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  • 301. Cameli, M.
    et al.
    Lisi, M.
    Reccia, R.
    Bigio, E.
    Bennati, E.
    Malandrino, A.
    Maccherini, M.
    Chiavarelli, M.
    Henein, Michael Y.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mondillo, S.
    Left atrial strain predicts postoperative atrial fibrillation in patients waiting for aortic valve replacement for aortic stenosis2012Ingår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, nr Suppl. 1, s. 826-826Artikel i tidskrift (Övrigt vetenskapligt)
  • 302. Camen, S.
    et al.
    Ojeda, F. M.
    Niiranen, T.
    Gianfagna, F.
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lochen, M. L.
    Kee, F.
    Blankenberg, S.
    Jørgensen, T.
    Zeller, T.
    Kuulasmaa, K.
    Linneberg, A.
    Salomaa, V.
    Iacoviello, L.
    Schnabel, R.
    Temporal relations between atrial fibrillation and ischemic stroke and their prognostic impact on mortality2018Ingår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, s. 204-205Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: Atrial fibrillation (AF) and stroke are common diseases and AF is a well-established risk factor for stroke. The physiological mechanism of atrial dysfunction, disturbed hemodynamics and arterial thromboembolism links the pathologies. However, limited evidence is available on the temporal relationship between stroke and AF and the impact of subsequent disease onset on mortality in the community.

    Methods and results: Across five prospective community cohorts (DanMONICA, FINRISK, Moli-Sani project, Northern Sweden MONICA study, The Tromsø Study) of the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE)-project we assessed baseline cardiovascular risk factors in 101164 individuals, median age 46.1 (25th, 75th percentile 35.8, 57.6) years, 48.4% men. We followed them for incident stroke and AF and determined the relation of subsequent disease diagnosis with overall mortality. Follow-up (FU) for stroke and AF was based upon linkage with national hospitalization registries or administrative registries for ambulatory visits to specialized hospitals.

    Over a median FU of 16.1 years N=4556 individuals were diagnosed solely with AF, N=2269 had a stroke but no AF diagnosed, and N=898 developed both stroke and AF during FU. Participants who developed either AF or stroke as the index event revealed a similar baseline risk factor profile. Temporal relations showed a peak of the diagnosis of both diseases within the years around the diagnosis of the other disease. The highest incidence rates of stroke were observed within a five-year interval prior to AF diagnosis. Cox regression showed an association of baseline stroke with diagnosis of AF during FU (hazard ratio (HR) 1.29; 95% confidence interval (CI) 1.11–1.50; p<0.001).

    In multivariable-adjusted Cox regression analyses with time-dependent covariates excluding individuals with diagnosis of both AF and stroke or death within 30 days, subsequent diagnosis of AF after stroke was associated with a higher overall mortality (HR, 3.51; 95% CI 1.87–6.59; p<0.001); subsequent stroke after the diagnosis of AF was associated with a HR of 2.39 (95% CI 1.59–3.60; p<0.001).

    Conclusions: Stroke and AF are common comorbidities in older adults with an overlapping risk factor profile. The temporal relations appear to be bidirectional, although uncertainty regarding disease onset remains due to the often paroxysmal and asymptomatic nature of AF. Stroke may precede detection of AF by years. The subsequent diagnosis of both diseases significantly increases mortality risk. Whether targeting modifiable risk factors or improved screening for AF after stroke would improve survival needs to be determined.

  • 303.
    Carlberg, B
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Blood Pressure in Acute Stroke: Causes and consequences1994Ingår i: Hypertension Research, ISSN 0916-9636, E-ISSN 1348-4214, Vol. 17, nr Suppl I, s. S77-S82Artikel i tidskrift (Övrigt vetenskapligt)
  • 304.
    Carlberg, B
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Asplund, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Hägg, E
    Course of blood pressure in different subsets of patients after acute stroke1991Ingår i: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 1, s. 281-287Artikel i tidskrift (Refereegranskat)
  • 305.
    Carlberg, B
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Asplund, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Hägg, E
    Factors influencing admission blood pressure levels in patients with acute stroke.1991Ingår i: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 22, nr 4, s. 527-30Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In clinical practice, patients with acute stroke often have high blood pressure. The aim of this study was to investigate factors correlated with blood pressure elevation in 843 consecutive stroke patients on hospital admission to a nonintensive stroke unit. Using a multivariate analysis model, we analyzed the influence on admission blood pressure of sex, age, previous hypertension, cardiac failure, diabetes, type of stroke, impaired consciousness, and latency between onset of symptoms and admission. Previous hypertension was the strongest predictor (p less than 0.001) of elevated blood pressure on admission, followed by the presence of intracerebral hemorrhage (p less than 0.001). The latency between onset of symptoms and admission showed no correlation with blood pressure levels at hospitalization. Previously, high blood pressure levels on hospital admission have been shown to decline within a few days in hospital. We therefore hypothesize that mental stress on hospital admission may be a major factor in the blood pressure elevation seen in acute stroke.

  • 306.
    Carlberg, B
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Asplund, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Hägg, E
    High blood pressure in acute stroke--is it white coat hypertension?1990Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 228, nr 3, s. 291-2Artikel i tidskrift (Refereegranskat)
  • 307.
    Carlberg, B
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Asplund, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Hägg, E
    The prognostic value of admission blood pressure in patients with acute stroke.1993Ingår i: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 24, nr 9, s. 1372-5Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND PURPOSE: Patients with acute stroke are often found to have high blood pressures at hospital admission. Previous studies have shown variable results regarding the prognostic value of high blood pressure in acute stroke. The aim of this study was to investigate the prognostic value of admission blood pressure in a population-based sample of patients with acute stroke.

    METHODS: Eighty-five patients with intracerebral hemorrhage and 831 with ischemic disease were included in the study. The relations between admission blood pressure and 30-day mortality were studied by logistic regression analyses.

    RESULTS: High blood pressure in patients with impaired consciousness on hospital admission was significantly related to 30-day mortality in patients with intracerebral hemorrhage (P = .037) and in patients with ischemic disease (P < .0001). In patients without impaired consciousness, high blood pressure at time of admission was not related to increased mortality at 30 days.

    CONCLUSIONS: High admission blood pressure in alert stroke patients was not related to increased mortality. Stroke patients with impaired consciousness showed higher mortality rates with increasing blood pressure. However, this does not provide a basis for recommending antihypertensive therapy for such patients.

  • 308.
    Carlberg, Bo
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Beta-blockers for hypertension.2007Ingår i: CMAJ, ISSN 1488-2329, Vol. 176, nr 7, s. 971; author reply 971-2Artikel i tidskrift (Refereegranskat)
  • 309.
    Carlberg, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Is lower really better?: Issue of the J curve hypothesis in hypertension2016Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 34, s. e196-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The J curve hypothesis propose that the relation between blood pressure and risk for cardiovascular events is non-linear. Instead of a decreased risk with lower blood pressure, the risk increases at lower blood pressures. This issue has been discussed for many years, and is still a hot topic. The debates have most often had its origin in the question about how far blood pressure should be lowered with antihypertensive drugs.One one hand, we know that many patients with hypertension is not treated to targets according to guidelines and that this contributes to the high risk for cardiovascular diseases in patients with hypertension. On the other hand, overtreatment could be one reason for the subobtimal effect of antihypertensive drugs on cardiovascular diseases.The issue about a J curve in the effect of antihypertensive drugs is complicated.The relation between blood pressure and cardiovascular risk is different for different cardiovascular outcomes. For example, the risk for intracerebral hemorrhage seem to increase steeper at higher blood pressure than for most other outcomes. On the other hand, the risk for abdominal aortic aneurysm increases only modestly with higher blood pressure. In addition, end stage renal disease and cognitive decline could have other relations between blood pressure and risk. Age, cardiovascular disease and diabetes have also been found to modify the relation between risk and outcome.Earlier this year, we published a meta-analysis of randomized controlled trials with antihypertensive drugs in patients with diabetes mellitus (ref). Included trials had to compare treatment with an antihypertensive drug against placebo, two antihypertensive agents against one or one blood pressure target against another target. The studies were stratified according to blood pressure at randomization (baseline blood pressure), mimicking the situation you as a clinician meet when you decide to recommend a patients additional antihypertensive therapy or not. We contacted authors to receive data from diabetic subgroups in large studies. Thus, we were able to include more studies than in previous systematic reviews in this field. All together, we included data from 49 randomized controlled trials, including 73 738 patients.The systematic review showed that the effect of antihypertensive drugs on cardiovascular outcomes is different at different blood pressure levels. For most outcomes, adding antihypertensive drugs were beneficial in patients with diabetes mellitus and high blood pressure. However, this benefit decreased with decreasing blood pressure. The risk for cardiovascular death increased when therapy was added in patents with diabetes and systolic blood pressure below 140 mmHg. The benefits of adding antihypertensive treatment at different blood pressure levels are summarized in the figure below.Thus, in patients with diabetes, the relations between treatment effect of antihypertensive drugs are different at different blood pressure levels. Treatment effects differ for different cardiovascular outcomes. These data question previous guidelines that recommend a systolic blood pressure target below 130 mmHg in patients with diabetes mellitus.In a very recent systematic review, we have reexamined the relation between randomization blood pressure and cardiovascular stratified for different baseline blood pressures. The meta-analyses include patients with and without diabetes, with and without previous cardiovascular disease etc. Altogether, 58 trials with 290 000 patients were included. The study shows that the effect of blood pressure lowering on cardiovascular outcomes is dependent on baseline systolic blood pressure but also differ between different subsets of patients. This study is under review and the results will be presented during the lecture.

  • 310.
    Carlberg, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Proteinuria early in the development of hypertension2014Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 32, nr 12, s. 2351-2352Artikel i tidskrift (Övrigt vetenskapligt)
  • 311.
    Carlberg, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    The challenge of preventing dementia by antihypertensive treatment2013Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 31, nr 9, s. 1780-1781Artikel i tidskrift (Övrigt vetenskapligt)
  • 312.
    Carlberg, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Time to lower treatment BP targets for hypertension?2009Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 374, nr 9689, s. 503-504Artikel i tidskrift (Övrigt vetenskapligt)
  • 313.
    Carlberg, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    What do we know about the risks of stopping antihypertensive treatment?2014Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 32, nr 7, s. 1400-1401Artikel i tidskrift (Övrigt vetenskapligt)
  • 314.
    Carlberg, Bo
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindholm, Lars Hjalmar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Comment: Stroke and blood-pressure variation: new permutations on an old theme.2010Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 375, nr 9718, s. 867-869Artikel i tidskrift (Refereegranskat)
  • 315.
    Carlberg, Bo
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nilsson, Peter M
    Hypertension in the elderly: what is the goal blood pressure target and how can this be attained?2010Ingår i: Current Hypertension Reports, ISSN 1522-6417, E-ISSN 1534-3111, Vol. 12, nr 5, s. 331-334Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    For the aging populations of Europe, many emerging health problems in addition to myocardial infarction and stroke are associated with hypertension. Recently, the role of hypertension in the risk of vascular cognitive impairment and dementia has been highlighted, and there are studies to show that control of hypertension may slow this process. Furthermore, as many elderly individuals will also develop type 2 diabetes or impaired renal function, the risk of hypertension in these patients is more pronounced. New guidelines have tried to provide evidence-based treatment algorithms in which control of hypertension is just one aspect of general risk factor control, with the aim of decreasing the total risk.

  • 316.
    Carlberg, Bo
    et al.
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Olsson, Tommy
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Cererovaskulära sjukdomar2009Ingår i: Diabetes / [ed] Agardh, Berne, Liber , 2009, s. 401-410Kapitel i bok, del av antologi (Övrigt vetenskapligt)
  • 317.
    Carlberg, Bo
    et al.
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Samuelsson, Ola
    Lindholm, Lars H
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Allmänmedicin.
    Atenolol in hypertension: is it a wise choice?2004Ingår i: Lancet, ISSN 1474-547X, Vol. 364, nr 9446, s. 1684-9Artikel i tidskrift (Refereegranskat)
  • 318.
    Carlberg, Bo
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Samuelsson, Ola
    Lindholm, Lars H
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Finns möjligen hela bilden om atenolol hos Kent Forsén?2005Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 102, nr 3, s. 151-152Artikel i tidskrift (Övrigt vetenskapligt)
  • 319. Carlsson, Axel C.
    et al.
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Ruge, Toralph
    Larsson, Anders
    Arnlov, Johan
    Levels of soluble tumor necrosis factor receptor 1 and 2, gender, and risk of myocardial infarction in Northern Sweden2018Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 272, s. 41-46Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and aims: Soluble receptors for tumor necrosis factor alpha (sTNFR1 and sTNFR2) have been associated with cardiovascular diseases, and some evidence points towards a difference in associated risk between men and women. We aimed to study the association between sTNFR1 and sTNFR2 and incident myocardial infarctions (MI) and to explore the influence of established cardiovascular risk factors in men and women.& para;& para;Methods: We conducted a nested case control study in three large Swedish cohorts, including 533 myocardial infarction cases, and 1003 age-, sex- and cohort-matched controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated.& para;& para;Results: An association between circulating sTNFR1 and sTNFR2 and an increased risk for MI was found when comparing cases and controls. The odds ratios were significant after adjustment for established cardiovascular risk factors and C-reactive protein in women (OR 1.44, 95% CI 1.08-1.93 for TNFR1, and 1.61, 95% CI 1.11-2.34 for TNFR2), but was abolished in men. Women with a combination of elevated CRP and values in the upper quartile of TNFR1 or TNFR2 had a 5-fold higher risk of myocardial infarction versus those with normal CRP and values in the lower three quartiles of TNFR1 or TNFR2.& para;& para;Conclusions: As the risk estimates for TNFR1 and TNFR2 were higher and remained significant after adjustments for established cardiovascular risk factors in women but not in men, a potential role for TNFR1 and TNFR2 in identifying women with a higher MI risk is possible. The future clinical role of TNFR1 and TNFR2 in combination with CRP to identify high risk patients for coronary heart disease has yet to be determined. 

  • 320. Carlsson, Leif
    et al.
    Danielsson, Åke
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    [Lhx2 seems to inhibit the development of liver cirrhosis. Gene discovery makes the development of drugs against this enormous health problem possible]2006Ingår i: Lakartidningen, ISSN 0023-7205, Vol. 103, nr 20, s. 1594-7Artikel i tidskrift (Refereegranskat)
  • 321. Carlsson, Per
    et al.
    Anders, Anell
    Eliasson, Mats
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    [Health economics play more and more important role in health care prioritization. Better utilization of the meager health care resources is the goal]2006Ingår i: Lakartidningen, ISSN 0023-7205, Vol. 103, nr 46, s. 3617-20, 3622Artikel i tidskrift (Övrigt vetenskapligt)
  • 322. Carrasquilla, German D.
    et al.
    Frumento, Paolo
    Berglund, Anita
    Borgfeldt, Christer
    Bottai, Matteo
    Chiavenna, Chiara
    Eliasson, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Engström, Gunnar
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Magnusson, Patrik K.
    Nilsson, Peter M.
    Pedersen, Nancy L.
    Wolk, Alicja
    Leander, Karin
    Postmenopausal hormone therapy and risk of stroke: A pooled analysis of data from population-based cohort studies2017Ingår i: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 14, nr 11, artikel-id e1002445Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Recent research indicates a favourable influence of postmenopausal hormone therapy (HT) if initiated early, but not late, on subclinical atherosclerosis. However, the clinical relevance of timing of HT initiation for hard end points such as stroke remains to be determined. Further, no previous research has considered the timing of initiation of HT in relation to haemorrhagic stroke risk. The importance of the route of administration, type, active ingredient, and duration of HT for stroke risk is also unclear. We aimed to assess the association between HT and risk of stroke, considering the timing of initiation, route of administration, type, active ingredient, and duration of HT.

    Methods and findings: Data on HT use reported by the participants in 5 population-based Swedish cohort studies, with baseline investigations performed during the period 1987-2002, were combined in this observational study. In total, 88,914 postmenopausal women who reported data on HT use and had no previous cardiovascular disease diagnosis were included. Incident events of stroke (ischaemic, haemorrhagic, or unspecified) and haemorrhagic stroke were identified from national population registers. Laplace regression was employed to assess crude and multivariable-adjusted associations between HT and stroke risk by estimating percentile differences (PDs) with 95% confidence intervals (CIs). The fifth and first PDs were calculated for stroke and haemorrhagic stroke, respectively. Crude models were adjusted for age at baseline only. The final adjusted models included age at baseline, level of education, smoking status, body mass index, level of physical activity, and age at menopause onset. Additional variables evaluated for potential confounding were type of menopause, parity, use of oral contraceptives, alcohol consumption, hypertension, dyslipidaemia, diabetes, family history of cardiovascular disease, and cohort. During a median follow-up of 14.3 years, 6,371 first-time stroke events were recorded; of these, 1,080 were haemorrhagic. Following multivariable adjustment, early initiation (<5 years since menopause onset) of HT was associated with a longer stroke-free period than never use (fifth PD, 1.00 years; 95% CI 0.42 to 1.57), but there was no significant extension to the time period free of haemorrhagic stroke (first PD, 1.52 years; 95% CI -0.32 to 3.37). When considering timing as a continuous variable, the stroke-free and the haemorrhagic stroke-free periods were maximal if HT was initiated approximately 0-5 years from the onset of menopause. If single conjugated equine oestrogen HT was used, late initiation of HT was associated with a shorter stroke-free (fifth PD, -4.41 years; 95% CI -7.14 to -1.68) and haemorrhagic stroke-free (first PD, -9.51 years; 95% CI -12.77 to -6.24) period than never use. Combined HT when initiated late was significantly associated with a shorter haemorrhagic stroke-free period (first PD, -1.97 years; 95% CI -3.81 to -0.13), but not with a shorter stroke-free period (fifth PD, -1.21 years; 95% CI -3.11 to 0.68) than never use. Given the observational nature of this study, the possibility of uncontrolled confounding cannot be excluded. Further, immortal time bias, also related to the observational design, cannot be ruled out.

    Conclusions: When initiated early in relation to menopause onset, HT was not associated with increased risk of incident stroke, regardless of the route of administration, type of HT, active ingredient, and duration. Generally, these findings held also for haemorrhagic stroke. Our results suggest that the initiation of HT 0-5 years after menopause onset, as compared to never use, is associated with a decreased risk of stroke and haemorrhagic stroke. Late initiation was associated with elevated risks of stroke and haemorrhagic stroke when conjugated equine oestrogen was used as single therapy. Late initiation of combined HT was associated with haemorrhagic stroke risk.

  • 323. Chan, Simon S. M.
    et al.
    Luben, Robert
    Olsen, Anja
    Tjonneland, Anne
    Kaaks, Rudolf
    Teucher, Birgit
    Lindgren, Stefan
    Grip, Olof
    Key, Timothy
    Crowe, Francesca L.
    Bergmann, Manuela M.
    Boeing, Heiner
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Overvad, Kim
    Palli, Domenico
    Masala, Giovanna
    Kennedy, Hugh
    vanSchaik, Fiona
    Bueno-de-Mesquita, Bas
    Oldenburg, Bas
    Khaw, Kay-Tee
    Riboli, Elio
    Hart, Andrew R.
    Body Mass Index and the Risk for Crohn's Disease and Ulcerative Colitis: Data From a European Prospective Cohort Study (The IBD in EPIC Study)2013Ingår i: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 108, nr 4, s. 575-582Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: Obesity is associated with a proinflammatory state that may be involved in the etiology of inflammatory bowel disease (IBD), for which there are plausible biological mechanisms. Our aim was to perform the first prospective cohort study investigating if there is an association between obesity and the development of incident IBD. METHODS: A total of 300,724 participants were recruited into the European Prospective Investigation into Cancer and Nutrition study. At recruitment, anthropometric measurements of height and weight plus physical activity and total energy intake from validated questionnaires were recorded. The cohort was monitored identifying participants who developed either Crohn's disease (CD) or ulcerative colitis (UC). Each case was matched with four controls and conditional logistic regression used to calculate odds ratios (ORs) for body mass index (BMI) adjusted for smoking, energy intake, and physical activity. RESULTS: In the cohort, 177 participants developed incident UC and 75 participants developed incident CD. There were no associations with the four higher categories of BMI compared with a normal BMI for UC (P-trend = 0.36) or CD (P-trend = 0.83). The lack of associations was consistent when BMI was analyzed as a continuous or binary variable (BMI 18.5 <25.0 vs. >= 25 kg/m(2)). Physical activity and total energy intake, factors that influence BMI, did not show any association with UC (physical activity, P-trend = 0.79; total energy intake, P-trend = 0.18) or CD (physical activity, P-trend = 0.42; total energy, P-trend = 0.11). CONCLUSIONS: Obesity as measured by BMI is not associated with the development of incident UC or CD. Alternative measures of obesity are required to further investigate the role of obesity in the development of incident IBD.

  • 324. Chan, Simon S. M.
    et al.
    Luben, Robert
    van Schaik, Fiona
    Oldenburg, Bas
    Bueno-De-Mesquita, H. Bas
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindgren, Stefan
    Grip, Olof
    Key, Timothy
    Crowe, Francesca L.
    Bergmann, Manuela M.
    Overvad, Kim
    Palli, Domenico
    Masala, Giovanna
    Khaw, Kay-Tee
    Racine, Antoine
    Carbonnel, Franck
    Boutron-Rualt, Marie-Christine
    Olsen, Anja
    Tjonneland, Anne
    Kaaks, Rudolf
    Tumino, Rosario
    Trichopoulou, Antonia
    Hart, Andrew R.
    Carbohydrate Intake in the Etiology of Crohn's Disease and Ulcerative Colitis2014Ingår i: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 20, nr 11, s. 2013-2021Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Diet may have a role in the etiology of inflammatory bowel disease. In previous studies, the associations between increased intakes of carbohydrates, sugar, starch, and inflammatory bowel disease are inconsistent. However, few prospective studies have investigated the associations between these macronutrients and incident Crohn's disease (CD) or ulcerative colitis (UC). Methods: A total of 401,326 men and women were recruited between 1991 and 1998. At recruitment, dietary intakes of carbohydrate, sugar, and starch were measured using validated food frequency questionnaires. The cohort was monitored identifying participants who developed incident CD or UC. Cases were matched with 4 controls, and odds ratios were calculated for quintiles of total carbohydrate, sugar, and starch intakes adjusted for total energy intake, body mass index, and smoking. Results: One hundred ten participants developed CD, and 244 participants developed UC during follow-up. The adjusted odds ratio for the highest versus the lowest quintiles of total carbohydrate intake for CD was 0.87, 95% CI = 0.24 to 3.12 and for UC 1.46, 95% CI = 0.62 to 3.46, with no significant trends across quintiles for either (CD, P-trend = 0.70; UC, P-trend = 0.41). Similarly, no associations were observed with intakes of total sugar (CD, P-trend = 0.50; UC, P-trend = 0.71) or starch (CD, P-trend = 0.69; UC, P-trend = 0.17). Conclusions: The lack of associations with these nutrients is in agreement with many case-control studies that have not identified associations with CD or UC. As there is biological plausibility for how specific carbohydrates could have an etiological role in inflammatory bowel disease, future epidemiological work should assess individual carbohydrates, although there does not seem to be a macronutrient effect.

  • 325. Chan, SSM
    et al.
    Luben, R
    Olsen, A
    Tjonneland, A
    Kaaks, R
    Lindgren, S
    Grip, O
    Bergmann, MM
    Boeing, H
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Overvad, K
    Veno, SK
    van Schaik, F
    Bueno-de-Mesquita, B
    Oldenburg, B
    Khaw, K-T
    Riboli, E
    Hart, AR
    Association between high dietary intake of the n-3 polyunsaturated fatty acid docosahexaenoic acid and reduced risk of Crohn's disease2014Ingår i: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 39, nr 8, s. 834-842Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background There are plausible mechanisms for how dietary docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, could prevent Crohn's disease (CD).

    Aim To conduct a prospective study to investigate the association between increased intake of DHA and risk of CD.

    Methods Overall, 229702 participants were recruited from nine European centres between 1991 and 1998. At recruitment, dietary intakes of DHA and fatty acids were measured using validated food frequency questionnaires. The cohort was monitored through to June 2004 to identify participants who developed incident CD. In a nested case-control analysis, each case was matched with four controls; odds ratios (ORs) were calculated for quintiles of DHA intake, adjusted for total energy intake, smoking, other dietary fatty acids, dietary vitamin D and body mass index.

    Results Seventy-three participants developed incident CD. All higher quintiles of DHA intake were inversely associated with development of CD; the highest quintile had the greatest effect size (OR=0.07; 95% CI=0.02-0.81). The OR trend across quintiles of DHA was 0.54 (95% CI=0.30-0.99, P-trend=0.04). Including BMI in the multivariate analysis, due to its correlation with dietary fat showed similar associations. There were no associations with the other dietary fatty acids studied.

    Conclusion There were inverse associations, with a biological gradient between increasing dietary docosahexaenoic acid intakes and incident Crohn's disease. Further studies in other populations should measure docosahexaenoic acid to determine if the association is consistent and the hypothesis tested in randomised controlled trials of purely docosahexaenoic acid supplementation.

  • 326. Chao, Guihua
    et al.
    Zheng, Chenguang
    Meng, Dahua
    Su, Jialing
    Xie, Xijin
    Li, Wei
    Henein, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Tei index: The earliest detectable cardiac structural and functional abnormality detectable in Hb Bart's foetal edema.2009Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 134, nr 3, s. e150-154Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Premature death and still births are common in Hb Bart's foetal edema which carries significant risk to mothers. We aimed to identify early changes in cardiac structure and function in a cohort of HB Bart's foetuses, using Doppler echocardiography. METHODS: We studied 97 HB Bart's foetuses in different gestation groups; I (20-24 weeks),..., V (37-42 weeks) and compared them with age matched controls. We measured right and left atrial diameters as well as right and left ventricular diameters. From the Doppler filling and ejection velocities of the right and left ventricles we measured Tei index in 30 foetuses and compared them with age matched normal controls. RESULTS: The four cardiac chamber dimensions were not significantly different from the respective controls (p=NS for all). The right atrial diameter was enlarged in groups II, III, IV and V (p<0.05 vs normal controls). The right ventricle was significantly dilated in group III, IV and V (p<0.05-0.01) compared with normals. The left atrium and left ventricle were enlarged in groups III and IV, respectively (p<0.05 vs normals). Transmitral and transtricuspid E/A ratio was significantly less than normal in groups III (p<0.01), IV (p<0.05) and IV (p<0.05). LV and RV fractional shortening and stroke distance of group IV and V were significantly less than the respective normals (p<0.05 for all). LV and RV Tei index increased progressively from 20-week gestation (p<0.05) with respect to controls. CONCLUSIONS: In HB Bart's foetuses left and right ventricular asynchrony develop earlier than overt cavity dilatation and impairment of systolic function. The use of such markers of ventricular asynchronous function may play an important role in optimum management of these pregnancies.

  • 327. Chinali, Marcello
    et al.
    Aurigemma, Gerard P
    de Simone, Giovanni
    Mishra, Rakesh K
    Gerdts, Eva
    Wachtell, Kristian
    Boman, Kurt
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Dahlöf, Björn
    Devereux, Richard B
    Mitral E wave deceleration time to peak E velocity ratio and cardiovascular outcome in hypertensive patients during antihypertensive treatment (from the LIFE echo-substudy).2009Ingår i: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 104, nr 8, s. 1098-1104Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The early mitral flow deceleration time (DTE) is a prognostically validated marker of left ventricular diastolic dysfunction. It has been reported that the DTE is influenced by the loading conditions, which can vary during antihypertensive treatment. We hypothesized that normalization of the DTE for mitral peak E-velocity (mitral deceleration index [MDI]) might better predict incident cardiovascular (CV) events in hypertensive patients during treatment compared to DTE alone or other traditional indexes of diastolic function, such as the mitral E/A ratio. We evaluated 770 hypertensive patients with electrocardiogram findings of left ventricular hypertrophy (age 66 +/- 7 years; 42% women) enrolled in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiographic substudy. Echocardiographic examinations were performed annually for 5 years during intensive antihypertensive treatment. We examined the utility of the MDI at baseline and as a time-varying predictor of incident CV events. Of the 770 patients, 70 (9%) had CV events. The baseline MDI was positively associated with age and relative wall thickness and negatively associated with gender and heart rate (all p <0.01). Unadjusted Cox regression analysis showed a positive association between the baseline MDI and CV events (hazard ratio 1.21, 95% confidence interval 1.07 to 1.37, p = 0.002). In the time-varied Cox models, a greater in-treatment MDI was associated with a greater rate of CV events (hazard ratio 1.43, 95% confidence interval 1.05 to 1.93, p = 0.022), independently of the covariates. No significant association was found for in-treatment DTE or any of the prognostically validated indexes of diastolic function. In conclusion, in our population of patients with treated hypertension with electrocardiographic findings of left ventricular hypertrophy, the MDI independently predicted future CV events. Normalization of DTE for E velocity might be preferred to other traditional diastolic function indexes in evaluating diastolic function during antihypertensive treatment.

  • 328. Chinali, Marcello
    et al.
    de Simone, Giovanni
    Wachtell, Kristian
    Gerdts, Eva
    Gardin, Julius M
    Boman, Kurt
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Nieminen, Markku S
    Papademetriou, Vasilios
    Dahlöf, Björn
    Devereux, Richard B
    Left atrial systolic force in hypertensive patients with left ventricular hypertrophy: the LIFE study.2008Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 26, nr 7, s. 1472-6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In hypertensive patients without prevalent cardiovascular disease, enhanced left atrial systolic force is associated with left ventricular hypertrophy and increased preload. It also predicts cardiovascular events in a population with high prevalence of obesity. Relations between left atrial systolic force and left ventricular geometry and function have not been investigated in high-risk hypertrophic hypertensive patients. Participants in the Losartan Intervention For Endpoint reduction in hypertension echocardiography substudy without prevalent cardiovascular disease or atrial fibrillation (n = 567) underwent standard Doppler echocardiography. Left atrial systolic force was obtained from the mitral orifice area and Doppler mitral peak A velocity. Patients were divided into groups with normal or increased left atrial systolic force (>14.33 kdyn). Left atrial systolic force was high in 297 patients (52.3%), who were older and had higher body mass index and heart rate (all P < 0.01) but similar systolic and diastolic blood pressure, in comparison with patients with normal left atrial systolic force. After controlling for confounders, increased left atrial systolic force was associated with larger left ventricular diameter and higher left ventricular mass index (both P < 0.01). Prevalence of left ventricular hypertrophy was greater (84 vs. 64%; P < 0.001). Participants with increased left atrial systolic force exhibited normal ejection fraction; higher stroke volume, cardiac output, transmitral peak E velocities and peak A velocities; and lower E/A ratio (all P < 0.01). Enhanced left atrial systolic force identifies hypertensive patients with greater left ventricular mass and prevalence of left ventricular hypertrophy, but normal left ventricular chamber systolic function with increased transmitral flow gradient occurring during early filling, consistent with increased preload.

  • 329.
    Chorell, Elin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Hall, Ulrika Andersson
    Gustavsson, Carolina
    Berntorp, Kerstin
    Puhkala, Jatta
    Luoto, Riitta
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Holmäng, Agneta
    Pregnancy to postpartum transition of serum metabolites in women with gestational diabetes2017Ingår i: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 72, s. 27-36Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context: Gestational diabetes is commonly linked to development of type 2 diabetes mellitus (T2DM). There is a need to characterize metabolic changes associated with gestational diabetes in order to find novel biomarkers for T2DM. Objective: To find potential pathophysiological mechanisms and markers for progression from gestational diabetes mellitus to T2DM by studying the metabolic transition from pregnancy to postpartum. Design: The metabolic transition profile from pregnancy to postpartum was characterized in 56 women by mass spectrometry-based metabolomics; 11 women had gestational diabetes mellitus, 24 had normal glucose tolerance, and 21 were normoglycaemic but at increased risk for gestational diabetes mellitus. Fasting serum samples collected during trimester 3 (gestational week 32 +/- 0.6) and postpartum (10.5 +/- 0.4 months) were compared in diagnosis-specific multivariate models (orthogonal partial least squares analysis). Clinical measurements (e.g., insulin, glucose, lipid levels) were compared and models of insulin sensitivity and resistance were calculated for the same time period. Results: Women with gestational diabetes had significantly increased postpartum levels of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine, and their circulating lipids did not return to normal levels after pregnancy. The increase in BCAAs occurred postpartum since the BCAAs did not differ during pregnancy, as compared to normoglycemic women. Conclusions: Postpartum levels of specific BCAAs, notably valine, are related to gestational diabetes during pregnancy.

  • 330.
    Chorell, Elin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Norrlands University Hospital, Umeå University, Umeå, Sweden .
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Larsson, Christel
    Department of Food and Nutrition and Sport Science, University of Gothenburg, Gothenburg, Sweden.
    Sandberg, Susanne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mellberg, Caroline
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindahl, Bernt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Plasma metabolomic response to postmenopausal weight loss induced by different diets2016Ingår i: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 12, nr 5, artikel-id 85Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Menopause is associated with increased abdominal fat and increased risk of developing diabetes and cardiovascular disease. Objectives The present study evaluated the plasma metabolic response in relation to insulin sensitivity after weight loss via diet intervention. Methods This work includes two studies; i) Ten women on a 5 weeks Paleolithic-type diet (PD, 30 energy percent (E%) protein, 40 E% fat, 30 E% carbohydrates), ii) 55 women on 6 months of either PD or Nordic Nutrition Recommendations diet (NNR, 15 E% protein, 30 E% fat, and 55 E% carbohydrates). Plasma metabolic profiles were acquired at baseline and post diet using gas chromatography time-of-flight/mass spectrometry and investigated in relation to insulin sensitivity using multivariate bioinformatics. Results Both the PD and NNR diet resulted in significant weight loss, reduced waist circumference, improved serum lipid profiles, and improved insulin sensitivity. We detected a baseline metabolic profile that correlated significantly with insulin sensitivity, and of which components increased significantly in the PD group compared to NNR. Specifically, a significant increase in myo-inositol (MI), a second messenger of insulin action, and beta-hydroxybutyric acid (beta-HB)increased while dihomogamma-linoleic acid (DGLA) decreased in PD compared to NNR, which correlated with improved insulin sensitivity. We also detected a significant decrease in tyrosine and tryptophan, potential markers of insulin resistance when elevated in the circulation, with the PD but not the NNR. Conclusions Using metabolomics, we detected changes in the plasma metabolite profiles associated with weight loss in postmenopausal women by different diets. The metabolic profiles following 6 months of PD were linked to beneficial effects on insulin sensitivity compared to NNR.

  • 331.
    Chorell, Elin
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Rydberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Larsson, Christel
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    A metabolomic evaluation of short and long term effects of different macronutrient intake in overweight and obese postmenopausal womenManuskript (preprint) (Övrigt vetenskapligt)
  • 332.
    Chorell, Elin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Videhult, Frida Karlsson
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    West, Christina E
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Impact of probiotic feeding during weaning on the serum lipid profile and plasma metabolome in infants2013Ingår i: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 110, nr 1, s. 116-126Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The gut microbiome interacts with the host in the metabolic response to diet, and early microbial aberrancies may be linked to the development of obesity and metabolic disorders later in life. Probiotics have been proposed to affect metabolic programming and blood lipid levels, although studies are lacking in infants. Here, we report on the lipid profile and global metabolic response following daily feeding of probiotics during weaning. A total of 179 healthy, term infants were randomised to daily intake of cereals with (n 89) or without (n 90) the addition of Lactobacillus paracasei ssp. paracasei F19 (LF19) 108 colony-forming units per serving from 4 to 13 months of age. Weight, length and skinfold thickness were monitored. Venous blood was drawn at 5·5 and 13 months of age for analysis of the serum lipid profile. In a subsample, randomly selected from each group, GC-time-of-flight/MS was used to metabolically characterise plasma samples from thirty-seven infants. A combination of multi- and univariate analysis was applied to reveal differences related to LF19 treatment based on 228 putative metabolites, of which ninety-nine were identified or classified. We observed no effects of probiotic feeding on anthropometrics or the serum lipid profile. However, we detected significantly lower levels of palmitoleic acid (16 : 1) (P < 0·05) and significantly higher levels of putrescine (P < 0·01) in LF19-treated infants. Palmitoleic acid is a major MUFA strongly linked to visceral obesity, while putrescine is a polyamine with importance for gut integrity. Whether the observed differences will have long-term health consequences are being followed.

  • 333.
    Chorell, Erik
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Chorell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Efficient Synthesis of 2-Substituted Phthalimides from Phthalic Acids in One Step2013Ingår i: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, Vol. 2013, nr 33, s. 7512-7516Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Efficient procedures for synthesizing 2-substituted phthalimide (isoindole-1,3-dione) analogues starting from phthalic acids have been developed by using experimental design. The phthalimide central fragment frequently appears in biologically active compounds, materials, catalysts, and fluorescent probes, and therefore the development of general, fast, and convenient synthetic methods to this scaffold under neutral, acidic, and basic conditions would be attractive. After an initial screening, the use of acetonitrile, acetic acid, or pyridine in combination with microwave heating proved most promising. Experimental design was applied to these conditions to optimize the time, temperature, and concentration. This strategy has successfully generated synthetic methods that have been used to synthesize a series of phthalimides from phthalic acids and various amines or anilines in excellent yields. The developed methods have proven to be general, fast, convenient, and economic, and thus are expected to have broad utility to efficiently construct novel compounds for future biological and chemical applications.

  • 334. Christensson, Eva
    et al.
    Franklin, Karl A.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Sahlin, Carin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Palm, Andreas
    Ulfberg, Jan
    Eriksson, Lars I.
    Lindberg, Eva
    Hagel, Eva
    Fagerlund, Malin Jonsson
    Can STOP-Bang and Pulse Oximetry Detect and Exclude Obstructive Sleep Apnea?2018Ingår i: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 127, nr 3, s. 736-743Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Obstructive sleep apnea (OSA) is related to postoperative complications and is a common disorder. Most patients with sleep apnea are, however, undiagnosed, and there is a need for simple screening tools. We aimed to investigate whether STOP-Bang and oxygen desaturation index can identify subjects with OSA.

    METHODS: In this prospective, observational multicenter trial, 449 adult patients referred to a sleep clinic for evaluation of OSA were investigated with ambulatory polygraphy, including pulse oximetry and the STOP-Bang questionnaire in 4 Swedish centers. The STOP-Bang score is the sum of 8 positive answers to Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index >35 kg/m2, Age >50 years, Neck circumference >40 cm, and male Gender.

    RESULTS: The optimal STOP-Bang cutoff score was 6 for moderate and severe sleep apnea, defined as apnea-hypopnea index (AHI) ≥15, and the sensitivity and specificity for this score were 63% (95% CI, 0.55–0.70) and 69% (95% CI, 0.64–0.75), respectively. A STOP-Bang score of <2 had a probability of 95% (95% CI, 0.92–0.98) to exclude an AHI >15 and a STOP-Bang score of ≥6 had a specificity of 91% (95% CI, 0.87–0.94) for an AHI >15. The items contributing most to the STOP-Bang were the Bang items. There was a positive correlation between AHI versus STOP-Bang and between AHI versus oxygen desaturation index, Spearman ρ 0.50 (95% CI, 0.43–0.58) and 0.96 (95% CI, 0.94–0.97), respectively.

    CONCLUSIONS: STOP-Bang and pulse oximetry can be used to screen for sleep apnea. A STOP-Bang score of <2 almost excludes moderate and severe OSA, whereas nearly all the patients with a STOP-Bang score ≥6 have OSA. We suggest the addition of nightly pulse oximetry in patients with a STOP-Bang score of 2–5 when there is a need for screening for sleep apnea (ie, before surgery).

  • 335. Chroinin, Danielle Ni
    et al.
    Asplund, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Asberg, Signild
    Callaly, Elizabeth
    Cuadrado-Godia, Elisa
    Diez-Tejedor, Exuperio
    Di Napoli, Mario
    Engelter, Stefan T.
    Furie, Karen L.
    Giannopoulos, Sotirios
    Gotto, Antonio M., Jr.
    Hannon, Niamh
    Jonsson, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Kapral, Moira K.
    Marti-Fabregas, Joan
    Martinez-Sanchez, Patricia
    Milionis, Haralampos J.
    Montaner, Joan
    Muscari, Antonio
    Pikija, Slaven
    Probstfield, Jeffrey
    Rost, Natalia S.
    Thrift, Amanda G.
    Vemmos, Konstantinos
    Kelly, Peter J.
    Statin Therapy and Outcome After Ischemic Stroke: Systematic Review and Meta-Analysis of Observational Studies and Randomized Trials2013Ingår i: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 44, nr 2, s. 448-456Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Background and Purpose-Although experimental data suggest that statin therapy may improve neurological outcome after acute cerebral ischemia, the results from clinical studies are conflicting. We performed a systematic review and meta-analysis investigating the relationship between statin therapy and outcome after ischemic stroke. Methods-The primary analysis investigated statin therapy at stroke onset (prestroke statin use) and good functional outcome (modified Rankin score 0 to 2) and death. Secondary analyses included the following: (1) acute poststroke statin therapy (<= 72 hours after stroke), and (2) thrombolysis-treated patients. Results-The primary analysis included 113 148 subjects (27 studies). Among observational studies, statin treatment at stroke onset was associated with good functional outcome at 90 days (pooled odds ratio [OR], 1.41; 95% confidence interval [CI], 1.29-1.56; P<0.001), but not 1 year (OR, 1.12; 95% CI, 0.9-1.4; P=0.31), and with reduced fatality at 90 days (pooled OR, 0.71; 95% CI, 0.62-0.82; P<0.001) and 1 year (OR, 0.80;95% CI, 0.67-0.95; P=0.01). In the single randomized controlled trial reporting 90-day functional outcome, statin treatment was associated with good outcome (OR, 1.5; 95% CI, 1.0-2.24; P=0.05). No reduction in fatality was observed on meta-analysis of data from 3 randomized controlled trials (P=0.9). In studies restricted to of thrombolysis-treated patients, an association between statins and increased fatality at 90 days was observed (pooled OR, 1.25; 95% CI, 1.02-1.52; P=0.03, 3 studies, 4339 patients). However, this association was no longer present after adjusting for age and stroke severity in the largest study (adjusted OR, 1.14; 95% CI, 0.90-1.44; 4012 patients). Conclusion-In the largest meta-analysis to date, statin therapy at stroke onset was associated with improved outcome, a finding not observed in studies restricted to thrombolysis-treated patients. Randomized trials of statin therapy in acute ischemic stroke are needed.

  • 336. Chung, R
    et al.
    Sutton, R
    Henein, Michael Y
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Beyond dyssynchrony in cardiac resynchronisation therapy.2008Ingår i: Heart (British Cardiac Society), ISSN 1468-201X, Vol. 94, nr 8, s. 991-4Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cardiac resynchronisation therapy (CRT) in the form of biventricular pacing has emerged as a therapeutic option for patients with refractory heart failure. Patient selection and optimisation for CRT is based on the measurement of electromechanical ventricular dyssynchrony by electrocardiogram and echocardiographic techniques. The final common pathway for raising cardiac output on exertion is to minimise isovolumic time and maximise useful diastolic filling time, but correction of dyssynchrony alone may not lead to global improvement in about one-third of patients. Insights into pressure relations and abnormal timing, as well as clinical management, may hold the key to optimum outcome.

  • 337. Chung, Robin
    et al.
    Zidan, Mamdouh
    Henein, Michael Y
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    One stop cardiac investigation 'CT or echocardiography': beyond ejection fraction.2008Ingår i: The international journal of cardiovascular imaging, ISSN 1569-5794, Vol. 24, nr 3, s. 327-9Artikel i tidskrift (Refereegranskat)
  • 338. Cicala, Silvana
    et al.
    de Simone, Giovanni
    Wachtell, Kristian
    Gerdts, Eva
    Boman, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nieminen, Markku S
    Dahlöf, Björn
    Devereux, Richard B
    Clinical impact of 'in-treatment' wall motion abnormalities in hypertensive patients with left ventricular hypertrophy: the LIFE study2008Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 26, nr 4, s. 806-812Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: Left ventricular systolic wall motion abnormalities have prognostic value. Whether wall motion detected by serial echocardiographic examinations predicts prognosis in hypertensive patients with left ventricular hypertrophy (LVH) without clinically recognized atherosclerotic disease has, however, never been investigated. We examined whether 'in-treatment' wall motion abnormalities predicted outcome in the Losartan Intervention For Endpoint (LIFE) reduction in hypertension echocardiographic substudy.

    METHODS: We studied 749 patients without coronary artery disease, myocardial infarction (MI), or stroke history. Echocardiographic segmental wall motion abnormalities at baseline and annual re-evaluations ('as time-varying covariate') were examined in relation to endpoints (cardiovascular mortality, MI, stroke, and hospitalized heart failure). Adjusted Cox regression was used to analyze the primary composite endpoint of cardiovascular death, MI, or stroke and, separately, for fatal and nonfatal MI and hospitalized heart failure.

    RESULTS: During a mean follow-up of 4.8 years, an event was recorded in 67 (9%) patients. In Cox models after adjusting for age, gender, treatment, blood pressure lowering, and serial change of left ventricular mass index, 'in-treatment' segmental wall motion abnormalities were associated with subsequent composite endpoint [hazard ratio = 2.1, 95% confidence interval (CI) 1.1-3.8; P = 0.019] and MI [hazard ratio = 3.7 (1.5-8.9); P = 0.004].

    CONCLUSION: In hypertensive patients with LVH and no history of cardiovascular disease, 'in-treatment' left ventricular wall motion abnormalities are associated with increased likelihood of subsequent cardiovascular events independent of age, gender, blood pressure lowering, treatment modality, and in-treatment left ventricular mass index.

  • 339. Cicala, Silvana
    et al.
    Devereux, Richard B
    de Simone, Giovanni
    Wachtell, Kristian
    Gerdts, Eva
    Boman, Kurt
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Nieminen, Markku S
    Papademetriou, Vasilios
    Dahlöf, Björn
    Okin, Peter M
    Electrocardiographic and echocardiographic detection of myocardial infarction in patients with left-ventricular hypertrophy. The LIFE Study.2007Ingår i: Am J Hypertens, ISSN 0895-7061, Vol. 20, nr 7, s. 771-6Artikel i tidskrift (Refereegranskat)
  • 340.
    Claesson, Maria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Birgander, Lisbeth Slunga
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Jansson, Jan-Håkan
    Lindahl, B
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Burell, G
    Asplund, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mattsson, Cecilia
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Cognitive-behavioural stress management does not improve biological cardiovascular risk indicators in women with ischaemic heart disease: a randomized-controlled trial.2006Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 260, nr 4, s. 320-331Artikel i tidskrift (Refereegranskat)
  • 341.
    Claesson, Maria
    et al.
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Burell, Gunilla
    Slunga Birgander, Lisbeth
    Lindahl, Bernt
    Asplund, Kjell
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Psychosocial distress and impaired quality of life - targets neglected in the secondary prevention in women with ischaemic heart disease2003Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 10, nr 4, s. 258-266Artikel i tidskrift (Refereegranskat)
  • 342. Clough, Rachel E
    et al.
    Vallely, Michael P
    Henein, Michael Y
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Pepper, John R
    Levitronix ventricular assist device as a bridge-to-recovery for post-cardiotomy cardiogenic shock.2009Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 134, nr 3, s. 408-409Artikel i tidskrift (Refereegranskat)
  • 343. Coelho, T
    et al.
    Maia, L
    Martins da Silva, A
    Waddington Cruz, M
    Plante-Bordeneuve, V
    Suhr, Ole B
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Conceicao, I
    Schmidt, H
    Trigo, P
    Packman, J
    Harnett, M
    Grogan, DR
    Long-term effects of tafamidis: a new therapeutic option for patients with transthyretin familial amyloid polyneuropathy (ttr-fap)2012Ingår i: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 56, nr Suppl 2, s. S543-S543Artikel i tidskrift (Övrigt vetenskapligt)
  • 344. Coelho, T.
    et al.
    Suhr, Ole
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Conceicao, I
    Waddington-Cruz, M.
    Schmidt, H.
    Buades, J.
    Campistol, J.
    Pouget, J.
    Berk, J.
    Falzone, R.
    White, L.
    Bettencourt, B.
    Cehelsky, J.
    Nochur, S.
    Vaishnaw, A.
    Gollob, J.
    Adams, D.
    Phase 2 open-label extension study (ole) of patisiran, an investigational sIRNA investigational agent for familial amyloid polyneuropathy (fap)2015Ingår i: Journal of the peripheral nervous system, ISSN 1085-9489, E-ISSN 1529-8027, Vol. 20, nr 2, s. 117-118Artikel i tidskrift (Övrigt vetenskapligt)
  • 345. Coelho, Teresa
    et al.
    Adams, David
    Silva, Ana
    Lozeron, Pierre
    Hawkins, Philip N
    Mant, Timothy
    Perez, Javier
    Chiesa, Joseph
    Warrington, Steve
    Tranter, Elizabeth
    Munisamy, Malathy
    Falzone, Rick
    Harrop, Jamie
    Cehelsky, Jeffrey
    Bettencourt, Brian R
    Geissler, Mary
    Butler, James S
    Sehgal, Alfica
    Meyers, Rachel E
    Chen, Qingmin
    Borland, Todd
    Hutabarat, Renta M
    Clausen, Valerie A
    Alvarez, Rene
    Fitzgerald, Kevin
    Gamba-Vitalo, Christina
    Nochur, Saraswathy V
    Vaishnaw, Akshay K
    Sah, Dinah W Y
    Gollob, Jared A
    Suhr, Ole B
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Safety and efficacy of RNAi therapy for transthyretin amyloidosis2013Ingår i: The New England journal of medicine, ISSN 1533-4406, Vol. 369, nr 9, s. 819-29Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Transthyretin amyloidosis is caused by the deposition of hepatocyte-derived transthyretin amyloid in peripheral nerves and the heart. A therapeutic approach mediated by RNA interference (RNAi) could reduce the production of transthyretin. METHODS: We identified a potent antitransthyretin small interfering RNA, which was encapsulated in two distinct first- and second-generation formulations of lipid nanoparticles, generating ALN-TTR01 and ALN-TTR02, respectively. Each formulation was studied in a single-dose, placebo-controlled phase 1 trial to assess safety and effect on transthyretin levels. We first evaluated ALN-TTR01 (at doses of 0.01 to 1.0 mg per kilogram of body weight) in 32 patients with transthyretin amyloidosis and then evaluated ALN-TTR02 (at doses of 0.01 to 0.5 mg per kilogram) in 17 healthy volunteers. RESULTS: Rapid, dose-dependent, and durable lowering of transthyretin levels was observed in the two trials. At a dose of 1.0 mg per kilogram, ALN-TTR01 suppressed transthyretin, with a mean reduction at day 7 of 38%, as compared with placebo (P=0.01); levels of mutant and nonmutant forms of transthyretin were lowered to a similar extent. For ALN-TTR02, the mean reductions in transthyretin levels at doses of 0.15 to 0.3 mg per kilogram ranged from 82.3 to 86.8%, with reductions of 56.6 to 67.1% at 28 days (P<0.001 for all comparisons). These reductions were shown to be RNAi-mediated. Mild-to-moderate infusion-related reactions occurred in 20.8% and 7.7% of participants receiving ALN-TTR01 and ALN-TTR02, respectively. CONCLUSIONS: ALN-TTR01 and ALN-TTR02 suppressed the production of both mutant and nonmutant forms of transthyretin, establishing proof of concept for RNAi therapy targeting messenger RNA transcribed from a disease-causing gene. (Funded by Alnylam Pharmaceuticals; ClinicalTrials.gov numbers, NCT01148953 and NCT01559077.).

  • 346. Coelho, Teresa
    et al.
    Ericzon, Bo-Göran
    Falk, Rodney
    Grogan, Donna
    Ikeda, Shu-ichi
    Maurer, Mathew
    Planté-Bordeneuve, Violaine
    Suhr, Ole B
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Trigo, Pedro
    A Physician's Guide to Transthyretin Amyloidosis2008Rapport (Övrigt vetenskapligt)
  • 347. Coelho, Teresa
    et al.
    Maia, Luis F.
    da Silva, Ana Martins
    Cruz, Marcia Waddington
    Plante-Bordeneuve, Violaine
    Lozeron, Pierre
    Suhr, Ole B.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Campistol, Josep M.
    Conceicao, Isabel Maria
    Schmidt, Hartmut H. -J.
    Trigo, Pedro
    Kelly, Jeffery W.
    Labaudinie, Richard
    Chan, Jason
    Packman, Jeff
    Wilson, Amy
    Grogan, Donna R.
    Tafamidis for transthyretin familial amyloid polyneuropathy: A randomized, controlled trial2012Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 79, nr 8, s. 785-792Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: To evaluate the efficacy and safety of 18 months of tafamidis treatment in patients with early-stage V30M transthyretin familial amyloid polyneuropathy (TTR-FAP). Methods: In this randomized, double-blind trial, patients received tafamidis 20 mg QD or placebo. Coprimary endpoints were the Neuropathy Impairment Score-Lower Limbs (NIS-LL) responder analysis (<2-point worsening) and treatment-group difference in the mean change from baseline in Norfolk Quality of Life-Diabetic Neuropathy total score (TQOL) in the intent-to-treat (ITT) population (n = 125). These endpoints were also evaluated in the efficacy-evaluable (EE; n = 87) population. Secondary endpoints, including changes in neurologic function, nutritional status, and TTR stabilization, were analyzed in the ITT population. Results: There was a higher-than-anticipated liver transplantation dropout rate. No differences were observed between the tafamidis and placebo groups for the coprimary endpoints, NIS-LL responder analysis (45.3% vs 29.5% responders; p = 0.068) and change in TQOL (2.0 vs 7.2; p = 0.116) in the ITT population. In the EE population, significantly more tafamidis patients than placebo patients were NIS-LL responders (60.0% vs 38.1%; p = 0.041), and tafamidis patients had better-preserved TQOL (0.1 vs 8.9; p = 0.045). Significant differences in most secondary endpoints favored tafamidis. TTR was stabilized in 98% of tafamidis and 0% of placebo patients (p < 0.0001). Adverse events were similar between groups. Conclusions: Although the coprimary endpoints were not met in the ITT population, tafamidis was associated with no trend toward more NIS-LL responders and a significant reduction in worsening of most neurologic variables, supporting the hypothesis that preventing TTR dissociation can delay peripheral neurologic impairment. Classification of evidence: This study provides Class II evidence that 20 mg tafamidis QD was associated with no difference in clinical progression in patients with TTR-FAP, as measured by the NIS-LL and the Norfolk QOL-DN score. Secondary outcomes demonstrated a significant delay in peripheral neurologic impairment with tafamidis, which was well tolerated over 18 months. Neurology (R) 2012;79:785-792

  • 348. Coelho, Teresa
    et al.
    Maia, Luis F
    da Silva, Ana Martins
    Cruz, Márcia W
    Planté-Bordeneuve, Violaine
    Suhr, Ole B
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Conceiçao, Isabel
    Schmidt, Hartmut H-J
    Trigo, Pedro
    Kelly, Jeffery W
    Labaudinière, Richard
    Chan, Jason
    Packman, Jeff
    Grogan, Donna R
    Long-term effects of tafamidis for the treatment of transthyretin familial amyloid polyneuropathy2013Ingår i: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 260, nr 11, s. 2802-2814Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Tafamidis, a transthyretin (TTR) kinetic stabilizer, delayed neuropathic progression in patients with Val30Met TTR familial amyloid polyneuropathy (TTR-FAP) in an 18-month randomized controlled trial (study Fx-005). This 12-month, open-label extension study evaluated the long-term safety, tolerability, and efficacy of tafamidis 20 mg once daily in 86 patients who earlier received blinded treatment with tafamidis or placebo. Efficacy measures included the Neuropathy Impairment Score in the Lower Limbs (NIS-LL), Norfolk Quality of Life-Diabetic Neuropathy total quality of life (TQOL) score, and changes in neurologic function and nutritional status. We quantified the monthly rates of change in efficacy measures, and TTR stabilization, and monitored adverse events (AEs). Patients who continued on tafamidis had stable rates of change in NIS-LL (from 0.08 to 0.11/month; p = 0.60) and TQOL (from -0.03 to 0.25; p = 0.16). In patients switched from placebo, the monthly rate of change in NIS-LL declined (from 0.34 to 0.16/month; p = 0.01), as did TQOL score (from 0.61 to -0.16; p < 0.001). Patients treated with tafamidis for 30 months had 55.9 % greater preservation of neurologic function as measured by the NIS-LL than patients in whom tafamidis was initiated later. Plasma TTR was stabilized in 94.1 % of patients treated with tafamidis for 30 months. AEs were similar between groups; no patients discontinued because of an AE. Long-term tafamidis was well tolerated, with the reduced rate of neurologic deterioration sustained over 30 months. Tafamidis also slowed neurologic impairment in patients previously given placebo, but treatment benefits were greater when tafamidis was begun earlier.

  • 349. Coelho, Teresa
    et al.
    Maurer, Mathew S.
    Suhr, Ole B.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    THAOS - The Transthyretin Amyloidosis Outcomes Survey: initial report on clinical manifestations in patients with hereditary and wild-type transthyretin amyloidosis2013Ingår i: Current Medical Research and Opinion, ISSN 0300-7995, E-ISSN 1473-4877, Vol. 29, nr 1, s. 63-76Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Transthyretin (TTR) amyloidosis is a rare, life-threatening, systemic, autosomal dominant condition occurring in adults, with two main forms: hereditary (associated with TTR gene mutations) and wild-type. Studies indicate considerable heterogeneity in disease presentation, with predominantly polyneuropathic, predominantly cardiac, or mixed phenotypes. Methods: THAOS - the Transthyretin Amyloidosis Outcomes Survey - is the first global, multicenter, longitudinal, observational survey that collects data on the natural history of TTR amyloidosis (ClinicalTrials.gov: NCT00628745). This paper presents data on signs and symptoms, neurological and cardiac assessments, biomarkers and quality of life in the patients enrolled in THAOS from its inception in December 2007 to September 2011. Results: At the time of this analysis, data were available from 611 symptomatic patients with hereditary TTR amyloidosis, 67 symptomatic patients with wild-type TTR amyloidosis, and 274 currently asymptomatic individuals with a TTR mutation. Nineteen countries were participating in the registry. The largest patient groups came from Portugal (n = 453), the USA (n = 129), Italy (n = 70), and Japan (n = 68). Predominant symptom presentation in patients with hereditary TTR amyloidosis differed according to the underlying disease-causing mutation (polyneuropathy for Val30Met, cardiomyopathy for Val122Ile and Leu111Met, and mixed for Glu89Gln). However, each mutation was associated with clear multisystem involvement. Similarly, although cardiomyopathy was predominant in patients with wild-type TTR amyloidosis, many also showed symptoms consistent with neuropathy. Quality of life in patients with hereditary TTR amyloidosis, but not asymptomatic carriers of disease-causing mutations, was severely impaired relative to that of the age-matched general US population. Conclusions: This preliminary analysis highlights the considerable phenotypic heterogeneity for neurological and cardiac manifestations in patients with hereditary and wild-type TTR amyloidosis and the necessity of providing multidisciplinary care. THAOS registry data will help better characterize the diverse presentation and course of TTR amyloidosis worldwide and aid in improving and standardizing diagnosis and treatment.

  • 350. Cohen, Gerald
    et al.
    Glorieux, Griet
    Thornalley, Paul
    Schepers, Eva
    Meert, Natalie
    Jankowski, Joachim
    Jankowski, Vera
    Argiles, Angel
    Anderstam, Björn
    Brunet, Philippe
    Cerini, Claire
    Dou, Laetitia
    Deppisch, Reinhold
    Marescau, Bart
    Massy, Ziad
    Perna, Alessandra
    Raupachova, Jana
    Rodriguez, Mariano
    Stegmayr, Bernd
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Vanholder, Raymond
    Hörl, Walter H
    Review on uraemic toxins III: recommendations for handling uraemic retention solutes in vitro towards a standardized approach for research on uraemia.2007Ingår i: Nephrol Dial Transplant, ISSN 0931-0509, Vol. 27Artikel i tidskrift (Refereegranskat)
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