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- Hjalmarsson, Clara, 1969, et al.
(författare)
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Impact of age and comorbidity on risk stratification in idiopathic pulmonary arterial hypertension
- 2018
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 51:5
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Tidskriftsartikel (refereegranskat)abstract
- Recent reports from worldwide pulmonary hypertension registries show a new demographic picture for patients with idiopathic pulmonary arterial hypertension (IPAH), with an increasing prevalence among the elderly. We aimed to investigate the effects of age and comorbidity on risk stratification and outcome of patients with incident IPAH. The study population (n=264) was categorised into four age groups: 18-45, 46-64, 65-74 and 75 years. Individual risk profiles were determined according to a risk assessment instrument, based on the European Society of Cardiology and the European Respiratory Society guidelines. The change in risk group from baseline to follow-up (median 5 months) and survival were compared across age groups. In the two youngest age groups, a significant number of patients improved (18-45 years, Z= −4.613, p<0.001; 46-64 years, Z= −2.125, p=0.034), but no significant improvement was found in the older patient groups. 5-year survival was highest in patients aged 18-45 years (88%), while the survival rates were 63%, 56% and 36% for patients in the groups 46-64, 65-74 and 75 years, respectively (p<0.001). Ischaemic heart disease and kidney dysfunction independently predicted survival. These findings highlight the importance of age and specific comorbidities as prognostic markers of outcome in addition to established risk assessment algorithms.
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| 7. |
- Hult, L., et al.
(författare)
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Post systolic shortening by speckle tracking echocardiography as a predictor for cardiovascular events in patients with type 2 diabetes
- 2022
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 43, s. 923-923
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Tidskriftsartikel (refereegranskat)abstract
- Background: Post systolic shortening (PSS), measured by speckle tracking echocardiography has emerged as a novel method to evaluate left ventricular function and has been linked to adverse outcomes. Purpose: Our aim was to assess if the presence of pathological PSS had prognostic value in the prediction of major cardiovascular events in a cohort of patients with type-II diabetes (T2D). Method: Three-hundred-and-sixty-four patients with T2D in the CARDIPP study (Cardiovascular Risk factors in Patients with Diabetes – a Prospective study in Primary care) underwent echocardiography between 2005 and 2009. All patients were evaluated with strain analysis by speckle tracking. PSS was defined as any myocardial contraction occurring after aortic valve closure (Figure 1). Pathological PSS was defined as a post systolic index (PSI) >5% where PSI was calculated as: (peak global longitudinal strain – peak systolic longitudinal strain) / (peak global longitudinal strain) x 100. The composite endpoint of any major cardiovascular event (MACE) was defined as the diagnosis of or death in heart failure, myocardial infarction, or stroke. Cox proportional hazard ratios (HR) with 95% confidence intervals were calculated and were adjusted for sex, age, body mass index, hypertension, smoking, previous cardiovascular events and HbA1c. Results: Mean follow-up time was 11.2±2.3 years. Patients with pathological PSS had an increased unadjusted risk of MACE, (HR 3.73, 95% CI 2.06–6.76), which persisted after adjustment (HR 2.20, 95% CI 1.11–4.37) as compared to subjects without pathological PSS. When adding PSS to a risk prediction model including Global Longitudinal Strain (GLS), the adjusted HR (95% CI) for MACE was 2.94 (1.33–6.52) for subjects with reduced GLS (lower limit of normal −16%) and PSI >5%, compared to those with normal GLS and PSI ≤5%. Adverse events were more common in subjects with the combination of pathological PSS and GLS (Figure 2). Conclusions: Our results suggest that PSS may provide important additional prognostic information in patients with T2D.
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| 9. |
- Kylhammar, D., et al.
(författare)
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Angiogenic and inflammatory biomarkers for screening and follow-up in patients with pulmonary arterial hypertension
- 2018
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 47:4, s. 319-324
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To identify circulating angiogenic and inflammatory biomarkers with potential in screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc), and in early diagnosis and determination of treatment response in PAH. Method: Plasma samples were taken at the time of PAH diagnosis and at treatment follow-up after a median (interquartile range) of 4 months (3–9.8 months) in idiopathic (n = 9) and SSc-associated PAH (n = 11). In patients with SSc-associated PAH, plasma samples had also been gathered a median of 2 years (0.8–3 years) before PAH diagnosis (n = 10). Additional plasma samples were retrieved at two time-points separated by a median of 12 years (10–13 years) from SSc patients who did not develop PAH (n = 10) and from controls (n = 8). Angiogenic and inflammatory biomarkers were analysed by multiplex immunoassays. Results: Plasma levels of placenta growth factor (PlGF), soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), and tumour necrosis factor-α (TNF-α) were higher (p < 0.05) in SSc patients who later developed PAH than in those who did not. Plasma vascular endothelial growth factor (VEGF)-D increased (p < 0.05) in SSc patients as PAH developed. Plasma levels of PlGF, VEGF-A, VEGF-D, sVEGFR-1, interleukin-6, and TNF-α were higher (p < 0.05) in PAH than controls. There were no significant differences in circulating biomarkers between idiopathic and SSc-associated PAH. Plasma sVEGFR-1 decreased (p < 0.05) after initiating PAH-targeted treatments. Conclusions: Plasma levels of PlGF, sVEGFR-1, TNF-α, and VEGF-D have potential in screening for SSc-associated PAH. Plasma sVEGFR-1 may be a biomarker of treatment response.
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| 10. |
- Kylhammar, D., et al.
(författare)
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Global longitudinal strain and mechanical dispersion in the general population aged 50-64 years - results from the echocardiography study of the Swedish CArdioPulmonary bioImage Study (SCAPIS)
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 40:1, s. 1859-1859
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe Swedish CArdioPulmonary bioImage Study (SCAPIS) was initiated to improve understanding of underlying mechanisms in order to prevent cardiovascular and pulmonary disease. 30 000 individuals aged 50–64 years, randomly selected from the general population, were included in the study. Six-thousand-eight-hundred of the individuals underwent transthoracic echocardiography.Global longitudinal strain (GLS) and mechanical dispersion (MD) are novel echocardiographic measures of left ventricular (LV) systolic function and electrical instability reflecting risk for malignant arrhythmia, respectively. Previous studies suggest that the limit of normal for GLS is −16% and that MD >70 ms may be associated with increased risk for malignant arrhythmias. GLS and MD have, however, not before been investigated in a large population-based study.PurposeThe purpose of this first project within the SCAPIS echocardiography study is to determine the prevalence of impaired GLS and MD in the general population aged 50–64 years.MethodsGLS and MD, defined as mean peak longitudinal strain of the 18 LV segments and standard deviation of time-to-peak strain for the 18 LV segments, respectively, were analysed using a commercially available software. For group comparisons, the independent-samples t-test, the Mann-Whitney U-test or One Way Analysis of Variance with the Bonferroni post hoc test were performed. Values are mean±standard deviation.Results1850 examinations have so far been reviewed, whereof image quality was considered adequate for strain analysis in 1480 individuals (80%). Image quality, assessed as the number of visually assessable LV segments, was better for the second half of the examinations, as compared to the first half (p<0.001). Of the 1480 individuals where GLS and MD were assessed, 51% were women and mean age was 57±4.4 years with no difference in age between the sexes (p=ns). Mean GLS was −20±2% and men had significantly more negative (p<0.001) GLS values than women (−21±2% vs. −19±2%). There was no significant difference (p=ns) in GLS when comparing individuals aged 50–54, 55–59 or 60–64 years, respectively. GLS values were less negative than −16% in 1.9% of the study population. Mean MD was 41±12 ms with no significant difference (p=ns) between the sexes. MD was significantly lower (p<0.001) among individuals aged 50–54 years, as compared to those aged 55–59 or 60–64 years, respectively. MD was >70 ms in 1.6% of the study population.ConclusionsThese preliminary data from the SCAPIS echocardiography study suggest that, in the general population aged 50–64 years, 1.9% have impaired GLS and 1.6% have increased MD, which is possibly associated with a higher risk for malignant arrhythmias. Men had more negative GLS values than women and MD was lower in the lowest age tertile. Further analyses are ongoing.Acknowledgement/FundingThe Swedish Heart and Lung Foundation. Grants from Linkoping University. ALF-grants from the Swedish government (LIO-700841).
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| 12. |
- Kylhammar, D., et al.
(författare)
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The principal pathways involved in the in vivo modulation of hypoxic pulmonary vasoconstriction, pulmonary arterial remodelling and pulmonary hypertension
- 2017
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1716 .- 1748-1708. ; 219:4, s. 728-756
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Forskningsöversikt (refereegranskat)abstract
- Hypoxic pulmonary vasoconstriction (HPV) serves to optimize ventilation-perfusion matching in focal hypoxia and thereby enhances pulmonary gas exchange. During global hypoxia, however, HPV induces general pulmonary vasoconstriction, which may lead to pulmonary hypertension (PH), impaired exercise capacity, right-heart failure and pulmonary oedema at high altitude. In chronic hypoxia, generalized HPV together with hypoxic pulmonary arterial remodelling, contribute to the development of PH. The present article reviews the principal pathways in the in vivo modulation of HPV, hypoxic pulmonary arterial remodelling and PH with primary focus on the endothelin-1, nitric oxide, cyclooxygenase and adenine nucleotide pathways. In summary, endothelin-1 and thromboxane A2 may enhance, whereas nitric oxide and prostacyclin may moderate, HPV as well as hypoxic pulmonary arterial remodelling and PH. The production of prostacyclin seems to be coupled primarily to cyclooxygenase-1 in acute hypoxia, but to cyclooxygenase-2 in chronic hypoxia. The potential role of adenine nucleotides in modulating HPV is unclear, but warrants further study. Additional modulators of the pulmonary vascular responses to hypoxia may include angiotensin II, histamine, serotonin/5-hydroxytryptamine, leukotrienes and epoxyeicosatrienoic acids. Drugs targeting these pathways may reduce acute and/or chronic hypoxic PH. Endothelin receptor antagonists and phosphodiesterase-5 inhibitors may additionally improve exercise capacity in hypoxia. Importantly, the modulation of the pulmonary vascular responses to hypoxia varies between species and individuals, with hypoxic duration and age. The review also define how drugs targeting the endothelin-1, nitric oxide, cyclooxygenase and adenine nucleotide pathways may improve pulmonary haemodynamics, but also impair pulmonary gas exchange by interference with HPV in chronic lung diseases.
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| 13. |
- Marcus, Gustaf, 1987-
(författare)
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Paria : Brottslingen och normaliseringen av människan i Strindbergs, Hanssons och Geijerstams författarskap
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Den här studien handlar om gestaltningar av brottslingar och den större kulturella frågan om normaliseringen av människan sedd genom tre svenska författarskap från sekelskiftet 1900: August Strindberg, Ola Hansson och Gustaf af Geijerstam. Frågan om brottslingens identitet blev aktuell vid den här tiden. Den studerades inom nya, prestigefulla vetenskapliga fält som använde sig av uppmärksammade fotografiska tekniker och statistiska metoder för att övervaka och kartlägga både det yttre stadsrummet och det inre rummet i själen. I de skönlitterära texterna framträder brottslingen som en central tematik som aktualiserar föreställningar om avvikelse, förfall och degeneration. Men brottslingen är en komplex figur som på en och samma gång betraktades som en avvikande individ som behöver normaliseras och som en överlägsen individ som ger uttryck för sin egen frihet och individualitet.De första kapitlen handlar om Strindbergs konfrontation med kriminalantropologin och framför allt sekelskiftets fotografiska gestaltningar av abnormitet. Det visar sig att Strindberg både använder sig av och tar avstånd från dessa moderna tekniker för att gestalta det avvikande. I de följande kapitlen spåras samma ambivalens i förhållande till vetenskapens kartläggande av det avvikande i Hanssons och Geijerstams författarskap. Först studeras Hanssons noveller från Sensitiva amorosa till den ofullbordade Tidens män. Hanssons sätt att förhålla sig till den abnorma individen går från intim identifikation till våldsamt avståndstagande, samtidigt som han tydligare börjar identifierar sig med projektet att normalisera människan. I de sista kapitlen studeras hur Geijerstams skönlitterära texter både utgör en förlängning av och en kritisk kommentar till hans egna socialvetenskapliga undersökningar av det avvikande hemmet i den moderna staden.Konfrontationen med det avvikande i de skönlitterära texterna kännetecknas av ambivalens på flera nivåer: i seendet (i diskussionerna av de samtida formerna av övervakning), i de typer av vetande som behövs för att säga sanningen om människan och i betraktarens identitet (det konstnärliga geniet gentemot vetenskapsmannen). I skärningspunkten mellan normaliseringen och idealiseringen av det avvikande uppträder den problematiska individualiteten. Individualiteten framträder paradoxalt både som normaliseringens mål och som utgångspunkten för en kritik mot normaliseringen. Den här ambivalenta processen, kallad ett ”normalitetsspel”, som utspelar sig i texterna studeras i sin tur med hjälp av Foucaults begrepp ”governmentalitet” som ett pågående formande av frihet och individualitet.
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| 14. |
- Sandqvist, Anna, et al.
(författare)
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Plasma l-arginine levels distinguish pulmonary arterial hypertension from left ventricular systolic dysfunction
- 2018
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Ingår i: Heart and Vessels. - : Springer. - 0910-8327 .- 1615-2573. ; 33:3, s. 255-263
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary arterial hypertension (PAH) is a life-threatening condition, characterized by an imbalance of vasoactive substances and remodeling of pulmonary vasculature. Nitric oxide, formed from l-arginine, is essential for homeostasis and smooth muscle cell relaxation in PAH. Our aim was to compare plasma concentrations of l-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) in PAH compared to left ventricular systolic dysfunction (LVSD) and healthy subjects. This was an observational, multicenter study comparing 21 patients with PAH to 14 patients with LVSD and 27 healthy subjects. Physical examinations were obtained and blood samples were collected. Plasma levels of ADMA, SDMA, l-arginine, l-ornithine, and l-citrulline were analyzed using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Plasma levels of ADMA and SDMA were higher, whereas l-arginine and l-arginine/ADMA ratio were lower in PAH patients compared to healthy subjects (p < 0.001). Patients with PAH also had lower levels of l-arginine than patients with LVSD (p < 0.05). l-Arginine correlated to 6 min walking distance (6MWD) (r s = 0.58, p = 0.006) and l-arginine/ADMA correlated to WHO functional class (r s = −0.46, p = 0.043) in PAH. In conclusion, l-arginine levels were significantly lower in treatment naïve PAH patients compared to patients with LVSD. Furthermore, l-arginine correlated with 6MWD in PAH. l-arginine may provide useful information in differentiating PAH from LVSD.
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