title: Circulating C-type natriuretic peptide and its relationship to cardiovascular disease in the general population.
abstract: C-type natriuretic peptide (CNP) is an endothelium-derived peptide that is released as a protective mechanism in response cardiovascular injury or disease. However, no studies have investigated circulating CNP, identifying clinical factors that may influence CNP and its relationship to cardiovascular disease in the general population. We studied 1841 randomly selected subjects from Olmsted County, MN (mean age, 63±11 years; 48% men). Plasma CNP was measured by a well-established radioimmunoassay and echocardiography, clinical characterization, and detailed medical record review were performed. We report that CNP circulates at various concentrations (median, 13 pg/mL), was unaffected by sex, was weakly associated by age, and that highest quartile of CNP identified a high-risk phenotype. Subjects with CNP in the highest quartile were associated with increased risk of myocardial infarction (multivariable-adjusted hazard ratio, 1.51; 95% confidence interval, 1.09-2.09; P=0.01) but not heart failure, cerebrovascular accidents, or death during a follow-up of 12 years. Addition of the highest quartile of CNP to clinical variables led to a modest increase in the integrated discrimination improvement for risk of myocardial infarction. In a large community-based cohort, elevated circulating CNP identified a high-risk phenotype that included cardiovascular comorbidities and left ventricular dysfunction, and provided evidence that highest concentrations of CNP potentially has prognostic value in predicting future risk of myocardial infarction. Together, these data from the general population highlight the potential value of CNP and support the need for additional studies to evaluate whether mechanisms regulating CNP could improve outcomes.
authors.affiliation: From the Cardiorenal Research Laboratory (S.J.S., P.M.M., T.I., D.M.H., H.H.C., M.M.R., J.C.B.), Divisions of Cardiovascular Diseases (S.J.S., P.M.M., T.I., D.M.H., H.H.C., M.M.R., R.J.R., J.C.B.), and Biomedical Statistics and Informatics (C.G.S., K.R.B.), Mayo Clinic, Rochester, MN. sangaralingham.jeson@mayo.edu.
authors.forename: S Jeson
authors.initials: SJ
authors.lastname: Sangaralingham
authors.affiliation: From the Cardiorenal Research Laboratory (S.J.S., P.M.M., T.I., D.M.H., H.H.C., M.M.R., J.C.B.), Divisions of Cardiovascular Diseases (S.J.S., P.M.M., T.I., D.M.H., H.H.C., M.M.R., R.J.R., J.C.B.), and Biomedical Statistics and Informatics (C.G.S., K.R.B.), Mayo Clinic, Rochester, MN.
authors.forename: Paul M
authors.initials: PM
authors.lastname: McKie
authors.affiliation: From the Cardiorenal Research Laboratory (S.J.S., P.M.M., T.I., D.M.H., H.H.C., M.M.R., J.C.B.), Divisions of Cardiovascular Diseases (S.J.S., P.M.M., T.I., D.M.H., H.H.C., M.M.R., R.J.R., J.C.B.), and Biomedical Statistics and Informatics (C.G.S., K.R.B.), Mayo Clinic, Rochester, MN.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ichiki
authors.affiliation: From the Cardiorenal Research Laboratory (S.J.S., P.M.M., T.I., D.M.H., H.H.C., M.M.R., J.C.B.), Divisions of Cardiovascular Diseases (S.J.S., P.M.M., T.I., D.M.H., H.H.C., M.M.R., R.J.R., J.C.B.), and Biomedical Statistics and Informatics (C.G.S., K.R.B.), Mayo Clinic, Rochester, MN.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Scott
authors.affiliation: From the Cardiorenal Research Laboratory (S.J.S., P.M.M., T.I., D.M.H., H.H.C., M.M.R., J.C.B.), Divisions of Cardiovascular Diseases (S.J.S., P.M.M., T.I., D.M.H., H.H.C., M.M.R., R.J.R., J.C.B.), and Biomedical Statistics and Informatics (C.G.S., K.R.B.), Mayo Clinic, Rochester, MN.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Heublein
authors.affiliation: From the Cardiorenal Research Laboratory (S.J.S., P.M.M., T.I., D.M.H., H.H.C., M.M.R., J.C.B.), Divisions of Cardiovascular Diseases (S.J.S., P.M.M., T.I., D.M.H., H.H.C., M.M.R., R.J.R., J.C.B.), and Biomedical Statistics and Informatics (C.G.S., K.R.B.), Mayo Clinic, Rochester, MN.
authors.forename: Horng H
authors.initials: HH
authors.lastname: Chen
authors.affiliation: From the Cardiorenal Research Laboratory (S.J.S., P.M.M., T.I., D.M.H., H.H.C., M.M.R., J.C.B.), Divisions of Cardiovascular Diseases (S.J.S., P.M.M., T.I., D.M.H., H.H.C., M.M.R., R.J.R., J.C.B.), and Biomedical Statistics and Informatics (C.G.S., K.R.B.), Mayo Clinic, Rochester, MN.
authors.forename: Kent R
authors.initials: KR
authors.lastname: Bailey
authors.affiliation: From the Cardiorenal Research Laboratory (S.J.S., P.M.M., T.I., D.M.H., H.H.C., M.M.R., J.C.B.), Divisions of Cardiovascular Diseases (S.J.S., P.M.M., T.I., D.M.H., H.H.C., M.M.R., R.J.R., J.C.B.), and Biomedical Statistics and Informatics (C.G.S., K.R.B.), Mayo Clinic, Rochester, MN.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Redfield
authors.affiliation: From the Cardiorenal Research Laboratory (S.J.S., P.M.M., T.I., D.M.H., H.H.C., M.M.R., J.C.B.), Divisions of Cardiovascular Diseases (S.J.S., P.M.M., T.I., D.M.H., H.H.C., M.M.R., R.J.R., J.C.B.), and Biomedical Statistics and Informatics (C.G.S., K.R.B.), Mayo Clinic, Rochester, MN.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Rodeheffer
authors.affiliation: From the Cardiorenal Research Laboratory (S.J.S., P.M.M., T.I., D.M.H., H.H.C., M.M.R., J.C.B.), Divisions of Cardiovascular Diseases (S.J.S., P.M.M., T.I., D.M.H., H.H.C., M.M.R., R.J.R., J.C.B.), and Biomedical Statistics and Informatics (C.G.S., K.R.B.), Mayo Clinic, Rochester, MN.
authors.forename: John C
authors.initials: JC
authors.lastname: Burnett
mesh_terms: D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000401:mortality / Q000503:physiopathology; D015331:Cohort Studies; D016001:Confidence Intervals; D016208:Databases, Factual; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000097:blood* / Q000401:mortality / Q000503:physiopathology; D020098:Natriuretic Peptide, C-Type / Q000097:blood*; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012720:Severity of Illness Index; D012737:Sex Factors; D015996:Survival Rate
chemical_list: D015415:Biomarkers; D020098:Natriuretic Peptide, C-Type
keywords: C-type natriuretic peptide; biological markers; cardiovascular diseases; endothelium; myocardial infarction