title: N-Terminal Pro-B-Type Natriuretic Peptide Is Related to Retinal Microvascular Damage: The Rotterdam Study.
abstract: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a marker of cardiac dysfunction and has been linked to various indices of large vessel disease. However, it remains unclear whether NT-proBNP also relates to microvascular damage. In a community-dwelling population, we studied the association between NT-proBNP and retinal microvascular damage.
  
  
  
  From the population-based Rotterdam Study, we included 8437 participants (mean age 64.1 years and 59% women) without a history of cardiovascular disease, with NT-proBNP data and gradable retinal images. NT-proBNP serum levels were measured using an immunoassay. Retinopathy signs, that is, exudates, microaneurysms, cotton wool spots, and dot/blot hemorrhages, present on fundus photographs were graded in the total study population; retinal vascular calibers, that is, arteriolar and venular calibers, were semiautomatically measured in a subsample (n=2763) of the study population. We conducted cross-sectional analyses on the association between NT-proBNP and retinal microvascular damage using logistic and linear regression models, adjusting for age, sex, and cardiovascular risk factors. We found that NT-proBNP was associated with the presence of retinopathy (adjusted odds ratio [95% confidence interval] per SD increase in natural log-transformed NT-proBNP: 1.14 [1.03-1.27]). We also found that higher NT-proBNP was associated with narrower arteriolar calibers (adjusted mean difference in arteriolar caliber per SD increase in natural log-transformed NT-proBNP: -0.89 µm [-1.54 to -0.24]). This association remained unchanged after excluding participants with retinopathy signs.
  
  
  
  In participants free of clinical cardiovascular disease, higher levels of NT-proBNP are associated with retinal microvascular damage, suggesting a potential role for NT-proBNP as marker for small vessel disease.
authors.affiliation: From the Departments of Epidemiology (U.M., M.A.I., A.H., C.C.W.K., M.K.I.), Ophthalmology (U.M., C.C.W.K.), Radiology (M.A.I.), and Neurology (M.A.I., M.K.I.), Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands (P.T.V.M.d.J.); Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands (P.T.V.M.d.J.); and Department of Retinal Signal Processing, Netherlands Institute of Neuroscience, Amsterdam, The Netherlands (P.T.V.M.d.J.).
authors.forename: Unal
authors.initials: U
authors.lastname: Mutlu
authors.affiliation: From the Departments of Epidemiology (U.M., M.A.I., A.H., C.C.W.K., M.K.I.), Ophthalmology (U.M., C.C.W.K.), Radiology (M.A.I.), and Neurology (M.A.I., M.K.I.), Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands (P.T.V.M.d.J.); Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands (P.T.V.M.d.J.); and Department of Retinal Signal Processing, Netherlands Institute of Neuroscience, Amsterdam, The Netherlands (P.T.V.M.d.J.).
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
authors.affiliation: From the Departments of Epidemiology (U.M., M.A.I., A.H., C.C.W.K., M.K.I.), Ophthalmology (U.M., C.C.W.K.), Radiology (M.A.I.), and Neurology (M.A.I., M.K.I.), Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands (P.T.V.M.d.J.); Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands (P.T.V.M.d.J.); and Department of Retinal Signal Processing, Netherlands Institute of Neuroscience, Amsterdam, The Netherlands (P.T.V.M.d.J.).
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: From the Departments of Epidemiology (U.M., M.A.I., A.H., C.C.W.K., M.K.I.), Ophthalmology (U.M., C.C.W.K.), Radiology (M.A.I.), and Neurology (M.A.I., M.K.I.), Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands (P.T.V.M.d.J.); Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands (P.T.V.M.d.J.); and Department of Retinal Signal Processing, Netherlands Institute of Neuroscience, Amsterdam, The Netherlands (P.T.V.M.d.J.).
authors.forename: Paulus T V M
authors.initials: PT
authors.lastname: de Jong
authors.affiliation: From the Departments of Epidemiology (U.M., M.A.I., A.H., C.C.W.K., M.K.I.), Ophthalmology (U.M., C.C.W.K.), Radiology (M.A.I.), and Neurology (M.A.I., M.K.I.), Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands (P.T.V.M.d.J.); Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands (P.T.V.M.d.J.); and Department of Retinal Signal Processing, Netherlands Institute of Neuroscience, Amsterdam, The Netherlands (P.T.V.M.d.J.).
authors.forename: Caroline C W
authors.initials: CC
authors.lastname: Klaver
authors.affiliation: From the Departments of Epidemiology (U.M., M.A.I., A.H., C.C.W.K., M.K.I.), Ophthalmology (U.M., C.C.W.K.), Radiology (M.A.I.), and Neurology (M.A.I., M.K.I.), Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.); Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands (P.T.V.M.d.J.); Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands (P.T.V.M.d.J.); and Department of Retinal Signal Processing, Netherlands Institute of Neuroscience, Amsterdam, The Netherlands (P.T.V.M.d.J.). m.ikram@erasmusmc.nl.
authors.forename: M Kamran
authors.initials: MK
authors.lastname: Ikram
mesh_terms: D000368:Aged; D001160:Arterioles / Q000473:pathology*; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007118:Immunoassay; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D009426:Netherlands; D016017:Odds Ratio; D010446:Peptide Fragments / Q000097:blood*; D010781:Photography; D011237:Predictive Value of Tests; D012164:Retinal Diseases / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D018570:Risk Assessment; D012307:Risk Factors; D015854:Up-Regulation; D014652:Vascular Diseases / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D014699:Venules / Q000473:pathology*
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: N-terminal pro-BNP; arterioles; biomarkers; etiology; heart diseases; venules