Plasma N-terminal Prosomatostatin and Risk of Incident Cardiovascular Disease and All-Cause Mortality in a Prospective Observational Cohort: the PREVEND Study

BACKGROUND Somatostatin is a component of the well-known insulin-like growth factor-1/growth hormone (GH) longevity axis. There is observational evidence that increased GH is associated with an increased risk of cardiovascular disease (CVD). We aimed to investigate the potential association of plasma N-terminal fragment prosomatostatin (NT-proSST) with incident CVD and all-cause mortality in apparently healthy adults. METHODS We studied 8134 participants without history of CVD (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 in baseline samples. Outcomes were incidence of CVD and all-cause mortality. RESULTS In cross-sectional analyses, NT-proSST [mean (SD), 384.0 (169.3) pmol/L] was positively associated with male sex and age (both P < 0.001). During a median follow-up of 10.5 (Q1-Q3: 9.9–10.8) years, 708 (8.7%) participants developed CVD and 517 (6.4%) participants died. In univariable analyses, NT-proSST was associated with an increased risk of incident CVD and all-cause mortality (both P < 0.001). In multivariable analyses, these associations were independent of the Framingham risk factors, with hazard ratios (95% CI) per doubling of NT-proSST of 1.17 (1.03–1.34; P = 0.02) for incident CVD and of 1.28 (1.09–1.49; P = 0.002) for all-cause mortality. Addition of NT-proSST to the updated Framingham Risk Score improved reclassification (integrated discrimination improvement (P < 0.001); net reclassification improvement was 2.5% (P = 0.04)). CONCLUSIONS Plasma NT-proSST is positively associated with increased risk of future CVD and all-cause mortality, partly independent of traditional CVD risk factors. Further research is needed to address the nature of associations.