and blood lipid concentrations in a general population. In 11,377 women and men aged between 40-99 participating in the population-based Tromsø Study 2015-2016, multivariable linear regression was used to examine associations between total intake of fermented dairy products, intake of yogurt (including regular-fat, low-fat, and semi-solid yogurt), cheese (including regular-fat and low-fat), and liquid fermented dairy, and serum concentrations of total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Dietary data was collected using a validated food frequency questionnaire. Analyses were adjusted for potential confounding factors, and cheese intake analyses were stratified by self-reported use of cholesterol-lowering drugs. Cheese intake was positively associated with HDL-C [regression coefficient 0.02 mmol/l (95 % CI 0.01, 0.03)], and inversely associated with LDL-C [regression coefficient-0.03 mmol/l (95 % CI-0.04,-0.01)] and triglycerides [relative change -1.34 % (95 % CI: -2.29 %, -0.37 %)] per 25 g/day among non-users of cholesterol-lowering drugs, while no associations were found among users. Total intake of fermented dairy was inversely associated with triglycerides [relative change -1.11 % (95 % CI: -1.96 %, -0.24 %)] per 250 g/day, while no associations were found for yogurt intake. Intake of low-fat cheese was more favorably associated with blood lipids compared to regular-fat cheese, and semi-solid yogurt was inversely associated with LDL-C and triglycerides, while intake of liquid fermented dairy was not associated with any of the blood lipids. This study highlights the importance of investigating specific types of dairy products separately, based on fat content and dairy matrix, when examining effects on blood lipid concentrations, and stratifying statistical models by use of cholesterol-lowering drugs when relevant.
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http://dx.doi.org/10.3389/fnut.2021.773468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8646841PMC
November 2021

Drug-eluting versus bare metal stents in saphenous vein grafts compared to native coronary vessels. The NORSTENT study.

Cardiology 2021 Dec 8. Epub 2021 Dec 8.

Background: Drug-eluting stents (DES) reduce target lesion revascularization (TLR) with no effect on mortality or myocardial infarction (MI) compared to bare metal stents (BMS) in native vessels. Randomized stent studies in saphenous vein grafts (SVG) are few and the reported effects are ambiguous. The NORSTENT study is the first to randomize lesions to percutaneous coronary intervention (PCI) in native vessels and SVG.

Aims: To compare rate of mortality, MI and TLR across stent and vessel types.

Methods: In this substudy 6087 patients with a single lesion in native vessels and 164 in SVG, were followed for 5 years.

Results: MI was more frequent in SVG (subdistributional hazard ratio (SHR) 4.95 (3.75 - 6.54, p<0.001), but not affected by stent type. In the first 500 days DES reduced TLR in native vessels (SHR 0.21 ( 0.15 - 0.30)p<0.001) and SVG (SHR 0.18 (0.04 - 0.80) p=0.02). Thereafter DES and BMS were equivalent in native vessels, but DES had a higher TLR rate than BMS in SVG (SHR 3.31 (1.23 - 8.94) p=0.02). After 5 years the TLR rate was still significantly lower for DES in native vessels (3.2 % versus 7.8 %, p<0.001) but not in SVG (21.4 % vs 18. 4%).

Conclusion: In SVG no difference in TLR between DES and BMS was observed after 5 years in contrast to persistent benefit in native vessels. The high rate of TLR and myocardial infarction in SVG makes treatment of native vessels a preference whenever feasible and better treatment options for SVG are warranted.  .
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http://dx.doi.org/10.1159/000521085DOI Listing
December 2021

Association of glycated hemoglobin A levels with cardiovascular outcomes in the general population: results from the BiomarCaRE (Biomarker for Cardiovascular Risk Assessment in Europe) consortium.

Cardiovasc Diabetol 2021 11 15;20(1):223. Epub 2021 Nov 15.

German Research Center for Environmental Health, Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany.

Background: Biomarkers may contribute to improved cardiovascular risk estimation. Glycated hemoglobin A (HbA) is used to monitor the quality of diabetes treatment. Its strength of association with cardiovascular outcomes in the general population remains uncertain. This study aims to assess the association of HbA with cardiovascular outcomes in the general population.

Methods: Data from six prospective population-based cohort studies across Europe comprising 36,180 participants were analyzed. HbA was evaluated in conjunction with classical cardiovascular risk factors (CVRFs) for association with cardiovascular mortality, cardiovascular disease (CVD) incidence, and overall mortality in subjects without diabetes (N = 32,496) and with diabetes (N = 3684).

Results: Kaplan-Meier curves showed higher event rates with increasing HbA levels (log-rank-test: p < 0.001). Cox regression analysis revealed significant associations between HbA (in mmol/mol) in the total study population and the examined outcomes. Thus, a hazard ratio (HR) of 1.16 (95% confidence interval (CI) 1.02-1.31, p = 0.02) for cardiovascular mortality, 1.13 (95% CI 1.03-1.24, p = 0.01) for CVD incidence, and 1.09 (95% CI 1.02-1.17, p = 0.01) for overall mortality was observed per 10 mmol/mol increase in HbA. The association with CVD incidence and overall mortality was also observed in study participants without diabetes with increased HbA levels (HR 1.12; 95% CI 1.01-1.25, p = 0.04) and HR 1.10; 95% CI 1.01-1.20, p = 0.02) respectively. HbA cut-off values of 39.9 mmol/mol (5.8%), 36.6 mmol/mol (5.5%), and 38.8 mmol/mol (5.7%) for cardiovascular mortality, CVD incidence, and overall mortality, showed also an increased risk.

Conclusions: HbA is independently associated with cardiovascular mortality, overall mortality and cardiovascular disease in the general European population. A mostly monotonically increasing relationship was observed between HbA levels and outcomes. Elevated HbA levels were associated with cardiovascular disease incidence and overall mortality in participants without diabetes underlining the importance of HbA levels in the overall population.
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http://dx.doi.org/10.1186/s12933-021-01413-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8594211PMC
November 2021

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

Stroke 2021 Nov 10:STROKEAHA121034782. Epub 2021 Nov 10.

Department of Neurosurgery, University of Helsinki and Helsinki University Hospital, Finland (I.R., M.K.).

Background And Purpose: 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], =0.004 between low BMI and smoking and 1.76 [0.98-3.13], =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.
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http://dx.doi.org/10.1161/STROKEAHA.121.034782DOI Listing
November 2021

Low Pain Tolerance Is Associated With Coronary Angiography, Coronary Artery Disease, and Mortality: The Tromsø Study.

J Am Heart Assoc 2021 11 3;10(22):e021291. Epub 2021 Nov 3.

Cardiovascular Research Group Department of Clinical Medicine UiT The Arctic University of Norway Tromsø Norway.

Background The initial presentation to coronary angiography and extent of coronary artery disease (CAD) vary greatly among patients, from ischemia with no obstructive CAD to myocardial infarction with 3-vessel disease. Pain tolerance has been suggested as a potential mechanism for the variation in presentation of CAD. We aimed to investigate the association between pain tolerance, coronary angiography, CAD, and death. Methods and Results We identified 9576 participants in the Tromsø Study (2007-2008) who completed the cold-pressor pain test, and had no prior history of CAD. The median follow-up time was 10.4 years. We applied Cox-regression models with age as time-scale to calculate hazard ratios (HR). More women than men aborted the cold pressor test (39% versus 23%). Participants with low pain tolerance had 19% increased risk of coronary angiography (HR, 1.19 [95% CI, 1.03-1.38]) and 22% increased risk of obstructive CAD (HR, 1.22 [95% CI, 1.01-1.47]) adjusted by age as time-scale and sex. Among women who underwent coronary angiography, low pain tolerance was associated with 54% increased risk of obstructive CAD (HR, 1.54 [95% CI, 1.09-2.18]) compared with high pain tolerance. There was no association between pain tolerance and nonobstructive CAD or clinical presentation to coronary angiography (ie, stable angina, unstable angina, and myocardial infarction). Participants with low pain tolerance had increased risk of mortality after adjustment for CAD and cardiovascular risk factors (HR, 1.40 [95% CI, 1.19-1.64]). Conclusions Low cold pressor pain tolerance is associated with a higher risk of coronary angiography and death.
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http://dx.doi.org/10.1161/JAHA.121.021291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8751909PMC
November 2021

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

Eur Urol Open Sci 2021 Oct 15;32:19-27. Epub 2021 Aug 15.

The Cancer Clinic, St. Olavs Hospital, Trondheim, Norway.

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 ( = 84) did not influence the risk of VTE (VTE incidence with or without prophylaxis 13% vs 8%,  = 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%,  < 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.
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http://dx.doi.org/10.1016/j.euros.2021.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505199PMC
October 2021

Drug-Eluting or Bare-Metal Stents for Left Anterior Descending or Left Main Coronary Artery Revascularization.

J Am Heart Assoc 2021 10 8;10(20):e018828. Epub 2021 Oct 8.

Department of Cardiology Bern University HospitalUniversity of Bern Switzerland.

Background New-generation drug-eluting stents (DES) reduce target-vessel revascularization compared with bare-metal stents (BMS), and recent data suggest that DES have the potential to decrease the risk of myocardial infarction and cardiovascular mortality. We evaluated the treatment effect of DES versus BMS according to the target artery (left anterior descending [LAD] and/or left main [LM] versus other territories [no-LAD/LM]). Methods and Results The Coronary Stent Trialist (CST) Collaboration gathered individual patient data of randomized trials of DES versus BMS for the treatment of coronary artery disease. The primary outcome was the composite of cardiac death or myocardial infarction. Hazard ratios (HRs) with 95% CIs were derived from a 1-stage individual patient data meta-analysis. We included 26 024 patients across 19 trials: 13 650 (52.4%) in the LAD/LM and 12 373 (47.6%) in the no-LAD/LM group. At 6-year follow-up, there was strong evidence that the treatment effect of DES versus BMS depended on the target vessel (-interaction=0.024). Compared with BMS, DES reduced the risk of cardiac death or myocardial infarction to a greater extent in the LAD/LM (HR, 0.76; 95% CI, 0.68-0.85) than in the no-LAD/LM territories (HR, 0.93; 95% CI, 0.83-1.05). This benefit was driven by a lower risk of cardiac death (HR, 0.83; 95% CI, 0.70-0.98) and myocardial infarction (HR, 0.74; 95% CI, 0.65-0.85) in patients with LAD/LM disease randomized to DES. An interaction (=0.004) was also found for all-cause mortality with patients with LAD/LM disease deriving benefit from DES (HR, 0.86; 95% CI, 0.76-0.97). Conclusions As compared with BMS, new-generation DES were associated with sustained reduction in the composite of cardiac death or myocardial infarction if used for the treatment of LAD or left main coronary stenoses. Registration URL: https://www.crd.york.ac.uk/PROSPERO; Unique identifier: CRD42017060520.
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http://dx.doi.org/10.1161/JAHA.120.018828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8751874PMC
October 2021

Longitudinal changes in concentrations of persistent organic pollutants (1986-2016) and their associations with type 2 diabetes mellitus.

Environ Res 2022 03 28;204(Pt B):112129. Epub 2021 Sep 28.

Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, NO-9037, Tromsø, Norway. Electronic address:

Background: Positive associations have been reported between persistent organic pollutants (POPs) and type 2 diabetes mellitus (T2DM); however, causality has not been established. Over the last decades, environmental exposure to legacy POPs has decreased, complicating epidemiological studies. In addition, physiological risk factors for T2DM may also influence POP concentrations, contributing to a complex network of factors that could impact associations with T2DM. Longitudinal studies on this topic are lacking, and few have assessed prospective and cross-sectional associations between repeated POP measurements and T2DM in the same individuals, which may shed light on causality.

Objectives: To compare longitudinal trends in concentrations of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in T2DM cases and controls, and to examine prospective and cross-sectional associations between PCBs, OCPs and T2DM at different time-points before and after T2DM diagnosis in cases.

Methods: We conducted a longitudinal, nested case-control study (1986-2016) of 116 T2DM cases and 139 controls from the Tromsø Study. All participants had three blood samples collected before T2DM diagnosis in cases, and up to two samples thereafter. We used linear mixed-effect models to assess temporal changes of POPs within and between T2DM cases and controls, and logistic regression models to investigate the associations between different POPs and T2DM at different time-points.

Results: PCBs, trans-nonachlor, cis-nonachlor, oxychlordane, cis-heptachlor epoxide, p,p'-DDE, and p,p'-DDT declined more slowly in cases than controls, whereas β-HCH and HCB declined similarly in both groups. Most POPs showed positive associations between both pre- and post-diagnostic concentrations and T2DM, though effect estimates were imprecise. These associations were most consistent for cis-heptachlor epoxide.

Discussion: The observed positive associations between certain POPs and T2DM may be because of higher POP concentrations within prospective T2DM cases, due to slower temporal declines as compared to controls.
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http://dx.doi.org/10.1016/j.envres.2021.112129DOI Listing
March 2022

Secular and longitudinal trends in body composition: The Tromsø Study, 2001 to 2016.

Obesity (Silver Spring) 2021 11 14;29(11):1939-1949. Epub 2021 Sep 14.

Department of Community Medicine, UiT - The Arctic University of Norway, Tromsø, Norway.

Objective: Overweight, defined as excessive fat mass, is a long-standing worldwide public health challenge. Traditional anthropometric measures used to identify overweight and obesity do not assess body composition. The aim of this study was to examine population trends in general and abdominal fat mass during the past two decades.

Methods: This study included participants from one or more consecutive surveys of the population-based Tromsø Study, including Tromsø 5 (conducted in 2001, n = 1,662, age 40-84 years), Tromsø 6 (2007-2008, n = 901, age 40-88 years), and Tromsø 7 (2015-2016, n = 3,670, age 40-87 years), with total body dual-energy x-ray absorptiometry scans. Trends in total fat and visceral adipose tissue (VAT) were analyzed by generalized estimation equation models in strata of sex and age groups.

Results: Total fat and VAT mass increased during 2001 to 2016, with a larger increase during 2007 to 2016 than from 2001 to 2007 and among the youngest age group (40-49 years), particularly in women. Women had higher total fat mass than men, whereas men had higher VAT mass than women.

Conclusions: General and abdominal dual-energy x-ray absorptiometry-derived fat mass increased during the past two decades in this general population. Of particular concern is the more pronounced increase in the past decade and in the younger age groups.
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http://dx.doi.org/10.1002/oby.23267DOI Listing
November 2021

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

Stroke 2021 12 9;52(12):3883-3890. Epub 2021 Sep 9.

Department of Clinical Medicine (M.C., S.H.J., L.-H.J., E.B.M.), UiT The Arctic University of Norway, Tromsø.

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%; <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.
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http://dx.doi.org/10.1161/STROKEAHA.120.032750DOI Listing
December 2021

Change in cardiovascular risk assessment tool and updated Norwegian guidelines for cardiovascular disease in primary prevention increase the population proportion at risk: the Tromsø Study 2015-2016.

Open Heart 2021 08;8(2)

Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.

Aims: To compare the population proportion at high risk of cardiovascular disease (CVD) using the Norwegian NORRISK 1 that predicts 10-year risk of CVD mortality and the Norwegian national guidelines from 2009, with the updated NORRISK 2 that predicts 10-year risk of both fatal and non-fatal risk of CVD and the Norwegian national guidelines from 2017.

Methods: We included participants from the Norwegian population-based Tromsø Study (2015-2016) aged 40-69 years without a history of CVD (n=16 566). The total proportion eligible for intervention was identified by NORRISK 1 and the 2009 guidelines (serum total cholesterol ≥8 mmol/L, systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg) and NORRISK 2 and the 2017 guidelines (serum total cholesterol ≥7 mmol/L, low density lipoprotein (LDL) cholesterol ≥5 mmol/L, systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg).

Results: The total proportion at high risk as defined by a risk score was 12.0% using NORRISK 1 and 9.8% using NORRISK 2. When including single risk factors specified by the guidelines, the total proportion eligible for intervention was 15.5% using NORRISK 1 and the 2009 guidelines and 18.9% using NORRISK 2 and the 2017 guidelines. The lowered threshold for total cholesterol and specified cut-off for LDL cholesterol stand for a large proportion of the increase in population at risk.

Conclusion: The population proportion eligible for intervention increased by 3.4 percentage points from 2009 to 2017 using the revised NORRISK 2 score and guidelines.
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http://dx.doi.org/10.1136/openhrt-2021-001777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407203PMC
August 2021

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

J Clin Oncol 2021 11 13;39(32):3561-3573. Epub 2021 Aug 13.

Department of Oncology, University Hospital of North Norway, Tromsø, Norway.

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.
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http://dx.doi.org/10.1200/JCO.21.00637DOI Listing
November 2021

Validating Acute Myocardial Infarction Diagnoses in National Health Registers for Use as Endpoint in Research: The Tromsø Study.

Clin Epidemiol 2021 3;13:675-682. Epub 2021 Aug 3.

Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.

Purpose: To assess whether acute myocardial infarction (MI) diagnoses in national health registers are sufficiently correct and complete to replace manual collection of endpoint data for a population-based, epidemiological study.

Patients And Methods: Using the Tromsø Study Cardiovascular Disease Register for 2013-2014 as gold standard, we calculated correctness (defined as positive predictive value (PPV)) and completeness (defined as sensitivity) of MI cases in the Norwegian Myocardial Infarction Register and the Norwegian Patient Register separately and in combination. We calculated the sensitivity and PPV with 95% confidence intervals using the Clopper-Pearson Exact test.

Results: We identified 153 MI cases in the gold standard. In the Norwegian Myocardial Infarction Register, we found a PPV of 97.1% (95% confidence interval (CI) 92.8-99.2) and a sensitivity of 88.2% (95% CI 82.0-92.9). In the Norwegian Patient Register, the PPV was 96.3% (95% CI 91.6-98.8) and the sensitivity was 85.6% (95% CI 79.0-90.8). The combined dataset of the Norwegian Myocardial Infarction Register and the Norwegian Patient Register had a PPV of 96.6% (95% CI 92.1-98.9) and a sensitivity of 91.5% (95% CI 85.9-95.4).

Conclusion: MI diagnoses in both the Norwegian Myocardial Infarction Register and the Norwegian Patient Register were highly correct and complete, and each of the registers could be considered as endpoint sources for the Tromsø Study. A combination of the two national registers seemed, however, to represent the most comprehensive data source overall. The benefits of using data from national registers as endpoints in epidemiological studies include faster, less resource-intensive access to nationwide data and considerably lower loss to follow-up, compared to manual data collection in a limited geographical area.
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http://dx.doi.org/10.2147/CLEP.S321293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349192PMC
August 2021

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

Open Heart 2021 07;8(2)

Department of Cardiology, University Heart and Vascular Center Hamburg, Hamburg, Germany.

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.
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http://dx.doi.org/10.1136/openhrt-2021-001624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330568PMC
July 2021

Data from national health registers as endpoints for the Tromsø Study: Correctness and completeness of stroke diagnoses.

Scand J Public Health 2021 Jun 14:14034948211021191. Epub 2021 Jun 14.

UiT The Arctic University of Norway, Tromsø, Norway.

Aim: To assess whether stroke diagnoses in national health registers are sufficiently correct and complete to replace manual collection of endpoint data for the Tromsø Study, a population-based epidemiological study.

Method: Using the Tromsø Study Cardiovascular Disease Register for 2013-2014 as the gold standard, we calculated correctness (defined as positive predictive value, PPV) and completeness (defined as sensitivity) of stroke cases in four different data subsets derived from the Norwegian Patient Register and the Norwegian Stroke Register. We calculated the sensitivity and PPV with 95% confidence intervals (CIs) assuming a normal approximation of the binomial distribution.

Results: In the Norwegian Stroke Register we found a sensitivity of 79.8% (95% CI 74.2-85.4) and a PPV of 97.5% (95% CI 95.1-99.9). In the Norwegian Patient Register the sensitivity was 86.4% (95% CI 81.6-91.1) and the PPV was 84.2% (95% CI 79.2-89.2). The overall highest levels were found in a subset based on a linkage between the Norwegian Stroke Register and the Norwegian Patient Register, with a sensitivity of 88.9% (95% CI 84.5-93.3), and a PPV of 89.3% (95% CI 85.0-93.6).

Conclusions: Data from the Norwegian Patient Register and from the linked data set between the Norwegian Patient Register and the Norwegian Stroke Register had acceptable levels of correctness and completeness to be considered as endpoint sources for the Tromsø Study Cardiovascular Disease Register. The benefits of using data from national registers as endpoints in epidemiological studies must be weighed against the impact of potentially decreased data quality.
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http://dx.doi.org/10.1177/14034948211021191DOI Listing
June 2021

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

Open Heart 2021 06;8(1)

Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.

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.
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http://dx.doi.org/10.1136/openhrt-2020-001457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174503PMC
June 2021

The trans-ancestral genomic architecture of glycemic traits.

Nat Genet 2021 06 31;53(6):840-860. Epub 2021 May 31.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
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http://dx.doi.org/10.1038/s41588-021-00852-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958PMC
June 2021

The bidirectional associations between leisure time physical activity change and body mass index gain. The Tromsø Study 1974-2016.

Int J Obes (Lond) 2021 08 18;45(8):1830-1843. Epub 2021 May 18.

School of Sport Sciences, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway.

Objectives: To examine whether leisure time physical activity changes predict subsequent body mass index (BMI) changes, and conversely, whether BMI changes predict subsequent leisure time physical activity changes.

Methods: This prospective cohort study included adults attending ≥3 consecutive Tromsø Study surveys (time: T1, T2, T3) during 1974-2016 (n = 10779). If participants attended >3 surveys, we used the three most recent surveys. We computed physical activity change (assessed by the Saltin-Grimby Physical Activity Level Scale) from T1 to T2, categorized as Persistently Inactive (n = 992), Persistently Active (n = 7314), Active to Inactive (n = 1167) and Inactive to Active (n = 1306). We computed BMI change from T2 to T3, which regressed on preceding physical activity changes using analyses of covariance. The reverse association (BMI change from T1 to T2 and physical activity change from T2 to T3; n = 4385) was assessed using multinomial regression.

Results: Average BMI increase was 0.86 kg/m (95% CI: 0.82-0.90) from T2 to T3. With adjustment for sex, birth year, education, smoking and BMI at T2, there was no association between physical activity change from T1 to T2 and BMI change from T2 to T3 (Persistently Inactive: 0.89 kg/m (95% CI: 0.77-1.00), Persistently Active: 0.85 kg/m (95% CI: 0.81-0.89), Active to Inactive: 0.90 kg/m (95% CI: 0.79-1.00), Inactive to Active 0.85 kg/m (95% CI: 0.75-0.95), p = 0.84). Conversely, increasing BMI was associated with Persistently Inactive (odds ratio (OR): 1.17, 95% CI: 1.08-1.27, p < 0.001) and changing from Active to Inactive (OR: 1.16, 95% CI: 1.07-1.25, p < 0.001) compared with being Persistently Active.

Conclusions: We found no association between leisure time physical activity changes and subsequent BMI changes, whereas BMI change predicted subsequent physical activity change. These findings indicate that BMI change predicts subsequent physical activity change at population level and not vice versa.
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http://dx.doi.org/10.1038/s41366-021-00853-yDOI Listing
August 2021

Sex-Specific Associations between Blood Pressure and Risk of Atrial Fibrillation Subtypes in the Tromsø Study.

J Clin Med 2021 Apr 5;10(7). Epub 2021 Apr 5.

Department of Community Medicine, UiT The Arctic University of Norway, 9019 Tromsø, Norway.

The aim of this study was to explore sex-specific associations between systolic blood pressure (SBP), hypertension, and the risk of incident atrial fibrillation (AF) subtypes, including paroxysmal, persistent, and permanent AF, in a general population. A total of 13,137 women and 11,667 men who participated in the fourth survey of the Tromsø Study (1994-1995) were followed up for incident AF until the end of 2016. Cox proportional hazards regression analysis was conducted using fractional polynomials for SBP to provide sex- and AF-subtype-specific hazard ratios (HRs) for SBP. An SBP of 120 mmHg was used as the reference. Models were adjusted for other cardiovascular risk factors. Over a mean follow-up of 17.6 ± 6.6 years, incident AF occurred in 914 (7.0%) women (501 with paroxysmal/persistent AF and 413 with permanent AF) and 1104 (9.5%) men (606 with paroxysmal/persistent AF and 498 with permanent AF). In women, an SBP of 180 mmHg was associated with an HR of 2.10 (95% confidence interval [CI] 1.60-2.76) for paroxysmal/persistent AF and an HR of 1.80 (95% CI 1.33-2.44) for permanent AF. In men, an SBP of 180 mmHg was associated with an HR of 1.90 (95% CI 1.46-2.46) for paroxysmal/persistent AF, while there was no association with the risk of permanent AF. In conclusion, increasing SBP was associated with an increased risk of both paroxysmal/persistent AF and permanent AF in women, but only paroxysmal/persistent AF in men. Our findings highlight the importance of sex-specific risk stratification and optimizing blood pressure management for the prevention of AF subtypes in clinical practice.
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http://dx.doi.org/10.3390/jcm10071514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038622PMC
April 2021

Prevalent diabetes and risk of total, colorectal, prostate and breast cancers in an ageing population: meta-analysis of individual participant data from cohorts of the CHANCES consortium.

Br J Cancer 2021 05 26;124(11):1882-1890. Epub 2021 Mar 26.

International Agency for Research on Cancer (IARC/WHO), Nutrition and Metabolism Branch, Lyon, France.

Background: We investigated whether associations between prevalent diabetes and cancer risk are pertinent to older adults and whether associations differ across subgroups of age, body weight status or levels of physical activity.

Methods: We harmonised data from seven prospective cohort studies of older individuals in Europe and the United States participating in the CHANCES consortium. Cox proportional hazard regression was used to estimate the associations of prevalent diabetes with cancer risk (all cancers combined, and for colorectum, prostate and breast). We calculated summary risk estimates across cohorts using pooled analysis and random-effects meta-analysis.

Results: A total of 667,916 individuals were included with an overall median (P25-P75) age at recruitment of 62.3 (57-67) years. During a median follow-up time of 10.5 years, 114,404 total cancer cases were ascertained. Diabetes was not associated with the risk of all cancers combined (hazard ratio (HR) = 0.94; 95% confidence interval (CI): 0.86-1.04; I = 63.3%). Diabetes was positively associated with colorectal cancer risk in men (HR = 1.17; 95% CI: 1.08-1.26; I = 0%) and a similar HR in women (1.13; 95% CI: 0.82-1.56; I = 46%), but with a confidence interval including the null. Diabetes was inversely associated with prostate cancer risk (HR = 0.81; 95% CI: 0.77-0.85; I = 0%), but not with postmenopausal breast cancer (HR = 0.96; 95% CI: 0.89-1.03; I = 0%). In exploratory subgroup analyses, diabetes was inversely associated with prostate cancer risk only in men with overweight or obesity.

Conclusions: Prevalent diabetes was positively associated with colorectal cancer risk and inversely associated with prostate cancer risk in older Europeans and Americans.
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http://dx.doi.org/10.1038/s41416-021-01347-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144608PMC
May 2021

Is the ongoing obesity epidemic partly explained by concurrent decline in cigarette smoking? Insights from a longitudinal population study. The Tromsø Study 1994-2016.

Prev Med 2021 06 23;147:106533. Epub 2021 Mar 23.

Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway.

The increase of obesity coincides with a substantial decrease in cigarette smoking. We assessed post-cessation weight change and its contribution to the obesity epidemic in a general population in Norway. A total of 14,453 participants (52.6% women), aged 25-54 years in 1994, who attended at least two of four surveys in the Tromsø Study between 1994 and 2016, were included in the analysis. Hereof 77% participated in both the first and the last survey. Temporal trends in mean body mass index (BMI), prevalence of obesity (BMI ≥ 30 kg/m) and daily smoking were estimated with generalized estimation equations. We assessed BMI change by smoking status (ex-smoker, quitter, never smoker, daily smoker), and also under a scenario where none quit smoking. In total, the prevalence of daily smoking was reduced over the 21 years between Tromsø 4 (1994-1995) and Tromsø 7 (2015-2016) by 22 percentage points. Prevalence of obesity increased from 5 - 12% in 1994-1995 to 21-26% in 2015-2016, where obesity in the youngest (age 25-44 in 1994) increased more than in the oldest (p < 0.0001). Those who quit smoking had a larger BMI gain compared to the other three smoking subgroups over the 21 years (p < 0.0001). The scenario where none quit smoking would imply a 13% reduction in BMI gain in the population, though substantial age-related differences were noted. We conclude that smoking cessation contributed to the increase in obesity in the population, but was probably not the most important factor. Public health interventions should continue to target smoking cessation, and also target obesity prevention.
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http://dx.doi.org/10.1016/j.ypmed.2021.106533DOI Listing
June 2021

Trends in known and undiagnosed diabetes, HbA1c levels, cardiometabolic risk factors and diabetes treatment target achievement in repeated cross-sectional surveys: the population-based Tromsø Study 1994-2016.

BMJ Open 2021 03 23;11(3):e041846. Epub 2021 Mar 23.

Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.

Objectives: The aim of this study was to investigate time trends in known and undiagnosed diabetes, glycated haemoglobin (HbA1c) levels and other cardiometabolic risk factors in the general population as well as treatment target achievement among those with diabetes.

Design And Setting: Repeated cross-sectional surveys in the population-based Tromsø Study.

Methods: We used age-adjusted generalised estimating equation models to study trends in self-reported and undiagnosed (HbA1c ≥6.5%) diabetes, cardiometabolic risk factors and the metabolic syndrome in 27 281 women and men aged 40-84 years examined in up to four surveys of the Tromsø Study between 1994 and 2016. Further, we analysed trends in diabetes treatment target achievement.

Results: During 1994-2016, diabetes prevalence increased in women (2.3% to 4.6%) and men (2.4% to 5.8%) and in all age groups, while the proportion of undiagnosed diabetes in women (32% to 17%) and men (37% to 24%) decreased. Blood pressure and total cholesterol decreased, while waist circumference increased in participants with and without diabetes, leading to a relatively stable prevalence of the metabolic syndrome throughout the study period. There was a marginal increase in HbA1c levels among participants without diabetes. Only half of those with diabetes achieved the treatment target of HbA1c ≤7.0%.

Conclusion: In the last two decades, diabetes prevalence increased, while the proportion of undiagnosed diabetes declined. The prevalence of the metabolic syndrome remained stable throughout, driven by opposing trends with an increase in obesity and a decrease in other cardiometabolic risk factors. HbA1c treatment target achievement did not improve.
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http://dx.doi.org/10.1136/bmjopen-2020-041846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993331PMC
March 2021

Analyses of Increased Mortality in New and Known Diabetes in Patients with Coronary Disease Enrolled in the NORSTENT Randomized Study.

Cardiology 2021 10;146(3):295-303. Epub 2021 Mar 10.

Clinic of Cardiology, St. Olavs University Hospital, and Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.

Background: NORSTENT trial randomized 9,013 patients to percutaneous coronary intervention with drug-eluting stents (DES) or bare-metal stents (BMS) with a 5-year follow-up. Among the patients, 5,512 had measured either fasting glucose level or percent glycated hemoglobin (HbA1c) at the index procedure. That cohort constitutes the present study population analyzing mortality and evaluating treatment heterogeneity of randomized stent in diabetic versus nondiabetic subgroups.

Results: The cohort consisted of 4,174 (75.7%) patients without diabetes, 716 (13.0%) with known diabetes, and 622 (11.3%) with no diabetes in history but elevated fasting glucose level >7.0 mmol/L or HbA1c >6.5% and therefore defined as new diabetes. Patients with known diabetes had a significantly increased all-cause (hazard ratio [HR] 1.99, 95% CI 1.51-2.62, p < 0.001), cardiac (subhazard ratio [SHR] 2.47, 95% CI 1.55-3.93, p < 0.001), and noncardiac (SHR 1.74, 95% CI 1.23-2.44, p = 0.002) mortality after adjustment for baseline variables. In the follow-up of 5 years, patients with new diabetes, however, had a marginally increased all-cause (HR 1.40, 95% CI 1.01-1.93, p = 0.043) and significantly increased noncardiac mortality (SHR 1.52, 95% CI 1.06-2.20, p = 0.025), but no increase in cardiac mortality (SHR 1.06, 95% CI 0.53-2.12, p = 0.86) after the same adjustment. The majority of the mortality was cardiac in the first 1-2 years after intervention; thereafter, noncardiac mortality dominated. However, the time period for when noncardiac mortality became the dominating cause varied considerably and significantly between the groups. There was no heterogeneity in mortality in response to randomized stent between diabetics and nondiabetics.

Conclusion: Known diabetes has increased cardiac and noncardiac mortality in contrast to new diabetes which is only associated with increased noncardiac mortality during the 5-year follow-up. Diabetic and nondiabetic patients have the same response to the treatment with BMS or DES.
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http://dx.doi.org/10.1159/000513514DOI Listing
August 2021

What factors explain the much higher diabetes prevalence in Russia compared with Norway? Major sex differences in the contribution of adiposity.

BMJ Open Diabetes Res Care 2021 03;9(1)

Department of Community Medicine, UiT The Arctic University of Norway, Tromso, Norway.

Introduction: Compared with many other countries Russia has a high prevalence of diabetes in men and women. However, contrary to what is found in most other populations, the risk is greater among women than men. The reasons for this are unclear.

Research Design And Methods: Prevalence and risk factors for diabetes at ages 40-69 years were compared in two population-based studies: Know Your Heart (KYH) (Russia, 2015-2018, n=4121) and the seventh wave of the Tromsø Study (Tromsø 7) (Norway, 2015-2016, n=17 649). Diabetes was defined by the level of glycated hemoglobin and/or self-reported diabetes and/or diabetes medication use. Marginal structural models were used to estimate the role of key risk factors for diabetes in differences between the studies.

Results: Age-standardized prevalence of diabetes was higher in KYH compared with Tromsø 7 in men (11.6% vs 6.2%) and in women (13.2% vs 4.3%). Age-adjusted ORs for diabetes in KYH compared with Tromsø 7 were 2.01 (95% CI 1.68 to 2.40) for men and 3.66 (95% CI 3.13 to 4.26) for women. Adiposity (body mass index and waist circumference) explained none of this effect for men but explained 46.0% (39.6, 53.8) for women. Addition of smoking and C reactive protein, as further mediators, slightly increased the percentage explained of the difference between studies to 55.5% (46.5, 66.0) for women but only to 9.9% (-0.6, 20.8) for men.

Conclusions: Adiposity is a key modifiable risk factor that appears to explain half of the almost threefold higher female prevalence of diabetes in Russia compared with Norway, but none of the twofold male difference.
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http://dx.doi.org/10.1136/bmjdrc-2020-002021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934764PMC
March 2021

Incidence and risk factors for major bleeding among patients undergoing percutaneous coronary intervention: Findings from the Norwegian Coronary Stent Trial (NORSTENT).

PLoS One 2021 4;16(3):e0247358. Epub 2021 Mar 4.

Clinic for Heart Disease, St. Olav's University Hospital, Trondheim, Norway.

Introduction: Bleeding is a concern after percutaneous coronary intervention (PCI) and subsequent dual antiplatelet therapy (DAPT). We herein report the incidence and risk factors for major bleeding in the Norwegian Coronary Stent Trial (NORSTENT).

Materials And Methods: NORSTENT was a randomized, double blind, pragmatic trial among patients with acute coronary syndrome or stable coronary disease undergoing PCI during 2008-11. The patients (N = 9,013) were randomized to receive either a drug-eluting stent or a bare-metal stent, and were treated with at least nine months of DAPT. The patients were followed for a median of five years, with Bleeding Academic Research Consortium (BARC) 3-5 major bleeding as one of the safety endpoints. We estimated cumulative incidence of major bleeding by a competing risks model and risk factors through cause-specific Cox models.

Results: The 12-month cumulative incidence of major bleeding was 2.3%. Independent risk factors for major bleeding were chronic kidney disease, low bodyweight (< 60 kilograms), diabetes mellitus, and advanced age (> 80 years). A myocardial infarction (MI) or PCI during follow-up increased the risk of major bleeding (HR = 1.67, 95% CI 1-29-2.15).

Conclusions: The 12-month cumulative incidence of major bleeding in NORSTENT was higher than reported in previous, explanatory trials. This analysis strengthens the role of chronic kidney disease, advanced age, and low bodyweight as risk factors for major bleeding among patients receiving DAPT after PCI. The presence of diabetes mellitus or recurrent MI among patients is furthermore a signal of increased bleeding risk.

Clinical Trial Registration: Unique identifier NCT00811772; http://www.clinicaltrial.gov.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247358PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932162PMC
August 2021

Tenecteplase in wake-up ischemic stroke trial: Protocol for a randomized-controlled trial.

Int J Stroke 2021 10 14;16(8):990-994. Epub 2021 Jan 14.

Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.

Background: Patients with wake-up ischemic stroke who have evidence of salvageable tissue on advanced imaging can benefit from intravenous thrombolysis. It is not known whether patients who do not fulfil such imaging criteria might benefit from treatment, but studies indicate that treatment based on non-contrast CT criteria may be safe. Tenecteplase has shown promising results in patients with acute ischemic stroke. The aim of the Tenecteplase in Wake-up Ischemic Stroke Trial (TWIST) is to compare the effect of thrombolytic treatment with tenecteplase and standard care versus standard care alone in patients with wake-up ischemic stroke selected by non-contrast CT.

Methods/design: TWIST is an international, investigator-initiated, multi-centre, prospective, randomized-controlled, open-label, blinded end-point trial of tenecteplase ( = 300) versus standard care ( = 300) in patients who wake up with an acute ischemic stroke and can be treated within 4.5 h upon awakening. Seventy-seven centres in 10 countries (Denmark, Estonia, Finland, Latvia, Lithuania, New Zealand, Norway, Sweden, Switzerland, and the United Kingdom) participate. The primary outcome is the modified Rankin Scale on the ordinal scale (0-6) at three months.

Discussion: TWIST aims to determine the effect and safety of thrombolytic treatment with tenecteplase in patients with wake-up ischemic stroke selected by non-contrast CT.

Trial Registration: ClinicalTrials.gov NCT03181360. EudraCT Number 2014-000096-80.
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http://dx.doi.org/10.1177/1747493020984073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554491PMC
October 2021

Metachronous Contralateral Testicular Cancer in the Cisplatin Era: A Population-Based Cohort Study.

J Clin Oncol 2021 02 23;39(4):308-318. Epub 2020 Dec 23.

Department of Oncology, University Hospital of North Norway, Tromsø, Norway.

Purpose: It is hypothesized that cisplatin-based chemotherapy (CBCT) reduces the occurrence of metachronous contralateral (second) germ cell testicular cancer (TC). However, studies including treatment details are lacking. The aim of this study was to assess the second TC risk, emphasizing the impact of previous TC treatment.

Patients And Methods: Based on the Cancer Registry of Norway, 5,620 men were diagnosed with first TC between 1980 and 2009. Treatment data regarding TC were retrieved from medical records. Cumulative incidences of second TC were estimated, and standardized incidence ratios were calculated. The effect of treatment intensity was investigated using Cox proportional hazard regression.

Results: Median follow-up was 18.0 years, during which 218 men were diagnosed with a second TC after median 6.2 years. Overall, the 20-year crude cumulative incidence was 4.0% (95% CI, 3.5 to 4.6), with lower incidence after chemotherapy (CT) (3.2%; 95% CI, 2.5 to 4.0) than after surgery only (5.4%; 95% CI, 4.2 to 6.8). The second TC incidence was also lower for those age ≥ 30 years (2.8%; 95% CI, 2.3 to 3.4) at first TC diagnosis than those age < 30 years (6.0%; 95% CI, 5.0 to 7.1). Overall, the second TC risk was 13-fold higher compared with the risk of developing TC in the general male population (standardized incidence ratio, 13.1; 95% CI, 11.5 to 15.0). With surgery only as reference, treatment with CT significantly reduced the second TC risk (hazard ratio [HR], 0.55). For each additional CBCT cycle administered, the second TC risk decreased significantly after three, four, and more than four cycles (HRs, 0.53, 0.41, and 0.21, respectively).

Conclusion: Age at first TC diagnosis and treatment intensity influenced the second TC risk, with significantly reduced risks after more than two CBCT cycles.
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http://dx.doi.org/10.1200/JCO.20.02713DOI Listing
February 2021

Do declines in occupational physical activity contribute to population gains in body mass index? Tromsø Study 1974-2016.

Occup Environ Med 2020 Dec 4. Epub 2020 Dec 4.

School of Sport Sciences, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Troms, Norway.

Objective: To examine whether occupational physical activity changes predict future body mass index (BMI) changes.

Methods: This longitudinal cohort study included adult participants attending ≥3 consecutive Tromsø Study surveys (examinations 1, 2 and 3) from 1974 to 2016 (N=11 308). If a participant attended >3 surveys, the three most recent surveys were included. Occupational physical activity change (assessed by the Saltin-Grimby Physical Activity Level Scale) was computed from the first to the second examination, categorised into persistently inactive (n=3692), persistently active (n=5560), active to inactive (n=741) and inactive to active (n=1315). BMI change was calculated from the second to the third examination (height being fixed at the second examination) and regressed on preceding occupational physical activity changes using analysis of covariance adjusted for sex, birth year, smoking, education and BMI at examination 2.

Results: Overall, BMI increased by 0.84 kg/m (95% CI 0.82 to 0.89). Following adjustments as described previously, we observed no differences in BMI increase between the occupational physical activity change groups (Persistently Inactive: 0.81 kg/m, 95% CI 0.75 to 0.87; Persistently Active: 0.87 kg/m, 95% CI 0.82 to 0.92; Active to Inactive: 0.81 kg/m, 95% CI 0.67 to 0.94; Inactive to Active: 0.91 kg/m, 95% CI 0.81 to 1.01; p=0.25).

Conclusion: We observed no prospective association between occupational physical activity changes and subsequent BMI changes. Our findings do not support the hypothesis that occupational physical activity declines contributed to population BMI gains over the past decades. Public health initiatives aimed at weight gain prevention may have greater success if focusing on other aspects than occupational physical activity.
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http://dx.doi.org/10.1136/oemed-2020-106874DOI Listing
December 2020

Physical activity and cold pain tolerance in the general population.

Eur J Pain 2021 03 29;25(3):637-650. Epub 2020 Nov 29.

Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway.

Background: The relationship between habitual physical activity (PA) and experimental pain tolerance has been investigated in small samples of young, healthy and/or single-sex volunteers. We used a large, population-based sample to assess this relationship in men and women with and without chronic pain.

Methods: We used data from the sixth and seventh Tromsø Study surveys (2007-2008; 2015-2016), with assessed pain tolerance of participants with the cold pressor test (CPT: dominant hand in circulating cold water at 3°C, maximum test time 106 s), and self-reported total amount of habitual PA in leisure time (n = 19,087), exercise frequency (n = 19,388), exercise intensity (n = 18,393) and exercise duration (n = 18,343). A sub-sample had PA measured by accelerometers (n = 4,922). We used Cox regression to compare CPT tolerance times between self-reported PA levels. For accelerometer-measured PA, we estimated hazard ratios for average daily activity counts, and for average daily minutes of moderate-to-vigorous PA done in bouts lasting 10 min or more. Models were tested for PA-sex, and PA-chronic pain and PA-moderate-to-severe chronic pain interactions.

Results: Leisure-time PA, exercise intensity and exercise duration were positively associated with CPT tolerance (p < .001; p = .011; p < .001). More PA was associated with higher CPT tolerance. At high levels of leisure-time PA and exercise intensity, men had a significantly higher CPT tolerance than women. Accelerometer-measured PA was not associated with CPT tolerance.

Conclusions: This study is one of the first to show that higher self-reported habitual PA was connected to higher experimental pain tolerance in a population-based sample, especially for men. This was not found for accelerometer-measured PA.

Significance: This study finds that higher level of self-reported leisure-time physical activity is associated with increased cold pressor pain tolerance in a large population-based sample. Though present in both sexes, the association is strongest among men. Despite the robust dose-response relationship between pain tolerance and self-reported activity level, no such relationship was found for accelerometer-measured activity, reflecting a possible discrepancy in the aspect of physical activity measured. Though the study design does not permit causal conclusions, the findings suggest that increasing physical activity may increase pain tolerance in the general population.
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http://dx.doi.org/10.1002/ejp.1699DOI Listing
March 2021
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