Life-threatening risk factors contribute to the development of diseases with the highest mortality through the induction of regulated necrotic cell death.

Chronic diseases affecting the cardiovascular system, diabetes mellitus, neurodegenerative diseases, and various other organ-specific conditions, involve different underlying pathological processes. However, they share common risk factors that contribute to the development and progression of these diseases, including air pollution, hypertension, obesity, high cholesterol levels, smoking and alcoholism. In this review, we aim to explore the connection between four types of diseases with different etiologies and various risk factors. We highlight that the presence of risk factors induces regulated necrotic cell death, leading to the release of damage-associated molecular patterns (DAMPs), ultimately resulting in sterile inflammation. Therefore, DAMP-mediated inflammation may be the link explaining how risk factors can lead to the development and maintenance of chronic diseases. To explore these processes, we summarize the main cell death pathways activated by the most common life-threatening risk factors, the types of released DAMPs and how these events are associated with the pathophysiology of diseases with the highest mortality. Various risk factors, such as smoking, air pollution, alcoholism, hypertension, obesity, and high cholesterol levels induce regulated necrosis. Subsequently, the release of DAMPs leads to chronic inflammation, which increases the risk of many diseases, including those with the highest mortality rates.