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  • 51.
    Fang, Fang
    et al.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, S-17177 Stockholm, Sweden.
    Hållmarker, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Mora Hosp, Dept Internal Med, Mora, Sweden.
    James, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Ingre, Caroline
    Karolinska Univ Hosp, Dept Neurol, Stockholm, Sweden.; Karolinska Inst, Dept Clin Neurosci, S-17177 Stockholm, Sweden.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Ahlbom, Anders
    Karolinska Inst, Inst Environm Med, S-17177 Stockholm, Sweden.
    Feychting, Maria
    Karolinska Inst, Inst Environm Med, S-17177 Stockholm, Sweden.
    Amyotrophic lateral sclerosis among cross-country skiers in Sweden.2016Ingår i: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 31, nr 3, s. 247-253Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A highly increased risk of amyotrophic lateral sclerosis (ALS) has been suggested among professional athletes. We aimed to examine whether long distance cross-country skiers have also a higher risk of ALS and whether the increased risk was modified by skiing performance. We followed 212,246 cross-country skiers in the Swedish Vasaloppet cohort and a random selection of 508,176 general Swedes not participating in the Vasaloppet during 1989-2010. The associations between cross-country skiing as well as skiing performance (i.e., type of race, finishing time and number of races) and the consequent risk of ALS were estimated through hazard ratios (HRs) derived from Cox model. During the study, 39 cases of ALS were ascertained among the skiers. The fastest skiers (100-150 % of winner time) had more than fourfold risk of ALS (HR 4.31, 95 % confidence interval [CI] 1.78-10.4), as compared to skiers that finished at >180 % of winner time. Skiers who participated >4 races during this period had also a higher risk (HR 3.13, 95 % CI 1.37-7.17) than those participated only one race. When compared to the non-skiers, the fastest skiers still had a higher risk (HR 2.08, 95 % CI 1.12-3.84), as skiers who had >4 races (HR 1.88, 95 % CI 1.05-3.35), but those finishing at >180 % of winner time had a lower risk (HR 0.46, 95 % CI 0.24-0.87). In conclusion, long distance cross-country skiing is associated with a higher risk of ALS, but only among the best skiers; recreational skiers appear to have a largely reduced risk.

  • 52. Farahmand, Bahman Y.
    et al.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Ahlbom, Anders
    Ljunghall, Sverker
    Baron, John A.
    Survival after hip fracture2005Ingår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 16, nr 12, s. 1583-90Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Although it is known that overall mortality is increased after hip fracture, the influence of hip fracture risk factors on the subsequent mortality and cause of death has not been well studied. The objective of this study was to establish the survival after hip fracture in women and to assess the impact of comorbidity on mortality. We identified a complete population-based set of 2,245 incident hip fracture cases and 4,035 randomly selected population-based controls among women 50-81 years old in Sweden and followed these subjects for an average of 5 years through the Swedish National Inpatient and Cause-of-Death Registers. Information on factors related to hip fracture was obtained through linkage to hospital discharge data and through a mailed questionnaire. We studied excess mortality of hip fracture patients compared to controls using survival curves and proportional hazard regression models. During follow-up, 896 hip fracture patients (40%) and 516 (13%) controls died. The relative risk (RR) of death, adjusted for age and previous hospitalization for serious disease, was 2.3 (95% CI 2.0-2.5). Although the highest mortality risks were in the 1st 6 months post-fracture, RRs for fractures versus controls were increased for at least 6 years. Increased mortality was apparent both in those with evidence of comorbidity and those without. Hip fracture patients have a substantially increased risk of death that persists for at least 6 years post-fracture. The relative excess mortality is independent of comorbidity and known hip fracture risk factors.

  • 53. Farahmand, Bahman Y.
    et al.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Baron, John A.
    Persson, Per-Gunnar
    Ljunghall, Sverker
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Body Size and Hip Fracture Risk: Swedish Hip Fracture Study Group2000Ingår i: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 11, nr 2, s. 214-9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The objective of this population-based case-control study was to determine the independent association between height, weight at different ages and adult weight change on hip fracture risk, and the joint effects of these factors. The study base comprised postmenopausal women 50-81 years of age who resided in six counties in Sweden during the period October 1993 to February 1995. The study included 1,327 cases with an incident hip fracture and 3,262 randomly selected controls. We obtained information on body measures and other factors possibly related to hip fracture through mailed questionnaires and telephone interviews. Height and weight change were dominant risk factors. Tall women (> or = 169 cm) had an odds ratio of 3.16 (95% confidence interval = 2.47-4.05) compared with women shorter than 159 cm. Weight gain during adult life was strongly protective: compared with those with moderate weight change (-3 to 3 kg), those with substantial weight gain (> or =12 kg) had a markedly decreased risk of hip fracture (odds ratio = 0.35; 95% confidence interval = 0.27-0.45), whereas weight loss was associated with an increased risk. Weight change retained important effects among all subjects, even after controlling for current weight and weight at age 18. In contrast, among women who gained weight, the separate effects of current weight and weight at age 18 were small or absent. Among women who lost weight, both current weight and weight at age 18 had effects that remained after controlling for weight change. Adult weight change and height are dominant body size risk factors for hip fracture. Weight loss vs weight changes demarcates different patterns of hip fracture risk.

  • 54. Farahmand, Bahman Y.
    et al.
    Persson, Per-Gunnar
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Baron, John A.
    Alberts, Akke
    Moradi, Tahere
    Ljunghall, Sverker
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Physical activity and hip fracture: a population-based case-control study2000Ingår i: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 29, nr 2, s. 308-14Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: A growing body of literature suggests that physical activity may be a protective factor against hip fracture. METHODS: To study the association between hip fracture risk and recreational physical activity at various ages, changes in activity during adult life, occupational physical activity and how risks vary by adult weight change, we performed a population-based case-control study among postmenopausal women aged 50-81 years residing in six counties in Sweden in 1993-1995. The analysis consisted of 1327 women with hip fracture and 3262 randomly selected controls. Information on leisure physical activity before age 18, at 18-30 years and during recent years was based on a questionnaire. Data on occupational physical activity were collected through an independent classification of job titles obtained from record linkage with census data from 1960, 1970 and 1980. RESULTS: There was a protective effect of recent leisure physical activity. Compared to women who reported no leisure activity, the odds ratios (OR) were 0.79 (95% CI: 0.62-1.00), 0.67 (95% CI: 0.54-0.84) and 0.48 (95% CI: 0.39-0.60) for women who exercised <1 h per week, 1-2 h per week, and 3+ h per week, respectively. These decreased OR were more pronounced in women who had lost weight after 18 years of age than in those who had gained weight. Women with high physical activity at both 18-30 years and during recent years did not have a stronger protection than those with isolated high activity late in life, after accounting for recent activity. Occupational physical activity was not associated with hip fracture risk in this study. CONCLUSIONS: Recent physical activity is protective against hip fracture. The protective effect is most pronounced in women who had lost weight after age 18.

  • 55. Farahmand, Bahman Y.
    et al.
    Persson, Per-Gunnar
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Baron, John A.
    Parker, M.G.
    Ljunghall, Sverker
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Socioeconomic status, marital status and hip fracture risk: a population-based case-control study2000Ingår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 11, nr 9, s. 803-8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Socioeconomic status and social support have been identified as important determinants of several diseases and overall mortality, but these factors have not been adequately examined in relation to hip fracture risk. The aim of this study was to determine the relationship of socioeconomic status and marital status to hip fracture risk. We used data from a population-based case-control study in postmenopausal women aged 50-81 years during 1993-1995 who resided in six counties in Sweden. The analysis was based on 1327 incident cases of hip fracture and 3262 randomly selected controls. Socioeconomic and marital status were obtained by record linkage with census data in 1960, 1970, 1980 and 1990. Information on other possible risk factors for hip fracture was collected by a mailed questionnaire. Women who were gainfully employed in 1990 had an odds ratio (OR) of 0.74 [95% confidence interval (CI) 0.56-0.96] compared with those not gainfully employed; those in the highest tertile of household income had an OR of 0.74 (95% CI 0.60-0.90) compared with those in the lowest tertile of income. Women who lived in a one-family house had an OR of 0.85 (95% CI 0.72-0.99) compared with those living in an apartment. Divorced, widowed or unmarried women had a higher risk of hip fracture than married or cohabiting women; the OR was 1.40 (95% CI 1.06-1.85). Married women who were both gainfully employed and were living in a one-family house had a substantially decreased risk of hip fracture compared with unemployed women living without a partner in an apartment (OR 0.39; 95% CI 0.22-0.71). Occupational affiliation among women ever employed, and educational level, were not associated with hip fracture risk. We conclude that employment, household income, type of housing and marital status seem to be risk indicators of hip fracture risk independent of known osteoporotic risk factors.

  • 56. Försth, P
    et al.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Sandén, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Does fusion improve the outcome after decompressive surgery for lumbar spinal stenosis?: a two-year follow-up study involving 5390 patients2013Ingår i: The Bone & Joint Journal, ISSN 2049-4408, Vol. 95-B, nr 7, s. 960-965Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Whether to combine spinal decompression with fusion in patients with symptomatic lumbar spinal stenosis remains controversial. We performed a cohort study to determine the effect of the addition of fusion in terms of patient satisfaction after decompressive spinal surgery in patients with and without a degenerative spondylolisthesis.                  

    The National Swedish Register for Spine Surgery (Swespine) was used for the study. Data were obtained for all patients in the register who underwent surgery for stenosis on one or two adjacent lumbar levels. A total of 5390 patients fulfilled the inclusion criteria and completed a two-year follow-up. Using multivariable models the results of 4259 patients who underwent decompression alone were compared with those of 1131 who underwent decompression and fusion. The consequence of having an associated spondylolisthesis in the operated segments pre-operatively was also considered.                

    At two years there was no significant difference in patient satisfaction between the two treatment groups for any of the outcome measures, regardless of the presence of a pre-operative spondylolisthesis. Moreover, the proportion of patients who required subsequent further lumbar surgery was also similar in the two groups.                  

    In this large cohort the addition of fusion to decompression was not associated with an improved outcome.

  • 57.
    Försth, Peter
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Sandén, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Fusion Surgery for Lumbar Spinal Stenosis REPLY2016Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 375, nr 6, s. 599-600Artikel i tidskrift (Övrigt vetenskapligt)
  • 58.
    Försth, Peter
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Sandén, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    More on Fusion Surgery for Lumbar Spinal Stenosis2016Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 375, nr 18, s. 1806-1807Artikel i tidskrift (Refereegranskat)
  • 59.
    Försth, Peter
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Karolinska Inst, Stockholm Spine Ctr, S-10401 Stockholm, Sweden..
    Olafsson, Gylfi
    Karolinska Inst, Dept Learning Informat Management & Eth, S-10401 Stockholm, Sweden.;Quantify Res, Stockholm, Sweden..
    Carlsson, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Frost, Anders
    Karolinska Inst, Stockholm Spine Ctr, S-10401 Stockholm, Sweden..
    Borgstrom, Fredrik
    Karolinska Inst, Dept Learning Informat Management & Eth, S-10401 Stockholm, Sweden.;Quantify Res, Stockholm, Sweden..
    Fritzell, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Futurum Acad Hlth & Care, Neuroorthoped Ctr, Ryhov, Sweden..
    Öhagen, Patrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Michaelsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Sanden, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    A Randomized, Controlled Trial of Fusion Surgery for Lumbar Spinal Stenosis2016Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 374, nr 15, s. 1413-1423Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND The efficacy of fusion surgery in addition to decompression surgery in patients who have lumbar spinal stenosis, with or without degenerative spondylolisthesis, has not been substantiated in controlled trials.

    METHODS We randomly assigned 247 patients between 50 and 80 years of age who had lumbar spinal stenosis at one or two adjacent vertebral levels to undergo either decompression surgery plus fusion surgery (fusion group) or decompression surgery alone (decompression-alone group). Randomization was stratified according to the presence of preoperative degenerative spondylolisthesis (in 135 patients) or its absence. Outcomes were assessed with the use of patient-reported outcome measures, a 6-minute walk test, and a health economic evaluation. The primary outcome was the score on the Oswestry Disability Index (ODI; which ranges from 0 to 100, with higher scores indicating more severe disability) 2 years after surgery. The primary analysis, which was a per-protocol analysis, did not include the 14 patients who did not receive the assigned treatment and the 5 who were lost to follow-up.

    RESULTS There was no significant difference between the groups in the mean score on the ODI at 2 years (27 in the fusion group and 24 in the decompression-alone group, P = 0.24) or in the results of the 6-minute walk test (397 m in the fusion group and 405 m in the decompression- alone group, P = 0.72). Results were similar between patients with and those without spondylolisthesis. Among the patients who had 5 years of follow-up and were eligible for inclusion in the 5-year analysis, there were no significant differences between the groups in clinical outcomes at 5 years. The mean length of hospitalization was 7.4 days in the fusion group and 4.1 days in the decompression-alone group (P< 0.001). Operating time was longer, the amount of bleeding was greater, and surgical costs were higher in the fusion group than in the decompression-alone group. During a mean follow-up of 6.5 years, additional lumbar spine surgery was performed in 22% of the patients in the fusion group and in 21% of those in the decompression-alone group.

    CONCLUSIONS Among patients with lumbar spinal stenosis, with or without degenerative spondylolisthesis, decompression surgery plus fusion surgery did not result in better clinical outcomes at 2 years and 5 years than did decompression surgery alone.

  • 60.
    Gedeborg, Rolf
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Chen, Li-Hui
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Thiblin, Ingemar
    Centers for Disease Control and Prevention, Hyattsville, Maryland; Department of Surgical Sciences—Forensic Medicine.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Warner, Margaret
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Prehospital injury deaths-Strengthening the case for prevention: Nationwide cohort study2012Ingår i: Journal of Trauma and Acute Care Surgery, ISSN 2163-0755, E-ISSN 2163-0763, Vol. 72, nr 3, s. 765-772Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: To determine the frequency and characteristics of prehospital deaths compared with hospital deaths in different subpopulations with severe injuries.

    METHODS: Population-based cohort study using person-based linkage of the Swedish nationwide hospital discharge register with death certificate data. In all, 28,715 injury deaths were identified among 419,137 cases of severe injury during 1998 to 2004. Prehospital deaths were defined as autopsied out-of-hospital deaths with injury as the underlying cause. Their impact on mortality prediction was assessed using the International Classification of Disease Injury Severity Score with the C statistic as a measure of discrimination.

    RESULTS: The majority of all injury deaths occurred either at the scene or before hospitalization. Among persons younger than 65 years, for each hospital death there were nine prehospital deaths. A high proportion of deaths from drowning, suffocation, and firearm injuries were prehospital (85, 82, and 67% of all cases, respectively). More than 90% of hospital deaths resulted from unintentional injuries, while only 43% of prehospital deaths were unintentional. The largest increase in a cause-specific case fatality risk estimate was seen for poisoning, where inclusion of prehospital deaths increased the risk estimate from 1.6% to 22.8%. Injury mortality prediction based on International Classification of Disease Injury Severity Score improved when prehospital deaths were added to hospital data (C statistic increased from 0.86 to 0.93).

    CONCLUSIONS: Prehospital deaths constitute the majority of trauma deaths and differ in major characteristics from hospital deaths. The high proportion of prehospital deaths among young and middle aged people highlights the potential impact of preventive efforts.

  • 61.
    Gedeborg, Rolf
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Engquist, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Identification of Incident Injuries in Hospital Discharge Registers2008Ingår i: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 19, nr 6, s. 860-867Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Hospital discharge data on injuries constitute a potentially powerful data source for epidemiologic studies. However, reliable identification of incident injury admissions is necessary. The objective of this study was to develop a prediction model for identifying incident hospital admissions, based on variables derived from a hospital discharge register.

    Methods: There were 743,022 hospital admissions for injury in Sweden 1998–2004. Of these, 23,920 were in the county of Uppsala and 24% of these people had previous injury admissions. To determine if these admissions were new injuries or readmissions for earlier injuries, we reviewed 817 randomly selected hospital records. A prediction model for incident injury admissions was developed on the basis of patient age, type of admission (urgent or elective), time interval from the previous injury admission, main diagnosis, and department type.

    Results: The final prediction model showed good discrimination (c-statistic = 0.969). This model was applied to the validation dataset using the optimal cut-off level, and the resulting sensitivity and specificity were adjusted according to the proportion with a previous injury admission in each injury category. The injury with the highest proportion of possible readmissions was hip contusion (35%). Nevertheless, using the prediction model, incident hip contusions were identified with a sensitivity of 94% (95% confidence interval = 93%–95%) and a specificity of 95% (94%–97%). The accuracy was higher for all other injury categories.

    Conclusions: Incident injury admissions can be accurately separated from readmissions using a prediction model based on information derived from hospital discharge data.

  • 62.
    Gedeborg, Rolf
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Furebring, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Diagnosis-dependent misclassification of infections using administrative data variably affected incidence and mortality estimates in ICU patients2007Ingår i: Journal of Clinical Epidemiology, ISSN 0895-4356, E-ISSN 1878-5921, Vol. 60, nr 2, s. 155-162Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To determine the accuracy of hospital discharge diagnoses in identifying severe infections among intensive care unit (ICU) patients, and estimate the impact of misclassification on incidence and 1-year mortality. STUDY DESIGN AND SETTING: Sepsis, pneumonia, and central nervous system (CNS) infections among 7,615 ICU admissions were identified using ICD-9 and ICD-10 diagnoses from the Swedish hospital discharge register (HDR). Sensitivity, specificity, and likelihood ratios were calculated using ICU database diagnoses as reference standard, with inclusion in sepsis trials (IST) as secondary reference for sepsis. RESULTS: CNS infections were accurately captured (sensitivity 95.4% [confidence interval (CI)=86.8-100] and specificity 99.6% [CI=99.4-99.8]). Community-acquired sepsis (sensitivity 51.1% [CI=41.0-61.2] and specificity 99.4% [CI=99.2-99.6]) and primary pneumonia (sensitivity 38.2% [CI=31.2-45.2] and specificity 98.6% [CI=98.2-99.0]) were more accurately detected than sepsis and pneumonia in general. One-year mortality was accurately estimated for primary pneumonia but underestimated for community-acquired sepsis. However, there were only small differences in sensitivity and specificity between HDR and ICU data in the ability to identify IST. ICD-9 appeared more accurate for sepsis, whereas ICD-10 was more accurate for pneumonia. CONCLUSION: Accuracy of hospital discharge diagnoses varied depending on diagnosis and case definition. The pattern of misclassification makes estimates of relative risk more accurate than estimates of absolute risk.

  • 63.
    Gedeborg, Rolf
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Svennblad, Bodil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Thiblin, Ingemar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Rättsmedicin.
    Prediction of mortality risk in victims of violent crimes2017Ingår i: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 281, s. 92-97Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: To predict mortality risk in victims of violent crimes based on individual injury diagnoses and other information available in health care registries.

    METHODS: Data from the Swedish hospital discharge registry and the cause of death registry were combined to identify 15,000 hospitalisations or prehospital deaths related to violent crimes. The ability of patient characteristics, injury type and severity, and cause of injury to predict death was modelled using conventional, Lasso, or Bayesian logistic regression in a development dataset and evaluated in a validation dataset.

    RESULTS: Of 14,470 injury events severe enough to cause death or hospitalization 3.7% (556) died before hospital admission and 0.5% (71) during the hospital stay. The majority (76%) of hospital survivors had minor injury severity and most (67%) were discharged from hospital within 1day. A multivariable model with age, sex, the ICD-10 based injury severity score (ICISS), cause of injury, and major injury region provided predictions with very good discrimination (C-index=0.99) and calibration. Adding information on major injury interactions further improved model performance. Modeling individual injury diagnoses did not improve predictions over the combined ICISS score.

    CONCLUSIONS: Mortality risk after violent crimes can be accurately estimated using administrative data. The use of Bayesian regression models provides meaningful risk assessment with more straightforward interpretation of uncertainty of the prediction, potentially also on the individual level. This can aid estimation of incidence trends over time and comparisons of outcome of violent crimes for injury surveillance and in forensic medicine.

  • 64.
    Gedeborg, Rolf
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Thiblin, Ingemar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Rättsmedicin.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lindbäck, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Population density and mortality among individuals in motor vehicle crashes2010Ingår i: Injury Prevention, ISSN 1353-8047, E-ISSN 1475-5785, Vol. 16, nr 5, s. 302-308Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective

    To assess whether higher mortality rates among individuals in motor vehicle crashes in areas with low population density depend on injury type and severity or are related to the performance of emergency medical services (EMS).

    Methods

    Prehospital and hospital deaths were studied in a population-based cohort of 41 243 motor vehicle crashes that occurred in Sweden between 1998 and 2004. The final multivariable analysis was restricted to 6884 individuals in motor vehicle crashes, to minimise the effects of confounding factors.

    Results

    Crude mortality rates following motor vehicle crashes were inversely related to regional population density. In regions with low population density, the unadjusted rate ratio for prehospital death was 2.2 (95% CI 1.9 to 2.5) and for hospital death 1.5 (95% CI 1.1 to 1.9), compared with a high-density population. However, after controlling for regional differences in age, gender and the type/severity of injuries among 6884 individuals in motor vehicle crashes, low population density was no longer associated with increased mortality. At 25 years of age, predicted prehospital mortality was 9% lower (95% CI 5% to 12%) in regions with low population density compared with high population density. This difference decreased with increasing age, but was still 3% lower (95% CI 0.5% to 5%) at 65 years of age.

    Conclusions

    The inverse relationship between population density and mortality among individuals in motor vehicle crashes is related to pre-crash factors that influence the type and severity of injuries and not to differences in EMS.

  • 65.
    Gedeborg, Rolf
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniskt forskningscentrum (UCR).
    Thiblin, Ingemar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Rättsmedicin.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wernroth, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniskt forskningscentrum (UCR).
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniskt forskningscentrum (UCR).
    The impact of clinically undiagnosed injuries on survival estimates2009Ingår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 37, nr 2, s. 449-55Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES:: Missed injury diagnoses may cause potentially preventable deaths. To estimate the effect of clinically undiagnosed injuries on injury-specific survival estimates and the accuracy of an injury severity score. To also estimate the potentially preventable mortality attributable to these injuries. DESIGN, SETTING, AND PATIENTS:: In a nation-wide, population-based study, data were collected from all hospital admissions for injuries in Sweden between 1998 and 2004. We studied 8627 deaths in hospital among 598,137 incident hospital admissions. MEASUREMENTS AND MAIN RESULTS:: New specific-injury categories were added in 7.4% (95% confidence interval [CI] 6.8-8.0) of all deaths with an autopsy rate of 24.2%. It was estimated that this proportion would have increased to 25.1% (95% CI 23.0-27.2), if all deaths had been autopsied. The most pronounced effect of clinically undiagnosed injuries was found for internal organ injury in the abdomen or pelvis, where they reduced the estimated survival from 0.83 to 0.69 (95% CI for the difference: 0.09-0.20). Autopsy diagnoses also revealed substantial bias of survival estimates for vascular injuries in the thorax and crush injuries to the head. The performance of the International Classification of Diseases Injury Severity Score improved when autopsy diagnoses were added to hospital discharge diagnoses. The maximum proportion of injury deaths attributable to missed injuries was estimated to be 6.5%. CONCLUSIONS:: Maintaining a high autopsy rate and merging accurate hospital discharge data and autopsy data are effective ways to improve the accuracy of survival estimates and mortality prediction models, and to estimate mortality attributable to diagnostic failures.

  • 66. Glynn, A. Wicklund
    et al.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Lind, Monica
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolutionsbiologi.
    Wolk, Alicja
    Aune, M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Atuma, S.
    Darnerud, P.O.
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Organochlorines and bone mineral density in Swedish men from the general population2000Ingår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 11, nr 12, s. 1036-1042Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Persistent organochlorines (POCs), such as polychlorinated biphenyls (PCBs) and DDT, are present at relatively high concentrations in food and show estrogenic, anti-estrogenic or anti-androgenic activity in biological test systems. Because bone mineral density (BMD) in men is influenced by sex hormones, we looked for associations between BMD and serum concentrations of POCs in 115 men (mean age 63 years, range 40-75 years) from the general Swedish population. Ten PCB congeners, five DDT isomers, hexachlorobenzene, three hexachlorocyclohexane isomers, trans-nonachlor and oxychlordane were analyzed by gas chromatography. Quantitative bone measurements were performed by dual-energy X-ray absorptiometry at three sites: whole body, the L2-L4 region of the lumbar spine, and the neck region of the proximal femur, as well as by quantitative ultrasound on the left os calcis (broadband ultrasound attenuation (BUA) and speed of sound (SOS)). After adjustment for confounding factors in linear regression analyses we found no strong association between serum concentrations of single POCs and the five BMD and ultrasound variables. When POCs were grouped according to hormonal activity (estrogenic, anti-estrogenic, anti-androgenic) and the study subjects were divided into organochlorine concentration quartiles, a weak association was indicated between increased serum concentrations of p,p'-DDE (antiandrogenic) and decreased BMD, BUA and SOS. This may suggest that p,p'-DDE could cause negative effects on bone density, but the findings might also be due to chance since multiple comparisons were made in the statistical analysis. Overall our results do not suggest that the studied POCs caused major effects on bone density in our study group.

  • 67.
    Grip, Olivia
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kärlkirurgi.
    Wanhainen, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kärlkirurgi.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Lindhagen, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Björck, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kärlkirurgi.
    Open versus endovascular revascularization in the treatment of acute lower limb ischaemia2018Ingår i: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 105, nr 12, s. 1598-1606Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Consensus is lacking regarding intervention for patients with acute lower limb ischaemia (ALI). The aim was to study amputation-free survival in patients treated for ALI by either primary open or endovascular revascularization.

    Methods: The Swedish Vascular Registry (Swedvasc) was combined with the Population Registry and National Patient Registry to determine follow-up on mortality and amputation rates. Revascularization techniques were compared by propensity score matching 1:1.

    Results: Of 9736 patients who underwent open surgery and 6493 who had endovascular treatment between 1994 and 2014, 3365 remained in each group after propensity score matching. Results are from the matched cohort only. Mean age of the patients was 74⋅7 years; 47⋅5 per cent were women and mean follow-up was 4⋅3 years. At 30-day follow-up, the endovascular group had better patency (83⋅0 versus 78⋅6 per cent; P < 0⋅001). Amputation rates were similar at 30 days (7⋅0 per cent in the endovascular group versus 8⋅2 per cent in the open group; P = 0⋅113) and at 1 year (13⋅8 versus 14⋅8 per cent; P = 0⋅320). The mortality rate was lower after endovascular treatment, at 30 days (6⋅7 versus 11⋅1 per cent; P < 0⋅001) and after 1 year (20⋅2 versus 28⋅6 per cent; P < 0⋅001). Accordingly, endovascular treatment had better amputation-free survival at 30 days (87⋅5 versus 82⋅1 per cent; P < 0⋅001) and 1 year (69⋅9 versus 61⋅1 per cent; P < 0⋅001). The number needed to treat to prevent one death within the rst year was 12 with an endovascular compared with an open approach. Five years after surgery, endovascular treatment still had improved survival (HR 0⋅78, 99 per cent c.i. 0⋅70 to 0⋅86) but the difference between the treatment groups occurred mainly in the rst year.

    Conclusion: Primary endovascular treatment for ALI appeared to reduce mortality compared with open surgery, without any difference in the risk of amputation.

  • 68.
    Hagforsen, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Dermatologi och venereologi.
    Hedstrand, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Dermatologi och venereologi.
    Nyberg, F.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Dermatologi och venereologi.
    Michaelsson, Gerd
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Novel findings of Langerhans cells and IL-17 expression in relation to the acrosyringium and pustule in palmoplantar pustulosis2010Ingår i: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 163, nr 3, s. 572-579Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Backgound Palmoplantar pustulosis (PPP) is a chronic and intensely inflammatory skin disease with pustules, erythema and scaling localized to the palms and soles. To date, no specific treatment is known. Earlier findings indicate the acrosyringium as the target for the inflammation.

    Objectives To identify specific features of the PPP inflammatory cell infiltrate and mediators of inflammation, which might provide insight into the pathogenesis and possible future treatment of the disease.

    Methods Skin biopsies were taken from 23 patients with typical PPP (23 from involved skin and seven from noninvolved skin) and from 18 healthy controls (10 nonsmokers, eight smokers). Cell infiltrates and inflammation mediators were studied with immunohistochemistry.

    Results A strong inflammation was observed in lesional skin of PPP. Our main findings of Langerhans cells and interleukin-17 close to or in the acrosyringium differs from findings in psoriasis vulgaris. Other inflammatory cells such as CD4+, CD8+, regulatory T cells and CD11a+ cells were also accumulated close to the sweat duct in epidermis and papillary dermis. More CD4+, CD8+, Langerhans cells, plasmacytoid dendritic cells and a higher proportion of regulatory T cells/CD3+ cells were seen in noninvolved palmar skin from patients with PPP compared with healthy controls.

    Conclusions Our novel findings indicate that the inflammation in PPP is initiated by the 'stand-by' innate immune system at the acrosyringium.

  • 69.
    Hagforsen, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Lundgren, Ewa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Olofsson, Helena
    Petersson, Axel
    Lagumdzija, Alena
    Hedstrand, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Michaelsson, Gerd
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Women with palmoplantar pustulosis have disturbed calcium homeostasis and a high prevalence of diabetes mellitus and psychiatric disorders: a case-control study2005Ingår i: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 85, nr 3, s. 225-232Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Palmoplantar pustulosis is characterized by pustule formation in the acrosyringium. Nearly 50% of palmoplantar pustulosis sera produce immunofluorescence of the palmar papillary endothelium from healthy subjects, but also of the endothelium of normal parathyroid gland. With a case-control design the levels of calcium and parathyroid hormone in serum were measured in 60 women with palmoplantar pustulosis and 154 randomly selected population-based control women. One-third of the controls had been smokers, whereas 95% of the cases were or had been smokers. Mean age-adjusted serum calcium was increased in the patients compared with the controls (2.43 vs 2.36 mmol/l; p<0.0001), whereas the parathyroid hormone concentration was suppressed (23.2 vs 31.1 ng/l; p<0.0001). The plasma levels of parathyroid hormone-related protein were normal in patients but there was a strong expression of this protein in the acrosyringium both in palmoplantar pustulosis and control skin. As even a marginal elevation of serum calcium is associated with an increased risk for diabetes, cardiovascular disease and psychiatric disease, we analysed the risk for these disorders in palmoplantar pustulosis patients compared with that in the control group. Both diabetes mellitus and psychiatric disorders were associated with palmoplantar pustulosis with an odds ratio of 8.7 (95% CI 3.3-22.8) and 5.6 (95% CI 2.2-14.4), respectively. Palmoplantar pustulosis is a complex disease with an increased risk for several non-dermatological disorders. The role of the mildly increased serum calcium for the high risk for diabetes and depression deserves to be studied.

  • 70.
    Hagforsen, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Dermatologi och venereologi.
    Pihl-Lundin, Inger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Dermatologi och venereologi.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Michaëlsson, Gerd
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Dermatologi och venereologi.
    Calcium homeostasis and body composition in patients with palmoplantar pustulosis: a case-control study2012Ingår i: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 166, nr 1, s. 74-81Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Palmoplantar pustulosis (PPP) is a common disease strongly associated with smoking, autoimmune comorbidities and a deranged calcium homeostasis. It is unclear whether these changes in calcium homeostasis are a consequence of vitamin D status, abnormal dermal vitamin D synthesis or whether they are substantiated in effects on bone mineral density (BMD).

    Objectives

    To study the vitamin D status and BMD in patients with PPP.

    Methods

    In comparisons with two sets of controls (n = 101 for serum analyses and n = 5123 for BMD analyses), we therefore aimed to investigate whether PPP (59 cases) was associated with serum levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, whether patients with PPP had decreased BMD and finally if the dermal expression of 25-hydroxyvitamin D(3) -1α-hydroxylase (CYP27B1) and the vitamin D receptor (VDR) were affected in PPP skin lesions.

    Results

    We found no differences in mean serum 25-hydroxyvitamin D levels between cases and controls, whereas PPP cases displayed 17·8 pmol L(-1) lower (P = 0·04) values in 1,25-dihydroxyvitamin D. BMD at the hip, lumbar spine or of total body did not differ substantially between cases and controls. Finally, patients with PPP had lower dermal expression of CYP27B1 and VDR in affected skin lesions.

    Conclusions

    The increase in serum calcium levels and suppressed parathyroid hormone in patients with PPP were not attributable to derangements in vitamin D status and these patients did not have lower BMD.

  • 71.
    Hagström, Emil
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Larsson, Tobias E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Held, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Plasma parathyroid hormone and the risk of cardiovascular mortality in the community2009Ingår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 119, nr 21, s. 2765-2771Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Diseases with elevated levels of parathyroid hormone (PTH) such as primary and secondary hyperparathyroidism are associated with increased incidence of cardiovascular disease and death. However, data on the prospective association between circulating PTH levels and cardiovascular mortality in the community are lacking. METHODS AND RESULTS: The Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men (mean age, 71 years; n=958), was used to investigate the association between plasma PTH and cardiovascular mortality. During follow-up (median, 9.7 years), 117 participants died of cardiovascular causes. In Cox proportional-hazards models adjusted for established cardiovascular risk factors (age, systolic blood pressure, diabetes, smoking, body mass index, total cholesterol, high-density lipoprotein cholesterol, antihypertensive treatment, lipid-lowering treatment, and history of cardiovascular disease), higher plasma PTH was associated with higher risk for cardiovascular mortality (hazard ratio for 1-SD increase in PTH, 1.38; 95% confidence interval, 1.18 to 1.60; P<0.001). This association remained essentially unaltered in participants without previous cardiovascular disease and in participants with normal PTH (<6.8 pmol/L) with no other signs of a disturbed mineral metabolism (normal serum calcium, 2.2 to 2.6 mmol/L; normal glomerular filtration rate, >50 mL . min(-1) . 1.73 m(-2) and without vitamin D deficiency, plasma 25-OH vitamin D >37.5 nmol/L). Interestingly, elevated plasma PTH (>5.27 pmol/L) accounted for 20% (95% confidence interval, 10 to 26) of the population-attributable risk proportion for cardiovascular mortality. CONCLUSIONS: Plasma PTH levels predict cardiovascular mortality in the community, even in individuals with PTH within the normal range. Further studies are warranted to evaluate the clinical implications of measuring PTH in cardiovascular risk prediction and to elucidate whether PTH is a modifiable risk factor.

  • 72.
    Hagström, Emil
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Larsson, Tobias E.
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Held, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Plasma parathyroid hormone and risk of congestive heart failure in the community2010Ingår i: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 12, nr 11, s. 1186-1192Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In experimental studies parathyroid hormone (PTH) has been associated with underlying causes of heart failure (HF) such as atherosclerosis, left ventricular hypertrophy, and myocardial fibrosis. Individuals with increased levels of PTH, such as primary or secondary hyperparathyroidism patients, have increased risk of ischaemic heart disease and HF. Moreover, increasing PTH is associated with worse prognosis in patients with overt HF. However, the association between PTH and the development HF in the community has not been reported. In a prospective, community-based study of 864 elderly men without HF or valvular disease at baseline (mean age 71 years, the ULSAM study) the association between plasma (P)-PTH and HF hospitalization was investigated adjusted for established HF risk factors (myocardial infarction, hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, and hypercholesterolaemia) and variables reflecting mineral metabolism (S-calcium, S-phosphate, P-vitamin D, S-albumin, dietary calcium and vitamin D intake, physical activity, glomerular filtration rate, and blood draw season). During follow-up (median 8 years), 75 individuals were hospitalized due to HF. In multivariable Cox-regression analyses, higher P-PTH was associated with increased HF hospitalization (hazard ratio for 1-SD increase of PTH, 1.41, 95% CI 1.12-1.77, P = 0.003). Parathyroid hormone also predicted hospitalization in participants without apparent ischaemic HF and in participants with normal P-PTH. In a large community-based sample of elderly men, PTH predicted HF hospitalizations, also after accounting for established risk factors and mineral metabolism variables. Our data suggest a role for PTH in the development of HF even in the absence of overt hyperparathyroidism.

  • 73.
    Hagström, Emil
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Nylander, Ruta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Arnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Plasma Parathyroid Hormone Is Associated with Vascular Dementia and Cerebral Hyperintensities in Two Community-Based Cohorts2014Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 99, nr 11, s. 4181-4189Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context:

    In diseases with increased PTH such as hyperparathyroidism and chronic renal failure, dementia is common. Little is known of PTH and dementia in the community.

    Objective:

    We sought to investigate relations between PTH, clinical dementia and cerebral micro-vascular disease.

    Setting and Design:

    The Uppsala Longitudinal Study Of Adult Men (ULSAM) was prospective, baseline, 1991-1995; followup, 15.8 years. The Prospective Investigation Of The Vasculature In Uppsala Seniors (PIVUS) was cross-sectional, baseline, 2001. Both settings were community based.

    Participants and Main Outcome Measure:

    In the ULSAM study of 998 men (age 71) the association between PTH and dementia was investigated. In the PIVUS study of 406 men and women (age 70) the relation between PTH and magnetic resonance imaging signs of cerebral small vascular disease was investigated.

    Results:

    During followup, 56 individuals were diagnosed with vascular, 91 with Alzheimer's, and 59 with other dementias. In Cox-regression analyses, higher PTH was associated with vascular dementia (hazard ratio per 1 SD increase of PTH, 1.41; P < .01), but not with other dementias. The top tertile of PTH accounted for 18.5% of the population-attributable risk for vascular dementia, exceeding all other risk factors. In linear regression analysis in PIVUS, PTH was associated with increasing white matter hyperintensities (WMHI), reflecting increasing burden of cerebral small vessel disease (1 SD PTH increase, 0.31 higher category of WMHI; P = .016). All models were adjusted for vascular risk factors and mineral metabolism.

    Conclusions:

    In two community-based samples, PTH predicted clinically diagnosed and neuroimaging indices of vascular dementia and cerebral small vessel disease. Our data suggest a role for PTH in the development of vascular dementia.

  • 74.
    Hagström, Emil
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Hansen, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Arnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Plasma-Parathyroid Hormone Is Associated With Subclinical and Clinical Atherosclerotic Disease in 2 Community-Based Cohorts2014Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 34, nr 7, s. 1567-73Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Cardiovascular risk factors have different impact on different arterial territories. Diseases with elevated circulating parathyroid hormone (PTH) such as primary hyperparathyroidism and chronic renal failure have been shown to be associated with an increased risk of cardiovascular disease, predominantly heart or cerebrovascular diseases. However, data on the associations between circulating PTH and peripheral atherosclerosis are limited.

    APPROACH AND RESULTS: Two prospective, community-based studies were used. In 306 men and women, who were 70 years old, from the Prospective investigation of the vasculature in Uppsala seniors (PIVUS) study, cross-sectional relations between PTH and atherosclerotic burden assessed by whole-body magnetic resonance angiography were investigated. In 998 men, who were 71 years old, from the Uppsala longitudinal study of adult men (ULSAM) study, the association between PTH concentration and risk of subsequent nonfatal atherosclerotic disease (excluding coronary or cerebrovascular disease) was investigated. Adjusting for established vascular risk factors, PTH was associated with burden of atherosclerosis (increase in total atherosclerotic score per SD PTH increase: 0.04, 0.003-0.08; P=0.03) in the PIVUS study. During follow-up in the ULSAM study (median 16.7 years), 89 men were diagnosed with nonfatal atherosclerotic disease. In Cox-regression analyses adjusting for established vascular risk factors and mineral metabolism, higher PTH was associated with an increased risk of nonfatal atherosclerotic disease (hazard ratio for 1 SD increase of PTH: 1.55, 1.33-1.88; P<0.0001). Results were similar when including fatal atherosclerotic disease in the outcome.

    CONCLUSIONS: In 2 independent community-based cohorts, PTH was associated to the degree of atherosclerosis and risk of clinically overt atherosclerotic disease, respectively. Our data confirm and extend previous studies supporting a role for PTH in the development of atherosclerotic disease.

  • 75.
    Hallberg, Pär
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Karlsson, J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Kurland, L.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kahan, Thomas
    Malmqvist, K.
    Öhman, K. P.
    Nyström, F.
    Liljedahl, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Gender-specific association between preproendothelin-1 genotype and reduction of systolic blood pressure during antihypertensive treatment: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA)2004Ingår i: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 27, nr 5, s. 287-290Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Studies suggest that endothelin-1 contributes to the pathogenesis of hypertension. A G5665T gene polymorphism of preproendothelin-1 has been shown to be associated with higher blood pressure in overweight patients. No study has yet determined the effect of this polymorphism on the change in blood pressure during antihypertensive treatment.

    HYPOTHESIS:

    This study aimed to determine this effect in hypertensive patients with left ventricular (LV) hypertrophy during antihypertensive treatment with either irbesartan or atenolol.

    METHODS:

    We determined the preproendothelin-1 genotype using minisequencing in 102 patients with essential hypertension and LV hypertrophy verified by echocardiography, randomized in a double-blind fashion to treatment with either the AT1-receptor antagonist irbesartan or the beta1-adrenoceptor antagonist atenolol.

    RESULTS:

    The change in systolic blood pressure (SBP) after 12 weeks of treatment was related to the preproendothelin-1 genotype in men; after adjustment for potential covariates (age, blood pressure, and LV mass index at study entry, dose of irbesartan/atenolol, and type of treatment), those carrying the T-allele responded on average with a more than two-fold greater reduction than those with the G/G genotype (-21.9 mmHg [13.9] vs. -8.9 [2.3], p = 0.007). No significant differences in blood pressure change between G/G and carriers of the T-allele were seen among women.

    CONCLUSIONS:

    Our finding suggests a gender-specific relationship between the G5665T preproendothelin-1 polymorphism and change in SBP in response to antihypertensive treatment with irbesartan or atenolol, suggesting the endothelin pathway to be a common mechanism included in the hypertensive action of the drugs.

  • 76.
    Hallberg, Pär
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Billberger, Katarina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Karlsson, Julia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kurland, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kahan, Thomas
    Malmqvist, Karin
    Öhman, K. Peter
    Nyström, Fredrik
    Liljedahl, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Syvänen, Ann-Christne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Transforming growth factor beta1 genotype and change in left ventricular mass during antihypertensive treatment: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA)2004Ingår i: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 27, nr 3, s. 169-73Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Angiotensin II, via the angiotensin II type 1 (AT1) receptor, may mediate myocardial fibrosis and myocyte hypertrophy seen in hypertensive left ventricular (LV) hypertrophy through production of transforming growth factor beta1 (TGF-beta1); AT1-receptor antagonists reverse these changes. The TGF-beta1 G + 915C polymorphism is associated with interindividual variation in TGF-beta1 production. No study has yet determined the impact of this polymorphism on the response to antihypertensive treatment. HYPOTHESIS: We aimed to determine whether the TGF-beta1 G + 915C polymorphism was related to change in LV mass during antihypertensive treatment with either an AT1-receptor antagonists or a beta1-adrenoceptor blocker. The polymorphism was hypothesized to have an impact mainly on the irbesartan group. METHODS: We determined the association between the TGF-beta1 genotype and regression of LV mass in 90 patients with essential hypertension and echocardiographically diagnosed LV hypertrophy, randomized in a double-blind study to receive treatment for 48 weeks with either the AT1-receptor antagonist irbesartan or the beta1-adrenoceptor blocker atenolol. RESULTS: Irbesartan-treated patients who were carriers of the C-allele, which is associated with low expression of TGF-beta1, responded with a markedly greater decrease in LV mass index (LVMI) than subjects with the G/G genotype (adjusted mean change in LVMI -44.7 g/m2 vs. -22.2 g/m2, p = 0.007), independent of blood pressure reduction. No association between genotype and change in LVMI was observed in the atenolol group. CONCLUSIONS: The TGF-beta1 G + 915C polymorphism is related to the change in LVMI in response to antihypertensive treatment with the AT1-receptor antagonist irbesartan.

  • 77.
    Hallberg, Pär
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Karlsson, Julia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kurland, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kahan, Thomas
    Malmqvist, Karin
    Öhman, K. Peter
    Nyström, Fredrik
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    B2 bradykinin receptor (B2BKR) polymorphism and change in left ventricular mass in response to antihypertensive treatment: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial2003Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 21, nr 3, s. 621-4Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Hypertension is associated with a number of adverse morphologic and functional changes in the cardiovascular system, including left ventricular (LV) hypertrophy. Studies have demonstrated that bradykinin, through the B2 bradykinin receptor (B2BKR), mediates important cardiovascular effects that may protect against LV hypertrophy. Recently, a +9/-9 exon 1 polymorphism of the B2BKR was shown to be strongly associated with LV growth response among normotensive males undergoing physical training. We aimed to clarify whether the processes found in exercise-induced LV growth in normotensive people also occur in pathological LV hypertrophy. DESIGN AND METHODS: We determined the B2BKR genotype of 90 patients with essential hypertension and echocardiographically diagnosed LV hypertrophy, included in a double-blind study to receive treatment for 48 weeks with either the angiotensin II type 1 (AT1) receptor antagonist irbesartan or the beta1-adrenoceptor antagonist atenolol. RESULTS: B2BKR +9/+9 genotypes responded poorly in LV mass regression, independent of blood pressure reduction or treatment, as compared to the other genotypes (adjusted mean change in LV mass index = -10.0 +/- 4.6 versus -21.6 +/- 2.2 g/m2, P = 0.03). CONCLUSIONS: Our results suggest an impact of the B2BKR polymorphism on LV mass regression during antihypertensive treatment.

  • 78.
    Hallberg, Pär
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Kurland, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kahan, Thomas
    Malmqvist, Karin
    Öhman, Karl Peter
    Nyström, Fredrik
    Liljedahl, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Adipocyte-derived leucine aminopeptidase genotype and response to antihypertensive therapy2003Ingår i: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 18, nr 3, s. 11-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Adipocyte-derived leucine aminopeptidase (ALAP) is a recently identified member of the M1 family of zinc-metallopeptidases and is thought to play a role in blood pressure control through inactivation of angiotensin II and/or generation of bradykinin. The enzyme seems to be particularly abundant in the heart. Recently, the Arg528-encoding allele of the ALAP gene was shown to be associated with essential hypertension.

    Methods

    We evaluated the influence of this polymorphism on the change in left ventricular mass index in 90 patients with essential hypertension and echocardiographically diagnosed left ventricular hypertrophy, randomised in a double-blind study to receive treatment with either the angiotensin II type I receptor antagonist irbesartan or the beta1-adrenoceptor blocker atenolol for 48 weeks. Genyotyping was performed using minisequencing.

    Results

    After adjustment for potential covariates (blood pressure and left ventricular mass index at baseline, blood pressure change, age, sex, dose and added antihypertensive treatment), there was a marked difference between the Arg/Arg and Lys/Arg genotypes in patients treated with irbesartan; those with the Arg/Arg genotype responded on average with an almost two-fold greater regression of left ventricular mass index than patients with the Lys/Arg genotype (-30.1 g/m2 [3.6] vs -16.7 [4.5], p = 0.03).

    Conclusions

    The ALAP genotype seems to determine the degree of regression of left ventricular hypertrophy during antihypertensive treatment with the angiotensin II type I receptor antagonist irbesartan in patients with essential hypertension and left ventricular hypertrophy. This is the first report of a role for ALAP/aminopeptidases in left ventricular mass regulation, and suggests a new potential target for antihypertensive drugs.

  • 79.
    Hallberg, Pär
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Digoxin for the treatment of heart failure2003Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 348, nr 7, s. 661-662Artikel i tidskrift (Refereegranskat)
  • 80. Hallmarker, Ulf
    et al.
    Michaëlsson, Karl
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lagerqvist, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lindbäck, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    James, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Outcome After Myocardial Infarction In A Cohort Study Of Cross Country Skiers In Sweden2014Ingår i: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 63, nr 12, s. A1345-A1345Artikel i tidskrift (Refereegranskat)
  • 81.
    Hallström, Helena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Glynn, Anders
    Livsmedelsverket.
    Warensjö Lemming, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wolk, Alicja
    Institutet för miljömedicin, Karolinska institutet.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Long-term coffee consumption in relation to fracture risk and bone mineral density in women2013Ingår i: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 178, nr 6, s. 898-909Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    High consumption of coffee has been suggested to reduce the risk of some late-onset diseases and death but also to contribute to the development of osteoporotic fractures. Results of previous fracture studies have been inconsistent, and a comprehensive study is needed. The longitudinal population-based Swedish Mammography Cohort, including 61,433 women born in 1914-1948, was followed up from 1987 through 2008. Coffeeconsumption was assessed with repeated food frequency questionnaires. During follow-up, 14,738 women experienced fracture of any type, and 3,871 had a hip fracture. In a subcohort (n = 5,022), bone density was measured and osteoporosis determined (n = 1,012). After multivariable adjustment, there was no evidence of a higher rate of any fracture (hazard ratio per 200 mL coffee = 0.99; 95% confidence interval: 0.98, 1.00) or hip fracture (hazard ratio per 200 mL coffee = 0.97, 95% confidence interval: 0.95, 1.00) with increasing coffeeconsumption. A high coffee intake (>= 4 cups daily) versus a low intake (<1 cup daily) was associated with a 2%-4% lower bone density, depending on site (P < 0.001), but the odds ratio for osteoporosis was only 1.28 (95% confidence interval: 0.88, 1.87). Thus, high coffeeconsumption was associated with a small reduction in bone density that did not translate into an increased risk of fracture.

  • 82.
    Hallström, Helena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniskt forskningscentrum (UCR).
    Glynn, Anders
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniskt forskningscentrum (UCR).
    Coffee consumption and CYP1A2 genotype in relation to bone mineral density of the proximal femur in elderly men and women: a cohort study2010Ingår i: Nutrition & metabolism, ISSN 1743-7075, Vol. 7, s. 12-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    ABSTRACT: BACKGROUND: Drinking coffee has been linked to reduced calcium conservation, but it is less clear whether it leads to sustained bone mineral loss and if individual predisposition for caffeine metabolism might be important in this context. Therefore, the relation between consumption of coffee and bone mineral density (BMD) at the proximal femur in men and women was studied, taking into account, for the first time, genotypes for cytochrome P450 1A2 (CYP1A2) associated with metabolism of caffeine. METHODS: Dietary intakes of 359 men and 358 women (aged 72 years), participants of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), were assessed by a 7-day food diary. Two years later, BMD for total proximal femur, femoral neck and trochanteric regions of the proximal femur were measured by Dual-energy X-ray absorptiometry (DXA). Genotypes of CYP1A2 were determined. Adjusted means of BMD for each category of coffee consumption were calculated. RESULTS: Men consuming 4 cups of coffee or more per day had 4% lower BMD at the proximal femur (p = 0.04) compared with low or non-consumers of coffee. This difference was not observed in women. In high consumers of coffee, those with rapid metabolism of caffeine (C/C genotype) had lower BMD at the femoral neck (p = 0.01) and at the trochanter (p = 0.03) than slow metabolizers (T/T and C/T genotypes). Calcium intake did not modify the relation between coffee and BMD. CONCLUSION: High consumption of coffee seems to contribute to a reduction in BMD of the proximal femur in elderly men, but not in women. BMD was lower in high consumers of coffee with rapid metabolism of caffeine, suggesting that rapid metabolizers of caffeine may constitute a risk group for bone loss induced by coffee.

  • 83.
    Hallström, Helena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wolk, A.
    Glynn, Anders
    Warensjö, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Coffee consumption in relation to osteoporotic fracture risk and bone mineral density: A prospective longitudinal cohort study2012Ingår i: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, s. S36-S36Artikel i tidskrift (Övrigt vetenskapligt)
  • 84.
    Hallström, Helena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Wolk, Alicja
    Glynn, A.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Coffee, tea and caffeine consumption in relation to osteoporotic fracture risk in a cohort of Swedish women2006Ingår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 17, nr 7, s. 1055-64Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Consumption of coffee and tea, and total intake of caffeine has been claimed to be associated with osteoporotic fracture risk. However, results of earlier studies lack consistency. METHODS: We examined this relation in a cohort of 31,527 Swedish women aged 40-76 years at baseline in 1988. The consumption of coffee, caffeinated tea and the intake of caffeine were estimated from a self-administered food frequency questionnaire (FFQ). Multivariate-adjusted hazards ratios (HRs) of fractures with 95% confidence intervals (95% CIs) were estimated by Cox proportional hazards models. RESULTS: During a mean follow-up of 10.3 years, we observed 3,279 cases with osteoporotic fractures. The highest (>330 mg/day) compared with the lowest (<200 mg/day) quintile of caffeine intake was associated with a modestly increased risk of fracture: HR 1.20 (95% CI: 1.07-1.35). A high coffee consumption significantly increased the risk of fracture (p for trend 0.002), whereas tea drinking was not associated with risk. The increased risk of fracture with both a high caffeine intake and coffee consumption was confined to women with a low calcium intake (<700 mg/day): HR 1.33 (95% CI: 1.07-1.65) with > or =4 cups (600 ml)/day of coffee compared to <1 cup (150 ml)/day. The same comparison but risk estimated for women with a high propensity for fractures (> or =2 fracture types) revealed a HR of 1.88 (95% CI: 1.17-3.00). CONCLUSIONS: In conclusion, our results indicate that a daily intake of 330 mg of caffeine, equivalent to 4 cups (600 ml) of coffee, or more may be associated with a modestly increased risk of osteoporotic fractures, especially in women with a low intake of calcium.

  • 85.
    Hallström, Helena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wolk, Alicja
    Institutet för Miljömedicin, Karolinska Institutet.
    Glynn, Anders
    Livsmedlesverket.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Coffee Consumption and Risk of Fracture in the Cohort of Swedish Men (COSM)2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 5, s. e97770-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Recent research in a large cohort of women showed that coffee consumption is not associated with increased risk of fracture. Whether this is the case also among men is less clear. Methods: In the Cohort of Swedish Men (COSM) study, 42,978 men aged 45-79 years old at baseline in 1997 answered a self-administered food frequency questionnaire covering coffee consumption and a medical and lifestyle questionnaire covering potential confounders. Our main outcomes first fracture at any site and first hip fracture were collected from the National Patient Registry in Sweden. The association between coffee consumption and fracture risk was investigated using Cox's proportional hazards regression. Results: During a mean follow-up of 11.2 years, 5,066 men had a first fracture at any site and of these, 1,186 (23%) were hip fractures. There was no association between increasing coffee consumption (per 200 ml) and rate of any fracture (hazard ratio [HR] 1.00; 95% confidence interval [CI] 0.99-1.02) or hip fracture (HR 1.02; 95% CI 0.99-1.06) after adjustment for potential confounders. For men consuming >= 4 cups of coffee/day compared to those consuming <1 cup of coffee/day, HR for any type of fracture was 0.91 (95% CI 0.80-1.02) and for hip fracture: 0.89 (95% CI 0.70-1.14). Conclusions: High coffee consumption was not associated with an increased risk of fractures in this large cohort of Swedish men.

  • 86.
    Hansson, Jonas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Vasan, Ramachandran S.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ingelsson, Erik
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Biomarkers of Extracellular Matrix Metabolism (MMP-9 and TIMP-1) and Risk of Stroke, Myocardial Infarction, and Cause-Specific Mortality: Cohort Study2011Ingår i: PLoS ONE, ISSN 1932-6203, Vol. 6, nr 1, s. e16185-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Turnover of the extracellular matrix in all solid organs is governed mainly by a balance between the degrading matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). An altered extracellular matrix metabolism has been implicated in a variety of diseases. We investigated relations of serum levels of MMP-9 and TIMP-1 to mortality risk from an etiological perspective.

    Design: The prospective Uppsala Longitudinal Study of Adult Men (ULSAM) cohort, followed from 1991-1995 for up to 18.1 years. A random population-based sample of 1,082 71-year-old men, no loss to follow-up. Endpoints were all-cause (n = 628), cardiovascular (n = 230), non-cardiovascular (n = 398) and cancer mortality (n = 178), and fatal or non-fatal myocardial infarction (n = 138) or stroke (n = 163).

    Results: Serum MMP-9 and TIMP-1 levels were associated with risk of all-cause mortality (Cox proportional hazard ratio [HR] per standard deviation 1.10, 95% confidence interval [CI] 1.03-1.19; and 1.11, 1.02-1.20; respectively). TIMP-1 levels were mainly related to risks of cardiovascular mortality and stroke (HR per standard deviation 1.22, 95% CI 1.09-1.37; and 1.18, 1.04-1.35; respectively). All relations except those of TIMP-1 to stroke risk were attenuated by adjustment for cardiovascular disease risk factors. Relations in a subsample without cardiovascular disease or cancer were similar to those in the total sample.

    Conclusion: In this community-based cohort of elderly men, serum MMP-9 and TIMP-1 levels were related to mortality risk. An altered extracellular matrix metabolism may be involved in several detrimental pathways, and circulating MMP-9 or TIMP-1 levels may be relevant markers thereof.

  • 87.
    Hantikainen, Essi
    et al.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, S-17177 Stockholm, Sweden..
    Grotta, Alessandra
    Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, S-17177 Stockholm, Sweden..
    Ye, Weimin
    Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, S-17177 Stockholm, Sweden..
    Adami, Hans-Olov
    Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, S-17177 Stockholm, Sweden.;Harvard Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA..
    Surkan, Pamela J.
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, 615 North Wolfe St,Room E8527, Baltimore, MD 21205 USA..
    Serafini, Mauro
    Council Agr Res & Econ, Ctr Nutr, Funct Food & Metab Stress Prevent Lab, Via Ardeatina 546, I-00100 Rome, Italy..
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Bellocco, Rino
    Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, S-17177 Stockholm, Sweden.;Univ Milano Bicocca, Dept Stat & Quantitat Methods, Edificio U7,Via Bicocca Arcimboldi 8, I-20126 Milan, Italy..
    Lagerros, Ylva Trolle
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, T2, SE-17176 Stockholm, Sweden.;Kamlinska Univ Hosp, Dept Med, C2 84, SE-14186 Stockholm, Sweden..
    Prospective study of dietary Non Enzymatic Antioxidant Capacity on the risk of hip fracture in the elderly2016Ingår i: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 90, s. 31-36Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Dietary antioxidants may play an important role in the prevention of bone loss and associated fractures by reducing levels of oxidative stress. We prospectively investigated the association between dietary Non Enzymatic Antioxidant Capacity (NEAC) and the risk of hip fracture and whether this effect was modified by smoking. Method: In the Swedish National March Cohort 13,409 men and women over the age of 55 who had not experienced cancer, cardiovascular disease or hip fracture, were followed through record-linkages from 1997 through 2010. NEAC was assessed by a validated food frequency questionnaire collected at baseline. We categorized the distribution of NEAC into sex-specific quartiles and used multivariable adjusted Cox proportional hazards regression models to estimate hazard ratios (HRs) with 95% confidence intervals (95% CI). Results: During a mean follow-up time of 12.4 years, we identified 491 incident cases of first hip fracture. Subjects in the highest quartile of dietary NEAC had a 39% lower risk of incident hip fracture compared to those in the lowest quartile (HR: 0.61; 95% CI: 0.44-0.85). The association was non-linear (p for non-linearity: 0.004) with a potential threshold between the first and the second quartile and no further risk reduction at higher levels of dietary NEAC. Due to a low smoking prevalence in our study population, we had limited power to detect effect modification between dietary NEAC and smoking on a multiplicative or additive scale. Conclusion: Higher dietary NEAC intake is associated with lower risk of hip fracture in the elderly.

  • 88.
    Hellström, Hans-Olov
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Larsson, Sune
    No association between the biomechanical properties and the aluminium content of boneManuskript (Övrigt vetenskapligt)
  • 89.
    Hellström, Hans-Olov
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Mjöberg, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    The aluminium content of bone, and mortality risk2008Ingår i: Age and Ageing, ISSN 0002-0729, E-ISSN 1468-2834, Vol. 37, nr 2, s. 217-20Artikel i tidskrift (Refereegranskat)
  • 90. Holvik, K
    et al.
    Gjesdal, C G
    Tell, G S
    Grimnes, G
    Schei, B
    Apalset, E M
    Samuelsen, S O
    Blomhoff, R
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Meyer, H E
    Low serum concentrations of alpha-tocopherol are associated with increased risk of hip fracture: A NOREPOS study2014Ingår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 25, nr 11, s. 2545-2554Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We investigated the risk of hip fracture according to circulating alpha-tocopherol, a plant-derived substance with antioxidant properties, in community-dwelling older Norwegians. We found a linear increasing risk of hip fracture with lower serum alpha-tocopherol concentrations, with a 51 % higher risk in the lowest compared to the highest quartile.

    INTRODUCTION:

    Oxidative stress is a suggested contributing cause of osteoporosis and fractures. Vitamin E (α-tocopherol) has potent antioxidant properties in humans. The relationship between circulating α-tocopherol and fracture risk is not established. The aim of this study was to investigate the association between serum α-tocopherol concentrations and risk of hip fracture during up to 11 years of follow-up.

    METHODS:

    We performed a case-cohort analysis among 21,774 men and women aged 65-79 years who participated in four community-based health studies in Norway 1994-2001. Serum α-tocopherol concentrations at baseline were determined in 1,168 men and women who subsequently suffered hip fractures (median follow-up 8.2 years) and in a random sample (n = 1,434) from the same cohort. Cox proportional hazard regression adapted for gender-stratified case-cohort data was performed.

    RESULTS:

    Median (25, 75 percentile) serum α-tocopherol was 30.0 (22.6, 38.3) μmol/L, and it showed a linear inverse association with hip fracture: hazard ratio (HR) 1.11 (95 % confidence interval (CI) 1.04-1.20) per 10-μmol/L decrease in serum α-tocopherol, adjusted for gender and study center. The lowest compared to the highest quartile conferred an HR of 1.51 (95 % CI 1.17-1.95), adjusted for gender and study center. Adjustment for smoking, month of blood sample, BMI, education, physical inactivity, self-rated health, and serum 25-hydroxyvitamin D (25(OH)D) yielded similar results. Taking serum total cholesterol concentration into account attenuated the association somewhat: HR of hip fracture was 1.37 (95 % CI 1.05-1.77) in first versus fourth quartile of serum α-tocopherol/total cholesterol ratio.

    CONCLUSIONS:

    Low serum concentrations of α-tocopherol were associated with increased risk of hip fracture in older Norwegians.

  • 91.
    Hultin, Hella
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Ribom, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Michaelsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Persisting disturbances in calcium homeostasis after gastric bypass surgeryManuskript (preprint) (Övrigt vetenskapligt)
  • 92.
    Hållmarker, Ulf
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    James, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Sandin, Fredrik
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Cancer incidence in participants in a long-distance ski race (Vasaloppet, Sweden) compared to the background population.2015Ingår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 51, nr 4, s. 558-568Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: We studied the association between taking part in a long distance ski race and cancer incidence to address the hypothesis that a lifestyle involving a high degree of physical activity (PA) lowers cancer incidence with a pattern that is different by cancer site.

    METHODS: Cancer incidence was estimated in a large cohort of skiers (n=185,412) participating in the Vasaloppet long distance ski race in Sweden 1989-2010 and non-participants in the ski race, randomly selected from the Swedish general population (n=184,617). Data include race finishing times as a measurement of physical fitness. Hazard ratios (HRs) and net probability of cancer over twenty years of follow-up were estimated for all invasive cancer, and separately for prostate, breast, colo-rectal and lung cancer, and groups of cancers with presumed relation to lifestyle.

    FINDINGS: Participating in Vasaloppet was associated with a relative risk reduction for all invasive cancer of 6% (95% confidence interval 2-9%) and a relative risk reduction of 32% (95% confidence interval 28-37%) of cancer sites where there is epidemiological evidence that smoking, bodyweight, regular PA and consumption of fruit and vegetables are aetiological factors. For skin cancer the risk was increased, as for prostate cancer. Skiers with shorter finishing times had lower incidence of cancer.

    INTERPRETATION: This study indicates that it is unrealistic to reduce overall population cancer incidence drastically with life style. However, cancers that are epidemiologically associated with life style factors were significantly reduced by what presumably is a blend of non-smoking, normal body weight, sound dietary habits and PA. Our data thus provide additional support for present days' recommendations about life style prevention. Higher health awareness is associated with attendance to screening, which may explain our results for prostate cancer.

    FUNDING: University fund, independent funds from an insurance company and a private foundation.

  • 93.
    Hållmarker, Ulf
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Mora Hosp, Dept Internal Med, S-79285 Mora, Sweden.
    Lindbäck, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Ärnlöv, Johan
    Dalarna Univ, Sch Hlth & Social Studies, S-79188 Falun, Sweden;Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, S-17177 Stockholm, Sweden.
    Åsberg, Signild
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Wester, Per
    Umea Univ, Dept Publ Hlth & Clin Sci, S-90185 Umea, Sweden;Danderyd Hosp, Karolinska Inst, Dept Clin Sci, S-18288 Stockholm, Sweden.
    Hellberg, Dan
    Ctr Clin Res, S-79182 Falun, Sweden.
    Lagerqvist, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    James, Stefan K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Survival and incidence of cardiovascular diseases in participants in a long-distance ski race (Vasaloppet, Sweden) compared to the background population2018Ingår i: European Heart Journal - Quality of Care and Clinical Outcomes, ISSN 2058-5225, E-ISSN 2058-1742, Vol. 4, nr 2, s. 91-97Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We studied the relationship between taking part in a long-distance ski race and incidence of cardiovascular diseases (CVDs) to address the hypothesis that lifestyle lowers the incidence. A cohort of 399 630 subjects in Sweden, half were skiers in the world's largest ski race, and half were non-skiers. Non-skiers were frequency matched for sex, age, and year of race. Individuals with severe diseases were excluded. The endpoints were death, myocardial infarction, or stroke. The subjects were followed up for a maximum of 21.8 years and median of 9.8 years. We identified 9399 death, myocardial infarction, or stroke events among non-skiers and 4784 among the Vasaloppet skiers. The adjusted hazard ratios (HRs) comparing skiers and non-skiers were 0.52 [95% confidence interval (CI) 0.49-0.54] for all-cause mortality, 0.56 (95% CI 0.52-0.60) for myocardial infarction and 0.63 (95% CI 0.58-0.67) for stroke and for all three outcomes 0.56 (95% CI 0.54-0.58). The results were consistent across subgroups: age, sex, family status, education, and race year. For skiers, a doubling of race time was associated with a higher age-adjusted risk of 19%, and male skiers had a doubled risk than female skiers, with a HR 2.06 (95% CI 1.89-2.41). The outcome analyses revealed no differences in risk of atrial fibrillation between skiers and non-skiers. This large cohort study provides additional support for the hypothesis that individuals with high level of physical activity representing a healthy lifestyle, as evident by their participation in a long-distance ski race, have a lower risk of CVD or death.

  • 94.
    Hållmarker, Ulf
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Michaelsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Arnlov, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    James, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Cardiac Arrest in a Long-Distance Ski Race (Vasaloppet) in Sweden2012Ingår i: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 60, nr 15, s. 1431-1432Artikel i tidskrift (Refereegranskat)
  • 95.
    Hållmarker, Ulf
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Medicinkliniken Mora Landstinget Dalarna.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Högskolan Dalarna, Falun.
    Hellberg, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi. Centrum för klinisk forskning, Dalarna, Falun.
    Lagerqvist, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Lindbäck, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    James, Stefan K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Risk of recurrent ischaemic events after myocardial infarction in long-distance ski race participants2016Ingår i: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, nr 3, s. 282-290Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS: To study whether a high level of physical activity prior to myocardial infarction (MI) also protects against recurrent MI (re-MI) or death.

    METHODS AND RESULTS: A longitudinal study of a primary cohort consisting of 204,038 skiers with a proved substantially high level of physical activity in the world's largest long-distance ski race, Vasaloppet, and 499,543 non-skiers selected from the Swedish population. Individuals with severe diseases at baseline were excluded. In the nationwide clinical register, Swedeheart, we identified 7092 individuals with a first MI incident between 1989 and 2010. Of these, 1039 (0.5%) were skiers and 6053 (1.2%) were non-skiers. One hundred and sixty-three (15.7%) skiers and 1352 (22.3%) non-skiers suffered a re-MI or died during follow-up (median 4.44 years), corresponding to an incidence rate of 38.9 (95% confidence interval (CI) 33.2-45.4)/1000 person-years and 55.6 (95% CI 52.7-58.7)/1000 person-years, respectively. Severity of MI in both groups was the same. For skiers compared to non-skiers the unadjusted hazard ratio (HR) for re-MI was 0.66 (95% CI 0.52-0.82). For death or re-MI, HR was 0.70 (95% CI 0.59-0.82) with consistent results in subgroups based on race year, age, gender, education level, marital status. After adjustment for also smoking, diabetes, hypertension and cardiovascular medication, HR was 0.80 (95% CI 0.67-0.97).

    CONCLUSIONS: This large cohort study supports the hypothesis that patients with MI and with prior physical activity and healthy lifestyle, as evidenced by their participation in a long-distance ski race, have a lower risk of subsequent re-MI or death.

  • 96.
    Hållmarker, Ulf
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    James, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Reply to" Airway Remodeling and Cardiac Arrest in Long-Distance Ski Races" Journal of the American College of Cardiology, Volume 61, Issue 3, 22 January 2013, Pages 388-3892013Ingår i: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 61, nr 3, s. 389-Artikel i tidskrift (Övrigt vetenskapligt)
  • 97.
    Hållmarker, Ulf
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Åsberg, Signild
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Högskolan Dalarna Falun.
    Hellberg, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi. Centrum klinisk forskning Dalarna Falun.
    Lindbäck, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Wester, Per
    Medicin och folhälsa Umeå Universitet.
    James, Stefan K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Risk of Recurrent Stroke and Death After First Stroke in Long‐Distance Ski Race Participants2015Ingår i: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, nr 10, artikel-id e002469Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Physical activity is of benefit for primary prevention of cardiovascular diseases, but it appears to increase the risk for atrial fibrillation. We aimed to study a cohort of patients following a first stroke in individuals with previous high physical activity, compare them to the general population with respect to recurrent stroke and death, and relate these to atrial fibrillation.

    Methods and Results From the participants of the Vasaloppet, the world's largest ski‐race, and matched individuals from the general population (n=708 604), we identified 5964 patients hospitalized with a first‐time stroke between 1994 and 2010. Individuals with severe diseases were excluded. One half percent of skiers and 1% of nonskiers were hospitalized due to stroke. The incidence rate was 8.3 per 100 person‐years among skiers and 11.1 among nonskiers. The hazard ratio (HR) for recurrent stroke or death between the 2 groups was 0.76 (95% CI 0.67 to 0.86). The result was consistent in subgroups. The HR for death was 0.66 (95% CI 0.56 to 0.78) and for recurrent stroke 0.82 (95% CI 0.70 to 0.96). After adjustment for smoking and socioeconomic factors, the HR for death was consistent at 0.70 (95% CI 0.56 to 0.87) while the HR for recurrent stroke was not statistically significant. Outcomes for skiers with atrial fibrillation tended to show a lower risk than for nonskiers.

    Conclusions This large cohort study supports the hypothesis that patients with a stroke and with prior regular physical activity have a lower risk of death, while their risk for recurrent stroke is similar to that of nonskiers. The skiers had a higher incidence of atrial fibrillation, but still no increased risk of recurring stroke.

  • 98.
    Ingelsson, Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Vasan, Ramachandran S.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Blomhoff, Rune
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Circulating retinol-binding protein 4, cardiovascular risk factors and prevalent cardiovascular disease in elderly2009Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 206, nr 1, s. 239-244Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Our aim was to examine relations of serum retinol-binding protein 4 (RBP4) to cardiovascular risk factors, and prevalent metabolic syndrome (MetS) and cardiovascular disease (CVD) in a large community-based sample of elderly. METHODS: We evaluated cross-sectional relations of serum RBP4 to cardiovascular risk factors including anthropometrical measures, blood pressure, lipid measures, fasting glucose and insulin, body fat distribution including truncal fat by dual-energy x-ray absorptiometry (DXA), homeostasis model assessment insulin resistance (HOMA-IR) and prevalent MetS in one thousand eight 70-year old participants (50% women) of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), and in five hundred seven 82-year old men from Uppsala Longitudinal Study of Adult Men (ULSAM). In ULSAM, we also examined associations with prevalent CVD. RESULTS: RBP4 concentrations were positively correlated with serum triglycerides (r=0.30; P<0.0001 in both samples), whereas correlations with body mass index (BMI), waist circumference, sagittal abdominal diameter, total and truncal fat mass, total cholesterol, fasting glucose and HOMA-IR were weak. In multivariable-adjusted models, RBP-4 was associated with MetS (odds ratio (OR), 1.16 and 1.33; 95% confidence interval (CI), 0.99-1.37 and 1.05-1.67 per 1-standard deviation (SD) increase in PIVUS and ULSAM, respectively), and prior cerebrovascular disease (OR, 1.37; 95% CI, 1.00-1.88 per 1-SD increase in ULSAM), but not with prior myocardial infarction. CONCLUSION: In elderly, RBP4 concentrations were associated with MetS and its components in both sexes, and prior cerebrovascular disease in men. These findings are consistent with the hypothesis that circulating RBP4 could be a marker of metabolic complications and possibly also atherosclerosis and overt CVD.

  • 99.
    Ingelsson, Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Relative importance and conjoint effects of obesity and physical inactivity for the development of insulin resistance2009Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 16, nr 1, s. 28-33Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Obesity and physical inactivity are related to the development of insulin resistance, but their relative importance and conjoint effects are unclear. METHODS: We related body mass index (BMI) and self-reported leisure-time physical activity (PA) at the age of 50 years to insulin sensitivity measured with euglycemic insulin clamp technique and the presence of metabolic syndrome (MetS) at a subsequent examination, 20 years later, in 862 men free from diabetes and MetS at baseline. RESULTS: In a multivariable model including BMI, PA, homeostasis model assessment insulin resistance index, erythrocyte sedimentation rate, and all components of MetS at baseline, both BMI (beta, -0.19 mg/kg bodyweight/min per 1 kg/m; P<0.0001) and PA (adjusted least square means, 5.1, 5.2, 5.4, and 6.2 mg/kg bodyweight/min in individuals with sedentary, moderate, regular, and athletic PA, respectively; P=0.0035) were significant predictors of insulin sensitivity at age 70. When categorizing individuals into four groups by BMI and PA at baseline, insulin sensitivity at the age of 70 years decreased significantly over the following categories: multivariable-adjusted least square means, 5.8 (low BMI/high PA); 5.6 (low BMI/low PA); 5.1 (high BMI/high PA); and 4.6 (high BMI/low PA) mg/kg bodyweight/min, respectively; P value of less than 0.0001. CONCLUSION: In our community-based sample of middle-aged men, BMI and PA were independent predictors of insulin resistance after 20 years of follow-up. Our results imply that obesity and physical inactivity may increase insulin resistance and metabolic risk by partly independent pathways, and emphasize the importance of strategies that address both obesity and physical inactivity to achieve increased public health.

  • 100.
    Jacobsson, Josefin A.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Sällman Almén, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Benedict, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Hedberg, Lilia A.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Brooks, Samantha
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Axelsson, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Fredriksson, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Schiöth, Helgi B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Detailed Analysis of Variants in FTO in Association with Body Composition in a Cohort of 70-Year-Olds Suggests a Weakened Effect among Elderly2011Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 5, s. e20158-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

     The rs9939609 single-nucleotide polymorphism (SNP) in the fat mass and obesity (FTO) gene has previously been associated with higher BMI levels in children and young adults. In contrast, this association was not found in elderly men. BMI is a measure of overweight in relation to the individuals' height, but offers no insight into the regional body fat composition or distribution.

    Objective

    To examine whether the FTO gene is associated with overweight and body composition-related phenotypes rather than BMI, we measured waist circumference, total fat mass, trunk fat mass, leg fat mass, visceral and subcutaneous adipose tissue, and daily energy intake in 985 humans (493 women) at the age of 70 years. In total, 733 SNPs located in the FTO gene were genotyped in order to examine whether rs9939609 alone or the other SNPs, or their combinations, are linked to obesity-related measures in elderly humans.

    Design

    Cross-sectional analysis of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort.

    Results

     Neither a single SNP, such as rs9939609, nor a SNP combination was significantly linked to overweight, body composition-related measures, or daily energy intake in elderly humans. Of note, these observations hold both among men and women.

    Conclusions

    Due to the diversity of measurements included in the study, our findings strengthen the view that the effect of FTO on body composition appears to be less profound in later life compared to younger ages and that this is seemingly independent of gender.

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