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Disease activity and increased risk of cardiovascular death among patients with psoriatic arthritis
Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
2016 (Engelska)Ingår i: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 43, nr 12, s. 2155-2161Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Objective: Recent studies indicate increased cardiovascular (CV) morbidity and mortality in patients with psoriatic arthritis (PsA), but results are inconsistent. This prompted our investigation of the mortality rate, cause of death, and incidence of acute CV events in patients from northern Sweden with PsA.

Methods: Patients with established PsA (464) were included. To calculate standardized mortality ratio (SMR) and standardized incidence ratio (SIR) for CV events, data were extracted from the National Causes of Death Register and the National Inpatient Care Register in Sweden, and compared with the general population. The study period was 1995-2011. To study the effect of inflammatory activity, a composite disease activity index (DAI) was used.

Results: The SMR (95% CI) for overall mortality and diseases of the circulatory system (International Classification of Diseases, 10th edition; I00-I99) was 1.22 (0.89-1.63) and 1.64 (1.02-2.52), respectively. In regression analysis, DAI was significantly associated with death (OR 1.99, 95% CI 1.41-2.80) when adjusted for age and sex (p < 0.001), and remained significant after stratifying patients into the 2 major causes of death: diseases of the circulatory system and malignant neoplasms. Peripheral and axial disease was associated with death (OR 4.02, 95% CI 1.84-8.84, p < 0.001) compared with peripheral disease only. The SIR (95% CI) for a CV event (myocardial infarction or stroke) was 0.597 (0.40-0.86); this association was only significant in men.

Conclusion: Patients with PsA had a small but significant increase in SMR for death due to diseases of the circulatory system compared with the general population. Among patients, death was associated with DAI, as well as axial involvement in combination with peripheral disease, indicating more aggressive disease phenotypes.

Ort, förlag, år, upplaga, sidor
2016. Vol. 43, nr 12, s. 2155-2161
Nyckelord [en]
cardiovascular diseases, disease activity, epidemiology, mortality, psoriatic arthritis
Nationell ämneskategori
Reumatologi och inflammation
Identifikatorer
URN: urn:nbn:se:umu:diva-150942DOI: 10.3899/jrheum.160070ISI: 000390237400012PubMedID: 27909142Scopus ID: 2-s2.0-85002909173OAI: oai:DiVA.org:umu-150942DiVA, id: diva2:1240191
Tillgänglig från: 2018-08-20 Skapad: 2018-08-20 Senast uppdaterad: 2018-08-22Bibliografiskt granskad
Ingår i avhandling
1. Psoriatic arthritis: a complex disease: analyses on genetic and serological biomarkers and of comorbidity
Öppna denna publikation i ny flik eller fönster >>Psoriatic arthritis: a complex disease: analyses on genetic and serological biomarkers and of comorbidity
2018 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Alternativ titel[sv]
Psoriasisartrit: en komplex sjukdom : analys av genetiska och serologiska markörer samt av komorbiditet
Abstract [en]

Psoriatic Arthritis (PsA) is a heterogonous inflammatory arthritis associated with psoriasis. The disease leads to inflammation of peripheral joints, axial skeleton and/or enthesites, and can result in severe destruction of affected joints. In contrast to rheumatoid arthritis (RA), most individuals with PsA are seronegative for rheumatoid factor (RF) and/or anti-citrullinated protein/peptide antibodies (ACPA) and the distal interphalangeal (DIP) joints are often involved. Dactylitis, a diffuse swelling of an entire digit (finger or toe), is also common. Traditional markers of systemic inflammation, such as erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) are elevated in only 50% of the individuals with PsA.

Underlying genetic factors are considered important for the aetiology, disease expression and prognosis of PsA. To date no specific biomarker for PsA disease or disease activity/severity is available and there is a need for diagnostic and prognostic tools to meet the challenge of early diagnosis and assessment of disease severity.

An increased risk of co-morbidity, particularly cardiovascular disease (CVD), has been demonstrated in patients suffering from different rheumatic diseases, e.g. systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Corresponding data for patients with PsA are more limited, but evidence exists for an increased risk of mortality and cardiovascular morbidity. However, published results are conflicting and heterogeneity among studies makes interpretation of data difficult.

The aim of this study was to investigate genetic and serological biomarkers, and also mortality and cardiovascular comorbidity, in different phenotypes of PsA and in comparison with healthy controls. Patients with PsA were included between 1995 and 2015, the majority from the county of Västerbotten, except for two cohorts from Örnsköldsvik (n=55) and Östersund (n=98).

The genetic polymorphism PTPN22+1858C/T, previously found to be associated with several autoimmune diseases, was also found associated with PsA, the results were later confirmed in a genome wide association study (GWAS). Additionally, among PsA patients, the minor allele, T, was associated with the number of deformed joints and dactylitis (Paper I). 

Genetic polymorphisms in genes related to the inflammasome were also investigated, both in comparison with healthy controls and in relation to different phenotypes of PsA (Paper II). An association was identified between patients with PsA and the polymorphism CARD8-C10X in comparison with controls. In addition, associations between various inflammasome polymorphisms and different clinical phenotypes of PsA were detected.

To investigate the relation of serological biomarkers and PsA, individuals with blood samples collected in conjunction with clinical investigation were selected (Paper III).  Associations with different biomarkers and different clinical phenotypes of PsA were identified In addition, associations were found with different biomarkers and patients with moderate/high disease activity at clinical investigation, confirming the inflammatory nature of the disease.

Mortality and incidence of acute cardiovascular disease were investigated with standardized mortality rateratio (SMR) and standardized incidence ratio (SIR) compared with the general population of Västerbotten (Paper IV). An increased SMR for diseases of the circulatory system in PsA compared with controls was found. Among PsA patients, death was associated with a composite disease activity index (DAI) and with a disease phenotype including both axial- and peripheral joint involvement. 

In conclusion, associations were found with different clinical phenotypes of PsA, both with genetic polymorphisms and serological biomarkers that confirm the inflammatory nature of the disease and illustrate the disease heterogeneity. As in many other inflammatory diseases, an increased cardiovascular mortality was found that highlights the importance of considering cardiovascular risk factors in patients with PsA.

Ort, förlag, år, upplaga, sidor
Umeå: Umeå universitet, 2018. s. 77
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1968
Nyckelord
Psoriatic Arthritis, genetics, inflammasomes, polymorphisms, biomarkers, disease expression, disease activity, cardiovascular diseases, mortality, epidemiology
Nationell ämneskategori
Reumatologi och inflammation
Identifikatorer
urn:nbn:se:umu:diva-150947 (URN)978-91-7601-910-8 (ISBN)
Disputation
2018-09-14, Sal D, Målpunkt T, våning 9, Norrlands Universitetssjukhus, Umeå, 13:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2018-08-24 Skapad: 2018-08-20 Senast uppdaterad: 2018-08-24Bibliografiskt granskad

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