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  • 1. Ahlqvist, Viktor H
    et al.
    Persson, Margareta
    Umeå University, Faculty of Medicine, Department of Nursing.
    Ortega, Francisco B
    Tynelius, Per
    Magnusson, Cecilia
    Berglind, Daniel
    Birth Weight and Cardiorespiratory Fitness Among Young Men Born at Term: The Role of Genetic and Environmental Factors2020In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 9, no 3, article id e014290Article in journal (Refereed)
    Abstract [en]

    Background: Preterm delivery and low birth weight are prospectively associated with low cardiorespiratory fitness (CRF). However, whether birth weight, within the at-term range, is associated with later CRF is largely unknown. Thus, the aim of the current study was to examine this issue and whether such association, if any, is explained by shared and/or nonshared familial factors.

    Methods and Results: We conducted a prospective cohort study, including 286 761 young male adults and a subset of 52 544 siblings born at-term. Objectively measured data were retrieved from total population registers. CRF was tested at conscription and defined as the maximal load obtained on a cycle ergometer. We used linear and nonlinear and fixed-effects regression analyses to explore associations between birth weight and CRF. Higher birth weight, within the at-term range, was strongly associated with increasing CRF in a linear fashion. Each SD increase in birth weight was associated with an increase of 7.9 (95% CI, 7.8-8.1) and 6.6 (95% CI; 5.9-7.3) Wmax in the total and sibling cohorts, respectively. The association did not vary with young adulthood body mass index.

    Conclusions: Birth weight is strongly associated with increasing CRF in young adulthood among men born at-term, across all categories of body mass index. This association appears to be mainly driven by factors that are not shared between siblings. Hence, CRF may to some extent be determined already in utero. Prevention of low birth weight, also within the at-term-range, can be a feasible mean of increasing adult CRF and health.

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  • 2.
    Ballin, Marcel
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Niklasson, Johan
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Nordström, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health. School of Sport Sciences, Ui T The Arctic University of Norway, Tromsø, Norway.
    Associations of visceral adipose tissue and skeletal muscle density with incident stroke, myocardial infarction, and all-cause mortality in community-dwelling 70-year-old individuals: A prospective cohort study2021In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 10, no 9, article id e020065Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Aging leads to increased visceral adipose tissue (VAT) and reduced skeletal muscle density. To which extent these are associated with the risk of stroke, myocardial infarction (MI), and all-cause mortality in older adults is unknown.

    METHODS AND RESULTS: A total of 3294 70-year-old individuals (49.6% women) underwent a health examination in Umeå, Sweden, during 2012 to 2018. VAT and muscle density were measured using dual-energy x-ray absorptiometry and peripheral quantitative computed tomography. Cases of stroke, MI, and all-cause mortality were collected through national registers. Cox regressions were used to calculate hazard ratios (HRs) and 95% CIs per SD greater VAT and per SD lower muscle density. During a mean follow-up of 3.6 years, there were 108 cases of stroke or MI, and 97 deaths. Greater VAT (adjusted HR [aHR], 1.56; 95% CI, 1.09– 2.22), but not lower muscle density (aHR, 1.14; 95% CI, 0.97–1.34), was associated with increased risk of stroke or MI. Neither VAT (aHR, 0.95; 95% CI, 0.65–1.41) nor muscle density (aHR, 1.11; 95% CI, 0.92–1.34) was associated with all-cause mortality. The association of VAT with stroke or MI was only significant in men (aHR, 1.86; 95% CI, 1.19– 2.91) but not women (aHR, 0.60; 95% CI, 0.25–1.42) (Pinteraction =0.038).

    CONCLUSIONS: With the limitation of being an observational study, these findings suggest that VAT is an important obesity-related predictor of cardiovascular risk in 70-year-old men, and by implication, that decreasing VAT may potentially reduce their risk of cardiovascular disease.

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  • 3. Bang, Casper N.
    et al.
    Greve, Anders M.
    Rossebø, Anne B.
    Ray, Simon
    Egstrup, Kenneth
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nienaber, Christoph
    Okin, Peter M.
    Devereux, Richard B.
    Wachtell, Kristian
    Antihypertensive treatment with β-blockade in patients with asymptomatic aortic stenosis and association with cardiovascular events2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 12, article id e006709Article in journal (Refereed)
    Abstract [en]

    Background: Patients with aortic stenosis (AS) often have concomitant hypertension. Antihypertensive treatment with a beta-blocker (Bbl) is frequently avoided because of fear of depression of left ventricular function. However, it remains unclear whether antihypertensive treatment with a Bbl is associated with increased risk of cardiovascular events in patients with asymptomatic mild to moderate AS.

    Methods and results: We did a post hoc analysis of 1873 asymptomatic patients with mild to moderate AS and preserved left ventricular ejection fraction in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study. Propensity-matched Cox regression and competing risk analyses were used to assess risk ratios for all-cause mortality, sudden cardiac death, and cardiovascular death. A total of 932 (50%) patients received Bbl at baseline. During a median follow-up of 4.3 +/- 0.9 years, 545 underwent aortic valve replacement, and 205 died; of those, 101 were cardiovascular deaths, including 40 sudden cardiovascular deaths. In adjusted analyses, Bbl use was associated with lower risk of all-cause mortality (hazard ratio 0.5, 95% confidence interval 0.3-0.7, P<0.001), cardiovascular death (hazard ratio 0.4, 95% confidence interval 0.2-0.7, P<0.001), and sudden cardiac death (hazard ratio 0.2, 95% confidence interval 0.1-0.6, P=0.004). This was confirmed in competing risk analyses (all P<0.004). No interaction was detected with AS severity (all P>0.1).

    Conclusions: In post hoc analyses Bbl therapy did not increase the risk of all-cause mortality, sudden cardiac death, or cardiovascular death in patients with asymptomatic mild to moderate AS. A prospective study may be warranted to determine if Bbl therapy is in fact beneficial.

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  • 4. Bonamy, Anna-Karin Edstedt
    et al.
    Mohlkert, Lilly-Ann
    Hallberg, Jenny
    Liuba, Petru
    Fellman, Vineta
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Norman, Mikael
    Blood Pressure in 6-Year-Old Children Born Extremely Preterm2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 8, article id e005858Article in journal (Refereed)
    Abstract [en]

    Background-Advances in perinatal medicine have increased infant survival after very preterm birth. Although this progress is welcome, there is increasing concern that preterm birth is an emerging risk factor for hypertension at young age, with implications for the lifetime risk of cardiovascular disease. Methods and Results-We measured casual blood pressures (BPs) in a population-based cohort of 6-year-old survivors of extremely preterm birth (< 27 gestational weeks; n=171) and in age-and sex-matched controls born at term (n=172). Measured BP did not differ, but sex, age-, and height-adjusted median z scores were 0.14 SD higher (P=0.02) for systolic BP and 0.10 SD higher (P=0.01) for diastolic BP in children born extremely preterm than in controls. Among children born extremely preterm, shorter gestation, higher body mass index, and higher heart rate at follow-up were all independently associated with higher BP at 6 years of age, whereas preeclampsia, smoking in pregnancy, neonatal morbidity, and perinatal corticosteroid therapy were not. In multivariate regression analyses, systolic BP decreased by 0.10 SD (P=0.08) and diastolic BP by 0.09 SD (P=0.02) for each week-longer gestation. Conclusions-Six-year-old children born extremely preterm have normal but slightly higher BP than their peers born at term. Although this finding is reassuring for children born preterm and their families, follow-up at older age is warranted.

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  • 5.
    Camen, Stephan
    et al.
    Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.
    Csengeri, Dora
    Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
    Geelhoed, Bastiaan
    Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
    Niiranen, Teemu
    Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Medicine, Turku University Hospital and University of Turku, Turku, Finland.
    Gianfagna, Francesco
    Research Center in Epidemiology and Preventive Medicine, Department of Medicine and Surgery, University of Insubria, Varese, Italy; Mediterranea Cardiocentro, Napoli, Italy.
    Vishram-Nielsen, Julie K.
    Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region of Denmark, Copenhagen, Denmark; Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
    Costanzo, Simona
    Department of Epidemiology and Prevention, Istituto Neurologico Mediterraneo è un Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Neuromed, Pozzilli, Italy.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Heart Centre, Umeå University, Umeå, Sweden.
    Vartiainen, Erkki
    Finnish Institute for Health and Welfare, Helsinki, Finland.
    Börschel, Christin S.
    Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.
    Donati, Maria Benedetta
    Department of Epidemiology and Prevention, Istituto Neurologico Mediterraneo è un Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Neuromed, Pozzilli, Italy.
    Løchen, Maja-Lisa
    Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
    Ojeda, Francisco M.
    Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
    Kontto, Jukka
    Finnish Institute for Health and Welfare, Helsinki, Finland.
    Mathiesen, Ellisiv B.
    Brain and Circulation Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway; Department of Neurology, University Hospital of North Norway, Tromsø, Norway.
    Jensen, Steen M.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Heart Centre, Umeå University, Umeå, Sweden.
    Koenig, Wolfgang
    German Heart Center Munich, Technical University of Munich, Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany; Institute of Epidemiology and Medical Biometry, University of Ulm, Germany.
    Kee, Frank
    Centre for Public Health, Queens University of Belfast, Belfast, United Kingdom.
    de Gaetano, Giovanni
    Department of Epidemiology and Prevention, Istituto Neurologico Mediterraneo è un Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Neuromed, Pozzilli, Italy.
    Zeller, Tanja
    Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.
    Jørgensen, Torben
    Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region of Denmark, Copenhagen, Denmark; Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Tunstall-Pedoe, Hugh
    Cardiovascular Epidemiology Unit, Institute of Cardiovascular Research, University of Dundee, Dundee, United Kingdom.
    Blankenberg, Stefan
    Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.
    Kuulasmaa, Kari
    Finnish Institute for Health and Welfare, Helsinki, Finland.
    Linneberg, Allan
    Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region of Denmark, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Salomaa, Veikko
    Finnish Institute for Health and Welfare, Helsinki, Finland.
    Iacoviello, Licia
    Research Center in Epidemiology and Preventive Medicine, Department of Medicine and Surgery, University of Insubria, Varese, Italy; Department of Epidemiology and Prevention, Istituto Neurologico Mediterraneo è un Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Neuromed, Pozzilli, Italy.
    Schnabel, Renate B.
    Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.
    Risk Factors, Subsequent Disease Onset, and Prognostic Impact of Myocardial Infarction and Atrial Fibrillation2022In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 11, no 7, article id e024299Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Although myocardial infarction (MI) and atrial fibrillation (AF) are frequent comorbidities and share common cardiovascular risk factors, the direction and strength of the association of the risk factors with disease onset, subsequent disease incidence, and mortality are not completely understood.

    METHODS AND RESULTS: In pooled multivariable Cox regression analyses, we examined temporal relations of disease onset and identified predictors of MI, AF, and all-cause mortality in 108 363 individuals (median age, 46.0 years; 48.2% men) free of MI and AF at baseline from 6 European population-based cohorts. During a maximum follow-up of 10.0 years, 3558 (3.3%) individuals were diagnosed exclusively with MI, 1922 (1.8%) with AF but no MI, and 491 (0.5%) individuals developed both MI and AF. Association of sex, systolic blood pressure, antihypertensive treatment, and diabetes appeared to be stronger with incident MI than with AF, whereas increasing age and body mass index showed a higher risk for incident AF. Total cholesterol and daily smoking were significantly related to incident MI but not AF. Combined population attributable fraction of cardiovascular risk factors was >70% for incident MI, whereas it was only 27% for AF. Subsequent MI after AF (hazard ratio [HR], 1.68; 95% CI, 1.03–2.74) and subsequent AF after MI (HR, 1.75; 95% CI, 1.31–2.34) both significantly increased overall mortality risk.

    CONCLUSIONS: We observed different associations of cardiovascular risk factors with both diseases indicating distinct pathophysiological pathways. Subsequent diagnoses of MI and AF significantly increased mortality risk.

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  • 6. Cameron, Adrian J.
    et al.
    Romaniuk, Helena
    Orellana, Liliana
    Dallongeville, Jean
    Dobson, Annette J.
    Drygas, Wojciech
    Ferrario, Marco
    Ferrieres, Jean
    Giampaoli, Simona
    Gianfagna, Francesco
    Iacoviello, Licia
    Jousilahti, Pekka
    Kee, Frank
    Moitry, Marie
    Niiranen, Teemu J.
    Pajak, Andrzej
    Palmieri, Luigi
    Palosaari, Tarja
    Satu, Männistö
    Tamosiunas, Abdonas
    Thorand, Barbara
    Toft, Ulla
    Vanuzzo, Diego
    Veikko, Salomaa
    Veronesi, Giovanni
    Wilsgaard, Tom
    Kuulasmaa, Kari
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Combined Influence of Waist and Hip Circumference on Risk of Death in a Large Cohort of European and Australian Adults2020In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 9, no 13, article id e015189Article in journal (Refereed)
    Abstract [en]

    Background: Waist circumference and hip circumference are both strongly associated with risk of death; however, their joint association has rarely been investigated.

    Methods and Results: The MONICA Risk, Genetics, Archiving, and Monograph (MORGAM) Project was conducted in 30 cohorts from 11 countries; 90 487 men and women, aged 30 to 74 years, predominantly white, with no history of cardiovascular disease, were recruited in 1986 to 2010 and followed up for up to 24 years. Hazard ratios were estimated using sex‐specific Cox models, stratified by cohort, with age as the time scale. Models included baseline categorical obesity measures, age, total and high‐density lipoprotein cholesterol, systolic blood pressure, antihypertensive drugs, smoking, and diabetes mellitus. A total of 9105 all‐cause deaths were recorded during a median follow‐up of 10 years. Hazard ratios for all‐cause death presented J‐ or U‐shaped associations with most obesity measures. With waist and hip circumference included in the same model, for all hip sizes, having a smaller waist was strongly associated with lower risk of death, except for men with the smallest hips. In addition, among those with smaller waists, hip size was strongly negatively associated with risk of death, with ≈20% more people identified as being at increased risk compared with waist circumference alone.

    Conclusions: A more complex relationship between hip circumference, waist circumference, and risk of death is revealed when both measures are considered simultaneously. This is particularly true for individuals with smaller waists, where having larger hips was protective. Considering both waist and hip circumference in the clinical setting could help to best identify those at increased risk of death.

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  • 7. Djekic, Demir
    et al.
    Shi, Lin
    Brolin, Harald
    Carlsson, Frida
    Sarnqvist, Charlotte
    Savolainen, Otto
    Cao, Yang
    Backhed, Fredrik
    Tremaroli, Valentina
    Landberg, Rikard
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Chalmers University of Technology, Gothenburg, Sweden.
    Frobert, Ole
    Effects of a Vegetarian Diet on Cardiometabolic Risk Factors, Gut Microbiota, and Plasma Metabolome in Subjects With Ischemic Heart Disease: A Randomized, Crossover Study2020In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 9, no 18, article id e016518Article in journal (Refereed)
    Abstract [en]

    Background: A vegetarian diet (VD) may reduce future cardiovascular risk in patients with ischemic heart disease.

    Methods and Results: A randomized crossover study was conducted in subjects with ischemic heart disease, assigned to 4‐week intervention periods of isocaloric VD and meat diet (MD) with individually designed diet plans, separated by a 4‐week washout period. The primary outcome was difference in oxidized low‐density lipoprotein cholesterol (LDL‐C) between diets. Secondary outcomes were differences in cardiometabolic risk factors, quality of life, gut microbiota, fecal short‐chain and branched‐chain fatty acids, and plasma metabolome. Of 150 eligible patients, 31 (21%) agreed to participate, and 27 (87%) participants completed the study. Mean oxidized LDL‐C (−2.73 U/L), total cholesterol (−5.03 mg/dL), LDL‐C (−3.87 mg/dL), and body weight (−0.67 kg) were significantly lower with the VD than with the MD. Differences between VD and MD were observed in the relative abundance of several microbe genera within the families Ruminococcaceae, Lachnospiraceae, and Akkermansiaceae. Plasma metabolites, including l‐carnitine, acylcarnitine metabolites, and phospholipids, differed in subjects consuming VD and MD. The effect on oxidized LDL‐C in response to the VD was associated with a baseline gut microbiota composition dominated by several genera of Ruminococcaceae.

    Conclusions: The VD in conjunction with optimal medical therapy reduced levels of oxidized LDL‐C, improved cardiometabolic risk factors, and altered the relative abundance of gut microbes and plasma metabolites in patients with ischemic heart disease. Our results suggest that composition of the gut microbiota at baseline may be related to the reduction of oxidized LDL‐C observed with the VD.

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  • 8.
    Eriksson, Marie
    et al.
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Grundberg, Anton
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Inge, Erik
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    von Euler, Mia
    Department of Neurology and Rehabilitation, Faculty of Medicine and Health Örebro University Örebro Sweden, Sweden.
    Stroke recurrence following 28 days after first stroke in men and women 2012 to 2020: observations from the Swedish stroke register2023In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 12, no 3, article id e028222Article in journal (Refereed)
    Abstract [en]

    Background: Stroke incidence, care, and survival show continuous improvements in Sweden, including no or decreasing disparities between men and women. In this study, we aimed to estimate and compare the risk of stroke recurrence in men and women over time, accounting for the competing risk of death.

    Methods and Results: We included adult patients with first-time stroke (ischemic or intracerebral hemorrhage) registered in Riksstroke (the Swedish Stroke Register), 2012 to 2020, and followed until December 2020. Stroke recurrences included new events registered in Riksstroke from 28 days after stroke. To account for the competing risk of death, we used the cumulative incidence function to estimate crude incidences, and multivariable Cox regression to estimate cause-specific hazard ratios (HRs) adjusting for differences in patients' risk factor profiles. The study included 72 148 (53.5%) men and 62 689 (46.5%) women. We observed 10 925 stroke recurrences and 81 811 deaths following the initial 28 days after the first stroke. The cumulative incidence of stroke recurrence was 3.7% (95% CI, 3.6-3.8) after 1 year, 7.0 (95% CI, 6.8-7.1) after 3 years, and 9.1% (95% CI, 8.9-9.3) after 5 years. The incidence decreased substantially during the study period (HR, 2019-2020 versus 2012, 0.824 [95% CI, 0.759-0.894]). Overall, men had a lower risk of stroke recurrence. After adjustments for differences in patient characteristics, men had a slightly higher risk of recurrence (of any type) after an ischemic stroke (HR, 1.090 [95% CI, 1.045-1.138]) and a lower risk after hemorrhagic stroke (HR, 0.880 [95% CI, 0.781-0.991]) compared with women.

    Conclusions: The risk of stroke recurrence has decreased in both men and women. Women's higher age and other differences in risk factors partly explain their higher risk of stroke recurrence compared with men.

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  • 9.
    Fricke, Katrin
    et al.
    Cardiology, Pediatric Heart Centre, Skåne University Hospital, Lund, Sweden; Pediatrics, Department of Clinical Sciences, Lund University, Lund, Sweden.
    Mellander, Mats
    Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden; Children´s Heart Centre, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Hanséus, Katarina
    Cardiology, Pediatric Heart Centre, Skåne University Hospital, Lund, Sweden; Pediatrics, Department of Clinical Sciences, Lund University, Lund, Sweden.
    Tran, Phan-Kiet
    Pediatrics, Department of Clinical Sciences, Lund University, Lund, Sweden; Cardiac Surgery, Pediatric Heart Centre, Skåne University Hospital, Lund, Sweden.
    Synnergren, Mats
    Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden; Children´s Heart Centre, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Ramgren, Jens Johansson
    Pediatrics, Department of Clinical Sciences, Lund University, Lund, Sweden; Cardiac Surgery, Pediatric Heart Centre, Skåne University Hospital, Lund, Sweden.
    Rydberg, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Sunnegårdh, Jan
    Children´s Heart Centre, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Dalén, Magnus
    Department of Cardiothoracic Surgery, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
    Sjöberg, Gunnar
    Department of Women’s and Children’s Health, Karolinska Institute, Stockholm, Sweden.
    Weismann, Constance G.
    Cardiology, Pediatric Heart Centre, Skåne University Hospital, Lund, Sweden.
    Liuba, Petru
    Cardiology, Pediatric Heart Centre, Skåne University Hospital, Lund, Sweden; Pediatrics, Department of Clinical Sciences, Lund University, Lund, Sweden.
    Impact of Left Ventricular Morphology on Adverse Outcomes Following Stage 1 Palliation for Hypoplastic Left Heart Syndrome: 20 Years of National Data From Sweden2022In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 11, no 7, article id e022929Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Hypoplastic left heart syndrome is associated with significant morbidity and mortality. We aimed to assess the influence of left ventricular morphology and choice of shunt on adverse outcome in patients with hypoplastic left heart syndrome and stage 1 palliation.

    METHODS AND RESULTS: This was a retrospective analysis of patients with hypoplastic left heart syndrome with stage 1 palliation between 1999 and 2018 in Sweden. Patients (n=167) were grouped based on the anatomic subtypes aortic-mitral atresia, aortic atresia-mitral stenosis (AA-MS), and aortic-mitral stenosis. The left ventricular phenotypes including globular left ventricle (Glob-LV), miniaturized and slit-like left ventricle (LV), and the incidence of major adverse events (MAEs) including mortality were assessed. The overall mortality and MAEs were 31% and 41%, respectively. AA-MS (35%) was associated with both mortality (all other subtypes versus AA-MS: interstage-I: hazard ratio [HR], 2.7; P=0.006; overall: HR, 2.2; P=0.005) and MAEs (HR, 2.4; P=0.0009). Glob-LV (57%), noticed in all patients with AA-MS, 61% of patients with aortic stenosis-mitral stenosis, and 19% of patients with aortic atresia-mitral atresia, was associated with both mortality (all other left ventricular phenotypes versus Glob-LV: interstage-I: HR, 4.5; P=0.004; overall: HR, 3.4; P=0.0007) and MAEs (HR, 2.7; P=0.0007). There was no difference in mortality and MAEs between patients with AA-MS and without AA-MS with Glob-LV (P>0.15). Patients with AA-MS (35%) or Glob-LV (38%) palliated with a Blalock-Taussig shunt had higher overall mortality compared with those palliated with Sano shunts, irrespective of the stage 1 palliation year (AA-MS: HR, 2.6; P=0.04; Glob-LV: HR, 2.1; P=0.03).

    CONCLUSIONS: Glob-LV and AA-MS are independent morphological risk factors for adverse short-and long-term outcome, especially if a Blalock-Taussig shunt is used as part of stage 1 palliation. These findings are important for the clinical management of patients with hypoplastic left heart syndrome.

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  • 10.
    Graipe, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Section of Cardiology, Department of Internal Medicine, Östersund Hospital, Östersund, Sweden.
    Binsell-Gerdin, Emil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Internal Medicine, Östersund Hospital, Östersund, Sweden .
    Söderström, Lars
    Mooe, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Incidence, Time Trends, and Predictors of Intracranial Hemorrhage During Long-Term Follow-up After Acute Myocardial Infarction2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 12, article id e002290Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: To address the lack of knowledge regarding the long-term risk of intracranial hemorrhage (ICH) after acute myocardial infarction (AMI), the aims of this study were to: (1) investigate the incidence, time trends, and predictors of ICH in a large population within 1 year of discharge after AMI; (2) investigate the comparative 1-year risk of ICH in AMI patients and a reference group; and (3) study the impact of previous ischemic stroke on ICH risk in patients treated with various antithrombotic therapies.

    METHODS AND RESULTS: Data about patients whose first AMI occurred between 1998 and 2010 were collected from the Swedish Register of Information and Knowledge about Swedish Heart-Intensive-Care Admissions (RIKS-HIA). Patients with an ICH after discharge were identified in the National Patient Register. Risk was compared against a matched reference population. Of 187 386 patients, 590 had an ICH within 1 year. The 1-year cumulative incidence (0.35%) was approximately twice that of the reference group, and it did not change significantly over time. Advanced age, previous ischemic or hemorrhagic stroke, and reduced glomerular filtration rate were associated with increased ICH risk, whereas female sex was associated with a decreased risk. Previous ischemic stroke did not increase risk of ICH associated with single or dual antiplatelet therapy, but increased risk with anticoagulant therapy.

    CONCLUSION: The 1-year incidence of ICH after AMI remained stable, at ≈0.35%, over the study period. Advanced age, decreased renal function, and previous ischemic or hemorrhagic stroke are predictive of increased ICH risk.

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  • 11. Grøntved, Anders
    et al.
    Koivula, Robert W
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Østergaard, Lars
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Skåne University Hospital Malmö, Malmö, Sweden.
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Skåne University Hospital Malmö, Malmö, Sweden.
    Bicycling to Work and Primordial Prevention of Cardiovascular Risk: A Cohort Study Among Swedish Men and Women2016In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 5, no 11, article id e004413Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Bicycling to work may be a viable approach for achieving physical activity that provides cardiovascular health benefits. In this study we investigated the relationship of bicycling to work with incidence of obesity, hypertension, hypertriglyceridemia, and impaired glucose tolerance across a decade of follow-up in middle-aged men and women.

    METHODS AND RESULTS: We followed 23 732 Swedish men and women with a mean age of 43.5 years at baseline who attended a health examination twice during a 10-year period (1990-2011). In multivariable adjusted models we calculated the odds of incident obesity, hypertension, hypertriglyceridemia, and impaired glucose tolerance, comparing individuals who commuted to work by bicycle with those who used passive modes of transportation. We also examined the relationship of change in commuting mode with incidence of these clinical risk factors. Cycling to work at baseline was associated with lower odds of incident obesity (odds ratio [OR]=0.85, 95% CI 0.73-0.99), hypertension (OR=0.87, 95% CI 0.79-0.95), hypertriglyceridemia (OR=0.85, 95% CI 0.76-0.94), and impaired glucose tolerance (OR=0.88, 95% CI 0.80-0.96) compared with passive travel after adjusting for putative confounding factors. Participants who maintained or began bicycling to work during follow-up had lower odds of obesity (OR=0.61, 95% CI 0.50-0.73), hypertension (OR=0.89, 95% CI 0.80-0.98), hypertriglyceridemia (OR=0.80, 95% CI 0.70-0.90), and impaired glucose tolerance (OR=0.82, 95% CI 0.74-0.91) compared with participants not cycling to work at both times points or who switched from cycling to other modes of transport during follow-up.

    CONCLUSIONS: These data suggest that commuting by bicycle to work is an important strategy for primordial prevention of clinical cardiovascular risk factors among middle-aged men and women.

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  • 12. Hållmarker, Ulf
    et al.
    Åsberg, Signild
    Michaëlsson, Karl
    Ärnlöv, Johan
    Hellberg, Dan
    Lindbäck, Johan
    Wester, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    James, Stefan
    Risk of Recurrent Stroke and Death After First Stroke in Long-Distance Ski Race Participants2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 10, article id e002469Article in journal (Refereed)
    Abstract [en]

    Background: Physical activity is of benefit for primary prevention of cardiovascular diseases, but it appears to increase the risk for atrial fibrillation. We aimed to study a cohort of patients following a first stroke in individuals with previous high physical activity, compare them to the general population with respect to recurrent stroke and death, and relate these to atrial fibrillation. Methods and Results: From the participants of the Vasaloppet, the world's largest ski-race, and matched individuals from the general population (n=708 604), we identified 5964 patients hospitalized with a first-time stroke between 1994 and 2010. Individuals with severe diseases were excluded. One half percent of skiers and 1% of nonskiers were hospitalized due to stroke. The incidence rate was 8.3 per 100 person-years among skiers and 11.1 among nonskiers. The hazard ratio (HR) for recurrent stroke or death between the 2 groups was 0.76 (95% CI 0.67 to 0.86). The result was consistent in subgroups. The HR for death was 0.66 (95% CI 0.56 to 0.78) and for recurrent stroke 0.82 (95% CI 0.70 to 0.96). After adjustment for smoking and socioeconomic factors, the HR for death was consistent at 0.70 (95% CI 0.56 to 0.87) while the HR for recurrent stroke was not statistically significant. Outcomes for skiers with atrial fibrillation tended to show a lower risk than for nonskiers. Conclusions: This large cohort study supports the hypothesis that patients with a stroke and with prior regular physical activity have a lower risk of death, while their risk for recurrent stroke is similar to that of nonskiers. The skiers had a higher incidence of atrial fibrillation, but still no increased risk of recurring stroke.

  • 13. Langrish, Jeremy P
    et al.
    Unosson, Jon
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bosson, Jenny
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Barath, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Muala, Ala
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blackwell, Scott
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Megson, Ian L
    Treweeke, Andrew
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Newby, David E
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mills, Nicholas L
    Altered nitric oxide bioavailability contributes to diesel exhaust inhalation-induced cardiovascular dysfunction in man2013In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 2, no 1, p. e004309-Article in journal (Refereed)
    Abstract [en]

    Background Diesel exhaust inhalation causes cardiovascular dysfunction including impaired vascular reactivity, increased blood pressure, and arterial stiffness. We investigated the role of nitric oxide (NO) bioavailability in mediating these effects.

    Methods and Results In 2 randomized double-blind crossover studies, healthy nonsmokers were exposed to diesel exhaust or filtered air. Study 1: Bilateral forearm blood flow was measured during intrabrachial infusions of acetylcholine (ACh; 5 to 20 mu g/min) and sodium nitroprusside (SNP; 2 to 8 mu g/min) in the presence of the NO clamp (NO synthase inhibitor N-G-monomethyl-L-arginine (L-NMMA) 8 mu g/min coinfused with the NO donor SNP at 90 to 540 ng/min to restore basal blood flow). Study 2: Blood pressure, arterial stiffness, and cardiac output were measured during systemic NO synthase inhibition with intravenous L-NMMA (3 mg/kg). Following diesel exhaust inhalation, plasma nitrite concentrations were increased (68 +/- 48 versus 41 +/- 32 nmol/L; P=0.006) despite similar L-NMMA-induced reductions in basal blood flow (-20.6 +/- 14.7% versus -21.1 +/- 14.6%; P=0.559) compared to air. In the presence of the NO clamp, ACh and SNP caused dose-dependent vasodilatation that was not affected by diesel exhaust inhalation (P>0.05 for both). Following exposure to diesel exhaust, L-NMMA caused a greater increase in blood pressure (P=0.048) and central arterial stiffness (P=0.007), but reductions in cardiac output and increases in systemic vascular resistance (P>0.05 for both) were similar to those seen with filtered air.

    Conclusions Diesel exhaust inhalation disturbs normal vascular homeostasis with enhanced NO generation unable to compensate for excess consumption. We suggest the adverse cardiovascular effects of air pollution are, in part, mediated through reduced NO bioavailability.

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    NO bioavailabiltiy
  • 14.
    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.

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  • 15.
    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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  • 16. Lu, Chun-Wei
    et al.
    Wang, Jou-Kou
    Yang, Hsiao-Ling
    Kovacs, Adrienne H.
    Luyckx, Koen
    Ruperti-Repilado, Francisco Javier
    Van De Bruaene, Alexander
    Enomoto, Junko
    Sluman, Maayke A.
    Jackson, Jamie L.
    Khairy, Paul
    Cook, Stephen C.
    Chidambarathanu, Shanthi
    Alday, Luis
    Oechslin, Erwin
    Eriksen, Katrine
    Dellborg, Mikael
    Berghammer, Malin
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Mackie, Andrew S.
    Menahem, Samuel
    Caruana, Maryanne
    Veldtman, Gruschen
    Soufi, Alexandra
    Fernandes, Susan M.
    White, Kamila
    Callus, Edward
    Kutty, Shelby
    Apers, Silke
    Moons, Philip
    Heart Failure and Patient-Reported Outcomes in Adults With Congenital Heart Disease from 15 Countries2022In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 11, no 9, article id e024993Article in journal (Refereed)
    Abstract [en]

    Background: Heart failure (HF) is the leading cause of mortality and associated with significant morbidity in adults with congenital heart disease. We sought to assess the association between HF and patient-report outcomes in adults with congenital heart disease.

    Methods and Results: As part of the APPROACH-IS (Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease-International Study), we collected data on HF status and patient-reported outcomes in 3959 patients from 15 countries across 5 continents. Patient-report outcomes were: perceived health status (12-item Short Form Health Survey), quality of life (Linear Analogue Scale and Satisfaction with Life Scale), sense of coherence-13, psychological distress (Hospital Anxiety and Depression Scale), and illness perception (Brief Illness Perception Questionnaire). In this sample, 137 (3.5%) had HF at the time of investigation, 298 (7.5%) had a history of HF, and 3524 (89.0%) had no current or past episode of HF. Patients with current or past HF were older and had a higher prevalence of complex congenital heart disease, arrhythmias, implantable cardioverter-defibrillators, other clinical comorbidities, and mood disorders than those who never had HF. Patients with HF had worse physical functioning, mental functioning, quality of life, satisfaction with life, sense of coherence, depressive symptoms, and illness perception scores. Magnitudes of differences were large for physical functioning and illness perception and moderate for mental functioning, quality of life, and depressive symptoms.

    Conclusions: HF in adults with congenital heart disease is associated with poorer patient-reported outcomes, with large effect sizes for physical functioning and illness perception.

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  • 17.
    Meidell Blylod, Viktor
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Rinnström, Daniel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Pennlert, Johanna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Ostenfeld, Ellen
    Department of Clinical Sciences Lund Clinical Physiology, Lund University Lund Sweden, Sweden.
    Dellborg, Mikael
    Department of Molecular and Clinical Medicine University of Gothenburg Gothenburg Sweden, Sweden.
    Sörensson, Peder
    Department of Medicine Solna Karolinska Institutet Stockholm Sweden, Sweden.
    Christersson, Christina
    Department of Medical Sciences Cardiology, Uppsala University Uppsala Sweden, Sweden.
    Thilén, Ulf
    Department of Clinical Sciences Lund Cardiology, Lund University Lund Sweden, Sweden.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Interventions in Adults With Repaired Coarctation of the Aorta2022In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 11, no 14, article id e023954Article in journal (Refereed)
    Abstract [en]

    Background: Coarctation of the aorta coexists with other cardiac anomalies and has long-term complications, including recoarctation, which may require intervention after the primary coarctation repair. This study aims to clarify the prevalence of and risk factors for interventions related to the coarctation complex as well as late mortality in a large contemporary patient population.

    Methods and Results: The Swedish National Register of Congenital Heart Disease was used, which comprised 683 adults with repaired coarctation of the aorta. Analysis was performed on freedom from intervention thereafter at the coarctation site, aortic valve, left ventricular outflow tract, or ascending aorta. One hundred ninety-six (29%) patients had at least 1 of these interventions. Estimated freedom from either of these interventions was 60% after 50 years. The risk of undergoing such an intervention was higher among men (hazard ratio, 1.6 [95% CI, 1.2-2.2]). Estimated freedom from another intervention at the coarctation site was 75% after 50 years. In women, there was an increase in interventions at the coarctation site after 45 years. Patients who underwent one of the previously mentioned interventions after the primary coarctation repair had poorer left ventricular function. Eighteen patients (3%) died during follow-up in the register. The standardized mortality ratio was 2.9 (95% CI, 1.7-4.3).

    Conclusions: Interventions are common after coarctation repair. The risk for and time of interventions are affected by sex. Our results have implications for planning follow-up and giving appropriate medical advice to the growing population of adults with repaired coarctation of the aorta.

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  • 18. Mohlkert, Lilly-Ann
    et al.
    Hallberg, Jenny
    Broberg, Olof
    Rydberg, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Pegelow Halvorsen, Cecilia
    Liuba, Petru
    Fellman, Vineta
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Sjöberg, Gunnar
    Norman, Mikael
    The Preterm Heart in Childhood: Left Ventricular Structure, Geometry, and Function Assessed by Echocardiography in 6-Year-Old Survivors of Periviable Births2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 2, article id e007742Article in journal (Refereed)
    Abstract [en]

    Background: Preterm birth has been associated with increased risk of cardiovascular morbidity in adult life. We evaluated whether preterm birth is associated with deviating cardiac structure and function before school start. Methods and Results: In total, 176 children aged 6 years and born extremely preterm (EXPT; gestational age of 22-26weeks) and 134 children born at term (control [CTRL]) were studied. We used echocardiography to assess left heart dimensions, geometry, and functions. Recording and off-line analyses of echocardiographic images were performed by operators blinded to group belonging. Body size, blood pressure, and heart rate were also measured. Rates of family history of cardiovascular disease and sex distribution were similar in the EXPT and CTRL groups. Heart rate and systolic blood pressure did not differ, whereas diastolic blood pressure was slightly higher in EXPT than CTRL participants. After adjusting for body surface area, left ventricular length, width, and aortic valve annulus diameter were 3% to 5% smaller in EXPT than CTRL participants. Left ventricular longitudinal shortening and systolic tissue velocity were 7% to 11% lower, and transversal shortening fraction was 6% higher in EXPT than CTRL participants. The EXPT group also exhibited lower atrial emptying velocities than the CTRL group. Sex, fetal growth restriction, or a patent ductus arteriosus in the neonatal period did not contribute to cardiac dimensions or performance. Conclusions: Six-year-old children born extremely preterm exhibit a unique cardiac phenotype characterized by smaller left ventricles with altered systolic and diastolic functions than same-aged children born at term.

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  • 19. Norman, Mikael
    et al.
    Håkansson, Stellan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Umeå University Hospital.
    Kusuda, Satoshi
    Vento, Maximo
    Lehtonen, Liisa
    Reichman, Brian
    Darlow, Brian A.
    Adams, Mark
    Bassler, Dirk
    Isayama, Tetsuya
    Rusconi, Franca
    Lee, Shoo
    Lui, Kei
    Yang, Junmin
    Shah, Prakesh S.
    Neonatal Outcomes in Very Preterm Infants With Severe Congenital Heart Defects: An International Cohort Study2020In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 9, no 5, article id e015369Article in journal (Refereed)
    Abstract [en]

    Background Very preterm infants are at high risk of death or severe morbidity. The objective was to determine the significance of severe congenital heart defects (CHDs) for these risks. Methods and Results This cohort study included infants from 10 countries born from 2007-2015 at 24 to 31 weeks' gestation with birth weights <1500 g. Severe CHDs were defined by International Classification of Diseases, Ninth Revision (ICD-9) and Tenth (ICD-10) codes and categorized as those compromising systemic output, causing sustained cyanosis, or resulting in congestive heart failure. The primary outcome was in-hospital mortality. Secondary outcomes were neonatal brain injury, necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity. Adjusted and propensity score-matched odds ratios (ORs) were calculated. Analyses were stratified by type of CHD, gestational age, and network. A total of 609 (0.77%) infants had severe CHD and 76 371 without any malformation served as controls. The mean gestational age and birth weight were 27.8 weeks and 1018 g, respectively. The mortality rate was 18.6% in infants with CHD and 8.9% in controls (propensity score-matched OR, 2.30; 95% CI, 1.61-3.27). Severe CHD was not associated with neonatal brain injury, necrotizing enterocolitis, or retinopathy of prematurity, whereas the OR for bronchopulmonary dysplasia increased. Mortality was higher in all types, with the highest propensity score-matched OR (4.96; 95% CI, 2.11-11.7) for CHD causing congestive heart failure. While mortality did not differ between groups at <27 weeks' gestational age, adjusted OR for mortality in infants with CHD increased to 10.9 (95% CI, 5.76-20.70) at 31 weeks' gestational age. Rates of CHD and mortality differed significantly between networks. Conclusions Severe CHD is associated with significantly increased mortality in very preterm infants.

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  • 20.
    Otten, Julia
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Andersson, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Ståhl, Jens
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Stomby, Andreas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Saleh, Ahmed
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Waling, Maria
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Ryberg, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Hauksson, Jon
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Department of Radiography and Biomedical Science, Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
    Svensson, Michael B.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Section of Sports Medicine.
    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, Section of Medicine.
    Exercise Training Adds Cardiometabolic Benefits of a Paleolithic Diet in Type 2 Diabetes Mellitus2019In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 8, no 2, article id e010634Article in journal (Refereed)
    Abstract [en]

    Background: The accumulation of myocardial triglycerides and remodeling of the left ventricle are common features in type 2 diabetes mellitus and represent potential risk factors for the development of diastolic and systolic dysfunction. A few studies have investigated the separate effects of diet and exercise training on cardiac function, but none have investigated myocardial changes in response to a combined diet and exercise intervention. This 12-week randomized study assessed the effects of a Paleolithic diet, with and without additional supervised exercise training, on cardiac fat, structure, and function.

    Methods and Results: Twenty-two overweight and obese subjects with type 2 diabetes mellitus were randomized to either a Paleolithic diet and standard-care exercise recommendations ( PD ) or to a Paleolithic diet plus supervised exercise training 3 hours per week ( PD - EX ). This study includes secondary end points related to cardiac structure and function, ie, myocardial triglycerides levels, cardiac morphology, and strain were measured using cardiovascular magnetic resonance, including proton spectroscopy, at baseline and after 12 weeks. Both groups showed major favorable metabolic changes. The PD - EX group showed significant decreases in myocardial triglycerides levels (-45%, P=0.038) and left ventricle mass to end-diastolic volume ratio (-13%, P=0.008) while the left ventricle end-diastolic volume and stroke volume increased significantly (+14%, P=0.004 and +17%, P=0.008, respectively). These variables were unchanged in the PD group.

    Conclusions: Exercise training plus a Paleolithic diet reduced myocardial triglycerides levels and improved left ventricle remodeling in overweight/obese subjects with type 2 diabetes mellitus.

    Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01513798.

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  • 21. Persson, Jonas
    et al.
    Strawbridge, Rona J.
    McLeod, Olga
    Gertow, Karl
    Silveira, Angela
    Baldassarre, Damiano
    Van Zuydam, Natalie
    Shah, Sonia
    Fava, Cristiano
    Gustafsson, Stefan
    Veglia, Fabrizio
    Sennblad, Bengt
    Larsson, Malin
    Sabater-Lleal, Maria
    Leander, Karin
    Gigante, Bruna
    Tabak, Adam
    Kivimaki, Mika
    Kauhanen, Jussi
    Rauramaa, Rainer
    Smit, Andries J.
    Mannarino, Elmo
    Giral, Philippe
    Humphries, Steve E.
    Tremoli, Elena
    de Faire, Ulf
    Lind, Lars
    Ingelsson, Erik
    Hedblad, Bo
    Melander, Olle
    Kumari, Meena
    Hingorani, Aroon
    Morris, Andrew D.
    Palmer, Colin N. A.
    Lundman, Pia
    Ohrvik, John
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Sex-Specific Effects of Adiponectin on Carotid Intima-Media Thickness and Incident Cardiovascular Disease2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 8, article id e001853Article in journal (Refereed)
    Abstract [en]

    Background-Plasma adiponectin levels have previously been inversely associated with carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis. In this study, we used a sex-stratified Mendelian randomization approach to investigate whether adiponectin has a causal protective influence on IMT. Methods and Results-Baseline plasma adiponectin concentrationwas tested for association with baseline IMT, IMT progression over 30 months, and occurrence of cardiovascular events within 3 years in 3430 participants (women, n=1777; men, n=1653) with high cardiovascular risk but no prevalent disease. Plasma adiponectin levels were inversely associated with baseline mean bifurcation IMT after adjustment for established risk factors (beta=-0.018, P<0.001) in men but not in women (beta=-0.006, P=0.185; P for interaction=0.061). Adiponectin levels were inversely associated with progression of mean common carotid IMT in men (beta=-0.0022, P=0.047), whereas no association was seen in women (0.0007, P=0.475; P for interaction=0.018). Moreover, we observed that adiponectin levels were inversely associated with coronary events in women (hazard ratio 0.57, 95% CI 0.37 to 0.87) but not in men (hazard ratio 0.82,95% CI0.54 to 1.25). Agenescore of adiponectin-raisingalleles in6loci, reported recently inalarge multi-ethnic metaanalysis, was inversely associated with baseline mean bifurcation IMT in men (beta=-0.0008, P=0.004) but not in women (beta=-0.0003, P=0.522; P for interaction=0.007). Conclusions-This report provides some evidence for adiponectin protecting against atherosclerosis, with effects being confined to men; however, compared with established cardiovascular risk factors, the effect of plasma adiponectin was modest. Further investigation involving mechanistic studies is warranted.

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  • 22. Poveda, Alaitz
    et al.
    Atabaki-Pasdar, Naeimeh
    Ahmad, Shafqat
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Malmö, Sweden; Division of Endocrinology and Diabetes, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Malmö, Sweden Department of Nutrition, Harvard Chan School of Public Health, Boston, MA.
    Association of Established Blood Pressure Loci With 10-Year Change in Blood Pressure and Their Ability to Predict Incident Hypertension2020In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 9, no 16, article id e014513Article in journal (Refereed)
    Abstract [en]

    Background: Genome‐wide association studies have identified >1000 genetic variants cross‐sectionally associated with blood pressure variation and prevalent hypertension. These discoveries might aid the early identification of subpopulations at risk of developing hypertension or provide targets for drug development, amongst other applications. The aim of the present study was to analyze the association of blood pressure‐associated variants with long‐term changes (10 years) in blood pressure and also to assess their ability to predict hypertension incidence compared with traditional risk variables in a Swedish population.

    Methods and Results: We constructed 6 genetic risk scores (GRSs) by summing the dosage of the effect allele at each locus of genetic variants previously associated with blood pressure traits (systolic blood pressure GRS (GRSSBP): 554 variants; diastolic blood pressure GRS (GRSDBP): 481 variants; mean arterial pressure GRS (GRSMAP): 20 variants; pulse pressure GRS (GRSPP): 478 variants; hypertension GRS (GRSHTN): 22 variants; combined GRS (GRScomb): 1152 variants). Each GRS was longitudinally associated with its corresponding blood pressure trait, with estimated effects per GRS SD unit of 0.50 to 1.21 mm Hg for quantitative traits and odds ratios (ORs) of 1.10 to 1.35 for hypertension incidence traits. The GRScomb was also significantly associated with hypertension incidence defined according to European guidelines (OR, 1.22 per SD; 95% CI, 1.10‒1.35) but not US guidelines (OR, 1.11 per SD; 95% CI, 0.99‒1.25) while controlling for traditional risk factors. The addition of GRScomb to a model containing traditional risk factors only marginally improved discrimination (Δarea under the ROC curve = 0.001–0.002).

    Conclusions: GRSs based on discovered blood pressure‐associated variants are associated with long‐term changes in blood pressure traits and hypertension incidence, but the inclusion of genetic factors in a model composed of conventional hypertension risk factors did not yield a material increase in predictive ability.

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  • 23.
    Rankin, Gregory D.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Kabéle, Mikael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Brown, Rachael
    School of Medicine Western Sydney University Sydney NSW Australia.
    Macefield, Vaughan G.
    Human Autonomic Neurophysiology Laboratory School of Medicine Baker Heart and Diabetes Institute Melbourne Vic. Australia; Department of Physiology School of Biomedical Sciences The University of Melbourne Melbourne Vic. Australia.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bosson, Jenny A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Acute Exposure to Diesel Exhaust Increases Muscle Sympathetic Nerve Activity in Humans2021In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 10, no 10, article id e018448Article in journal (Refereed)
    Abstract [en]

    Background: Diesel exhaust (DE) emissions are a major contributor to ambient air pollution and are strongly associated with cardiovascular morbidity and mortality. Exposure to traffic-related particulate matter is linked with acute adverse cardiovascular events; however, the mechanisms are not fully understood. We examined the role of the autonomic nervous system during exposure to DE that has previously only been indirectly investigated.

    Methods and Results: Using microneurography, we measured muscle sympathetic nerve activity (MSNA) directly in the peroneal nerve of 16 healthy individuals. MSNA, heart rate, and respiration were recorded while subjects rested breathing filtered air, filtered air with an exposure mask, and standardized diluted DE (300 µg/m3) through the exposure mask. Heart rate variability was assessed from an ECG. DE inhalation rapidly causes an increase in number of MSNA bursts as well as the size of bursts within 10 minutes, peaking by 30 minutes (P<0.001), compared with baseline filtered air with an exposure mask. No significant changes occurred in heart rate variability indices during DE exposure; however, MSNA frequency correlated negatively with total power (r2=0.294, P=0.03) and low frequency (r2=0.258, P=0.045). Heart rate correlated positively with MSNA frequency (r2=0.268, P=0.04) and the change in percentage of larger bursts (burst amplitude, height >50% of the maximum burst) from filtered air with an exposure mask (r2=0.368, P=0.013).

    Conclusions: Our study provides direct evidence for the rapid modulation of the autonomic nervous system after exposure to DE, with an increase in MSNA. The quick increase in sympathetic outflow may explain the strong epidemiological data associating traffic-related particulate matter to acute adverse cardiovascular events such as myocardial infarction.

    Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02892279.

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  • 24.
    Rietz, Helene
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Franklin, Karl A.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Sahlin-Ingridsson, Carin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Marklund, Marie E.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Nocturnal Blood Pressure Is Reduced by a Mandibular Advancement Device for Sleep Apnea in Women: Findings From Secondary Analyses of a Randomized Trial2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 13, article id e008642Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Obstructive sleep apnea is associated with high blood pressure. The magnitude of blood pressure effects from sleep apnea treatment is unclear. We aimed to determine the effect of mandibular advancement device therapy on ambulatory nighttime and daytime blood pressure in women and men with daytime sleepiness and snoring or mild to moderate sleep apnea (apnea-hypopnea index, <30).

    METHODS AND RESULTS: In this 4-month, double-blind, randomized controlled trial comprising 96 untreated patients, 27 women and 58 men, aged 31 to 70 years, completed the study. The active group received individually made adjustable mandibular advancement devices, and the control group was given individually made sham devices, to be used during sleep. Polysomnographic sleep recordings and ambulatory 24-hour blood pressure measurements were performed at baseline and at follow-up. In women with mandibular advancement devices, the mean nighttime systolic blood pressure was 10.8 mm Hg (95% confidence interval, 4.0-17.7 mm Hg; P=0.004) lower than in the women in the sham group, adjusted for baseline blood pressure, age, body mass index, and the apnea-hypopnea index. The mean nighttime adjusted diastolic blood pressure was 6.6 mm Hg (95% confidence interval, 2.7-10.4 mm Hg; P=0.002) lower in the mandibular advancement device group. In men, there were no significant differences in blood pressure at night or during the daytime between the intervention groups.

    CONCLUSIONS: A mandibular advancement device for obstructive sleep apnea reduces nocturnal blood pressure in women.

    CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00477009.

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  • 25.
    Schophuus Jensen, Annette
    et al.
    Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
    Højsgaard Jørgensen, Troels
    Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
    Christersson, Christina
    Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.
    Nagy, Edit
    Department of Medicine, Heart and Vascular Theme, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Sinisalo, Juha
    Heart and Lung Center, Helsinki University Central Hospital, Helsinki, Finland; Helsinki University, Helsinki, Finland.
    Furenäs, Eva
    Department of Cardiology, Sahlgrenska Academy, University of Göteborg, Gothenburg, Sweden.
    Gjesdal, Ola
    Department of Cardiology, Rikshospitalet, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Norway.
    Eriksson, Peter
    Department of Cardiology, Sahlgrenska Academy, University of Göteborg, Gothenburg, Sweden.
    Vejlstrup, Niels
    Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Hlebowicz, Joanna
    Department of Cardiology, Lund University Hospital, Lund, Sweden.
    Greve, Gottfried
    Department of Cardiology, Haukeland University Hospital, Bergen, Norway.
    Dellborg, Mikael
    Department of Cardiology, Sahlgrenska Academy, University of Göteborg, Gothenburg, Sweden.
    Skulstad, Helge
    Department of Cardiology, Rikshospitalet, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Norway.
    Kvidal, Per
    Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.
    Jokinen, Eero
    Heart and Lung Center, Helsinki University Central Hospital, Helsinki, Finland; Helsinki University, Helsinki, Finland.
    Sairanen, Heikki
    Heart and Lung Center, Helsinki University Central Hospital, Helsinki, Finland; Helsinki University, Helsinki, Finland.
    Thilén, Ulf
    Department of Cardiology, Lund University Hospital, Lund, Sweden.
    Søndergaard, Lars
    Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
    Cause-Specific Mortality in Patients During Long-Term Follow-Up After Atrial Switch for Transposition of the Great Arteries2022In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 11, no 14, article id e023921Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Little is known about the cause of death (CoD) in patients with transposition of the great arteries palliated with a Mustard or Senning procedure. The aim was to describe the CoD for patients with the Mustard and Senning procedure during short-(<10 years), mid-(10–20 years), and long-term (>20 years) follow-up after the operation.

    METHODS AND RESULTS: This is a retrospective, descriptive multicenter cohort study including all Nordic patients (Denmark, Finland, Norway, and Sweden) who underwent a Mustard or Senning procedure between 1967 and 2003. Patients who died within 30 days after the index operation were excluded. Among 968 patients with Mustard/Senning palliated transposition of the great arteries, 814 patients were eligible for the study, with a mean follow-up of 33.6 years. The estimated risk of all-cause mortality reached 36.0% after 43 years of follow-up, and the risk of death was highest among male patients as compared with female patients (P=0.004). The most common CoD was sudden cardiac death (SCD), followed by heart failure/heart transplantation accounting for 29% and 27%, respectively. During short-, mid-, and long-term follow-up, there was a change in CoD with SCD accounting for 23.7%, 46.6%, and 19.0% (P=0.002) and heart failure/heart transplantation 18.6%, 22.4%, and 46.6% (P=0.0005), respectively.

    CONCLUSIONS: Among patients corrected with Mustard or Senning transposition of the great arteries, the most common CoD is SCD followed by heart failure/heart transplantation. The CoD changes as the patients age, with SCD as the most common cause in adolescence and heart failure as the dominant cause in adulthood. Furthermore, the risk of all-cause mortality, SCD, and death attributable to heart failure or heart transplantation was increased in men >10 years after the Mustard/Senning operation.

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  • 26. Schrage, Benedikt
    et al.
    Geelhoed, Bastiaan
    Niiranen, Teemu J.
    Gianfagna, Francesco
    Vishram-Nielsen, Julie K. K.
    Costanzo, Simona
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Ojeda, Francisco M.
    Vartiainen, Erkki
    Donati, Maria Benedetta
    Magnussen, Christina
    Di Castelnuovo, Augusto
    Camen, Stephan
    Kontto, Jukka
    Koenig, Wolfgang
    Blankenberg, Stefan
    de Gaetano, Giovanni
    Linneberg, Allan
    Jorgensen, Torben
    Zeller, Tanja
    Kuulasmaa, Kari
    Tunstall-Pedoe, Hugh
    Hughes, Maria
    Iacoviello, Licia
    Salomaa, Veikko
    Schnabel, Renate B.
    Comparison of Cardiovascular Risk Factors in European Population Cohorts for Predicting Atrial Fibrillation and Heart Failure, Their Subsequent Onset, and Death2020In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 9, no 9, article id e015218Article in journal (Refereed)
    Abstract [en]

    Background: Differences in risk factors for atrial fibrillation (AF) and heart failure (HF) are incompletely understood. Aim of this study was to understand whether risk factors and biomarkers show different associations with incident AF and HF and to investigate predictors of subsequent onset and mortality.

    Methods and Results: In N=58 693 individuals free of AF/HF from 5 population-based European cohorts, Cox regressions were used to find predictors for AF, HF, subsequent onset, and mortality. Differences between associations were estimated using bootstrapping. Median follow-up time was 13.8 years, with a mortality of 15.7%. AF and HF occurred in 5.0% and 5.4% of the participants, respectively, with 1.8% showing subsequent onset. Age, male sex, myocardial infarction, body mass index, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) showed similar associations with both diseases. Antihypertensive medication and smoking were stronger predictors of HF than AF. Cholesterol, diabetes mellitus, and hsCRP (high-sensitivity C-reactive protein) were associated with HF, but not with AF. No variable was exclusively associated with AF. Population-attributable risks were higher for HF (75.6%) than for AF (30.9%). Age, male sex, body mass index, diabetes mellitus, and NT-proBNP were associated with subsequent onset, which was associated with the highest all-cause mortality risk.

    Conclusions: Common risk factors and biomarkers showed different associations with AF and HF, and explained a higher proportion of HF than AF risk. As the subsequent onset of both diseases was strongly associated with mortality, prevention needs to be rigorously addressed and remains challenging, as conventional risk factors explained o:nly 31% of AF risk.

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  • 27.
    Shimanda, Panduleni Penipawa
    et al.
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Shumba, Tonderai W
    Department of Occupational Therapy and Physiotherapy University of Namibia Windhoek Namibia.
    Brunström, Mattias
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Iipinge, Scholastika N
    Clara Barton School of Nursing, Welwitchia Health Training Centre Windhoek Namibia.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lindholm, Lars
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Norström, Fredrik
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Preventive interventions to reduce the burden of rheumatic heart disease in populations at risk: a systematic review2024In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, E-ISSN 2047-9980, Vol. 13, no 5, article id e032442Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Rheumatic heart disease (RHD) is a devastating yet preventable condition that disproportionately affects low-middle-income countries and indigenous populations in some high-income countries. Various preventive interventions have been implemented across the globe, but evidence for the effectiveness of these measures in reducing the incidence or prevalence of acute rheumatic fever and RHD is scattered. This systematic review aims to assess the effectiveness of preventive interventions and identify the strategies used to reduce the burden of RHD.

    METHODS AND RESULTS: A comprehensive search was conducted to identify relevant studies on RHD prevention interventions including interventions for primordial, primary, and secondary prevention. Effectiveness measures for the interventions were gathered when available. The findings indicate that school-based primary prevention services targeting the early detection and treatment of Group A Streptococcus pharyngitis infection with penicillin have the potential to reduce the incidence of Group A Streptococcus pharyngitis and acute rheumatic fever. Community-based programs using various prevention strategies also reduced the burden of RHD. However, there is limited evidence from low-middle-income countries and a lack of rigorous evaluations reporting the true impact of the interventions. Narrative synthesis was performed, and the methodological quality appraisal was done using the Joanna Briggs Institute critical appraisal tools.

    CONCLUSIONS: This systematic review underscores the importance of various preventive interventions in reducing the incidence and burden of Group A Streptococcus pharyngitis, acute rheumatic fever, and RHD. Rigorous evaluations and comprehensive analyses of interventions are necessary for guiding effective strategies and informing public health policies to prevent and reduce the burden of these diseases in diverse populations.

    REGISTRATION: URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42020170503.

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  • 28. Steur, Marinka
    et al.
    Johnson, Laura
    Sharp, Stephen J
    Imamura, Fumiaki
    Sluijs, Ivonne
    Key, Timothy J
    Wood, Angela
    Chowdhury, Rajiv
    Guevara, Marcela
    Jakobsen, Marianne U
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Koulman, Albert
    Overvad, Kim
    Sánchez, Maria-José
    van der Schouw, Yvonne T
    Trichopoulou, Antonia
    Weiderpass, Elisabete
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Zheng, Ju-Sheng
    Boeing, Heiner
    Boer, Jolanda M A
    Boutron-Ruault, Marie-Christine
    Ericson, Ulrika
    Heath, Alicia K
    Huybrechts, Inge
    Imaz, Liher
    Kaaks, Rudolf
    Krogh, Vittorio
    Kühn, Tilman
    Kyrø, Cecilie
    Masala, Giovanna
    Melander, Olle
    Moreno-Iribas, Conchi
    Panico, Salvatore
    Quirós, José R
    Rodríguez-Barranco, Miguel
    Sacerdote, Carlotta
    Santiuste, Carmen
    Skeie, Guri
    Tjønneland, Anne
    Tumino, Rosario
    Verschuren, W M Monique
    Zamora-Ros, Raul
    Dahm, Christina C
    Perez-Cornago, Aurora
    Schulze, Matthias B
    Tong, Tammy Y N
    Riboli, Elio
    Wareham, Nicholas J
    Danesh, John
    Butterworth, Adam S
    Forouhi, Nita G
    Dietary Fatty Acids, Macronutrient Substitutions, Food Sources and Incidence of Coronary Heart Disease: Findings From the EPIC-CVD Case-Cohort Study Across Nine European Countries2021In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 10, no 23, article id e019814Article in journal (Refereed)
    Abstract [en]

    Background: There is controversy about associations between total dietary fatty acids, their classes (saturated fatty acids [SFAs], monounsaturated fatty acids, and polyunsaturated fatty acids), and risk of coronary heart disease (CHD). Specifically, the relevance of food sources of SFAs to CHD associations is uncertain.

    Methods and Results: We conducted a case-cohort study involving 10 529 incident CHD cases and a random subcohort of 16 730 adults selected from a cohort of 385 747 participants in 9 countries of the EPIC (European Prospective Investigation into Cancer and Nutrition) study. We estimated multivariable adjusted country-specific hazard ratios (HRs) and 95% CIs per 5% of energy intake from dietary fatty acids, with and without isocaloric macronutrient substitutions, using Prentice-weighted Cox regression models and pooled results using random-effects meta-analysis. We found no evidence for associations of the consumption of total or fatty acid classes with CHD, regardless of macronutrient substitutions. In analyses considering food sources, CHD incidence was lower per 1% higher energy intake of SFAs from yogurt (HR, 0.93 [95% CI, 0.88-0.99]), cheese (HR, 0.98 [95% CI, 0.96-1.00]), and fish (HR, 0.87 [95% CI, 0.75-1.00]), but higher for SFAs from red meat (HR, 1.07 [95% CI, 1.02-1.12]) and butter (HR, 1.02 [95% CI, 1.00-1.04]).

    Conclusions: This observational study found no strong associations of total fatty acids, SFAs, monounsaturated fatty acids, and polyunsaturated fatty acids, with incident CHD. By contrast, we found associations of SFAs with CHD in opposite directions dependent on the food source. These findings should be further confirmed, but support public health recommendations to consider food sources alongside the macronutrients they contain, and suggest the importance of the overall food matrix.

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  • 29.
    Tschiderer, Lena
    et al.
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands; Institute of Health Economics, Medical University of Innsbruck, Innsbruck, Austria.
    Peters, Sanne A. E.
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands; The George Institute for Global Health, School of Public Health, Imperial College London, London, United Kingdom; The George Institute for Global Health, University of New South Wales, NSW, Sydney, Australia.
    van der Schouw, Yvonne T.
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
    van Westing, Anniek C.
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands; Division of Human Nutrition and Health, Wageningen University, Wageningen, Netherlands.
    Tong, Tammy Y. N.
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Willeit, Peter
    Institute of Health Economics, Medical University of Innsbruck, Innsbruck, Austria; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
    Seekircher, Lisa
    Institute of Health Economics, Medical University of Innsbruck, Innsbruck, Austria.
    Moreno-Iribas, Conchi
    Instituto de Salud Pública y Laboral de Navarra, Pamplona, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
    Huerta, José María
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Epidemiology, Murcia Regional Health Council-IMIB, Murcia, Spain.
    Crous-Bou, Marta
    Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO)– Bellvitge Biomedical Research Institute, (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain; Department of Epidemiology, Harvard T.H. Chan School of Public Health, MA, Boston, United States.
    Söderholm, Martin
    Department of Neurology, Skåne University Hospital, Malmö, Lund and Malmö, Sweden; Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden.
    Schulze, Matthias B.
    Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
    Johansson, Cecilia
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Själander, Sara
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Heath, Alicia K.
    SwedenDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Macciotta, Alessandra
    Centre for Biostatistics, Epidemiology, and Public Health (C-BEPH), Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
    Dahm, Christina C.
    Department of Public Health, Aarhus University, Aarhus, Denmark.
    Ibsen, Daniel B.
    Department of Public Health, Aarhus University, Aarhus, Denmark; Steno Diabetes Center Aarhus, Aarhus, Denmark; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom; Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark.
    Pala, Valeria
    Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
    Mellemkjær, Lene
    Danish Cancer Society Research Center, Copenhagen, Denmark.
    Burgess, Stephen
    Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; Heart and Lung Research Institute, University of Cambridge, Cambridge, United Kingdom; MRC Biostatistics Unit, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom.
    Wood, Angela
    Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
    Kaaks, Rudolf
    Division of Cancer Epidemiology, German Cancer Research Center, DKFZ, Heidelberg, Germany.
    Katzke, Verena
    Division of Cancer Epidemiology, German Cancer Research Center, DKFZ, Heidelberg, Germany.
    Amiano, Pilar
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Ministry of Health of the Basque Government, Sub Directorate for Public Health and Addictions of Gipuzkoa, San Sebastian, Spain; Biodonostia Health Research Institute, Epidemiology of Chronic and Communicable Diseases Group, San Sebastian, Spain.
    Rodriguez-Barranco, Miguel
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Escuela Andaluza de Salud Pública (EASP), Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain.
    Engström, Gunnar
    Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden.
    Weiderpass, Elisabete
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Tjønneland, Anne
    Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Public Health, Section of Environmental Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Halkjær, Jytte
    Danish Cancer Society Research Center, Copenhagen, Denmark.
    Panico, Salvatore
    School of Medicine, Federico II University, Naples, Italy.
    Danesh, John
    BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; National Institute for Health and Care Research Cambridge Biomedical Research Centre, Cambridge University Hospitals, Cambridge, United Kingdom; The National Institute for Health and Care Research Blood and Transplant Unit (NIHR BTRU) in Donor Health and Genomics, University of Cambridge, Cambridge, United Kingdom; Human Genetics, Wellcome Sanger Institute, Saffron Walden, United Kingdom; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, United Kingdom; British Heart Foundation Centre of Research Excellence, Division of Cardiovascular Medicine, Addenbrooke’s Hospital, Cambridge, United Kingdom.
    Butterworth, Adam
    Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; Heart and Lung Research Institute, University of Cambridge, Cambridge, United Kingdom; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, United Kingdom; NIHR Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, United Kingdom; BHF Centre of Research Excellence, School of Clinical Medicine, Addenbrooke’s Hospital, Cambridge, United Kingdom.
    Onland-Moret, N. Charlotte
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
    Age at menopause and the risk of stroke: observational and mendelian randomization analysis in 204 244 postmenopausal women2023In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 12, no 18, article id e030280Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Observational studies have shown that women with an early menopause are at higher risk of stroke compared with women with a later menopause. However, associations with stroke subtypes are inconsistent, and the causality is unclear.

    METHODS AND RESULTS: We analyzed data of the UK Biobank and EPIC-CVD (European Prospective Investigation Into Cancer and Nutrition-Cardiovascular Diseases) study. A total of 204 244 postmenopausal women without a history of stroke at baseline were included (7883 from EPIC-CVD [5292 from the subcohort], 196 361 from the UK Biobank). Pooled mean baseline age was 58.9 years (SD, 5.8), and pooled mean age at menopause was 47.8 years (SD, 6.2). Over a median follow-up of 12.6 years (interquartile range, 11.8–13.3), 6770 women experienced a stroke (5155 ischemic strokes, 1615 hemorrhagic strokes, 976 intracerebral hemorrhages, and 639 subarachnoid hemorrhages). In multivariable adjusted observational Cox regression analyses, the pooled hazard ratios per 5 years younger age at menopause were 1.09 (95% CI, 1.07–1.12) for stroke, 1.09 (95% CI, 1.06–1.13) for ischemic stroke, 1.10 (95% CI, 1.04–1.16) for hemorrhagic stroke, 1.14 (95% CI, 1.08–1.20) for intracerebral hemorrhage, and 1.00 (95% CI, 0.84–1.20) for subarachnoid hemorrhage. When using 2-sample Mendelian randomization analysis, we found no statistically significant association between genetically proxied age at menopause and risk of any type of stroke.

    CONCLUSIONS: In our study, earlier age at menopause was related to a higher risk of stroke. We found no statistically significant association between genetically proxied age at menopause and risk of stroke, suggesting no causal relationship.

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  • 30.
    Winbo, Annika
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Department of Physiology, University of Auckland, Auckland, New Zealand.
    Diamant, Ulla-Britt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Persson, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Jensen, Steen M.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Rydberg, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    To Modify or Not to Modify: Allele-Specific Effects of 3’UTR-KCNQ1 Single Nucleotide Polymorphisms on Clinical Phenotype in a Long QT 1 Founder Population Segregating a Dominant-Negative Mutation2022In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 11, no 18, article id e025981Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There are conflicting reports with regard to the allele-specific gene suppression effects of single nucleotide polymorphisms (SNPs) in the 3’untranslated region (3’UTR) of the KCNQ1 gene in long QT syndrome type 1 (LQT1) populations. Here we assess the allele-specific effects of 3 previously published 3’UTR-KCNQ1’s SNPs in a LQT1 founder population segregating a dominant-negative mutation.

    METHODS AND RESULTS: Bidirectional sequencing of the KCNQ1’s 3’UTR was performed in the p.Y111C founder population (n=232, 147 genotype positive), with a minor allele frequency of 0.1 for SNP1 (rs2519184) and 0.6 for linked SNP2 (rs8234) and SNP3 (rs107980). Allelic phase was assessed in trios aided by haplotype data, revealing a high prevalence of derived SNP2/3 in cis with p.Y111C (89%). Allele-specific association analyses, corrected using a relatedness matrix, were performed between 3’UTR-KCNQ1 SNP genotypes and clinical phenotypes. SNP1 in trans was associated with a significantly higher proportion of symptomatic phenotype compared with no derived SNP1 allele in trans (58% versus 32%, corrected P=0.027). SNP2/3 in cis was associated with a significantly lower proportion of symptomatic phenotype compared with no derived SNP2/3 allele in cis (32% versus 69%, corrected P=0.010).

    CONCLUSIONS: Allele-specific modifying effects on symptomatic phenotype of 3’UTR-KCNQ1 SNPs rs2519184, rs8234, and rs107980 were seen in a LQT1 founder population segregating a dominant-negative mutation. The high prevalence of sup-pressive 3’UTR-KCNQ1 SNPs segregating with the founder mutation could contribute to the previously documented low incidence of cardiac events in heterozygous carriers of the p.Y111C KCNQ1 mutation.

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  • 31. Öhman, Annika
    et al.
    El-Segaier, Milad
    Bergman, Gunnar
    Hanséus, Katarina
    Malm, Torsten
    Nilsson, Boris
    Pivodic, Aldina
    Rydberg, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Sonesson, Sven-Erik
    Mellander, Mats
    Changing Epidemiology of Hypoplastic Left Heart Syndrome: Results of a National Swedish Cohort Study2019In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 8, no 2, article id e010893Article in journal (Refereed)
    Abstract [en]

    Background Norwood surgery provides a palliative surgical option for hypoplastic left heart syndrome and has been available in Sweden since 1993. The practice of prenatal ultrasound screening was gradually implemented in the same era, resulting in an increased prenatal detection rate. Our primary aims were to study changes in the incidence of live births, prenatal detection rate, and the termination of pregnancies over time. The secondary aims were to study the proportion of live-borns undergoing surgery and to identify factors that influenced whether surgery was or was not performed. Methods and Results Neonates with hypoplastic left heart syndrome with aortic atresia born 1990-2010 were identified through national databases, surgical files, and medical records. The fetal incidence was estimated from the period when prenatal screening was rudimentary. The study period was divided into the presurgical, early surgical, and late surgical periods. The incidence was calculated as the overall yearly incidence for each time period and sex separately. Factors influencing whether surgery was performed were analyzed using Cox-logistic regression. The incidence at live birth decreased from 15.4 to 8.4 per 100 000. The prenatal detection rate increased from 27% to 63%, and terminations increased from 19% to 56%. The odds of having surgery was higher in the late period and higher in the group with prenatal diagnosis. Conclusions We observed a decrease in incidence of live-borns with hypoplastic left heart syndrome aortic atresia. There was in increase in prenatal detection rate and an increase in termination of pregnancy. The proportion of live-borns who underwent surgery increased between time periods.

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