This paper, edited by Prof. Thomas Lüscher, explores the impact of non-traditional risk factors on ischemic heart disease (IHD), including environmental pollution, mental health disorders, and infectious diseases. The authors highlight that while traditional risk factors such as hypertension, diabetes, dyslipidaemia, and smoking have been effectively addressed, other factors remain significant contributors to IHD. The concept of the "exposome" is introduced to describe the totality of exposure to these new risk factors, which interact nonlinearly and unpredictably to enhance the detrimental effects of single or multiple factors. The review discusses the role of various environmental pollutants, such as air, water, and soil contamination, and their impact on cardiovascular health. Air pollution, particularly PM2.5, is identified as a major contributor to IHD, reducing life expectancy and increasing the risk of cardiovascular events. The paper also examines the effects of climate change, soil pollution, water contamination, light pollution, and acoustic pollution on IHD. Mental health disorders, including depression and social isolation, are highlighted as significant risk factors. Chronic stress, often associated with mental conditions, can lead to adverse health consequences, including hypertension and metabolic abnormalities. Social isolation and loneliness are also linked to increased cardiovascular risk. Infectious diseases, such as respiratory infections, periodontal diseases, and COVID-19, are discussed for their role in triggering or exacerbating IHD. The paper emphasizes the need for comprehensive strategies to mitigate these risks, including policy measures to reduce exposure to environmental pollutants, personal protective behaviors, and therapeutic approaches to manage mental health and infectious diseases. The authors conclude that while there is growing awareness and guidelines addressing these non-traditional risk factors, more research and intervention trials are needed to fully understand and manage their impact on cardiovascular health.This paper, edited by Prof. Thomas Lüscher, explores the impact of non-traditional risk factors on ischemic heart disease (IHD), including environmental pollution, mental health disorders, and infectious diseases. The authors highlight that while traditional risk factors such as hypertension, diabetes, dyslipidaemia, and smoking have been effectively addressed, other factors remain significant contributors to IHD. The concept of the "exposome" is introduced to describe the totality of exposure to these new risk factors, which interact nonlinearly and unpredictably to enhance the detrimental effects of single or multiple factors. The review discusses the role of various environmental pollutants, such as air, water, and soil contamination, and their impact on cardiovascular health. Air pollution, particularly PM2.5, is identified as a major contributor to IHD, reducing life expectancy and increasing the risk of cardiovascular events. The paper also examines the effects of climate change, soil pollution, water contamination, light pollution, and acoustic pollution on IHD. Mental health disorders, including depression and social isolation, are highlighted as significant risk factors. Chronic stress, often associated with mental conditions, can lead to adverse health consequences, including hypertension and metabolic abnormalities. Social isolation and loneliness are also linked to increased cardiovascular risk. Infectious diseases, such as respiratory infections, periodontal diseases, and COVID-19, are discussed for their role in triggering or exacerbating IHD. The paper emphasizes the need for comprehensive strategies to mitigate these risks, including policy measures to reduce exposure to environmental pollutants, personal protective behaviors, and therapeutic approaches to manage mental health and infectious diseases. The authors conclude that while there is growing awareness and guidelines addressing these non-traditional risk factors, more research and intervention trials are needed to fully understand and manage their impact on cardiovascular health.