Relationship of Quantitative Retinal Capillary Network and Myocardial Remodeling in Systemic Hypertension

Jacqueline Chua, Thu-Thao Le, Yin Ci Sim, Hui Yi Chye, Bingyao Tan, Xinwen Yao, Damon Wong, Briana W Y Ang, Desiree-Faye Toh, Huishan Lim, Jennifer A Bryant, Tien Yin Wong, Calvin Woon Loong Chin, Leopold Schmetterer, Jacqueline Chua, Thu-Thao Le, Yin Ci Sim, Hui Yi Chye, Bingyao Tan, Xinwen Yao, Damon Wong, Briana W Y Ang, Desiree-Faye Toh, Huishan Lim, Jennifer A Bryant, Tien Yin Wong, Calvin Woon Loong Chin, Leopold Schmetterer

Abstract

Background This study examined the associations between quantitative optical coherence tomography angiography (OCTA) parameters and myocardial abnormalities as documented on cardiovascular magnetic resonance imaging in patients with systemic hypertension. Methods and Results We conducted a cross-sectional study of 118 adults with hypertension (197 eyes). Patients underwent cardiovascular magnetic resonance imaging and OCTA (PLEX Elite 9000, Carl Zeiss Meditec). Associations between OCTA parameters (superficial and deep retinal capillary density) and adverse cardiac remodeling (left ventricular mass, remodeling index, interstitial fibrosis, global longitudinal strain, and presence of left ventricular hypertrophy) were studied using multivariable linear regression analysis with generalized estimating equations. Of the 118 patients with hypertension enrolled (65% men; median [interquartile range] age, 59 [13] years), 29% had left ventricular hypertrophy. After adjusting for age, sex, systolic blood pressure, diabetes, and signal strength of OCTA scans, patients with lower superficial capillary density had significantly higher left ventricular mass (β=-0.150; 95% CI, -0.290 to -0.010), higher interstitial volume (β=-0.270; 95% CI, -0.535 to -0.0015), and worse global longitudinal strain (β=-0.109; 95% CI, -0.187 to -0.032). Lower superficial capillary density was found in patients with hypertension with replacement fibrosis versus no replacement fibrosis (16.53±0.64 mm-1 versus 16.96±0.64 mm-1; P=0.003). Conclusions We showed significant correlations between retinal capillary density and adverse cardiac remodeling markers in patients with hypertension, supporting the notion that the OCTA could provide a non-invasive index of microcirculation alteration for vascular risk stratification in people with hypertension.

Keywords: cardiovascular magnetic resonance; optical coherence tomography angiography; systemic hypertension.

Figures

Figure 1. Lower superficial capillary density in…
Figure 1. Lower superficial capillary density in a patient with hypertension (A and B; 14.5 mm‐1) with (C) lower remodeling index, (D) higher interstitial volume and extracellular volume fraction, and (E) worse global longitudinal strain as compared with a denser superficial capillary density in a patient with hypertension (F and G; 21.7 mm‐1) with (H) higher remodeling index, (I) lower interstitial volume, and (J) better global longitudinal strain.
Presence of larger non‐perfused area (blue regions demarcated by red arrows) (B) can be seen in patient with adverse cardiac remodeling markers as compared with (C) a patient with favorable cardiac remodeling markers. Foveal avascular zone area (in black; B and G) and large vessels (seen as a black outline of vessels in A and F) were excluded from the calculation of capillary density. ECV indicates extracellular volume fraction; GLS, global longitudinal strain; and RI, remodeling index.
Figure 2. Scatterplots showing the associations between…
Figure 2. Scatterplots showing the associations between lower superficial capillary density in patients with hypertension with (A) increased left ventricular mass, (B) increased interstitial volume, and (C) reduced global longitudinal strain, adjusted for age, sex, body mass index, systolic blood pressure, diabetes, and signal strength of scans.
The equation is the fit line of the scattered plot, where y denotes the dependent variable (superficial capillary density), and x represents the independent variable (left ventricular mass/interstitial volume/global longitudinal strain).
Figure 3. Lower superficial capillary density in…
Figure 3. Lower superficial capillary density in patients with hypertension with replacement fibrosis vs no replacement fibrosis (P=0.004).
Results presented in box‐and‐whiskers plots (Tukey method), P value adjusted for age, sex, body mass index, systolic blood pressure, diabetes, and signal strength of scans. Scattered data points are outliers.

References

    1. Dai H, Bragazzi NL, Younis A, Zhong W, Liu X, Wu J, Grossman E. Worldwide trends in prevalence, mortality, and disability‐adjusted life years for hypertensive heart disease from 1990 to 2017. Hypertension. 2021;77:1223–1233. doi: 10.1161/HYPERTENSIONAHA.120.16483
    1. Shimizu I, Minamino T. Physiological and pathological cardiac hypertrophy. J Mol Cell Cardiol. 2016;97:245–262. doi: 10.1016/j.yjmcc.2016.06.001
    1. Diez J, Gonzalez A, Lopez B, Querejeta R. Mechanisms of disease: pathologic structural remodeling is more than adaptive hypertrophy in hypertensive heart disease. Nat Clin Pract Cardiovasc Med. 2005;2:209–216. doi: 10.1038/ncpcardio0158
    1. Gonzalez A, Ravassa S, Lopez B, Moreno MU, Beaumont J, San Jose G, Querejeta R, Bayes‐Genis A, Diez J. Myocardial remodeling in hypertension. Hypertension. 2018;72:549–558. doi: 10.1161/HYPERTENSIONAHA.118.11125
    1. Messroghli DR, Moon JC, Ferreira VM, Grosse‐Wortmann L, He T, Kellman P, Mascherbauer J, Nezafat R, Salerno M, Schelbert EB, et al. Clinical recommendations for cardiovascular magnetic resonance mapping of T1, T2, T2* and extracellular volume: a consensus statement by the Society for Cardiovascular Magnetic Resonance (SCMR) endorsed by the European Association for Cardiovascular Imaging (EACVI). J Cardiovasc Magn meric. 2017;19:75. doi: 10.1186/s12968-017-0389-8
    1. Goh VJ, Le TT, Bryant J, Wong JI, Su B, Lee CH, Pua CJ, Sim CPY, Ang B, Aw TC, et al. Novel index of maladaptive myocardial remodeling in hypertension. Circ Cardiovasc Imaging. 2017;10. doi: 10.1161/CIRCIMAGING.117.006840
    1. Le TT, Lim V, Ibrahim R, Teo MT, Bryant J, Ang B, Su B, Aw TC, Lee CH, Bax J, et al. The remodelling index risk stratifies patients with hypertensive left ventricular hypertrophy. Eur Heart J Cardiovasc Imaging. 2021;22:670–679. doi: 10.1093/ehjci/jeaa040
    1. Frojdh F, Fridman Y, Bering P, Sayeed A, Maanja M, Niklasson L, Olausson E, Pi H, Azeem A, Wong TC, et al. Extracellular volume and global longitudinal strain both associate with outcomes but correlate minimally. JACC Cardiovasc Imaging. 2020;13:2343–2354. doi: 10.1016/j.jcmg.2020.04.026
    1. Camici PG, Crea F. Coronary microvascular dysfunction. New Engl J Med. 2007;356:830–840. doi: 10.1056/NEJMra061889
    1. Feihl F, Liaudet L, Waeber B, Levy BI. Hypertension: a disease of the microcirculation? Hypertension. 2006;48:1012–1017. doi: 10.1161/01.HYP.0000249510.20326.72
    1. Vegsundvag J, Holte E, Wiseth R, Hegbom K, Hole T. Coronary flow velocity reserve in the three main coronary arteries assessed with transthoracic Doppler: a comparative study with quantitative coronary angiography. J Am Soc Echocardiogr. 2011;24:758–767. doi: 10.1016/j.echo.2011.03.010
    1. Schindler TH, Schelbert HR, Quercioli A, Dilsizian V. Cardiac pet imaging for the detection and monitoring of coronary artery disease and microvascular health. JACC Cardiovasc Imaging. 2010;3:623–640. doi: 10.1016/j.jcmg.2010.04.007
    1. Thomson LEJ, Wei J, Agarwal M, Haft‐Baradaran A, Shufelt C, Mehta PK, B. Gill E, Johnson BD, Kenkre T, M. Handberg E, et al. Cardiac magnetic resonance myocardial perfusion reserve index is reduced in women with coronary microvascular dysfunction. A national heart, lung, and blood institute‐sponsored study from the women’s ischemia syndrome evaluation. Circ Cardiovasc Imaging. 2015;8:e002481. doi: 10.1161/CIRCIMAGING.114.002481
    1. Cheung CY, Ikram MK, Sabanayagam C, Wong TY. Retinal microvasculature as a model to study the manifestations of hypertension. Hypertension. 2012;60:1094–1103. doi: 10.1161/HYPERTENSIONAHA.111.189142
    1. Duncan BB, Wong TY, Tyroler HA, Davis CE, Fuchs FD. Hypertensive retinopathy and incident coronary heart disease in high risk men. Br J Ophthalmol. 2002;86:1002–1006. doi: 10.1136/bjo.86.9.1002
    1. Wong TY, Klein R, Sharrett AR, Duncan BB, Couper DJ, Tielsch JM, Klein BE, Hubbard LD. Retinal arteriolar narrowing and risk of coronary heart disease in men and women. The atherosclerosis risk in communities study. JAMA. 2002;287:1153–1159. doi: 10.1001/jama.287.9.1153
    1. Wong TY, Rosamond W, Chang PP, Couper DJ, Sharrett AR, Hubbard LD, Folsom AR, Klein R. Retinopathy and risk of congestive heart failure. JAMA. 2005;293:63–69. doi: 10.1001/jama.293.1.63
    1. Liew G, Wong TY, Mitchell P, Cheung N, Wang JJ. Retinopathy predicts coronary heart disease mortality. Heart. 2009;95:391–394. doi: 10.1136/hrt.2008.146670
    1. Wong TY, Klein R, Nieto FJ, Klein BE, Sharrett AR, Meuer SM, Hubbard LD, Tielsch JM. Retinal microvascular abnormalities and 10‐year cardiovascular mortality: a population‐based case‐control study. Ophthalmology. 2003;110:933–940. doi: 10.1016/S0161-6420(03)00084-8
    1. Sairenchi T, Iso H, Yamagishi K, Irie F, Okubo Y, Gunji J, Muto T, Ota H. Mild retinopathy is a risk factor for cardiovascular mortality in Japanese with and without hypertension: the Ibaraki prefectural health study. Circulation. 2011;124:2502–2511. doi: 10.1161/CIRCULATIONAHA.111.049965
    1. Kashani AH, Chen CL, Gahm JK, Zheng F, Richter GM, Rosenfeld PJ, Shi Y, Wang RK. Optical coherence tomography angiography: a comprehensive review of current methods and clinical applications. Prog Retin Eye Res. 2017;60:66–100. doi: 10.1016/j.preteyeres.2017.07.002
    1. Spaide RF, Fujimoto JG, Waheed NK, Sadda SR, Staurenghi G. Optical coherence tomography angiography. Prog Retin Eye Res. 2018;64:1–55. doi: 10.1016/j.preteyeres.2017.11.003
    1. Hong J, Tan B, Quang ND, Gupta P, Lin E, Wong D, Ang M, Lamoureux E, Schmetterer L, Chua J. Intra‐session repeatability of quantitative metrics using widefield optical coherence tomography angiography (OCTA) in elderly subjects. Acta Ophthalmol. 2019;98:e570–e578. doi: 10.1111/aos.14327
    1. You Q, Freeman WR, Weinreb RN, Zangwill L, Manalastas PIC, Saunders LJ, Nudleman E. Reproducibility of vessel density measurement with optical coherence tomography angiography in eyes with and without retinopathy. Retina. 2017;37:1475–1482. doi: 10.1097/IAE.0000000000001407
    1. Chua J, Chin CWL, Hong J, Chee ML, Le TT, Ting DSW, Wong TY, Schmetterer L. Impact of hypertension on retinal capillary microvasculature using optical coherence tomographic angiography. J Hypertens. 2019;37:572–580. doi: 10.1097/HJH.0000000000001916
    1. Sun C, Ladores C, Hong J, Nguyen DQ, Chua J, Ting D, Schmetterer L, Wong TY, Cheng CY, Tan ACS. Systemic hypertension associated retinal microvascular changes can be detected with optical coherence tomography angiography. Sci Rep. 2020;10:9580. doi: 10.1038/s41598-020-66736-w
    1. Xu Q, Sun H, Huang X, Qu Y. Retinal microvascular metrics in untreated essential hypertensives using optical coherence tomography angiography. Graefes Arch Clin Exp Ophthalmol. 2021;259:395–403. doi: 10.1007/s00417-020-04714-8
    1. Donati S, Maresca AM, Cattaneo J, Grossi A, Mazzola M, Caprani SM, Premoli L, Docchio F, Rizzoni D, Guasti L, et al. Optical coherence tomography angiography and arterial hypertension: a role in identifying subclinical microvascular damage? Eur J Ophthalmol. 2021;31:158–165. doi: 10.1177/1120672119880390
    1. Terheyden JH, Wintergerst MWM, Pizarro C, Pfau M, Turski GN, Holz FG, Finger RP. Retinal and choroidal capillary perfusion are reduced in hypertensive crisis irrespective of retinopathy. Transl vis Sci Technol. 2020;9:42. doi: 10.1167/tvst.9.8.42
    1. Peng Q, Hu Y, Huang M, Wu Y, Zhong P, Dong X, Wu Q, Liu B, Li C, Xie J, et al. Retinal neurovascular impairment in patients with essential hypertension: an optical coherence tomography angiography study. Invest Ophthalmol Vis Sci. 2020;61:42. doi: 10.1167/iovs.61.8.42
    1. Hua D, Xu Y, Zeng X, Yang N, Jiang M, Zhang X, Yang J, He T, Xing Y. Use of optical coherence tomography angiography for assessment of microvascular changes in the macula and optic nerve head in hypertensive patients without hypertensive retinopathy. Microvasc Res. 2020;129:103969. doi: 10.1016/j.mvr.2019.103969
    1. Hua D, Xu Y, Zhang X, He T, Chen C, Chen Z, Xing Y. Retinal microvascular changes in hypertensive patients with different levels of blood pressure control and without hypertensive retinopathy. Curr Eye Res. 2021;46:107–114. doi: 10.1080/02713683.2020.1775260
    1. Frost S, Nolde JM, Chan J, Joyson A, Gregory C, Carnagarin R, Herat LY, Matthews VB, Robinson L, Vignarajan J, et al. Retinal capillary rarefaction is associated with arterial and kidney damage in hypertension. Sci Rep. 2021;11:1001. doi: 10.1038/s41598-020-79594-3
    1. Du Bois D & Du Bois EF A formula to estimate the approximate surface area if height and weight be known. 1916. Nutrition. 1989; 5:303‐311; discussion 312‐303
    1. Le TT, Tan RS, De Deyn M, Goh EP, Han Y, Leong BR, Cook SA, Chin CW. Cardiovascular magnetic resonance reference ranges for the heart and aorta in Chinese at 3T. J Cardiovasc Magn meric. 2016;18:21. doi: 10.1186/s12968-016-0236-3
    1. Chin CW, Semple S, Malley T, White AC, Mirsadraee S, Weale PJ, Prasad S, Newby DE, Dweck MR. Optimization and comparison of myocardial T1 techniques at 3T in patients with aortic stenosis. Eur Heart J Cardiovasc Imaging. 2014;15:556–565. doi: 10.1093/ehjci/jet245
    1. Chin CWL, Everett RJ, Kwiecinski J, Vesey AT, Yeung E, Esson G, Jenkins W, Koo M, Mirsadraee S, White AC, et al. Myocardial fibrosis and cardiac decompensation in aortic stenosis. JACC Cardiovasc Imaging. 2017;10:1320–1333. doi: 10.1016/j.jcmg.2016.10.007
    1. Hong J, Ke M, Tan B, Lau A, Wong D, Yao X, Liu X, Schmetterer L, Chua J. Effect of vessel enhancement filters on the repeatability of measurements obtained from widefield swept‐source optical coherence tomography angiography. Sci Rep. 2020;10:22179. doi: 10.1038/s41598-020-79281-3
    1. Lin E, Ke M, Tan B, Yao X, Wong D, Ong L, Schmetterer L, Chua J. Are choriocapillaris flow void features robust to diurnal variations? A swept‐source optical coherence tomography angiography (OCTA) study. Sci Rep. 2020;10:11249. doi: 10.1038/s41598-020-68204-x
    1. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, Clement DL, Coca A, de Simone G, Dominiczak A, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: the TASK force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens. 2018;36:1953–2041. doi: 10.1097/HJH.0000000000001940
    1. Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APHA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. Hypertension. 2018;71:e13–e115. doi: 10.1161/HYP.0000000000000065
    1. Drazner MH. The progression of hypertensive heart disease. Circulation. 2011;123:327–334. doi: 10.1161/CIRCULATIONAHA.108.845792
    1. Gonzalez A, Ravassa S, Beaumont J, Lopez B, Diez J. New targets to treat the structural remodeling of the myocardium. J Am Coll Cardiol. 2011;58:1833–1843. doi: 10.1016/j.jacc.2011.06.058
    1. Kanellakis P, Dinh TN, Agrotis A, Bobik A. Cd4(+)cd25(+)foxp3(+) regulatory T cells suppress cardiac fibrosis in the hypertensive heart. J Hypertens. 2011;29:1820–1828. doi: 10.1097/HJH.0b013e328349c62d
    1. Fabbiano S, Menacho‐Márquez M, Robles‐Valero J, Pericacho M, Matesanz‐Marín A, García‐Macías C, Sevilla MA, Montero MJ, Alarcón B, López‐Novoa JM, et al. Immunosuppression‐independent role of regulatory T cells against hypertension‐driven renal dysfunctions. Mol Cell Biol. 2015;35:3528–3546. doi: 10.1128/MCB.00518-15
    1. Diez J, Querejeta R, Lopez B, Gonzalez A, Larman M, Martinez Ubago JL. Losartan‐dependent regression of myocardial fibrosis is associated with reduction of left ventricular chamber stiffness in hypertensive patients. Circulation. 2002;105:2512–2517. doi: 10.1161/01.CIR.0000017264.66561.3D
    1. Lee WH, Park JH, Won Y, Lee MW, Shin YI, Jo YJ, Kim JY. Retinal microvascular change in hypertension as measured by optical coherence tomography angiography. Sci Rep. 2019;9:156. doi: 10.1038/s41598-018-36474-1
    1. Seidelmann SB, Claggett B, Bravo PE, Gupta A, Farhad H, Klein BE, Klein R, Di Carli M, Solomon SD. Retinal vessel calibers in predicting long‐term cardiovascular outcomes: the atherosclerosis risk in communities study. Circulation. 2016;134:1328–1338. doi: 10.1161/CIRCULATIONAHA.116.023425
    1. Gopinath B, Chiha J, Plant AJ, Thiagalingam A, Burlutsky G, Kovoor P, Liew G, Mitchell P. Associations between retinal microvascular structure and the severity and extent of coronary artery disease. Atherosclerosis. 2014;236:25–30. doi: 10.1016/j.atherosclerosis.2014.06.018
    1. Forrester JV, Dick AD, McMenamin PG, Roberts F, Pearlman E. The eye: Basic sciences in practice: Chapter 1: Anatomy of the eye and orbit . 2016;1–102.
    1. Rakusiewicz K, Kanigowska K, Hautz W, Ziolkowska L. The impact of chronic heart failure on retinal vessel density assessed by optical coherence tomography angiography in children with dilated cardiomyopathy. J Clin Med. 2021;10:2659. doi: 10.3390/jcm10122659
    1. Wang J, Jiang J, Zhang Y, Qian YW, Zhang JF, Wang ZL. Retinal and choroidal vascular changes in coronary heart disease: an optical coherence tomography angiography study. Biomed Opt Express. 2019;10:1532–1544. doi: 10.1364/BOE.10.001532
    1. Chua J, Sim R, Tan B, Wong D, Yao X, Liu X, Ting DSW, Schmidl D, Ang M, Garhöfer G, et al. Optical coherence tomography angiography in diabetes and diabetic retinopathy. J Clin Med. 2020;9:1723. doi: 10.3390/jcm9061723
    1. Chen QI, Ma Q, Wu C, Tan F, Chen F, Wu Q, Zhou R, Zhuang X, Lu F, Qu J, et al. Macular vascular fractal dimension in the deep capillary layer as an early indicator of microvascular loss for retinopathy in type 2 diabetic patients. Invest Ophthalmol vis Sci. 2017;58:3785–3794. doi: 10.1167/iovs.17-21461
    1. Li C, Zhong P, Yuan H, Dong X, Peng Q, Huang M, Wu Q, Liu B, Xu M, Kuang YU, et al. Retinal microvasculature impairment in patients with congenital heart disease investigated by optical coherence tomography angiography. Clin Exp Ophthalmol. 2020;48:1219–1228. doi: 10.1111/ceo.13846
    1. Yeung L, Wu IW, Sun CC, Liu CF, Chen SY, Tseng CH, Lee HC, Lee CC. Early retinal microvascular abnormalities in patients with chronic kidney disease. Microcirculation. 2019;26:e12555. doi: 10.1111/micc.12555
    1. Vadala M, Castellucci M, Guarrasi G, Terrasi M, La Blasca T, Mule G. Retinal and choroidal vasculature changes associated with chronic kidney disease. Graefes Arch Clin Exp Ophthalmol. 2019;257:1687–1698. doi: 10.1007/s00417-019-04358-3
    1. Tan B, Sim R, Chua J, Wong DWK, Yao X, Garhofer G, Schmidl D, Werkmeister RM, Schmetterer L. Approaches to quantify optical coherence tomography angiography metrics. Ann Transl Med. 2020;8:1205. doi: 10.21037/atm-20-3246
    1. Chui TY, Zhong Z, Song H, Burns SA. Foveal avascular zone and its relationship to foveal pit shape. Optom Vis Sci. 2012;89:602–610. doi: 10.1097/OPX.0b013e3182504227
    1. Chua J, Schmetterer L. Letter to the editor on “macular OCT‐angiography parameters to predict the clinical stage of nonproliferative diabetic retinopathy: an exploratory analysis”. Eye (Lond). 2020;34:2341–2342. doi: 10.1038/s41433-020-0788-1
    1. Chua J, Hu Q, Ke M, Tan B, Hong J, Yao X, Hilal S, Venketasubramanian N, Garhöfer G, Cheung CY, et al. Retinal microvasculature dysfunction is associated with alzheimer’s disease and mild cognitive impairment. Alzheimers Res Ther. 2020;12:161. doi: 10.1186/s13195-020-00724-0
    1. Wong TY, Mitchell P. The eye in hypertension. Lancet. 2007;369:425–435. doi: 10.1016/S0140-6736(07)60198-6
    1. Yau JWY, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T, Chen S‐J, Dekker JM, Fletcher A, Grauslund J, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012;35:556–564. doi: 10.2337/dc11-1909
    1. Age‐Related Eye Disease Study Research Group . Risk factors associated with age‐related macular degeneration. A case‐control study in the age‐related eye disease study: age‐related eye disease study report number 3. Ophthalmology. 2000;107:2224–2232. doi: 10.1016/s0161-6420(00)00409-7
    1. Wong TY, Klein R, Sharrett AR, Manolio TA, Hubbard LD, Marino EK, Kuller L, Burke G, Tracy RP, Polak JF, et al. The prevalence and risk factors of retinal microvascular abnormalities in older persons: the cardiovascular health study. Ophthalmology. 2003;110:658–666. doi: 10.1016/S0161-6420(02)01931-0

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