Understanding peripheral arterial disease in the current era

Atherosclerotic cardiovascular disease is the primary driver of premature death in global populations in recent decades. Mortality statistics, most publications, and guidelines in the atherosclerotic cardiovascular disease field have traditionally focused on cardiac and cerebrovascular adverse events and causes of death. However, given the increasing prevalence of lower extremity peripheral arterial disease and its expanding burden on global health systems, such an emphasis might represent a skewed perception of vascular risk within the broader atherosclerotic spectrum. Although common risk factors appear similar in all atherosclerotic cardiovascular disease subgroups, several crucial differences exist, including pathophysiological details and lesion patterns, as well as adherence to guideline-based recommendations. Individuals with peripheral arterial disease frequently remain asymptomatic for many years, often decades, and are typically diagnosed only at an advanced stage of the condition. By this time, however, the expected long-term outcomes are already extremely poor. When diagnosed at this point, the overall 5-year mortality is between 30% and 50%, thus even surpassing outcomes of severe cancer and acute myocardial infarction. Compared with cardiac and cerebrovascular disease, peripheral arterial disease receives lower priority in research and clinical practice, which is compounded by poor patient adherence to preventive care, lifestyle modification, and pharmacological therapy. This clinical Series of three papers aims to improve this distressing situation. For this purpose, it is important to recognise the underacknowledgment, underdiagnosis, and undertreatment of peripheral arterial disease and to understand the complex inter-relationships behind it before suitable interdisciplinary measures can be initiated. In this Series paper, we want to reach the broad interdisciplinary community, and above all, those who see these patients every day in general practice and internal medicine. The focus is primarily on the global importance of peripheral atherosclerosis and its drivers. In paper 2 of this Series, readers are introduced to modern complementary therapy, ranging from the optimisation of risk factors and optimal pharmacological therapies to innovative endovascular procedures and traditional surgical treatments. In the sense of integrated care and a stepwise approach, the described therapy alternatives can be combined individually for each patient. Paper 3 of this Series provides readers with a deep insight into the global significance and burden of peripheral arterial disease. Since this disease is primarily characterised by its long-term, chronically progressive course, improving long-term outcomes represents a central aspect of this paper. It aims to further illuminate striking disparities between geographical regions, sexes, and socioeconomic groups. With strong recommendations, this clinical Series can help to guide both clinicians and policy makers towards effective preventive measures.