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  • 1. Abarca-Gómez, L.
    et al.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Yngve, Agneta
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Food, Nutrition and Dietetics.
    Ezzati, M
    Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults.2017In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 390, no 10113, p. 2627-2642Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Underweight, overweight, and obesity in childhood and adolescence are associated with adverse health consequences throughout the life-course. Our aim was to estimate worldwide trends in mean body-mass index (BMI) and a comprehensive set of BMI categories that cover underweight to obesity in children and adolescents, and to compare trends with those of adults.

    METHODS: We pooled 2416 population-based studies with measurements of height and weight on 128·9 million participants aged 5 years and older, including 31·5 million aged 5-19 years. We used a Bayesian hierarchical model to estimate trends from 1975 to 2016 in 200 countries for mean BMI and for prevalence of BMI in the following categories for children and adolescents aged 5-19 years: more than 2 SD below the median of the WHO growth reference for children and adolescents (referred to as moderate and severe underweight hereafter), 2 SD to more than 1 SD below the median (mild underweight), 1 SD below the median to 1 SD above the median (healthy weight), more than 1 SD to 2 SD above the median (overweight but not obese), and more than 2 SD above the median (obesity).

    FINDINGS: Regional change in age-standardised mean BMI in girls from 1975 to 2016 ranged from virtually no change (-0·01 kg/m(2) per decade; 95% credible interval -0·42 to 0·39, posterior probability [PP] of the observed decrease being a true decrease=0·5098) in eastern Europe to an increase of 1·00 kg/m(2) per decade (0·69-1·35, PP>0·9999) in central Latin America and an increase of 0·95 kg/m(2) per decade (0·64-1·25, PP>0·9999) in Polynesia and Micronesia. The range for boys was from a non-significant increase of 0·09 kg/m(2) per decade (-0·33 to 0·49, PP=0·6926) in eastern Europe to an increase of 0·77 kg/m(2) per decade (0·50-1·06, PP>0·9999) in Polynesia and Micronesia. Trends in mean BMI have recently flattened in northwestern Europe and the high-income English-speaking and Asia-Pacific regions for both sexes, southwestern Europe for boys, and central and Andean Latin America for girls. By contrast, the rise in BMI has accelerated in east and south Asia for both sexes, and southeast Asia for boys. Global age-standardised prevalence of obesity increased from 0·7% (0·4-1·2) in 1975 to 5·6% (4·8-6·5) in 2016 in girls, and from 0·9% (0·5-1·3) in 1975 to 7·8% (6·7-9·1) in 2016 in boys; the prevalence of moderate and severe underweight decreased from 9·2% (6·0-12·9) in 1975 to 8·4% (6·8-10·1) in 2016 in girls and from 14·8% (10·4-19·5) in 1975 to 12·4% (10·3-14·5) in 2016 in boys. Prevalence of moderate and severe underweight was highest in India, at 22·7% (16·7-29·6) among girls and 30·7% (23·5-38·0) among boys. Prevalence of obesity was more than 30% in girls in Nauru, the Cook Islands, and Palau; and boys in the Cook Islands, Nauru, Palau, Niue, and American Samoa in 2016. Prevalence of obesity was about 20% or more in several countries in Polynesia and Micronesia, the Middle East and north Africa, the Caribbean, and the USA. In 2016, 75 (44-117) million girls and 117 (70-178) million boys worldwide were moderately or severely underweight. In the same year, 50 (24-89) million girls and 74 (39-125) million boys worldwide were obese.

    INTERPRETATION: The rising trends in children's and adolescents' BMI have plateaued in many high-income countries, albeit at high levels, but have accelerated in parts of Asia, with trends no longer correlated with those of adults.

  • 2.
    Ahlström, Tommy
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Rudberg, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Correlation between plasma calcium, parathyroid hormone (PTH) and the metabolic syndrome (MetS) in a community-based cohort of men and women2009In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 71, no 5, p. 673-678Article in journal (Refereed)
    Abstract [en]

    CONTEXT: In recent years, an association has been noted between several abnormalities that characterize the metabolic syndrome (MetS) and primary hyperparathyroidism (pHPT). These abnormalities include dyslipidaemia, obesity, insulin resistance and hypertension. The correlations between plasma calcium, parathyroid hormone (PTH) and the variables in the MetS in a normal population are still unclear.

    OBJECTIVE: To describe correlations between plasma calcium and PTH and the various abnormalities present in the MetS in a healthy population.

    DESIGN: We studied 1016 healthy individuals from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) population of 70 years old, by means of plasma analyses of calcium, PTH, creatinine, lipids, insulin and glucose, as well as by standardized blood pressure measurements. Further, body mass index (BMI) and waist circumference were determined.

    RESULTS: The more National Cholesterol Education Program (NCEP) criteria for the MetS that were met, the higher the s-PTH and albumin-corrected s-calcium. Further, positive correlations between plasma calcium and BMI (P = 0.0003), waist circumference (P = 0.0009) and insulin resistance (P = 0.079) were found. PTH and BMI (P < 0.0001), waist circumference (P < 0.0001), systolic blood pressure (P = 0.0034), diastolic blood pressure (P = 0.0008), serum triglycerides (P = 0.0003) and insulin resistance (P = 0.0003) were positively correlated, whereas serum high density lipoproteins (HDL) (P = 0.036) and PTH were negatively correlated.

    CONCLUSIONS: We conclude that PTH correlates with several of the metabolic factors included in the MetS within a normocalcaemic population. In addition, individuals with mild pHPT present significantly more NCEP criteria for MetS. We postulate that increased levels of PTH in pHPT may be associated with the increased cardiovascular morbidity and mortality seen in pHPT.

  • 3. Alshakarchi, J.
    et al.
    Terént, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    [HAS-BLED shows bleeding risk in ischemic stroke and atrial fibrillation. But adjustments are needed for safer assessment, according to quality study]2012In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, no 38, p. 1670-1672Article in journal (Refereed)
  • 4. Alshakarchi, J.
    et al.
    Terént, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    HAS-BLED visar blödningsrisk vid ischemisk stroke och förmaksflimmer2012In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, no 38, p. 1670-1672Article in journal (Refereed)
  • 5.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Daniela, Mariosa
    Adami, Hans-Olov
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Lagerros, Ylva Trolle
    Nyren, Olof
    Ye, Weimin
    Bellocco, Rino
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Dose–Response Relationship of Total and Leisure Time Physical Activity to Risk of Heart Failure: a prospective cohort study2014In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 7, no 5, p. 16p. 701-708Article in journal (Refereed)
    Abstract [en]

    Background—The nature of the association between levels of physical activity and risk of heart failure is little known. We investigated nonlinear associations of total and leisure time physical activity with risk of heart failure.

    Methods and Results—In 1997, 39 805 persons without heart failure completed a questionnaire of lifestyle factors and medical history. We used Cox regression models to investigate total (adjusting for education and previous myocardial infarction) and direct (multivariable-adjusted) effects of self-reported total and leisure time physical activity on risk of heart failure of any cause and heart failure of nonischemic origin. Heart failure diagnoses were obtained until December 31, 2010. Higher leisure time physical activity was associated with lower risk of heart failure of any cause; hazard ratio of the total effect of leisure time physical activity was for fifth versus first quintile 0.54; 95% confidence interval was 0.44 to 0.66. The direct effect was similar. High total daily physical activity level was associated with lower risk of heart failure, although the effect was less pronounced than for leisure time physical activity (total effect hazard ratio, 0.81; 95% confidence interval, 0.69–0.95; fifth versus first quintile). A similar direct effect observed.

    Conclusions—Leisure time physical activity was inversely related to risk of developing heart failure in a dose–response fashion. This was reflected in a similar but less pronounced association of total physical activity with risk of heart failure. Only part of the effects appeared to be mediated by traditional risk factors.

  • 6.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Farahmand, Bahman
    Ahlbom, Anders
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ljunghall, Sverker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Risk of arrhythmias in 52 755 long-distance cross-country skiers: a cohort study2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no 47, p. 3624-3631Article in journal (Refereed)
    Abstract [en]

    AIMS:

    We aimed to investigate the association of number of completed races and finishing time with risk of arrhythmias among participants of Vasaloppet, a 90 km cross-country skiing event.

    METHODS AND RESULTS:

    All the participants without cardiovascular disease who completed Vasaloppet during 1989-98 were followed through national registries until December 2005. Primary outcome was hospitalization for any arrhythmia and secondary outcomes were atrial fibrillation/flutter (AF), bradyarrhythmias, other supraventricular tachycardias (SVT), and ventricular tachycardia/ventricular fibrillation/cardiac arrest (VT/VF/CA). Among 52 755 participants, 919 experienced arrhythmia during follow-up. Adjusting for age, education, and occupational status, those who completed the highest number of races during the period had higher risk of any arrhythmias [hazard ratio (HR)1.30; 95% CI 1.08-1.58; for ≥5 vs. 1 completed race], AF (HR 1.29; 95% CI 1.04-1.61), and bradyarrhythmias (HR 2.10; 95% CI 1.28-3.47). Those who had the fastest relative finishing time also had higher risk of any arrhythmias (HR 1.30; 95% CI 1.04-1.62; for 100-160% vs. >240% of winning time), AF (1.20; 95% CI 0.93-1.55), and bradyarrhythmias (HR 1.85; 95% CI 0.97-3.54). SVT or VT/VF/CA was not associated with finishing time or number of completed races.

    CONCLUSIONS:

    Among male participants of a 90 km cross-country skiing event, a faster finishing time and a high number of completed races were associated with higher risk of arrhythmias. This was mainly driven by a higher incidence of AF and bradyarrhythmias. No association with SVT or VT/VF/CA was found.

  • 7.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Neovius, Martin
    Tynelius, Per
    Rasmussen, Finn
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Exercise capacity and muscle strength and risk of vascular disease and arrhythmias: A cohort study of 1.26 million young menManuscript (preprint) (Other academic)
    Abstract [en]

    Background:

    While physical activity and exercise protects against cardiovascular disease, athletes have higher risk of atrial fibrillation and other arrhythmias. Graded independent and joint influences of exercise capacity and muscle strength on these diseases are unknown.

    Methods:

    All 1.26 million Swedish men who participated in mandatory military conscription between 1972 and 1995 (at a median age of 18.2 years) contributed. Multivariable-adjusted Cox proportional hazards models were used to evaluate the associations of maximal exercise capacity and muscle strength at conscription to subsequent risk of vascular disease and arrhythmias, as identified in national registries.

    Results:

    During a median follow-up of 26.3 years, about 26,000 hospitalizations for vascular disease events and 17,000 for arrhythmias occurred. Exercise capacity was inversely associated with risk of vascular disease (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.61-0.67]; for 5th vs. 1st quintile) and so was muscle strength (HR 0.79; 0.76-0.83; for 5th vs. 1st quintile ). Similar associations were seen across a range of major vascular disease events. Exercise capacity was associated with incidence of arrhythmias in a U-shaped fashion (HR 0.91; 0.86-0.96; for 3rd vs. 1st quintile, and 0.99; 0.94-1.04; for 5th vs. 1st quintile). Higher muscle strength was associated with lower risk of arrhythmias (HR 0.87; 0.83-0.91; for 5th vs. 1st quintile). 

    Conclusion:

    Exercise capacity and muscle strength in late adolescence are independently and jointly associated with long-term risk of vascular disease and arrhythmias. The lower risk of vascular events with higher exercise capacity was not outweighed by higher risk of arrhythmias.

  • 8.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Skeletal muscle morphology and risk of cardiovascular disease in elderly men2015In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 22, no 2, p. 231-239Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    While it is well known that physical inactivity is a major risk factor for cardiovascular disease, there is still a search for the mechanisms by which exercise exerts its positive effect. Skeletal muscle fibre type can be affected to some extent by exercise, and different fibre types possess different anti-inflammatory and glucometabolic properties that may influence cardiovascular disease risk.

    DESIGN:

    Population-based cohort study.

    METHODS:

    We investigated relations of skeletal muscle morphology to risk of cardiovascular events in a sample of 466 71-year-old men without cardiovascular disease, of which 295 were physically active (strenuous physical activity at least 3 h/week).

    RESULTS:

    During a median of 13.1 years of follow up, 173 major cardiovascular events occurred. Among physically active men, 10% higher proportion of type-I (slow-twitch oxidative) fibres was associated with a hazard ratio (HR) of 0.84 (95% confidence interval 0.74-0.95) for cardiovascular events, and 10% higher proportion of type-IIx (fast-twitch glycolytic) fibres was associated with a HR of 1.24 (1.06-1.45), adjusting for age. Similar results were observed in several sets of multivariable-adjusted models. No association of muscle fibre type with risk of cardiovascular events was observed among physically inactive men.

    CONCLUSIONS:

    Higher skeletal muscle proportion of type-I fibres was associated with lower risk of cardiovascular events and a higher proportion of type-IIx fibres was associated with higher risk of cardiovascular events. These relations were only observed in physically active men. Skeletal muscle fibre composition may be a mediator of the protective effects of exercise against cardiovascular disease.

  • 9.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Mariosa, D.
    Adami, H. O.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ingelsson, E.
    Lagerros, Y.
    Nyren, O.
    Weimin, Y.
    Bellocco, R.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Total and leisure time physical activity and risk of heart failure: a prospective cohort study2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no Suppl 1, p. 1052-1052Article in journal (Other academic)
  • 10.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Rasmussen, F.
    Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden..
    Neovius, M.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden..
    Tynelius, P.
    Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Anthropometric measures and risk of atrial fibrillation - a cohort study of 1.2 million young men2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no Suppl. 1, p. 910-910Article in journal (Other academic)
  • 11.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Rasmussen, F.
    Lund Univ, Dept Hlth Sci, Lund, Sweden.
    Neovius, M.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.
    Tynelius, P.
    Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden;Stockholm Cty Council, Ctr Epidemiol & Community Med, Stockholm, Sweden.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Body size and risk of atrial fibrillation: a cohort study of 1.1 million young men2018In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 4, p. 346-355Article in journal (Refereed)
    Abstract [en]

    Background: Whilst tall stature has been related to lower risk of vascular disease, it has been proposed as a risk factor for atrial fibrillation. Little is known about other anthropometric measures and their joint effects on risk of atrial fibrillation.

    Objectives: We aim to investigate associations and potential joint effects of height, weight, body surface area (BSA) and body mass index (BMI) with risk of atrial fibrillation.

    Methods: In a cohort covering 1 153 151 18-year-old men participating in the Swedish military conscription (1972-1995), Cox regression was used to investigate associations of height, weight, BSA and BMI with risk of atrial fibrillation.

    Results: During a median of 26.3 years of follow-up, higher height was associated with higher risk of atrial fibrillation (hazard ratio [HR] 2.80; 95% CI 2.63-2.98; for 5th vs. 1st quintile) and so was larger BSA (HR 3.05; 95% CI 2.82-3.28; for 5th vs. 1st quintile). Higher weight and BMI were to a lesser extent associated with risk of atrial fibrillation (BMI: 1.42; 95% CI 1.33-1.52, for 5th vs. 1st quintile). We found a multiplicative joint effect of height and weight. Adjusting for muscle strength, exercise capacity and diseases related to atrial fibrillation attenuated these measures.

    Conclusions: Higher height and weight are strongly associated with higher risk of atrial fibrillation. These associations are multiplicative and independent of each other and are summarized in a strong association of body surface area with risk of atrial fibrillation. The mechanisms remain unknown but may involve increased atrial volume load with larger body size.

  • 12.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Rasmussen, Finn
    Karolinska Inst, Dept Publ Hlth Sci, Child & Adolescent Publ Hlth Epidemiol Unit, Stockholm, Sweden..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Neovius, Martin
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden..
    Tynelius, Per
    Karolinska Inst, Dept Publ Hlth Sci, Child & Adolescent Publ Hlth Epidemiol Unit, Stockholm, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Exercise capacity and muscle strength and risk of vascular disease and arrhythmia in 1.1 million young Swedish men: cohort study2015In: BMJ-BRITISH MEDICAL JOURNAL, ISSN 1756-1833, Vol. 351, article id h4543Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To investigate the associations of exercise capacity and muscle strength in late adolescence with risk of vascular disease and arrhythmia. DESIGN Cohort study. SETTING General population in Sweden. PARTICIPANTS 1.1 million men who participated in mandatory military conscription between 1 August 1972 and 31 December 1995, at a median age of 18.2 years. Participants were followed until 31 December 2010. MAIN OUTCOMES Associations between exercise capacity and muscle strength with risk of vascular disease and subgroups (ischaemic heart disease, heart failure, stroke, and cardiovascular death) and risk of arrhythmia and subgroups (atrial fibrillation or flutter, bradyarrhythmia, supraventricular tachycardia, and ventricular arrhythmia or sudden cardiac death). Maximum exercise capacity was estimated by the ergometer bicycle test, and muscle strength was measured as handgrip strength by a hand dynamometer. High exercise capacity or muscle strength was deemed as above the median level. RESULTS During a median follow-up of 26.3 years, 26 088 vascular disease events and 17 312 arrhythmia events were recorded. Exercise capacity was inversely associated with risk of vascular disease and its subgroups. Muscle strength was also inversely associated with vascular disease risk, driven by associations of higher muscle strength with lower risk of heart failure and cardiovascular death. Exercise capacity had a U shaped association with risk of arrhythmia, driven by a direct association with risk of atrial fibrillation and a U shaped association with bradyarrhythmia. Higher muscle strength was associated with lower risk of arrhythmia (specifically, lower risk of bradyarrhythmia and ventricular arrhythmia). The combination of high exercise capacity and high muscle strength was associated with a hazard ratio of 0.67 (95% confidence interval 0.65 to 0.70) for vascular events and 0.92 (0.88 to 0.97) for arrhythmia compared with the combination of low exercise capacity and low muscle strength. CONCLUSIONS Exercise capacity and muscle strength in late adolescence are independently and jointly associated with long term risk of vascular disease and arrhythmia. The health benefit of lower risk of vascular events with higher exercise capacity was not outweighed by higher risk of arrhythmia.

  • 13.
    Andersson, Helén
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Rönn, Monika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Eva, Brittebo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Experimental studies of bisphenol A in cardiovascular cells and tissues: effects on genes that regulate angiogenesis and vascular tone2012In:  , 2012Conference paper (Refereed)
  • 14. Andersson, P.
    et al.
    Londahl, M.
    Abdon, N. -J
    Terént, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    The prevalence of atrial fibrillation in a geographically well-defined population in Northern Sweden: implications for anticoagulation prophylaxis2012In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 272, no 2, p. 170-176Article in journal (Refereed)
    Abstract [en]

    Objectives. The aims of this study were to evaluate the community-based prevalence of atrial fibrillation (AF) in a western society using a geographically well-defined population in the northern part of Sweden as a reference and to estimate the proportion of patients eligible for oral anticoagulation (OAC) prophylactic therapy according to the stroke risk indices CHADS2 and CHA2DS2-VASc. Bleeding risk was assessed using the HAS-BLED score.

    Design. The study population was recruited from AURICULA, a Swedish national quality register for patients receiving anticoagulation treatment. All patients with the diagnosis AF in the catchment area are registered in AURICULA.

    Results. Of the 65 532 inhabitants in the catchment area, 1616 were diagnosed with AF (1200 cases were characterized as chronic AF). Thus, the overall prevalence of AF was 2.5%. The prevalence increased with age from 6.3% in patients over 55 years of age to 13.8% in those over 80 years. The prevalence was higher in men than in women in all age groups. Overall, 56.3% and 85.1% of the population were at high risk of stroke (=2 points) according to CHADS2 and CHA2DS2-VASc, respectively. In addition, 26.9% had an increased bleeding risk according to HAS-BLED.

    Conclusion. Within this large Caucasian population, we identified the highest community-based prevalence of AF to date. The prevalence was strongly associated with increasing age and male gender. Using CHA2DS2-VASc instead of CHADS2 widened the indication for OAC prophylactic therapy of AF in this population.

  • 15. Andersson, Tommy
    et al.
    Magnuson, Anders
    Bryngelsson, Ing-Liss
    Frobert, Ole
    Henriksson, Karin M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Edvardsson, Nils
    Poci, Dritan
    Gender-related differences in risk of cardiovascular morbidity and all-cause mortality in patients hospitalized with incident atrial fibrillation without concomitant diseases: A nationwide cohort study of 9519 patients2014In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 177, no 1, p. 91-99Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies of patients with "lone" and "idiopathic" atrial fibrillation (AF) have provided conflicting evidence concerning the development, management and prognosis of this condition. Methods: In this nation-wide, retrospective, cohort study, we studied patients diagnosed with incidental AF recorded in national Swedish registries between 1995 and 2008. Controls were matched for age, sex and calendar year of the diagnosis of AF in patients. All subjects were free of any in-hospital diagnosis from 1987 and until patients were diagnosed with AF and also free of any diagnosis within one year from the time of inclusion. Follow-up continued until 2009. We identified 9519 patients (31% women) and 12,468 matched controls. Results: Relative risks (RR) versus controls for stroke or transient ischemic attack (TIA) in women were 19.6, 4.4, 3.4 and 2.5 in the age categories <55, 55-64, 65-74 and 75-85, years respectively. Corresponding figures for men were 3.4, 2.5, 1.7 and 1.9. RR for heart failure were 6.6, 6.6, 6.3 and 3.8 in women and 7.8, 4.6, 4.9 and 2.9 in men. All RR were statistically significant with p < 0.01. RR for myocardial infarction and all-cause mortality were statistically significantly increased only in the two oldest age categories in women and 65-74 years in men. Conclusions: Patients with AF and no co-morbidities at inclusion had at least a doubled risk of stroke or TIA and a tripled risk of heart failure, through all age categories, as compared to controls. Women were at higher RR of stroke or TIA than men. 

  • 16.
    Andersson, Tommy
    et al.
    Orebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden..
    Magnuson, Anders
    Orebro Univ, Sch Med Sci, Clin Epidemiol & Biostat, Orebro, Sweden..
    Bryngelsson, Ing-Liss
    Orebro Univ, Dept Occupat & Environm Med, Orebro, Sweden..
    Frobert, Ole
    Orebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden..
    Henriksson, Karin M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Edvardsson, Nils
    Sahlgrens Univ Hosp, Sahlgrenska Acad, Gothenburg, Sweden..
    Poci, Dritan
    Orebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden..
    Patients with atrial fibrillation and outcomes of cerebral infarction in those with treatment of warfarin versus no warfarin with references to CHA(2)DS(2)-VASc score, age and sex - A Swedish nationwide observational study with 48 433 patients2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 5, article id e0176846Article in journal (Refereed)
    Abstract [en]

    Aims: There is controversy in the guidelines as to whether patients with atrial fibrillation and a low risk of stroke should be treated with anticoagulation, especially those with a CHA(2)DS(2)-VASc score of 1 point.

    Methods: In a retrospective, nationwide cohort study, we used the Swedish National Patient Registry, the National Prescribed Drugs Registry, the Swedish Registry of Education and the Population and Housing Census Registry. 48 433 patients were identified between 1 January 2006 and 31 December 2008 with incident atrial fibrillation who were divided in age categories, sex and a CHA(2)DS(2)-VASc score of 0, 1, 2 and >= 3 and they were included in a time-varying analysis of warfarin treatment versus no treatment. The primary end-point was cerebral infarction and stroke, and patients were followed until 31 December 2009.

    Results: Patients with 1 point from the CHA(2)DS(2)-VASc score showed the following adjusted hazard ratios (HR) with a 95% confidence interval: men 65-74 years 0.46 (0.25-0.83), men < 65 years 1.11 (0.56-2.23) and women < 65 years 2.13 (0.94-4.82), where HR < 1 indicates protection with warfarin. In patients < 65 years and 2 points, HR in men was 0.35 (0.18-0.69) and in women 1.84 (0.86-3.94) while, in women with at least 3 points, HR was 0.31 (0.16-0.59). In patients 65-74 years and 2 points, HR in men was 0.37 (0.23-0.59) and in women 0.39 ( 0.21-0.73). Categories including age >= 65 years or >= 3 points showed a statistically significant protection from warfarin.

    Conclusions: Our results support that treatment with anticoagulation may be considered in all patients with an incident atrial fibrillation diagnosis and an age of 65 years and older, i.e. also when the CHA(2)DS(2)-VASc score is 1.

  • 17.
    Andersson, Tommy
    et al.
    Orebro Univ, Sch Med Sci, Dept Cardiol, Orebro, Sweden..
    Magnuson, Anders
    Orebro Univ, Sch Med Sci, Clin Epidemiol & Biostat, Orebro, Sweden..
    Bryngelsson, Ing-Liss
    Orebro Univ, Sch Med Sci, Dept Occupat & Environm Med, Orebro, Sweden..
    Frobert, Ole
    Orebro Univ, Sch Med Sci, Dept Cardiol, Orebro, Sweden..
    Henriksson, Karin M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. AstraZeneca R&D, Molndal, Sweden..
    Edvardsson, Nils
    Sahlgrens Univ Hosp, Sahlgrenska Acad, Gothenburg, Sweden..
    Poci, Dritan
    Orebro Univ, Sch Med Sci, Dept Cardiol, Orebro, Sweden..
    Patients without comorbidities at the time of diagnosis of atrial fibrillation: causes of death during long-term follow-up compared to matched controls2017In: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 40, no 11, p. 1076-1082Article in journal (Refereed)
    Abstract [en]

    BackgroundLittle is known about the long-term, cause-specific mortality risk in patients without comorbidities at the time of diagnosis of atrial fibrillation (AF). MethodsFrom a nation-wide registry of patients hospitalized with incident AF between 1995 and 2008 we identified 9 519 patients with a first diagnosed AF and no comorbidities at the time of AF diagnosis. They were matched with 12 468 controls. The follow-up continued until December 2008. Causes of death were classified according to the ICD-10 codes. ResultsDuring follow-up, 11.1% of patients with AF and 8.3% of controls died. Cardiovascular diseases were the most common causes of death and the only diagnoses which showed significantly higher relative risk in patients with AF than controls (HR 2.0, 95% CI 1.8-2.3), and the relative risk was significantly higher in women than in men. Stroke was a more common cause among patients with AF, 13.1% versus 9.7% (HR 2.7, 95% CI 1.8-4.0), while cerebral hemorrhage was more common among controls, 4.7% versus 10.2% (HR 0.9, 95% CI 0.6-1.5). The time from AF diagnosis to death was 6.03.1years. ConclusionsIn patients with incident AF and no known comorbidities at the time of AF diagnosis, only cardiovascular diseases were more often causes of death as compared to controls. Women carried a significantly higher relative risk than men.

  • 18.
    Andersén, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Larsson, Kjerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden..
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences. Univ Uppsala Hosp, ArbetsRehab Occupat & Environm Med, Uppsala, Sweden..
    Kristiansson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Anderzén, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine. Univ Uppsala Hosp, ArbetsRehab Occupat & Environm Med, Uppsala, Sweden..
    Predictors of self-efficacy in women on long-term sick leave2015In: International Journal of Rehabilitation Research, ISSN 0342-5282, E-ISSN 1473-5660, Vol. 38, no 4, p. 320-326Article in journal (Refereed)
    Abstract [en]

    Self-efficacy has been shown to be related to sick leave and to be a predictor of return to work after sickness absence. The aim of this study was to investigate whether factors related to sick leave predict self-efficacy in women on long-term sick leave because of pain and/or mental illness. This cross-sectional study uses baseline data from 337 Swedish women with pain and/or mental illness. All included women took part in vocational rehabilitation. Data were collected through a sick leave register and a baseline questionnaire. General self-efficacy, sociodemographics, self-rated health, anxiety, depression, view of the future, and social support were measured and analyzed by univariate and multivariate linear regression analyses. The full multivariate linear regression model, which included mental health factors together with all measured factors, showed that anxiety and depression were the only predictive factors of lower self-efficacy (adjusted R-2 = 0.46, P < 0.001) and explained 46% of the variance in self-efficacy. The mean scores of general self-efficacy were low, especially in women born abroad, those with low motivation, those with uncertainties about returning to work, and women reporting distrust. Anxiety and depression are important factors to consider when targeting self-efficacy in vocational rehabilitation.

  • 19.
    Andreasson, Anna
    et al.
    Karolinska Inst, Dept Med, Stockholm, Sweden.;Stockholm Univ, Stress Res Inst, Stockholm, Sweden.;Macquarie Univ, Dept Psychol, N Ryde, NSW, Australia..
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med, Huddinge, Sweden.
    Önnerhag, Kristina
    Skane Univ Hosp, Dept Gastroenterol & Hepatol, Malmo, Sweden..
    Hagström, Hannes
    Karolinska Inst, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Digest Dis, Div Hepatol, Stockholm, Sweden..
    Waist/Hip Ratio Better Predicts Development of Severe Liver Disease Within 20 Years Than Body Mass Index: A Population-based Cohort Study2017In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 15, no 8, p. 1294-1301Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Obesity, commonly assessed based on body mass index (BMI), is associated with an increased risk for severe liver disease. It is not known if other measures of body composition are better determinants of risk for severe liver disease, and/or if these differ between women and men. We investigated the body composition measures that best predict the development of severe liver disease.

    METHODS: We collected data from the Malmo Diet and Cancer study in Sweden, comprising 16,784 women and 10,833 (mean age, 58.1 years at baseline), and followed patients for a median 19.8 years. We analyzed data on measures of body composition including BMI, waist/hip ratio, and others. We determined whether subjects were diagnosed with severe liver disease, or died from severe liver disease, until the end of 2014 using Swedish national registers. Associations between body composition measures and severe liver disease were assessed using Cox regression models, stratified by sex and adjusted for age, alcohol consumption, smoking, education, and physical activity.

    RESULTS: All studied measures of body composition were significantly associated with severe liver disease. Waist/hip ratio was the best predictor of severe liver disease in women (hazard ratio [HR] per standard deviation increment, 1.30; 95% confidence interval [CI], 1.16-1.46) and men (HR, 1.46; 95% CI, 1.31-1.63). BMI had the lowest HR in women (HR, 1.12; 95% CI, 1.00-1.27) and men (HR, 1.26; 95% CI, 1.12-1.42). The association between waist/hip ratio and development of liver disease was independent of BMI.

    CONCLUSIONS: In a Swedish population-based cohort study, we associated all measures of body composition with risk of severe liver disease. However, measures of abdominal obesity were best at predicting development of severe liver disease.

  • 20.
    Appelros, Peter
    et al.
    Örebro Univ Hosp.
    Farahmand, Bahman
    Alzheimer Dis Res Ctr, Epiconsultant Formerly Karolinska Inst, Stockholm, Sweden..
    Terént, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    To Treat or Not to Treat: Anticoagulants as Secondary Preventives to the Oldest Old With Atrial Fibrillation2017In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 48, no 6, p. 1617-1622Article in journal (Refereed)
    Abstract [en]

    Background and Purpose-Anticoagulant treatment is effective for preventing recurrent ischemic strokes in patients who have atrial fibrillation. This benefit is paid by a small increase of hemorrhages. Anticoagulant-related hemorrhages seem to increase with age, but there are few studies showing whether the benefits of treatment persist in old age.

    Methods-For this observational study, 4 different registers were used, among them Riksstroke, the Swedish Stroke Register. Patients who have had a recent ischemic stroke, were 80 to 100 years of age, and had atrial fibrillation, were included from 2006 through 2013. The patients were stratified into 3 age groups: 80 to 84, 85 to 89, and ?90 years of age. Information on stroke severity, risk factors, drugs, and comorbidities was gathered from the registers. The patients were followed with respect to ischemic or hemorrhagic stroke, other hemorrhages, or death.

    Results-Of all 23 356 patients with atrial fibrillation, 6361 (27%) used anticoagulants after an ischemic stroke. Anticoagulant treatment was associated with less recurrent ischemic stroke in all age groups. Hemorrhages increased most in the >= 90-year age group, but this did not offset the overall beneficial effect of the anticoagulant. Apart from age, no other cardiovascular risk factor or comorbidity was identified that influenced the risk of anticoagulant-associated hemorrhage. Drugs other than anticoagulants did not influence the incidence of major hemorrhage.

    Conclusions-Given the patient characteristics in this study, there is room for more patients to be treated with anticoagulants, without hemorrhages to prevail. In nonagenarians, hemorrhages increased somewhat more, but this did not affect the overall outcome in this age stratum.

  • 21. Appelros, Peter
    et al.
    Jonsson, Fredrik
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Asplund, Kjell
    Glader, Eva-Lotta
    Asberg, Kerstin Hulter
    Norrving, Bo
    Stegmayr, Birgitta
    Terént, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Trends in Stroke Treatment and Outcome between 1995 and 2010: Observations from Riks-Stroke, the Swedish Stroke Register2014In: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 37, no 1, p. 22-29Article in journal (Refereed)
    Abstract [en]

    Background: Continuous changes in stroke treatment and care, as well as changes in stroke characteristics, may alter stroke outcome over time. The aim of this paper is to describe time trends for treatment and outcome data, and to discuss if any such changes could be attributed to quality changes in stroke care. Methods: Data from Riks-Stroke, the Swedish stroke register, were analyzed for the time period of 1995 through 2010. The total number of patients included was 320,181. The following parameters were included: use of computed tomography (CT), stroke unit care, thrombolysis, medication before and after the stroke, length of stay in hospital, and discharge destination. Three months after stroke, data regarding walking, toileting and dressing ability, as well social situation, were gathered. Survival status after 7, 27 and 90 days was registered. Results: In 1995, 53.9% of stroke patients were treated in stroke units. In 2010 this proportion had increased to 87.5%. Fewer patients were discharged to geriatric or rehabilitation departments in later years (23.6% in 2001 compared with 13.4% in 2010), but more were discharged directly home (44.2 vs. 52.4%) or home with home rehabilitation (0 vs. 10.7%). The need for home help service increased from 18.2% in 1995 to 22.1% in 2010. Regarding prevention, more patients were on warfarin, antihypertensives and statins both before and after the stroke. The functional outcome measures after 3 months did improve from 2001 to 2010. In 2001, 83.8% of patients were walking independently, while 85.6% were independent in 2010. For toileting, independence increased from 81.2 to 84.1%, and for dressing from 78.0 to 80.4%. Case fatality (CF) rates after 3 months increased from 18.7% (2001) to 20.0% (2010). This trend is driven by patients with severe strokes. Conclusions: Stroke outcomes may change over a relatively short time period. In some ways, the quality of care has improved. More stroke patients have CT, more patients are treated in stroke units and more have secondary prevention. Patients with milder strokes may have benefited more from these measures than patients with severe strokes. Increased CF rates for patients with severe stroke may be caused by shorter hospital stays, shorter in-hospital rehabilitation periods and lack of suitable care after discharge from hospital.

  • 22. Appelros, Peter
    et al.
    Terént, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Thrombolysis in acute stroke2015In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 385, no 9976, p. 1394-1394Article in journal (Refereed)
  • 23.
    Arefalk, Gabriel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Smokeless Tobacco (Snus) and Cardiovascular Disease: Associations with Heart Failure and Prognosis after Myocardial Infarction2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Previous investigations of snus use (oral moist snuff, a Swedish form of smokeless tobacco) and cardiovascular disease have generally focused on atherosclerotic events such as myocardial infarction and stroke, likely because smoking is such a well-established risk factor for atherosclerotic disease. Smokeless administration of tobacco circumvents most of the atherogenic effects of the combusted products from smoked tobacco, but it is possible that the potent autonomic and hemodynamic effects of snus and nicotine per se are detrimental for cardiovascular tissues.

    The aim of this thesis was to investigate if snus is associated with development of heart failure and the prognosis after myocardial infarction. We used data from Swedish cohort studies and the national quality register for myocardial infarctions (SWEDEHEART), with linkages to national registers.

    Snus use was associated with a higher risk of heart failure in a dose-response manner. This association was specific to non-ischemic heart failure, implying a direct myocardial effect, rather than an atherogenic effect (papers I and II).

    Acute, short-term or long-term outcomes following a myocardial infarction were not consistently worse among snus users relative to snus non-users, although snus use was associated with an increased risk of death after myocardial infarction among never-smokers (paper III).

    Discontinuation of snus use after a myocardial infarction was associated with an almost halved mortality risk, similar to the benefit associated with smoking cessation (paper IV).

    Although smoking was consistently stronger related to all adverse outcomes, and with reservations due to the observational design, the findings from this thesis indicate that snus should not be regarded as harmless. Snus use was associated with a higher risk of heart failure and post-myocardial infarction mortality, which may have public health implications for the risk assessment of snus, and potentially other modes of smokeless nicotine.

    List of papers
    1. Smokeless Tobacco (Snus) and Risk of Heart Failure: Results from Two Swedish Cohorts
    Open this publication in new window or tab >>Smokeless Tobacco (Snus) and Risk of Heart Failure: Results from Two Swedish Cohorts
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    2012 (English)In: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 19, no 5, p. 1120-1127Article in journal (Refereed) Published
    Abstract [en]

    Background:

    Oral moist snuff (snus) is discussed as a safer alternative to smoking, and its use is increasing. Based on its documented effect on blood pressure, we hypothesized that use of snus increases the risk of heart failure.

    Design:

    Two independent Swedish prospective cohorts; the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based sample of 1076 elderly men, and the Construction Workers Cohort (CWC), a sample of 118,425 never-smoking male construction workers.

    Methods:

    Cox proportional hazards models were used to investigate possible associations of snus use with risk of a first hospitalization for heart failure.

    Results:

    In ULSAM, 95 men were hospitalized for heart failure, during a median follow up of 8.9 years. In a model adjusted for established risk factors including past and present smoking exposure, current snus use was associated with a higher risk of heart failure [hazard ratio (HR) 2.08, 95% confidence interval (CI) 1.03-4.22] relative to non-use. Snus use was particularly associated with risk of non-ischaemic heart failure (HR 2.55, 95% CI 1.12-5.82). In CWC, 545 men were hospitalized for heart failure, during a median follow up of 18 years. In multivariable-adjusted models, current snus use was moderately associated with a higher risk of heart failure (HR 1.28, 95% CI 1.00-1.64) and non-ischaemic heart failure (HR 1.28, 95% CI 0.97-1.68) relative to never tobacco use.

    Conclusion:

    Data from two independent cohorts suggest that use of snus may be associated with a higher risk of heart failure.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-164695 (URN)10.1177/1741826711420003 (DOI)000309527700022 ()21828223 (PubMedID)
    Note

    De två första författarna delar förstaförfattarskapet.

    Available from: 2011-12-22 Created: 2011-12-22 Last updated: 2018-03-22
    2. Smokeless Tobacco (Snus) and Risk of Heart Failure of Ischemic and Non-Ischemic Origin: a Pooled Analysis of Eight Prospective Cohort Studies
    Open this publication in new window or tab >>Smokeless Tobacco (Snus) and Risk of Heart Failure of Ischemic and Non-Ischemic Origin: a Pooled Analysis of Eight Prospective Cohort Studies
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background

    Snus, a Swedish type of smokeless tobacco, has potent acute hemodynamic effects, which could provoke stress on the cardiovascular system, including the myocardium. Snus has, however, not been linked to risk of ischemic heart disease. Therefore, we hypothesized that snus use increases the risk for heart failure of non-ischemic origin.

    Methods

    We conducted a pooled analysis of eight Swedish prospective cohort studies involving individual participant data from 350,711 men. Shared frailty models with random effects at the cohort level, were used to estimate hazard ratios (HRs) with 95 % confidence intervals (CIs) of heart failure in relation to snus use. We investigated dose-response associations, and association with ischemic and non-ischemic heart failure in separate. For positive control purposes, we also investigated associations between smoking and risk of heart failure.

    Results

    During a median follow-up time of 16 years, 5,404 men were hospitalized for heart failure. In models adjusting for age, smoking, previous myocardial infarction and educational level, current snus use was associated with a higher risk of heart failure (HR 1.27, 95 % CI 1.07-1.50), relative to non-current snus use. A dose-response pattern was observed, with higher risk with more snus cans used per week. We observed an association of snus use with non-ischemic heart failure, HR 1.34 (95 % CI 1.11-1.63), but not with ischemic heart failure, HR 1.01 (95 % CI 0.72-1.42). Smoking was more strongly associated with heart failure, particularly of ischemic origin, than snus use.

    Conclusions

    Snus use was associated with a modestly increased risk for heart failure of non-ischemic origin in a dose-response manner. This finding has public health implications for the risk assessment of snus use, and potentially other modes of smokeless use of nicotine.

    National Category
    Cardiac and Cardiovascular Systems Public Health, Global Health, Social Medicine and Epidemiology
    Research subject
    Cardiology; Epidemiology
    Identifiers
    urn:nbn:se:uu:diva-345868 (URN)
    Available from: 2018-03-18 Created: 2018-03-18 Last updated: 2018-03-22
    3. Smokeless Tobacco (Snus) and Outcome of Myocardial Infarction: a SWEDEHEART Study
    Open this publication in new window or tab >>Smokeless Tobacco (Snus) and Outcome of Myocardial Infarction: a SWEDEHEART Study
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background

    Based on effects of nicotine and snus (a smokeless tobacco) on hemodynamics, pro-arrhythmia and remodelling, in combination with indications of increased risk for fatal myocardial infarction (MI) in snus users; we hypothesised that the outcome of an MI may be worse in snus users.

    Methods

    Data was extracted from the SWEDEHEART registry for all patients who underwent coronary angiography in Sweden due to MI between December 2009 and December 2014. In snus users (n=4,950) relative to snus non-users (n=55,412), we compared risks of a large MI (defined as hs-cTnT of  > 10,000 ng/L, cTnT > 10 μg/L or cTnI > 10 μg/L) and death in the acute (in-hospital) setting, and death+HF (a combined endpoint of all-cause death or hospitalization for heart failure) and all-cause death at short- (<28 days) and long-term follow-up. Relations of snus use to outcomes were also analysed in pre-specified subgroups of never, previous and current smokers.

    Results

    A large MI was diagnosed in 10,975 patients. During long-term follow-up (median 1.9 years), 7,758 either died (n=6,044) or were hospitalized due to heart failure (n=1,714). In models adjusting for age, gender, smoking, previous MI and occupational classification (employed, unemployed/sick leave and retired), snus use was not associated with risk of large MI (odds ratio 1.01; 95% confidence interval (CI) 0.93-1.09) or death+HF (long-term Cox proportional hazard ratio (HR) 0.99; 95% CI 0.90-1.10). Nonetheless, among never-smokers snus use was associated with an increased risk for death+HF (long-term HR 1.26, 95% CI 1.03-1.55), driven by a higher mortality risk (long-term HR for death of any cause 1.29, 95% CI 1.02-1.64).

    Conclusions

    In this study, snus use was unrelated to acute, short-term or long-term adverse outcomes after an MI. Among never-smokers, snus use was associated with an increased risk of post-MI death.

    National Category
    Medical and Health Sciences Cardiac and Cardiovascular Systems
    Research subject
    Cardiology; Epidemiology; Medical Science
    Identifiers
    urn:nbn:se:uu:diva-342247 (URN)
    Available from: 2018-03-18 Created: 2018-03-18 Last updated: 2018-06-26
    4. Discontinuation of Smokeless Tobacco and Mortality Risk After Myocardial Infarction
    Open this publication in new window or tab >>Discontinuation of Smokeless Tobacco and Mortality Risk After Myocardial Infarction
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    2014 (English)In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 130, no 4, p. 325-323Article in journal (Refereed) Published
    Abstract [en]

    Background-Given the indications of increased risk for fatal myocardial infarction (MI) in people who use snus, a moist smokeless tobacco product, we hypothesized that discontinuation of snus use after an MI would reduce mortality risk. Methods and Results-All patients who were admitted to coronary care units for an MI in Sweden between 2005 and 2009 and were <75 years of age underwent a structured examination 2 months after discharge (the baseline of the present study). We investigated the risk of mortality in post-MI snus quitters (n=675) relative to post-MI continuing snus users (n=1799) using Cox proportional hazards analyses. During follow-up (mean 2.1 years), 83 participants died. The mortality rate was 9.7 (95% confidence interval, 5.7-16.3) per 1000 person-years at risk in post-MI snus quitters and 18.7 (14.8-23.6) per 1000 person-years at risk in post-MI continuing snus users. After adjustment for age and sex, post-MI snus quitters had half the mortality risk of post-MI continuing snus users (hazard ratio, 0.51; 95% confidence interval, 0.29-0.91). In a multivariable-adjusted model, the hazard ratio was 0.57 (95% confidence interval, 0.32-1.02). The corresponding estimate for people who quit smoking after MI versus post-MI continuing smokers was 0.54 (95% confidence interval, 0.42-0.69). Conclusions-In this study, discontinuation of snus use after an MI was associated with a nearly halved mortality risk, similar to the benefit associated with smoking cessation. These observations suggest that the use of snus after MI should be discouraged.

    Keywords
    mortality, myocardial infarction, prognosis, risk factors, smokeless tobacco
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:uu:diva-230084 (URN)10.1161/CIRCULATIONAHA.113.007252 (DOI)000339392300009 ()24958793 (PubMedID)
    Available from: 2014-09-03 Created: 2014-08-19 Last updated: 2018-03-18
  • 24.
    Arefalk, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Galanti, Rosaria
    Lundberg, Michael
    Ye, Weimin
    Norberg, Margareta
    Lindmark, Krister
    Pedersen, Nancy
    Trolle Lagerros, Ylva
    Bellocco, Rino
    Lager, Anton
    Wennberg, Patrik
    Eriksson, Marie
    Östergren, Per-Olof
    Alfredsson, Lars
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Magnusson, Cecilia
    Smokeless Tobacco (Snus) and Risk of Heart Failure of Ischemic and Non-Ischemic Origin: a Pooled Analysis of Eight Prospective Cohort StudiesManuscript (preprint) (Other academic)
    Abstract [en]

    Background

    Snus, a Swedish type of smokeless tobacco, has potent acute hemodynamic effects, which could provoke stress on the cardiovascular system, including the myocardium. Snus has, however, not been linked to risk of ischemic heart disease. Therefore, we hypothesized that snus use increases the risk for heart failure of non-ischemic origin.

    Methods

    We conducted a pooled analysis of eight Swedish prospective cohort studies involving individual participant data from 350,711 men. Shared frailty models with random effects at the cohort level, were used to estimate hazard ratios (HRs) with 95 % confidence intervals (CIs) of heart failure in relation to snus use. We investigated dose-response associations, and association with ischemic and non-ischemic heart failure in separate. For positive control purposes, we also investigated associations between smoking and risk of heart failure.

    Results

    During a median follow-up time of 16 years, 5,404 men were hospitalized for heart failure. In models adjusting for age, smoking, previous myocardial infarction and educational level, current snus use was associated with a higher risk of heart failure (HR 1.27, 95 % CI 1.07-1.50), relative to non-current snus use. A dose-response pattern was observed, with higher risk with more snus cans used per week. We observed an association of snus use with non-ischemic heart failure, HR 1.34 (95 % CI 1.11-1.63), but not with ischemic heart failure, HR 1.01 (95 % CI 0.72-1.42). Smoking was more strongly associated with heart failure, particularly of ischemic origin, than snus use.

    Conclusions

    Snus use was associated with a modestly increased risk for heart failure of non-ischemic origin in a dose-response manner. This finding has public health implications for the risk assessment of snus use, and potentially other modes of smokeless use of nicotine.

  • 25.
    Arefalk, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hambraeus, Kristina
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Discontinuation of Smokeless Tobacco and Mortality Risk After Myocardial Infarction2014In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 130, no 4, p. 325-323Article in journal (Refereed)
    Abstract [en]

    Background-Given the indications of increased risk for fatal myocardial infarction (MI) in people who use snus, a moist smokeless tobacco product, we hypothesized that discontinuation of snus use after an MI would reduce mortality risk. Methods and Results-All patients who were admitted to coronary care units for an MI in Sweden between 2005 and 2009 and were <75 years of age underwent a structured examination 2 months after discharge (the baseline of the present study). We investigated the risk of mortality in post-MI snus quitters (n=675) relative to post-MI continuing snus users (n=1799) using Cox proportional hazards analyses. During follow-up (mean 2.1 years), 83 participants died. The mortality rate was 9.7 (95% confidence interval, 5.7-16.3) per 1000 person-years at risk in post-MI snus quitters and 18.7 (14.8-23.6) per 1000 person-years at risk in post-MI continuing snus users. After adjustment for age and sex, post-MI snus quitters had half the mortality risk of post-MI continuing snus users (hazard ratio, 0.51; 95% confidence interval, 0.29-0.91). In a multivariable-adjusted model, the hazard ratio was 0.57 (95% confidence interval, 0.32-1.02). The corresponding estimate for people who quit smoking after MI versus post-MI continuing smokers was 0.54 (95% confidence interval, 0.42-0.69). Conclusions-In this study, discontinuation of snus use after an MI was associated with a nearly halved mortality risk, similar to the benefit associated with smoking cessation. These observations suggest that the use of snus after MI should be discouraged.

  • 26.
    Arefalk, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hambraeus, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Response to Letter Regarding Article, "Discontinuation of Smokeless Tobacco and Mortality Risk After Myocardial Infarction"2015In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 131, no 17, p. E423-E423Article in journal (Refereed)
  • 27.
    Arefalk, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hergens, Maria-Pia
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ye, Weimin
    Nyrén, Olof
    Lambe, Mats
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Smokeless Tobacco (Snus) and Risk of Heart Failure: Results from Two Swedish Cohorts2012In: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 19, no 5, p. 1120-1127Article in journal (Refereed)
    Abstract [en]

    Background:

    Oral moist snuff (snus) is discussed as a safer alternative to smoking, and its use is increasing. Based on its documented effect on blood pressure, we hypothesized that use of snus increases the risk of heart failure.

    Design:

    Two independent Swedish prospective cohorts; the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based sample of 1076 elderly men, and the Construction Workers Cohort (CWC), a sample of 118,425 never-smoking male construction workers.

    Methods:

    Cox proportional hazards models were used to investigate possible associations of snus use with risk of a first hospitalization for heart failure.

    Results:

    In ULSAM, 95 men were hospitalized for heart failure, during a median follow up of 8.9 years. In a model adjusted for established risk factors including past and present smoking exposure, current snus use was associated with a higher risk of heart failure [hazard ratio (HR) 2.08, 95% confidence interval (CI) 1.03-4.22] relative to non-use. Snus use was particularly associated with risk of non-ischaemic heart failure (HR 2.55, 95% CI 1.12-5.82). In CWC, 545 men were hospitalized for heart failure, during a median follow up of 18 years. In multivariable-adjusted models, current snus use was moderately associated with a higher risk of heart failure (HR 1.28, 95% CI 1.00-1.64) and non-ischaemic heart failure (HR 1.28, 95% CI 0.97-1.68) relative to never tobacco use.

    Conclusion:

    Data from two independent cohorts suggest that use of snus may be associated with a higher risk of heart failure.

  • 28.
    Arefalk, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Andersen, Kasper
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Smokeless Tobacco (Snus) and Outcome of Myocardial Infarction: a SWEDEHEART StudyManuscript (preprint) (Other academic)
    Abstract [en]

    Background

    Based on effects of nicotine and snus (a smokeless tobacco) on hemodynamics, pro-arrhythmia and remodelling, in combination with indications of increased risk for fatal myocardial infarction (MI) in snus users; we hypothesised that the outcome of an MI may be worse in snus users.

    Methods

    Data was extracted from the SWEDEHEART registry for all patients who underwent coronary angiography in Sweden due to MI between December 2009 and December 2014. In snus users (n=4,950) relative to snus non-users (n=55,412), we compared risks of a large MI (defined as hs-cTnT of  > 10,000 ng/L, cTnT > 10 μg/L or cTnI > 10 μg/L) and death in the acute (in-hospital) setting, and death+HF (a combined endpoint of all-cause death or hospitalization for heart failure) and all-cause death at short- (<28 days) and long-term follow-up. Relations of snus use to outcomes were also analysed in pre-specified subgroups of never, previous and current smokers.

    Results

    A large MI was diagnosed in 10,975 patients. During long-term follow-up (median 1.9 years), 7,758 either died (n=6,044) or were hospitalized due to heart failure (n=1,714). In models adjusting for age, gender, smoking, previous MI and occupational classification (employed, unemployed/sick leave and retired), snus use was not associated with risk of large MI (odds ratio 1.01; 95% confidence interval (CI) 0.93-1.09) or death+HF (long-term Cox proportional hazard ratio (HR) 0.99; 95% CI 0.90-1.10). Nonetheless, among never-smokers snus use was associated with an increased risk for death+HF (long-term HR 1.26, 95% CI 1.03-1.55), driven by a higher mortality risk (long-term HR for death of any cause 1.29, 95% CI 1.02-1.64).

    Conclusions

    In this study, snus use was unrelated to acute, short-term or long-term adverse outcomes after an MI. Among never-smokers, snus use was associated with an increased risk of post-MI death.

  • 29. Arking, Dan E
    et al.
    Pulit, Sara L
    Crotti, Lia
    van der Harst, Pim
    Munroe, Patricia B
    Koopmann, Tamara T
    Sotoodehnia, Nona
    Rossin, Elizabeth J
    Morley, Michael
    Wang, Xinchen
    Johnson, Andrew D
    Lundby, Alicia
    Gudbjartsson, Daníel F
    Noseworthy, Peter A
    Eijgelsheim, Mark
    Bradford, Yuki
    Tarasov, Kirill V
    Dörr, Marcus
    Müller-Nurasyid, Martina
    Lahtinen, Annukka M
    Nolte, Ilja M
    Smith, Albert Vernon
    Bis, Joshua C
    Isaacs, Aaron
    Newhouse, Stephen J
    Evans, Daniel S
    Post, Wendy S
    Waggott, Daryl
    Lyytikäinen, Leo-Pekka
    Hicks, Andrew A
    Eisele, Lewin
    Ellinghaus, David
    Hayward, Caroline
    Navarro, Pau
    Ulivi, Sheila
    Tanaka, Toshiko
    Tester, David J
    Chatel, Stéphanie
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kumari, Meena
    Morris, Richard W
    Naluai, Asa T
    Padmanabhan, Sandosh
    Kluttig, Alexander
    Strohmer, Bernhard
    Panayiotou, Andrie G
    Torres, Maria
    Knoflach, Michael
    Hubacek, Jaroslav A
    Slowikowski, Kamil
    Raychaudhuri, Soumya
    Kumar, Runjun D
    Harris, Tamara B
    Launer, Lenore J
    Shuldiner, Alan R
    Alonso, Alvaro
    Bader, Joel S
    Ehret, Georg
    Huang, Hailiang
    Kao, W H Linda
    Strait, James B
    Macfarlane, Peter W
    Brown, Morris
    Caulfield, Mark J
    Samani, Nilesh J
    Kronenberg, Florian
    Willeit, Johann
    Smith, J Gustav
    Greiser, Karin H
    Meyer Zu Schwabedissen, Henriette
    Werdan, Karl
    Carella, Massimo
    Zelante, Leopoldo
    Heckbert, Susan R
    Psaty, Bruce M
    Rotter, Jerome I
    Kolcic, Ivana
    Polašek, Ozren
    Wright, Alan F
    Griffin, Maura
    Daly, Mark J
    Arnar, David O
    Hólm, Hilma
    Thorsteinsdottir, Unnur
    Denny, Joshua C
    Roden, Dan M
    Zuvich, Rebecca L
    Emilsson, Valur
    Plump, Andrew S
    Larson, Martin G
    O'Donnell, Christopher J
    Yin, Xiaoyan
    Bobbo, Marco
    D'Adamo, Adamo P
    Iorio, Annamaria
    Sinagra, Gianfranco
    Carracedo, Angel
    Cummings, Steven R
    Nalls, Michael A
    Jula, Antti
    Kontula, Kimmo K
    Marjamaa, Annukka
    Oikarinen, Lasse
    Perola, Markus
    Porthan, Kimmo
    Erbel, Raimund
    Hoffmann, Per
    Jöckel, Karl-Heinz
    Kälsch, Hagen
    Nöthen, Markus M
    den Hoed, Marcel
    Loos, Ruth J F
    Thelle, Dag S
    Gieger, Christian
    Meitinger, Thomas
    Perz, Siegfried
    Peters, Annette
    Prucha, Hanna
    Sinner, Moritz F
    Waldenberger, Melanie
    de Boer, Rudolf A
    Franke, Lude
    van der Vleuten, Pieter A
    Beckmann, Britt Maria
    Martens, Eimo
    Bardai, Abdennasser
    Hofman, Nynke
    Wilde, Arthur A M
    Behr, Elijah R
    Dalageorgou, Chrysoula
    Giudicessi, John R
    Medeiros-Domingo, Argelia
    Barc, Julien
    Kyndt, Florence
    Probst, Vincent
    Ghidoni, Alice
    Insolia, Roberto
    Hamilton, Robert M
    Scherer, Stephen W
    Brandimarto, Jeffrey
    Margulies, Kenneth
    Moravec, Christine E
    Greco M, Fabiola Del
    Fuchsberger, Christian
    O'Connell, Jeffrey R
    Lee, Wai K
    Watt, Graham C M
    Campbell, Harry
    Wild, Sarah H
    El Mokhtari, Nour E
    Frey, Norbert
    Asselbergs, Folkert W
    Mateo Leach, Irene
    Navis, Gerjan
    van den Berg, Maarten P
    van Veldhuisen, Dirk J
    Kellis, Manolis
    Krijthe, Bouwe P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Franco, Oscar H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hofman, Albert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kors, Jan A
    Uitterlinden, André G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Witteman, Jacqueline C M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kedenko, Lyudmyla
    Lamina, Claudia
    Oostra, Ben A
    Abecasis, Gonçalo R
    Lakatta, Edward G
    Mulas, Antonella
    Orrú, Marco
    Schlessinger, David
    Uda, Manuela
    Markus, Marcello R P
    Völker, Uwe
    Snieder, Harold
    Spector, Timothy D
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Sundström, Johan
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kivimaki, Mika
    Kähönen, Mika
    Mononen, Nina
    Raitakari, Olli T
    Viikari, Jorma S
    Adamkova, Vera
    Kiechl, Stefan
    Brion, Maria
    Nicolaides, Andrew N
    Paulweber, Bernhard
    Haerting, Johannes
    Dominiczak, Anna F
    Nyberg, Fredrik
    Whincup, Peter H
    Hingorani, Aroon D
    Schott, Jean-Jacques
    Bezzina, Connie R
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ferrucci, Luigi
    Gasparini, Paolo
    Wilson, James F
    Rudan, Igor
    Franke, Andre
    Mühleisen, Thomas W
    Pramstaller, Peter P
    Lehtimäki, Terho J
    Paterson, Andrew D
    Parsa, Afshin
    Liu, Yongmei
    van Duijn, Cornelia M
    Siscovick, David S
    Gudnason, Vilmundur
    Jamshidi, Yalda
    Salomaa, Veikko
    Felix, Stephan B
    Sanna, Serena
    Ritchie, Marylyn D
    Stricker, Bruno H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stefansson, Kari
    Boyer, Laurie A
    Cappola, Thomas P
    Olsen, Jesper V
    Lage, Kasper
    Schwartz, Peter J
    Kääb, Stefan
    Chakravarti, Aravinda
    Ackerman, Michael J
    Pfeufer, Arne
    de Bakker, Paul I W
    Newton-Cheh, Christopher
    Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.2014In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, no 8, p. 826-836Article in journal (Refereed)
    Abstract [en]

    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.

  • 30. Arnlov, Johan
    et al.
    Carlsson, Axel C.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Larsson, Tobias E.
    Serum FGF23 and Risk of Cardiovascular Events in Relation to Mineral Metabolism and Cardiovascular Pathology2013In: American Society of Nephrology. Clinical Journal, ISSN 1555-9041, E-ISSN 1555-905X, Vol. 8, no 5, p. 781-786Article in journal (Refereed)
    Abstract [en]

    Background and objectives Circulating fibroblast growth factor-23 is associated with adverse cardiovascular outcomes in CKD and non-CKD individuals, but the underlying mechanism remains unclear. This study tested whether this association is independent of mineral metabolism and indices of subclinical cardiovascular pathology. Design, setting, participants, & measurements The prospective association between fibroblast growth factor-23 and major cardiovascular events (a composite of hospital-treated myocardial infarction, hospital-treated stroke, or all-cause mortality) was investigated in the community-based Prospective Investigation of the Vasculature in Uppsala Seniors (n=973; mean age=70 years, 50% women) using multivariate logistic regression. Subjects were recruited between January of 2001 and June of 2004. Results During follow-up (median=5.1 years), 112 participants suffered a major cardiovascular event. In logistic regression models adjusted for age, sex, and estimated GFR, higher fibroblast growth factor-23 was associated with increased risk for major cardiovascular events (odds ratio for tertiles 2 and 3 versus tertile 1=1.92, 95% confidence interval=1.19-3.09, P<0.01). After additional adjustments in the model, adding established cardiovascular risk factors, confounders of mineral metabolism (calcium, phosphate, parathyroid hormone, and 25 (OH)-vitamin D), and indices of subclinical pathology (flow-mediated vasodilation, endothelial-dependent and -independent vasodilation, arterial stiffness, and atherosclerosis and left ventricular mass) attenuated this relationship, but it remained significant (odds ratio for tertiles 2 and 3 versus tertile 1=1.69, 95% confidence interval=1.01-2.82, P<0.05). Conclusions Fibroblast growth factor-23 is an independent predictor of cardiovascular events in the community, even after accounting for mineral metabolism abnormalities and subclinical cardiovascular damage. Circulating fibroblast growth factor-23 may reflect novel and important aspects of cardiovascular risk yet to be unraveled.

  • 31. Asayama, Kei
    et al.
    Thijs, Lutgarde
    Li, Yan
    Gu, Yu-Mei
    Hara, Azusa
    Liu, Yan-Ping
    Zhang, Zhenyu
    Wei, Fang-Fei
    Lujambio, Ines
    Mena, Luis J.
    Boggia, Jose
    Hansen, Tine W.
    Björklund-Bodegård, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Nomura, Kyoko
    Ohkubo, Takayoshi
    Jeppesen, Jorgen
    Torp-Pedersen, Christian
    Dolan, Eamon
    Stolarz-Skrzypek, Katarzyna
    Malyutina, Sofia
    Casiglia, Edoardo
    Nikitin, Yuri
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Luzardo, Leonella
    Kawecka-Jaszcz, Kalina
    Sandoya, Edgardo
    Filipovsky, Jan
    Maestre, Gladys E.
    Wang, Jiguang
    Imai, Yutaka
    Franklin, Stanley S.
    O'Brien, Eoin
    Staessen, Jan A.
    Setting Thresholds to Varying Blood Pressure Monitoring Intervals Differentially Affects Risk Estimates Associated With White-Coat and Masked Hypertension in the Population2014In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 64, no 5, p. 935-942Article in journal (Refereed)
    Abstract [en]

    Outcome-driven recommendations about time intervals during which ambulatory blood pressure should be measured to diagnose white-coat or masked hypertension are lacking. We cross-classified 8237 untreated participants (mean age, 50.7 years; 48.4% women) enrolled in 12 population studies, using >= 140/>= 90, >= 130/>= 80, >= 135/>= 85, and >= 120/>= 70 mm Hg as hypertension thresholds for conventional, 24-hour, daytime, and nighttime blood pressure. White-coat hypertension was hypertension on conventional measurement with ambulatory normotension, the opposite condition being masked hypertension. Intervals used for classification of participants were daytime, nighttime, and 24 hours, first considered separately, and next combined as 24 hours plus daytime or plus nighttime, or plus both. Depending on time intervals chosen, white-coat and masked hypertension frequencies ranged from 6.3% to 12.5% and from 9.7% to 19.6%, respectively. During 91 046 person-years, 729 participants experienced a cardiovascular event. In multivariable analyses with normotension during all intervals of the day as reference, hazard ratios associated with white-coat hypertension progressively weakened considering daytime only (1.38; P=0.033), nighttime only (1.43; P=0.0074), 24 hours only (1.21; P=0.20), 24 hours plus daytime (1.24; P=0.18), 24 hours plus nighttime (1.15; P=0.39), and 24 hours plus daytime and nighttime (1.16; P=0.41). The hazard ratios comparing masked hypertension with normotension were all significant (P<0.0001), ranging from 1.76 to 2.03. In conclusion, identification of truly low-risk white-coat hypertension requires setting thresholds simultaneously to 24 hours, daytime, and nighttime blood pressure. Although any time interval suffices to diagnose masked hypertension, as proposed in current guidelines, full 24-hour recordings remain standard in clinical practice.

  • 32.
    Asberg, Signild
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Henriksson, Karin M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Terént, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Farahmand, B.
    Statin therapy and the risk of death and recurrent intracerebral hemorrhage2015In: International Journal of Stroke, ISSN 1747-4930, E-ISSN 1747-4949, Vol. 10, p. 43-43Article in journal (Other academic)
  • 33.
    Athlin, Åsa Muntlin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Univ Uppsala Hosp, Dept Emergency Care & Internal Med, Entrance 40, S-75185 Uppsala, Sweden.;Univ Adelaide, Sch Nursing, Adelaide, SA, Australia..
    Engström, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Univ Gavle, Fac Hlth & Occupat Studies, Dept Hlth & Caring Sci, Gavle, Sweden.;Lishui Univ, Sch Med & Hlth, Dept Nursing, Lishui, Peoples R China..
    Gunningberg, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Univ Uppsala Hosp, Qual Dept, Uppsala, Sweden..
    Baath, Carina
    Karlstad Univ, Fac Hlth Sci & Technol, Dept Hlth Sci, Karlstad, Sweden.;Cty Council Varmland, Karlstad, Sweden..
    Heel pressure ulcer, prevention and predictors during the care delivery chain - when and where to take action?: A descriptive and explorative study2016In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 24, article id 134Article in journal (Refereed)
    Abstract [en]

    Background: Hazardous healthcare settings, for example acute care, need to focus more on preventing adverse events and preventive actions across the care delivery chain (i.e pre-hospital and emergency care, and further at the hospital ward) should be more studied. Pressure ulcer prevalence is still at unreasonably high levels, causing increased healthcare costs and suffering for patients. Recent biomedical research reveals that the first signs of cell damage could arise within minutes. However, few studies have investigated optimal pressure ulcer prevention in the initial stage of the care process, e.g. in the ambulance care or at the emergency department. The aim of the study was to describe heel pressure ulcer prevalence and nursing actions in relation to pressure ulcer prevention during the care delivery chain, for older patients with neurological symptoms or reduced general condition. Another aim was to investigate early predictors for the development of heel pressure ulcer during the care delivery chain. Methods: Existing data collected from a multi-centre randomized controlled trial investigating the effect of using a heel prevention boot to reduce the incidence of heel pressure ulcer across the care delivery chain was used. Totally 183 patients participated. The settings for the study were five ambulance stations, two emergency departments and 16 wards at two hospitals in Sweden. Results: A total of 39 individual patients (21 %) developed heel pressure ulcer at different stages across the care delivery chain. Findings revealed that 47-64 % of the patients were assessed as being at risk for developing heel pressure ulcer. Preventive action was taken. However, all patients who developed pressure ulcer during the care delivery chain did not receive adequate pressure ulcer prevention actions during their hospital stay. Discussion and Conclusions: In the ambulance and at the emergency department, skin inspection seems to be appropriate for preventing pressure ulcer. However, carrying out risk assessment with a validated instrument is of significant