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Arterioscler Thromb Vasc Biol. 2016 Aug;36(8):1692-7. doi: 10.1161/ATVBAHA.116.307847. Epub 2016 Jun 16.

Circulating Proneurotensin Concentrations and Cardiovascular Disease Events in the Community: The Framingham Heart Study.

Author information

1
From the Framingham Heart Study, MA (J.L.J., A.L., H.G., R.B.D.A., T.J.W., J.M., R.S.V.); Cardiology Division, Massachusetts General Hospital, Boston (J.L.J., H.G.); Departments of Cardiometabolic Trials (J.L.J, H.G., A.T.) and Biostatistics (A.L., Y.L., R.B.D., J.M.), Harvard Clinical Research Institute, Boston, MA; Department of Mathematics and Statistics, Boston University, MA (A.L., R.B.D.A.); Departments of Biostatistics (Y.L., J.M.) and Preventative Medicine (R.S.V.), Boston University Medical Center, MA; Heart Failure Section, Veterans Affairs Medical Center, San Diego, CA (A.S.M.); and Cardiology Division, Vanderbilt Medical Center, Nashville, TN (T.J.W.). jjanuzzi@mgh.harvard.edu.
2
From the Framingham Heart Study, MA (J.L.J., A.L., H.G., R.B.D.A., T.J.W., J.M., R.S.V.); Cardiology Division, Massachusetts General Hospital, Boston (J.L.J., H.G.); Departments of Cardiometabolic Trials (J.L.J, H.G., A.T.) and Biostatistics (A.L., Y.L., R.B.D., J.M.), Harvard Clinical Research Institute, Boston, MA; Department of Mathematics and Statistics, Boston University, MA (A.L., R.B.D.A.); Departments of Biostatistics (Y.L., J.M.) and Preventative Medicine (R.S.V.), Boston University Medical Center, MA; Heart Failure Section, Veterans Affairs Medical Center, San Diego, CA (A.S.M.); and Cardiology Division, Vanderbilt Medical Center, Nashville, TN (T.J.W.).

Abstract

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.

KEYWORDS:

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

PMID:
27312221
PMCID:
PMC4965295
DOI:
10.1161/ATVBAHA.116.307847
[Indexed for MEDLINE]
Free PMC Article

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