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  • 1.
    Brunstrom, Mattias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Carlberg, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Lindholm, Lars H.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Perspective from Sweden on the global impact of the 2017 american college of cardiology/american heart association hypertension guidelines: a "sprint" beyond evidence in the United States2018Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 137, nr 9, s. 886-888Artikkel i tidsskrift (Annet vitenskapelig)
  • 2.
    Connolly-Andersen, Anne-Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Hammargren, Edvin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Whitaker, Heather
    Eliasson, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Holmgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Klingstrom, Jonas
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Increased Risk of Acute Myocardial Infarction and Stroke During Hemorrhagic Fever With Renal Syndrome A Self-Controlled Case Series Study2014Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 129, nr 12, s. 1295-1302Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background We recently observed that cardiovascular causes of death are common in patients with hemorrhagic fever with renal syndrome (HFRS), which is caused by hantaviruses. However, it is not known whether HFRS is a risk factor for the acute cardiovascular events of acute myocardial infarction (AMI) and stroke. Methods and Results Personal identification numbers from the Swedish HFRS patient database (1997-2012; n=6643) were cross-linked with the National Patient Register from 1987 to 2011. Using the self-controlled case series method, we calculated the incidence rate ratio of AMI/stroke in the 21 days after HFRS against 2 different control periods either excluding (analysis 1) or including (analysis 2) fatal AMI/stroke events. The incidence rate ratios for analyses 1 and 2 for all AMI events were 5.53 (95% confidence interval [CI], 2.6-11.8) and 6.02 (95% CI, 2.95-12.3) and for first AMI events were 3.53 (95% CI, 1.25-9.96) and 4.64 (95% CI, 1.83-11.77). The incidence rate ratios for analyses 1 and 2 for all stroke events were 12.93 (95% CI, 5.62-29.74) and 15.16 (95% CI, 7.21-31.87) and for first stroke events were 14.54 (95% CI, 5.87-36.04) and 17.09 (95% CI, 7.49-38.96). The majority of stroke events occurred in the first week after HFRS. Seasonal effects were not observed, and apart from 1 study, neither sex nor age interacted with the associations observed in this study. Conclusions There is a significantly increased risk for AMI and stroke in the immediate time period after HFRS. Therefore, HFRS patients should be carefully monitored during the acute phase of disease to ensure early recognition of symptoms of impending AMI or stroke.

  • 3. Di Castelnuovo, Augusto Filippo
    et al.
    Costanzo, Simona
    Bonaccio, Marialaura
    McElduff, Patrick
    Linneberg, Allan
    Salomaa, Veikko
    Mannisto, Satu
    Moitry, Marie
    Ferrieres, Jean
    Dallongeville, Jean
    Thorand, Barbara
    Brenner, Hermann
    Ferrario, Marco
    Tamosiunas, Abdonas
    Njolstad, Inger
    Drygas, Wojciech
    Nikitin, Yuri
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Kee, Frank
    Zeller, Tanja
    Kuulasmaa, Kari
    Blankenberg, Stefan
    Donati, Maria Benedetta
    de Gaetano, Giovanni
    Iacoviello, Licia
    Association of Alcohol Intake with Cardiovascular and Total Mortality2019Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139Artikkel i tidsskrift (Annet vitenskapelig)
  • 4. Diller, Gerhard-Paul
    et al.
    Dimopoulos, Konstantinos
    Okonko, Darlington
    Li, Wei
    Babu-Narayan, Sonya V
    Broberg, Craig S
    Johansson, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Bouzas, Beatriz
    Mullen, Michael J
    Poole-Wilson, Philip A
    Francis, Darrel P
    Gatzoulis, Michael A
    Exercise intolerance in adult congenital heart disease: comparative severity, correlates, and prognostic implication.2005Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 112, nr 6, s. 828-35Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

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

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

  • 5. Greve, Anders M.
    et al.
    Boman, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Gohlke-Baerwolf, Christa
    Kesaniemi, Y. Antero
    Nienaber, Christoph
    Ray, Simon
    Egstrup, Kenneth
    Rossebo, Anne B.
    Devereux, Richard B.
    Kober, Lars
    Willenheimer, Ronnie
    Wachtell, Kristian
    Clinical implications of electrocardiographic left ventricular strain and hypertrophy in asymptomatic patients with aortic stenosis the simvastatin and ezetimibe in aortic stenosis study2012Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 125, nr 2, s. 346-353Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background-The prognostic impact of ECG left ventricular strain and left ventricular hypertrophy (LVH) in asymptomatic aortic stenosis is not well described.

    Methods and Results-Data were obtained in asymptomatic patients randomized to simvastatin/ezetimibe combination versus placebo in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Primary end point was the first of myocardial infarction, nonhemorrhagic stroke, heart failure, aortic valve replacement, or cardiovascular death. The predictive value of ECG left ventricular strain (defined as T-wave inversion in leads V(4) through V(6)) and LVH, assessed by Sokolow-Lyon voltage criteria (R(V5-6) +/- S(V1) >= 35 mV) and Cornell voltage-duration criteria {[RaVL + S(V3) + (6 mV in women)] x QRS duration >= 2440 mV.ms}, was evaluated by adjustment for other prognostic covariates. A total of 1533 patients were followed for 4.3 +/- 0.8 years (6592 patient-years of follow-up), and 627 cardiovascular events occurred. ECG strain was present in 340 patients (23.6%), with LVH by Sokolow-Lyon voltage in 260 (17.1%) and by Cornell voltage-duration product in 220 (14.6%). In multivariable analyses, ECG left ventricular strain was associated with 3.1-fold higher risk of in-study myocardial infarction (95% confidence interval, 1.4-6.8; P = 0.004). Similarly, ECG LVH by both criteria predicted, compared with no ECG LVH, 5.8-fold higher risk of heart failure (95% confidence interval, 2.0 -16.8), 2.0-fold higher risk of aortic valve replacement (95% confidence interval, 1.3-3.1; both P = 0.001), and 2.5-fold higher risk of a combined end point of myocardial infarction, heart failure, or cardiovascular death (95% confidence interval, 1.3-4.9; P = 0.008).

    Conclusions-ECG left ventricular strain and LVH were independently predictive of poor prognosis in patients with asymptomatic aortic stenosis.

  • 6. Hvidtfeldt, Ulla A
    et al.
    Tolstrup, Janne S
    Jakobsen, Marianne U
    Heitmann, Berit L
    Grønbaek, Morten
    O'Reilly, Eilis
    Bälter, Katarina
    Goldbourt, Uri
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Knekt, Paul
    Liu, Simin
    Pereira, Mark
    Pietinen, Pirjo
    Spiegelman, Donna
    Stevens, June
    Virtamo, Jarmo
    Willett, Walter C
    Rimm, Eric B
    Ascherio, Alberto
    Alcohol intake and risk of coronary heart disease in younger, middle-aged, and older adults2010Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 121, nr 14, s. 1589-1597Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Light to moderate alcohol consumption is associated with a reduced risk of coronary heart disease. This protective effect of alcohol, however, may be confined to middle-aged or older individuals. Coronary heart disease incidence is low in men <40 years of age and in women <50 years of age; for this reason, study cohorts rarely have the power to investigate the effects of alcohol on coronary heart disease risk in younger adults. This study examined whether the beneficial effect of alcohol on coronary heart disease depends on age. METHODS AND RESULTS: In this pooled analysis of 8 prospective studies from North America and Europe including 192,067 women and 74,919 men free of cardiovascular diseases, diabetes, and cancers at baseline, average daily alcohol intake was assessed at baseline with a food frequency or diet history questionnaire. An inverse association between alcohol and risk of coronary heart disease was observed in all age groups; hazard ratios among moderately drinking men (5.0 to 29.9 g/d) 39 to 50, 50 to 59, and >or=60 years of age were 0.58 (95% confidence interval [CI], 0.36 to 0.93), 0.72 (95% CI, 0.60 to 0.86), and 0.85 (95% CI, 0.75 to 0.97) compared with abstainers. However, the analyses indicated a smaller incidence rate difference between abstainers and moderate consumers in younger adults (incidence rate difference, 45 per 100,000; 90% CI, 8 to 84) than in middle-aged (incidence rate difference, 64 per 100,000; 90% CI, 24 to 102) and older (incidence rate difference, 89 per 100,000; 90% CI, 44 to 140) adults. Similar results were observed in women. CONCLUSIONS: Alcohol is also associated with a decreased risk of coronary heart disease in younger adults; however, the absolute risk was small compared with middle-aged and older adults.

  • 7. Jander, Nikolaus
    et al.
    Minners, Jan
    Holme, Ingar
    Gerdts, Eva
    Boman, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Brudi, Philippe
    Chambers, John B.
    Egstrup, Kenneth
    Kesaniemi, Y. Antero
    Malbecq, William
    Nienaber, Christoph A.
    Ray, Simon
    Rossebo, Anne
    Pedersen, Terje R.
    Skjaerpe, Terje
    Willenheimer, Ronnie
    Wachtell, Kristian
    Neumann, Franz-Josef
    Gohlke-Baerwolf, Christa
    Outcome of Patients With Low-Gradient "Severe" Aortic Stenosis and Preserved Ejection Fraction2011Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 123, nr 8, s. 887-895Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background-Retrospective studies have suggested that patients with a low transvalvular gradient in the presence of an aortic valve area <1.0 cm(2) and normal ejection fraction may represent a subgroup with an advanced stage of aortic valve disease, reduced stroke volume, and poor prognosis requiring early surgery. We therefore evaluated the outcome of patients with low-gradient "severe" stenosis (defined as aortic valve area < 1.0 cm(2) and mean gradient <= 40 mm Hg) in the prospective Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study.

    Methods and Results-Outcome in patients with low-gradient "severe" aortic stenosis was compared with outcome in patients with moderate stenosis (aortic valve area 1.0 to 1.5 cm(2); mean gradient 25 to 40 mm Hg). The primary end point of aortic valve events included death from cardiovascular causes, aortic valve replacement, and heart failure due to aortic stenosis. Secondary end points were major cardiovascular events and cardiovascular death. In 1525 asymptomatic patients (mean age, 67 +/- 10 years; ejection fraction, >= 55%), baseline echocardiography revealed low-gradient severe stenosis in 435 patients (29%) and moderate stenosis in 184 (12%). Left ventricular mass was lower in patients with low-gradient severe stenosis than in those with moderate stenosis (182 +/- 64 versus 212 +/- 68 g; P < 0.01). During 46 months of follow-up, aortic valve events occurred in 48.5% versus 44.6%, respectively (P=0.37; major cardiovascular events, 50.9% versus 48.5%, P=0.58; cardiovascular death, 7.8% versus 4.9%, P=0.19). Low-gradient severe stenosis patients with reduced stroke volume index (<= 35 mL/m(2); n=223) had aortic valve events comparable to those in patients with normal stroke volume index (46.2% versus 50.9%; P=0.53).

    Conclusions-Patients with low-gradient "severe" aortic stenosis and normal ejection fraction have an outcome similar to that in patients with moderate stenosis.

  • 8. Jander, Nikolaus
    et al.
    Minners, Jan
    Neumann, Franz-Josef
    Gohlke-Baerwolf, Christa
    Holme, Ingar
    Gerdts, Eva
    Boman, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Brudi, Philippe
    Chambers, John B.
    Egstrup, Kenneth
    Kesaniemi, Y. Antero
    Malbecq, William
    Nienaber, Christoph A.
    Ray, Simon
    Rossebo, Anne
    Pedersen, Terje R.
    Skjaerpe, Terje
    Willenheimer, Ronnie
    Wachtell, Kristian
    Response to Letters Regarding Article, "Outcome of Patients With Low-Gradient "Severe" Aortic Stenosis and Preserved Ejection Fraction"2011Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 124, nr 13, s. E362-E363Artikkel i tidsskrift (Fagfellevurdert)
  • 9. Jernberg, Tomas
    et al.
    Lindahl, Bertil
    Alfredsson, Joakim
    Berglund, Ellinor
    Bergström, Olle
    Engström, Anders
    Erlinge, David
    Herlitz, Johan
    Jumatate, Raluca
    Kellerth, Thomas
    Lauermann, Jörg
    Lindmark, Krister
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Lingman, Markus
    Ljung, Lina
    Nilsson, Carina
    Omerovic, Elmir
    Pernow, John
    Ravn-Fischer, Annica
    Sparv, David
    Yndigegn, Troels
    Östlund, Ollie
    James, Stefan K.
    Hofmann, Robin
    Long-Term Effects of Oxygen Therapy on Death or Hospitalization for Heart Failure in Patients With Suspected Acute Myocardial Infarction2018Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 138, nr 24, s. 2754-2762Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: In the DETO2X-AMI trial (Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction), we compared supplemental oxygen with ambient air in normoxemic patients presenting with suspected myocardial infarction and found no significant survival benefit at 1 year. However, important secondary end points were not yet available. We now report the prespecified secondary end points cardiovascular death and the composite of all-cause death and hospitalization for heart failure.

    Methods: In this pragmatic, registry-based randomized clinical trial, we used a nationwide quality registry for coronary care for trial procedures and evaluated end points through the Swedish population registry (mortality), the Swedish inpatient registry (heart failure), and cause of death registry (cardiovascular death). Patients with suspected acute myocardial infarction and oxygen saturation of ≥90% were randomly assigned to receive either supplemental oxygen at 6 L/min for 6 to 12 hours delivered by open face mask or ambient air.

    Results: A total of 6629 patients were enrolled. Acute heart failure treatment, left ventricular systolic function assessed by echocardiography, and infarct size measured by high-sensitive cardiac troponin T were similar in the 2 groups during the hospitalization period. All-cause death or hospitalization for heart failure within 1 year after randomization occurred in 8.0% of patients assigned to oxygen and in 7.9% of patients assigned to ambient air (hazard ratio, 0.99; 95% CI, 0.84–1.18; P=0.92). During long-term follow-up (median [range], 2.1 [1.0–3.7] years), the composite end point occurred in 11.2% of patients assigned to oxygen and in 10.8% of patients assigned to ambient air (hazard ratio, 1.02; 95% CI, 0.88–1.17; P=0.84), and cardiovascular death occurred in 5.2% of patients assigned to oxygen and in 4.8% assigned to ambient air (hazard ratio, 1.07; 95% CI, 0.87–1.33; P=0.52). The results were consistent across all predefined subgroups.

    Conclusions: Routine use of supplemental oxygen in normoxemic patients with suspected myocardial infarction was not found to reduce the composite of all-cause mortality and hospitalization for heart failure, or cardiovascular death within 1 year or during long-term follow-up.

    Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01787110.

  • 10. Key, Timothy J.
    et al.
    Appleby, Paul N.
    Bradbury, Kathryn E.
    Sweeting, Michael
    Wood, Angela
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Kühn, Tilman
    Steur, Marinka
    Weiderpass, Elisabete
    Wennberg, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Würtz, Anne Mette Lund
    Agudo, Antonio
    Andersson, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Arriola, Larraitz
    Boeing, Heiner
    Boer, Jolanda M. A.
    Bonnet, Fabrice
    Boutron-Ruault, Marie-Christine
    Cross, Amanda J.
    Ericson, Ulrika
    Fagherazzi, Guy
    Ferrari, Pietro
    Gunter, Marc
    Huerta, José María
    Katzke, Verena
    Khaw, Kay-Tee
    Krogh, Vittorio
    La Vecchia, Carlo
    Matullo, Giuseppe
    Moreno-Iribas, Conchi
    Naska, Androniki
    Nilsson, Lena Maria
    Umeå universitet, Arktiskt centrum vid Umeå universitet (Arcum).
    Olsen, Anja
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Molina-Portillo, Elena
    Quirós, J. Ramón
    Skeie, Guri
    Sluijs, Ivonne
    Sonestedt, Emily
    Stepien, Magdalena
    Tjønneland, Anne
    Trichopoulou, Antonia
    Tumino, Rosario
    Tzoulaki, Ioanna
    van der Schouw, Yvonne T.
    Verschuren, W. M. Monique
    Di Angelantonio, Emanuele
    Langenberg, Claudia
    Forouhi, Nita
    Wareham, Nick
    Butterworth, Adam
    Riboli, Elio
    Danesh, John
    Consumption of Meat, Fish, Dairy Products, Eggs and Risk of Ischemic Heart Disease: A Prospective Study of 7198 Incident Cases Among 409,885 Participants in the Pan-European EPIC Cohort2019Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139, nr 25, s. 2835-2845Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: There is uncertainty about the relevance of animal foods to the etiology of ischemic heart disease (IHD). We examined meat, fish, dairy products and eggs and risk for IHD in the pan-European EPIC cohort.

    METHODS: A prospective study of 409,885 men and women in nine European countries. Diet was assessed using validated questionnaires, calibrated using 24-hour recalls. Lipids and blood pressure were measured in a subsample. During 12.6 years mean follow up, 7198 participants had a myocardial infarction or died from IHD. The relationships of animal foods with risk were examined using Cox regression with adjustment for other animal foods and relevant covariates.

    RESULTS: The hazard ratio (HR) for IHD was 1.19 (95% CI 1.06-1.33) for a 100 g/d increment in intake of red and processed meat, and this remained significant after excluding the first 4 years of follow-up (HR 1.25 [1.09-1.42]). Risk was inversely associated with intakes of yogurt (HR 0.93 [0.89-0.98] per 100 g/d increment), cheese (HR 0.92 [0.86-0.98] per 30 g/d increment) and eggs (HR 0.93 [0.88-0.99] per 20 g/d increment); the associations with yogurt and eggs were attenuated and non-significant after excluding the first 4 years of follow-up. Risk was not significantly associated with intakes of poultry, fish or milk. In analyses modelling dietary substitutions, replacement of 100 kcal/d from red and processed meat with 100 kcal/d from fatty fish, yogurt, cheese or eggs was associated with approximately 20% lower risk of IHD. Consumption of red and processed meat was positively associated with serum non-HDL cholesterol concentration and systolic blood pressure, and consumption of cheese was inversely associated with serum non-HDL cholesterol.

    CONCLUSIONS: Risk for IHD was positively associated with consumption of red and processed meat, and inversely associated with consumption of yogurt, cheese and eggs, although the associations with yogurt and eggs may be influenced by reverse causation bias. It is not clear whether the associations with red and processed meat and cheese reflect causality, but they were consistent with the associations of these foods with plasma non-HDL cholesterol, and for red and processed meat with systolic blood pressure, which could mediate such effects.

    Fulltekst (pdf)
    fulltext
  • 11.
    Ljungberg, Johan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Janiec, Mikael
    Bergdahl, Ingvar
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Holmgren, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Johansson, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Näslund, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Siegbahn, Agneta
    Fall, Tove
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Proteomic Biomarkers for Incident Aortic Stenosis Requiring Valvular Replacement2018Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 138, nr 6Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 12. Lucking, Andrew J
    et al.
    Lundbäck, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Barath, Stefan L
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Mills, Nicholas L
    Sidhu, Manjit K
    Langrish, Jeremy P
    Boon, Nicholas A
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Badimon, Juan J
    Gerlofs-Nijland, Miriam E
    Cassee, Flemming R
    Boman, Christoffer
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik, Energiteknik och termisk processkemi.
    Donaldson, Kenneth
    Sandstrom, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Newby, David E
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Particle traps prevent adverse vascular and prothrombotic effects of diesel engine exhaust inhalation in men2011Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 123, nr 16, s. 1721-1728Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: In controlled human exposure studies, diesel engine exhaust inhalation impairs vascular function and enhances thrombus formation. The aim of the present study was to establish whether an exhaust particle trap could prevent these adverse cardiovascular effects in men.

    METHODS AND RESULTS: Nineteen healthy volunteers (mean age, 25±3 years) were exposed to filtered air and diesel exhaust in the presence or absence of a particle trap for 1 hour in a randomized, double-blind, 3-way crossover trial. Bilateral forearm blood flow and plasma fibrinolytic factors were assessed with venous occlusion plethysmography and blood sampling during intra-arterial infusion of acetylcholine, bradykinin, sodium nitroprusside, and verapamil. Ex vivo thrombus formation was determined with the use of the Badimon chamber. Compared with filtered air, diesel exhaust inhalation was associated with reduced vasodilatation and increased ex vivo thrombus formation under both low- and high-shear conditions. The particle trap markedly reduced diesel exhaust particulate number (from 150 000 to 300 000/cm(3) to 30 to 300/cm(3); P<0.001) and mass (320±10 to 7.2±2.0 μg/m(3); P<0.001), and was associated with increased vasodilatation, reduced thrombus formation, and an increase in tissue-type plasminogen activator release.

    CONCLUSIONS: Exhaust particle traps are a highly efficient method of reducing particle emissions from diesel engines. With a range of surrogate measures, the use of a particle trap prevents several adverse cardiovascular effects of exhaust inhalation in men. Given these beneficial effects on biomarkers of cardiovascular health, the widespread use of particle traps on diesel-powered vehicles may have substantial public health benefits and reduce the burden of cardiovascular disease.

  • 13. Magnussen, Christina
    et al.
    Niiranen, Teemu J.
    Ojeda, Francisco M.
    Gianfagna, Francesco
    Blankenberg, Stefan
    Njølstad, Inger
    Vartiainen, Erkki
    Sans, Susana
    Pasterkamp, Gerard
    Hughes, Maria
    Costanzo, Simona
    Donati, Maria Benedetta
    Jousilahti, Pekka
    Linneberg, Allan
    Palosaari, Tarja
    de Gaetano, Giovanni
    Bobak, Martin
    den Ruijter, Hester M.
    Mathiesen, Ellisiv
    Jørgensen, Torben
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Kuulasmaa, Kari
    Zeller, Tanja
    Iacoviello, Licia
    Salomaa, Veikko
    Schnabel, Renate B.
    Sex Differences and Similarities in Atrial Fibrillation Epidemiology, Risk Factors, and Mortality in Community Cohorts Results From the BiomarCaRE Consortium (Biomarker for Cardiovascular Risk Assessment in Europe)2017Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 136, nr 17, s. 1588-1597Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Atrial fibrillation (AF) is a common cardiac disease in aging populations with high comorbidity and mortality. Sex differences in AF epidemiology are insufficiently understood.

    Methods: In N=79 793 individuals without AF diagnosis at baseline (median age, 49.6 years; age range, 24.1–97.6 years; 51.7% women) from 4 community-based European studies (FINRISK, DanMONICA, Moli-sani Northern Sweden) of the BiomarCaRE consortium (Biomarker for Cardiovascular Risk Assessment in Europe), we examined AF incidence, its association with mortality, common risk factors, biomarkers, and prevalent cardiovascular disease, and their attributable risk by sex. Median follow-up time was 12.6 (to a maximum of 28.2) years.

    Results: Fewer AF cases were observed in women (N=1796; 4.4%), than in men (N=2465; 6.4%). Cardiovascular risk factor distribution and lipid profile at baseline were less beneficial in men than in women, and cardiovascular disease was more prevalent in men. Cumulative incidence increased markedly after the age of 50 years in men and after 60 years in women. The lifetime risk was similar (>30%) for both sexes. Subjects with incident AF had a 3.5-fold risk of death in comparison with those without AF. Multivariable-adjusted models showed sex differences for the association of body mass index and AF (hazard ratio per standard deviation increase, 1.18; 95% confidence interval [CI], 1.12–1.23 in women versus 1.31; 95% CI 1.25–1.38 in men; interaction P value of 0.001). Total cholesterol was inversely associated with incident AF with a greater risk reduction in women (hazard ratio per SD, 0.86; 95% CI, 0.81–0.90 versus 0.92; 95% CI, 0.88–0.97 in men; interaction P value of 0.023). No sex differences were seen for C-reactive protein and N-terminal pro B-type natriuretic peptide. The population-attributable risk of all risk factors combined was 41.9% in women and 46.0% in men. About 20% of the risk was observed for body mass index.

    Conclusions: Lifetime risk of AF was high, and AF was strongly associated with increased mortality both in women and men. Body mass index explained the largest proportion of AF risk. Observed sex differences in the association of body mass index and total cholesterol with AF need to be evaluated for underlying pathophysiology and relevance to sex-specific prevention strategies.

  • 14. Marklund, Matti
    et al.
    Wu, Jason H Y
    Imamura, Fumiaki
    Del Gobbo, Liana C
    Fretts, Amanda
    de Goede, Janette
    Shi, Peilin
    Tintle, Nathan
    Wennberg, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Aslibekyan, Stella
    Chen, Tzu-An
    de Oliveira Otto, Marcia C
    Hirakawa, Yoichiro
    Eriksen, Helle Højmark
    Kröger, Janine
    Laguzzi, Federica
    Lankinen, Maria
    Murphy, Rachel A
    Prem, Kiesha
    Samieri, Cécilia
    Virtanen, Jyrki
    Wood, Alexis C
    Wong, Kerry
    Yang, Wei-Sin
    Zhou, Xia
    Baylin, Ana
    Boer, Jolanda M A
    Brouwer, Ingeborg A
    Campos, Hannia
    Chaves, Paulo H M
    Chien, Kuo-Liong
    de Faire, Ulf
    Djoussé, Luc
    Eiriksdottir, Gudny
    El-Abbadi, Naglaa
    Forouhi, Nita G
    Gaziano, J Michael
    Geleijnse, Johanna M
    Gigante, Bruna
    Giles, Graham
    Guallar, Eliseo
    Gudnason, Vilmundur
    Harris, Tamara
    Harris, William S
    Helmer, Catherine
    Hellénius, Mai-Lis
    Hodge, Allison
    Hu, Frank B
    Jacques, Paul F
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Kalsbeek, Anya
    Khaw, Kay-Tee
    Koh, Woon-Puay
    Laakso, Markku
    Leander, Karin
    Lin, Hung-Ju
    Lind, Lars
    Luben, Robert
    Luo, Juhua
    McKnight, Barbara
    Mursu, Jaakko
    Ninomiya, Toshiharu
    Overvad, Kim
    Psaty, Bruce M
    Rimm, Eric
    Schulze, Matthias B
    Siscovick, David
    Skjelbo Nielsen, Michael
    Smith, Albert V
    Steffen, Brian T
    Steffen, Lyn
    Sun, Qi
    Sundström, Johan
    Tsai, Michael Y
    Tunstall-Pedoe, Hugh
    Uusitupa, Matti I J
    van Dam, Rob M
    Veenstra, Jenna
    Verschuren, W M Monique
    Wareham, Nicholas
    Willett, Walter
    Woodward, Mark
    Yuan, Jian-Min
    Micha, Renata
    Lemaitre, Rozenn N
    Mozaffarian, Dariush
    Risérus, Ulf
    Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality: An Individual-Level Pooled Analysis of 30 Cohort Studies2019Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139, nr 21, s. 2422-2436Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies.

    METHODS: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease (CHD), ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytical plan. Levels of LA and AA, measured as % of total fatty acids, were evaluated linearly according to their interquintile range (i.e., the range between the mid-point of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available).

    RESULTS: In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15,198 incident cardiovascular events occurred among 68,659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI: 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower CHD risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; comparing extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships.

    CONCLUSIONS: In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.

  • 15. Mills, Nicholas L
    et al.
    Robinson, Simon D
    Boon, Nicholas A
    Newby, David E
    Törnqvist, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Gonzalez, Manuel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Darnley, Kareen
    MacNee, William
    Donaldson, Ken
    Response to letter regarding article "Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis"2006Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 113, nr 24, artikkel-id e872Artikkel i tidsskrift (Annet vitenskapelig)
  • 16. Mills, NL
    et al.
    Törnqvist, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Robinson, SD
    Gonzalez, M
    Darnley, K
    MacNee, W
    Boon, NA
    Donaldson, K
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Newby, DE
    Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis.2005Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 112, nr 25, s. 3930-3936Artikkel i tidsskrift (Fagfellevurdert)
  • 17. Nielsen, Olav W.
    et al.
    Sajadieh, Ahmad
    Sabbah, Muhammad
    Greve, Anders M.
    Olsen, Michael H.
    Boman, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nienaber, Christoph A.
    Kesaniemi, Y. Antero
    Pedersen, Terje R.
    Willenheimer, Ronnie
    Wachtell, Kristian
    Assessing Optimal Blood Pressure in Patients With Asymptomatic Aortic Valve Stenosis The Simvastatin Ezetimibe in Aortic Stenosis Study (SEAS)2016Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 134, nr 6, s. 455-468Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Evidence for treating hypertension in patients with asymptomatic aortic valve stenosis is scarce. We used data from the SEAS trial (Simvastatin Ezetimibe in Aortic Stenosis) to assess what blood pressure (BP) would be optimal. METHODS: A total of 1767 patients with asymptomatic aortic stenosis and no manifest atherosclerotic disease were analyzed. Outcomes were all-cause mortality, cardiovascular death, heart failure, stroke, myocardial infarction, and aortic valve replacement. BP was analyzed in Cox models as the cumulative average of serially measured BP and a time-varying covariate. RESULTS: The incidence of all-cause mortality was highest for average follow-up systolic BP >= 160 mm Hg (4.3 per 100 person-years; 95% confidence interval [CI], 3.1-6.0) and lowest for average systolic BP of 120 to 139 mm Hg (2.0 per 100 person-years; 95% CI, 1.6-2.6). In multivariable analysis, all-cause mortality was associated with average systolic BP < 120 mm Hg (hazard ratio [HR], 3.4; 95% CI, 1.9-6.1), diastolic BP >= 90 mm Hg (HR, 1.8; 95% CI, 1.1-2.9), and pulse pressure < 50 mm Hg (HR, 1.8; 95% CI, 1.1-2.9), with systolic BP of 120 to 139 mm Hg, diastolic BP of 70 to 79 mm Hg, and pulse pressure of 60 to 69 mm Hg taken as reference. Low systolic and diastolic BPs increased risk in patients with moderate aortic stenosis. With a time-varying systolic BP from 130 to 139 mm Hg used as reference, mortality was increased for systolic BP >= 160 mm Hg (HR, 1.7; P=0.033) and BP of 120 to 129 mm Hg (HR, 1.6; P= 0.039). CONCLUSIONS: Optimal BP seems to be systolic BP of 130 to 139 mm Hg and diastolic BP of 70 to 90 mm Hg in these patients with asymptomatic aortic stenosis and no manifest atherosclerotic disease or diabetes mellitus.

  • 18.
    Okin, Peter M
    et al.
    Weill Cornell Med College, New York, NY.
    Kjeldsen, Sverre
    Univ of Oslo, Ullevål Hosp, Oslo, Norway.
    Lindholm, Lars H
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Dahlöf, Björn
    Sahlgrenska Univ Hosp/Östra, Göteborg, Sweden.
    Devereux, Richard B
    Weill Cornell Med College, New York, NY.
    Competing effects of hypokalemia and hydrochlororothiazide treatment  on regression of Cornell product left ventricular hypertrophy  in hypertensive patients: implications for the development of potassium-sparing diuretics2009Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 120, nr Suppl. 18, s. s1015-s1015Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Background: Hydrochlorothiazide (HCTZ) treatment is associated with blood pressure reduction and regression of left ventricular hypertrophy (LVH). HCTZ is also associated with hypokalemia (hypoK), which increases blood pressure and is associated with a greater likelihood and severity of electrocardiographic (ECG) LVH. However, the competing effects of HCTZ use and concomitant hypoK on LVH regression have not been examined.

    Methods: Baseline and yearly Cornell product (CP) ECG LVH levels were examined in relation to hypoK (serum K 3.90, the lowest quartile) and HCTZ use in 7816 patients in the LIFE study with baseline and year-1 K levels. Patients were randomized to losartan vs atenolol-based treatment and additional HCTZ as needed.

    Results: Patients on HCTZ had lower serum K levels at year 1 (4.05 ± 0.38 vs 4.24 ± 0.38), year 2 (4.04 ± 0.38 vs 4.25 ± 0.38), year 3 (4.04 ± 0.39 vs 4.27 ± 0.39) and year 4 (4.05 ± 0.41 vs 4.26 ± 0.38) of the study (all p < 0.001). In 2-way analysis of covariance adjusting for age, sex, race, prior and randomized treatment, yearly body mass index, serum glucose and creatinine, and for baseline and change in diastolic and systolic pressure, hypoK was associated with less mean reduction of CP LVH whereas HCTZ use was associated with greater regression of CP LVH between baseline and years 1 to 4. Multivariate logistic regression analyses with the same covariates revealed that hypoK was associated with a statistically significant 15 to 19% lower likelihood of median (236 mm·ms) reduction in CP LVH while HCTZ use was associated with an 18 to 33% greater likelihood of CP LVH regression of 236 mm·ms between baseline and years 1 to 4.

    Conclusions: HCTZ therapy is independently associated with a greater likelihood and magnitude of LVH regression whereas concomitant hypoK is associated with a competing lower likelihood and magnitude of LVH regression during antihypertensive therapy. These findings suggest that hypoK may blunt regression of LVH during treatment.

  • 19. Solomon, Scott D.
    et al.
    Adams, David
    Kristen, Arnt
    Grogan, Martha
    Gonzalez-Duarte, Alejandra
    Maurer, Mathew S.
    Merlini, Giampaolo
    Damy, Thibaud
    Slama, Michel S.
    Brannagan, Thomas H., III
    Dispenzieri, Angela
    Berk, John L.
    Shah, Amil M.
    Garg, Pushkal
    Vaishnaw, Akshay
    Karsten, Verena
    Chen, Jihong
    Gollob, Jared
    Vest, John
    Suhr, Ole B.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Effects of Patisiran, an RNA Interference Therapeutic, on Cardiac Parameters in Patients With Hereditary Transthyretin-Mediated Amyloidosis: Analysis of the APOLLO Study2019Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139, nr 4, s. 431-443Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Hereditary transthyretin-mediated (hATTR) amyloidosis is a rapidly progressive, multisystem disease that presents with cardiomyopathy or polyneuropathy. The APOLLO study assessed the efficacy and tolerability of patisiran in patients with hATTR amyloidosis. The effects of patisiran on cardiac structure and function in a prespecified subpopulation of patients with evidence of cardiac amyloid involvement at baseline were assessed.

    Methods: APOLLO was an international, randomized, double-blind, placebo-controlled phase 3 trial in patients with hATTR amyloidosis. Patients were randomized 2:1 to receive 0.3 mg/kg patisiran or placebo via intravenous infusion once every 3 weeks for 18 months. The prespecified cardiac subpopulation comprised patients with a baseline left ventricular wall thickness 13 mm and no history of hypertension or aortic valve disease. Prespecified exploratory cardiac end points included mean left ventricular wall thickness, global longitudinal strain, and N-terminal prohormone of brain natriuretic peptide. Cardiac parameters in the overall APOLLO patient population were also evaluated. A composite end point of cardiac hospitalizations and all-cause mortality was assessed in a post hoc analysis.

    Results: In the cardiac subpopulation (n=126; 56% of total population), patisiran reduced mean left ventricular wall thickness (least-squares mean difference SEM: -0.90.4 mm, P=0.017), interventricular septal wall thickness, posterior wall thickness, and relative wall thickness at month 18 compared with placebo. Patisiran also led to increased end-diastolic volume (8.3 +/- 3.9 mL, P=0.036), decreased global longitudinal strain (-1.4 +/- 0.6%, P=0.015), and increased cardiac output (0.38 +/- 0.19 L/min, P=0.044) compared with placebo at month 18. Patisiran lowered N-terminal prohormone of brain natriuretic peptide at 9 and 18 months (at 18 months, ratio of fold-change patisiran/placebo 0.45, P<0.001). A consistent effect on N-terminal prohormone of brain natriuretic peptide at 18 months was observed in the overall APOLLO patient population (n=225). Median follow-up duration was 18.7 months. The exposure-adjusted rates of cardiac hospitalizations and all-cause death were 18.7 and 10.1 per 100 patient-years in the placebo and patisiran groups, respectively (Andersen-Gill hazard ratio, 0.54; 95% CI, 0.28-1.01).

    Conclusions: Patisiran decreased mean left ventricular wall thickness, global longitudinal strain, N-terminal prohormone of brain natriuretic peptide, and adverse cardiac outcomes compared with placebo at month 18, suggesting that patisiran may halt or reverse the progression of the cardiac manifestations of hATTR amyloidosis.

  • 20.
    Thøgersen, AM
    et al.
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin.
    Jansson, JH
    Boman, K.
    Nilsson, TK
    Weinehall, L.
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Epidemiologi och folkhälsovetenskap.
    Huhtasaari, F.
    Hallmans, G.
    High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infarction in both men and women.: Evidence for the fibrinolytic system as an independent primary risk factor1998Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 98, nr 21, s. 2241-2247Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: In patients with established ischemic heart disease, prospective cohort studies have indicated that plasminogen activator inhibitor (PAI-1), the inhibitor of the fibrinolytic system, may predict cardiovascular events. So far, there have been no primary prospective studies of PAI-1. METHODS AND RESULTS: The aim of the present study was to test whether plasma levels of PAI-1, tissue-type plasminogen activator (tPA), von Willebrand factor (vWF), and thrombomodulin (TM) could predict the occurrence of a first acute myocardial infarction (AMI) in a population with high prevalence of coronary heart disease by use of a prospective nested case-control design. Mass concentrations of PAI-1 and tPA were significantly higher for the 78 subjects who developed a first AMI compared with the 156 references matched for age, sex, and sampling time; for tPA, this increase was independent of smoking habits, body mass index, hypertension, diabetes, cholesterol, and apolipoprotein A-I. The ratio of quartile 4 to 1 for tPA was 5.9 for a patient to develop a first AMI. The association between tPA and AMI was seen in both men and women. Increased levels of vWF were associated with AMI in a univariate analysis. High levels of TM were associated with AMI in women but not in men. CONCLUSIONS: The plasma levels of PAI-1, tPA, and vWF are associated with subsequent development of a first AMI; for PAI-1 and tPA, this relation was found in both men and women. For tPA but not for PAI-1 and vWF, this association is independent of established risk factors.

  • 21.
    Valham, Fredrik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Mooe, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Rabben, Terje
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurofysiologi.
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och folkhälsovetenskap.
    Wiklund, Urban
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Franklin, Karl A
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Increased risk of stroke in patients with coronary artery disease and sleep apnea: a 10-year follow-up2008Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 118, nr 9, s. 955-960Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background The effect of sleep apnea on mortality and cardiovascular morbidity is mainly unknown. We aimed to study whether sleep apnea is related to stroke, death, or myocardial infarction in patients with symptomatic coronary artery disease.

    Methods and Results A total of 392 men and women with coronary artery disease referred for coronary angiography were examined by use of overnight sleep apnea recordings. Sleep apnea, defined as an apnea-hypopnea index ≥5, was recorded in 54% of the patients. All patients were followed up prospectively for 10 years, and no one was lost to follow-up. Stroke occurred in 47 (12%) of 392 patients during follow-up. Sleep apnea was associated with an increased risk of stroke, with an adjusted hazard ratio of 2.89 (95% confidence interval 1.37 to 6.09, P=0.005), independent of age, body mass index, left ventricular function, diabetes mellitus, gender, intervention, hypertension, atrial fibrillation, a previous stroke or transient ischemic attack, and smoking. Patients with an apnea-hypopnea index of 5 to 15 and patients with an apnea-hypopnea index ≥15 had a 2.44 (95% confidence interval 1.08 to 5.52) and 3.56 (95% confidence interval 1.56 to 8.16) times increased risk of stroke, respectively, than patients without sleep apnea, independent of confounders (P for trend=0.011). Death and myocardial infarction were not related to sleep apnea. Intervention in the form of coronary artery bypass grafting or percutaneous coronary intervention was related to a longer survival but did not affect the incidence of stroke.

    Conclusions Sleep apnea is significantly associated with the risk of stroke among patients with coronary artery disease who are being evaluated for coronary intervention.

  • 22.
    Vejlstrup, Niels
    et al.
    Copenhagen, Denmark .
    Sörensen, Keld
    Aarhus, Denmark .
    Mattsson, Eva
    Stockholm, Sweden .
    Thilen, Ulf
    Lund University, Sweden.
    Kvidal, Per
    Uppsala, Sweden.
    Johansson, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Iversen, Kasper
    Herlev County Hospital, Denmark .
    Söndergaard, Lars
    Copenhagen, Denmark .
    Dellborg, Mikael
    Göteborg, Sweden .
    Eriksson, Peter
    Göteborg, Sweden .
    Long-Term Outcome of Mustard/Senning Correction for Transposition of the Great Arteries in Sweden and Denmark2015Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 132, nr 8, s. 633-638Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background The atrial switch operation, the Mustard or Senning operation, for the transposition of the great arteries (TGA) was introduced in the late 1950s and was the preferred surgery for TGA until the early 1990s. The Mustard and Senning operation involves extensive surgery in the atria and leaves the right ventricle as the systemic ventricle. The Mustard and Senning cohort is now well into adulthood and we begin to see the long-term outcome. Methods and Results All the 6 surgical centers that performed Mustard and Senning operations in Sweden and Denmark identified all operated TGA patients. Information about death was obtained in late 2007 and early 2008 from the Danish and Swedish Centralised Civil Register by using the patients' unique national Civil Registration Numbers. Four hundred sixty-eight patients undergoing the atrial switch operation were identified. Perioperative 30-day mortality was 20%, and 60% were alive after 30 years of follow-up. Perioperative mortality was significantly increased by the presence of a ventricular septal defect, left ventricular outflow obstruction, surgery early in the Mustard and Senning era. However, only pacemaker implantation is predictive of long-term outcome (hazard ratio, 1.90; 95% confidence interval, 1.05-3.46, P=0.04), once the TGA patient has survived the perioperative period. The risk of reoperation was correlated to the presence of associated defects and where the first Mustard/Senning operation was performed. Conclusions The long-term survival of patients with Mustard and Senning correction for TGA appears to be primarily determined by factors in the right ventricle and tricuspid valve and not the timing of or the type of surgery in childhood. Cardiac function necessitating the implantation of a pacemaker is associated with an increase in mortality.

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