Abstract 15837: Circulating Proneurotensin Concentrations Predict Cardiovascular Disease Events in the Community: The Framingham Heart Study
Introduction: Neurotensin is a 13-amino acid peptide whose receptor (SORT1) is strongly linked to cardiovascular disease (CVD) development through several mechanisms, including a role in hepatic low density lipoprotein (LDL) metabolism. We measured concentrations of proneurotensin (PNT; the stable pro-fragment of neurotensin) in subjects from the Framingham Heart Study (FHS) Offspring cohort.
Hypothesis: Concentrations of PNT provide incremental information for incident CV events, possibly through interactions with LDL.
Methods: Blood samples from 3439 fasting subjects (mean age 59.2 years, 47.1% male) were tested for PNT (Sphingotec, Hennigsdorf, GE). The primary outcome of interest was incident hard CVD (composite of myocardial infarction [MI], stroke, and CV death). Incident hard CHD (MI and CV death) was also examined.
Results: Compared to subjects in PNT quartiles 1-3, those in the highest quartile were more likely to be younger and heavier, more likely to smoke (all P <0.007), and across PNT quartiles more likely to have prevalent CVD (from 24.4% to 31.1%; P =0.003) and diabetes mellitus (from 5.5% to 13.4%; P<0.001). No association between PNT and LDL concentrations was observed. In age and sex-adjusted Cox proportional hazards models, log-PNT concentrations predicted incident hard CVD (hazard ratio [HR] = 1.24 per one standard deviation [SD] change in log-PNT; 95% confidence intervals [CI] = 1.11-1.39; P <0.001). Greatest risk for incident hard CVD was observed in log-PNT quartile 4 (HR = 1.53 per one SD change in log-PNT vs quartile 1; P =0.005). In models adjusted for standard risk factors, log-PNT remained significantly associated with incident hard CVD (HR = 1.13 per one SD change in log-PNT; 95% CI = 1.01-1.27; P = 0.03). Addition of log-PNT to the FHS Risk Score resulted in modest risk reclassification (NRI = 0.024; 95% CI=-0.0008-0.048), and in Kaplan Meier analyses, shorter time to first event was seen in higher log-PNT values (log rank P = 0.02). Similar results were found for hard CHD. We did not observe effect modification by LDL.
Conclusions: Higher concentrations of PNT are associated with a greater risk of incident hard CVD and CHD in the community independent of LDL concentrations and other risk factors.
Author Disclosures: J. Januzzi: Research Grant; Significant; Siemens, Singulex, Thermo Fisher, Prevencio. Other Research Support; Significant; Amgen, Boeringer Ingelheim, Novartis. Consultant/Advisory Board; Modest; Critical Diagnostics, Sphingotec. Consultant/Advisory Board; Significant; Roche Diagnostics. A. Lyass: None. Y. Liu: None. H.K. Gaggin: None. A. Trebnick: None. R.B. D'Agostino: None. T.J. Wang: Other Research Support; Modest; Diasorin. Consultant/Advisory Board; Modest; Takeda. J. Massaro: None. V. Ramachandran: None.
- © 2015 by American Heart Association, Inc.