This post-hoc analysis of the PANDORA Study represents the largest study on the general Italian population to date that has focussed on the prevalence of asymptomatic PAD in the community setting. Previously, another study investigated the prevalence of PAD in Italian subjects, but only patients with symptomatic PAD were evaluated . The present study is in agreement with findings from the original PANDORA study since it confirms the prevalence of a low ABI in patients who would otherwise be classified as intermediate and even low CV risk . The prevalence of asymptomatic PAD within the Italian population was 22.9%. Limited use of statins in the total cohort of Italian subjects (10.5%) was also confirmed within the subgroup diagnosed with dyslipidemia (24%). Other participant countries had a higher percentage of patients on statins. The risk of developing PAD is also increased in subjects with a higher consumption of saturated fatty acids , which is common in northern Europe . In contrast, risk is reduced in subjects with higher intake of cereal fiber, Vitamin E and wine consumption [31, 33, 34], which are typical components in the so-called "Mediterranean diet" . These food preferences in Italian people may have a favourable action to decrease cardiovascular risk for PAD. Although gender was equally matched in the present study, this may be a potential factor to consider when comparing across differences in other European countries. However, two separate studies, performed on a Turkish and a US population respectively, have demonstrated that the prevalence of PAD does not vary by gender [22, 35]. Subjects without symptoms of the lower limbs and overt CV disease who are at risk of PAD, including those less than 50 years with diabetes and one additional risk factor (smoking, dyslipidemia, hypertension, or hyperhomocysteinemia), or aged 50 to 69 with a history of smoking or diabetes, or aged 70 and older need to be further screened for PAD
as highlighted in the PARTNERS study . These patients need to be submitted to clinical, diagnostic and instrumental assessment, according to recommendations mainly derived from the PARTNERS study . Another ABI study performed in Germany on 6, 880 unselected outpatients in Primary Care, aged ≥65 years, who underwent ABI testing by family physicians in 344 centres, showed a prevalence of PAD of 18% [36, 37]. This frequency is in agreement with results of the present study, even though in the Get ABI study 2.8% of the subjects with low ABI had PAD symptoms. In addition, risk profile in the Get ABI population showed differences from that of PANDORA, which was due to fewer previous cardiovascular events or the presence of diabetes. Nevertheless, as evidenced by PANDORA, the Get ABI also confirmed the usefulness of expanding measurement of ABI over to other risk categories beyond those indicated by guidelines. A more recent study performed in Turkey showed a 20% prevalence of PAD, corroborating findings observed in our study . Moreover, demographic and clinical characteristics of this Turkish population were similar to the Italian cohort (i.e., age, gender ratio, associated risk factors, etc.), suggesting that a relatively high prevalence of PAD can be observed in other Mediterranean-like lifestyles. Previous data reported from the National Health and Nutrition Examination Study (NHANES; 1999-2004) showed a 3% prevalence of low ABI in the low or intermediate risk population . Furthermore, Sumner et al. analyzed data from three NHANES between the years 1999 -2004 and showed that the prevalence of PAD is consistently increasing in asymptomatic adults in the US population. Prevalence rose from 3.7 to 4.6% (p = 0.001) over a six year period . Marked differences between these results and those from the PANDORA study were observed, where even in countries with minimal prevalence of low ABI, frequencies of over 3% were reported, thus emphasizing the need for periodical measurement of ABI in many risk-groups. There are some notable findings resulting from this study, such as the relationship between restricted use of statins and the prevalence of low ABI. The well recognised beneficial prognostic effect of statin treatment on the prevention of vascular events in patients with symptomatic PAD  should be emphasized, with the view to improving their lower extremity motor performance . Our findings from the PANDORA study show a possible protective action of statins against the occurrence of PAD and may assist in re-evaluating the pathogenetic role of dyslipidemia in this condition, especially considering the fact that other characteristics normally altered by statins, such as inflammation, were not taken into account.
It is also worth highlighting the association between marital status and the presence of low ABI, with unmarried or widowed subjects more likely affected by low ABI than married subjects. This shows unexpected evidence on the relationship between marital status and prevalence of PAD, although previous reports have described the role of marital status, as part of a more general social support, as influencing clinical symptoms of PAD . Although we have not directly examined what underlying factors may influence the link between marital status (divorced/separated/unmarried) and prevalence of PAD, it is recognised that the rate of depressive symptoms is increased in these individuals [43, 44]. It is well documented that patients with PAD have a higher rate of depression and that this is also correlated with the reduced activity/sedentary lifestyle that they lead . However, our findings did not reveal any discernible difference in sedentary lifestyle between patients with or without PAD, suggesting that this cause-and-effect relationship between marital status and prevalence of PAD is more complex.
The major interest of psycho-social factors as cardiovascular risk factors is also suggested by these PANDORA findings . The explanation for the different frequency distribution of PAD among countries may be related to the variability of subject characteristics, in terms of both frequency distribution and type of risk factors, and could have been influenced by several lifestyle habits  in addition to differences in use of statins between several countries.
This study has some limitations, including the lack of a follow-up period on the occurrence of cardiovascular events, over an appropriate period after ABI assessment, in subjects presenting with a low ABI but otherwise classified as being at low or moderate risk and, as such, not considered candidates for more aggressive preventive treatment. However, the adverse prognostic implications of a low ABI (≤0.90) are widely known and are derived from many previous studies that have definitively confirmed this instrumental examination as an independent predictor of high cardiovascular risk [2, 4]. Therefore, the standard use of Doppler remains indispensable for an adequate ABI measurement in family practice, as reported in healthy subjects, patients at risk and patients clinically suspected for PAD . It should be emphasized that most recent epidemiological studies on PAD have been performed only  or almost only  in primary care service, placing ABI measurement in the daily clinical practice of the general practitioner. The ABI value may be limited in some patients because of the calcification of tibial arteries that are less compressible, resulting in unusually high ABI values (> 1.40) . Data from a recent study by Cacoub and coworkers  in a subset of 2, 077 patients older than 55 years and with 2 or more cardiovascular risk factors (including diabetes) in which the ABI was measured by general practitioners in France, provided a prevalence of low ABI (below 0.90) of 10.4%, which is similar to that of the French population of the PANDORA study, confirming the satisfactory reliability of the data collected . The results reported in the present study are in agreement to other previous studies in the general population [22, 36, 37]. The prevalence of PAD evaluated using the ABI was found to be 18-19% in subjects aged above 55 or 65 years in The Netherlands, Germany, the UK, and at approximately 30% in patients with selected vascular risk factors in North America and France [18, 19, 48–50]. Given the very high prevalence of PAD, we observed in moderate-risk patients and the CV morbidity and mortality associated with PAD [1, 2], undoubtedly better public and health professional awareness would help preserve individual CV health and achieve public health goals.