Somatostatin concentrations associated with increased risk of CVD and mortality
Plasma N-terminal Prosomatostatin and Risk of Incident Cardiovascular Disease and All-Cause Mortality in a Prospective Observational Cohort: the PREVEND StudyAbbasi A, Kieneker LM, Eva Corpeleijn E, et al. - Clinical Chemistry 2017;63(1): 278–287
Somatostatin, present in many tissues, plays an important role in neuroendocrine regulation through: inhibition of growth hormone (GH)7 release from the pituitary gland , inhibition of glucagon secretion and suppression of the release of insulin-like growth factor-1 (IGF-1) that has been associated with CV outcomes , inhibition of several hormones, including serotonin, vasoactive intestinal polypeptide (VIP), gastrin, insulin, glucagon, secretin, and motilin , and regulatory effects on the gastrointestinal tract, the endocrine pancreas, the immune system, and the CV system .
The N-terminal fragment prosomatostatin 1–64 (NT-proSST) is a stable fragment of endogenous somatostatin precursor and reflects somatostatin concentrations and may be a marker for acute HF and mortality .
This study evaluated the associations of plasma NT-proSST with incident CVD and all-cause mortality in participants without a history of CVD at baseline (aged 28-75 years), from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study. Furthermore, the predictive value of NT-proSST when added to the Framingham Risk Score (FRS) was assessed in this population.
- Of 8134 participants with mean plasma NT-proSST concentrations of 412 (SD: 169) pmol/L in men and 364 (SD: 167) pmol/L in women (P < 0.001), 8.7% developed first CVD events, and 6.4% participants died.
- Age- and gender-adjusted HRs of cumulative survival for the highest tertile compared with the lowest tertile of NT-proSST were 1.28 (95% CI: 1.06 –1.54; P = 0.01) for incident CVD and 1.49 (95% CI: 1.19 –1.87; P < 0.001) for all-cause mortality.
- After adjustment for traditional CVD risk factors included in the FRS, higher values of NT-proSST were associated with increased risk of incident CVD (HR: 1.22; 95% CI: 1.01–1.48) and all-cause mortality (HR: 1.32; 95% CI: 1.05–1.65).
- There was a 17% (95% CI: 3%–34%) increased risk of incident CVD and a 28% (95% CI: 9%–49%) increased risk of all-cause mortality per doubling NT-proSST concentrations for each outcome, after adjusting for the Framingham risk factors (HR for CV mortality: 1.22; 95% CI: 0.90 –1.64; HR for cerebrovascular events: 1.05; 95% CI: 0.82–1.35).
- Addition of NT-proSST to the updated FRS as continuous variable led to an integrated discrimination improvement of 0.004 (95% CI: 0.002– 0.007; P < 0.001) for the 10-year risk of CVD (correct reclassification of 2.5%).
- The addition of hsTNT or NT-proBNP into the FRS improved the c-index from 0.785 (95% CI: 0.770–0.800) to 0.796 (95% CI: 0.781–0.812; P for difference <0.001) or 0.787 (95% CI: 0.770–0.802; P for difference <0.001), respectively.
NT-proSST concentrations were associated with an increased risk of incident CVD and all-cause mortality, after adjusting for traditional CVD risk factors and emerging biomarkers, in a population-based cohort of men and women without a history of CVD. These findings support a possible future predictive role of NT-proSST concentrations.