The difference of the negative predictive value of NT-proBNP between the genders could probably be explained by association between NT-proBNP levels and severity of CAD. It is also well-known, that despite Fulvestrant similar risk factors men develop atherosclerosis earlier in life and with a higher incidence than women. However, we have not examined the severity of CAD in the present study, so this remains purely speculative, but we the age between the genders did not differ significantly but we could document 3 times as many men than women with a history of CAD. Although the predominant pathophysiological process underlying increased circulating levels of NT-proBNP is regional and global impairment of left ventricular systolic or diastolic function leading to increased left ventricular wall stretch, recent studies have suggested that ischemia itself promotes release of BNP. The responsible mechanisms still remain to be fully elucidated, but both experimental and clinical myocardial infarction is associated with gradual and sustained elevation of circulating BNP levels and cardiac BNP expression as verified by cardiac biopsies of hypoxic ventricular areas is of the same magnitude in patients with CAD and with normal left ventricular function as in patients with congestive heart failure but no myocardial ischemia. Furthermore, NT-proBNP has emerged as a potential tool in the diagnosis and therapy of CVD besides heart failure. NT-proBNP concentrations are found to be a prognosticator of long-tem mortality in patients with stable CAD, of subsequent MI in patients with unstable CAD and of short term cardiac risk in patients with ACS. Finally, NT-proBNP concentrations below the thresholds used to diagnose heart failure have been found to be associated with an increased mortality risk and risk of cardiovascular events in individuals without heart failure. Our finding of an independent correlation between NTproBNP and myocardial perfusion defects supports that high NT-proBNP levels also could be predictive of reversible respectively irreversible myocardial perfusion defects at specific concentration intervals. This is in accordance with a recent epidemiologic study where multiple biomarkers including NT-proBNP substantially improve the risk stratification and prediction of cardiovascular death in individuals with and without CVD. However, this is contradicted by a larger study which investigated the usefulness of NT-proBNP as a predictive marker of angiographic ally significant CAD and CAD severity, where NT-proBNP could not predict significant angiographic lesions following inclusion of traditional risk factors. This objective is investigated further in current studies of our research group.