Unal Mutlu1, M Arfan Ikram1, Albert Hofman1, Paulus T V M de Jong1, Caroline C W Klaver1, M Kamran Ikram2. 1. 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.). 2. 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.
Abstract
OBJECTIVE: 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. APPROACH AND RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE: 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. APPROACH AND RESULTS: 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. CONCLUSIONS: 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.
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