A study of cardiovascular disease mechanism in life course using multi-national cohorts

Abstract

According to the latest Global Burden of Disease study, cardiovascular disease including stroke and circulatory disorder continues to be the number one cause of death and disability worldwide. Cardiometabolic disorders develop as a manifestation of maladaptive interplay between genetic and environmental factors early in the life course that accelerate with ageing. The convergence of global ageing and ageing-related multimorbidity including cardiovascular disease complications and cardiometabolic disorders are concerning due to their very large socioeconomic impact on the human population in the coming decades. The use of longitudinal follow-up and survival analysis of population-based cohorts provide invaluable opportunities to characterise and delineate the pathophysiology and mechanisms that lead to morbidity and mortality. This thesis embodies the research work investigating three diverse aspects of cardiometabolism that may drive morbidity and/or mortality associated with ageing: 1) cardiorespiratory fitness and frailty; 2) circulating branched- chain amino acids that underlie the biochemical derangements in hypertension, diabetes mellitus and obesity; and 3) hyperglycaemia/dysglycaemia burden and frailty in older adults with type 2 diabetes on long-term insulin therapy.