Di Minno, Matteo (2015) PRIMARY AND SECONDARY HAEMOSTATIC PARAMETERS AND SURROGATE MARKERS OF ATHEROSCLEROSIS IN PATIENTS WITH PSORIATIC ARTHRITIS: FROM EPIDEMIOLOGICAL EVIDENCE TO EXPERIMENTAL STUDIES. [Tesi di dottorato]

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Tipologia del documento: Tesi di dottorato
Lingua: English
Titolo: PRIMARY AND SECONDARY HAEMOSTATIC PARAMETERS AND SURROGATE MARKERS OF ATHEROSCLEROSIS IN PATIENTS WITH PSORIATIC ARTHRITIS: FROM EPIDEMIOLOGICAL EVIDENCE TO EXPERIMENTAL STUDIES.
Autori:
AutoreEmail
Di Minno, Matteodario.diminno@hotmail.it
Data: 29 Marzo 2015
Numero di pagine: 44
Istituzione: Università degli Studi di Napoli Federico II
Dipartimento: Medicina Clinica e Chirurgia
Scuola di dottorato: Medicina clinica e sperimentale
Dottorato: Fisiopatologia clinica e medicina sperimentale
Ciclo di dottorato: 27
Coordinatore del Corso di dottorato:
nomeemail
Marone, Giannogianni.marone@unina.it
Tutor:
nomeemail
Rubba, Paolo Osvaldo[non definito]
Data: 29 Marzo 2015
Numero di pagine: 44
Parole chiave: Cardiovascular risk, platelet reactivity, haemostasis, fibrinolysis, atherosclerosis, endothelial function.
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/09 - Medicina interna
Area 06 - Scienze mediche > MED/11 - Malattie dell'apparato cardiovascolare
Area 06 - Scienze mediche > MED/15 - Malattie del sangue
Area 06 - Scienze mediche > MED/16 - Reumatologia
Area 06 - Scienze mediche > MED/50 - Scienze tecniche mediche applicate
Aree tematiche (7° programma Quadro): SALUTE e TUTELA DEL CONSUMATORE > Biotecnologie, strumenti e tecnologie generiche per la salute umana
SALUTE e TUTELA DEL CONSUMATORE > Ottimizzazione per la prestazione delle cure sanitarie per i cittadini in Europa
Depositato il: 07 Apr 2015 12:36
Ultima modifica: 29 Set 2015 08:12
URI: http://www.fedoa.unina.it/id/eprint/10186
DOI: 10.6092/UNINA/FEDOA/10186

Abstract

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy affecting up to 40% of patients with psoriasis and leading to severe physical limitations and disability. Beyond skin and joint involvement, PsA is characterized by a high prevalence of comorbidities, such as autoimmune, infectious, and neoplastic diseases. Moreover, metabolic syndrome (MetS) and its major features (obesity, hypertension, impaired fasting glucose, hyperlipidemia) have been frequently found in PsA patients, and a shortened life expectancy was reported in this clinical setting, with CV disease accounting for up to 36% of the overall mortality. Growing evidence on CV morbidity and mortality in PsA patients suggests that a 62% increased mortality has been reported in PsA subjects compared with the general population. By assessing cardiovascular risk factors, PsA patients exhibit an increased prevalence of MetS as compared to both subjects with AR or with AS, (38% vs 20% and vs 11%, respectively). Similarly, an increased prevalence of hypertension, hyperlipidemia, obesity and type II diabetes (Odds Ratios ranging from 1.54 to 2.59) has been found in PsA subjects as compared with those with psoriasis. However, the presence of traditional CV risk factors does not entirely explain the CV morbidity and mortality found in PsA patients, inflammation appearing to act synergistically with traditional CV risk factors, thus contributing to the atherosclerotic process and to the increased CV risk. Thus, EULAR suggested the need of studies evaluating the intimate mechanisms of the interaction between inflammation and the CV risk. The primary aim of this project was to evaluate primary and secondary haemostatic parameters, as well as surrogate markers of atherosclerosis in PsA patients to understand underlying mechanisms leading to the increased CV risk in this clinical setting. Interestingly we found that platelet reactivity is increased in PsA patient, especially in those with an active disease. In particular, lower concentrations of pro-aggregating agents were needed by PsA subjects to achieve a stable platelet aggregation (LT-50%) than controls and the maximal aggregation (max-A%) was higher in PsA subjects than in controls. However, by stratifying for the disease activity, we found that LT-50% and max-A% of PsA subjects in Minimal Disease Activity (MDA) were comparable to controls and lower than PsA subjects with active disease. In addition, we documented that PsA patients with an active disease have significantly increased levels of several haemostatic and fibrinolytic factors. On the other hand, we found that the control of the inflammatory process is associated with a significant improvement of haemostatic and fibrinolytic parameters in PsA subjects, maximal changes being documented in patients achieving MDA. The assessment of CV risk surrogate markers showed that PsA is associated with subclinical atherosclerosis and endothelial dysfunction. In particular, we demonstrated an increased carotid IMT with a high prevalence of carotid plaques and impaired FMD in patients with PsA. The link between inflammation and the subclinical atherosclerosis has been further addressed showing that, IMT was lower in PsA subjects on TNF-α blockers than in those on traditional DMARDs and the co-existence of a MetS was associated with an higher CCA-IMT in subjects on DMARDs than in those under TNF-α blockers. Overall, results of our project suggest that PsA patients have a increased platelet reactivity, impaired fibrinolysis and subclinical atherosclerosis accompanied by an impaired endothelial function. Most of these alterations seem to be associated with the inflammatory status and are likely to be modified by the anti-rheumatic treatments. All these data are in line with many literature data that support the possibility of an increased CV risk in patients with PsA.

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