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Increased carotid intima thickness and decreased media thickness in premenopausal women with systemic lupus erythematosus: an investigation by non-invasive high-frequency ultrasound
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Gynekologisk endokrinologi/Naessén)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
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2011 (English)In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 40, no 4, 279-282 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE:

To determine whether high-frequency ultrasound (US) yielding separate assessments of intima and media thickness gives additional information about the vascular morphology compared with the total common carotid artery intima-media thickness (CCA-IMT).

METHODS:

Using a 22 MHz US instrument, we determined the near-wall CCA-IMT, the intima and media layers, and the intima/media (I/M) ratio in 47 premenopausal women with systemic lupus erythematosus (SLE), 20 healthy women, and 17 postmenopausal women (mean ages 37, 40, and 69 years, respectively).

RESULTS:

In SLE, the carotid intima was thicker (0.19 ± 0.04 vs. 0.12 ± 0.02 mm), the media thinner (0.45 ± 0.12 vs. 0.68 ± 0.24 mm), the I/M ratio higher (0.45 ± 0.17 vs. 0.20 ± 0.07) (all p < 0.0001), and the CCA-IMT lower (0.64 ± 0.13 vs. 0.80 ± 0.25 mm, p < 0.01) compared to age-matched controls. The SLE patients had a thicker carotid intima compared to the postmenopausal women (0.19 ± 0.04 vs. 0.14 ± 0.03 mm, p < 0.0001) and a similar I/M ratio.

CONCLUSION:

Separate assessment of carotid artery wall layers demonstrated a thicker intima, thinner media, and a higher I/M ratio in women with SLE compared to healthy controls and indicated an artery wall status in SLE comparable to 30-years-older healthy women. Separate estimates of carotid intima and media layers may be preferable to CCA-IMT in SLE patients.

Place, publisher, year, edition, pages
2011. Vol. 40, no 4, 279-282 p.
National Category
Rheumatology and Autoimmunity
Research subject
Medicine
Identifiers
URN: urn:nbn:se:uu:diva-163533DOI: 10.3109/03009742.2011.556146ISI: 000294068000005PubMedID: 21469940OAI: oai:DiVA.org:uu-163533DiVA: diva2:464285
Available from: 2011-12-13 Created: 2011-12-13 Last updated: 2017-12-08Bibliographically approved
In thesis
1. Carotid Artery Wall Layer Dimensions during and after Pre-eclampsia: An investigation using non-invasive high-frequency ultrasound
Open this publication in new window or tab >>Carotid Artery Wall Layer Dimensions during and after Pre-eclampsia: An investigation using non-invasive high-frequency ultrasound
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Pre-eclampsia is associated with increased risk of cardiovascular disease (CVD) later in life. The ‘gold standard’ for estimating cardiovascular risk - ultrasound assessment of the common carotid artery intima-media thickness (CCA-IMT) - does not convincingly demonstrate this increased risk. The aim of this thesis was to examine whether high-frequency (22 MHz) ultrasound assessment of the individual CCA intima and media layers and calculation of the intima/media (I/M) ratio - can indicate the increased cardiovascular risk after pre-eclampsia. After validation of the method in premenopausal women with systemic lupus erythematosus (SLE) who have a recognized increased risk of CVD, women during and after normal and preeclamptic pregnancies were investigated.

Assessment of the individual artery wall layers reliably demonstrated the increased cardiovascular risk in premenopausal women with SLE, while CCA-IMT did not. The artery wall layer dimensions in women with SLE were comparable to those of postmenopausal women without SLE and were 30 years older.

Among the women with normal pregnancies negative changes to the artery wall later on in the pregnancy were seen in those with lower serum estradiol, older age, higher body mass index or higher blood pressure early in the pregnancy. About one year postpartum, both the mean intima thickness and the I/M ratio had improved, compared to values during pregnancy. These findings support the theory that normal pregnancy is a stress on the vascular system.

Women who developed pre-eclampsia (mean age 31 years) had thicker intima layers, thinner media layers and higher I/M ratios, both at diagnosis and one year postpartum, than women with normal pregnancies, indicating increased cardiovascular risk.

Women with a history of severe pre-eclampsia (mean age 44 years; mean 11 years since the last delivery) had thicker intima layers and higher I/M ratios than women with a history of normal pregnancies, indicating long-standing negative vascular effects.

Assessment of individual CCA wall layers, but not of CCA-IMT, provided clear evidence of the well-known increased cardiovascular risk in women with SLE or pre-eclampsia. The method has the potential to become an important tool in reducing cardiovascular morbidity and mortality in these women through early diagnosis and intervention.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 66 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 890
Keyword
Systemic lupus erythematosus, normal pregnancy, pre-eclampsia, high-frequency ultrasound, common carotid artery, intima/media ratio, cardiovascular disease.
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
urn:nbn:se:uu:diva-197200 (URN)978-91-554-8641-9 (ISBN)
Public defence
2013-05-23, Sal IX, Universitetshuset, S:t Olofsgatan 10B, Box 256, 751 05 Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2013-05-02 Created: 2013-03-18 Last updated: 2013-08-30Bibliographically approved
2. Cardiovascular Disease and Immune Mechanisms in Systemic Lupus Erythematosus
Open this publication in new window or tab >>Cardiovascular Disease and Immune Mechanisms in Systemic Lupus Erythematosus
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Systemic lupus erythematosus (SLE) is an autoimmune, inflammatory disease characterized by autoantibody production and an activated type I interferon system. Cardiovascular disease (CVD) is as a major cause of morbidity and mortality. The aim of this thesis was to identify genetic risk factors for CVD in SLE. The role of T cells in regulation of the interferon-α (IFNα) production by plasmacytoid dendritic cells (pDCs) was also investigated.

   In paper I, a thicker intima, thinner media and increased intima/media ratio was found in young premenopausal women with SLE compared to healthy controls indicating increased cardiovascular risk. As traditional ultrasound assessment of the common carotid intima-media thickness (CCA-IMT) in SLE has given conflicting results separate measurement of the intima and media can be a useful tool to identify SLE patients at increased risk of CVD.

   In paper II, an association was demonstrated in SLE between a STAT4 risk allele and ischemic cerebrovascular disease and presence of anti-phospholipid antibodies (aPL). The association remained after adjustment for traditional CVD risk factors. A possible mechanism for this association is that the risk allele leads to increased production of aPL, which promotes thromboembolism.

   In paper III, a genetic locus in IRF8 was identified to be associated to coronary heart disease (CHD) in SLE. The association remained after adjustment of other CHD risk factors.  Patients with the IRF8 risk variant had increased CCA-IMT, more carotid plaques and reduced frequency of circulating B cells. Weaker binding of nuclear protein to the risk allele was demonstrated, suggesting a regulatory function of the IRF8 risk variant.

   In paper IV, activated T cells were found to strongly enhance the IFNα production by pDC stimulated with RNA-containing immune complexes via GM-CSF and IL-3. Activated SLE T cells enhanced the IFNα production to the same extent as T cells from healthy controls. This finding together with previous observations in SLE of increased levels of GM-CSF and IL-3 suggests that T cells contribute to the activated type I interferon system in SLE.

   In conclusion, this thesis demonstrates that genetic predisposition is important for CVD in SLE and describes a new role for T cells in the pathogenesis of SLE.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. 75 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 994
Keyword
Systemic Lupus Erythematosus, Cardiovascular Disease, Intima-Media Thickness, STAT4, IRF8, Interferon-α, Plasmacytoid dendritic cell, GM-CSF, IL-3
National Category
Medical and Health Sciences Rheumatology and Autoimmunity
Research subject
Medicine; Genetics; Immunology
Identifiers
urn:nbn:se:uu:diva-221808 (URN)978-91-554-8940-3 (ISBN)
Public defence
2014-06-03, Gunnesalen, Akademiska sjukhuset, psykiatrins hus, ingång 10, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2014-05-12 Created: 2014-04-04 Last updated: 2014-06-30

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