Circulating Proneurotensin Concentrations and Cardiovascular Disease Events in the Community

James L. Januzzi, Asya Lyass, Yuyin Liu, Hanna Gaggin, April Trebnick, Alan S. Maisel, Ralph B. D'Agostino, Thomas J. Wang, Joseph Massaro, Ramachandran S. Vasan

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Objective - Neurotensin is a peptide whose receptor (sortilin receptor 1) is linked to cardiovascular disease (CVD) development. We hypothesized concentrations of proneurotensin (stable profragment of neurotensin) would predict incident cardiovascular events in community-based subjects. Approach and Results - Blood samples from 3439 participants in the Framingham Heart Study (FHS) Offspring cohort (mean age 59.2 years, 47.1% male) were tested for proneurotensin. Primary outcome of interest was incident hard CVD (myocardial infarction, stroke, and cardiovascular death); interaction between proneurotensin concentration with sex, low-density lipoprotein concentrations, and sortilin receptor 1 single-nucleotide polymorphisms was sought. At baseline, those in the highest log-proneurotensin quartile were younger and heavier (P<0.001); across proneurotensin quartiles, more prevalent hard CVD (from 3% to 7%; P<0.001) and diabetes mellitus (from 6% to 14%; P<0.001) were present. In age- and sex-adjusted models, log-proneurotensin concentrations predicted incident hard CVD (hazard ratio [HR], 1.24 per SD change in log-proneurotensin; 95% confidence intervals [CIs], 1.11-1.39; P<0.001), a finding that remained on adjustment for standard CVD risk factors (HR, 1.13; 95% CI, 1.01-1.27; P=0.03). Elevated log-proneurotensin concentrations were associated with shorter time to first event (P=0.02). We found no effect modification by sex, low-density lipoprotein concentration, or sortilin receptor 1 single-nucleotide polymorphisms. Concentrations of proneurotensin were modestly associated with left ventricular mass and coronary artery calcium in these subjects. Conclusions - Higher concentrations of proneurotensin are associated with a greater risk of incident cardiovascular events in the community. This association did not vary according to sex, baseline low-density lipoprotein, or sortilin receptor 1 genotype.

Original languageEnglish (US)
Pages (from-to)1692-1697
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number8
StatePublished - Aug 1 2016
Externally publishedYes


  • diabetes mellitus
  • myocardial infarction
  • nucleotides
  • risk factors
  • stroke

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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