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Circulating biomarkers in patients with abdominal aortic aneurysm

Flondell-Sité, Despina LU (2010) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2010:64.
Abstract (Swedish)
Popular Abstract in Swedish

Systemiska biomarkörer hos patienter med aortaaneurysm.

Kroppspulsådern eller aorta är huvudstammen som för syrerikt blod från hjärtat till perifera delar av kroppen. Kroppspulsåderbråck (aneurysm) i buken kännetecknas av försvagning i kärlväggen som i sin tur leder till vidgning av kroppspulsådern. Aneurysm är fyra gånger vanligare hos män än hos kvinnor över 65 års ålder (4:1) och förekommer hos 3-6% av befolkningen i denna ålder. Riskfaktorer för utveckling av aneurysm är ärftlig benägenhet, högt blodtryck, rökning, hjärtsjukdom och vissa lungsjukdomar. Förändringar i kärlväggens bindväv och det höga blodflödet som finns i aorta kan orsaka kärlvidgning och aneurysmutveckling.... (More)
Popular Abstract in Swedish

Systemiska biomarkörer hos patienter med aortaaneurysm.

Kroppspulsådern eller aorta är huvudstammen som för syrerikt blod från hjärtat till perifera delar av kroppen. Kroppspulsåderbråck (aneurysm) i buken kännetecknas av försvagning i kärlväggen som i sin tur leder till vidgning av kroppspulsådern. Aneurysm är fyra gånger vanligare hos män än hos kvinnor över 65 års ålder (4:1) och förekommer hos 3-6% av befolkningen i denna ålder. Riskfaktorer för utveckling av aneurysm är ärftlig benägenhet, högt blodtryck, rökning, hjärtsjukdom och vissa lungsjukdomar. Förändringar i kärlväggens bindväv och det höga blodflödet som finns i aorta kan orsaka kärlvidgning och aneurysmutveckling. Aortaaneurysm i buken kan växa med tiden, men orsaken till denna tillväxt är okänd. Vid tillväxt ökar risken för att aneurysmet brister. Bristningen orsakar en livshotande blödning i buken, vilken omedelbart leder till döden för minst 50 % av de drabbade om de inte kommer till vård. Aortaaneurysm kan avbildas med hjälp av ultraljud och datortomografi.

Om man skulle kunna hitta bra metoder för att i blodprov påvisa substanser som markerar aneurysmtillväxt ledande till ökad risk för bristning, skulle enbart de patienter som löper störst risk kunna erbjudas operation. Forskning pågår för att hitta en medicinsk behandling att erbjuda patienterna för att undvika tillväxt och ruptur.

I denna avhandling studerades hur markörer för inflammation (cytokiner) är relaterade till förekomst och tillväxt av aortaaneurysm. Nivåerna av flera markörer visade sig vara klart förhöjda hos aneurysmpatienter jämfört med hos en kontrollgrupp.

Vi studerade även om blodfettsänkande behandling med så kallade statiner påverkade dessa markörer hos patienter med aortaaneurysm. Statinbehandlade aneurysmpatienter visade sig ha högre nivåer av APC-PCI komplexet och lägre nivåer av homocystein, ämnen av betydelse för blodkoagulation respektive inflammation.

Däremot fanns det ingen relation mellan olika markörer i blodet (MMPs, TIMP-1, serpine-1 t-Pa-serpine-1, APC-PCI komplexet) och aneurysmtillväxt.

Endothelin-1 (ET-1) är en signalsubstans som ger en stark kärlsammandragning. Nivån av cirkulerande endotelin är förhöjd hos patienter med aortaaneurysm. Vi fann dessutom att högre nivåer av ET-1 och större aneurysmdiameter innebär mer uttalad tillväxt av aneurysmet under uppföljning.

Vi studerade även ovanstående markörer och deras förhållande till pulsåderbråckets tillväxt under flera års uppföljning. Inga av ovanstående markörer visade sig erbjuda möjligheten att prediktera tillväxt eller bristning av aneurysmet. Ingen av de markörer vi studerade kan därför ersätta ultraljudsuppföljning av patienter med mindre kroppspulsåderbråck.

Sammanfattningsvis kunde i vår studie inte tillväxt av ett aneurysm predikteras genom analys av någon systemisk markör. Fynden i vår studie kan dock i framtiden bli värdefulla för att följa medikamentell behandling syftande till tillväxtreduktion av aortaaneurysm. Ett flertal olika mekanismer bidrar sannolikt till att aneurysm expanderar storleksmässigt. (Less)
Abstract
Abdominal aortic aneurysm (AAA) develops in 3-6% of the population over 65 years and affects mainly men. AAA has a complex etiology involving inflammation, proteolysis, fibrinolysis and coagulation. The general aim of the present thesis was to study the associations between markers of inflammation, proteolysis, fibrinolysis and coagulation with aneurysm size and growth.

In paper I associations between markers for these mechanisms and AAA size were evaluated. Patients with AAA had significantly increased levels of several markers ([endothelin] ET-1, [interleukin] IL-6, [tumour necrosis factor] TNF-α, APC-PCI) compared to age matched healthy controls. Correlations existed between aneurysm size, decreased platelet count, increased... (More)
Abdominal aortic aneurysm (AAA) develops in 3-6% of the population over 65 years and affects mainly men. AAA has a complex etiology involving inflammation, proteolysis, fibrinolysis and coagulation. The general aim of the present thesis was to study the associations between markers of inflammation, proteolysis, fibrinolysis and coagulation with aneurysm size and growth.

In paper I associations between markers for these mechanisms and AAA size were evaluated. Patients with AAA had significantly increased levels of several markers ([endothelin] ET-1, [interleukin] IL-6, [tumour necrosis factor] TNF-α, APC-PCI) compared to age matched healthy controls. Correlations existed between aneurysm size, decreased platelet count, increased high sensitive-C-reactive protein, IL-6 and APC-PCI complex levels.

In paper II effects of statin treatment were investigated, showing that patients on statins had lower levels of cholesterol, but also of homocysteine, ceruloplasmin, orosomucoid, (matrix metallo-proteinase) MMP-9 and ET-1 in plasma, but higher levels of albumin, and the APC-PCI complex.

In paper III relationships between markers of proteolysis, fibrinolysis and coagulation and aneurysm size and growth during follow-up were studied. MMP-2 levels were lower in AAA patients than in healthy controls. Only MMP-2 was related to AAA size.

In paper IV relationships between markers of inflammation and endothelial function and aneurysm growth were studied. We confirmed that initial aneurysm diameter is related to yearly AAA growth. Furthermore, age and initial levels of ET-1 were also related to AAA growth during 7 years follow-up.

In paper V patterns of systemic biomarkers and their relationship to aneurysm growth during yearly follow-up of patients with AAA were analyzed. Few relationships were demonstrated between the development of mediators and aneurysm growth during annual analysis of this patient material, which was extended compared to the previous analyses.

In conclusion, none of the above biomarkers can predict aneurysm growth or replace ultrasound surveillance. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Associate Professor Wanhainen, Anders, Kärlkirurgiska enheten, Kirurgkliniken, Akademiska sjukhuset, Uppsala
organization
publishing date
type
Thesis
publication status
published
subject
keywords
matrix metalloproteinases, biomarkers, risk factors, fibrinolysis, coagulation, inflammation, Abdominal aortic aneurysm, statin, interleukin 6., APC-PCI complex, serpine-1, endothelin-1
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2010:64
pages
82 pages
publisher
Department of Vascular diseases, Skåne University Hospital Malmö, Lund University
defense location
MFC ingång 59, lilla aulan
defense date
2010-06-04 13:00
ISSN
1652-8220
ISBN
978-91-86443-80-1
language
English
LU publication?
yes
id
debfad48-d8a0-42fa-934d-cf248bbbd6b7 (old id 1594472)
date added to LUP
2010-05-05 08:40:28
date last changed
2018-05-29 09:28:49
@phdthesis{debfad48-d8a0-42fa-934d-cf248bbbd6b7,
  abstract     = {Abdominal aortic aneurysm (AAA) develops in 3-6% of the population over 65 years and affects mainly men. AAA has a complex etiology involving inflammation, proteolysis, fibrinolysis and coagulation. The general aim of the present thesis was to study the associations between markers of inflammation, proteolysis, fibrinolysis and coagulation with aneurysm size and growth.<br/><br>
In paper I associations between markers for these mechanisms and AAA size were evaluated. Patients with AAA had significantly increased levels of several markers ([endothelin] ET-1, [interleukin] IL-6, [tumour necrosis factor] TNF-α, APC-PCI) compared to age matched healthy controls. Correlations existed between aneurysm size, decreased platelet count, increased high sensitive-C-reactive protein, IL-6 and APC-PCI complex levels.<br/><br>
In paper II effects of statin treatment were investigated, showing that patients on statins had lower levels of cholesterol, but also of homocysteine, ceruloplasmin, orosomucoid, (matrix metallo-proteinase) MMP-9 and ET-1 in plasma, but higher levels of albumin, and the APC-PCI complex.<br/><br>
In paper III relationships between markers of proteolysis, fibrinolysis and coagulation and aneurysm size and growth during follow-up were studied. MMP-2 levels were lower in AAA patients than in healthy controls. Only MMP-2 was related to AAA size.<br/><br>
In paper IV relationships between markers of inflammation and endothelial function and aneurysm growth were studied. We confirmed that initial aneurysm diameter is related to yearly AAA growth. Furthermore, age and initial levels of ET-1 were also related to AAA growth during 7 years follow-up.<br/><br>
In paper V patterns of systemic biomarkers and their relationship to aneurysm growth during yearly follow-up of patients with AAA were analyzed. Few relationships were demonstrated between the development of mediators and aneurysm growth during annual analysis of this patient material, which was extended compared to the previous analyses.<br/><br>
In conclusion, none of the above biomarkers can predict aneurysm growth or replace ultrasound surveillance.},
  author       = {Flondell-Sité, Despina},
  isbn         = {978-91-86443-80-1},
  issn         = {1652-8220},
  keyword      = {matrix metalloproteinases,biomarkers,risk factors,fibrinolysis,coagulation,inflammation,Abdominal aortic aneurysm,statin,interleukin 6.,APC-PCI complex,serpine-1,endothelin-1},
  language     = {eng},
  pages        = {82},
  publisher    = {Department of Vascular diseases, Skåne University Hospital Malmö, Lund University},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Circulating biomarkers in patients with abdominal aortic aneurysm},
  volume       = {2010:64},
  year         = {2010},
}