Although there were important improvements in treatment of cardiovascular diseases (CVDs) morbidity and mortality in the course of recent decades, the CVDs burden continues to be very significant. CVDs are multifactorial and linked to complex metabolic pathways. The identification of holistic risks and protective factors for CVDs continues to be a priority in epidemiological research. Previous studies considered associations of inflammation, physical fitness (determined by cardiorespiratory and muscle fitness) and cachexia were associated with increased mortality. Moreover, recent studies identified dietary patterns (such as plant-based and high-fat), beyond the isolated effect of single nutrients on lipid subfractions, and early life stressors, such as childhood maltreatment (CM), as significant contributors to long-term cardiometabolic risk, including atherosclerosis, hypertension, diabetes, hepatic steatosis, obesity, and renal dysfunction. The combination of CM and depression, particularly through sex-specific mechanisms, is still not well explored. Besides that, several organs dysfunctions such as various brain diseases, including cognitive disorders, dementia and Alzheimer’s, decreased renal function, and hepatic steatosis were associated with CVDs. Noteworthy, cardiovascular risk factors that have been linked to impaired function in one organ can thus result in alterations in the other and contribute to an acceleration of the ageing process in each organ. The aim of this proposal is to analyse, sex-specifically, how much modifiable and non-modifiable traditional risk factors, such as genomics, hypertension, T2D, hepatic steatosis, obesity, complete lipid profile, inflammation, physical fitness, and renal dysfunction, and new risk factors, such as cachexia, dietary patterns (plant-based and high-fat), and childhood maltreatment (CM), influence end-organ (brain, heart, kidney, liver) diseases and the interplay between these organs and their biological ageing.
