**1. Introduction**

As a consequence of demographic changes and the proliferation of the western lifestyle, peripheral arterial occlusive disease (PAOD) has developed into a widespread disease with globally over 200 million persons affected [1–3]. PAOD preferably effects the peripheral limb vessels of the lower extremity. It limits a person's ability to walk, may require revascularization, or worse yet, can result in the loss of a limb. But it is not simply a disease of the legs. PAOD is one of multiple clinical manifestations of atherosclerotic vascular disease. It is a clinical manifestation of a systemic disease, that is frequently associated with ischemic heart disease, stroke, abdominal aortic aneurysms, and

other serious health issues [4]. In addition to its clinical aspects that limit the patient's quality of life, it has a profound cost impact on the healthcare system [5].

Despite the benefit of modern medicine, to date, there is no curative treatment available, and all non-invasive or invasive approaches aim to address the symptoms or disease progression. Hence, screening and prevention programs have gained more attention to identify new PAOD risk factors. It is well known that PAOD is associated with tobacco use, diabetes, high cholesterol, and higher age [3]. With respect to prevention of PAOD, the identification of additional risk factors is of high clinical importance.

Nowadays, there is scientific consensus that the development of PAOD is also associated with chronic subclinical inflammation [6–8]. The inflammatory genesis has been demonstrated to be multifactorial, and there is evidence that local inflammatory processes can spread systemically and trigger inflammation of the vessel wall [9]. One inflammatory focus in humans is the oral cavity, and it was proposed that chronic oral inflammations, e.g., periodontitis (PD) and caries, lead to degradation of the tooth-supporting structures [8] and may, in concert with other established risk factors, be able to trigger PAOD. PD is caused by the outgrowth of oral microorganisms, which induce a destructive host inflammatory response that contributes to progressive periodontal tissue destruction and loss of the alveolar bone around the teeth, resulting in gingival pocket formation and clinical attachment loss and, if untreated, tooth loss [10]. Tailored options are available for periodontitis treatment at various stages [11]. Approximately 47% of adults aged ≥30 years in the United States have chronic periodontitis (CP), with 30% having moderate and 8.5% severe PD [12]. PD is a complex inflammatory disease, with genetic and epigenetic factors having a role along with lifestyle and environmental factors, such as smoking, oral hygiene, nutrition, and stress, as well as other widespread systemic diseases, such as diabetes. Hereditary factors, age-dependent mutagenesis, and epigenetic changes have also been involved in the development of certain head and neck cancers, such as squamous cell carcinomas [13]. Chronic PD and obesity have been shown to be associated with pro-atherogenic lipid profiles, which are also risk factors for PAOD [14].

PD has been shown to be associated with atherosclerotic vascular disease. At least four basic pathogenic mechanisms are currently hypothesized that may explain how PD may promote atherosclerosis [15]: (1) Oral bacteria enter the blood stream and invade the arterial wall by chronic low level bacteremia; (2) inflammatory mediators released from the sites of the oral inflammation into the blood stream cause an acute phase reaction, which is pro-atherogenic; (3) specific components of oral pathogens trigger a host immune response, thereby promoting autoimmunity; (4) specific bacterial toxins that are produced by oral pathogenic bacteria have pro-atherogenic e ffects. A connection between PD as a trigger for the development of PAOD has been controversially discussed for years.

Therefore, the goals of this systematic review were: (1) to collect evidence for an association between PD or tooth loss and PAOD from the published literature and (2) to look for clinical studies that investigated the pathomechanism that might be involved in a potential cause-e ffect relationship between PD and PAOD.
