RA is a systemic immune and inflammatory disease associated with accelerated atherosclerosis and excess cardiovascular morbidity and mortality [1, 36]. This inflammation may act to impair endothelial function, arterial compliance and arterial elasticity and as a contributing factor in the initiation or the progression of atherosclerosis. Some studies showed that arterial elasticity is reduced in patients with RA [37, 38]. Recently, we also found that carotid-femoral PWV (8.29 ± 0.64 m/s vs 7.52 ± 0.63 m/s) is increased, arterial elasticity is decreased, in young patients with RA (21-34 years old, 7 women, mean RA duration: 13.8 ± 12.6 months), as compared with control (p=0.03) [27]. In the young patients with RA pulse wave propagation time (it is inversely related to the arterial PWV to the classical formula “PWV (m/s)=Distance (m)/Transit time (s)”) between measurement sites was significantly shorter than in the control group (p=0.02) [27].

SLE is a chronic inflammatory autoimmune disease affecting young women associated with increased atherosclerotic vascular diseases [39]. In SLE, the degree of systemic inflammation correlates with development of atherosclerosis [40]. Antiphospholipid antibodies (aPL) (a family of autoantibodies that recognize various combinations of phospholipids and phospholipid-binding proteins) and immune complexes occur more commonly in patients with SLE [41]. In SLE, although Farzaneh-Far et al. [42] suggest that aPL are not associated with increased preclinical or clinical atherosclerosis and arterial stiffening, these antibodies may be a cause of arterial damage which initiates atherogenesis [39]. These complexes bind to receptors on the endothelium, triggering an upregulation of adhesion molecules such as E-selectin, intercellular adhesion molecules 1 (ICAM-1) and vascular cell adhesion molecules 1 (VCAM-1). Also, oxidized low density lipoprotein (LDL), lipoprotein (a) and CD40-CD40L have role in the pathogenesis of atherosclerosis, thrombosis and inflammatory processes [43-46]. Recently, we found that carotid-femoral (aortic) PWV (8.98 ± 2.05 m/s vs 8.05 ± 0.94 m/s) is increased in premenopausal women with SLE (mean age: 33.6±9.6 vs 30.2±9.2 years old, 24 women, mean SLE duration: 5.3 ± 4.6 years), as compared with control (p=0.04) [28]. Aortic PWV was determined by using an automatic device, the Complior Colson (France), which allowed on-line pulse wave recording and automatic calculation of PWV.

WG is a rare disease, affecting only 1 in every 30.000-50.000 people, that often begins with inflammation of the upper airways or lungs and may progress to an inflammation of blood vessels throughout the body [47-51]. There is a strong and specific association of WG with presence of anti-neutrophil cytoplasmic antibodies (ANCA) to a defined target antigen, proteinase 3 (PR3-ANCA), which is present within primary azurophil granules of neutrophils and lysozymes of monocytes [48]. Upon cytokine priming of neutrophils, this enzyme translocates to the cell surface, where PR3-ANCAs can interact with their antigens and activate neutrophils [49]. The presence of ANCA in the plasma of patients and genetic involvement of the human leukocyte antigen system reflects an autoimmune background of the disease. de Leeuw et al. [52] demonstrated that atherosclerosis, a systemic inflammatory disease, as determined by carotid intima-media thickness, was increased in patients with WG. Recently, we showed that carotid-femoral (aortic) PWV is increased in patients with WG, as compared with control (p=0.04) [29].

Psoriasis is a hereditary and chronic inflammatory skin disorder affecting 2-3% of the Caucasian population [53]. It is mediated by T cells, dendritic cells and inflammatory cytokines and characterized by marked increases in keratinocyte proliferation, prominent alterations in dermal capillary vasculature [54]. Psoriatic arthritis has been defined as an inflammatory arthritis associated with psoriasis, usually seronegative for rheumatoid factor. Psoriatic arthritis affects men and women almost equally. The prevalence of Psoriatic arthritis among patients with psoriasis has varied from 6% to 42% [55]. It is demonstrated that psoriasis and psoriatic arthritis appear to be associated with an increased cardiovascular mortality and morbidity [56]. We and others have demonstrated an increase in the carotid-femoral (aortic) PWV [30, 57].

FMF is an autosomal recessive disorder virtually restricted to certain ethnic groups originating from the Middle East: Sephardic Jews, Armenians, Arabs, Druze and Turks [58]. It is characterized by recurrent episodes of serosal inflammation, chest pain, and arthritis usually accompanied by fever [58]. The main complication of untreated patients is the development of amyloidosis [58]. In most FMF patients, colchicine treatment prevents febrile attacks and development of amyloidosis [59]. During the febrile attacks, an acute phase response develop, manifested by a marked increase in erythrocyte sedimentation rate (ESR), CRP, serum amyloid A, fibrinogen and leucocytes [58]. Histopathologic examination of FMF involves inflammation with infiltration by neutrophils [58]. In our study, the carotid-femoral PWV (8.53±1.65 m/s vs 7.75±0.86 m/s) is slightly increased in patients with FMF which compared with control group (p=0.05) [31, 32]. We found significant correlation between PWV and age (p<0.001, r=0.67), body mass index (p<0.001, r=0.52) and leukocytes (p<0.001, r=0.66) in all groups and in patients with FMF group (p<0.001, r=0.73; p=0.01, r=0.52; p<0.001, r=0.69, respectively).

We found significant correlation between PWV and leukocytes. FMF is an autosomal recessive disorder characterized by mutations in the MEFV gene located on 16p [60]. The gene encodes a 781-amino acid protein called pyrin expressed in cells of the myeloid lineage. Although the role of MEFV gene in the development of FMF attacks does not yet known clearly, its malfunction results eventually in inflammation. And it has been proposed that in FMF any minor stimulus leads to an uncontrolled inflammatory reaction with complement activation, due to absence of an inhibitor of C5a and excessive tumor necrosis factor (TNF) release [61, 62]. The inflammatory process of FMF is also caused by leukotriene B4, a potent lipid chemoattractant and mediator of acute inflammation [63]. Circulating leucocytes play important roles in atherosclerosis which is an inflammatory disease [64]. Positive associations between total leukocyte count and risk factors of atherosclerosis or coronary artery diseases are frequently mentioned [65, 66].

Sarcoidosis is a systemic inflammatory multiorgan disease, characterized in the affected organs by T-lymphocyte-mononuclear phagocyte infiltration, granuloma formation, and distortion of normal microarchitecture. Histology of granulomas shows a central zone with macrophages, epithelioid cells, and multinucleated giant cells in addition to activated CD4 lymphocytes, and a peripheral zone with macrophages, fibroblasts, CD4 and CD8 lymphocytes [67-71]. The reported prevalence of sarcoidosis varies from 9 to 64 per 100.000 populations (in Sweden and in Italy, respectively) [68]. Although, sarcoidosis is known to be a systemic inflammatory disease which can affect virtually any organ system, it unusually complicates vascular involvement. However in fact, several authors have suggested that vasculitis may be a feature of sarcoidosis; but, such reports usually related to cutaneous vasculitis [3, 4]. In a one study, granulomatous angiitis and microangiopathy were reported in 30.8% of sarcoidosis patients with cutaneous involvement [69]. On the other hand, reports on the coexistence of sarcoidosis and vasculitis had led us to think the possibility that sarcoidosis and vasculitis may be etiopathgenetically related. This inflammation of sarcoidosis may act to impair endothelial function, arterial compliance and arterial elasticity and as a contributing factor in the initiation or the progression of atherosclerosis. Recently, we demonstrated that the carotid-femoral (aortic) PWV (10.04±1.73 vs 9.05±1.18 m/s) was higher in patients with sarcoidosis (12 women, 7 man, sarcoidosis duration: 124.8 ± 85.9 months) than in control subjects (p=0.04) [33].

BD is a chronic, multisystem disorder characterized by genital and oral aphtae, skin lesions and uveitis [72]. In some patients, manifestations of vascular complications, which may include deep vein and arterial thrombosis, aortic and arterial aneurysm, may dominate the clinical picture [72]. The cause of vascular disease in BD is unknown. Histopathologic studies have demonstrated that the predominant lesion is vasculitis. The vessel wall and perivascular tissue are infiltrated by lymphocytes, monocytes, plasma cells and neutrophils [72]. Recent studies suggest that activated leukocytes may contribute to vascular injury in BD [73]. In vivo, neutrophils from patients with BD generate high levels of oxygen derived free radicals and cause endothelial cell lysis [73]. Concentrations of circulating lipid peroxidation products are elevated in patients with BD [74]. Orem et al. [75] studied plasma lipoprotein (a) and its relationship with disease activity in patients with BD. They concluded that the fluctuations of plasma lipoprotein levels with the activity of disease may be a contributing risk factor in the development of thrombogenic complications in patients with BD. Other study showed that the levels of autoantibodies against oxidized LDL were significantly higher in patients than controls [76]. These autoantibodies may be a factor responsible for endothelial dysfunction and development of vascular pathology in BD [76]. Lipid peroxidation was found increased in the active period compared to the inactive period of BD. Therefore, patients with active BD may be much more susceptible to the atherogenic events than those in the inactive period of the disease and control subjects. We studied 14 patients with BD (18-44 years old, 10 men) and 28 healthy subjects (18-39 years old, 21 men) without known cardiovascular disease. Arterial distensibility was assessed by automatic carotid-femoral PWV measurement using the Complior Colson device. The carotid-femoral PWV (8.4±1.4 vs 8.5±1.1 m/s) is not increased in patients with BD compared with control subjects (p>0.05) [35]. This finding may explain the decrease of mortality rate within time in patients with BD. In contrast to our study Chang et al. [77] showed that patients with BD had significantly higher PWV values than in controls.

SS is a clinically heterogeneous generalized disorder which affects the connective tissue of the skin and internal organs such as gastrointestinal tract, lungs, heart and kidneys. It is characterized by alterations of the microvasculature, disturbances of the immune system and by massive deposition of collagen [78]. Endothelial dysfunction and vasculopathy of the small and large vessels are crucial pathogenic factors in SS. Timár et al. [79] showed that increased augmentation index, is used as clinical measurements of arterial stiffness, and PWV of the aorta in comparison to age and sex matched healthy controls in patients with SS. Cypiene et al. [80] also demonstrated that SS patients have increased augmentation index and PWV and lower flow-mediated dilatation (is an ultrasound-based technique that measures nitric oxide mediated vasodilatation of the brachial artery in response to increased arterial wall shear stress) as compared to control subjects.

TA is a rare, chronic, inflammatory disease primarily of the aorta and its branches [81, 82]. The subclavian, renal and carotid arteries can also be involved. Inflammation of large blood vessels may cause segments of the vessels to weaken and stretch, resulting in an aneurysm. Vessels can also become narrowed or even completely blocked. TA is more common in women than in men and usually begins in the 2^nd or 3^rd decade [82]. The diagnosis of TA is based on a combination of factors, including angiography, computed axial tomography and magnetic resonance imaging. Cardiovascular disease is a major cause of mortality and morbidity in patients with TA. Ng et al. [83] demonstrated that the mean carotid-femoral PWV (p=0.03), aortic augmentation index derived from the radial artery (p=0.002) and carotid augmentation index (p=0.03) were higher in patients with TA compared with controls.

In conclusion, the arterial distensibility was assessed by automatic carotid-femoral (aortic) PWV measurement using the Complior Colson device was decreased in chronic inflammatory rheumatic diseases. Decrease of arterial distensibility in chronic inflammatory rheumatic diseases are especially due to inflammation that is triggered by cardiovascular risk factors such as hypertension, hyperlipidemia, hyperglycemia. In these disorders there is increased risk of developing premature cardiovascular disease but clear guidelines on the management of cardiovascular risk factors is still missing. As inflammation is the basic pathology in these diseases, anti-inflammatory theraphy would be the main stay treatment strategy for the protection of cardiovascular events in the near future.