In the setting of PsA subjects, several clinical and laboratory predictors of six-month and three-month response to TNF-α blockers have been identified [21, 22]. In PsA subjects starting treatment with TNF-α blockers, this prospective study shows that HS or CPs at baseline are associated per se with a high risk of not achieving MDA.
A variety of variables (CRP, complement C3, IL-6 and TNF-α) implicated in the regulation of the inflammatory process  and, in turn, in the pathophysiology of arthritides , are relevant in the etiology and the development of atherosclerosis [25–27]. Major markers of atherosclerosis (HS and CPs) that assess the global damage due to metabolic and inflammatory determinants  are affected in PsA subjects [9, 13, 16]. Accordingly, subjects who exhibit a high prevalence of HS and of CPs are likely to have experienced a more severe inflammatory state [12–15].
Among the 98/270 PsA patients who achieved MDA at 12 months, the prevalence of HS and of CPs was significantly lower than in those who did not. Accordingly, the presence of one of these atherosclerosis markers was associated with a high risk of not achieving MDA. Moreover, the presence of HS or of CPs was associated with a poor probability of sustained MDA at the 24-month follow-up. However, because of the relatively small number of patients included in this sub-analysis, the evaluation of the impact of CPs and/or HS on achieving sustained MDA, although statistically significant, should be considered only as a proof of concept.
The combined data lend credence to the possibility that the presence of CPs and/or HS is a negative predictor of achieving and maintaining MDA.
By evaluating such a large number of consecutive PsA patients (270 PsA subjects), the MetS was diagnosed in 33.7%, HS was found in 28.1% and CPs in 21.5% of subjects. These data are in line with previous literature data obtained on smaller size samples [3, 5, 6]. Further strengthening the link between cardiometabolic variables and inflammation, in a previous analysis on the present population, we have found that obesity (defined as a Body Mass Index > 30) is associated with a statistically significant increase in the risk of a poor treatment response in PsA subjects receiving TNF-α blockers . At variance with the already published data, in this study the presence of obesity is defined according to the waist circumference measurement (which is a major NCEP criterion for the diagnosis of the MetS) . However, as highlighted in Table 2 also in this case, the prevalence of obesity is higher in those not achieving MDA. Moreover, since obesity is a major feature of the MetS, and being known to impact on HS and CPs presence, a multivariate regression analysis was performed to adjust all the results of this study for the presence of MetS and of its features and to exclude collinearity in the prediction of achieving MDA. In this respect, we are confident to have excluded some important bias in this study.
In addition to CPs and HS, other demographic (male gender) and rheumatologic (CRP and TJC) variables predicted the achieving of MDA. The relevance of CPs and HS as MDA predictors has been adjusted (regression model) for the large majority of clinical and laboratory variables known to predict the achieving of MDA .
All the carotid and liver ultrasound evaluations were performed only at the study baseline evaluation. A prospective evaluation of changes in these parameters during the treatment with TNF-α blockers could have further clarified the interrelation between IMT, HS and PsA disease activity. Although some literature data  suggest that treatment with 'biologic agents' is associated with the lowering of the IMT as well as of the degree of liver steatosis, further ad hoc designed studies are needed to address this important issue.
The link between inflammation and atherosclerosis is strongly supported by the finding of a direct correlation between CRP and ESR with the IMT in the present setting. All these inflammatory reactants have been included in the regression model to adjust for their values. The finding that the achieving of MDA is directly associated with a high CRP level and negatively associated with HS and CPs might sound like a contrasting result. However, these findings are in line with the possibility that HS and the presence of CPs are atherosclerosis markers influenced both by inflammation and by other variables (that is, obesity, aging) known to negatively impact on the achieving of MDA [22, 28]. Although further studies are needed to describe better the underlying pathophysiologic mechanisms, this finding suggests that the presence of HS and CPs can be reliable markers of a cumulative (inflammatory + metabolic) damage.
A noteworthy finding is that the presence of CPs was found in 87.5% of those with the mutilans PsA subset. Because of the rarity of this clinical subset, the number of subjects evaluated was extremely low and no statistical inferences are possible from these data. However, that the CPs prevalence is maximal in the most severe PsA subset needs to be further evaluated in properly designed studies.
A series of markers is involved in the interrelation between inflammation and atherosclerosis [9, 27]. In addition to ESR and CRP, the evaluation of TNF-α and IL-6 levels could have been of interest in the present setting. However, these measurements were not available in all cases.
Among PsA subjects enrolled in the present setting, the prevalence of an axial involvement is high (23.7%). At variance with most data in the literature, we have enrolled subjects experiencing a failure of treatment with traditional DMARDs and with the indication to start treatment with TNF-α blockers. Because of its high rate of refractoriness to DMARDs, the presence of an axial subset has been recognized as a major criterion to start treatment with TNF-α blockers . The selection criteria used could have caused such a high prevalence of the axial subset in our study population. However (Table 2), there was no significant difference in the achieving of MDA after stratifying the population according to the different PsA clinical subsets.
Most previous studies in PsA subjects employed different criteria to define a good clinical response. We have chosen the criteria of achieving MDA proven to be appropriate in providing an outcome measure for clinical trials . As to clinical and demographic variables known to predict MDA, the hazard ratios found in the present study are in line with those of previous reports .
In addition to their obvious pathophysiological significance, these data may have pharmaco-economic implications . Because of their high cost and their side effects (that is, a higher than normal risk of infections and of malignancies) , the identification of predictors of the success of TNF-α blockers is mandatory. By stratifying the achieving of a good clinical response, a risk/benefit evaluation may be performed in each case and for each patient. This, in turn, would hinder the use of TNF-α blockers in subjects with a low probability of success. Further studies with higher numbers of subjects are needed to address this important issue.