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  • 1.
    Andersson, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mellberg, Caroline
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Otten, Julia
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ryberg, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rinnström, Daniel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Larsson, Christel
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Hauksson, Jon
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. d Department of Radiography and Biomedical Science, Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Left ventricular remodelling changes without concomitant loss of myocardial fat after long-term dietary intervention2016In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 216, p. 92-96Article in journal (Refereed)
    Abstract [en]

    Background: Accumulation of myocardial triglycerides (MTG) is associated with impaired left ventricular (LV) remodelling and function in obese and diabetic subjects. The role of MTG accumulation in development of heart failure in this group of patients is unknown. Short-term studies suggest that diets that lead to weight loss could mobilize MTG, with a favourable effect on cardiac remodelling. In a 24-month, randomized, investigator-blinded study, we assessed the effect of two different diets and subsequent weight loss on cardiac function and MTG in postmenopausal women. Methods: Sixty-eight healthy postmenopausal women with body mass index [BMI] >= 27 kg/m(2) were randomized to an ad libitum Palaeolithic diet (PD) or a Nordic Nutrition Recommendation (NNR) diet for 24 months. Morphology, cardiac function, and MTG levels were measured using magnetic resonance (MR) scanning, including proton spectroscopy at baseline and 6 and 24 months. Results: Despite mean weight losses of 4.9 (1.0) kg (NNR) and 7.8 (1.1) kg (PD), the MTG content did not change over time (p = 0.98 in the NNR and p = 0.11 in the PD group at 24 months). Reduced left ventricular mass was observed in both diet groups over 24 months. Blood pressure was reduced at 6 months, but returned to baseline levels at 24 months. End diastolic volume, stroke volume, and cardiac output decreased over time. No differences between diet groups were observed. Conclusions: Diet intervention and moderate weight loss over 24 months improved LV remodelling but did not alter MTG levels in overweight/obese postmenopausal women.

  • 2. Apers, Silke
    et al.
    Kovacs, Adrienne H.
    Luyckx, Koen
    Alday, Luis
    Berghammer, Malin
    Budts, Werner
    Callus, Edward
    Caruana, Maryanne
    Chidambarathanu, Shanthi
    Cook, Stephen C.
    Dellborg, Mikael
    Enomoto, Junko
    Eriksen, Katrine
    Fernandes, Susan M.
    Jackson, Jamie L.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Khairy, Paul
    Kutty, Shelby
    Menahem, Samuel
    Rempel, Gwen
    Sluman, Maayke A.
    Soufi, Alexandra
    Thomet, Corina
    Veldtman, Gruschen
    Wang, Jou-Kou
    White, Kamila
    Moons, Philip
    Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease - International Study (APPROACH-IS): Rationale, design, and methods2015In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 179, p. 334-342Article in journal (Refereed)
    Abstract [en]

    Background: Data on patient-reported outcomes (PROs) in adults with congenital heart disease (CHD) are inconsistent and vary across the world. Better understanding of PROs and their differences across cultural and geographic barriers can best be accomplished via international studies using uniform research methods. The APPROACH-IS consortium (Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease - International Study) was created for this purpose and investigates PROs in adults with CHD worldwide. This paper outlines the project rationale, design, and methods. Methods/design: APPROACH-IS is a cross-sectional study. The goal is to recruit 3500-4000 adults with CHD from 15 countries in five major regions of the world (Asia, Australia, Europe, North and South America). Self-report questionnaires are administered to capture information on PRO domains: (i) perceived health status (12-item Short-form Health Survey & EuroQOL-5D); (ii) psychological functioning (Hospital Anxiety and Depression Scale); (iii) health behaviors (Health-Behavior Scale-Congenital Heart Disease); and (iv) quality of life (Linear Analog Scale & Satisfaction With Life Scale). Additionally, potential explanatory variables are assessed: (i) socio-demographic variables; (ii) medical history (chart review); (iii) sense of coherence (Orientation to Life Questionnaire); and (iv) illness perceptions (Brief Illness Perception Questionnaire). Descriptive analyses and multilevel models will examine differences in PROs and investigate potential explanatory variables. Discussion: APPROACH-IS represents a global effort to increase research understanding and capacity in the field of CHD, and will have major implications for patient care. Results will generate valuable information for developing interventions to optimize patients' health and well-being. 

  • 3.
    Backman, Christer
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Tossavainen, Erik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Unusual arrhythmogenic myocardial disease2014In: International Cardiovascular Forum Journal, ISSN 2410-2636, Vol. 1, no 4, p. 195-196Article in journal (Refereed)
  • 4.
    Bay, Annika
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Berghammer, M.
    Lämås, Kristina
    Umeå University, Faculty of Medicine, Department of Nursing.
    Sandberg, Camilla
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Facilitators and barriers for physical activity in adults with congenital heart disease2018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, p. 1120-1121Article in journal (Other academic)
    Abstract [en]

    Background: A majority of adults with congenital heart disease (CHD) have reduced exercise capacity and do not reach the recommended level of physical activity. A physically active lifestyle is essential to maintain health and counteract acquired cardiovascular disease. This study illuminates aspects that may be relevant for performing physical activity.

    Purpose: To describe facilitators and barriers for physical activity in adults with CHD.

    Methods: Semi-structured interviews were performed individually with fourteen adults (age 19–68 years, women=7) with complex CHD. The interviews were analyzed using qualitative content analysis.

    Results: Aspects that may enable or inhibit physical activity were found in two domains; Facilitators and Barriers, which both consisted of four categories physical, psychological, psychosocial and environmental aspects (Table 1).

    This can be exemplified by the category physical aspects; where persons expressed being limited by the CHD to perform physical activity, but also that improved aerobic fitness allows for being more active, and in the category psychosocial aspects; the person's previous negative experiences and lack of support constituted barriers while encouragement from others and being active as a child facilitated an active lifestyle in adult age.

    Conclusion: The present study identifies barriers and facilitators for being physically active in adults living with CHD. It is essential to identify prerequisites for supporting and promoting physical activity and thereby hopefully prevent long-term adverse outcomes. Barriers can potentially be transformed to facilitators through increased knowledge in both the adult with CHD and the healthcare provider.

  • 5.
    Bay, Annika
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Berghammer, Malin
    Lämås, Kristina
    Umeå University, Faculty of Medicine, Department of Nursing.
    Sandberg, Camilla
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Facilitators and barriers for physical activity in adults with congenital heart disease2018In: European Heart Journal: ESC Congress 2018 25 - 29 August Munich, Germany, Oxford University Press, 2018, Vol. 39, article id P5433Conference paper (Refereed)
  • 6.
    Bay, Annika
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Dellborg, Mikael
    Berghammer, Malin
    Sandberg, Camilla
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Engström, Gunnar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Moons, Philip
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Patient reported outcomes are associated with physical activity level in adults with congenital heart disease2017In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 243, p. 174-179Article in journal (Refereed)
    Abstract [en]

    Background: In general, adults with congenital heart disease (CHD) have impaired exercise capacity, and approximately 50% do not reach current recommendations on physical activity. Herein we analysed factors associated with physical activity level (PAL) in adults with CHD by using patient-reported outcomes (PRO). Methods: Patients with CHD (n = 471) were randomly selected from the national register on CHD and categorized according to complexity of lesions -simple (n = 172, 39.1 +/- 14.6 years), moderate (n = 212, 39 +/- 14.1 years), and severe (n = 87, 31.7 +/- 10.7 years). Participants completed a standardized questionnaire measuring PRO-domains including PAL. Variables associated with PAL were tested in multivariate logistic regression. Results: PAL was categorized into high (>= 3 METs = 2.5 h/week, n = 192) and low (>= 3 METs <2.5 h/week, n = 279). Patients with low PAL were older (42.6 vs. 35.8 years, p = 0.001), had more prescribed medications (51% vs. 39%, p = 0.009), more symptoms (25% vs. 16%, p = 0.02) and comorbidity (45% vs. 34% p= 0.02). Patients with low PAL rated a lower quality of life (76.6 vs. 83.4, p < 0.001), satisfaction with life (25.6 vs. 27.3, p = 0.003), a lower Physical Component Summary score (PCS) (78.1 vs. 90.5, p < 0.001) andMental Component Summary score (MCS) (73.5 vs. 79.5, p < 0.001). Complexity of heart lesion was not associated with PAL. The included PROs-separately tested in the model, together with age were associated with PAL. Conclusions: PCS and MCS are stronger associated with PAL than age and medical factors. The use of these PROs could therefore provide valuable information of benefit for individualized advice regarding physical activity to patients with CHD.

  • 7.
    Bay, Annika
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lämås, Kristina
    Umeå University, Faculty of Medicine, Department of Nursing.
    Berghammer, Malin
    Sandberg, Camilla
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Section of Physiotherapy.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Enablers and barriers for physical activity in adults with congenital heart disease2019Conference paper (Refereed)
  • 8.
    Bay, Annika
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lämås, Kristina
    Umeå University, Faculty of Medicine, Department of Nursing.
    Berghammer, Malin
    Sandberg, Camilla
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    It ́s like balancing on a slackline: A description from adults living with congenital heart disease2018In: Cardiology in the Young, ISSN 1047-9511, E-ISSN 1467-1107, Vol. 28, no Suppl. S1, p. S37-S37Article in journal (Refereed)
    Abstract [en]

    Introduction: Several studies have shown that adults with congenital heart disease have reduced exercise capacity and do not reach the recommended daily level of physical activity. With this in view, it is of great importance to investigate how this population experiences physical activity. The aim of the study is to illuminate how adults with congenital heart disease describes themselves in relation to physical activity.

    Methods: Semi-structured interviews with fourteen adults with complex congenital heart disease were performed. Patients were recruited from the clinic waiting list, based on their scheduled follow up and diagnosis. Interviews were analysed by qualitative content analysis.

    Results: The overall theme It´s like balancing on a slackline illustrates how adults with congenital heart disease described themselves in relation to physical activity. The overall theme consists of four themes: Being an adventurer- enjoying the challenges of physical activity, Being a realist- adapting to physical ability, Beinga non-doer- lacking prerequisites for physical activity and Being an outsider- feeling excluded depending on physical ability.

    Conclusions: The descriptions on themselves as a physically active were not constant or one-dimensional and the descriptions varied during the interviews, related to different time periods in life. It meant that they could described themselves as being an adventurer liking tough challenges, but at the same time describing themselves as being a non-doer with uncertainty over their physical strength. The findings point out specific factors for adults with CHD that might constitute as obstacles, but also possibilities for being physically active.

  • 9.
    Bay, Annika
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lämås, Kristina
    Umeå University, Faculty of Medicine, Department of Nursing.
    Berghammer, Malin
    Sandberg, Camilla
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    It's like balancing on a slackline: a description of how adults with congenital heart disease describe themselves in relation to physical activity2018In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 27, no 15-16, p. 3131-3138Article in journal (Refereed)
    Abstract [en]

    AIMS AND OBJECTIVES: To illuminate how adults with CHD describe themselves in relation to physical activity.

    BACKGROUND: Several studies have shown that adults with congenital heart disease (CHD) have reduced exercise capacity and do not reach the recommended daily level of physical activity. With this in view, it is of immense importance to investigate how this population experiences physical activity.

    DESIGN: Qualitative study with semi-structured interviews analysed with qualitative content analysis.

    METHODS: Semi-structured interviews were individually performed with fourteen adults (women=7, age 19-68 years) with complex CHD. Patients were purposively recruited from the clinic waiting list, based on a scheduled follow-up and diagnosis.

    RESULTS: The overall theme, It's like balancing on a slackline, illustrates how adults with CHD described themselves in relation to physical activity. This overall theme consisted of four subthemes: (1) Being an adventurer- enjoying the challenges of physical activity; (2) Being a realist- adapting to physical ability; (3) Being a non-doer- lacking prerequisites for physical activity; and (4) Being an outsider- feeling excluded depending on physical ability.

    CONCLUSIONS: Adults with CHD seem to have a diverse relationship to physical activity and it involves various aspects throughout the lifespan. The findings point out factors that might constitute as obstacles for being physically active, specific for people with chronic conditions like CHD. This highlights the importance of further exploring the hindering and facilitating factors for being physically active in order to get a deeper understanding of how to support adults with CHD to be physically active.

    RELEVANCE TO CLINICAL PRACTICE: Given the diverse relationship to physical activity, nurses have to further investigate the patients' relationship to physical activity, in order to support a healthy lifestyle. Nurses and allied health professionals should offer individualized exercise prescriptions and education about suitable physical activities in relation to physical ability. This article is protected by copyright. All rights reserved.

  • 10.
    Bay, Annika
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Sandberg, Camilla
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Thilen, U.
    Wadell, Karin
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Exercise self-efficacy (ESE) in adults with congential heart disease2017In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 38, no Suppl. 1, article id ehx501.P618Article in journal (Refereed)
    Abstract [en]

    Background: Many adults with congenital heart disease (CHD) have reduced aerobic exercise capacity and impaired muscle function. However, it is largely unknown which factors have influence on the confidence to perform exercise training, i.e. Exercise Self-Efficacy (ESE).

    Aims: To identify factors related to low ESE, and thus identify potential targets for rehabilitation and thereby enhance the potential for being physically active.

    Methods: Seventy-nine adults with CHD; simple lesions n=38 (women n=16), complex lesions n=41 (women n=17) (mean age 36.7±14.6 years) and 42 age and sex matched controls were recruited. All participants completed questionnaires on ESE, quality of life (EQ-5D), and physical activity (international physical activity questionnaire, IPAQ), and performed muscle endurance tests.

    Results: ESE was categorised into low (<26 points, n=24) and high (≥26 points, n=55). Patients with low ESE were older (45.2±15.4 vs. 32.6±12.5 years, p=0.002), more often had prescribed medication (67% vs. 44%, p=0.06), higher New York Heart Association functional class (NYHA) (≥ III) (25% vs. 7%, p=0.03) and performed fewer shoulder flexions (30.9±16.1 vs. 45.9±23.9, p=0.01) compared with those with high ESE. In the high ESE group, ESE did not differ from controls (33.8±3.9 vs. 33.4±6.1, p=0.74). In linear multivariate analysis age (B;-0.18, 95% CI -0.28- -0.08), smoking (B;-3.73, 95% CI -7.17- -0.28), EQ-5Dindex <1 (B;-3.33, 95% CI -6.08- -0.57) and number of shoulder flexions (B; 0.09, 95% CI 0.03–0.16) were independently associated with ESE.

    Conclusion: Many adults with CHD have low ESE. Rehabilitation targeting quality of life, smoking cessation and muscle training may improve ESE, and thus enhance the potential for being physically active in this population.

  • 11.
    Bay, Annika
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Sandberg, Camilla
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Thilén, Ulf
    Wadell, Karin
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Exercise self-efficacy in adults with congenital heart disease2018In: International Journal of Cardiology: Heart and vasculature, E-ISSN 2352-9067, Vol. 18, p. 7-11Article in journal (Refereed)
    Abstract [en]

    Background: Physical activity improves health, exercise tolerance and quality of life in adults with congenital heart disease (CHD), and exercise training is in most patients a high-benefit low risk intervention. However, factors that influence the confidence to perform exercise training, i.e. exercise self-efficacy (ESE), in CHD patients are virtually unknown. We aimed to identify factors related to low ESE in adults with CHD, and potential strategies for being physically active.

    Methods: Seventy-nine adults with CHD; 38 with simple lesions (16 women) and 41 with complex lesions (17 women) with mean age 36.7 ± 14.6 years and 42 matched controls were recruited. All participants completed questionnaires on ESE and quality of life, carried an activity monitor (Actiheart) during four consecutive days and performed muscle endurance tests.

    Results: ESE in patients was categorised into low, based on the lowest quartile within controls, (≤ 29 points, n = 34) and high (> 29 points, n = 45). Patients with low ESE were older (42.9 ± 15.1 vs. 32.0 ± 12.4 years, p = 0.001), had more complex lesions (65% vs. 42%, p = 0.05) more often had New York Heart Association functional class III (24% vs. 4%, p = 0.01) and performed fewer shoulder flexions (32.5 ± 15.5 vs. 47.7 ± 25.0, p = 0.001) compared with those with high ESE. In a logistic multivariate model age (OR; 1.06, 95% CI 1.02-1.10), and number of shoulder flexions (OR; 0.96, 95% CI 0.93-0.99) were associated with ESE.

    Conclusion: In this study we show that many adults with CHD have low ESE. Age is an important predictor of low ESE and should, therefore, be considered in counselling patients with CHD. In addition, muscle endurance training may improve ESE, and thus enhance the potential for being physically active in this population.

  • 12. Berghammer, M.
    et al.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Mattson, E.
    Moons, P.
    Dellborg, M.
    Exploration of disagreement between the patient's self reported limitations and limitations assessed by caregivers in adults with congenital heart disease2018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, p. 468-468Article in journal (Other academic)
    Abstract [en]

    Background: The New York Heart Association (NYHA) classification is applied in a wide spectrum of heart diseases including adult patients with congenital heart disease (ACHD). The NYHA-class assessment is often based on the evaluation by the caregiver, but to what extent it correlates with the patient's view of their function is not fully known.

    Purpose: To investigate the relation between the patient's self-reported physical limitations, symptoms, other heart defect related factors and NYHA-class assessed by the caregiver.

    Methods: Eligible patients (n=333, age 39.2±13.6 years) were identified and randomly selected from the national registry for CHD. All of the patients completed a standardized questionnaire measuring different PRO-domains. By combing self-reported data with registry data including NYHA-class, analyses of agreement of physical limitations were performed.

    Results: Almost 30% of the patients rated their limitations higher compared to the NYHA-class estimated by the caregiver. Patients with self-reported limitations and their NYHA-class underestimated by caregivers, more often reported symptoms, anxiety, lower health and worked fewer hours/week compared to other patients with CHD. There were no differences regarding sex, type of symptoms, prescribed medications, or complexity of cardiac lesion. In patients without self-reported limitations agreement with NYHA-class estimated by caregivers was 97%.

    Conclusion: Adult patients with CHD and self-reported limitations may not be correctly identified by the care-giver. Instruments for patient reported outcomes might improve the assessment of physical limitations and could further improve the correctness in evaluating the patient's status.

  • 13. Berghammer, Malin C.
    et al.
    Mattsson, Eva
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Moons, Philip
    Dellborg, Mikael
    Comparison of participants and non-participants in patient-reported outcome surveys: the case of Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease - International Study2017In: Cardiology in the Young, ISSN 1047-9511, E-ISSN 1467-1107, Vol. 27, no 3, p. 427-434Article in journal (Refereed)
    Abstract [en]

    Background: The last decade has seen a vast increase in the use of patient-reported outcomes. As patientreported outcomes are used in order to capture patients' perspectives of their health and illness, it is a prerequisite for accurate patient-reported outcome evaluations to use representative samples. In order to evaluate representativeness, the present study focussed on the comparison between participants and non-participants in the Swedish branch of the international study APPROACH-IS (Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease - International Study), regarding demographic, clinical, and health status characteristics. Methods: Eligible patients for APPROACH-IS were identified and selected from SWEDCON, the Swedish registry for congenital heart disease (CHD). Overall, 912 eligible patients were identified, of whom 471 participated, 398 did not participate, and 43 were either unreachable or declined to participate in APPROACH-IS. The participants and nonparticipants were compared in terms of statistical significance and effect sizes. Results: Significant differences were observed between participants and non-participants for sex, age, primary diagnosis, number of cardiac operations, and fatigue; however, the effect sizes were in general small, except for the difference in primary diagnosis. No differences between the two groups were found in number of catheterisations, implanted device, the distribution of NYHA functional class, or health status and symptoms. Conclusions: This study shows that participants and non-participants are relatively comparable groups, which confirms the representativeness of the participants. The Swedish data from APPROACH-IS can therefore be reliably generalised to the population of adults with CHD in Sweden.

  • 14.
    Berglund, Elisabeth
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Dellborg, Mikael
    Sörensson, Peder
    Christersson, Christina
    Nielsen, Niels-Eric
    Rinnström, Daniel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Thilén, Ulf
    High incidence of infective endocarditis in adults with congenital ventricular septal defect2016In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 102, no 22, p. 1835-1839Article in journal (Refereed)
    Abstract [en]

    Objective: Ventricular septal defects (VSDs), if haemodynamically important, are closed whereas small shunts are left without intervention. The long-term prognosis in congenital VSD is good but patients are still at risk for long-term complications. The aim of this study was to clarify the incidence of infective endocarditis (IE) in adults with VSD. Methods: The Swedish registry for congenital heart disease (SWEDCON) was searched for adults with VSD. 779 patients were identified, 531 with small shunts and 248 who had the VSD previously closed. The National Patient Register was then searched for hospitalisations due to IE in adults during a 10-year period. Results: Sixteen (2%) patients were treated for IE, 6 men and 10 women, with a mean age of 46.3 +/- 12.2 years. The incidence of IE was 1.7-2.7/1000 years in patients without previous intervention, 20-30 times the risk in the general population. Thirteen had small shunts without previous intervention. There was no mortality in these 13 cases. Two patients had undergone repair of their VSD and also aortic valve replacement before the episode of endocarditis and a third patient with repaired VSD had a bicuspid aortic valve, all of these three patients needed reoperation because of their IE and one patient died. No patient with isolated and operated VSD was diagnosed with IE. Conclusions: A small unoperated VSD in adults carries a substantially increased risk of IE but is associated with a low risk of mortality.

  • 15.
    Bäckstrom, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Forensic Medicine. Department of Forensic Medicine, National Board of Forensic Medicine, PO Box 7616, SE-907 12, Umeå.
    Johansson, Bengt
    Eriksson, Anders
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Forensic Medicine.
    Death from Nitrous Oxide2015In: Journal of Forensic Sciences, ISSN 0022-1198, E-ISSN 1556-4029, Vol. 60, no 6, p. 1662-1665Article in journal (Refereed)
    Abstract [en]

    Nitrous oxide is an inflammable gas that gives no smell or taste. It has a history of abuse as long as its clinical use, and deaths, although rare, have been reported. We describe two cases of accidental deaths related to voluntary inhalation of nitrous oxide, both found dead with a gas mask covering the face. In an attempt to find an explanation to why the victims did not react properly to oncoming hypoxia, we performed experiments where a test person was allowed to breath in a closed system, with or without nitrous oxide added. Vital signs and gas concentrations as well as subjective symptoms were recorded. The experiments indicated that the explanation to the fact that neither of the descendents had reacted to oncoming hypoxia and hypercapnia was due to the inhalation of nitrous oxide. This study raises the question whether nitrous oxide really should be easily, commercially available.

  • 16.
    Camilla, Sandberg
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Pomeroy, Jeremy
    Thilén, Ulf
    Gradmark, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Wadell, Karin
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Habitual Physical Activity in Adults with Congenital Heart Disease Compared with Age- and Sex- Matched Controls2016In: Canadian Journal of Cardiology, ISSN 0828-282X, E-ISSN 1916-7075, Vol. 32, no 4, p. 547-553Article in journal (Refereed)
    Abstract [en]

    Background: Most adult patients with congenital heart disease (CHD) have reduced aerobic exercise capacity. Their habitual physical activity (PA) level is, however, less well studied. In this study habitual PA level in a cohort of adults with CHD compared to healthy age and gender matched controls was investigated.

    Methods: Eighty adults with CHD, classed as either “complex” (n=40) or “simple” (n=40), and 42 healthy controls were studied with a combined uniaxial accelerometer and heart rate monitor worn during 4 consecutive days. We analysed 1) the time spent during ≥ moderate/vigorous PA, 2) accelerometer counts/day and 3) to what extent the World Health Organization recommendations on PA were reached.

    Results: Patients with simple lesions had higher total accelerometer counts/day compared to both patients with complex lesions and controls (simple lesions; median (IQR) 107.7(63.4) vs. complex lesions; 72.8(53.5) and controls; 78.3(49.6), p≤0.001 and p=0.002). Furthermore, no differences in time spent during ≥ moderate-to-vigorous PA was found between patients and controls. In addition 46% of the patients with simple lesions, 55% of the patients with complex lesions and 44% of the controls did not reach the W.H.O.-recommended level of daily PA, but no significant differences between groups were found. There were no differences in achieving recommended PA level between patients in NYHA I vs. NYHA II+III.

    Conclusions: Patients with CHD follow the same PA-level pattern as the general population. Broad strategies promoting an active lifestyle are needed across the population and especially for patients with complex CHD and impaired NYHA class.

  • 17. Caruana, Maryanne
    et al.
    Apers, Silke
    Kovacs, Adrienne H.
    Luyckx, Koen
    Thomet, Corina
    Budts, Werner
    Sluman, Maayke
    Eriksen, Katrine
    Dellborg, Mikael
    Berghammer, Malin
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Soufi, Alexandra
    Callus, Edward
    Moons, Philip
    Grech, Victor
    Red Flags for Maltese Adults with Congenital Heart Disease: Poorer Dental Care and Less Sports Participation Compared to Other European Patients-An APPROACH-IS Substudy2017In: Pediatric Cardiology, ISSN 0172-0643, E-ISSN 1432-1971, Vol. 38, no 5, p. 965-973Article in journal (Refereed)
    Abstract [en]

    Studies in recent years have explored lifestyle habits and health-risk behaviours in adult congenital heart disease (ACHD) patients when compared to controls. The aim of this study was to investigate differences in lifestyle habits between Maltese and other European ACHD patients. Data on alcohol consumption, cigarette smoking, substance misuse, dental care and physical activity collected in 2013-2015 during "Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease-International Study" (APPROACH-IS) were analysed. Responses from 119 Maltese participants were compared to those of 1616 participants from Belgium, France, Italy, Norway, Sweden, Switzerland and the Netherlands. Significantly fewer Maltese patients with simple (Maltese 84.1% vs. European 97.5%, p < 0.001) and moderately complex CHD (Maltese 83.6% vs. European 97.4%, p < 0.001) brushed their teeth daily. Only 67.2% of Maltese with moderately complex disease had dental reviews in the previous year compared to 80.3% of Europeans (p = 0.02). Maltese patients with simple (Maltese 31.8% vs. European 56.1%, p = 0.002) and moderately complex lesions (Maltese 30.0% vs. European 59.2%, p < 0.001) performed less regular sport activities. Comparison by country showed Maltese patients to have significantly poorer tooth brushing and sports participation than patients from any other participating country. Alcohol consumption, cigarette smoking and substance misuse were not significantly different. This study highlights lifestyle aspects that Maltese ACHD patients need to improve on, which might not be evident upon comparing patients to non-CHD controls. These findings should also caution researchers against considering behaviours among patients in one country as necessarily representative of patients on the larger scale.

  • 18. Diller, Gerhard-Paul
    et al.
    Dimopoulos, Konstantinos
    Okonko, Darlington
    Li, Wei
    Babu-Narayan, Sonya V
    Broberg, Craig S
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Bouzas, Beatriz
    Mullen, Michael J
    Poole-Wilson, Philip A
    Francis, Darrel P
    Gatzoulis, Michael A
    Exercise intolerance in adult congenital heart disease: comparative severity, correlates, and prognostic implication.2005In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 112, no 6, p. 828-35Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Although some patients with adult congenital heart disease (ACHD) report limitations in exercise capacity, we hypothesized that depressed exercise capacity may be more widespread than superficially evident during clinical consultation and could be a means of assessing risk.

    METHODS AND RESULTS: Cardiopulmonary exercise testing was performed in 335 consecutive ACHD patients (age, 33+/-13 years), 40 non-congenital heart failure patients (age, 58+/-15 years), and 11 young (age, 29+/-5 years) and 12 older (age, 59+/-9 years) healthy subjects. Peak oxygen consumption (peak VO2) was reduced in ACHD patients compared with healthy subjects of similar age (21.7+/-8.5 versus 45.1+/-8.6; P<0.001). No significant difference in peak VO2 was found between ACHD and heart failure patients of corresponding NYHA class (P=NS for each NYHA class). Within ACHD subgroups, peak VO2 gradually declined from aortic coarctation (28.7+/-10.4) to Eisenmenger (11.5+/-3.6) patients (P<0.001). Multivariable correlates of peak VO2 were peak heart rate (r=0.33), forced expiratory volume (r=0.33), pulmonary hypertension (r=-0.26), gender (r=-0.23), and body mass index (r=-0.19). After a median follow-up of 10 months, 62 patients (18.5%) were hospitalized or had died. On multivariable Cox analysis, peak VO2 predicted hospitalization or death (hazard ratio, 0.937; P=0.01) and was related to the frequency and duration of hospitalization (P=0.01 for each).

    CONCLUSIONS: Exercise capacity is depressed in ACHD patients (even in allegedly asymptomatic patients) on a par with chronic heart failure subjects. Lack of heart rate response to exercise, pulmonary arterial hypertension, and impaired pulmonary function are important correlates of exercise capacity, as is underlying cardiac anatomy. Poor exercise capacity identifies ACHD patients at risk for hospitalization or death.

  • 19.
    Hannuksela, Matias
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Aortic stiffness in families with inherited non-syndromic thoracic aortic disease2018In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 52, no 6, p. 301-307Article in journal (Refereed)
    Abstract [en]

    Background. In families with an inherited form of non-syndromic thoracic aortic disease (TAAD), aortic diameter alone is not a reliable marker for disease occurrence or progression. To identify other parameters of aortic function, we studied aortic stiffness in families with TAAD. We also compared diameter measurements obtained by transthoracic echocardiography (TTE) and magnetic resonance imaging (MRI).

    Methods. Seven families, including 116 individuals, with non-syndromic TAAD, were studied. The aortic diameter was measured by TTE and MRI. Aortic stiffness was assessed as local distensibility in the ascending aorta and as regional and global pulse wave velocity (PWV). Individuals with a dilated thoracic aorta (n = 21) were compared with those without aortic dilatation (n = 95).

    Results. Ascending aortic diameter measured by TTE strongly correlated with the diameter measured by MRI (r2 = 0.93). The individuals with dilated aortas were older than those without dilatation (49 vs 37 years old). Ascending aortic diameter increased and distensibility decreased with increasing age; while, PWV increased with age and diameter. Some young subjects without aortic dilatation showed increased aortic stiffness. Individuals with a dilated thoracic aorta had significantly higher PWV and lower distensibility, measured by MRI than individuals without dilatation.

    Conclusions. Diameters measured with TTE agree with those measured by MRI. Aortic stiffness might be a complementary marker for aortic disease and progression when used with aortic diameter, especially in young individuals.

  • 20.
    Hannuksela, Matias
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Stattin, Eva-Lena
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Screening for familial thoracic aortic aneurysms with aortic imaging does not detect all potential aarriers of the disease2015In: Aorta, ISSN 2325-4637, Vol. 3, no 1, p. 1-8Article in journal (Refereed)
    Abstract [en]

    Background: About 20% of patients with thoracic aortic aneurysm or dissection (TAAD) have a first-degree relative with a similar disease. The familial form (FTAAD) of the disease is inherited in an autosomal-dominant pattern. Current guidelines for thoracic aortic disease recommend screening of first-degree relatives of TAAD patients. In known familial disease, screening of both first- and second-degree relatives is recommended. However, the outcomes of such a screening program are unknown.

    Methods: We screened all first- and second-degree relatives in seven families with known FTAAD with echo- cardiography. No underlying gene defect had been detected in these families.

    Results: Of 119 persons investigated, 13 had known thoracic aortic disease. In the remaining 106 cases, we diagnosed 19 additional individuals with a dilated ascending thoracic aorta; for an autosomal-dominant disease, the expected number of individuals in this group would have been 40 (p<0.0001). Further, only one of the 20 first-degree relatives younger than 40 years had a dilated aorta, although the expected number of individuals with a disease-causing mutation would have been 10.

    Conclusions: In most families with TAAD, a diagnosis still relies on measuring the diameter of the thoracic aorta. We show that a substantial number of previously unknown cases of aortic dilatation can be identified by screening family members. It is, however, not possible to consider anyone free of the condition, even if the aortic diameter is normal, especially at a younger age.

  • 21.
    Hannuksela, Matias
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Stattin, Eva-Lena
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics. Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Klar, Joakim
    Ameur, Adam
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Sorensen, Karen
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    A novel variant in MYLK causes thoracic aortic dissections: genotypic and phenotypic description2016In: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 17, article id 61Article in journal (Refereed)
    Abstract [en]

    Background: Mutations in MYLK cause non- syndromic familial thoracic aortic aneurysms and dissections (FTAAD). Very little is known about the phenotype of affected families. We sought to characterize the aortic disease and the presence of other vascular abnormalities in FTAAD caused by a deletion in MYLK and to compare thoracic aortic diameter and stiffness in mutation carriers and non-carriers.

    Methods: We studied FTAAD in a 5-generation family that included 19 living members. Exome sequencing was performed to identify the underlying gene defect. Aortic elastic properties measured by TTE, MRI and pulse wave velocity were then compared between mutation carriers and non-carriers.

    Results: Exome sequencing led to the identification of a 2-bp deletion in MYLK (c3272_ 3273del, p. Ser1091*) that led to a premature stop codon and nonsense-mediated decay. Eleven people were mutation carriers and eight people were non-carriers. Five aortic ruptures or dissections occurred in this family, with two survivors. There were no differences in aortic diameter or stiffness between carriers and non-carriers of the mutation.

    Conclusions: Individuals carrying this deletion in MYLK have a high risk of presenting with an acute aortic dissection or rupture. Aortic events occur over a wide range of ages and are not always preceded by obvious aortic dilatation. Aortic elastic properties do not differ between carriers and non-carriers of this mutation, rendering it uncertain whether and when carriers should undergo elective prophylactic surgery.

  • 22.
    Hedlund, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Lindelöf, Nina
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Danish Research Center for Magnetic Resonance, Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark.
    Rosendahl, Erik
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Development and Feasibility of a Regulated, Supramaximal High-Intensity Training Program Adapted for Older Individuals2019In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 10, article id 590Article in journal (Refereed)
    Abstract [en]

    Background: High-intensity training (HIT) with extremely short intervals (designated here as supramaximal HIT) is a time-efficient training method for health and performance. However, a protocol for regulation and control of intensity is missing, impeding implementation in various groups, such as older individuals.

    Methods: This study presents the development and characteristics of a novel training protocol with regulated and controlled supramaximal intervals adapted for older people. Using both quantitative and qualitative analyses, we explored the feasibility of the program, performed in a group training setting, with physically active older individuals (aged 65–75, n = 7; five women). The developed supramaximal HIT program consisted of 10 × 6 s cycle sprint intervals with ∼1 min of active recovery with the following key characteristics: (1) an individual target power output was reached and maintained during all intervals and regulated and expressed as the percentage of the estimated maximum mean power output for the duration of the interval (i.e., 6 s); (2) pedaling cadence was standardized for all participants, while resistance was individualized; and (3) the protocol enabled controlled and systematic adjustments of training intensity following standardized escalation criteria.

    Aim: Our aim was to test the feasibility of a novel training regimen with regulated and controlled supramaximal HIT, adapted for older people. The feasibility criteria for the program were to support participants in reaching a supramaximal intensity (i.e., power output > 100% of estimated VO2 max), avoid inducing a negative affective response, and have participants perceive it as feasible and acceptable.

    Results: All feasibility criteria were met. The standardized escalation procedure provided safe escalation of training load up to a supramaximal intensity (around three times the power output at estimated VO2 max). The participants never reported negative affective responses, and they perceived the program as fun and feasible.

    Conclusion: This novel program offers a usable methodology for further studies on supramaximal HIT among older individuals with different levels of physical capacity. Future research should explore the effects of the program in various populations of older people and their experiences and long-term adherence compared with other forms of training.

  • 23.
    Hellström, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Engström-Laurent, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Hyaluronan and collagen in human hypertrophic cardiomyopathy: a morphological analysis2012In: Cardiology Research and Practice, ISSN 2090-8016, E-ISSN 2090-0597, Vol. 2012, p. 545219-Article in journal (Refereed)
    Abstract [en]

    The hypertrophic cardiomyopathy (HCM) disease process is not only limited to cardiomyocyte abnormalities but also engages the extracellular matrix. Hyaluronan (HA) and its receptor CD44 are involved in cellular growth and tissue proliferation but have so far been less studied in myocardial hypertrophy. In HCM, collagens are abundant but their histological distribution and relation to hyaluronan have not been described. Material and Methods. Myocardial specimens from 5 patients with symptomatic left ventricular tract obstruction undergoing myectomy due to HCM were processed for histochemistry and immunohistochemistry. Results. HA staining was more intense in HCM patients. The histological distribution of HA was the same in patients and controls, that is, interstitial staining including the space between cardiomyocytes, in fibrous septa, and in the adventitia of intramyocardial blood vessels. CD44 was not detected in the myocardium of patients or controls. Collagen I showed the same general localisation as HA but detailed distribution differed. Conclusions. This is the first study that describes the distribution of hyaluronan in human HCM. HA staining is more intense in HCM patients but without coexpression of its receptor CD44, at least not in the chronic phase of HCM. HA and collagen I have the same localisation.

  • 24.
    Hellström, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ericsson, Madelene
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Faraz, Mahmood
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Anderson, Fredrick
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Regional Cancer Center Stockholm/Gotland, Stockholm, Sweden.
    Nilsson, Stefan K.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Cardiac hypertrophy and decreased high-density lipoprotein cholesterol in Lrig3-deficient mice2016In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 310, no 11, p. R1045-R1052Article in journal (Refereed)
    Abstract [en]

    Genetic factors confer risk for cardiovascular disease. Recently, large genome-wide population studies have shown associations between genomic loci close to LRIG3 and heart failure and plasma high-density lipoprotein (HDL) cholesterol level. Here, we ablated Lrig3 in mice and investigated the importance of Lrig3 for heart function and plasma lipid levels. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to analyze Lrig3 expression in the hearts of wild-type and Lrig3-deficient mice. In addition, molecular, physiological, and functional parameters such as organ weights, heart rate, blood pressure, heart structure and function, gene expression in the heart, and plasma insulin, glucose, and lipid levels were evaluated. The Lrig3-deficient mice were smaller than the wild-type mice but otherwise appeared grossly normal. Lrig3 was expressed at detectable but relatively low levels in adult mouse hearts. At 9 mo of age, ad libitum-fed Lrig3-deficient mice had lower insulin levels than wildtype mice. At 12 mo of age, Lrig3-deficient mice exhibited increased blood pressure, and the Lrig3-deficient female mice displayed signs of cardiac hypertrophy as assessed by echocardiography, heart-to-body weight ratio, and expression of the cardiac hypertrophy marker gene Nppa. Additionally, Lrig3-deficient mice had reduced plasma HDL cholesterol and free glycerol. These findings in mice complement the human epidemiological results and suggest that Lrig3 may influence heart function and plasma lipid levels in mice and humans.

  • 25.
    Hellström, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Engström Laurent, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hyaluronan and its receptor CD44 in the heart of newborn and adult rats.2006In: Anatomical record part A: discoveries in molecular, cellular, and evolutionary biology, ISSN 1552-4884, Vol. 288, no 6, p. 587-592Article in journal (Refereed)
  • 26.
    Henein, Michael
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Bengrid, Tarek
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Zhao, Y.
    Ultrasound Department, Capital Medical University, Beijing, China.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Schmermund, A.
    Medicine, Bethanien Hospital, Frankfurt, Germany.
    Extensive coronary calcification compromises myocardial perfusion in the absence of high grade stenosis2014In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 235, no 2, p. E68-E68Article in journal (Other academic)
  • 27.
    Henein, Michael Y.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Bengrid, Tarek
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Zhao, Ying
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Schmermund, Axel
    Coronary calcification compromises myocardial perfusion irrespective of luminal stenosis2017In: IJC HEART & VASCULATURE, ISSN 2352-9067, Vol. 14, p. 41-45Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of this study was to evaluate the relationship between coronary artery calcification (CAC) assessed by multi-detector computed tomography (MDCT) and myocardial perfusion assessed by cardiac magnetic resonance imaging (CMR) in a group of symptomatic patients. Method: Retrospective analysis of 120 patients (age 65.1 +/- 8.9 years, 88 males) who presented with atypical chest pain to Bethanien Hospital, Frankfurt, Germany, between 2007 and 2010 and who underwent CAC scoring using MDCT, CMR, and conventional coronary angiography. Patients were divided into those with high-grade (HG) stenosis (n = 67, age 65.1 +/- 9.4 years) and those with no-HG stenosis (n = 53, age 65.1 +/- 8.6 years). Results: There were more males with HG stenosis (82.1% vs. 62.3%, p = 0.015), in whom the percentage and number of abnormal perfusion segments were higher at rest (37.3% vs. 17%, p = 0.014) but not different with stress (p = 0.83) from those with no-HG stenosis. Thirty-four patients had myocardial perfusion abnormalities at rest and 26 patients developed perfusion defects with stress. Stress-induced myocardial perfusion defects were 22.4% sensitive and 79.2% specific for detecting HG stenosis. The CAC score was lower in patients with no-HG stenosis compared to those with HG stenosis (p < 0.0001). On the ROC curve, a CAC score of 293 had a sensitivity of 71.6% and specificity of 83% in predicting HG stenosis [(AUC 0.80 (p < 0.0001)]. A CAC score of 293 or the presence of at least 1 segment myocardial perfusion abnormality was 74.6% sensitive and 71.7% specific in detecting HG stenosis, the respective values for the 2 abnormalities combined being 19.4% and 90.6%. The severity of CAC correlated with the extent of myocardial perfusion in the patient group as a whole with stress (r = 0.22, p = 0.015), particularly in those with no-HG stenosis (r = 0.31, p = 0.022). A CAC score of 293 was 31.6% sensitive and 87.3% specific in detecting myocardial perfusion abnormalities. Conclusion: In a group of patients with exertional angina, coronary calcification is more accurate in detecting high-grade luminal stenosis than myocardial perfusion defects. In addition, in patients with no stenosis, the incremental relationship between coronary calcium score and the extent of myocardial perfusion suggests coronary wall hardening as an additional mechanism for stress-induced angina other than luminal narrowing. These preliminary findings might have a clinical impact on management strategies of these patients other than conventional therapy.

  • 28. Hjortshoj, Cristel Sorensen
    et al.
    Jensen, Annette Schophuus
    Sorensen, Keld
    Nagy, Edit
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Kronvall, Thomas
    Dellborg, Mikael
    Estensen, Mette-Elise
    Holmstrom, Henrik
    Turanlahti, Maila
    Thilen, Ulf
    Sondergaard, Lars
    Epidemiological changes in Eisenmenger syndrome in the Nordic region in 1977-20122017In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 103, no 17, p. 1353-1358Article in journal (Refereed)
    Abstract [en]

    Objective: Improved diagnostic tools, timely closure of the shunt and a better understanding of the complexity of Eisenmenger syndrome (ES) have led to improved care and treatment in tertiary centres. These may have decreased the incidence of ES and improved survival of patients with ES, although evidence is still lacking. The aim of this study was to investigate temporal changes in incidence, prevalence and mortality in patients with ES for 35 years in the Nordic region.

    Methods: This was a retrospective population-based study including 714 patients with ES. Survival analysis was performed based on all-cause mortality and accounting for immortal time bias.

    Results: The incidence of ES decreased from 2.5/million inhabitants/year in 1977 to 0.2/million inhabitants/year in 2012. Correspondingly, prevalence decreased from 24.6 to 11.9/million inhabitants. The median survival was 38.4 years, with 20-year, 40-year and 60-year survival of 72.5%, 48.4%, and 21.3%, respectively. Complex lesions and Down syndrome were independently associated with worse survival (HR 2.2, p<0.001 and HR 1.8, p<0.001, respectively). Age at death increased from 27.7 years in the period from 1977 to 1992, to 46.3 years from July 2006 to 2012 (p<0.001).

    Conclusions: The incidence and prevalence of ES in the Nordic region have decreased markedly during the last decades. Furthermore, the median age at death increased throughout the study period, indicating prolonged life expectancy in the ES population. However, increasing age represents decreased incidence, rather than improved survival. Nonetheless, longevity with ES is still shorter than in the background population.

  • 29. Holbein, Christina E.
    et al.
    Fogleman, Nicholas D.
    Hommel, Kevin
    Apers, Silke
    Rassart, Jessica
    Moons, Philip
    Luyckx, Koen
    Sluman, Maayke A.
    Enomoto, Junko
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Yang, Hsiao-Ling
    Dellborg, Mikael
    Subramanyan, Raghavan
    Jackson, Jamie L.
    Budts, Werner
    Kovacs, Adrienne H.
    Morrison, Stacey
    Tomlin, Martha
    Gosney, Kathy
    Soufi, Alexandra
    Eriksen, Katrine
    Thomet, Corina
    Berghammer, Malin
    Alday, Luis
    Callus, Edward
    Fernandes, Susan M.
    Caruana, Maryanne
    Menahem, Samuel
    Cook, Stephen C.
    Rempel, Gwen R.
    White, Kamila
    Khairy, Paul
    Kutty, Shelby
    Veldtman, Gruschen
    A multinational observational investigation of illness perceptions and quality of life among patients with a Fontan circulation2018In: Congenital Heart Disease, ISSN 1747-079X, E-ISSN 1747-0803, Vol. 13, no 3, p. 392-400Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: First, to compare QOL and illness perceptions between patients with a Fontan circulation and patients with anatomically simple defects (ie, atrial septal defects [ASD] or ventricular septal defects [VSD]). Second, to explore illness perceptions as a mediator of the association between congenital heart disease (CHD) diagnosis and QOL.

    DESIGN: Cross-sectional observational study.

    SETTING: Twenty-four cardiology centers from 15 countries across five continents.

    PATIENTS: Four hundred thirty-five adult patients with congenital heart disease (177 Fontan and 258 ASD/VSD) ages 18-83 years.

    OUTCOME MEASURES: QOL and illness perceptions were assessed by the Satisfaction With Life Scale and the Brief Illness Perceptions Questionnaire, respectively.

    RESULTS: Patients with a Fontan circulation reported lower QOL (Wald Z = -3.59, p = <.001) and more negative perceptions of their CHD (Wald Z = -7.66, p < .001) compared with patients with ASD/VSD. After controlling for demographics, anxiety, depressive symptoms, and New York Heart Association functional class, path analyses revealed a significant mediation model, αβ = 0.15, p = .002, 95% CI = 0.06-0.25, such that CHD diagnosis was indirectly related to QOL through illness perceptions.

    CONCLUSIONS: The Fontan sample's more negative perceptions of CHD were likely a reflection of life with a more complex defect. Illness perceptions appear to account for unique differences in QOL between groups of varying CHD complexity. Psychosocial screening and interventions may be important treatment components for patients with CHD, particularly those with Fontan circulations.

  • 30. Holbein, Christina E.
    et al.
    Veldtman, Gruschen R.
    Moons, Philip
    Kovacs, Adrienne H.
    Luyckx, Koen
    Apers, Silke
    Chidambarathanu, Shanti
    Soufi, Alexandra
    Eriksen, Katrine
    Jackson, Jamie L.
    Enomoto, Junko
    Fernandes, Susan M.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Alday, Luis
    Dellborg, Mikael
    Berghammer, Malin
    Menahem, Samuel
    Caruana, Maryanne
    Kutty, Shelby
    Mackie, Andrew S.
    Thomet, Corina
    Budts, Werner
    White, Kamila
    Sluman, Maayke A.
    Callus, Edward
    Cook, Stephen C.
    Khairy, Paul
    Cedars, Ari
    Perceived Health Mediates Effects of Physical Activity on Quality of Life in Patients With a Fontan Circulation2019In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 124, no 1, p. 144-150Article in journal (Refereed)
    Abstract [en]

    Patients with a Fontan circulation are at risk of a sedentary lifestyle. Given the direct relationship between physical activity and health, promotion of physical activity has the potential to improve outcomes, including quality of life (QOL). This study aimed to describe self-reported physical activity levels in adult Fontan patients and examine associations between physical activity, perceived health status and QOL. The sample consisted of 177 Fontan patients (M-age = 27.5 +/- 7.6 years, 52% male) who reported their physical activity, perceived health status, and QOL as part of the cross-sectional Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease - International Study. Descriptive statistics and univariate analyses of variance with planned contrasts were computed to describe physical activity characteristics. Mediation analyses tested whether perceived health status variables mediated the association between physical activity and QOL. Forty-six percent of patients were sedentary while only 40% met international physical activity guidelines. Higher physical activity was associated with younger age, lower NYHA class, higher perceived general health, and greater QOL. Patients who commuted by walking and engaged in sports reported better perceived health and QOL. Mediation analyses revealed that perceived general health but not NYHA functional class mediated the association between physical activity and QOL (alpha beta = 0.22, 95% confidence interval = 0.04 to 0.49). In conclusion, Fontan patients likely benefit from regular physical activity, having both higher perceived general health and functional capacity; greater perceived health status may contribute to enhanced QOL. In conclusion, these data support the pivotal role of regular physical activity for Fontan patients.

  • 31.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Cardiovascular Magnetic Resonance in Heart Failure2010In: Heart Failure in Clinical Practice / [ed] Michael Y. Henein, Springer London, 2010, p. 241-253Chapter in book (Refereed)
    Abstract [en]

    Cardiovascular magnetic resonance (CMR) is an increasingly used imaging tool in cardiology. Initially, technical resources and access to trained staff were limited to a few centers. As scanners become more available and thanks to widespread training of cardiologists and technicians, CMR can now be performed in most cardiology centers. Without exposing the patient to ionizing radiation, a comprehensive cardiac study can be performed in 30–45 min, depending on clinical problem and scanner capabilities. A typical cardiac exam consists of anatomical images for gross anatomy and cine images for the evaluation of ventricular function. Depending on the clinical problem, a number of additional techniques can be added. Using chelated gadolinium contrast agents, first pass myocardial perfusion can be analyzed during pharmacological stress for the diagnosis of coronary artery disease. After injection of contrast in a peripheral vein, high resolution angiography can be performed. Phase contrast velocity maps (which despite the terminology it does not include contrast agents) can also be used to analyze intrathoracic vascular blood flow and flow velocity.

  • 32.
    Johansson, Bengt
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Babu-Narayan, Sonya V
    Kilner, Philip J
    The effects of breath-holding on pulmonary regurgitation measured by cardiovascular magnetic resonance velocity mapping.2009In: Journal of Cardiovascular Magnetic Resonance, ISSN 1097-6647, E-ISSN 1532-429X, Vol. 11, no 1, p. 1-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Pulmonary regurgitation is a common and clinically important residual lesion after repair of tetralogy of Fallot. Cardiovascular magnetic resonance (CMR) phase contrast velocity mapping is widely used for measurement of pulmonary regurgitant fraction. Breath-hold acquisitions, usually acquired during held expiration, are more convenient than the non-breath-hold approach, but we hypothesized that breath-holding might affect the amount of pulmonary regurgitation. METHODS: Forty-three adult patients with a previous repair of tetralogy of Fallot and residual pulmonary regurgitation were investigated with CMR. In each, pulmonary regurgitant fraction was measured from velocity maps transecting the pulmonary trunk, acquired during held expiration, held inspiration, by non-breath-hold acquisition, and also from the difference of right and left ventricular stroke volume measurements. RESULTS: Pulmonary regurgitant fraction was lower when measured by velocity mapping in held expiration compared with held inspiration, non-breath-hold or stroke volume difference (30.8 vs. 37.0, 35.6, 35.4%, p = 0.00017, 0.0035, 0.026). The regurgitant volume was lower in held expiration than in held inspiration (41.9 vs. 48.3, p = 0.0018). Pulmonary forward flow volume was larger during held expiration than during non-breath-hold (132 vs. 124 ml, p = 0.0024). CONCLUSION: Pulmonary regurgitant fraction was significantly lower in held expiration compared with held inspiration, free breathing and stroke volume difference. Altered airway pressure could be a contributory factor. This information is relevant if breath-hold acquisition is to be substituted for non-breath-hold in the investigation of patients with a view to re-intervention.

  • 33.
    Johansson, Bengt
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Babu-Narayan, Sonya V
    Kilner, Philip J
    Cannell, Timothy M
    Mohiaddin, Raad H
    3-dimensional time-resolved contrast-enhanced magnetic resonance angiography for evaluation late after the mustard operation for transposition2010In: Cardiology in the Young, ISSN 1047-9511, E-ISSN 1467-1107, Vol. 20, no 1, p. 1-7Article in journal (Refereed)
    Abstract [en]

    3-dimensional dynamic angiography is a useful method for detecting anatomically moderate-to-severe, but not mild, obstructions in the systemic venous channels following Mustard repair for transposition. This technique can be used as a single imaging method and/or as complimentary to standard two dimensional cardiovascular magnetic resonance techniques for detection of clinically important obstructions in the systemic venous channels.

  • 34.
    Johansson, Bengt
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Bédard, E
    Intracardiac Thrombus in the fontan circulation2010In: Cases in adult congenital heart disease / [ed] Gatzoulis M Michael A., Gary D. Webb, MD, Craig Broberg, MD and Hideki Uemura, London: Churchill Livingstone , 2010Chapter in book (Other academic)
  • 35.
    Johansson, Bengt
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Engström, Karl-Gunnar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Dellborg, M.
    Kronvall, T.
    Kvidal, P.
    Mattsson, E.
    Thilen, U.
    Functional class, symptoms, medications, arrhythmia devices and quality of life in adults with congenital aortic valve disease. Data from the national registry of congenital heart disease2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no Supplement: 1, p. 375-375Article in journal (Other academic)
    Abstract [en]

    Purpose: Despite the relative high prevalence of congenital aorticvalve disease, the outcome in contemporary cohorts of adults is not well established. In the present study, we have analysed data in the National Registry on Adult Congenital Heart Disease in order to elucidate the long-term outcome regarding functional class,symptoms, quality of life, medications and need for arrhythmiadevices in this cohort.

    Methods: Six hundred fifty-one adult patients with isolated congenitalaortic valve disease met the criteria and were grouped according to: if their first aortic valve intervention was < 18 years (group 1) (n=152), first aortic valve intervention > 18 years (group 2) (n=129) or no aorticvalve intervention (group 0) (n=370).

    Results: 92% of the patients were in NYHA I. Symptoms were reportedin 12.7% but more commonly in group 2 compared with group 1 (20.7% vs. 9.6%, p = 0.039). The overall quality of life assessed with EQ-VAS was 90% and equal between groups. The use of cardiovascularmedications, anticoagulation excluded, was higher in group 2 than ingroups 0 and 1 (29.1% vs. 9.1% and 11.6%, p = 0.001, p < 0.001). Warfarin was prescribed in 55.3% of the patients in group 2, in 34.5% ingroup 1 and 1.7% in group 0 (p < 0.001 for all comparisons) whichindicates that non-mechanical valve prostheses or other alternatives are common in group 1 and 2. Implanted arrhythmia devices were more common in group 2 compared with group 0 (5.1 vs. 0.6%, p = 0.01).

    Conclusion: Functional status and quality of life is generally goodand not obviously related to previous interventions. Symptoms, cardiovascular medications, including warfarin, and anti-arrhythmiadevices were more common in patients with their initial valveintervention in adult age. Many patients with a previous intervention have alternatives to mechanical heart valve prostheses and may thus need future re-interventions.

  • 36.
    Johansson, Bengt
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Damus-Kaye-Stansel anastomosis in a patient with tricuspid atresia, transposition of the great arteries, VSD and total cavo-pulmonary connection (TCPC).2009In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 140, no 3, p. e43-e44Article in journal (Refereed)
    Abstract [en]

    A Damus-Kaye-Stansel (DKS) anastomosis, i.e. an end-to-side anastomosis between the pulmonary artery and the aorta, has been applied in a wide spectrum of congenital heart disease including the Fontan circulation. We hereby present a 19-year-old woman with tricuspid atresia, transposition of great arteries, hypoplastic right ventricle, and a ventricular septal defect who was operated with total cavo-pulmonary connection (TCPC) and a DKS anastomosis. The Cardiovascular Magnetic Resonance (CMR) study showed that the systemic ventricular outflow tract is not obstructed with a good overall result of the previous interventions. CMR therefore, is an ideal mean for studying detailed anatomy and physiology without any need for radiation or contrast media.

  • 37.
    Johansson, Bengt
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Holmer, Fredrik
    Department of Thoracic Surgery, Umeå University Hospital, Umeå, Sweden.
    Ottander, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lund, Björn
    Diagnostic Radiology, Umeå University Hospital, Umeå, Sweden.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    CMR diagnosis of coronary graft fistula2014In: International Cardiovascular Forum Journal, ISSN 2410-2636, Vol. 1, no 3, p. 157-158Article in journal (Refereed)
  • 38.
    Johansson, Bengt
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Holmgren, Anders
    Hedström, Magnus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Engström-Laurent, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Engström, Karl Gunnar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Evaluation of hyaluronan and calcifications in stenotic and regurgitant aortic valves.2011In: European Journal of Cardio-Thoracic Surgery, ISSN 1010-7940, E-ISSN 1873-734X, Vol. 39, no 1, p. 27-32Article in journal (Refereed)
    Abstract [en]

    Objective: Hyaluronan (HA) is a major component of the interstitium and has been observed in normal heart valves. The function of HA in heart valves is unknown but contribution to biomechanical function has been proposed. The purpose of this investigation was to study the distribution of HA in relation to calcifications in diseased human aortic valves. Methods: Human aortic valves were collected at aortic valve replacement, of whom nine patients had regurgitation and 13 stenotic disease. The valves were decalcified and stained for the visualisation of HA. The specimens were macroscopically evaluated for magnitude of calcification using image analysis. The microscopic amount and distribution of HA and calcifications were semiquantitatively evaluated using histochemistry. Results: The overall HA staining showed an inverse relationship against the magnitude of observed valve calcifications (p<0.001) and type of disease (p=0.014). Multiple-group comparison revealed regionally reduced HA staining in diffuse and heavy calcified regions inside the valve (both p<0.001) compared with normal-structured parts of the valve. HA was concentrated on the ventricular side of the valve (p=0.002). Conclusions: The content of HA was reduced in calcified aortic valves and had a heterogeneous distribution, potentially contributing to poor valve function. HA may also be involved in the pathophysiological process in degenerative aortic stenosis.

  • 39.
    Johansson, Bengt
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Maceira, Alicia M
    Babu-Narayan, Sonya V
    Moon, James C
    Pennell, Dudley J
    Kilner, Philip J
    Clefts can be seen in the basal inferior wall of the left ventricle and the interventricular septum in healthy volunteers as well as patients by cardiovascular magnetic resonance.2007In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, ISSN 1558-3597, Vol. 50, no 13, p. 1294-1295Article in journal (Refereed)
  • 40.
    Johansson, Bengt
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Myocardial capillary supply is limited in hypertrophic cardiomyopathy: a morphological analysis2008In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 126, no 2, p. 252-257Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To clarify the morphological basis of the limited coronary reserve in hypertrophic cardiomyopathy (HCM). BACKGROUND: Some of the symptoms in Hypertrophic cardiomyopathy (HCM), such as chest pain, dyspnea and arrhythmia, may be explained by myocardial ischemia. Many patients with HCM are known to exhibit these symptoms in the absence of atherosclerosis in the major coronary vessels. Decreased myocardial perfusion has been demonstrated in HCM, however, little is known about the myocardial capillary morphology in this disease. METHODS: Using immunohistochemistry and morphometry, we analysed capillaries and cardiomyocytes in myectomy specimens from 5 patients with HCM with moderate hypertrophy and left ventricular outflow tract obstruction and in 5 control hearts. RESULTS: The number of capillaries per cardiomyocyte (p<0.009) and number of capillaries per cardiomyocyte area unit, reflecting cardiomyocyte mass (p=0.009), were lower in individuals with HCM, i.e. indicating loss of capillaries. In HCM, the capillary density was 33% lower (p<0.05). CONCLUSIONS: Our morphologic findings show that the capillary supply, and thus the coronary reserve, is impaired in HCM with moderate hypertrophy and left ventricular outflow tract obstruction. These data may partly explain the limitation of myocardial perfusion in HCM, which is associated with worse prognosis. Furthermore, we present evidence of actual loss of myocardial capillaries in HCM and a defective capillary growth.

  • 41. Ko, Jong Mi
    et al.
    White, Kamila S.
    Kovacs, Adrienne H.
    Tecson, Kristen M.
    Apers, Silke
    Luyckx, Koen
    Thomet, Corina
    Budts, Werner
    Enomoto, Junko
    Sluman, Maayke A.
    Wang, Jou-Kou
    Jackson, Jamie L.
    Khairy, Paul
    Cook, Stephen C.
    Chidambarathanu, Shanthi
    Alday, Luis
    Eriksen, Katrine
    Dellborg, Mikael
    Berghammer, Malin
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Mackie, Andrew S.
    Menahem, Samuel
    Caruana, Maryanne
    Veldtman, Gruschen
    Soufi, Alexandra
    Fernandes, Susan M.
    Callus, Edward
    Kutty, Shelby
    Moons, Philip
    Cedars, Ari M.
    Differential impact of physical activity type on depression in adults with congenital heart disease: A multi-center international study2019In: Journal of Psychosomatic Research, ISSN 0022-3999, E-ISSN 1879-1360, Vol. 124, article id 109762Article in journal (Refereed)
    Abstract [en]

    Objective: This study aimed to examine the association between physical activity (PA) and depression in a large international cohort of adults with congenital heart disease (ACHD) as data about the differential impact of PA type on depression in this population are lacking.

    Methods: In 2018, we conducted a cross-sectional assessment of 3908 ACHD recruited from 24 ACHD-specialized centers in 15 countries between April 2013 to March 2015. The Hospital Anxiety and Depression Scale was used to assess self-reported depressive symptoms and the Health-Behavior Scale-Congenital Heart Disease was used to collect PA information. Cochran-Armitage tests were performed to assess trends between depressive symptom levels and PA participation. Chi-Square and Wilcoxon Rank Sum tests were utilized to examine relations between depressive symptom levels and patient characteristics. Stepwise multivariable models were then constructed to understand the independent impact of PA on depressive symptoms.

    Results: The overall prevalence of elevated depressive symptoms in this sample was 12% with significant differences in rates between countries (p < .001). Physically active individuals were less likely to be depressed than those who were sedentary. Of the 2 PA domains examined, sport participation rather than active commute was significantly associated with reduced symptoms of depression. After adjustment in multivariable analysis, sport participation was still significantly associated with 38% decreased probability of depressive symptoms (p < .001).

    Conclusions: Sport participation is independently associated with reduced depressive symptoms. The development and promotion of sport-related exercise prescriptions uniquely designed for ACHD may improve depression status in this unique population.

  • 42. Ko, Jong Mi
    et al.
    White, Kamila S.
    Kovacs, Adrienne H.
    Tecson, Kristen M.
    Apers, Silke
    Luyckx, Koen
    Thomet, Corina
    Budts, Werner
    Enomoto, Junko
    Sluman, Maayke A.
    Wang, Jou-Kou
    Jackson, Jamie L.
    Khairy, Paul
    Cook, Stephen C.
    Subramanyan, Raghavan
    Alday, Luis
    Eriksen, Katrine
    Dellborg, Mikael
    Berghammer, Malin
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Mackie, Andrew S.
    Menahem, Samuel
    Caruana, Maryanne
    Veldtman, Gruschen
    Soufi, Alexandra
    Fernandes, Susan M.
    Callus, Edward
    Kutty, Shelby
    Gandhi, Amarendra
    Moons, Philip
    Cedars, Ari M.
    Physical activity-related drivers of perceived health status in adults with congenital heart disease2018In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 122, no 8, p. 1437-1442Article in journal (Refereed)
    Abstract [en]

    Data on the differential impact of physical activity on perceived health status (PHS) in a large adult congenital heart disease (ACHD) patient population are lacking. We conducted a cross-sectional assessment of 4,028 ACHD patients recruited from 24 ACHD-specialized centers in 15 countries across 5 continents to examine the association between physical activity and PHS in a large international cohort of ACHD patients. A linear analog scale of the EuroQol-5D 3 level version and the 12-item Short Form Health Survey-version 2 were used to assess self-reported health status and the Health-Behavior Scale-Congenital Heart Disease was used as a subjective measurement of physical activity type, participation, and level. Correlation analyses and Wilcoxon Rank Sum tests examined bivariate relations between sample characteristics and PHS scores. Then, multivariable models were constructed to understand the impact of physical activity on PHS. Only 30% of our sample achieved recommended physical activity levels. Physically active patients reported better PHS than sedentary patients; however, the amount of physical activity was not associated with PHS. Further statistical analyses demonstrated that specifically sport participation regardless of physical activity level was a predictor of PHS. In conclusion, the majority of ACHD patients across the world are physically inactive. Sport participation appears to be the primary physical activity-related driver of PHS. By promoting sport-related exercise ACHD specialists thus may improve PHS in ACHD patients. 

  • 43.
    Larsson, Lena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Sandberg, Camilla
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Section of Physiotherapy.
    Apers, Silke
    Kovacs, Adrienne H.
    Luyckx, Koen
    Thomet, Corina
    Budts, Werner
    Enomoto, Junko
    Sluman, Maayke A.
    Wang, Jou-Kou
    Jackson, Jamie L.
    Khairy, Paul
    Cook, Stephen C.
    Alday, Luis
    Eriksen, Katrine
    Dellborg, Mikael
    Berghammer, Malin
    Rempel, Gwen
    Menahem, Samuel
    Caruana, Maryanne
    Tomlin, Martha
    Soufi, Alexandra
    Fernandes, Susan M.
    White, Kamila
    Callus, Edward
    Kutty, Shelby
    Moons, Philip
    Geographical variation and predictors of physical activity level in adults with congenital heart disease2019In: IJC Heart & Vasculature, ISSN 2352-9067, Vol. 22, p. 20-25Article in journal (Refereed)
    Abstract [en]

    Background: Physical activity is important to maintain and promote health. This is of particular interest in patients with congenital heart disease (CHD) where acquired heart disease should be prevented. The World Health Organization (WHO) recommends a minimum of 2.5 h/week of physical activity exceeding 3 metabolic equivalents(METS) to achieve positive health effects. It is unknown whether physical activity levels (PAL) in adult CHD patients differ by country of origin.

    Methods: 3896 adults with CHD recruited from 15 countries over 5 continents completed self-reported instruments, including the Health Behaviour Scale (HBS-CHD), within the APPROACH-IS project. For each patient, we calculated whether WHO recommendations were achieved or not. Associated factors were investigated using Generalized Linear Mixed Models.

    Results: On average, 31% reached the WHO recommendations but with a great variation between geographical areas (India: 10%–Norway: 53%). Predictors for physical activity level in line with the WHO recommendations, with country of residence as random effect, were male sex (OR 1.78, 95%CI 1.52–2.08), NYHA-class I (OR 3.10, 95%CI 1.71–5.62) and less complex disease (OR 1.46, 95%CI 1.16–1.83). In contrast, older age (OR 0.97, 95%CI 0.96–0.98), lower educational level (OR 0.41, 95%CI 0.26–0.64) and being unemployed (OR 0.57, 95%CI 0.42–0.77) were negatively associated with reaching WHO recommendations.

    Conclusions: A significant proportion of patients with CHD did not reach the WHO physical activity recommendations. There was a large variation in physical activity level by country of origin. Based on identified predictors, vulnerable patients may be identified and offered specific behavioral interventions.

  • 44.
    Larsson, Lena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Sandberg, Camilla
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Moons, P.
    Geographical variation in and predictors of physical activity level in adults with congenital heart disease2018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, p. 242-243Article in journal (Other academic)
    Abstract [en]

    Background: Physical activity is important to maintain and promote health. This is of particular interest in patients with congenital heart disease (CHD) where acquired heart disease should be prevented. The World Health Organization (WHO) recommends a minimum of 2.5 hours/week of physical activity exceeding 3 metabolic equivalents (METS) to achieve positive health effects. It is unknown whether physical activity levels (PAL) in adult CHD patients differ by country of origin.

    Methods: 4028 adults with CHD recruited from 15 countries over 5 continents completed self-reported instruments, including the Health Behaviour Scale (HBS-CHD), within a multicenter project. For each patient, we calculated whether WHO recommendations were achieved or not. Associated factors were investigated using Generalized Linear Mixed Models.

    Results: On average, 27% reached the WHO recommendations but with a great variation between geographical areas (Japan: 9% - Norway: 49%) (Figure). Predictors for PAL in line with the WHO recommendations, with country of residence as random effect, were male sex (OR 1.68, 95% CI 1.43–1.97), NYHA-class I (OR 2.79, 95% CI 1.54–5.06) and less complex disease (OR 1.28, 95% CI 1.02–1.62). In contrast, older age (OR 0.97, 95% CI 0.97–0.98), lower educational level (OR 0.41, 95% CI 0.26–0.65) and being unemployed (OR 0.58, 95% CI 042–0.78) were negatively associated with reaching WHO recommendations.

    Conclusions: A significant proportion of patients with CHD did not reach the WHO physical activity recommendations. There was a large variation in PAL by country of origin. Based on identified predictors, vulnerable patients may be identified and offered specific behavioural interventions.

  • 45.
    Larsson, Lena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Wadell, Karin
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Section of Physiotherapy.
    Thilen, Ulf
    Sandberg, Camilla
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Section of Physiotherapy.
    Adults with congenital heart disease overestimate their physical activity level2019In: IJC Heart & Vasculature, ISSN 2352-9067, Vol. 22, p. 13-17Article in journal (Refereed)
    Abstract [en]

    Background: Physical activity reduces the risk of acquired cardiovascular disease, which is of great importance in patients with congenital heart disease (CHD). There are diverging data whether physical activity level (PAL) differs between patients with CHD and controls. Furthermore, it is unknown if PAL can be reliably assessed in patients with CHD using self-reported instruments.

    Methods: Seventy-five patients with CHD (mean age 37.5 ± 15.5 years, women n = 29 [38.7%]) and 42 age and sex matched controls completed the International Physical Activity Questionnaire (IPAQ) and carried the activity monitor Actiheart over 4 days. Time spent at ≥3 METS ≥21.4 min/day, i.e. reaching the WHO recommendation for PAL to promote health, was used as the outcome measure. Data on PAL obtained from IPAQ were compared with Actiheart.

    Results: The proportion of individuals reaching target PAL according to IPAQ was similar in patients with CHD and controls (70.7%vs.76.2%, p = 0.52) as well as between patients with simple and complex lesions. There was an overall difference between IPAQ and Actiheart in detecting recommended PAL (72.6%vs.51.3%, p b 0.001). In a subgroup analysis, this difference was also detected in patients but was borderline for controls. The negative predictive value for IPAQ in detecting insufficient PAL was higher in patients than in controls (73%vs.40%).

    Conclusions: The proportion of persons reaching sufficient PAL to promote health was similar in patients and controls. The self-reported instrument overestimated PAL in relation to objective measurements. However, with a high negative predictive value, IPAQ is a potentially useful tool for detecting patients with insufficient PAL.

  • 46.
    Larsson, Lena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Rinnström, Daniel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Sandberg, Camilla
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Högström, Gabriel
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Thilen, Ulf
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Aerobic capacity in adolescence is associated with time to intervention in adult men with atrial septal defects2019In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 280, p. 57-60Article in journal (Refereed)
    Abstract [en]

    Background: Atrial septal defect (ASD) is a congenital heart lesion that often remains undiagnosed until adulthood. The reasons for this may be multifactorial. It is, however, known that closure of a hemodynamically significant ASD improves exercise capacity. This study aimed to explore whether the aerobic capacity in late adolescence is associated with time to diagnosis and intervention in adult men with late diagnosis of an atrial shunt.

    Methods: The Swedish Military Conscription Service Register contains data on exercise tests performed in late adolescence. By linking these data with the National Patient Register, 254 men with a later intervention for an ASD were identified.

    Results: Interventions were performed at a mean of 26.5 +/- 7.9 years after the initial exercise tests. The mean absolute workload among those with a later diagnosed ASD was similar to those without a later diagnosed ASD (274 +/- 51W vs. 276 +/- 52 W, p = 0.49). Men with a higher exercise capacity (>= 1 SD) had their intervention earlier (21.9 +/- 8.6 years vs. 27.5 +/- 7.4 years, p < 0.001).

    Conclusions: The aerobic exercise capacity was similar in adolescent men with later interventions for ASD compared to the reference population. Furthermore, those with high exercise capacity appeared to be diagnosed earlier. Thus, low exercise capacity may not be a feature of ASD during adolescence, but rather develop later in life as a natural progression of the disease.

  • 47.
    Ljungberg, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Bergdahl, Ingvar A.
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Norberg, Margareta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lipoprotein(a) and the Apolipoprotein B/A1 Ratio Independently Associate With Surgery for Aortic Stenosis Only in Patients With Concomitant Coronary Artery Disease2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 12, article id e007160Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Aortic stenosis (AS) has different clinical phenotypes, including AS with or without concomitant coronary artery disease (CAD). It is unknown whether these phenotypes share the same risk factors. In particular, lipoprotein(a) [Lp(a)] and apolipoproteins (Apo) are associated with AS, but it is unknown whether these associations differ among phenotypes. In this prospective analysis we examined the impact of Lp(a) and Apo in subgroups of patients with AS.

    METHODS AND RESULTS: We identified 336 patients (mean age at survey 56.7 years, 48% female) who underwent surgery for AS after a median 10.9 years (interquartile range 9.3 years), participants in 1 of 3 large population surveys. For each patient, 2 matched referents were allocated. Lp(a) and Apo were analyzed in the baseline samples. Uni- and multivariable logistic regression analyses were used to estimate risks related to a 1 (ln) standard deviation increase in Lp(a) and the ratio of Apo B to Apo A1 (Apo B/A1 ratio). High levels of Lp(a) predicted surgery for AS in 203 patients with concomitant CAD (odds ratio [95% confidence intervals]) (1.29 [1.07-1.55]), but not in 132 patients without CAD (1.04 [0.83-1.29]) in the fully adjusted model. Similarly, a high Apo B/A1 ratio predicted surgery in patients with concomitant CAD (1.43 [1.16-1.76]) but not in those without CAD (0.87 [0.69-1.10]).

    CONCLUSIONS: High levels of Lp(a) and a high Apo B/A1 ratio were associated with surgery for AS in patients with concomitant CAD but not in those with isolated AS. This finding may lead to a new avenue of research for targeted risk factor interventions in this population.

  • 48.
    Ljungberg, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Janiec, Mikael
    Bergdahl, Ingvar
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Siegbahn, Agneta
    Fall, Tove
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Proteomic Biomarkers for Incident Aortic Stenosis Requiring Valvular Replacement2018In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 138, no 6Article in journal (Refereed)
    Abstract [en]

    Background: Aortic valve stenosis (AS) is the most common indication for cardiac valve surgery; untreated AS is linked to high mortality. The etiological background of AS is unknown. Previous human studies were typically based on case-control studies. Biomarkers identified in prospective studies could lead to novel mechanistic insights. Methods: Within a large population survey with blood samples obtained at baseline, 334 patients were identified who later underwent surgery for AS (median age [interquartile range], 59.9 [10.4] years at survey and 68.3 [12.7] at surgery; 48% female). For each case, 2 matched referents were allocated. Plasma was analyzed with the multiplex proximity extension assay for screening of 92 cardiovascular candidate proteins. Conditional logistic regression models were used to assess associations between each protein and AS, with correction for multiple testing. A separate set of 106 additional cases with 212 matched referents was used in a validation study. Results: Six proteins (growth differentiation factor 15, galectin-4, von Willebrand factor, interleukin 17 receptor A, transferrin receptor protein 1, and proprotein convertase subtilisin/kexin type 9) were associated with case status in the discovery cohort; odds ratios ranged from 1.25 to 1.37 per SD increase in the protein signal. Adjusting the multivariable models for classical cardiovascular risk factors at baseline yielded similar results. Subanalyses of case-referent triplets (n=133) who showed no visible coronary artery disease at the time of surgery in the index person supported associations between AS and growth differentiation factor 15 (odds ratio, 1.40; 95% confidence interval, 1.10-1.78) and galectin-4 (odds ratio, 1.27; 95% confidence interval, 1.02-1.59), but these associations were attenuated after excluding individuals who donated blood samples within 5 years before surgery. In triplets (n=201), which included index individuals with concurrent coronary artery disease at the time of surgery, all 6 proteins were robustly associated with case status in all sensitivity analyses. In the validation study, the association of all but 1 (interleukin 17 receptor A) of these proteins were replicated in patients with AS with concurrent coronary artery disease but not in patients with AS without coronary artery disease. Conclusions: We provide evidence that 5 proteins were altered years before AS surgery and that the associations seem to be driven by concurrent atherosclerotic disease.

  • 49.
    Ljungberg, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Bergdahl, Ingvar
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Mild impairment of renal function (shrunken pore syndrome) is associated with increased risk for future surgery for aortic stenosis2019In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 79, no 7, p. 524-530Article in journal (Refereed)
    Abstract [en]

    Recently, a new approach was proposed to detect mild impairment in renal function: a reduced ratio between estimated glomerular filtration rate (eGFR) calculated by cystatin C and eGFR calculated by creatinine. We aimed to evaluate if this ratio is associated with aortic stenosis (AS) requiring surgery. We identified 336 patients that first participated in population surveys and later underwent surgery for AS (median age [interquartile range] 59.8 [10.3] years at survey and 68.3 [12.7] at surgery, 48% females). For each patient, two matched referents were allocated. Cystatin C and creatinine were determined in stored plasma. eGFR(cystatin C) and eGFR(creatinine) and their ratio were estimated. Conditional logistic regression analyses were used to estimate the risk (odds ratio (OR) with [95% confidence interval (CI)]) related to one (ln) standard deviation increase in the ratio between eGFR(cystatin C) and eGFR(creatinine). A high ratio was associated with lower risk for AS requiring surgery (OR [95% CI]) (OR 0.84 [0.73-0.97]), especially in women (0.74 [0.60-0.92] vs. 0.93 [0.76-1.13] in men). After further stratification for coronary artery disease (CAD), the association remained in women with CAD but not in women without CAD (0.60 [0.44-0.83] and 0.89 [0.65-1.23], respectively). In conclusion, a high ratio between eGFR(cystatin C) and eGFR(creatinine) was associated with lower risk for surgery for AS, especially in women. Mild impairment of renal function is thus associated with future risk for AS requiring surgery.

  • 50.
    Ljungberg, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Engström, Karl Gunnar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Albertsson, Elin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Holmer, Paul
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Norberg, Margareta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Bergdahl, Ingvar A.
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Traditional Cardiovascular Risk Factors and Their Relation to Future Surgery for Valvular Heart Disease or Ascending Aortic Disease: A Case-Referent Study2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 5, article id e005133Article in journal (Refereed)
    Abstract [en]

    Background: Risk factors for developing heart valve and ascending aortic disease are based mainly on retrospective data. To elucidate these factors in a prospective manner, we have performed a nested case-referent study using data from large, population-based surveys. Methods and Results: A total of 777 patients operated for heart valve disease or disease of the ascending aorta had previously participated in population-based health surveys in Northern Sweden. Median time (interquartile range) from survey to surgery was 10.5 (9.0) years. Primary indications for surgery were aortic stenosis (41%), aortic regurgitation (12%), mitral regurgitation (23%), and dilatation/dissection of the ascending aorta (17%). For each case, referents were allocated, matched for age, sex, and geographical area. In multivariable models, surgery for aortic stenosis was predicted by hypertension, high cholesterol levels, diabetes mellitus, and active smoking. Surgery for aortic regurgitation was associated with a low cholesterol level, whereas a high cholesterol level predicted surgery for mitral regurgitation. Hypertension, blood pressure, and previous smoking predicted surgery for disease of the ascending aorta whereas diabetes mellitus was associated with reduced risk. After exclusion of cases with coronary atherosclerosis, only the inverse associations between cholesterol and aortic regurgitation and between diabetes mellitus and disease of the ascending aorta remained. Conclusions: This is the first truly prospective study of traditional cardiovascular risk factors and their association with valvular heart disease and disease of the ascending aorta. We confirm the strong association between traditional risk factors and aortic stenosis, but only in patients with concomitant coronary artery disease. In isolated valvular heart disease, the impact of traditional risk factors is varying.

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