Online Supplement and Ambulatory as Predictors of Retinal Arteriolar Narrowing Fang-Fei Wei 1, Zhen-Yu Zhang 1, Lutgarde Thijs 1, Wen-Yi Yang 1, Lotte Jacobs 1, Nicholas Cauwenberghs 1, Yu-Mei Gu 1, Tatiana Kuznetsova 1, Karel Allegaert 2, Peter Verhamme 3, Yan Li 4, Harry AJ Struijker-Boudier 5, Jan A. Staessen 1,6 Author Affiliations: 1 Studies Coordinating Centre, Research Unit and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Siciences, University of Leuven, Leuven, Belgium; 2 Department of Development and Regeneration, University of Leuven, Belgium; 3 Centre for Molecular and Vascular Biology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Belgium; 4 Center for Epidemiological Studies and Clinical Trials and Center for Vascular Evaluations, Shanghai Institute of, Shanghai Key Laboratory of, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; 5 Department of Pharmacology, Maastricht University, Maastricht, The Netherlands; 6 R&D Group VitaK, Maastricht University, Maastricht, The Netherlands Corresponding Author: Jan A. Staessen, jan.staessen@med.kuleuven.be or ja.staessen@maastrichtuniversity.nl, Kapucijnenvoer 35, Box 7001, BE-3000 Leuven, Belgium
Supplementary Online Content This appendix formed part of the original submission and has been peer reviewed. We posted it as supplied by the authors. Supplement to: and Ambulatory as Predictors of Retinal Arteriolar Narrowing. Table S1. CRAE in Relation to Baseline BP Adjusted for Covariables at Follow-Up p2 Table S2. Retinal Phenotypes in Relation to Baseline and Concurrent BPs p3 Table S3. CRVE in Relation to Baseline BP Adjusted for Covariables at Baseline Table S4. CRVE in Relation to Baseline BP Adjusted for Covariables at Follow-Up Table S5. AVR in Relation to Baseline BP Adjusted for Covariables at Baseline Table S6. AVR in Relation to Baseline BP Adjusted for Covariables at Follow-Up Table S7. Retinal Phenotypes by Category Participants Untreated at Baseline p4 p5 p6 p7 p8 Table S8. Retinal Phenotypes by Category Adjusted for Covariables at Follow-Up p9 Figure S1. Multivariable-Adjusted Associations of CRAE with Baseline SBP and DBP p10
Page 3 of 10 Table S1. Central Retinal Arteriolar Equivalent in Relation to Adjusted for Covariables at Follow-Up s Including a Single Type of Measurement of Measurement Adjusted 1.70 ( 2.70 to 0.70) 2.15 ( 3.11 to 1.20) 0.67 ( 1.86 to 0.52) 1.79 ( 2.94 to 0.65) Fully adjusted 1.97 ( 3.04 to 0.91) 2.30 ( 3.29 to 1.30) 0.95 ( 2.19 to 0.29) 1.83 ( 3.00 to 0.66) Adjusted 1.34 ( 2.33 to 0.34) 1.72 ( 2.68 to 0.76) 0.64 ( 1.77 to 0.48) 1.42 ( 2.52 to 0.33)* Fully adjusted 1.36 ( 2.40 to 0.32) 1.79 ( 2.80 to 0.79) 0.68 ( 1.82 to 0.47) 1.51 ( 2.62 to 0.39) Abbreviations: CRAE, central retinal arteriolar equivalent. Effect size (95% confidence interval) express the risk associated with a 1-SD increase in conventional or daytime blood pressures. All estimates account for clustering within families. Adjusted estimates account for follow-up characteristics including sex, age, and smoking. Fully adjusted estimates were additionally adjusted for body mass index, serum total cholesterol, plasma glucose, and drinking at follow-up, for follow-up duration, and for three indicator variables coding for starting, stopping or continuing antihypertensive drug treatment from baseline to follow-up. Significance of the effect sizes: * P 0.05, P 0.01, and P 0.001.
Page 4 of 10 Table S2. Retinal Phenotypes in Relation to Baseline and Concurrent s Including a Single Type of Measurement Baseline Concurrent Baseline of Measurement Concurrent CRAE, µm 2.30 ( 3.29 to 1.30) 3.10 ( 4.18 to 2.03) 1.61 ( 2.63 to 0.58) 2.60 ( 3.71 to 1.48) AVR 0.011 ( 0.017 to 0.005) 0.014 ( 0.020 to 0.007) 0.009 ( 0.015 to 0.002) 0.011 ( 0.018 to 0.004) CRAE, µm 1.79 ( 2.80 to 0.79) 2.74 ( 3.74 to 1.74) 1.04 ( 2.08 to 0.004)* 0.007 ( 0.013 to 0.001)* AVR 0.012 ( 0.018 to 0.006) 0.017 ( 0.023 to 0.011) 2.40 ( 3.45 to 1.35) 0.014 ( 0.021 to 0.008) Abbreviations: CRAE, central retinal arteriolar equivalent; CRVE, central retinal venular equivalent; AVR, arteriole-to-venule ratio. Effect size (95% confidence interval) express the risk associated with a 1-SD increase in baseline daytime or concurrent blood pressures. All estimates account for clustering within families, sex, age, body mass index, serum total cholesterol, plasma glucose, and drinking at follow-up, for follow-up duration, and for three indicator variables coding for starting, stopping or continuing antihypertensive drug treatment from baseline to follow-up. Significance of the effect sizes: * P 0.05, P 0.01, and P 0.001.
Page 5 of 10 Table S3. Central Retinal Venular Equivalent in Relation to Adjusted for Covariables at Baseline s Including a Single Type of Measurement of Measurement Unadjusted 1.26 ( 2.60 to 0.10) 0.93 ( 2.28 to 0.42 ) 1.09 ( 2.76 to 0.59) 0.28 ( 1.96 to 1.39) Adjusted 0.96 ( 0.50 to 2.43) 0.11 ( 1.49 to 1.27) 1.49 ( 0.27 to 3.25) 0.89 ( 2.55 to 0.76) Fully adjusted 0.99 ( 0.54 to 2.53) 0.08 ( 1.53 to 1.37) 1.40 ( 0.38 to 3.19) 0.76 ( 2.44 to 0.93) Unadjusted 0.90 ( 2.25 to 0.45) 0.62 ( 1.97 to 0.74) 0.80 ( 2.41 to 0.82) 0.18 ( 1.79 to 1.43) Adjusted 1.37 ( 0.07 to 2.82) 0.75 ( 0.64 to 2.15) 1.28 ( 0.35 to 2.92) 0.18 ( 1.40 to 1.75) Fully adjusted 1.20 ( 0.32 to 2.72) 0.69 ( 0.78 to 2.15) 1.09 ( 0.57 to 2.76) 0.25 ( 1.36 to 1.86) Abbreviations: CRVE, central retinal venular equivalent. Effect size (95% confidence interval) express the risk associated with a 1-SD increase in conventional or daytime blood pressures. All estimates account for clustering within families. Adjusted estimates account for baseline characteristics including sex, age, and smoking. Fully adjusted estimates were additionally adjusted for body mass index, serum total cholesterol, plasma glucose, and drinking at baseline, for followup duration, and for three indicator variables coding for starting, stopping or continuing antihypertensive drug treatment from baseline to follow-up. All effect sizes were not significant.
Page 6 of 10 Table S4. Central Retinal Venular Equivalent in Relation to Adjusted for Covariables at Follow-Up s Including a Single Type of Measurement of Measurement Adjusted 0.75 ( 0.68 to 2.18) 0.12 ( 1.49 to 1.26) 1.18 ( 0.53 to 2.89) 0.75 ( 2.40 to 0.90) Fully adjusted 0.91 ( 0.60 to 2.43) 0.19 ( 1.63 to 1.24) 1.41 ( 0.38 to 3.20) 0.89 ( 2.57 to 0.79) Adjusted 1.22 ( 0.20 to 2.63) 0.75 ( 0.62 to 2.13) 1.10 ( 0.51 to 2.71) 0.24 ( 1.32 to 1.81) Fully adjusted 1.09 ( 0.39 to 2.56) 0.60 ( 0.83 to 2.03) 1.01 ( 0.63 to 2.66) 0.17 ( 1.43 to 1.76) Abbreviations: CRVE, central retinal venular equivalent. Effect size (95% confidence interval) express the risk associated with a 1-SD increase in conventional or daytime blood pressures. All estimates account for clustering within families. Adjusted estimates account for follow-up characteristics including sex, age, and smoking. Fully adjusted estimates were additionally adjusted for body mass index, serum total cholesterol, plasma glucose, and drinking at follow-up, for followup duration, and for three indicator variables coding for starting, stopping or continuing antihypertensive drug treatment from baseline to follow-up. All effect sizes were not significant.
Page 7 of 10 Table S5. Retinal Arteriole-to-Venule Ratio in Relation to Adjusted for Covariables at Baseline s Including a Single Type of Measurement of Measurement Unadjusted 0.010 ( 0.016 to 0.005) 0.012 ( 0.018 to 0.007) 0.004 ( 0.011 to 0.002) 0.010 ( 0.016 to 0.003) Adjusted 0.011 ( 0.017 to 0.005) 0.011 ( 0.017 to 0.005) 0.007 ( 0.014 to 0.0005) 0.007 ( 0.014 to 0.0003)* Fully adjusted 0.012 ( 0.019 to 0.006) 0.011 ( 0.017 to 0.005) 0.009 ( 0.016 to 0.001)* 0.007 ( 0.014 to 0.0000)* Unadjusted 0.010 ( 0.015 to 0.004) 0.012 ( 0.017 to 0.006) 0.005 ( 0.011 to 0.002) 0.010 ( 0.016 to 0.002) Adjusted 0.011 ( 0.017 to 0.004) 0.012 ( 0.018 to 0.006) 0.006 ( 0.013 to 0.0005) 0.009 ( 0.015 to 0.002) Fully adjusted 0.010 ( 0.017 to 0.004) 0.012 ( 0.018 to 0.006) 0.007 ( 0.014 to 0.0005) 0.009 ( 0.016 to 0.002) Abbreviations: AVR, arteriole-to-venule ratio. Effect size (95% confidence interval) express the risk associated with a 1-SD increase in conventional or daytime blood pressures. All estimates account for clustering within families. Adjusted estimates account for baseline characteristics including sex, age, and smoking. Fully adjusted estimates were additionally adjusted for body mass index, serum total cholesterol, plasma glucose, and drinking at baseline, for follow-up duration, and for three indicator variables coding for starting, stopping or continuing antihypertensive drug treatment from baseline to follow-up. Significance of the effect sizes: * P 0.05, P 0.01, and P 0.001.
Page 8 of 10 Table S6. Retinal Arteriole-to-Venule Ratio in Relation to Adjusted for Covariables at Follow-Up s Including a Single Type of Measurement of Measurement Adjusted 0.010 ( 0.016 to 0.004) 0.011 ( 0.017 to 0.005) 0.006 ( 0.013 to 0.002) 0.008 ( 0.015 to 0.0008)* Fully adjusted 0.013 ( 0.019 to 0.006) 0.012 ( 0.017 to 0.005) 0.009 ( 0.016 to 0.001)* 0.007 ( 0.014 to 0.0000)* Adjusted 0.010 ( 0.016 to 0.004) 0.011 ( 0.017 to 0.006) 0.005 ( 0.012 to 0.001) 0.009 ( 0.016 to 0.002) Fully adjusted 0.010 ( 0.016 to 0.004) 0.012 ( 0.018 to 0.006) 0.006 ( 0.013 to 0.001) 0.009 ( 0.016 to 0.002) Abbreviations: AVR, arteriole-to-venule ratio. Effect size (95% confidence interval) express the risk associated with a 1-SD increase in conventional or daytime blood pressures. All estimates account for clustering within families. Adjusted estimates account for follow-up characteristics including sex, age, and smoking. Fully adjusted estimates were additionally adjusted for body mass index, serum total cholesterol, plasma glucose, and drinking at follow-up, for follow-up duration, and for three indicator variables coding for starting, stopping or continuing antihypertensive drug treatment from baseline to follow-up. Significance of the effect sizes: * P 0.05, P 0.01, and P 0.001.
Page 9 of 10 Table S7. Retinal Phenotypes by Category Participants Untreated at Baseline Retinal microvascular trait Normotension White-Coat Masked Sustained PNT PWT PMT Unadjusted CRAE, µm 152.9±0.56 149.7±2.2 147.9±1.6 143.9±2.2 <0.001 0.060 0.13 CRVE, µm 219.3±0.80 224.4±3.1 217.8±2.2 216.4±3.1 0.36 0.069 0.71 AVR 0.70±0.003 0.67±0.012 0.68±0.009 0.67±0.012 0.008 0.95 0.32 Adjusted CRAE, µm 152.4±0.54 152.5±2.1 149.0±1.5 146.6±2.1 0.009 0.047 0.36 CRVE, µm 218.8±0.78 227.7±3.1 218.3±2.2 219.6±3.0 0.81 0.056 0.72 AVR 0.70±0.003 0.67±0.012 0.68±0.009 0.67±0.012 0.015 0.94 0.26 Fully adjusted CRAE, µm 152.4±0.54 152.2±2.1 149.3±1.5 146.1±2.2 0.006 0.043 0.22 CRVE, µm 218.8±0.78 227.0±3.1 218.4±2.2 219.4±3.1 0.85 0.081 0.78 AVR 0.70±0.003 0.67±0.012 0.68±0.009 0.67±0.013 0.012 0.84 0.17 Abbreviations: CRAE, central retinal arteriolar equivalent; CRVE, central retinal venular equivalent; AVR, arteriole-to-venule ratio. Values are mean ±SE. All estimates account for clustering within families. Adjusted estimates account for follow-up characteristics including sex, age, and smoking. Fully adjusted estimates were additionally adjusted for body mass index, serum total cholesterol, plasma glucose, drinking, and antihypertensive drug treatment at follow-up, and for follow-up duration. P-values indicate significance of the difference with sustained hypertension.
Page 10 of 10 Table S8. Retinal Phenotypes by Category Adjusted for Covariables at Follow-Up Retinal microvascular trait Normotension White-Coat Masked Sustained PNT PWT PMT Adjusted CRAE, µm 152.1±0.53 153.0±2.0 148.7±1.5 148.0±1.8 0.032 0.062 0.78 CRVE, µm 218.1±0.76 226.0±2.9 218.5±2.1 220.2±2.6 0.42 0.12 0.59 AVR 0.70±0.003 0.68±0.012 0.68±0.009 0.67±0.011 0.018 0.81 0.50 Fully adjusted CRAE, µm 152.1±0.54 152.9±2.0 148.8±1.5 147.6±1.9 0.022 0.047 0.62 CRVE, µm 218.0±0.76 225.8±2.9 218.4±2.1 221.2±2.7 0.28 0.20 0.40 AVR 0.70±0.003 0.68±0.012 0.68±0.009 0.67±0.012 0.005 0.57 0.23 Abbreviations: CRAE, central retinal arteriolar equivalent; CRVE, central retinal venular equivalent; AVR, arteriole-to-venule ratio. Values are mean ±SE. All estimates account for clustering within families. Adjusted estimates account for follow-up characteristics including sex, age, and smoking. Fully adjusted estimates were additionally adjusted for body mass index, serum total cholesterol, plasma glucose, and drinking at follow-up, for follow-up duration, and for three indicator variables coding for starting, stopping or continuing antihypertensive drug treatment from baseline to follow-up. P-values indicate significance of the difference with sustained hypertension.
Page 11 of 10 Figure S1. Multivariable-Adjusted Associations of Central Retinal Arteriolar Equivalent with Systolic and Diastolic The plane shows the independent associations of CRAE (central retinal arteriolar equivalent) with systolic (A) and diastolic (B) blood pressure, based on conventional and daytime blood pressure measurement. The plotted plane was standardized to the midpoints of the distributions (means or ratios) of sex, age, body mass index, serum total cholesterol, plasma glucose, and drinking at follow-up, to follow-up duration, and to three indicator variables coding for starting, stopping or continuing antihypertensive drug treatment from baseline to follow-up.