Circulating Proneurotensin Concentrations and Cardiovascular Disease Events in the Community

• DOI: 10.1161/atvbaha.116.307847
• Publication Date: 2016-06-17T03:11:19Z
• Authors: 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. V...
• Keywords: Male; 0301 basic medicine; Incidence; Cholesterol, LDL; Kaplan-Meier Estimate; Middle Aged; Prognosis; Polymorphism, Single Nucleotide; 3. Good health; Adaptor Proteins, Vesicular Transport; 03 medical and health sciences; Cross-Sectional Studies; Massachusetts; Cardiovascular Diseases; Multivariate Analysis; Linear Models; Prevalence; Humans; Female; Genetic Testing; Biomarkers; Neurotensin; Aged

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.