Abstract 13967: Plasma Pro-Somatostatin and Risk of Cardiovascular Events and All-Cause Mortality in the General Population

Abstract

BACKGROUND Somatostatin is a proximal component of the well-known IGF-1/growth hormone longevity axis. However, prospective data on somatostatin are not available in humans, most likely because of the low stability of somatostatin. Recently, an assay has been developed for assessment of the stable N-terminal fragment of prosomatostatin (NT-proSST). We aimed to prospectively investigate the potential association of plasma levels of NT-proSST with cardiovascular events and all-cause mortality in apparently healthy adults. METHODS We performed prospective cohort analyses in 8,134 participants without history of cardiovascular disease (aged 28-75 years; women 52.6%) from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study in Groningen, the Netherlands. Plasma NT-proSST was measured by a novel immunoassay at baseline. Main outcomes were incident cardiovascular events and all-cause mortality during a median follow-up of 10 years. RESULTS Cross-sectionally, NT-proSST (median 306, interquartile range 279-465 pmol/L) was positively associated with male gender and age (P<0.001). In total, 708 (7.7%) participants developed a cardiovascular event and 517 (6.3%) participants died. Prospectively, NT-proSST was associated with increased risk of incident cardiovascular events and mortality (P<0.001). In multivariable models in which was adjusted for the Framingham risk factors, hazard ratios were 1.17 (95%CI 1.03-1.34; P=0.02) for cardiovascular events and 1.28 (95%CI 1.09-1.49; P=0.002) for all-cause mortality per doubling of NT-proSST. Addition of NT-proSST to the FRS, led to improved reclassification, IDI (P<0.001) and NRI (4.0%; P=0.05) for cardiovascular events. CONCLUSIONS Elevated plasma NT-proSST levels are positively associated with increased risk of future cardiovascular events and all-cause mortality, independent of common risk factors. Further studies are needed to investigate the role of pro-somatostatin as a marker of longevity and healthy-ageing in humans.