Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved. Retinal vessel metrics: normative data and their use in systemic hypertension: results from the Gutenberg Health Study Katharina A. Ponto a,f , David J. Werner a , Linn Wiedemer a , Dagmar Laubert-Reh b , Alexander K. Schuster a , Stefan Nickels a , Rene ´ Ho ¨ hn a,h , Andreas Schulz b , Harald Binder c , Manfred Beutel d , Karl J. Lackner e , Philipp S. Wild b,f,g , Norbert Pfeiffer a , and Alireza Mirshahi a,i See editorial comment on page 1573 Purpose of review: In-vivo measurement of retinal vascular calibers may be used as a tool to study the pathophysiology and clinical status of the microvasculature of the retina. The aim of this study was to generate normative data for retinal vessel parameters, and to evaluate the clinical relevance in systemic hypertension. Methods: Fundus photographs from 4309 participants of the Gutenberg Health Study were assessed using the ‘retinal vessel analyzer’ software (IMEDOS). We generated age and sex-specific nomograms in a disease-free subpopulation of 890 participants for determining the central retinal arteriolar equivalent (CRAE), the central retinal venular equivalent, and the arteriovenous ratio (AVR). Results: Women had higher values of CRAE, central retinal venular equivalent, and AVR than men, and the decrease in measures with increasing age was less steep in women than in men. Systemic hypertension was associated with lower values [odds ratio (OR), 95% confidence interval (CI) referring to area below the 5% percentile] of AVR (men: OR 2.41, 95% CI 1.669–3.490, P < 0.001; women: OR 3.01, 95% CI 2.126–4.268, P < 0.001) and CRAE (men: OR 2.60, 95% CI 1.563–4.326, P < 0.001, women: OR 3.00, 95% CI 2.004–4.487, P < 0.001). Both median CRAE and AVR were lower in participants with uncontrolled hypertension (172.28, range 83.05–251.04; and 0.81, range 0.56–1.04) versus those with screening- detected hypertension (175.72, range 101.23–222.09, P < 0.001; and 0.82, range 0.64–1.05, P ¼ 0.001), and versus those with controlled (179.10, range 108.19– 221.92, P < 0.001; and 0.84, range 0.60–1.08, P < 0.001) hypertension. Conclusion: The study provides sex and age-specific normative data for retinal vasculature. Persons with untreated or insufficiently treated hypertension are more likely to have retinal vessel equivalents outside the reference range. Keywords: arteriovenous ratio, epidemiology, hypertension, retinal vessel metrics, stroke Abbreviations: AVR, arteriovenous ratio; CRAE, central retinal arteriolar equivalent; CRVE, centra retinal venular equivalent; GHS, Gutenberg Health Study; PROCAM, Prospective Cardiovascular Mu ¨ nster Study; SAS, Statistical Analysis System; SCORE, Systematic Coronary Risk Evaluation; SPSS, Statistical Package for the Social Sciences INTRODUCTION T he retinal vasculature provides a unique window to assess human vessels noninvasively and directly in vivo [1,2]. Retinal vascular caliber changes reflect cumulative responses to aging, cardiovascular risk factors, inflammation, endothelial dysfunction, and other processes [3,4]. Identification of early microvascular changes using reliable and reproducible imaging techniques may there- fore be used as a screening modality for the assessment of cardiovascular disease, and especially for the management of both the ocular and systemic complications of hyper- tension [5]. In a cross-sectional study, the Prospective Cardiovascular Mu ¨nster Study (PROCAM) and Systematic Coronary Risk Evaluation (SCORE) risk estimates were associated with retinal vessel equivalents [6]. Recently, it has been shown that retinal vessel parameters are associ- ated with long-term mortality in the general adult Dutch population [7]. Retinal vascular calibers are associated with a wide range of subclinical (e.g. atherosclerosis, inflam- mation, and endothelial dysfunction) and clinical cardio- vascular diseases (hypertension, coronary heart disease, Journal of Hypertension 2017, 35:1635–1645 a Department of Ophthalmology, b Department of Preventive Cardiology and Preven- tive Medicine, Center for Cardiology I, c Institute of Medical Biostatistics, Epidemiology and Informatics, Division of Biostatistics and Bioinformatics, d Department of Psycho- somatic Medicine and Psychotherapy, e Institute of Clinical Chemistry and Laboratory Medicine, f Center for Thrombosis and Hemostasis, University Medical Center, g DZHK (German Center for Cardiovascular Research), Partner Site Rhine Main, Langen- beckstr. 1, Mainz, Germany, h Department of Ophthalmology, University Hospital Bern, Bern, Switzerland and i Dardenne Eye Hospital, Bonn-Bad Godesberg, Germany Correspondence to Katharina A. Ponto, MD, FEBO, Department of Ophthalmology, University Medical Center Mainz, Langenbeckstr. 1, 55131 Mainz, Germany. Tel: +49 6131/17 7085; fax: +49 6131 17 473339; e-mail: katharina.ponto@unimedizin-mainz.de Received 30 November 2016 Revised 26 February 2017 Accepted 22 March 2017 J Hypertens 35:1635–1645 Copyright ß 2017 Wolters Kluwer Health, Inc. All rights reserved. DOI:10.1097/HJH.0000000000001380 Journal of Hypertension www.jhypertension.com 1635 Original Article