| 41. |
- Michaëlsson, Karl, 1959-, et al.
(author)
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Oral contraceptive use and hip fracture risk : a case-control study
- 1999
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In: The Lancet. - 0140-6736 .- 1474-547X. ; 353:9175, s. 1481-1484
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Journal article (peer-reviewed)abstract
- BACKGROUND: Epidemiological studies indicate a protective effect of postmenopausal oestrogen therapy on the risk of osteoporotic fractures. Whether premenopausal oestrogen exposure in the form of oral contraceptives also reduces the risk of osteoporotic fractures remains uncertain. METHOD: We did a population-based case control study of hip fracture among Swedish postmenopausal women, 50-81 years of age, through mailed questionnaires and telephone interviews. Of those women who were eligible, 1327 (82.5%) cases and 3312 (81.6%) randomly selected controls responded. FINDINGS: 130 (11.6%) cases and 562 (19.1%) controls reported ever-use of oral contraceptives. Ever-use of oral contraceptives was associated with a 25% reduction in hip fracture risk (odds ratio 0.75 [95% CI 0.59-0.96]). Women who had ever used a high-dose pill (equivalent to > or = 50 microg ethinylestradiol per tablet) had a 44% lower risk for hip fracture than never-users (0.56 [0.42-0.75]). No overall trend was observed with duration of oral-contraceptive use, or time since last use. However, when making comparisons with women who have never used oral contraceptives, the odds ratios for hip-fracture were 0.69 (0.51-0.94) for use after age 40, 0.82 (0.57-1.16) for use at ages 30-39, and 1.26 (0.76-2.09) for use before age 30. INTERPRETATION: Our results imply that in postmenopausal women, oral-contraceptive use late in reproductive life may reduce the risk of hip fracture, although we recognise the limitations of the case-control method.
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| 42. |
- Michaëlsson, Karl, et al.
(author)
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Serum 25-hydroxyvitamin D is associated with fracture risk only during periods of seasonally high levels in women with a high body mass index
- 2021
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In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 36:10, s. 1957-1966
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Journal article (peer-reviewed)abstract
- Serum 25-hydroxyvitamin D (S-25OHD) is used to assess vitamin D status and is known to be affected by season and fat mass. Because these factors are often ignored when interpreting S-25OHD, assessment of vitamin D associations with disease outcomes may be distorted. We aimed to investigate the impact of season of blood draw and fat mass on the association of S25OHD with fracture risk. We enrolled 5000 women, mean ± SD age 68 ± 7 years, with dual-energy x-ray absorptiometry (DXA) scans and blood collection in a population-based cohort. Proportional hazards regression, stratified by season and fat mass, was used to determine hazard ratios (HRs) of fracture according to categories of S-25OHD. Our secondary exposures were serum 1,25-dihydroxycholecalciferol (1,25-(OH)2 D3 ), the most active vitamin D metabolite and plasma parathyroid hormone (P-PTH). During an average of 9.2 years of follow-up, 1080 women had a fracture. Women with S-25OHD <30 nmol/L drawn during sunny months (May-October) had a multivariable-adjusted fracture HR of 2.06 (95% CI, 1.27-3.35) compared with those with S-25OHD >60 nmol/L; those with S-25OHD 30-40 nmol/L had an HR of 1.59 (95% CI, 1.12-2.26). In contrast, S-25OHD drawn during November through April was unrelated to fracture risk. The increased risk with low sunny season S-25OHD was seen only among women with body mass index (BMI) ≥25 kg/m2 or fat mass index (FMI) ≥9.8 kg/m2 . High fat mass and low S-25OHD were independently related to lower S-1,25-dihydroxycholecalciferol, which itself predicted fracture risk with samples collected during the sunny season. Irrespective of season, P-PTH was unrelated to fracture risk. We conclude that S-25OHD is associated with fracture risk only if drawn during periods of seasonally high levels in women with a high BMI. These results have implications for the evaluation of vitamin D status and can explain the lack of effect seen with vitamin D supplementation in many fracture trials. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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| 43. |
- Michaëlsson, Madeleine, 1968-, et al.
(author)
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The impact and causal directions for the associations between diagnosis of ADHD, socioeconomic status, and intelligence by use of a bi-directional two-sample Mendelian randomization design
- 2022
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In: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 20:1
-
Journal article (peer-reviewed)abstract
- Background Previous studies have reported associations between attention-deficit/hyperactivity disorder (ADHD) and lower socioeconomic status and intelligence. We aimed to evaluate the causal directions and strengths for these associations by use of a bi-directional two-sample Mendelian randomization (MR) design. Methods We used summary-level data from the largest available genome-wide association studies (GWAS) to identify genetic instruments for ADHD, intelligence, and markers of socioeconomic status including the Townsend deprivation index, household income, and educational attainment. Effect estimates from individual genetic variants were combined using inverse-variance weighted regression. Results A genetically predicted one standard deviation (SD) increment in the Townsend deprivation index conferred an odds ratio (OR) of 5.29 (95% confidence interval (CI) 1.89-14.76) for an ADHD diagnosis (p<0.001). A genetically predicted one SD higher education level conferred an OR of 0.30 (95% CI 0.25-0.37) (p<0.001), and a genetically predicted one SD higher family income provided an OR of 0.35 (95% CI 0.25-0.49; p<0.001). The associations remained after adjustment for intelligence whereas the lower odds of an ADHD diagnosis with higher intelligence did not persist after adjustment for liability to greater educational attainment (adjusted OR 1.03, 95% CI 0.68-1.56; p=0.87). The MR analysis of the effect of ADHD on socioeconomic markers found that genetic liability to ADHD was statistically associated with each of them (p<0.001) but not intelligence. However, the average change in the socioeconomic markers per doubling of the prevalence of ADHD corresponded only to 0.05-0.06 SD changes. Conclusions Our results indicate that an ADHD diagnosis may be a direct and strong intelligence-independent consequence of socioeconomic related factors, whereas ADHD appears to lead only to modestly lowered socioeconomic status. Low intelligence seems not to be a major independent cause or consequence of ADHD.
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| 44. |
- Roettenbacher, Rachael M., et al.
(author)
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Contemporaneous Imaging Comparisons of the Spotted Giant sigma Geminorum Using Interferometric, Spectroscopic, and Photometric Data
- 2017
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 849:2
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Journal article (peer-reviewed)abstract
- Nearby active stars with relatively rapid rotation and large starspot structures offer the opportunity to compare interferometric, spectroscopic, and photometric imaging techniques. In this paper, we image a spotted star with three different methods for the first time. The giant primary star of the RS Canum Venaticorum binary sigma. Geminorum (sigma Gem) was imaged for two epochs of interferometric, high-resolution spectroscopic, and photometric observations. The light curves from the reconstructions show good agreement with the observed light curves, supported by the longitudinally consistent spot features on the different maps. However, there is strong disagreement in the spot latitudes across the methods.
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| 45. |
- Stattin, Karl, et al.
(author)
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Fracture risk across a wide range of physical activity levels, from sedentary individuals to elite athletes.
- 2021
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In: Bone. - : Elsevier. - 8756-3282 .- 1873-2763. ; 153
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To examine how physical activity is associated with risk of different fracture outcomes across the full range of physical activity.METHODS: By combining information from three cohort studies and using generalized structural equation modelling, we estimated a continuous unitless latent variable reflecting physical activity that ranged from sedentary through elite athlete levels. Associations between physical activity and fracture outcomes were assessed with proportional hazards regression using restricted cubic splines with the mean physical activity (corresponding to 20-40 min walking or bicycling/day or 2-3 h exercise/week) as reference.RESULTS: Among 63,980 men and women (49-68 years) and during 13 years of follow-up, 8506 fractures occurred, including 2164 distal forearm, 779 proximal humerus, 346 clinical spine, and 908 hip fractures. Both lower and higher physical activity was associated with higher risk of any fracture compared to the mean. Physical activity at 1 standard deviation (SD) below the mean, corresponding to walking/bicycling <20 min/day or exercising <1-1 h/week, was associated with a lower risk of distal forearm fracture (hazard ratio [HR]: 0.92, 95% confidence interval [CI]: 0.85-0.99) and higher risk of hip fracture (HR: 1.24, 95% CI: 1.13-1.37), but no associations were seen above the mean physical activity level for these fractures. Physical activity was not associated with proximal humerus fracture but had a possible U-shaped association with clinical spine fracture.CONCLUSION: Physical activity was non-linearly associated with fracture risk and the association differed across fracture sites. Up to 2-3 h weekly exercise is beneficial for the prevention of hip fracture but may increase the risk of distal forearm fracture.
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| 46. |
- Sörensen, Jens, et al.
(author)
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Myocardial Efficiency : A Fundamental Physiological Concept on the Verge of Clinical Impact
- 2020
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In: JACC Cardiovascular Imaging. - : Elsevier BV. - 1936-878X .- 1876-7591. ; 13:7, s. 1564-1576
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Journal article (peer-reviewed)abstract
- Myocardial external efficiency is the relation of mechanical energy generated by the left (or right) ventricle to the consumed chemical energy from aerobic metabolism. Efficiency can be calculated invasively, and, more importantly, noninvasively by using positron emission tomography, providing a single parameter by which to judge the adequacy of myocardial metabolism to generated mechanical output. This parameter has been found to be impaired in heart failure of myocardial or valvular etiology, and it changes in a characteristic manner with medical or interventional cardiac therapy. The authors discuss the concept, strengths, and limitations, known applications, and future perspectives of the use of myocardial efficiency.
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| 47. |
- Terry, Paul, et al.
(author)
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Dietary calcium and vitamin D intake and risk of colorectal cancer : a prospective cohort study in women
- 2002
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In: Nutrition and Cancer. - 0163-5581 .- 1532-7914. ; 43:1, s. 39-46
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Journal article (peer-reviewed)abstract
- Although laboratory data and a few adenoma prevention trials suggest that calcium supplementation may reduce the risk of colorectal neoplasia, the results of observational studies of calcium intake and colorectal cancer risk are contradictory. However, few studies have examined the association among women or effects in specific colon subsites. Women with colorectal cancer diagnosed through 31 December 2000 were identified by linkage to regional cancer registries. During an average 11.3 yr of follow-up of 61,463 women, we observed 572 incident cases of colorectal cancer. Using data obtained from a 67-item food frequency questionnaire and Cox proportional hazards models to estimate rate ratios and 95% confidence intervals, we found an inverse association between dietary calcium intake and colorectal cancer risk. Women with the highest calcium intake (median 914 mg/day) had a reduced risk of colorectal cancer (rate ratio = 0.72, 95% confidence interval = 0.056-0.93, P for trend = 0.02) compared with women with the lowest intake (median 486 mg/day). Furthermore, our results suggest that the inverse association may be strongest in relation to distal cancers and among older women. The association with dairy products was less clear, suggesting that calcium intake per se is more important than specific calcium sources. Vitamin D intake was not clearly associated with risk. In sum, our data suggest that high calcium intake may lower colorectal cancer risk.
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| 48. |
- Titova, Olga E, et al.
(author)
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Anger frequency and risk of cardiovascular morbidity and mortality
- 2022
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In: European Heart Journal Open. - : Oxford University Press. - 2752-4191. ; 2:4, s. 1-8
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Journal article (peer-reviewed)abstract
- Aims: Anger may increase the risk of cardiovascular diseases (CVDs) but previous findings are inconclusive and large prospective studies are needed. We investigated whether frequency of strong anger is associated with the incidence of specific CVDs and CVD mortality, and if sex, age, and cardiometabolic risk factors modify these associations.Methods and results: We used data from a population-based cohort of 47 077 Swedish adults (56-94 years of age) who completed questionnaires regarding their experience of anger, lifestyle habits, and health characteristics. Participants were followed for incident cardiovascular outcomes and death up to 9 years through linkage to the Swedish National Patient and Death Registers. Hazard ratios and confidence intervals adjusted for potential confounders were assessed.In multivariable analyses, frequent episodes of strong anger were associated with an increased risk of heart failure, atrial fibrillation, and CVD mortality [hazard ratios (95% confidence intervals) = 1.19 (1.04-1.37), 1.16 (1.06-1.28), and 1.23 (1.09-1.40), respectively]. The link between anger frequency and heart failure was more pronounced in men and participants with a history of diabetes. No evidence of an independent association of anger frequency with risk of myocardial infarction, aortic valve stenosis, and abdominal aortic aneurysm was found.Conclusion: Our findings indicate that anger may contribute to the development of specific CVDs and CVD mortality, especially heart failure in men and in those with diabetes.
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| 49. |
- Titova, Olga E., et al.
(author)
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Comprehensive analyses of circulating cardiometabolic proteins and objective measures of fat mass
- 2023
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In: International Journal of Obesity. - : Springer Nature. - 1476-5497 .- 0307-0565. ; 47:11, s. 1043-1049
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Journal article (peer-reviewed)abstract
- Background: The underlying molecular pathways for the effect of excess fat mass on cardiometabolic diseases is not well understood. Since body mass index is a suboptimal measure of body fat content, we investigated the relationship of fat mass measured by dual-energy X-ray absorptiometry with circulating cardiometabolic proteins. Methods: We used data from a population-based cohort of 4950 Swedish women (55–85 years), divided into discovery and replication samples; 276 proteins were assessed with three Olink Proseek Multiplex panels. We used random forest to identify the most relevant biomarker candidates related to fat mass index (FMI), multivariable linear regression to further investigate the associations between FMI characteristics and circulating proteins adjusted for potential confounders, and principal component analysis (PCA) for the detection of common covariance patterns among the proteins. Results: Total FMI was associated with 66 proteins following adjustment for multiple testing in discovery and replication multivariable analyses. Five proteins not previously associated with body size were associated with either lower FMI (calsyntenin-2 (CLSTN2), kallikrein-10 (KLK10)), or higher FMI (scavenger receptor cysteine-rich domain-containing group B protein (SSC4D), trem-like transcript 2 protein (TLT-2), and interleukin-6 receptor subunit alpha (IL-6RA)). PCA provided an efficient summary of the main variation in FMI-related circulating proteins involved in glucose and lipid metabolism, appetite regulation, adipocyte differentiation, immune response and inflammation. Similar patterns were observed for regional fat mass measures. Conclusions: This is the first large study showing associations between fat mass and circulating cardiometabolic proteins. Proteins not previously linked to body size are implicated in modulation of postsynaptic signals, inflammation, and carcinogenesis.
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| 50. |
- Titova, Olga E, et al.
(author)
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Self-reported symptoms of sleep-disordered breathing and risk of cardiovascular diseases : Observational and Mendelian randomization findings
- 2022
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In: Journal of Sleep Research. - : John Wiley & Sons. - 0962-1105 .- 1365-2869. ; 31:6
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Journal article (peer-reviewed)abstract
- Sleep-disordered breathing may increase the risk of cardiovascular diseases, but observational findings are inconclusive. We investigated whether sleep-disordered breathing-related symptoms are associated with risk of several cardiovascular diseases using data from a cohort study and by performing Mendelian randomization analyses. The cohort study included 43,624 adults (56-94 years old) who completed questionnaires regarding symptoms of snoring and cessation of breathing, lifestyle habits and health characteristics. Participants were followed up for incident cardiovascular diseases and death over 8 years through linkage to the Swedish National Patient and Death Registers. The Mendelian randomization analyses were conducted using single-nucleotide polymorphisms robustly associated with sleep apnea in a recent genome-wide association study and summary-level data for major cardiovascular diseases from large-scale consortia. In the cohort study, an increased risk of atrial fibrillation was observed in participants who reported both snoring and cessation of breathing (hazard ratio [95% confidence interval] = 1.16 [1.03-1.30]) compared with those without sleep-disordered breathing symptoms. There was no association between sleep-disordered breathing symptoms and risk of myocardial infarction, heart failure, aortic valve stenosis or abdominal aortic aneurysm in multivariable analyses. Mendelian randomization analyses showed no association of genetic liability to sleep apnea with myocardial infarction, heart failure or atrial fibrillation, but revealed a suggestive association with coronary artery disease (odds ratio [95% confidence interval] = 1.24 [1.02-1.52]).
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