More than 70 years have passed since the first description of Klinefelter Syndrome (KS), the most
frequent chromosome disorder causing male infertility and hypogonadism. KS is associated with increased cardiovascular
(CV) mortality due to several comorbidities, including hypogonadism, as well as metabolic syndrome
and type 2 diabetes, which are highly prevalent in these patients. Aside from metabolic disturbances, patients
with KS suffer from both acquired and congenital CV abnormalities, cerebrovascular thromboembolic disease,
subclinical atherosclerosis and endothelial dysfunction, which may all contribute to increased CV mortality.
The mechanisms involved in this increased risk of CV morbidity and mortality are not entirely understood.
More research is needed to better characterise the CV manifestations, elucidate the pathophysiological mechanisms
and define the contribution of testosterone replacement to restoring CV health in KS patients. This review
explores the complex association between KS, metabolic syndrome and CV risk in order to plan future
studies and improve strategies to reduce mortality in this high-risk population.
