Depression, Type D and alexithymia were found to be strongly related to cardiovascular risk in several populations 
, but HIV patients were not yet considered. This cohort study investigated for the first time the potential role of such psychological traits, in addition to traditional cardiovascular risk factors, in predicting CVD in the HIV population.
Despite an association between CVD and depression was repeatedly documented, and several studies showed a role of immune parameters in such a relationship, making its investigation particularly interesting in the setting of HIV infection 
, we observed a possible association between higher depression scores and the presence of CPs in univariate models, but failed to demonstrate an independent association when contextually evaluating the other psychological constructs.
Some prospective studies suggested a potential association of Type D with hypercholesterolemia, hypertension, metabolic syndrome and increased mortality rates in patients with established CVD 
. As for depression, the association among Type D personality and investigated outcomes was not confirmed in our cohort.
In contrast, we found that higher alexithymia scores were associated with higher c-IMT, presence of CPs and vascular events, both in univariate analyses and in all final multivariate models. Indeed, several studies investigated the relationships between alexithymia, cardiovascular risk factors, CVD and cardiovascular mortality in the general population 
. In particular, two large population-based studies linked the alexithymic trait with a previous diagnosis of coronary heart disease and subclinical atherosclerosis and, more recently, with increased cardiovascular mortality 
. The preliminary, mechanistic explanation of such findings may be provided by the fact that subjects with the alexithymic trait were shown to suffer amplified and prolonged neurovegetative reactions to stress stimuli, using models of skin-conductance response 
. Such investigations suggested that the alexithymic trait may disturb the autonomic system and the pituitary-adrenal axis, leading to increased neuroendocrine insult of the vasculature 
. In fact, in the HIV setting, the association between the alexithymic trait and CVD risk is in line with the predictions of the cognitive-emotional interaction model 
, according to which the high prevalence of alexithymia in HIV may reflect the effects of the virus on sub-cortical areas of the brain, involved in cognitive emotional regulation and the relative autonomic responses mediating vascular damage 
An alternative explanation for the observed association between alexithymia and CVD would be that alexithymic patients might have an intrinsic higher risk of CVD simply because they more frequently present traditional cardiovascular risk factors. For instance, if subjects with alexithymia were more commonly diabetics, hypertensive, obese and smokers, their higher risk of CVD would not be caused by the psychological trait, but rather by such well-known risk factors (a typical example of confounding). Also, in this scenario, the co-inclusion of such factors and alexithymia in multivariate analysis might have covered the statistical significance of single risk factors due to a certain degree of multicollinearity (which may also explain why we did not observe a significant association between CVD and other well-known CVD risk factors). However, in our sample alexithymic patients were not significantly more hypertensive (p
0.6), smokers (p
0.2) or obese (p
0.2). They were older (48.3 y vs 42.8 y, p<0.001), and more frequently diabetics (27.1% vs 11.2%, p
0.004). Nevertheless, when analyses were stratified by age-class and diabetes, alexithymia remained significantly and strongly associated with the presence of plaques as well as with vascular events both in patients <50 y and in non diabetics (see Table S1
Our data would therefore suggest a true association between the alexithymic trait and CVD risk in HIV patients, in agreement with the above mentioned cognitive-emotional interaction model 
. Alexithymia may thus represent a novel and unexpected determinant of accelerated atherothrombosis in the setting of HIV infection.
Importantly, in our sample 42.3% of the patients had a TAS-20 score ≥50; a prevalence of the alexithymic trait including borderline cases that is nearly three times higher than in the general population 
. Such proportion rose to 70.4% in patients aged ≥55 (p
0.002, data not shown). Thus, besides the relatively small sample size and short follow-up, our data can only provide preliminary findings, to be interpreted with caution, because the high prevalence of the alexithymic trait may partly reflect a secondary effect of HIV-mediated vascular damage on such brain areas 
. On the other side, if the observed association will be confirmed, the high prevalence of alexithymia in our sample may explain the high incidence of vascular events that we observed in a relatively short follow-up: approximately 10% of patients suffered a vascular event (lethal in one third of cases), a remarkable and unexpected rate at the time of cohort setting.
It is worth noting, in any case, that this is the first evaluation of the prevalence of alexithymia in an unselected sample of HIV patients. Notably, the alexithymic trait was not associated with either current (p
0.8) or Nadir CD4 T-cell counts (p
0.9), duration of HIV infection (p
0.8), AIDS diagnosis (p
0.5) or baseline HIV viremia (p
0.4, data not shown), suggesting either a relation with behaviors at risk of getting HIV infection, such as drug addiction 
, or with the early phases of HIV infection 
. Furthermore, data collected on a fraction (n
70) of patients in our sample, who were retested for psychological traits after a mean of 18 months, revealed that alexithymic scores were only minimally modified (data not shown), indicating a remarkable stability of such a psychological phenotype over time, in line with other reports in the general population 
The major strengths of our study are the accurate consecutive enrolment of the study sample, the contextual evaluation of both the psychological traits and c-IMT, each operated by a single certified investigator, and the active follow-up for vascular events, that allowed limiting data censoring to a minimum in the final Cox’s multivariate models. In addition to the limitations mentioned above, shortcomings of the study are the single experimental site and the inclusion of 95% of Caucasian subjects.
In conclusion, HIV alexithymic patients may be at a significantly and persistently increased risk of both preclinical and clinically overt vascular damage. Such a result is preliminary and require confirmation from studies with larger sample size and longer follow-up. In fact, further research is strongly warranted: should our findings be confirmed, they may pave the way to an array of additional interventions to control cardiovascular disorders in the HIV population.