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  • 1. Aavik, Einari
    et al.
    Lumivuori, Henri
    Leppänen, Olli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Wirth, Thomas
    Hakkinen, Sanna-Kaisa
    Braesen, Jan-Hinrich
    Beschorner, Ulrich
    Zeller, Thomas
    Braspenning, Maarten
    van Criekinge, Wim
    Makinen, Kimmo
    Yla-Herttuala, Seppo
    Global DNA methylation analysis of human atherosclerotic plaques reveals extensive genomic hypomethylation and reactivation at imprinted locus 14q32 involving induction of a miRNA cluster2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no 16, p. 993-U23Article in journal (Refereed)
    Abstract [en]

    Aims Genetics can explain just above 10% of the observed heritability in cardiovascular diseases. Epigenetics is about to provide some further explanations, but the information needed for that is in the accumulation phase. Genome-wide DNA methylation analysis has revealed thousands of genes, which are epigenetically differentially regulated in atherosclerotic plaques. Our results point to an additional level of complexity that needs to be integrated into the aetiology of atherogenesis.We conducted a genome-wide analysis to identify differentially methylated genes in atherosclerotic lesions. Methods DNA methylation at promoters, exons and introns was identified by massive parallel sequencing. Gene expression was analysed by microarrays, qPCR, immunohistochemistry and western blots. Results Globally, hypomethylation of chromosomal DNA predominates in atherosclerotic plaques and two-thirds of genes showing over 2.5-fold differential in DNA methylation are up-regulated in comparison to healthy mammary arteries. The imprinted chromatin locus 14q32 was identified for the first time as an extensively hypomethylated area in atherosclerosis with highly induced expression of miR127, -136, -410, -431, -432, -433 and capillary formation-associated gene RTL1. The top 100 list of hypomethylated promoters exhibited over 1000-fold enrichment for miRNAs, many of which mapped to locus 14q32. Unexpectedly, also gene body hypermethylation was found to correlate with stimulated mRNA expression. Conclusion Significant changes in genomic methylation were identified in atherosclerotic lesions. The most prominent gene cluster activated via hypomethylation was detected at imprinted chromosomal locus 14q32 with several clustered miRNAs that were up-regulated. These results suggest that epigenetic changes are involved in atherogenesis and may offer new potential therapeutic targets for vascular diseases.

  • 2.
    Abbassi, Fariba
    et al.
    Univ Hosp Zurich, Dept Surg & Transplantat, Zurich, Switzerland..
    Gero, Daniel
    Univ Hosp Zurich, Dept Surg & Transplantat, Zurich, Switzerland..
    Muller, Xavier
    Croix Rousse Hosp, Dept Gen Abdominal & Transplant Surg, Lyon, France..
    Bueno, Alba
    Kings Coll Hosp London, Inst Liver Studies, London, England..
    Figiel, Wojciech
    Med Univ Warsaw, Dept Gen Transplant & Liver Surg, Warsaw, Poland..
    Robin, Fabien
    Univ Hosp Rennes, Dept HPB Surg & Transplantat, Rennes, France..
    Laroche, Sophie
    Hop Paul Brousse, Hepatobiliary Ctr, Dept Surg & Transplantat, Villejuif, France..
    Picard, Benjamin
    Hop Beaujon, APHP Nord, DMU PARABOL, Dept Anesthesiol Crit Care & Perioperat Med, Clichy, Nord, France..
    Shankar, Sadhana
    Leeds Teaching Hosp trust, Dept Abdominal Transplant & Hepatobiliary Surg, Leeds, W Yorkshire, England..
    Ivanics, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Univ Toronto, Univ Hlth Network, Multiorgan Transplant Program, Toronto, ON, Canada.;Henry Ford Hosp, Dept Surg, Detroit, MI USA..
    van Reeven, Marjolein
    Univ Med Ctr Rotterdam, Erasmus MC Transplant Inst, Dept Surg, Div HPB & Transplant Surg, Rotterdam, Netherlands..
    van Leeuwen, Otto B.
    Univ Groningen, Univ Med Ctr Groningen, Div HPB Surg & Liver Transplantat, Groningen, Netherlands..
    Braun, Hillary J.
    Univ Calif San Francisco, Div Transplant Surg, San Francisco, CA USA..
    Monbaliu, Diethard
    Univ Hosp Leuven, Dept Abdominal Transplant Surg & Transplant Coord, Leuven, Belgium..
    Breton, Antoine
    Croix Rousse Hosp, Dept Gen Abdominal & Transplant Surg, Lyon, France..
    Vachharajani, Neeta
    Washington Univ, St Louis Sch Med, Div Abdominal Transplantat, Dept Surg, St Louis, MO USA..
    Bonaccorsi Riani, Eliano
    Univ Hosp St Luc, Dept Abdominal & Transplant Surg, Brussels, Belgium..
    Nowak, Greg
    Karolinska Univ, Hosp Huddinge, Dept Transplantat Surg, Stockholm, Sweden..
    McMillan, Robert R.
    Houston Methodist Hosp, Weill Cornell Med Ctr, Houston, TX USA..
    Abu-Gazala, Samir
    Hosp Univ Penn, Penn Transplant Inst, Dept Surg, Philadelphia, PA USA..
    Nair, Amit
    Univ Rochester, Div Transplantat & Hepatobiliary Surg, Rochester, MN USA..
    Bruballa, Rocio
    Hosp Italiano Buenos Aires, HPB & Liver Transplant Unit, Buenos Aires, Argentina..
    Paterno, Flavio
    Univ Hosp, Rutgers New Jersey Med Sch, Div Liver Transplant, Newark, NJ USA..
    Weppler Sears, Deborah
    Cleveland Clin Florida, Dept Abdominal & Transplant Surg, Weston, FL USA..
    Pinna, Antonio D.
    Cleveland Clin Florida, Dept Abdominal & Transplant Surg, Weston, FL USA..
    Guarrera, James V.
    Univ Hosp, Rutgers New Jersey Med Sch, Div Liver Transplant, Newark, NJ USA..
    de Santibanes, Eduardo
    Hosp Italiano Buenos Aires, HPB & Liver Transplant Unit, Buenos Aires, Argentina..
    de Santibanes, Martin
    Hosp Italiano Buenos Aires, HPB & Liver Transplant Unit, Buenos Aires, Argentina..
    Hernandez-Alejandro, Roberto
    Univ Rochester, Div Transplantat & Hepatobiliary Surg, Rochester, MN USA..
    Olthoff, Kim
    Hosp Univ Penn, Penn Transplant Inst, Dept Surg, Philadelphia, PA USA..
    Ghobrial, R. Mark
    Houston Methodist Hosp, Weill Cornell Med Ctr, Houston, TX USA..
    Ericzon, Bo-Goran
    Karolinska Univ, Hosp Huddinge, Dept Transplantat Surg, Stockholm, Sweden..
    Ciccarelli, Olga
    Univ Hosp St Luc, Dept Abdominal & Transplant Surg, Brussels, Belgium..
    Chapman, William C.
    Washington Univ, St Louis Sch Med, Div Abdominal Transplantat, Dept Surg, St Louis, MO USA..
    Mabrut, Jean-Yves
    Croix Rousse Hosp, Dept Gen Abdominal & Transplant Surg, Lyon, France..
    Pirenne, Jacques
    Univ Hosp Leuven, Dept Abdominal Transplant Surg & Transplant Coord, Leuven, Belgium..
    Mullhaupt, Beat
    Univ Hosp Zurich, Dept Gastroenterol & Hepatol, Zurich, Switzerland..
    Ascher, Nancy L.
    Univ Calif San Francisco, Div Transplant Surg, San Francisco, CA USA..
    Porte, Robert J.
    Univ Groningen, Univ Med Ctr Groningen, Div HPB Surg & Liver Transplantat, Groningen, Netherlands..
    de Meijer, Vincent E.
    Univ Groningen, Univ Med Ctr Groningen, Div HPB Surg & Liver Transplantat, Groningen, Netherlands..
    Polak, Wojciech G.
    Univ Med Ctr Rotterdam, Erasmus MC Transplant Inst, Dept Surg, Div HPB & Transplant Surg, Rotterdam, Netherlands..
    Sapisochin, Gonzalo
    Univ Toronto, Univ Hlth Network, Multiorgan Transplant Program, Toronto, ON, Canada..
    Attia, Magdy
    Leeds Teaching Hosp trust, Dept Abdominal Transplant & Hepatobiliary Surg, Leeds, W Yorkshire, England..
    Soubrane, Olivier
    Hop Beaujon, APHP Nord, DMU DIGEST, Dept HPB Surg & Liver Transplantat, Clichy, France..
    Weiss, Emmanuel
    Hop Beaujon, APHP Nord, DMU PARABOL, Dept Anesthesiol Crit Care & Perioperat Med, Clichy, Nord, France..
    Adam, Rene A.
    Hop Paul Brousse, Hepatobiliary Ctr, Dept Surg & Transplantat, Villejuif, France..
    Cherqui, Daniel
    Hop Paul Brousse, Hepatobiliary Ctr, Dept Surg & Transplantat, Villejuif, France..
    Boudjema, Karim
    Univ Hosp Rennes, Dept HPB Surg & Transplantat, Rennes, France..
    Zieniewicz, Krzysztof
    Med Univ Warsaw, Dept Gen Transplant & Liver Surg, Warsaw, Poland..
    Jassem, Wayel
    Kings Coll Hosp London, Inst Liver Studies, London, England..
    Dutkowski, Philipp
    Univ Hosp Zurich, Dept Surg & Transplantat, Zurich, Switzerland..
    Clavien, Pierre-Alain
    Univ Hosp Zurich, Dept Surg & Transplantat, Zurich, Switzerland..
    Novel Benchmark Values for Redo Liver Transplantation Does the Outcome Justify the Effort?2022In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 276, no 5, p. 860-867Article in journal (Refereed)
    Abstract [en]

    Objective: To define benchmark cutoffs for redo liver transplantation (redo-LT). Background: In the era of organ shortage, redo-LT is frequently discussed in terms of expected poor outcome and wasteful resources. However, there is a lack of benchmark data to reliably evaluate outcomes after redo-LT. Methods: We collected data on redo-LT between January 2010 and December 2018 from 22 high-volume transplant centers. Benchmark cases were defined as recipients with model of end stage liver disease (MELD) score <= 25, absence of portal vein thrombosis, no mechanical ventilation at the time of surgery, receiving a graft from a donor after brain death. Also, high-urgent priority and early redo-LT including those for primary nonfunction (PNF) or hepatic artery thrombosis were excluded. Benchmark cutoffs were derived from the 75th percentile of the medians of all benchmark centers. Results: Of 1110 redo-LT, 373 (34%) cases qualified as benchmark cases. Among these cases, the rate of postoperative complications until discharge was 76%, and increased up to 87% at 1-year, respectively. One-year overall survival rate was excellent with 90%. Benchmark cutoffs included Comprehensive Complication Index CCI (R) at 1-year of <= 72, and in-hospital and 1-year mortality rates of <= 13% and <= 15%, respectively. In contrast, patients who received a redo-LT for PNF showed worse outcomes with some values dramatically outside the redoLT benchmarks. Conclusion: This study shows that redo-LT achieves good outcome when looking at benchmark scenarios. However, this figure changes in high-risk redo-LT, as for example in PNF. This analysis objectifies for the first-time results and efforts for redo-LT and can serve as a basis for discussion about the use of scarce resources.

  • 3. Abbott, A. L.
    et al.
    Adelman, M. A.
    Alexandrov, A. V.
    Barnett, H. J. M.
    Beard, J.
    Bell, P.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Blacker, D.
    Buckley, C. J.
    Cambria, R. P.
    Comerota, A. J.
    Connolly, E. S., Jr.
    Davies, A. H.
    Eckstein, H. H.
    Faruqi, R.
    Fraedrich, G.
    Gloviczki, P.
    Hankey, G. J.
    Harbaugh, R. E.
    Heldenberg, E.
    Kittner, S. J.
    Kleinig, T. J.
    Mikhailidis, D. P.
    Moore, W. S.
    Naylor, R.
    Nicolaides, A.
    Paraskevas, K. I.
    Pelz, D. M.
    Prichard, J. W.
    Purdie, G.
    Ricco, J. B.
    Riles, T.
    Rothwell, P.
    Sandercock, P.
    Sillesen, H.
    Spence, J. D.
    Spinelli, F.
    Tan, A.
    Thapar, A.
    Veith, F. J.
    Zhou, W.
    Why the United States Center for Medicare and Medicaid Services (CMS) Should not Extend Reimbursement Indications for Carotid Artery Angioplasty/Stenting2012In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 43, no 3, p. 247-251Article in journal (Refereed)
  • 4. Abbott, Anne L.
    et al.
    Adelman, Mark A.
    Alexandrov, Andrei V.
    Barnett, Henry J. M.
    Beard, Jonathan
    Bell, Peter
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Blacker, David
    Buckley, Clifford J.
    Cambria, Richard P.
    Comerota, Anthony J.
    Connolly, E. Sander
    Davies, Alun H.
    Eckstein, Hans-Henning
    Faruqi, Rishad
    Fraedrich, Gustav
    Gloviczki, Peter
    Hankey, Graeme J.
    Harbaugh, Robert E.
    Heldenberg, Eitan
    Kittner, Steven J.
    Kleinig, Timothy J.
    Mikhailidis, Dimitri P.
    Moore, Wesley S.
    Naylor, Ross
    Nicolaides, Andrew
    Paraskevas, Kosmas I.
    Pelz, David M.
    Prichard, James W.
    Purdie, Grant
    Ricco, Jean-Baptiste
    Riles, Thomas
    Rothwell, Peter
    Sandercock, Peter
    Sillesen, Henrik
    Spence, J. David
    Spinelli, Francesco
    Tan, Aaron
    Thapar, Ankur
    Veith, Frank J.
    Zhou, Wei
    Why the United States Center for Medicare and Medicaid Services should not extend reimbursement indications for carotid artery angioplasty/stenting2012In: VASCULAR, ISSN 1708-5381, Vol. 20, no 1, p. 1-7Article in journal (Other academic)
  • 5. Abdelhalim, Mohamed A.
    et al.
    Tenorio, Emanuel R.
    Oderich, Gustavo S.
    Haulon, Stephan
    Warren, Gasper
    Adam, Donald
    Claridge, Martin
    Butt, Talha
    Abisi, Said
    Dias, Nuno V.
    Kölbel, Tilo
    Gallitto, Enrico
    Gargiulo, Mauro
    Gkoutzios, Panos
    Panuccio, Giuseppe
    Kuzniar, Marek
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Mees, Barend M.
    Schurink, Geert W.
    Sonesson, Björn
    Spath, Paolo
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Schanzer, Andres
    Beck, Adam W.
    Schneider, Darren B.
    Timaran, Carlos H.
    Eagleton, Matthew
    Farber, Mark A.
    Modarai, Bijan
    Multicenter trans-Atlantic experience with fenestrated-branched endovascular aortic repair of chronic post-dissection thoracoabdominal aortic aneurysms2023In: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809, Vol. 78, no 4, p. 854-862.e1Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: This multicenter international study aimed to describe outcomes of fenestrated-branched endovascular aortic repairs (FB-EVAR) in a cohort of patients treated for chronic post-dissection thoracoabdominal aortic aneurysms (PD-TAAAs).

    METHODS: We reviewed the clinical data of all consecutive patients treated by FB-EVAR for repair of extent I to III PD-TAAAs in 16 centers from the United States and Europe (2008-2021). Data were extracted from institutional prospectively maintained databases and electronic patient records. All patients received off-the-shelf or patient-specific manufactured fenestrated-branched stent grafts. Endpoints were any cause mortality and major adverse events at 30 days, technical success, target artery (TA) patency, freedom from TA instability, minor (endovascular with <12 Fr sheath) and major (open or ≥12 Fr sheath) secondary interventions, patient survival, and freedom from aortic-related mortality (ARM).

    RESULTS: A total of 246 patients (76% male; median age, 67 years [interquartile range, 61-73 years]) were treated for extent I (7%), extent II (55%), and extent III (35%) PD-TAAAs by FB-EVAR. The median aneurysm diameter was 65 mm (interquartile range, 59-73 mm). Eighteen patients (7%) were octogenarians, 212 (86%) were American Society of Anesthesiologists class ≥3, and 21 (9%) presented with contained ruptured or symptomatic aneurysms. There were 917 renal-mesenteric vessels targeted by 581 fenestrations (63%) and 336 directional branches (37%), with a mean of 3.7 vessels per patient. Technical success was 96%. Mortality and rate of major adverse events at 30 days was 3% and 28%, including disabling complications such as new onset dialysis in 1%, major stroke in 1%, and permanent paraplegia in 2%. Mean follow-up was 24 months. Kaplan-Meier (KM) estimated patient survival at 3 and 5 years was 79% ± 6% and 65% ± 10%. KM estimated freedom from ARM was 95% ± 3% and 93% ± 5% at the same intervals. Unplanned secondary interventions were needed in 94 patients (38%), including minor procedures in 64 (25%) and major procedures in 30 (12%). There was one conversion to open surgical repair (<1%). KM estimated freedom from any secondary intervention was 44% ± 9% at 5 years. KM estimated primary and secondary TA patency were 93% ± 2% and 96% ± 1% at 5 years, respectively.

    CONCLUSIONS: FB-EVAR for chronic PD-TAAAs was associated with high technical success and a low rate of mortality (3%) and disabling complications at 30 days. Although the procedure is effective in the prevention of ARM, patient survival was low at 5 years (65%), likely due to the significant comorbidities in this cohort of patients. Freedom from secondary interventions at 5 years was 44%, although most procedures were minor. The significant rate of reinterventions highlights the need for continued patient surveillance.

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  • 6. Aboyans, Victor
    et al.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Brodmann, Marianne
    Collet, Jean-Philippe
    Czerny, Martin
    De Carlo, Marco
    Naylor, A Ross
    Roffi, Marco
    Tendera, Michal
    Vlachopoulos, Charalambos
    Ricco, Jean-Baptiste
    Questions and answers on diagnosis and management of patients with Peripheral Arterial Diseases: a companion document of the 2017 ESC Guidelines for the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS)2018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 9, p. E35-E41Article in journal (Refereed)
  • 7. Aboyans, Victor
    et al.
    Ricco, Jean-Baptiste
    Bartelink, Marie-Louise E L
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Brodmann, Marianne
    Cohnert, Tina
    Collet, Jean-Philippe
    Czerny, Martin
    De Carlo, Marco
    Debus, Sebastian
    Espinola-Klein, Christine
    Kahan, Thomas
    Kownator, Serge
    Mazzolai, Lucia
    Naylor, A Ross
    Roffi, Marco
    Röther, Joachim
    Sprynger, Muriel
    Tendera, Michal
    Tepe, Gunnar
    Venermo, Maarit
    Vlachopoulos, Charalambos
    Desormais, Ileana
    2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries2018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 9, p. 763-816Article in journal (Refereed)
  • 8. Aboyans, Victor
    et al.
    Ricco, Jean-Baptiste
    Bartelink, Marie-Louise E L
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Brodmann, Marianne
    Cohnert, Tina
    Collet, Jean-Philippe
    Czerny, Martin
    De Carlo, Marco
    Debus, Sebastian
    Espinola-Klein, Christine
    Kahan, Thomas
    Kownator, Serge
    Mazzolai, Lucia
    Naylor, A Ross
    Roffi, Marco
    Röther, Joachim
    Sprynger, Muriel
    Tendera, Michal
    Tepe, Gunnar
    Venermo, Maarit
    Vlachopoulos, Charalambos
    Desormais, Ileana
    Widimsky, Petr
    Kolh, Philippe
    Agewall, Stefan
    Bueno, Héctor
    Coca, Antonio
    De Borst, Gert J
    Delgado, Victoria
    Dick, Florian
    Erol, Cetin
    Ferrini, Marc
    Kakkos, Stavros
    Katus, Hugo A
    Knuuti, Juhani
    Lindholt, Jes
    Mattle, Heinrich
    Pieniazek, Piotr
    Piepoli, Massimo Francesco
    Scheinert, Dierk
    Sievert, Horst
    Simpson, Iain
    Sulzenko, Jakub
    Tamargo, Juan
    Tokgozoglu, Lale
    Torbicki, Adam
    Tsakountakis, Nikolaos
    Tuñón, José
    de Ceniga, Melina Vega
    Windecker, Stephan
    Zamorano, Jose Luis
    2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS)2018In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 55, no 3, p. 305-368Article in journal (Refereed)
  • 9. Abtan, Jeremie
    et al.
    Bhatt, Deepak L
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Simon, Tabassome
    Fox, Kim
    Mehta, Shamir R
    Harrington, Robert A
    Gao, Qi
    Leiter, Lawrence A
    Steg, Ph Gabriel
    Incidence of Myocardial Infarction Types in Patients Treated With Ticagrelor in the THEMIS Trial2021In: Circulation. Cardiovascular Interventions, ISSN 1941-7640, E-ISSN 1941-7632, Vol. 14, no 12, article id 011035Article in journal (Refereed)
  • 10.
    Acosta, S.
    et al.
    Lund Univ, Dept Clin Sci, Vasc Ctr, Malmo, Sweden..
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Negative-pressure wound therapy for prevention and treatment of surgical-site infections after vascular surgery2017In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 104, no 2, p. E75-E84Article, review/survey (Refereed)
    Abstract [en]

    BackgroundIndications for negative-pressure wound therapy (NPWT) in vascular surgical patients are expanding. The aim of this review was to outline the evidence for NPWT on open and closed wounds. MethodsA PubMed, EMBASE and Cochrane Library search from 2007 to June 2016 was performed combining the medical subject headings terms wound infection', abdominal aortic aneurysm (AAA)', fasciotomy', vascular surgery' and NPWT' or VAC'. ResultsNPWT of open infected groin wounds was associated with shorter duration of wound healing by 47 days, and was more cost-effective than alginate dressings in one RCT. In one RCT and six observational studies, NPWT-related major bleeding and graft preservation rates were 0-10 and 83-100 per cent respectively. One retrospective comparative study showed greater wound size reduction per day, fewer dressing changes, quicker wound closure and shorter hospital stay with NPWT compared with gauze dressings for lower leg fasciotomy. NPWT and mesh-mediated fascial traction after AAA repair and open abdomen was associated with high primary fascial closure rates (96-100 per cent) and low risk of graft infection (0-7 per cent). One retrospective comparative study showed a significant reduction in surgical-site infection, from 30 per cent with standard wound care to 6 per cent with closed incisional NPWT. ConclusionNPWT has a central role in open and infected wounds after vascular surgery; the results of prophylactic care of closed incisions are promising.

  • 11.
    Acosta, S.
    et al.
    Lund Univ, Vasc Ctr, Dept Clin Sci, Malmo, Sweden..
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Temporary Abdominal Closure After Abdominal Aortic Aneurysm Repair: A Systematic Review of Contemporary Observational Studies2016In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 51, no 3, p. 371-378Article, review/survey (Refereed)
    Abstract [en]

    Objectives: The aim of this paper was to review the literature on temporary abdominal closure (TAC) after abdominal aortic aneurysm (AAA) repair. Methods: This was a systematic review of observational studies. A PubMed, EM BASE and Cochrane search from 2007 to July 2015 was performed combining the Medical Subject Headings "aortic aneurysm" and "temporary abdominal closure", "delayed abdominal closure", "open abdomen", "abdominal compartment syndrome", "negative pressure wound therapy", or "vacuum assisted wound closure". Results: Seven original studies were found. The methods used for TAC were the vacuum pack system with (n = 1) or without (n = 2) mesh bridge, vacuum assisted wound closure (VAWC; n = 1) and the VAWC with mesh mediated fascial traction (VACM; n = 3). The number of patients included varied from four to 30. Three studies were exclusively after open repair, one after endovascular aneurysm repair, and three were mixed series. The frequency of ruptured AAA varied from 60% to 100%. The primary fascia] closure rate varied from 79% to 100%. The median time to closure of the open abdomen was 10.5 and 17 days in two prospective studies with a fascia] closure rate of 100% and 96%, respectively; the inclusion criterion was an anticipated open abdomen therapy time >= 5 days using the VACM method. The graft infection rate was 0% in three studies. No patient with longterm open abdomen therapy with the VACM in the three studies was left with a planned ventral hernia. The in hospital survival rate varied from 46% to 80%. Conclusions: A high fascial closure rate without planned ventral hernia is possible to achieve with VACM, even after long-term open abdomen therapy. There are, however, few publications reporting specific results of open abdomen treatment after AAA repair, and there is a need for randomized controlled trials to determine the most efficient and safe TAC method during open abdomen treatment after AAA repair.

  • 12.
    Adam, Lina N.
    et al.
    Univ Zakho, Coll Sci, Dept Biol, Duhok, Kurdistan Regio, Iraq..
    Al-Habib, Omar A. M.
    Univ Nawroz, Coll Sci, Dept Biol, Duhok, Kurdistan Regio, Iraq..
    Oraha, Ashur Y.
    Univ Duhok, Coll Med, Dept Cardiothorac & Vasc Surg, Duhok, Kurdistan Regio, Iraq..
    Shekha, Mudhir S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Salahaddin Univ Erbil, Coll Sci, Dept Biol, Erbil, Kurdistan Regio, Iraq..
    Genetic and clinical study of myeloperoxidase's association with coronary artery disease2024In: EGYPTIAN HEART JOURNAL, ISSN 1110-2608, Vol. 76, no 1, article id 27Article in journal (Refereed)
    Abstract [en]

    BackgroundUnraveling myeloperoxidase's (MPO) correlation with coronary artery disease (CAD) and genetic variations, this study seeks to enhance diagnostic precision and therapeutic strategies.ResultsCAD patients were found to be older and more male than controls. Several clinical parameters, including glucose, total bilirubin, alkaline phosphatase, creatinine, and troponin levels, showed significant variations. Moreover, CAD patients had lower red cell distribution width (RDW%) and mean platelet volume (MPV) than controls. Serum MPO levels did not differ significantly between CAD patients and controls, and no correlation was found with other clinical parameters except for glucose, creatinine, and total bilirubin.ConclusionsThe data suggest that serum MPO levels are not substantially related to CAD patients, as indicated by lower MPO levels in CAD patients compared to controls. While highlighting the potential of MPV and RDW% as predictors of severe atherosclerosis in CAD. Further research is needed to validate the diagnostic and prognostic value of RDW%, MPV, and MPO levels in CAD.Trial registration: 15092021-9-12. Registered 15 September 2021.ConclusionsThe data suggest that serum MPO levels are not substantially related to CAD patients, as indicated by lower MPO levels in CAD patients compared to controls. While highlighting the potential of MPV and RDW% as predictors of severe atherosclerosis in CAD. Further research is needed to validate the diagnostic and prognostic value of RDW%, MPV, and MPO levels in CAD.Trial registration: 15092021-9-12. Registered 15 September 2021.

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  • 13.
    Adam, Lina N.
    et al.
    Univ Zakho, Fac Sci, Dept Biol, Duhok, Kurdistan, Iraq..
    Oraha, Ashur Y.
    Univ Duhok, Coll Med, Dept Cardiothorac & Vasc Surg, Duhok, Kurdistan, Iraq..
    Shekha, Mudhir S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Salahaddin Univ Erbil, Coll Sci, Dept Biol, Erbil, Kurdistan, Iraq..
    Al-Habib, Omar A. M.
    Univ Nawroz, Coll Sci, Dept Biol, Duhok, Kurdistan, Iraq..
    Exploring nitric oxide as a crucial prognostic biomarker of coronary artery disease2023In: Prostaglandins & other lipid mediators, ISSN 1098-8823, E-ISSN 2212-196X, Vol. 165, article id 106717Article in journal (Refereed)
    Abstract [en]

    Purpose: The study aimed to examine if the polymorphism of the endothelial nitric oxide synthase (eNOS) gene variable number of tandem repeats (VNTR) and the serum NO levels are associated with CAD.

    Materials/methods: Case-control study, 70 CAD and 30 control subjects were enrolled. The eNOS gene poly-morphism was measured by polymerase chain reaction-agarose gel electrophoresis and the serum NO was assessed by using an ELISA plate and reader covering 540 nm.

    Results: Uncovering the area under curve (AUC) for serum NO, which was (0.6821), indicating that NO seemed to be a critical prognostic biomarker of CAD; also, glucose, serum creatinine and total bilirubin proved to be sig-nificant predictors of CAD with AUC (0.6793, 0.6717 and 0.6662) respectively. Furthermore, higher serum NO levels were associated with the eNOS (ab) genotype. Revealing the intron (a) allele was protective against CAD. Moreover, diminished levels of serum NO in CAD groups compared to controls (P < 0.05). Additionally, Multiple logistic regression analysis shows a significantly high Odds ratio associated with CAD in the Duhok population.

    Conclusions: The eNOS (ab) variant seems to be a protective CAD factor for patients. Low serum NO levels are another risk factor for the advancement of CAD, suggesting their involvement in atherosclerosis. The (a) allele's protective effect is mediated through changes in eNOS promoter activity and higher NO levels.

  • 14.
    Adamski, Jan
    et al.
    Univ Warmia & Mazury, Fac Med Sci, Dept Anaesthesiol & Intens Care, Ul Warszawska 30, PL-10082 Olsztyn, Poland..
    Weigl, Wojciech
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Musialowicz, Tadeusz
    Kuopio Univ Hosp, Dept Anaesthesiol & Intens Care Med, Kuopio, Finland..
    Lahtinen, Pasi
    Cent Hosp South Ostrobothnia, Anaesthesiol & Intens Care Dept, Seinajoki, Finland..
    Reinikainen, Matti
    Kuopio Univ Hosp, Dept Anaesthesiol & Intens Care Med, Kuopio, Finland.;Univ Eastern Finland, Fac Hlth Sci, Sch Med, Inst Clin Med, Kuopio, Finland..
    Predictors of treatment limitations in Finnish intensive care units2022In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 66, no 4, p. 526-538Article in journal (Refereed)
    Abstract [en]

    Background Few studies have examined the factors that predict the limitations of life-sustaining treatment (LST) to patients in intensive care units (ICUs). We aimed to identify variables associated with the decision of withholding of life support (WHLS) at admission, WHLS during ICU stay and the withdrawal of ongoing life support (WDLS). Methods This retrospective observational study comprised 17,772 adult ICU patients who were included in the nationwide Finnish ICU Registry in 2016. Factors associated with LST limitations were identified using hierarchical logistic regression. Results The decision of WHLS at admission was made for 822 (4.6%) patients, WHLS during ICU stay for 949 (5.3%) patients, and WDLS for 669 (3.8%) patients. Factors strongly predicting WHLS at admission included old age (adjusted odds ratio [OR] for patients aged 90 years or older in reference to those younger than 40 years was 95.6; 95% confidence interval [CI], 47.2-193.5), dependence on help for activities of daily living (OR, 3.55; 95% CI, 3.01-4.2), and metastatic cancer (OR, 4.34; 95% CI, 3.16-5.95). A high severity of illness predicted later decisions to limit LST. Diagnoses strongly associated with WHLS at admission were cardiac arrest, hepatic failure and chronic obstructive pulmonary disease. Later decisions were strongly associated with cardiac arrest, hepatic failure, non-traumatic intracranial hemorrhage, head trauma and stroke. Conclusion Early decisions to limit LST were typically associated with old age and chronic poor health whereas later decisions were related to the severity of illness. Limitations are common for certain diagnoses, particularly cardiac arrest and hepatic failure.

  • 15.
    Agarwal, Anubha
    et al.
    Washington Univ St Louis, Sch Med, St Louis, MO 63110 USA..
    Tromp, Jasper
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Natl Univ Hlth Syst, Singapore, Singapore..
    Almahmeed, Wael
    Cleveland Clin, Heart & Vasc Inst, Abu Dhabi, U Arab Emirates..
    Angermann, Christiane
    Univ Hosp Wuerzburg, Comprehens Heart Failure Ctr, Wurzburg, Germany..
    Chandramouli, Chanchal
    Natl Heart Ctr Singapore, Singapore, Singapore.;Duke NUS Med Sch, Singapore, Singapore..
    Cho, Hyunjai
    Seoul Natl Univ Hosp, Seoul, South Korea..
    Choi, Don-Ju
    Seoul Natl Univ Hosp, Seoul, South Korea..
    Damasceno, Albertino
    Eduardo Mondlane Univ, Maputo, Mozambique..
    Filippatos, Gerasimos
    Univ Cyprus, Sch Med, Nicosia, Cyprus.;Natl & Kapodistrian Univ Athens, Attikon Univ Hosp, Sch Med, Dept Cardiol, Athens, Greece..
    Fonarow, Gregg C.
    Ronald Reagan UCLA Med Ctr, Radiol, Los Angeles, CA USA..
    Harikrishnan, Sivadasanpillai
    Sree Chitra Tirunal Inst Med Sci & Technol, Trivandrum, Kerala, India..
    Lund, Lars
    Karolinska Univ Hosp, Stockholm, Sweden..
    Masoudi, Fred
    Univ Colorado, Sch Med, Anschutz Med Campus, Aurora, CO 80045 USA..
    Mensah, George A.
    NHLBI, NIH, Ctr Translat Res & Implementat Sci, Bethesda, MD USA..
    Pathan, Asad
    Tabba Heart Inst, Karachi, Pakistan..
    Perel, Pablo
    London Sch Hyg & Trop Med, London, England..
    Pinto, Fausto
    Univ Lisbon, Santa Maria Univ Hosp, Lisbon, Portugal..
    Ribeiro, Antonio Luiz
    Unversidade Fed Minas Gerais, Hosp Clin, Belo Horizonte, Brazil.;Unversidade Fed Minas Gerais, Sch Med, Belo Horizonte, Brazil..
    Rich, Stuart
    Northwestern Univ, Feinberg Sch Med, Chicago, IL USA..
    Sakata, Yasuhiko
    Tohoku Univ, Grad Sch Med, Sendai, Japan.;Natl Cerebral & Cardiovasc Ctr, Cardiovasc Surg, Suita, Japan..
    Sliwa, Karen
    Univ Cape Town, Cape Town, South Africa..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Wong, Renee
    NHLBI, NIH, Div Cardiovasc Sci, Heart Failure & Arrhythmias Branch, Bethesda, MD USA..
    Yancy, Clyde
    Northwestern Univ, Feinberg Sch Med, Chicago, IL USA..
    Yiu, Kelvin
    Univ Hong Kong, Inst Cardiovasc Sci & Med, Hong Kong, Peoples R China.;Univ Hong Kong, Shenzhen Hosp, Dept Med, Hong Kong, Peoples R China..
    Zhang, Jian
    Chinese Acad Med Sci & Peking Union Med Coll, Beijing, Peoples R China..
    Zhang, Yuhui
    Chinese Acad Med Sci & Peking Union Med Coll, Beijing, Peoples R China..
    Lam, Carolyn S. P.
    Natl Heart Ctr, Singapore, Singapore.;Duke NUS Med Sch, Singapore, Singapore.;Univ Med Ctr Groningen, Groningen, Netherlands..
    Roth, Gregory A.
    Univ Washington, Seattle, DC USA.;Populat Hlth Bldg Hans Rosling Ctr, Inst Hlth Metr & Evaluat, 3980 15th Ave NE, Seattle, WA 98195 USA..
    Toward a Universal Definition of Etiologies in Heart Failure: Categorizing Causes and Advancing Registry Science2024In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 17, no 4, article id e011095Article, review/survey (Refereed)
    Abstract [en]

    Heart failure (HF) is a well-described final common pathway for a broad range of diseases however substantial confusion exists regarding how to describe, study, and track these underlying etiologic conditions. We describe (1) the overlap in HF etiologies, comorbidities, and case definitions as currently used in HF registries led or managed by members of the global HF roundtable; (2) strategies to improve the quality of evidence on etiologies and modifiable risk factors of HF in registries; and (3) opportunities to use clinical HF registries as a platform for public health surveillance, implementation research, and randomized registry trials to reduce the global burden of noncommunicable diseases. Investment and collaboration among countries to improve the quality of evidence in global HF registries could contribute to achieving global health targets to reduce noncommunicable diseases and overall improvements in population health.

  • 16. Ahl, Matilda
    et al.
    Avdic, Una
    Strandberg, Maria Compagno
    Chugh, Deepti
    Andersson, Emelie
    Hållmarker, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Department of Internal Medicine, Mora Hospital, Mora, Sweden.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Deierborg, Tomas
    Ekdahl, Christine T
    Physical Activity Reduces Epilepsy Incidence: a Retrospective Cohort Study in Swedish Cross-Country Skiers and an Experimental Study in Seizure-Prone Synapsin II Knockout Mice2019In: Sports medicine - open, ISSN 2199-1170, Vol. 5, no 1, article id 52Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Epilepsy patients commonly exercise less than the general population. Animal studies indicate beneficial effects of physical activity in established epilepsy, while its effect on the development is currently less known.

    METHODS: Here, we investigated the incidence of epilepsy during 20 years in a cohort of participants from the long-distance Swedish cross-country ski race Vasaloppet (n = 197,685) and compared it to the incidence of non-participating-matched controls included in the Swedish population register (n = 197,684). Individuals diagnosed with diseases such as stroke and epilepsy before entering the race were excluded from both groups. Experimentally, we also determined how physical activity could affect the development of epilepsy in epilepsy-prone synapsin II knockout mice (SynIIKO), with and without free access to a running wheel.

    RESULTS: We identified up to 40-50% lower incidence of epilepsy in the Vasaloppet participants of all ages before retirement. A lower incidence of epilepsy in Vasaloppet participants was seen regardless of gender, education and occupation level compared to controls. The participants included both elite and recreational skiers, and in a previous survey, they have reported a higher exercise rate than the general Swedish population. Sub-analyses revealed a significantly lower incidence of epilepsy in participants with a faster compared to slower finishing time. Dividing participants according to specified epilepsy diagnoses revealed 40-50% decrease in focal and unspecified epilepsy, respectively, but no differences in generalized epilepsy. Voluntary exercise in seizure-prone SynIIKO mice for 1 month before predicted epilepsy development decreased seizure manifestation from > 70 to 40%. Brain tissue analyses following 1 month of exercise showed increased hippocampal neurogenesis (DCX-positive cells), while microglial (Iba1) and astrocytic activation (GFAP), neuronal Map2, brain-derived neurotrophic factor and its receptor tyrosine receptor kinase B intensity were unaltered. Continued exercise for additionally 2 months after predicted seizure onset in SynIIKO mice resulted in a 5-fold reduction in seizure manifestation (from 90 to 20%), while 2 months of exercise initiated at the time of predicted seizure development gave no seizure relief, suggesting exercise-induced anti-epileptogenic rather than anti-convulsive effect.

    CONCLUSION: The clinical study and the experimental findings in mice indicate that physical activity may prevent or delay the development of epilepsy.

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  • 17. Ahmad, S.
    et al.
    Demler, O.
    Sun, Q.
    Moorthy, M.V.
    Li, C.
    Lee, I.M.
    Ridker, P.M.
    Manson, J.E.
    Hu, F.B.
    Fall, T.
    Chasman, D.I.
    Cheng, S.
    Pradhan, A.D.
    Mora, S.
    Mediterranean Diet And Reduced Risk Of Diabetes: Potential Mediating Mechanisms2019In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 287, p. e43-e44Article in journal (Other academic)
  • 18.
    Ahmad, Shafqat
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Harvard Med Sch, Brigham & Womens Hosp, Prevent Med Div, Boston, MA 02215 USA;Harvard Med Sch, Brigham & Womens Hosp, Ctr Lipid Metabol, 900 Commonwealth Ave, Boston, MA 02215 USA;Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA;Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Div, Boston, MA 02215 USA.
    Moorthy, M. Vinayaga
    Harvard Med Sch, Brigham & Womens Hosp, Prevent Med Div, Boston, MA 02215 USA;Harvard Med Sch, Brigham & Womens Hosp, Ctr Lipid Metabol, 900 Commonwealth Ave, Boston, MA 02215 USA.
    Demler, Olga, V
    Harvard Med Sch, Brigham & Womens Hosp, Prevent Med Div, Boston, MA 02215 USA;Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Div, Boston, MA 02215 USA.
    Hu, Frank B.
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02215 USA.
    Ridker, Paul M.
    Harvard Med Sch, Brigham & Womens Hosp, Prevent Med Div, Boston, MA 02215 USA;Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Div, Boston, MA 02215 USA.
    Chasman, Daniel, I
    Harvard Med Sch, Brigham & Womens Hosp, Prevent Med Div, Boston, MA 02215 USA.
    Mora, Samia
    Harvard Med Sch, Brigham & Womens Hosp, Prevent Med Div, Boston, MA 02215 USA;Harvard Med Sch, Brigham & Womens Hosp, Ctr Lipid Metabol, 900 Commonwealth Ave, Boston, MA 02215 USA;Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Div, Boston, MA 02215 USA.
    Assessment of Risk Factors and Biomarkers Associated With Risk of Cardiovascular Disease Among Women Consuming a Mediterranean Diet2018In: JAMA Network Open, E-ISSN 2574-3805, Vol. 1, no 8, article id e185708Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Higher Mediterranean diet (MED) intake has been associated with lower risk of cardiovascular disease (CVD), but limited data are available about the underlying molecular mechanisms of this inverse disease association in human populations.

    OBJECTIVE To better characterize the relative contribution of traditional and novel factors to the MED-related risk reduction in CVD events in a US population.

    DESIGN, SETTING, AND PARTICIPANTS Using a prospective cohort design, baseline MED intake was assessed in 25 994 initially healthy US women in theWomen's Health Study who were followed up to 12 years. Potential mediating effects of a panel of 40 biomarkers were evaluated, including lipids, lipoproteins, apolipoproteins, inflammation, glucose metabolism and insulin resistance, branched-chain amino acids, small-molecule metabolites, and clinical factors. Baseline study information and samples were collected between April 30, 1993, and January 24, 1996. Analyses were conducted between August 1, 2017, and October 30, 2018.

    EXPOSURES Intake of MED is a 9-category measure of adherence to a Mediterranean dietary pattern. Participants were categorized into 3 levels based on their adherence to the MED.

    MAIN OUTCOMES AND MEASURES Incident CVD confirmed through medical records and the proportion of CVD risk reduction explained by mediators.

    RESULTS Among 25 994women (mean [SD] age, 54.7 [7.1] years), those with low, middle, and upper MED intakes composed 39.0%, 36.2%, and 24.8% of the study population and experienced 428 (4.2%), 356 (3.8%), and 246 (3.8%) incident CVD events, respectively. Compared with the reference group who had low MED intake, CVD risk reductions were observed for the middle and upper groups, with respective HRs of 0.77 (95% CI, 0.67-0.90) and 0.72 (95% CI, 0.61-0.86) (P for trend < .001). The largest mediators of the CVD risk reduction of MED intake were biomarkers of inflammation (accounting for 29.2% of the MED-CVD association), glucose metabolism and insulin resistance (27.9%), and body mass index (27.3%), followed by blood pressure (26.6%), traditional lipids (26.0%), high-density lipoprotein measures (24.0%) or very low-density lipoprotein measures (20.8%), with lesser contributions from low-density lipoproteins (13.0%), branched-chain amino acids (13.6%), apolipoproteins (6.5%), or other small-molecule metabolites (5.8%).

    CONCLUSIONS AND RELEVANCE In this study, higher MED intake was associated with approximately one-fourth relative risk reduction in CVD events, which could be explained in part by known risk factors, both traditional and novel.

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  • 19.
    Ahmad, Shafqat
    et al.
    Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA;Preventive Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
    Mora, Samia
    Preventive Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA;Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA;Center for Lipid Metabolomics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
    Franks, Paul W
    Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA;Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Clinical Research Centre, Lund University, Skåne University Hospital, Malmö, Sweden;Department of Public Health and Clinical Medicine, Section for Medicine, Umeå University, Umeå, Sweden.
    Orho-Melander, Marju
    Diabetes and Cardiovascular Disease–Genetic Epidemiology, Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Ridker, Paul M
    Preventive Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA;Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
    Hu, Frank B
    Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA;Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
    Chasman, Daniel I
    Preventive Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
    Adiposity and Genetic Factors in Relation to Triglycerides and Triglyceride-Rich Lipoproteins in the Women's Genome Health Study2018In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 64, no 1, p. 231-241Article in journal (Refereed)
    Abstract [en]

    Background: Previous results from Scandinavian cohorts have shown that obesity accentuates the effects of common genetic susceptibility variants on increased triglycerides (TG). Whether such interactions are present in the US population and further selective for particular TG-rich lipoprotein subfractions is unknown.

    Methods: We examined these questions using body mass index (BMI) and waist circumference (WC) among women of European ancestry from the Women's Genome Health Study (WGHS) (n = 21840 for BMI; n = 19313 for WC). A weighted genetic risk score (TG-wGRS) based on 40 published TG-associated single-nucleotide polymorphisms was calculated using published effect estimates.

    Results: Comparing overweight (BMI ≥ 25 kg/m2) and normal weight (BMI < 25 kg/m2) WGHS women, each unit increase of TG-wGRS was associated with TG increases of 1.013% and 1.011%, respectively, and this differential association was significant (Pinteraction = 0.014). Metaanalyses combining results for WGHS BMI with the 4 Scandinavian cohorts (INTER99, HEALTH2006, GLACIER, MDC) (total n = 40026) yielded a more significant interaction (Pinteraction = 0.001). Similarly, we observed differential association of the TG-wGRS with TG (Pinteraction = 0.006) in strata of WC (<80 cm vs ≥80 cm). Metaanalysis with 2 additional cohorts reporting WC (INTER99 and HEALTH2006) (total n = 27834) was significant with consistent effects (Pinteraction = 0.006). We also observed highly significant interactions of the TG-wGRS across the strata of BMI with very large, medium, and small TG-rich lipoprotein subfractions measured by nuclear magnetic resonance spectroscopy (all Pinteractions < 0.0001). The differential effects were strongest for very large TG-rich lipoprotein.

    Conclusions: Our results support the original findings and suggest that obese individuals may be more susceptible to aggregated genetic risk associated with common TG-raising alleles, with effects accentuated in the large TG-rich lipoprotein subfraction.

  • 20.
    Ahmad, Shafqat
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA;Harvard Med Sch, Div Prevent Med, Boston, MA USA.
    Mora, Samia
    Harvard Med Sch, Div Prevent Med, Boston, MA USA;Harvard Med Sch, Cardiovasc Div, Boston, MA USA;Harvard Med Sch, Ctr Lipid Metabol, Boston, MA USA.
    Ridker, Paul M.
    Harvard Med Sch, Div Prevent Med, Boston, MA USA;Harvard Med Sch, Cardiovasc Div, Boston, MA USA;Harvard Med Sch, Ctr Lipid Metabol, Boston, MA USA.
    Hu, Frank B.
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA;Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Network Med, Boston, MA USA.
    Chasman, Daniel I.
    Harvard Med Sch, Div Prevent Med, Boston, MA USA.
    Gene-Based Elevated Triglycerides and Type 2 Diabetes Mellitus Risk in the Women's Genome Health Study2019In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 39, no 1, p. 97-106Article in journal (Refereed)
    Abstract [en]

    Objective- Higher triglyceride (TG) is a risk factor for incident type 2 diabetes mellitus (T2DM), but paradoxically, genetic susceptibility for higher TG has been associated with lower T2DM risk. There is also evidence that the genetic association may be modified by baseline TG. Whether such associations can be replicated and the interaction is selective for certain TG-rich lipoprotein particles remains to be explored.

    Approach and Results-Cox regression involving TG, TG-rich lipoprotein particles, and genetic determinants of TG was performed among 15 813 participants with baseline fasting status in the WGHS (Women's Genome Health Study), including 1453 T2DM incident cases during a mean 18.6 (SD= 5.3) years of follow-up. A weighted, 40-single-nucleotide polymorphism TG genetic risk score was inversely associated with incident T2DM (hazard ratio [95% CI], 0.66 [0.580.75]/ 10-TG risk alleles; P< 0.0001) with adjustment for baseline body mass index, HDL (high-density lipoprotein) cholesterol, and TG. TG-associated risk was higher among individuals in the low compared with the high 40-singlenucleotide polymorphism TG genetic risk score tertile (hazard ratio [95% CI], 1.98 [1.83-2.14] versus 1.68 [1.58-1.80] per mmol/L; P-interaction = 0.0007). In TG-adjusted analysis, large and medium but not small TG-rich lipoprotein particles were associated with higher T2DM incidence for successively lower 40-single-nucleotide polymorphism TG genetic risk score tertiles, P-interaction = 0.013, 0.012, and 0.620 across tertiles, respectively.

    Conclusions-Our results confirm the previous observations of the paradoxical associations of TG with T2DM while focusing attention on the larger TG-rich lipoprotein particle subfractions, suggesting their importance in clinical profiling of T2DM risk.

  • 21. Ahmed, Fozia Z.
    et al.
    Blomström-Lundqvist, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Bloom, Heather
    Cooper, Christopher
    Ellis, Christopher
    Goette, Andreas
    Greenspon, Arnold J.
    Love, Charles J.
    Johansen, Jens Brock
    Philippon, Francois
    Tarakji, Khaldoun G.
    Holbrook, Reece
    Sherfesee, Lou
    Xia, Ying
    Seshadri, Swathi
    Lexcen, Daniel R.
    Krahn, Andrew D.
    Use of healthcare claims to validate the Prevention of Arrhythmia Device Infection Trial cardiac implantable electronic device infection risk score2021In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 23, no 9, p. 1446-1455Article in journal (Refereed)
    Abstract [en]

    AIM: The Prevention of Arrhythmia Device Infection Trial (PADIT) infection risk score, developed based on a large prospectively collected data set, identified five independent predictors of cardiac implantable electronic device (CIED) infection. We performed an independent validation of the risk score in a data set extracted from U.S. healthcare claims.

    METHODS AND RESULTS: Retrospective identification of index CIED procedures among patients aged ≥18 years with at least one record of a CIED procedure between January 2011 and September 2014 in a U.S health claims database. PADIT risk factors and major CIED infections (with system removal, invasive procedure without system removal, or infection-attributable death) were identified through diagnosis and procedure codes. The data set was randomized by PADIT score into Data Set A (60%) and Data Set B (40%). A frailty model allowing multiple procedures per patient was fit using Data Set A, with PADIT score as the only predictor, excluding patients with prior CIED infection. A data set of 54 042 index procedures among 51 623 patients with 574 infections was extracted. Among patients with no history of prior CIED infection, a 1 unit increase in the PADIT score was associated with a relative 28% increase in infection risk. Prior CIED infection was associated with significant incremental predictive value (HR 5.66, P < 0.0001) after adjusting for PADIT score. A Harrell's C-statistic for the PADIT score and history of prior CIED infection was 0.76.

    CONCLUSION: The PADIT risk score predicts increased CIED infection risk, identifying higher risk patients that could potentially benefit from targeted interventions to reduce the risk of CIED infection. Prior CIED infection confers incremental predictive value to the PADIT score.

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  • 22.
    Ahmed, Hanna N.
    et al.
    Univ Wisconsin, Dept Med & Clin Oncol, Madison, WI USA..
    Levitan, Emily B.
    Beth Israel Deaconess Med Ctr, Cardiovasc Epidemiol Res Unit, Dept Med, Boston, MA 02215 USA.;Harvard Univ, Sch Med, Boston, MA USA..
    Wolk, Alicja
    Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol, S-10401 Stockholm, Sweden..
    Mittleman, Murray A.
    Beth Israel Deaconess Med Ctr, Cardiovasc Epidemiol Res Unit, Dept Med, Boston, MA 02215 USA.;Harvard Univ, Sch Med, Boston, MA USA.;Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA..
    Coffee consumption and risk of heart failure in men: An analysis from the Cohort of Swedish Men2009In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 158, no 4, p. 667-672Article in journal (Refereed)
    Abstract [en]

    Background A previous study found that consuming 5 or more cups of coffee per day was associated with increased incidence of heart failure (HF). We sought to evaluate this association in a larger population. Methods We measured coffee consumption using food frequency questionnaires among 37,315 men without history of myocardial infarction, diabetes, or HE They were observed for HF hospitalization or mortality from January 1, 1998, until December 3 1, 2006, using record linkage to the Swedish inpatient and cause of death registries. Cox proportional hazards models adjusted for age, dietary, and demographic factors were used to calculate incidence rate ratios (RR) and 95% confidence intervals (CIs). Results For 9 years of follow-up, 784 men experienced an HF event. Compared to men who drank! l cup of coffee per day (unadjusted rate 29.9 HF events/ 10,000 person-years), RR were 0.87 (95% CI 0.69-1.11, unadjusted rate 29.2/10,000 person-years) for 2 cups/d, 0.89 (95% CI 0.70-1.14, unadjusted rate 25.1/10,000 person-years) for 3 cups/d, 0.89 (95% CI 0.69-1.15, unadjusted rate 25.0/10,000 person-years) for 4 cups/d, and 0.89 (95% CI 0.69-1.15, unadjusted rate 18.1/10,000 person-years) for >= 5 cups/d (P for trend in RR = .61). Conclusions This study did not support the hypothesis that high coffee consumption is associated with increased rates of HF hospitalization or mortality. (Am Heart J 2009;158:667-72.)

  • 23.
    Ai, Sizhi
    et al.
    Chinese Univ Hong Kong, Fac Med, Sha Tin Dist,Dept Psychiat, Li Chiu Kong Family Sleep Assessment Unit, 33 A Kung Kok St, Hong Kong 000000, Peoples R China.;Guangdong Prov Peoples Hosp, Guangdong Acad Med Sci, Guangdong Mental Hlth Ctr, Yuexiu Dist, 123 Huifu West Rd, Guangzhou 510000, Peoples R China.;Xinxiang Med Univ, Heart Ctr, Dept Cardiol, Affiliated Hosp 1, 88 Jiankang Rd, Weihui 453100, Peoples R China..
    Zhang, Jihui
    Chinese Univ Hong Kong, Fac Med, Sha Tin Dist,Dept Psychiat, Li Chiu Kong Family Sleep Assessment Unit, 33 A Kung Kok St, Hong Kong 000000, Peoples R China.;Guangdong Prov Peoples Hosp, Guangdong Acad Med Sci, Guangdong Mental Hlth Ctr, Yuexiu Dist, 123 Huifu West Rd, Guangzhou 510000, Peoples R China.;Southern Med Univ, Sch Clin Med 2, 253 Ind Ave Middle, Guangzhou 510280, Peoples R China..
    Zhao, Guoan
    Xinxiang Med Univ, Heart Ctr, Dept Cardiol, Affiliated Hosp 1, 88 Jiankang Rd, Weihui 453100, Peoples R China..
    Wang, Ningjian
    Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Inst & Dept Endocrinol & Metab, Sch Med, 639 Mfg Bur Rd, Shanghai 200011, Peoples R China..
    Li, Guohua
    Xinxiang Med Univ, Heart Ctr, Dept Cardiol, Affiliated Hosp 1, 88 Jiankang Rd, Weihui 453100, Peoples R China..
    So, Hon-Cheong
    Chinese Univ Hong Kong, Fac Med,Sch Biomed Sci,Sha Tin Dist, Horse Mat Water,Cheung Res Ctr Management Parkins, Dept Psychiat,KIZ CUHK Joint Lab Bioresources & M, Da Xue Rd, Hong Kong 000000, Peoples R China..
    Liu, Yaping
    Chinese Univ Hong Kong, Fac Med, Sha Tin Dist,Dept Psychiat, Li Chiu Kong Family Sleep Assessment Unit, 33 A Kung Kok St, Hong Kong 000000, Peoples R China..
    Chau, Steven Wai-Ho
    Chinese Univ Hong Kong, Fac Med, Sha Tin Dist,Dept Psychiat, Li Chiu Kong Family Sleep Assessment Unit, 33 A Kung Kok St, Hong Kong 000000, Peoples R China..
    Chen, Jie
    Chinese Univ Hong Kong, Fac Med, Sha Tin Dist,Dept Psychiat, Li Chiu Kong Family Sleep Assessment Unit, 33 A Kung Kok St, Hong Kong 000000, Peoples R China..
    Tan, Xiao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Jia, Fujun
    Guangdong Prov Peoples Hosp, Guangdong Acad Med Sci, Guangdong Mental Hlth Ctr, Yuexiu Dist, 123 Huifu West Rd, Guangzhou 510000, Peoples R China..
    Tang, Xiangdong
    Sichuan Univ, State Key Lab Biotherapy,West China Hosp, Sleep Med Ctr,Mental Hlth Ctr, Translat Neurosci Ctr,Dept Resp & Crit Care Med, 37 Guoxue Alley, Chengdu 610041, Peoples R China..
    Shi, Jie
    Peking Univ, Peking Univ Hosp 6, Natl Inst Drug Dependence, 38 Xueyuan Rd, Beijing 100191, Peoples R China..
    Lu, Lin
    Peking Univ, Peking Univ Hosp 6, Natl Inst Drug Dependence, 38 Xueyuan Rd, Beijing 100191, Peoples R China..
    Wing, Yun-Kwok
    Chinese Univ Hong Kong, Fac Med, Sha Tin Dist,Dept Psychiat, Li Chiu Kong Family Sleep Assessment Unit, 33 A Kung Kok St, Hong Kong 000000, Peoples R China..
    Causal associations of short and long sleep durations with 12 cardiovascular diseases: linear and nonlinear Mendelian randomization analyses in UK Biobank2021In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 42, no 34, p. 3349-3357Article in journal (Refereed)
    Abstract [en]

    Aims Observational studies have suggested strong associations between sleep duration and many cardiovascular diseases (CVDs), but causal inferences have not been confirmed. We aimed to determine the causal associations between genetically predicted sleep duration and 12 CVDs using both linear and nonlinear Mendelian randomization (MR) designs. Methods and results Genetic variants associated with continuous, short (<= 6 h) and long (>= 9 h) sleep durations were used to examine the causal associations with 12 CVDs among 404 044 UK Biobank participants of White British ancestry. Linear MR analyses showed that genetically predicted sleep duration was negatively associated with arterial hypertension, atrial fibrillation, pulmonary embolism, and chronic ischaemic heart disease after correcting for multiple tests (P <0.001). Nonlinear MR analyses demonstrated nonlinearity (L-shaped associations) between genetically predicted sleep duration and four CVDs, including arterial hypertension, chronic ischaemic heart disease, coronary artery disease, and myocardial infarction. Complementary analyses provided confirmative evidence of the adverse effects of genetically predicted short sleep duration on the risks of 5 out of the 12 CVDs, including arterial hypertension, pulmonary embolism, coronary artery disease, myocardial infarction, and chronic ischaemic heart disease (P< 0.001), and suggestive evidence for atrial fibrillation (P < 0.05). However, genetically predicted long sleep duration was not associated with any CVD. Conclusion This study suggests that genetically predicted short sleep duration is a potential causal risk factor of several CVDs, while genetically predicted long steep duration is unlikely to be a causal risk factor for most CVDs. [GRAPHICS] .

  • 24.
    Aimo, Alberto
    et al.
    Univ Hosp Pisa, Cardiol Div, Pisa, Italy.
    Januzzi, James L., Jr.
    Massachusetts Gen Hosp, Boston, MA 02114 USA;Baim Inst Clin Res, Boston, MA USA.
    Vergaro, Giuseppe
    Scuola Super Sant Anna, Inst Life Sci, Pisa, Italy;Fdn Toscana G Monasterio, Pisa, Italy.
    Clerico, Aldo
    Scuola Super Sant Anna, Inst Life Sci, Pisa, Italy;Fdn Toscana G Monasterio, Pisa, Italy.
    Latini, Roberto
    IRCCS, Dept Cardiovasc Res, Ist Ric Farmacolog Mario Negri, Milan, Italy.
    Meessen, Jennifer
    IRCCS, Dept Cardiovasc Res, Ist Ric Farmacolog Mario Negri, Milan, Italy.
    Anand, Inder S.
    Univ Minnesota, Div Cardiovasc Med, Minneapolis, MN USA;VA Med Ctr, Dept Cardiol, Minneapolis, MN USA.
    Cohn, Jay N.
    Univ Minnesota, Div Cardiovasc Med, Minneapolis, MN USA.
    Gravning, Jorgen
    Oslo Univ Hosp, Dept Cardiol, Oslo, Norway;Univ Oslo, Ctr Heart Failure Res, Oslo, Norway.
    Ueland, Thor
    Oslo Univ Hosp, Rikshosp, Res Inst Internal Med, Oslo, Norway;Univ Oslo, Fac Med, Oslo, Norway;Univ Tromso, KG Jebsen Thrombosis Res & Expertise Ctr, Tromso, Norway.
    Nymo, Stale H.
    Oslo Univ Hosp, Rikshosp, Res Inst Internal Med, Oslo, Norway.
    Brunner-La Rocca, Hans-Peter
    Maastricht Univ, Dept Cardiol, Med Ctr, Maastricht, Netherlands.
    Bayes-Genis, Antoni
    Hosp Badalona Germans Trias & Pujol, Badalona, Barcelona, Spain.
    Lupon, Josep
    Hosp Badalona Germans Trias & Pujol, Badalona, Barcelona, Spain.
    de Boer, Rudolf A.
    Univ Med Ctr Groningen, Groningen, Netherlands.
    Yoshihisa, Akiomi
    Fukushima Med Univ, Dept Cardiovasc Med, Fukushima, Japan.
    Takeishi, Yasuchika
    Fukushima Med Univ, Dept Cardiovasc Med, Fukushima, Japan.
    Egstrup, Michael
    Copenhagen Univ Hosp, Dept Cardiol, Rigshosp, Copenhagen, Denmark.
    Gustafsson, Ida
    Copenhagen Univ Hosp, Dept Cardiol, Rigshosp, Copenhagen, Denmark.
    Gagging, Hanna K.
    Massachusetts Gen Hosp, Boston, MA 02114 USA;Baim Inst Clin Res, Boston, MA USA.
    Eggers, Kai M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Huber, Kurt
    Wilhelminenspital & Sigmund Freud Univ, Fac Internal Med, Med Sch, Vienna, Austria.
    Tentzeris, Ioannis
    Wilhelminenspital & Sigmund Freud Univ, Fac Internal Med, Med Sch, Vienna, Austria.
    Ripoli, Andrea
    Fdn Toscana G Monasterio, Pisa, Italy.
    Passino, Claudio
    Scuola Super Sant Anna, Inst Life Sci, Pisa, Italy;Fdn Toscana G Monasterio, Pisa, Italy.
    Emdin, Michele
    Scuola Super Sant Anna, Inst Life Sci, Pisa, Italy;Fdn Toscana G Monasterio, Pisa, Italy.
    Revisiting the obesity paradox in heart failure: Per cent body fat as predictor of biomarkers and outcome2019In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 26, no 16, p. 1751-1759Article in journal (Refereed)
    Abstract [en]

    Aims Obesity defined by body mass index (BMI) is characterized by better prognosis and lower plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure. We assessed whether another anthropometric measure, per cent body fat (PBF), reveals different associations with outcome and heart failure biomarkers (NT-proBNP, high-sensitivity troponin T (hs-TnT), soluble suppression of tumorigenesis-2 (sST2)). Methods In an individual patient dataset, BMI was calculated as weight (kg)/height (m) (2) , and PBF through the Jackson-Pollock and Gallagher equations. Results Out of 6468 patients (median 68 years, 78% men, 76% ischaemic heart failure, 90% reduced ejection fraction), 24% died over 2.2 years (1.5-2.9), 17% from cardiovascular death. Median PBF was 26.9% (22.4-33.0%) with the Jackson-Pollock equation, and 28.0% (23.8-33.5%) with the Gallagher equation, with an extremely strong correlation (r = 0.996, p < 0.001). Patients in the first PBF tertile had the worst prognosis, while patients in the second and third tertile had similar survival. The risks of all-cause and cardiovascular death decreased by up to 36% and 27%, respectively, per each doubling of PBF. Furthermore, prognosis was better in the second or third PBF tertiles than in the first tertile regardless of model variables. Both BMI and PBF were inverse predictors of NT-proBNP, but not hs-TnT. In obese patients (BMI >= 30 kg/m(2), third PBF tertile), hs-TnT and sST2, but not NT-proBNP, independently predicted outcome. Conclusion In parallel with increasing BMI or PBF there is an improvement in patient prognosis and a decrease in NT-proBNP, but not hs-TnT or sST2. hs-TnT or sST2 are stronger predictors of outcome than NT-proBNP among obese patients.

  • 25. Aimo, Alberto
    et al.
    Januzzi, James L
    Vergaro, Giuseppe
    Eggers, Kai M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Circulating levels and prognostic value of soluble ST2 in heart failure are less influenced by age than N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T2020In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 22, no 11, p. 2078-2088Article in journal (Refereed)
    Abstract [en]

    Aims N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT) and soluble suppression of tumorigenesis-2 (sST2) predict outcome in chronic heart failure (HF). We assessed the influence of age on circulating levels and prognostic significance of these biomarkers. Methods and results Individual data from 5301 patients with chronic HF and NT-proBNP, hs-TnT, and sST2 data were evaluated. Patients were stratified according to age: <60 years (n = 1332, 25%), 60-69 years (n = 1628, 31%), 70-79 years (n = 1662, 31%), and >= 80 years (n = 679, 13%). Patients (median age 66 years, 75% men, median left ventricular ejection fraction 28%, 64% with ischaemic HF) had median NT-proBNP 1564 ng/L, hs-TnT 21 ng/L, and sST2 29 ng/mL. Age independently predicted NT-proBNP and hs-TnT, but not sST2. The best NT-proBNP and hs-TnT cut-offs for 1-year and 5-year all-cause and cardiovascular mortality and 1- to 12-month HF hospitalization increased with age, while the best sST2 cut-offs did not. When stratifying patients according to age- and outcome-specific cut-offs, this stratification yielded independent prognostic significance over NT-proBNP levels only, or the composite of NT-proBNP and hs-TnT, and improved risk prediction for most endpoints. Finally, absolute NT-proBNP, hs-TnT, and sST2 levels predicted outcomes independent of age, sex, left ventricular ejection fraction category, ethnic group, and other variables. Conclusions Soluble ST2 is less influenced by age than NT-proBNP or hs-TnT; all these biomarkers predict outcome regardless of age. The use of age- and outcome-specific cut-offs of NT-proBNP, hs-TnT and sST2 allows more accurate risk stratification than NT-proBNP alone or the combination of NT-proBNP and hs-TnT.

  • 26.
    Aimo, Alberto
    et al.
    Scuola Super Sant Anna, Pisa, Italy.
    Januzzi, James L
    Massachusetts Gen Hosp, Boston, MA, USA; Harvard Clin Res Inst, Boston, MA USA.
    Vergaro, Giuseppe
    Scuola Super Sant Anna, Pisa, Italy; Fdn Toscana Gabriele Monasterio, Pisa, Italy.
    Ripoli, Andrea
    Fdn Toscana Gabriele Monasterio, Pisa, Italy.
    Latini, Roberto
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
    Masson, Serge
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
    Magnoli, Michela
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
    Anand, Inder S
    Univ Minnesota, Div Cardiovasc Med, Minneapolis, MN, USA; VA Med Ctr, Dept Cardiol, Minneapolis, MN USA.
    Cohn, Jay N
    Univ Minnesota, Div Cardiovasc Med, Minneapolis, MN, USA.
    Tavazzi, Luigi
    ES Hlth Sci Fdn, GVM Hosp Care & Res, Cotignola, Italy.
    Tognoni, Gianni
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
    Gravning, Jørgen
    Oslo Univ Hosp, Dept Cardiol, Ulleval, Norway; Univ Oslo, Ctr Heart Failure Res, Oslo, Norway.
    Ueland, Thor
    Oslo Univ Hosp, Rikshosp, Internal Med Res Inst, Oslo, Norway; Univ Oslo, Fac Med, Oslo, Norway; Univ Tromso, Jebsen Thrombosis Res & Expertise Ctr, Tromso, Norway.
    Nymo, Ståle H
    Oslo Univ Hosp, Rikshosp, Internal Med Res Inst, Oslo, Norway.
    Brunner-La Rocca, Hans-Peter
    Maastricht Univ, Med Ctr, Dept Cardiol, Maastricht, Netherlands.
    Bayes-Genis, Antoni
    Hosp Badalona Germans Trias & Pujol, Badalona, Barcelona, Spain.
    Lupón, Josep
    Hosp Badalona Germans Trias & Pujol, Badalona, Barcelona, Spain.
    de Boer, Rudolf A
    Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands.
    Yoshihisa, Akiomi
    Fukushima Med Univ, Dept Cardiovasc Med, Fukushima, Japan.
    Takeishi, Yasuchika
    Fukushima Med Univ, Dept Cardiovasc Med, Fukushima, Japan.
    Egstrup, Michael
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Copenhagen, Denmark.
    Gustafsson, Ida
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Copenhagen, Denmark.
    Gaggin, Hanna K
    Massachusetts Gen Hosp, Boston, MA, USA; Harvard Clin Res Inst, Boston, MA, USA.
    Eggers, Kai M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Huber, Kurt
    Wilhelminenspital Stadt Wien, Fac Internal Med, Vienna, Austria; Sigmund Freud Univ, Med Sch, Vienna, Austria.
    Tentzeris, Ioannis
    Wilhelminenspital Stadt Wien, Fac Internal Med, Vienna, Austria; Sigmund Freud Univ, Med Sch, Vienna, Austria.
    Tang, Wai H.W.
    Cleveland Clin, Inst Heart & Vasc, Cleveland, OH, USA.
    Grodin, Justin
    Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX USA.
    Passino, Claudio
    Scuola Super Sant Anna, Pisa, Italy; Fdn Toscana Gabriele Monasterio, Pisa, Italy.
    Emdin, Michele
    Scuola Super Sant Anna, Pisa, Italy; Fdn Toscana Gabriele Monasterio, Pisa, Italy.
    Prognostic Value of High-Sensitivity Troponin T in Chronic Heart Failure: An Individual Patient Data Meta-Analysis2018In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 137, no 3, p. 286-297Article in journal (Refereed)
    Abstract [en]

    Background: Most patients with chronic heart failure have detectable troponin concentrations when evaluated by high-sensitivity assays. The prognostic relevance of this finding has not been clearly established so far. We aimed to assess high-sensitivity troponin assay for risk stratification in chronic heart failure through a meta-analysis approach.

    Methods: Medline, EMBASE, Cochrane Library, and Scopus were searched in April 2017 by 2 independent authors. The terms were “troponin” AND “heart failure” OR “cardiac failure” OR “cardiac dysfunction” OR “cardiac insufficiency” OR “left ventricular dysfunction.” Inclusion criteria were English language, clinical stability, use of a high-sensitivity troponin assay, follow-up studies, and availability of individual patient data after request to authors. Data retrieved from articles and provided by authors were used in agreement with the PRISMA statement. The end points were all-cause death, cardiovascular death, and hospitalization for cardiovascular cause.

    Results: Ten studies were included, reporting data on 11 cohorts and 9289 patients (age 66±12 years, 77% men, 60% ischemic heart failure, 85% with left ventricular ejection fraction <40%). High-sensitivity troponin T data were available for all patients, whereas only 209 patients also had high-sensitivity troponin I assayed. When added to a prognostic model including established risk markers (sex, age, ischemic versus nonischemic etiology, left ventricular ejection fraction, estimated glomerular filtration rate, and N-terminal fraction of pro-B-type natriuretic peptide), high-sensitivity troponin T remained independently associated with all-cause mortality (hazard ratio, 1.48; 95% confidence interval, 1.41–1.55), cardiovascular mortality (hazard ratio, 1.40; 95% confidence interval, 1.33–1.48), and cardiovascular hospitalization (hazard ratio, 1.42; 95% confidence interval, 1.36–1.49), over a median 2.4-year follow-up (all P<0.001). High-sensitivity troponin T significantly improved risk prediction when added to a prognostic model including the variables above. It also displayed an independent prognostic value for all outcomes in almost all population subgroups. The area under the curve–derived 18 ng/L cutoff yielded independent prognostic value for the 3 end points in both men and women, patients with either ischemic or nonischemic etiology, and across categories of renal dysfunction.

    Conclusions: In chronic heart failure, high-sensitivity troponin T is a strong and independent predictor of all-cause and cardiovascular mortality, and of hospitalization for cardiovascular causes, as well. This biomarker then represents an additional tool for prognostic stratification.

  • 27.
    Aimo, Alberto
    et al.
    Scuola Super Sant Anna, Pisa, Italy.
    Januzzi, James L.
    Massachusetts Gen Hosp, Harvard Clin Res Inst, Boston, MA USA.
    Vergaro, Giuseppe
    Scuola Super Sant Anna, Pisa, Italy; Fdn Toscana G Monasterio, Pisa, Italy.
    Ripoli, Andrea
    Fdn Toscana G Monasterio, Pisa, Italy.
    Latini, Roberto
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
    Masson, Serge
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
    Magnoli, Michela
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
    Anand, Inder S.
    Univ Minnesota, Div Cardiovasc Med, Minneapolis, MN USA; VA Med Ctr, Dept Cardiol, Minneapolis, MN USA.
    Cohn, Jay N
    Univ Minnesota, Div Cardiovasc Med, Minneapolis, MN USA.
    Tavazzi, Luigi
    ES Hlth Sci Fdn, GVM Hosp Care & Res, Cotignola, Italy.
    Tognoni, Gianni
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
    Gravning, Jørgen
    Oslo Univ Hosp, Dept Cardiol, Oslo, Norway; Univ Oslo, Ctr Heart Failure Res, Oslo, Norway.
    Ueland, Thor
    Oslo Univ Hosp, Res Inst Internal Med, Rikshosp, Oslo, Norway; Univ Oslo, Fac Med, Oslo, Norway; Univ Tromso, KG Jebsen Thrombosis Res & Expertise Ctr, Tromso, Norway .
    Nymo, Ståle H
    Oslo Univ Hosp, Res Inst Internal Med, Rikshosp, Oslo, Norway.
    Rocca, Hans-Peter Brunner-La
    Maastricht Univ, Med Ctr, Dept Cardiol, Maastricht, Netherland.
    Bayes-Genis, Antoni
    Hosp Badalona Germans Trias & Pujol, Barcelona, Spain.
    Lupón, Josep
    Hosp Badalona Germans Trias & Pujol, Barcelona, Spain.
    de Boer, Rudolf A.
    Univ Med Ctr Groningen, Groningen, Netherlands.
    Yoshihisa, Akiomi
    Fukushima Med Univ, Dept Cardiovasc Med, Fukushima, Japan.
    Takeishi, Yasuchika
    Fukushima Med Univ, Dept Cardiovasc Med, Fukushima, Japan.
    Egstrup, Michael
    Copenhagen Univ Hosp, Dept Cardiol, Rigshosp, Copenhagen, Denmark.
    Gustafsson, Ida
    Copenhagen Univ Hosp, Dept Cardiol, Rigshosp, Copenhagen, Denmark.
    Gaggin, Hanna K.
    Massachusetts Gen Hosp, Harvard Clin Res Inst, Boston, MA USA.
    Eggers, Kai M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Huber, Kurt
    Wilhelminenspital Stadt Wien, Fac Internal Med, Vienna, Austria; Sigmund Freud Univ, Med Sch, Vienna, Austria.
    Tentzeris, Ioannis
    Wilhelminenspital Stadt Wien, Fac Internal Med, Vienna, Austria; Sigmund Freud Univ, Med Sch, Vienna, Austria.
    Wilson Tang, W. H.
    Cleveland Clin, Heart & Vasc Inst, Cleveland, OH USA.
    Grodin, Justin L
    Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Div Cardiol, Dallas, TX USA.
    Passino, Claudio
    Scuola Super Sant Anna, Pisa, Italy; Fdn Toscana G Monasterio, Pisa, Italy.
    Emdin, Michele
    Scuola Super Sant Anna, Pisa, Italy; Fdn Toscana G Monasterio, Pisa, Italy.
    High-sensitivity troponin T, NT-proBNP and glomerular filtration rate: A multimarker strategy for risk stratification in chronic heart failure2019In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 277, p. 166-172, article id S0167-5273(18)32769-4Article in journal (Refereed)
    Abstract [en]

    Background: In a recent individual patient data meta-analysis, high-sensitivity troponin T (hs-TnT) emerged as robust predictor of prognosis in stable chronic heart failure (HF). In the same population, we compared the relative predictive performances of hs-TnT, N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP), hs-C-reactive protein (hs-CRP), and estimated glomerular filtration rate (eGFR) for prognosis.

    Methods and results: 9289 patients (66 ± 12 years, 77% men, 85% LVEF <40%, 60% ischemic HF) were evaluated over a 2.4-year median follow-up. Median eGFR was 58 mL/min/1.73 m2 (interquartile interval 46–70; n = 9220), hs-TnT 16 ng/L (8–20; n = 9289), NT-proBNP 1067 ng/L (433–2470; n = 8845), and hs-CRP 3.3 mg/L (1.4–7.8; n = 7083). In a model including all 3 biomarkers, only hs-TnT and NT-proBNP were independent predictors of all-cause and cardiovascular mortality and cardiovascular hospitalization. hs-TnT was a stronger predictor than NT-proBNP: for example, the risk for all-cause death increased by 54% per doubling of hs-TnT vs. 24% per doubling of NT-proBNP. eGFR showed independent prognostic value from both hs-TnT and NT-proBNP. The best hs-TnT and NT-proBNP cut-offs for the prediction of all-cause death increased progressively with declining renal function (eGFR ≥ 90: hs-TnT 13 ng/L and NT-proBNP 825 ng/L; eGFR < 30: hs-TnT 40 ng/L and NT-proBNP 4608 ng/L). Patient categorization according to these cut-offs effectively stratified patient prognosis across all eGFR classes.

    Conclusions: hs-TnT conveys independent prognostic information from NT-proBNP, while hs-CRP does not. Concomitant assessment of eGFR may further refine risk stratification. Patient classification according to hs-TnT and NT-proBNP cut-offs specific for the eGFR classes holds prognostic significance.

  • 28.
    Akesson, Agneta
    et al.
    Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden..
    Larsson, Susanna C.
    Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden..
    Discacciati, Andrea
    Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden..
    Wolk, Alicja
    Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden..
    Low-Risk Diet and Lifestyle Habits in the Primary Prevention of Myocardial Infarction in Men A Population-Based Prospective Cohort Study2014In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 64, no 13, p. 1299-1306Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Adherence to a combination of healthy dietary and lifestyle practices may have an impressive impact on the primary prevention of myocardial infarction (MI). OBJECTIVES The aim of this study was to examine the benefit of combined low-risk diet and healthy lifestyle practices on the incidence of MI in men. METHODS The population-based, prospective cohort of Swedish men comprised 45-to 79-year-old men who completed a detailed questionnaire on diet and lifestyle at baseline in 1997. In total, 20,721 men with no history of cancer, cardiovascular disease, diabetes, hypertension, or high cholesterol levels were followed through 2009. Low-risk behavior included 5 factors: a healthy diet (top quintile of Recommended Food Score), moderate alcohol consumption (10 to 30 g/day), no smoking, being physically active (walking/bicycling >= 40 min/day and exercising >= 1 h/week), and having no abdominal adiposity (waist circumference <95 cm). RESULTS During 11 years of follow-up, we ascertained 1,361 incident cases of MI. The low-risk dietary choice together with moderate alcohol consumption was associated with a relative risk of 0.65 (95% confidence interval [CI]: 0.48 to 0.87) compared with men having 0 of 5 low-risk factors. Men having all 5 low-risk factors compared with those with 0 low-risk factors had a relative risk of 0.14 (95% CI: 0.04 to 0.43). This combination of healthy behaviors, present in 1% of the men, could prevent 79% (95% CI: 34% to 93%) of the MI events on the basis of the study population. CONCLUSIONS Almost 4 of 5 MIs in men may be preventable with a combined low-risk behavior. (C) 2014 by the American College of Cardiology Foundation.

  • 29.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology.
    Sub-clinical atherosclerosis in the common carotid artery in women with/without previous pre-eclampsia: A seven-year follow-up2019In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 290, p. 206-213Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: Pre-eclampsia is associated with increased risk of cardiovascular disease and premature death. However, conventional common carotid artery intima-media thickness (CCA-IMT) measurement does not reflect this. In contrast, measurement of the individual CCA intima and media thicknesses clearly indicates increased vascular risk both at diagnosis and about one year after pre-eclampsia. This study examined whether individual CCA wall layers, risk factors for cardiovascular disease, and markers of endothelial dysfunction had normalized or remained unfavorable seven years after pre-eclampsia.

    METHODS: The individual CCA intima and media thicknesses were measured using 22 MHz ultrasound. Conventional cardiovascular risk factors were recorded. A thick intima, thin media and high intima/media thickness ratio (I/M) are signs of sub-clinical atherosclerosis.

    RESULTS: The median age of women with previous pre-eclampsia (cases = 23) or normal pregnancies (controls = 35) was 39/37 years. At follow-up (median about seven years), the intima remained thicker and the I/M was higher in cases than in controls [all p < 0.0001; p < 0.001 after adjustment for time to follow-up, body mass index (BMI), and mean arterial pressure (MAP)], whereas the CCA-IMT was illogically thinner. Further, BMI, MAP, hip circumference, abdominal height, serum endostatin and apolipoprotein B levels were higher in cases (all p < 0.05). Intima and I/M measurements were correlated with age, MAP, endostatin and apolipoprotein B, whereas no logical correlations were found for CCA-IMT.

    CONCLUSIONS: The arteries in cases but not controls were still adversely affected after seven years. Measuring intima thickness and I/M appears preferable to measuring CCA-IMT for demonstrating vascular risk after pre-eclampsia.

  • 30.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Larsson, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Bondesson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hedeland, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Dimethylarginines correlate to common carotid artery wall layer dimensions and cardiovascular risk factors in pregnant women with and without preeclampsia2018In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 275, p. E69-E70Article in journal (Other academic)
  • 31. Aktaa, Suleman
    et al.
    Abdin, Amr
    Arbelo, Elena
    Burri, Haran
    Vernooy, Kevin
    Blomström-Lundqvist, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Boriani, Giuseppe
    Defaye, Pascal
    Deharo, Jean-Claude
    Drossart, Inga
    Foldager, Dan
    Gold, Michael R
    Johansen, Jens Brock
    Leyva, Francisco
    Linde, Cecilia
    Michowitz, Yoav
    Kronborg, Mads Brix
    Slotwiner, David
    Steen, Torkel
    Tolosana, José Maria
    Tzeis, Stylianos
    Varma, Niraj
    Glikson, Michael
    Nielsen, Jens Cosedis
    Gale, Chris P
    European Society of Cardiology Quality Indicators for the care and outcomes of cardiac pacing: developed by the Working Group for Cardiac Pacing Quality Indicators in collaboration with the European Heart Rhythm Association of the European Society of Cardiology2022In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 24, no 1, p. 165-172Article in journal (Refereed)
    Abstract [en]

    AIMS: To develop a suite of quality indicators (QIs) for the evaluation of the care and outcomes for adults undergoing cardiac pacing.

    METHODS AND RESULTS: Under the auspice of the Clinical Practice Guideline Quality Indicator Committee of the European Society of Cardiology (ESC), the Working Group for cardiac pacing QIs was formed. The Group comprised Task Force members of the 2021 ESC Clinical Practice Guidelines on Cardiac Pacing and Cardiac Resynchronization Therapy, members of the European Heart Rhythm Association, international cardiac device experts, and patient representatives. We followed the ESC methodology for QI development, which involved (i) the identification of the key domains of care by constructing a conceptual framework of the management of patients receiving cardiac pacing, (ii) the development of candidate QIs by conducting a systematic review of the literature, (iii) the selection of the final set of QIs using a modified-Delphi method, and (iv) the evaluation of the feasibility of the developed QIs. Four domains of care were identified: (i) structural framework, (ii) patient assessment, (iii) pacing strategy, and (iv) clinical outcomes. In total, seven main and four secondary QIs were selected across these domains and were embedded within the 2021 ESC Guidelines on Cardiac Pacing and Cardiac Resynchronization therapy.

    CONCLUSION: By way of a standardized process, 11 QIs for cardiac pacing were developed. These indicators may be used to quantify adherence to guideline-recommended clinical practice and have the potential to improve the care and outcomes of patients receiving cardiac pacemakers.

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  • 32.
    Aktaa, Suleman
    et al.
    Univ Leeds, Leeds Inst Cardiovasc & Metab Med, Leeds, W Yorkshire, England.;Univ Leeds, Leeds Inst Data Analyt, Leeds, W Yorkshire, England.;Leeds Teaching Hosp NHS Trust, Dept Cardiol, Leeds, W Yorkshire, England.
    Batra, Gorav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Cleland, John G. F.
    Univ Glasgow, Glasgow Royal Infirm, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.;Univ Glasgow, Glasgow Royal Infirm, Glasgow Clin Trials Unit, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland.;Imperial Coll London, Natl Heart & Lung Inst, London, England.
    Coats, Andrew
    Univ Warwick, Coventry, W Midlands, England.;European Soc Cardiol, Heart Failure Assoc, Brussels, Belgium.
    Lund, Lars H.
    Karolinska Inst, Dept Med, Unit Cardiol, Stockholm, Sweden.;Karolinska Univ Hosp, Heart & Vasc Theme, Stockholm, Sweden.
    McDonagh, Theresa
    Kings Coll Hosp London, Dept Cardiol, Denmark Hill, London, England.;Kings Coll London, British Heart Fdn, Ctr Excellence, Sch Cardiovasc Med & Sci, London, England.
    Rosano, Giuseppe
    St Georges Hosp NHS Trust Univ London, Cardiovasc Clin Acad Grp, London, England.;IRCCS San Raffaele Pisana, Rome, Italy.
    Seferovic, Petar
    Univ Belgrade, Serbian Acad Sci & Arts, Fac Med, Heart Failure Ctr,Med Ctr, Belgrade, Serbia.
    Vasko, Peter
    Univ Hosp, Dept Cardiol, Linköping, Sweden.;SWEDEHEART Swedish Web Syst Enhancement & Dev Evi, Växjö, Sweden.;SwedeHF Swedish Heart Failure Registry, Växjö, Sweden.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Maggioni, Aldo P.
    Natl Assoc Hosp Cardiologists Res Ctr ANMCO, Florence, Italy.
    Casadei, Barbara
    Univ Oxford, NIHR Oxford Biomed Res Ctr, Div Cardiovasc Med, Oxford, England.
    Gale, Chris P.
    Univ Leeds, Leeds Inst Cardiovasc & Metab Med, Leeds, W Yorkshire, England.;Univ Leeds, Leeds Inst Data Analyt, Leeds, W Yorkshire, England.;Leeds Teaching Hosp NHS Trust, Dept Cardiol, Leeds, W Yorkshire, England.
    Data standards for heart failure: the European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart)2022In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 43, no 23, p. 2185-+Article in journal (Refereed)
    Abstract [en]

    Standardized data definitions are essential for assessing the quality of care and patient outcomes in observational studies and randomized controlled trials. The European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart) project of the European Society of Cardiology (ESC) aims to create contemporary pan-European data standards for cardiovascular diseases, including heart failure (HF). We followed the EuroHeart methodology for cardiovascular data standard development. A Working Group including experts in HF registries, representatives from the Heart Failure Association of the ESC, and the EuroHeart was formed. Using Embase and Medline (2016-21), we conducted a systematic review of the literature on data standards, registries, and trials to identify variables pertinent to HF. A modified Delphi method was used to reach a consensus on the final set of variables. For each variable, the Working Group developed data definitions and agreed on whether it was mandatory (Level 1) or additional (Level 2). In total, 84 Level 1 and 79 Level 2 variables were selected for nine domains of HF care. These variables were reviewed by an international Reference Group with the Level 1 variables providing the dataset for registration of patients with HF on the EuroHeart IT platform. By means of a structured process and interaction with international stakeholders, harmonized data standards for HF have been developed. In the context of the EuroHeart, this will facilitate quality improvement, international observational research, registry-based randomized trials, and post-marketing surveillance of devices and pharmacotherapies across Europe.

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  • 33. Aktaa, Suleman
    et al.
    Batra, Gorav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Blackman, Daniel J
    Ludman, Peter F
    Mamas, Mamas A
    Abdel-Wahab, Mohamed
    Angelini, Gianni D
    Czerny, Martin
    Delgado, Victoria
    De Luca, Giuseppe
    Eustachio, Agricola
    Foldager, Dan
    Hamm, Christian W
    Iung, Bernard
    Mangner, Norman
    Mehilli, Julinda
    Murphy, Gavin J
    Mylotte, Darren
    Parma, Radoslaw
    Petronio, Anna Sonia
    Popescu, Bodgan A
    Sondergaard, Lars
    Teles, Rui C
    Sabaté, Manel
    Terkelsen, Christian J
    Testa, Luca
    Wu, Jianhua
    Maggioni, Aldo P
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Casadei, Barbara
    Gale, Chris P
    Data standards for transcatheter aortic valve implantation: the European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart).2023In: European Heart Journal - Quality of Care and Clinical Outcomes, ISSN 2058-5225, E-ISSN 2058-1742, Vol. 9, no 5, p. 529-536, article id qcac063Article in journal (Refereed)
    Abstract [en]

    AIMS: Standardized data definitions are necessary for the quantification of quality of care and patient outcomes in observational studies and randomised controlled trials (RCTs). The European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart) project of the European Society of Cardiology (ESC) aims to create pan-European data standards for cardiovascular diseases and interventions, including transcatheter aortic valve implantation (TAVI).

    METHODS AND RESULTS: We followed the EuroHeart methodology for cardiovascular data standard development. A Working Group of 29 members representing 12 countries was established and included a patient representative, as well as experts in the management of valvular heart disease from the European Association of Percutaneous Cardiovascular Interventions (EAPCI), the European Association of Cardiovascular Imaging (EACVI) and the Working Group on Cardiovascular Surgery. We conducted a systematic review of the literature and used a modified Delphi method to reach consensus on a final set of variables. For each variable, the Working Group provided a definition, permissible values and categorized the variable as mandatory (Level 1) or additional (Level 2) based on its clinical importance and feasibility. In total, 93 Level 1 and 113 Level 2 variables were selected, with the level 1 variables providing the dataset for registration of patients undergoing TAVI on the EuroHeart IT platform.

    CONCLUSION: This document provides details of the EuroHeart data standards for TAVI processes of care and in-hospital outcomes. In the context of EuroHeart, this will facilitate quality improvement, observational research, registry-based RCTs and post-marketing surveillance of devices and pharmacotherapies.

  • 34. Aktaa, Suleman
    et al.
    Batra, Gorav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Baigent, Colin
    Erlinge, David
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Ludman, Peter
    Maggioni, Aldo P.
    Price, Susanna
    Weston, Clive
    Casadei, Barbara
    Gale, Chris P.
    European Society of Cardiology methodology for the development of quality indicators for the quantification of cardiovascular care and outcomes2022In: European Heart Journal - Quality of Care and Clinical Outcomes, ISSN 2058-5225, E-ISSN 2058-1742, Vol. 8, no 1, p. 4-13Article, review/survey (Refereed)
    Abstract [en]

    AIMS: It is increasingly recognised that tools are required for assessing and benchmarking quality of care in order to improve it. The European Society of Cardiology (ESC) is developing a suite of quality indicators (QIs) to evaluate cardiovascular care and support the delivery of evidence-based care. This paper describes the methodology used for their development.

    METHODS AND RESULTS: We propose a four-step process for the development of the ESC QIs. For a specific clinical area with a gap in care delivery, the QI development process includes: 1) the identification of key domains of care by constructing a conceptual framework of care; 2) the construction of candidate QIs by conducting a systematic review of the literature; 3) the selection of a final set of QIs by obtaining expert opinions using the modified Delphi method; and 4) the undertaking of a feasibility assessment by evaluating different ways of defining the QI specifications for the proposed data collection source. For each of the four steps, key methodological areas need to be addressed to inform the implementation process and avoid misinterpretation of the measurement results.

    CONCLUSION: Detailing the methodology for the ESC QIs construction enables healthcare providers to develop valid and feasible metrics to measure and improve the quality of cardiovascular care. As such, high-quality evidence may be translated into clinical practice and the 'evidence-practice' gap closed.

  • 35.
    Alabas, O. A.
    et al.
    Univ Leeds, Leeds, W Yorkshire, England..
    Rutherford, M.
    Univ Leicester, Leicester, Leics, England..
    Hall, M.
    Univ Leeds, Leeds, W Yorkshire, England..
    Szummer, K.
    Karolinska Univ Hosp, Dept Med H7, Stockholm, Sweden..
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Gale, C. P.
    Univ Leeds, Leeds, W Yorkshire, England..
    Jernberg, T.
    Karolinska Univ Hosp, Dept Med H7, Stockholm, Sweden..
    Lower long term relative survival and higher excess mortality in women and in elderly after acute myocardial infarction: a national cohort study using 180,368 cases from the SWEDEHEART registry2016In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 37, no Suppl. 1, p. 1385-1385Article in journal (Refereed)
  • 36.
    Alabas, Oras A.
    et al.
    Univ Leeds, Leeds Inst Cardiovasc & Metab Med, Bioinformat Ctr, MRC, Leeds, W Yorkshire, England..
    Gale, Chris P.
    Univ Leeds, Leeds Inst Cardiovasc & Metab Med, Bioinformat Ctr, MRC, Leeds, W Yorkshire, England.;York Teaching Hosp NHS Fdn Trust, Dept Cardiol, York, N Yorkshire, England..
    Hall, Marlous
    Univ Leeds, Leeds Inst Cardiovasc & Metab Med, Bioinformat Ctr, MRC, Leeds, W Yorkshire, England..
    Rutherford, Mark J.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Szummer, Karolina
    Dept Med, Huddinge, Sweden..
    Lawesson, Sofia Sederholm
    Linkoping Univ, Dept Cardiol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Alfredsson, Joakim
    Linkoping Univ, Dept Cardiol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jernberg, Tomas
    Karolinska Inst, Danderyds Hosp, Dept Clin Sci, Stockholm, Sweden..
    Sex Differences in Treatments, Relative Survival, and Excess Mortality Following Acute Myocardial Infarction: National Cohort Study Using the SWEDEHEART Registry2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 12, article id e007123Article in journal (Refereed)
    Abstract [en]

    Background - This study assessed sex differences in treatments, all-cause mortality, relative survival, and excess mortality following acute myocardial infarction.

    Methods and Results - A population-based cohort of all hospitals providing acute myocardial infarction care in Sweden (SWEDEHEART [Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies]) from 2003 to 2013 was included in the analysis. Excess mortality rate ratios (EMRRs), adjusted for clinical characteristics and guideline-indicated treatments after matching by age, sex, and year to background mortality data, were estimated. Although there were no sex differences in all-cause mortality adjusted for age, year of hospitalization, and comorbidities for ST-segment-elevation myocardial infarction (STEMI) and non-STEMI at 1 year (mortality rate ratio: 1.01 [95% confidence interval (CI), 0.96-1.05] and 0.97 [95% CI, 0.95-.99], respectively) and 5 years (mortality rate ratio: 1.03 [95% CI, 0.99-1.07] and 0.97 [95% CI, 0.95-.99], respectively), excess mortality was higher among women compared with men for STEMI and non-STEMI at 1 year (EMRR: 1.89 [95% CI, 1.66-2.16] and 1.20 [95% CI, 1.16-1.24], respectively) and 5 years (EMRR: 1.60 [95% CI, 1.48-1.72] and 1.26 [95% CI, 1.21-1.32], respectively). After further adjustment for the use of guideline-indicated treatments, excess mortality among women with non-STEMI was not significant at 1 year (EMRR: 1.01 [95% CI, 0.97-1.04]) and slightly higher at 5 years (EMRR: 1.07 [95% CI, 1.02-1.12]). For STEMI, adjustment for treatments attenuated the excess mortality for women at 1 year (EMRR: 1.43 [95% CI, 1.26-1.62]) and 5 years (EMRR: 1.31 [95% CI, 1.19-1.43]).

    Conclusions - Women with acute myocardial infarction did not have statistically different all-cause mortality, but had higher excess mortality compared with men that was attenuated after adjustment for the use of guideline-indicated treatments. This suggests that improved adherence to guideline recommendations for the treatment of acute myocardial infarction may reduce premature cardiovascular death among women.

  • 37.
    Alabas, Oras A.
    et al.
    Univ Leeds, Leeds Inst Rheumat & Musculoskeletal Med, Leeds, W Yorkshire, England.
    Jernberg, Tomas
    Karolinska Inst, Danderyd Univ Hosp, Dept Clin Sci, Stockholm, Sweden.
    Pujades-Rodriguez, Mar
    Univ Leeds, Leeds Inst Hlth Sci, Leeds, W Yorkshire, England.
    Rutherford, Mark J.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
    West, Robert M.
    Univ Leeds, Leeds Inst Hlth Sci, Leeds, W Yorkshire, England.
    Hall, Marlous
    Univ Leeds, Leeds Inst Cardiovasc & Metab Med, Leeds, W Yorkshire, Sweden.
    Timmis, Adam
    Barts Heart Ctr, Dept Cardiol, London, England.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Fox, Keith A. A.
    Univ Edinburgh, Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland.
    Hemingway, Harry
    UCL, Hlth Data Res UK London, London, England;UCL, Inst Hlth Informat, London, England;UCL, Natl Inst Hlth Res, Univ Coll London Hosp, Biomed Res Ctr, London, England.
    Gale, Chris P.
    Univ Leeds, Leeds Inst Cardiovasc & Metab Med, Leeds, W Yorkshire, Sweden;Univ Leeds, Leeds Inst Data Analyt, Leeds, W Yorkshire, England.
    Statistics on mortality following acute myocardial infarction in 842 897 Europeans2020In: Cardiovascular Research, ISSN 0008-6363, E-ISSN 1755-3245, Vol. 116, no 1, p. 149-157Article in journal (Refereed)
    Abstract [en]

    Aims: To compare ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) mortality between Sweden and the UK, adjusting for background population rates of expected death, case mix, and treatments.

    Methods and results: National data were collected from hospitals in Sweden [n = 73 hospitals, 180 368 patients, Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART)] and the UK [n = 247, 662 529 patients, Myocardial Ischaemia National Audit Project (MINAP)] between 2003 and 2013. There were lower rates of revascularization [STEMI (43.8% vs. 74.9%); NSTEMI (27.5% vs. 43.6%)] and pharmacotherapies at time of hospital discharge including [aspirin (82.9% vs. 90.2%) and (79.9% vs. 88.0%), beta-blockers (73.4% vs. 86.4%) and (65.3% vs. 85.1%)] in the UK compared with Sweden, respectively. Standardized net probability of death (NPD) between admission and 1 month was higher in the UK for STEMI [8.0 (95% confidence interval 7.4-8.5) vs. 6.7 (6.5-6.9)] and NSTEMI [6.8 (6.4-7.2) vs. 4.9 (4.7-5.0)]. Between 6 months and 1 year and more than 1 year, NPD remained higher in the UK for NSTEMI [2.9 (2.5-3.3) vs. 2.3 (2.2-2.5)] and [21.4 (20.0-22.8) vs. 18.3 (17.6-19.0)], but was similar for STEMI [0.7 (0.4-1.0) vs. 0.9 (0.7-1.0)] and [8.4 (6.7-10.1) vs. 8.3 (7.5-9.1)].

    Conclusion: Short-term mortality following STEMI and NSTEMI was higher in the UK compared with Sweden. Mid- and longer-term mortality remained higher in the UK for NSTEMI but was similar for STEMI. Differences in mortality may be due to differential use of guideline-indicated treatments.

  • 38.
    Albaba, Adnan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology.
    Medvedev, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control.
    Online Model-Based Beat-by-beat Heart Rate Estimation2020In: 2020 American Control Conference (ACC), 2020, p. 539-544Conference paper (Refereed)
    Abstract [en]

    A method for estimating the instantaneous heart rate (HR) using the morphological features of one electrocardiogram (ECG) cycle (beat) at a time is proposed. This work is not aimed at introducing an alternative way for HR estimation, but rather illustrates the utility of model-based ECG analysis in online individualized monitoring of the heart function. The HR estimation problem is reduced to fitting one parameter, whose value is related to the nine parameters of a realistic nonlinear model of the ECG and estimated from data by nonlinear least-squares optimization. The method feasibility is evaluated on synthetic ECG signals as well as signals acquired from MIT-BIH databases at Physionet website. Moreover, the performance of the method was tested under realistic free-moving conditions using a wearable ECG and HR monitor with encouraging results.

  • 39.
    Albåge, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    The effect of the atrial kick after Cox-Maze surgery for atrial fibrillation2021In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 326, p. 73-74Article in journal (Other academic)
  • 40.
    Albåge, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Jideus, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Liden, Hans
    Schersten, Henrik
    The Berglin apical stitch: a simple technique to straighten things out in atrial fibrillation surgery2014In: Interactive Cardiovascular and Thoracic Surgery, ISSN 1569-9293, E-ISSN 1569-9285, Vol. 19, no 4, p. 685-686Article in journal (Refereed)
    Abstract [en]

    In the Cox-Maze IV procedure, or in endocardial left atrial ablation, correct positioning of the surgical ablation probe within the left atrium might be difficult due to bulging or folds in the posterior left atrial wall. The Berglin apical stitch is a simple trick of the trade to create a smooth surface in the posterior left atrium that facilitates performing a safe transmural lesion and, consequently, may increase antiarrhythmic efficiency.

  • 41.
    Alehagen, Urban
    et al.
    Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
    Aaseth, Jan
    Research Department, Innlandet Hospital Trust, N-2381 Brumunddal, Norway.
    Alexander, Jan
    Norwegian Institute of Public Health, P.O. Box 222 Skøyen, N-0213 Oslo, Norway.
    Johansson, Peter
    Department of Social and Welfare studies & Department of Medical and Health Sciences, Linköping University, SE-601 74 Norrköping, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Supplemental selenium and coenzyme Q10 reduce glycation along with cardiovascular mortality in an elderly population with low selenium status: A four-year, prospective, randomised, double-blind placebo-controlled trial2020In: Journal of Trace Elements in Medicine and Biology, ISSN 0946-672X, E-ISSN 1878-3252, Vol. 61, article id 126541Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A low intake of selenium has been shown to increase the risk of cardiovascular mortality, and supplementation of selenium and coenzyme Q10 influences this. The mechanism behind is unclear although effects on inflammation, oxidative stress and microRNA expression have been reported. Fructosamine, a marker of long-term glycaemic control, is also a marker of increased risk of heart disease and death, even in non-diabetics.

    OBJECTIVE: To analyse the impact of selenium and coenzyme Q10 supplementation on the concentration of fructosamine. Also, the relation between pre-intervention serum selenium concentration and the effect on fructosamine of the intervention was studied.

    METHODS: Fructosamine plasma concentration was determined in 219 participants after six and 42 months of intervention with selenium yeast (200 μg/day) and coenzyme Q10 (200 mg/ day) (n = 118 of which 20 had diabetes at inclusion), or placebo (n = 101 of which 18 had diabetes at inclusion). Pre-intervention, the serum selenium levels were 67 μg/L (active treatment group: 66.6 μg/L; placebo group: 67.4 μg/L), corresponding to an estimated intake of 35 μg/day. Changes in concentrations of fructosamine following intervention were assessed by the use of T-tests, repeated measures of variance, and ANCOVA analyses.

    RESULTS: Post-intervention selenium concentrations were 210 μg/L in the active group and 72 μg/L in the placebo group. A lower concentration of fructosamine could be seen as a result of the intervention in the total population (P = 0.001) in both the males (P = 0.04) and in the females (P = 0.01) in the non-diabetic population (P = 0.002), and in both the younger (<76 years) (P = 0.01) and the older (≥76 years) participants (P = 0.03). No difference could be demonstrated in fructosamine concentration in the diabetic patients, but the total sample was small (n = 38). In subjects with a low pre-intervention level of serum selenium the intervention gave a more pronounced decrease in fructosamine compared with those with a higher baseline selenium level.

    CONCLUSION: A significantly lower concentration of fructosamine was observed in the elderly community-living participants supplemented with selenium and coenzyme Q10 for 42 months compared to those on the placebo. As oxidative mechanisms are involved in the glycation of proteins, less glycoxidation could be a result of the supplementation of selenium and coenzyme Q10, which could have contributed to lower cardiac mortality and less inflammation, as has earlier been reported.

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  • 42. Alehagen, Urban
    et al.
    Aaseth, Jan
    Alexander, Jan
    Svensson, Erland
    Johansson, Peter
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Less fibrosis in elderly subjects supplemented with selenium and coenzyme Q10-A mechanism behind reduced cardiovascular mortality?2018In: Biofactors, ISSN 0951-6433, E-ISSN 1872-8081, Vol. 44, no 2, p. 137-147Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In an intervention study where 221 healthy elderly persons received selenium and coenzyme Q10 as a dietary supplement, and 222 received placebo for 4 years we observed improved cardiac function and reduced cardiovascular mortality. As fibrosis is central in the aging process, we investigated the effect of the intervention on biomarkers of fibrogenic activity in a subanalysis of this intervention study.

    MATERIAL AND METHODS: In the present subanalysis 122 actively treated individuals and 101 controls, the effect of the treatment on eight biomarkers of fibrogenic activity were assessed. These biomarkers were: Cathepsin S, Endostatin, Galectin 3, Growth Differentiation Factor-15 (GDF-15), Matrix Metalloproteinases 1 and 9, Tissue Inhibitor of Metalloproteinases 1 (TIMP 1) and Suppression of Tumorigenicity 2 (ST-2). Blood concentrations of these biomarkers after 6 and 42 months were analyzed by the use of T-tests, repeated measures of variance, and factor analyses.

    RESULTS: Compared with placebo, in those receiving supplementation with selenium and coenzyme Q10, all biomarkers except ST2 showed significant decreased concentrations in blood. The changes in concentrations, that is, effects sizes as given by partial eta2 caused by the intervention were considered small to medium.

    CONCLUSION: The significantly decreased biomarker concentrations in those on active treatment with selenium and coenzyme Q10 compared with those on placebo after 36 months of intervention presumably reflect less fibrogenic activity as a result of the intervention. These observations might indicate that reduced fibrosis precedes the reported improvement in cardiac function, thereby explaining some of the positive clinical effects caused by the intervention. © 2017 BioFactors, 2017.

  • 43.
    Alehagen, Urban
    et al.
    Division of Cardiovascular Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, 81 85 Linköping, Sweden..
    Aaseth, Jan
    Research Department, Innlandet Hospital Trust, 2381 Brumunddal, Norway..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Alexander, Jan
    Norwegian Institute of Public Health, 0403 Oslo, Norway..
    Decreased Concentration of Fibroblast Growth Factor 23 (FGF-23) as a Result of Supplementation with Selenium and Coenzyme Q10 in an Elderly Swedish Population: A Sub-Analysis.2022In: Cells, E-ISSN 2073-4409, Vol. 11, no 3, article id 509Article in journal (Refereed)
    Abstract [en]

    There is a reduced intake of selenium in many countries due to low levels of selenium in the soil. This results in an increased cardiovascular risk. Fibroblast growth factor 23 (FGF-23) is active mainly in the metabolism of vitamin D and phosphorus. However, there are indications that FGF-23 may also provide information both on cardiovascular function and prognosis. The aim of the study was to evaluate the effect of supplementation with selenium and coenzyme Q10 on the FGF-23 concentration in an elderly population with low concentrations of both selenium and coenzyme Q10 and in which the supplementation improved cardiac function and mortality. In a randomised double-blind placebo-controlled trial, FGF-23 was measured in 219 individuals at the start and after 48 months. Selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) (n = 118) or placebo (n = 101) were given as a dietary supplement. The intervention time was 48 months. t-Tests, repeated measures of variance, and ANCOVA analyses were used to evaluate the differences in FGF-23 concentration. Following supplementation with selenium and coenzyme Q10, a significantly lower level of FGF-23 could be seen (p = 0.01). Applying 10 years of follow-up, those who later died a cardiovascular death had a significantly higher FGF-23 concentration after 48 months compared with those who survived (p = 0.036), and a significantly lower FGF-23 concentration could be seen in those with a normal renal function compared to those with an impaired renal function (p = 0.027). Supplementation with selenium and coenzyme Q10 to an elderly community-living population low in both substances prevented an increase of FGF-23 and also provided a reduced cardiovascular risk.

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  • 44.
    Alehagen, Urban
    et al.
    Division of Cardiovascular Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, SE-581 85 Linköping, Sweden..
    Aaseth, Jan
    Research Department, Innlandet Hospital Trust, N-2381 Brumunddal, Norway..
    Lindahl, Tomas L
    Division of Clinical Chemistry and Pharmacology, Department of Biomedical and Clinical Sciences, Linköping University, SE-581 85 Linköping, Sweden..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Alexander, Jan
    Norwegian Institute of Public Health, N-0403 Oslo, Norway..
    Dietary supplementation with selenium and coenzyme Q10 prevents increase in plasma D-dimer while lowering cardiovascular mortality in an elderly Swedish population.2022In: Nutrition, Exercise, and End-of-LifeDiscussion in the Cardiovascular Field / [ed] Fukumoto Y, Basel: MDPI, 2022, p. 43-56Chapter in book (Refereed)
    Abstract [en]

    A low intake of selenium is associated with increased cardiovascular mortality. This could be reduced by supplementation with selenium and coenzyme Q10. D-dimer, a fragment of fibrin mirroring fibrinolysis, is a biomarker of thromboembolism, increased inflammation, endothelial dysfunction and is associated with cardiovascular mortality in ischemic heart disease. The objective was to examine the impact of selenium and coenzyme Q10 on the level of D-dimer, and its relationship to cardiovascular mortality. D-dimer was measured in 213 individuals at the start and after 48 months of a randomised double-blind placebo-controlled trial with selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) (n = 106) or placebo (n = 107). The follow-up time was 4.9 years. All included individuals were low in selenium (mean 67 μg/L, SD 16.8). The differences in D-dimer concentration were evaluated by the use of T-tests, repeated measures of variance and ANCOVA analyses. At the end, a significantly lower D-dimer concentration was observed in the active treatment group in comparison with those on placebo (p = 0.006). Although D-dimer values at baseline were weakly associated with high-sensitive CRP, while being more strongly associated with soluble tumour necrosis factor receptor 1 and sP-selectin, controlling for these in the analysis there was an independent effect on D-dimer. In participants with a D-dimer level above median at baseline, the supplementation resulted in significantly lower cardiovascular mortality compared to those on placebo (p = 0.014). All results were validated with a persisting significant difference between the two groups. Therefore, supplementation with selenium and coenzyme Q10 in a group of elderly low in selenium and coenzyme Q10 prevented an increase in D-dimer and reduced the risk of cardiovascular mortality in comparison with the placebo group. The obtained results also illustrate important associations between inflammation, endothelial function and cardiovascular risk.

  • 45.
    Alehagen, Urban
    et al.
    Division of Cardiovascular Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, SE-581 85 Linköping, Sweden..
    Aaseth, Jan
    Research Department, Innlandet Hospital Trust, N-2381 Brumunddal, Norway..
    Lindahl, Tomas L
    Division of Clinical Chemistry and Pharmacology, Department of Biomedical and Clinical Sciences, Linköping University, SE-581 85 Linköping, Sweden..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Alexander, Jan
    Norwegian Institute of Public Health, N-0403 Oslo, Norway..
    Dietary Supplementation with Selenium and Coenzyme Q10 Prevents Increase in Plasma D-Dimer While Lowering Cardiovascular Mortality in an Elderly Swedish Population.2021In: Nutrients, E-ISSN 2072-6643, Vol. 13, no 4, article id 1344Article in journal (Refereed)
    Abstract [en]

    A low intake of selenium is associated with increased cardiovascular mortality. This could be reduced by supplementation with selenium and coenzyme Q10. D-dimer, a fragment of fibrin mirroring fibrinolysis, is a biomarker of thromboembolism, increased inflammation, endothelial dysfunction and is associated with cardiovascular mortality in ischemic heart disease. The objective was to examine the impact of selenium and coenzyme Q10 on the level of D-dimer, and its relationship to cardiovascular mortality. D-dimer was measured in 213 individuals at the start and after 48 months of a randomised double-blind placebo-controlled trial with selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) (n = 106) or placebo (n = 107). The follow-up time was 4.9 years. All included individuals were low in selenium (mean 67 μg/L, SD 16.8). The differences in D-dimer concentration were evaluated by the use of T-tests, repeated measures of variance and ANCOVA analyses. At the end, a significantly lower D-dimer concentration was observed in the active treatment group in comparison with those on placebo (p = 0.006). Although D-dimer values at baseline were weakly associated with high-sensitive CRP, while being more strongly associated with soluble tumour necrosis factor receptor 1 and sP-selectin, controlling for these in the analysis there was an independent effect on D-dimer. In participants with a D-dimer level above median at baseline, the supplementation resulted in significantly lower cardiovascular mortality compared to those on placebo (p = 0.014). All results were validated with a persisting significant difference between the two groups. Therefore, supplementation with selenium and coenzyme Q10 in a group of elderly low in selenium and coenzyme Q10 prevented an increase in D-dimer and reduced the risk of cardiovascular mortality in comparison with the placebo group. The obtained results also illustrate important associations between inflammation, endothelial function and cardiovascular risk.

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  • 46.
    Alehagen, Urban
    et al.
    Linkoping Univ, Dept Med & Hlth Sci, Div Cardiovasc Med, SE-58185 Linkoping, Sweden.
    Alexander, Jan
    Norwegian Inst Publ Hlth, N-0403 Oslo, Norway.
    Aaseth, Jan
    Innlandet Hosp Trust, Res Dept, Brumunddal, Norway;Inland Norway Univ Appl Sci, N-2411 Elverum, Norway.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Decrease in inflammatory biomarker concentration by intervention with selenium and coenzyme Q10: a subanalysis of osteopontin, osteoprotergerin, TNFr1, TNFr2 and TWEAK2019In: Journal of Inflammation, E-ISSN 1476-9255, Vol. 16, article id 5Article in journal (Refereed)
    Abstract [en]

    Background:

    Inflammation is central to the pathogenesis of many diseases. Supplementation with selenium and coenzyme Q10 has been shown to reduce cardiovascular mortality, and increase cardiac function in elderly persons with a low intake of selenium. There are indications that one of the mechanisms of this positive effect is a decrease in inflammation.

    Methods:

    Osteopontin, osteoprotegerin, sTNF receptor 1, sTNF receptor 2 and the tumor necrosis factor-like weak inducer of apoptosis called TWEAK, were determined in plasma after 6 months and 42months in 219 community-living elderly persons, of whom 119 received supplements of selenium (200g/day) and coenzyme Q10 (200mg/day), and 101 received a placebo. Repeated measures of variance were used to evaluate the levels, and the results were validated through ANCOVA analyses with adjustments for important covariates.

    Results:

    Significantly lower concentrations of four of the five biomarkers for inflammation were observed as a result of the intervention with the supplements. Only TWEAK did not show significant differences.

    Conclusion:

    In this sub-analysis of the intervention with selenium and coenzyme Q10 or placebo in an elderly community-living population, biomarkers for inflammation were evaluated. A significantly lower concentration in four of the five biomarkers tested could be demonstrated as a result of the supplementation, indicating a robust effect on the inflammatory system. The decrease in inflammation could be one of the mechanisms behind the positive clinical results on reduced cardiovascular morbidity and mortality reported earlier as a result of the intervention. The study is small and should be regarded as hypothesis-generating, but nonetheless adds important data about mechanisms presently known to increase the risk of clinical effects such as reduced cardiovascular mortality, increased cardiac function and better health-related quality of life scoring, as previously demonstrated in the active treatment group.

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  • 47.
    Alehagen, Urban
    et al.
    Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, 581 85, Linköping, Sweden..
    Alexander, Jan
    Norwegian Institute of Public Health, Oslo, Norway..
    Aaseth, Jan O
    Department of Research, Innlandet Hospital Trust, Brumunddal, Norway..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Opstad, Trine B
    Center for Clinical Heart Research - Laboratory, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway..
    Supplementation with selenium and coenzyme Q10 in an elderly Swedish population low in selenium - positive effects on thyroid hormones, cardiovascular mortality, and quality of life2024In: BMC Medicine, E-ISSN 1741-7015, Vol. 22, no 1, article id 191Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Selenium-dependent deiodinases play a central role in thyroid hormone regulation and metabolism. In many European countries, insufficient selenium intake may consequently lead to adverse effects on thyroid function. In this randomised placebo-controlled double-blind study, we examined the effect of supplementation with selenium and coenzyme Q10 on thyroid hormonal status, cardiovascular (CV) mortality and health-related quality of life (Hr-QoL).

    METHODS: Free T3, free T4, reverse T3, and TSH were determined in 414 individuals at baseline, and the effect of selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) supplementation on hormone concentrations, CV mortality and Hr-QoL was evaluated after 48 months using Short Form 36 (SF-36). Pre-intervention plasma selenium was low, mean 67 µg/L, corresponding to an estimated intake of 35 µg/day. Changes in concentrations of thyroid hormones following the intervention were assessed using T-tests, repeated measures of variance, and ANCOVA analyses.

    RESULTS: In the total population, the group with the lowest selenium concentration at baseline presented with significantly higher levels of TSH and lower levels of fT3 as compared to subjects with the highest selenium concentration. Supplementation with selenium and coenzyme Q10 for 4 years significantly increased fT3 and rT3, decreased fT4, and diminished the increase in TSH levels compared with placebo treatment (p = 0.03, all). In the placebo group, TSH and fT4 values above the median were associated with an increase in 10-year CV mortality, as compared with the mortality rate among those with TSH and fT4 below the median (p < 0.04, both), with no difference in mortality rate according to TSH and fT4 levels in the active intervention group. Similarly, TSH > median and fT3 < median were associated with a decline in mental Hr-QoL measures vs. TSH < and fT3 > median in the placebo group during 4 years of follow-up, but this was wiped out in the active group.

    CONCLUSIONS: Supplementation with selenium and coenzyme Q10 had a beneficial effect on thyroid hormones with respect to CV mortality and Hr-QoL outcomes. The initial deficient selenium status was associated with an impaired thyroid function and the changes in thyroid hormone levels can be explained by increased activity of deiodinases. We conclude that a substantial part of the elderly study population might suffer from suboptimal thyroidal function with adverse clinical implications due to selenium deficiency.

    TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov and has the identifier NCT01443780. Since it was not mandatory to register at the time the study began, the study has been registered retrospectively.

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  • 48.
    Alehagen, Urban
    et al.
    Linköping Univ, Fac Hlth Sci, Dept Med & Hlth Sci, Div Cardiovasc Med, SE-58185 Linköping, Sweden..
    Shamoun, Levar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Dept Lab Med, Div Med Diagnost, SE-55305 Jönköping, Sweden..
    Dimberg, Jan Ingvar
    Jönköping Univ, Sch Hlth & Welf, Dept Nat Sci & Biomed, SE-55318 Jönköping, Sweden..
    Wågsäter, Dick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Increased mortality in the A/A genotype of the SNP rs28372698 of interleukin 322021In: Experimental and Therapeutic Medicine, ISSN 1792-0981, E-ISSN 1792-1015, Vol. 21, no 2, article id 127Article in journal (Refereed)
    Abstract [en]

    One of the major causes of mortality in the western hemisphere is cardiovascular disease. Therefore, a variety of markers to identify those at risk are required. Interleukin-32 (IL-32) is a cytokine that is associated with inflammation. The aim of the current study was to investigate variations in single nucleotide polymorphisms (SNPs) of IL-32 and plasma expression, and their associations with mortality. A population of 486 elderly community-living persons were evaluated. The participants were followed for 7.1 years and underwent a clinical examination and blood sampling. SNP analyses of IL-32 rs28372698 using allelic discrimination and plasma measurement of IL-32, using ELISA, were performed. During the follow-up period, 140 (28.8%) all-cause and 87 (17.9%) cardiovascular deaths were registered. No significant difference between mortality and plasma concentration of IL-32 was observed. The A/A genotype group exhibited significantly higher all-cause mortality (P=0.036), and an almost two-fold increased risk in a multivariate Cox regression model for all-cause and cardiovascular mortality. A highly significant difference in all-cause and cardiovascular mortality between the A/A and the T/T groups was demonstrated (P=0.015 resp. P=0.014). In the present study, the cytokine IL-32 was demonstrated to have prognostic information, with an increased risk of all-cause and cardiovascular mortality for those with the A/A genotype rs28372698 of IL-32. The A/A genotype could therefore be regarded as a possible biomarker for mortality risk that may be used to offer optimized cardiovascular patient handling in the future. However, the present study sample was small, and the results should be regarded as hypothesis-generating.

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  • 49.
    Alehagen, Urban
    et al.
    Linköping Univ, Fac Med, Dept Hlth Med & Caring Sci, Div Cardiovasc Med, SE-58185 Linköping, Sweden.
    Shamoun, Levar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Jönköping Cty, Div Med Diagnost, Dept Lab Med, SE-55305 Jönköping, Sweden.
    Wågsäter, Dick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Genetic variance and plasma concentration of CD93 is associated with cardiovascular mortality: Results from a 6.7-year follow-up of a healthy community-living elderly population2020In: Molecular Medicine Reports, ISSN 1791-2997, E-ISSN 1791-3004, Vol. 22, no 6, p. 4629-4636Article in journal (Refereed)
    Abstract [en]

    Inflammation is one of the fundamental processes in numerous diseases. Cluster of differentiation (CD) 93, a glycoprotein, has been reported to be associated with a number of these diseases. There are reports indicating that a high plasma level of CD93 is associated with adverse events in ischaemic heart disease. Additionally, there are reports indicating different cardiovascular risks between different single nucleotide polymorphisms (SNPs) of CD93. Therefore, the present study aimed to determine whether the plasma concentration of CD93 and polymorphism of rs2749812 in CD93 were associated with clinical conditions and mortality in an elderly population. In 470 healthy elderly community-living individuals a novel clinical examination involving echocardiography and blood sampling was performed. The population was followed for 6.7 years. Plasma levels of CD93 and SNP analyses of rs2749812 of CD93 using PCR methodology were used. During the follow-up period, 106 (22.6%) all-cause and 61 (13.0%) cardiovascular deaths were registered. Those with the highest plasma concentration had markedly higher all-cause mortality. Evaluating the A/A, A/G and G/G genotypes, the G/G group exhibited significantly higher cardiovascular mortality (P=0.026), and an almost two-fold increased risk in a multivariate Cox regression model compared with the A/G genotype. Evaluation of subgroups with respect to sex, diabetes and hypertension revealed markedly increased cardiovascular risk in the G/G genotype in all subgroups. All results persisted in the multiple models used. In the present study, the glycoprotein CD93 was demonstrated to have prognostic cardiovascular information, with increased risk for those with a high plasma concentration. Furthermore, the G/G genotype of rs2749812 of CD93 has a significantly higher cardiovascular risk, as demonstrated here, and could therefore be regarded as a possible cardiovascular risk biomarker that might in the future be used to offer optimised cardiovascular patient handling. However, this was a small study, and more research is required.

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  • 50.
    Alehagen, Urban
    et al.
    Linköping Univ, Inst Med & Hlth Sci, Div Cardiovasc Med, Dept Med & Hlth Sci, Fac Hlth Sci, SE-58185 Linköping, Sweden.
    Shamoun, Levar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Jönköping Cty, Div Med Diagnost, Dept Lab Med, Jönköping, Sweden.
    Wågsäter, Dick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Increased cardiovascular mortality in females with the a/a genotype of the SNPs rs1478604 and rs2228262 of thrombospondin-12020In: BMC Medical Genetics, E-ISSN 1471-2350, Vol. 21, no 1, article id 179Article in journal (Refereed)
    Abstract [en]

    Background

    Cardiovascular diseases are still the major cause of death in the Western world, with different outcomes between the two genders. Efforts to identify those at risk are therefore given priority in the handling of health resources. Thrombospondins (TSP) are extracellular matrix proteins associated with cardiovascular diseases. The aim of this study was to investigate variations in single nucleotide polymorphisms (SNPs) of TSP-1 and plasma expression, and associations with mortality from a gender perspective.

    Methods

    A population of 470 community-living persons were invited to participate. The participants were followed for 7.9 years and underwent a clinical examination and blood sampling. SNP analyses of TSP-1 rs1478604 and rs2228262 using allelic discrimination and plasma measurement of TSP-1 using ELISA were performed,

    Results

    During the follow-up period, 135 (28.7%) all-cause and 83 (17.7%) cardiovascular deaths were registered.

    In the female population, the A/A genotype of rs2228262 and the T/T genotype of rs1478604 exhibited significantly more cardiovascular deaths compared with the A/G and G/G, or the T/C and C/C genotypes amalgamated (rs2228262: 13.7% vs 2.0%; Χ2:5.29; P = 0.02; rs1478604:17.7% vs 4.7%; Χ2:9.50; P = 0.002). Applied in a risk evaluation, the A/A, or T/T genotypes exhibited an increased risk of cardiovascular mortality (rs2228262: HR: 7.1; 95%CI 1.11–45.8; P = 0.04; rs1478604: HR: 3.18; 95%CI 1.35–7.50; p = 0.008). No differences among the three genotypes could be seen in the male group.

    Conclusion

    In this study the female group having the A/A genotype of rs2228262, or the T/T genotype of rs1478604 of TSP-1 exhibited higher cardiovascular mortality after a follow-up of almost 8 years. No corresponding genotype differences could be found in the male group. Genotype evaluations should be considered as one of the options to identify individuals at risk. However, this study should be regarded as hypothesis-generating, and more research in the field is needed.

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