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Summary Background Thyroid cancer tends to be diagnosed at a younger age (median age 51 years) compared with most other malignancies (such as breast cancer [62 years] or lung cancer [71 years]). The incidence of thyroid cancer is higher in women than men diagnosed from early adolescence. However, few in-utero and early life risk exposures associated with increased risk of thyroid cancer have been identified. Methods In this population-based nested case-control study we used registry data from four Nordic countries to assess thyroid cancer risk in offspring in relation to maternal medical history, pregnancy complications, and birth characteristics. Patient with thyroid cancer (cases) were individuals born and subsequently diagnosed with first primary thyroid cancer from 1973 to 2013 in Denmark, 1987 to 2014 in Finland, 1967 to 2015 in Norway, or 1973 to 2014 in Sweden. Each case was matched with up to ten individuals without thyroid cancer (controls) based on birth year, sex, country, and county of birth. Cases and matched controls with a previous diagnosis of any cancer, other than non-melanoma skin cancer, at the time of thyroid cancer diagnosis were excluded. Cases and matched controls had to reside in the country of birth at the time of thyroid cancer diagnosis. Conditional logistic regression models were used to calculate odds ratios (ORs) with 95% CIs. Results Of the 2437 cases, 1967 (81·4%) had papillary carcinomas, 1880 (77·1%) were women, and 1384 (56·7%) were diagnosed before age 30 years (range 0–48). Higher birth weight (OR per kg 1·14 [95% CI 1·05–1·23]) and congenital hypothyroidism (4·55 [1·58–13·08]); maternal diabetes before pregnancy (OR 1·69 [0·98–2·93]) and postpartum haemorrhage (OR 1·28 [1·06–1·55]); and (from registry data in Denmark) maternal hypothyroidism (18·12 [10·52–31·20]), hyperthyroidism (11·91 [6·77–20·94]), goiter (67·36 [39·89–113·76]), and benign thyroid neoplasms (22·50 [6·93–73·06]) were each associated with an increased risk of thyroid cancer in offspring. Interpretation In-utero exposures, particularly those related to maternal thyroid disorders, might have a long-term influence on thyroid cancer risk in offspring. Funding Intramural Research Program of the National Cancer Institute (National Institutes of Health).

Background: As distinct from mentally-active sedentary behaviors (e.g. reading), passive sedentary behaviors (e.g. TV-viewing) have been linked to a higher risk of depression, but the underlying mechanisms are unclear. We examined the potential mediating role of sleep problems in prospective relationships of passive sedentary behaviors with major depressive disorder (MDD). Method: In 1997, 43 863 adults were surveyed and responses linked to clinician diagnoses of MDD until 2010. The questionnaire included items on sedentary behavior and sleep problems (Karolinska Sleep Questionnaire). Cox proportional hazard models and the ‘counterfactual approach’ were used to identify potential mediating effects of sleep problems in the association of passive sedentary behavior and MDD. Results: Of the total sample, 3,065 (7.6%) were excluded for having indications of depression at baseline. Of 33,116 participants with complete data (mean age = 51.3 years, SD = 15.7, 64% female); 472 (1.4%) incident cases of MDD were identified during the 13-year follow-up. In Cox regression analyses, higher durations of passive sedentary behavior (≥3 h/day versus

Objective Regular physical activity (PA) is associated with less self-reported anxiety, but prospective studies linked to clinician diagnoses of anxiety disorder remain scarce. We examined whether the PA levels recommended for general health are related to anxiety symptoms and disorders. Method In total, 43,863 Swedish adults were surveyed in 1997 and responses linked to medical registers until 2010. Weekly durations of habitual moderate and vigorous leisure time PA were self-reported. Cross-sectional and prospective relationships between the total duration (minutes) of PA, 0–149 (‘below’), 150–299 (‘achieve’), and ≥300 min (‘exceed’) with self-reported anxiety symptoms and incident anxiety disorder were explored. Associations were explored using logistic and Cox proportional hazard regression models. Results Of 27,053 participants with complete data (mean age = 49.0 years, SD = 15.9, 66% female), 76% met the recommended duration of PA (≥150 min), and 38% exceeded this duration. At baseline, 2573 participants (9.5%) reported elevated anxiety symptoms. In cross-sectional analyses, engaging in ≥150 min of MVPA/week was associated with 24% (OR = 0.76, 95% CI = 0.68–0.86) lower odds of anxiety symptoms. Exceeding the weekly duration was associated with 36% (OR = 0.64, 95% CI = 0.57–0.72) lower odds. During the 13-year follow-up, 198 incident cases of anxiety disorder (0.8%) were identified. No significant prospective relationships were found. Conclusions Engaging in leisure time PA at levels recommended for general health may reduce the risk of elevated anxiety symptoms. As the incidence of anxiety disorder was likely under-estimated, further prospective studies are needed to determine the relationship between PA and incident anxiety disorder.

Regular physical activity (PA) appears to protect against the emergence of depression, but prospective studies linked to clinician diagnoses of major depressive disorder (MDD) remain scarce. It is also unclear whether PA levels recommended for general health are prospectively related to depression onset. We explored these relationships in a cohort of adults followed over 13 years. In total, 43,863 Swedish adults were surveyed in 1997 and responses linked to clinician-diagnosed MDD obtained from specialist medical registers until 2010. Weekly durations of habitual moderate (including walking) and vigorous PA were self-reported. Relationships between total durations of PA, 0-149 ('below'), 150-299 ('achieve'), and ≥300 min ('exceed') with incident MDD were explored using survival analysis with Cox proportional hazards regression. Models were adjusted for relevant covariates. Those with indications of depression at baseline were removed from the primary analyses. Of 25,520 participants with complete data (mean age = 49 years, SD = 16, 65% female), 76% met the recommended weekly duration of PA (≥150 min), and 38% exceeded this duration (≥300 min). During 13-years follow-up 549 MDD cases (1.5%) were identified (incidence rate = 111 cases per 100,000 person-years). Compared to participants who were below, those who exceeded the recommended weekly duration (≥300 min/week) had 29% reduced risk of depression onset (HR 0.71, 95% CI = 0.53-0.96). A non-significant inverse association was observed among those who achieved the minimum duration of 150-min/week (HR 0.86, 95% CI = 0.64-1.14). Habitual PA levels that exceed the duration recommended for general health may reduce the risk of clinician-diagnosed major depression in adults. ispartof: PREVENTIVE MEDICINE vol:118 pages:38-43 ispartof: location:United States status: published

Background: Ideal cardiovascular health (CVH) can be measured by 7 metrics (smoking, body mass index, physical activity, diet, hypertension, dyslipidemia and diabetes) proposed by the American Heart Association. We examined the association of ideal CVH metrics with risk of all-cause, CVD and non-CVD death in a large cohort. Methods: A total of 29,557 participants in the Swedish National March Cohort were included in this study. We ascertained 3,799 deaths during a median follow-up of 19 years. Cox regression models were used to estimate hazard ratios with 95% confidence intervals (95% CIs) of the association between CVH metrics with risk of death. Laplace regression was used to estimate 25 th , 50 th and 75 th percentiles of age at death. Findings: Compared with those having 6-7 ideal CVH metrics, participants with 0-2 ideal metrics had 107% (95% CI=46%-192%) excess risk of all-cause, 224% (95% CI=72%-509%) of CVD and 108% (31%-231%) of non-CVD death. The discrimination of ideal CVH metrics together with age, sex and education was 88% (95% CI=0.87-0.88) for predicting risk of all-cause, 91% (95% CI=0.90-0.91) for CVD and 83% (95% CI=0.82-0.83) for non-CVD death. The median age at death among those with 6-7 vs 0-2 ideal metrics was extended by 4.2 years for all-causes, 5.8 years for CVD and 2.9 years for non-CVD. Interpretation: The strong inverse association between ideal CVH metrics and risk of death supports the application of the proposed seven metrics for individual risk assessment and general health promotion. Funding Statement: The Swedish Cancer Society, ICA AB and Telefonaktiebolaget LM Ericsson. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: The study was approved by the Regional Ethical Review Board at Karolinska Institutet and all study participants provided informed consent.

Rationale & Objective Chronic kidney disease (CKD) is a global health problem with increasing prevalence. Several sex-specific differences have been reported for disease progression and mortality. Selection and survival bias might have influenced the results of previous cohort studies. The objective of this study was to investigate sex-specific differences of CKD progression and mortality among patients with CKD not receiving maintenance dialysis. Study Design Observational cohort study. Setting & Participants Adult patients with incident CKD glomerular filtration rate categories 3b to 5 (G3b-G5) identified between 2010 and 2018 within the nationwide Swedish Renal Registry-CKD (SRR-CKD). Exposure Sex. Outcomes Time to CKD progression (defined as a change of at least 1 CKD stage or initiation of kidney replacement therapy [KRT]) or death. Repeated assessments of estimated glomerular filtration rate (eGFR). Analytical Approach CKD progression and mortality before KRT were assessed by the cumulative incidence function methods and Fine and Gray models, with death handled as a competing event. Sex differences in eGFR slope were estimated using mixed effects linear regression models. Results 7,388 patients with incident CKD G3b, 18,282 with incident CKD G4, and 9,410 with incident CKD G5 were identified. Overall, 19.6 (95% CI, 19.2-20.0) patients per 100 patient-years progressed, and 10.1 (95% CI, 9.9-10.3) patients per 100 person-years died. Women had a lower risk of CKD progression (subhazard ratio [SHR], 0.88 [95% CI, 0.85-0.92]), and a lower all-cause (SHR, 0.90 [95% CI, 0.85-0.94]) and cardiovascular (SHR, 0.83 [95% CI, 0.76-0.90]) mortality risk. Risk factors related to a steeper decline in eGFR included age, sex, albuminuria, and type of primary kidney disease. Limitations Incomplete data for outpatient visits and laboratory measurements and regional differences in reporting. Conclusions Compared to women, men had a higher rate of all-cause and cardiovascular mortality, an increased risk of CKD progression, and a steeper decline in eGFR.

Objective Both observational studies and randomized trials have shown that a diet rich in antioxidants can reduce systemic inflammation and oxidative stress, two conditions that, together with obesity and smoking, are established risk factors for stroke. However, the association between antioxidant intake and risk for stroke is poorly understood, particularly when studying possible interaction with sex. We investigated the relationship of nonenzymatic antioxidant capacity (NEAC) on risk for stroke in a large Swedish prospective cohort. Methods The cohort study included 34 555 men and women from the Swedish National March Cohort. NEAC was assessed using a detailed food frequency questionnaire, collected at baseline. We achieved complete follow-up from enrollment in 1997 through 2010 by record linkage to nationwide registers. We identified 1186 incident cases of a first stroke, of which 860 were ischemic, 201 hemorrhagic, and 125 unspecified. We used multivariable Cox proportional hazards models to estimate adjusted hazard ratios (HR) with 95% confidence intervals (CIs). Results Compared with women in the lowest quartile of NEAC, women in the highest quartile had a 27% lower incidence of total stroke (HR, 0.73; 95% CI, 0.53–0.99; P trend = 0.03) and 35% lower incidence of ischemic stroke (HR, 0.65; 95% CI, 0.43–0.99; P trend = 0.01). Among men, the relationship between NEAC and risk for stroke was not statistically significant and all HRs were close to unity. Conclusion Findings from the present study suggest that dietary antioxidant capacity from different foods and beverages is inversely associated with risk for stroke, more specifically ischemic stroke, in women.

Objective Consumption of antioxidant-rich foods has been associated with a reduced risk for stroke. However, antioxidant supplementation is not recommended owing to controversial findings reported in clinical trials. The aim of this study was to better understand the effect of dietary antioxidants by investigating the effect of dietary non-enzymatic antioxidant capacity (NEAC), reflecting the antioxidant potential of the whole diet, on the risk for stroke. Methods In the Women's Lifestyle and Health Cohort, 45 882 women 30 to 49 y of age and free from cardiovascular diseases were followed through record linkages from 1991 to 2012. Dietary NEAC was assessed by a validated food frequency questionnaire collected at baseline and categorized into quintiles. Multivariable Cox proportional hazard regression models were fitted to estimate hazard ratios with 95% confidence intervals for overall stroke and ischemic and hemorrhagic stroke separately. Results During a mean follow-up time of 20.2 y, we detected 871 incidence cases of stroke (516 ischemic, 296 hemorrhagic, and 59 unspecified strokes). After adjusting for potential confounders, we did not find any association between dietary NEAC and stroke, either overall, or ischemic or hemorrhagic stroke (Ptrend > 0.05). Conclusion Higher dietary NEAC was not associated with any type of stroke in young and middle-aged Swedish women.

Background & Aims Type 2 diabetes is a risk factor for development of cirrhosis and hepatocellular carcinoma. However, risk factors that identify persons with the highest risk for these outcomes are missing from unselected, population-based cohorts. Methods The National Diabetes Register contains data on about 90% of persons in Sweden with type 2 diabetes. In this cohort study, persons with type 2 diabetes listed in the National Diabetes Register were compared with 5 individuals from the general population (controls), matched for age, sex, and county. In total, 406 770 persons with type 2 diabetes and 2 033 850 controls were included and followed for 21 596 934 person-years. We used population-based registers to determine the incidence of severe liver disease, defined as a diagnosis of hepatocellular carcinoma, cirrhosis, decompensation, liver failure and/or death due to liver disease during follow up. Cox regression was performed to estimate the risk of severe liver disease and to examine risk factors in persons with type 2 diabetes. Results Risk for severe liver disease was increased in patients with type 2 diabetes compared to controls (hazard ratio, 2.28; 95% CI, 2.21–2.36). Risk factors associated with severe liver disease in persons with type 2 diabetes were higher age, male sex, hypertension, higher body mass index, lower glomerular filtration rate, microalbuminuria, and smoking. Statins were associated with a decreased risk of severe liver disease. Conclusions Persons with type 2 diabetes have an increased risk for severe liver disease. Knowledge of risk factors can be helpful in identifying persons with type 2 diabetes who have a high risk for severe liver disease.

The growing obesity epidemic cannot go unnoticed. It is amajor concern leading to fatal health conditions and high socioeconomic costs. Methods for losing weight are continuously being proposed in themedia [1], in the pharmaceutical field [2], in research [3] and in the general healthcare setting [4] – the expanding communication sources in modern times make it possible to distribute health information at most settings. Concurrently, the promotion of unhealthy foods and beverages reaches similar heights. The uneven battle between science and industry creates counterprevailing messages about healthy behaviors. Despite competing health messages, the major key behind successful weight loss is still behavioral changes [5], or put differently, ‘‘lifestyle-medicine’’ according to Egger et al. [6]. Once the desired bodyweight has been achieved, weight maintenance becomes the primary challenge [6]. Previous research shows that frequent contacts and follow-ups significantly increase the chance ofmaintaining newbehaviors [7–9]. In addition, asweight changes impinge upon individuals’ daily life, a supportive and understanding environment is a vital component of sustaining weight. The use of modern technology in weight loss interventions is expanding. By taking advantage of the potentials of technology

Background: Erectile dysfunction (ED) is associated with an increased risk of cardiovascular disease in healthy men. However, the association between ED and death or cardiovascular outcomes after a first MI is unknown. Methods: In a Swedish nation-wide cohort study all men < 80 years of age

Introduction and Objectives: Experimental research suggests that sleep deprivation may alter physiological factors associated with an increased risk for cardiovascular diseases (CVDs). Prior observational studies examining the effects of sleep duration have focused on narrowly defined CVD outcomes, such as myocardial infarction or stroke only. A more comprehensive measure of CVDs is lacking. Therefore, we examined the relationship between sleep duration and Major Adverse Cardiac Events (MACE).Materials and Methods: In 1997, 39,047 Swedish residents (women: 64%, age: 18-94 years) were enrolled in the National March cohort study and asked to self-report their habitual sleep duration in a questionnaire. They were followed-up over approximately 7 years to study incidents of MACE. Events were defined as death from all CVDs, nonfatal myocardial infarction, stroke, or heart failure. The relationship between sleep duration and MACE was analyzed using Cox proportional hazards models.Results: A total of 1,730 events were observed during a median follow-up period of 7.25 years. We found 665 nonfatal myocardial infarctions, 641 nonfatal strokes, 212 nonfatal heart failures, and 198 deaths from all CVDs. Age- and sex-adjusted hazard ratios (95% confidence intervals) of MACE (with 7 hours of sleep/day as the reference group) for individuals reporting ≤5, 6, and ≥ 8 hours of sleep were 1.24 (1.05-1.47), 1.03 (0.91-1.16), and 1.09 (0.97-1.23), respectively. Adjusting for BMI and physical activity did not change the hazard ratios. When adjusting for additional confounders, e.g., depressive symptoms, sleep apnea, and smoking, the association between ≤5h of sleep and MACE was attenuated (HR: 1.22, 95% CI: 0.98-1.52).Conclusion: Sleep duration was not associated with the risk of Major Adverse Cardiac Events. Sleep duration, however, may not in itself explain the effects of inadequate sleep on cardiovascular diseases. Yet, it may serve as an essential component in the understanding of cardiovascular diseases. Copyright © 2011 Elsevier B.V. All rights reserved.