Endocrine-Metabolic Dysfunction and Thrombogenicity: Pathophysiological Links to Cardiovascular Risk

Abstract

Endocrine-metabolic disorders are increasingly recognized as major determinants of cardiovascular risk because their effects extend beyond alterations in glucose and lipid metabolism and involve inflammatory, vascular, and hemostatic pathways. This review analyzed the interaction between endocrine-metabolic abnormalities, the development of a prothrombotic state, and cardiovascular risk, with particular emphasis on obesity, insulin resistance, type 2 diabetes mellitus, metabolic syndrome, thyroid dysfunction, and hypercortisolism. A structured integrative review was conducted using scientific evidence from clinical guidelines, systematic reviews, meta-analyses, mechanistic studies, and epidemiological investigations. The findings showed that obesity, diabetes mellitus, and metabolic syndrome presented the greatest overlap of pathophysiological mechanisms, particularly chronic inflammation, oxidative stress, endothelial dysfunction, platelet hyperreactivity, coagulation activation, and impaired fibrinolysis. Coagulation activation was one of the most consistently identified pathways, while reduced fibrinolytic capacity, frequently associated with increased plasminogen activator inhibitor-1 activity, contributed to thrombus persistence. Diabetes was additionally associated with structural alterations of fibrin and increased platelet responsiveness, whereas visceral adiposity was linked to inflammatory and procoagulant signaling. Thyroid dysfunction and hypercortisolism also demonstrated relevant hemostatic alterations, supporting the broader relationship between endocrine regulation and thrombosis. Overall, the evidence indicates that cardiovascular risk in endocrine-metabolic disease results from an interconnected network in which metabolic dysfunction promotes inflammation and oxidative stress, followed by endothelial injury, platelet and coagulation activation, impaired fibrinolysis, and ultimately atherothrombotic events. The prothrombotic state therefore represents an important intermediate pathophysiological phenotype between endocrine-metabolic dysfunction and cardiovascular disease. These findings support comprehensive cardiovascular prevention and highlight the need for future studies evaluating integrated metabolic and hemostatic biomarkers for improved risk stratification.