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N-Terminal Pro-B-Type Natriuretic Peptide Is Related to Retinal Microvascular Damage: The Rotterdam Study
Unal Mutlu1, M Arfan Ikram1, Albert Hofman1
1From 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.).
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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