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Retinal Microvascular Signs as Screening and Prognostic Factors for Cardiac Disease: A Systematic Review of Current Evidence

      Abstract

      The substantial burden of heart disease promotes an interest in new ways of screening for early disease diagnosis, especially by means of noninvasive imaging. Increasing evidence for association between retinal microvascular signs and heart disease prompted us to systematically investigate the relevant current literature on the subject. We scrutinized the current literature by searching PubMed and Embase databases from 2000 to 2020 for clinical studies of the association between retinal microvascular signs and prevalent or incident heart disease in humans. Following exclusions, we extracted the relevant data from 42 publications (comprising 14 prospective, 26 cross-sectional, and 2 retrospective studies). Our search yielded significant associations between retinal vascular changes, including diameter, tortuosity, and branching, and various cardiac diseases, including acute coronary syndrome, coronary artery disease, heart failure, and conduction abnormalities. The findings of our research suggest that the retinal microvasculature can provide essential data about concurrent cardiac disease status and predict future risk of cardiac-related events.

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      References

      1. World Health Organization. The top 10 causes of death. Available at:http://www.who.int/mediacentre/factsheets/fs310/en/. Accessed September 14, 2019.

        • Murphy SL
        • Xu J
        • Kochanek KD
        • Arias E
        Mortality in the United States, 2017.
        NCHS Data Brief. 2018; : 1-8
        • Neglia D
        • Rovai D
        • Caselli C
        • et al.
        Detection of significant coronary artery disease by noninvasive anatomical and functional imaging.
        Circ Cardiovasc Imaging. 2015; 8e002179https://doi.org/10.1161/CIRCIMAGING.114.002179
        • Scheie HG
        Evaluation of ophthalmoscopic changes of hypertension and arteriolar sclerosis.
        AMA Arch Ophthalmol. 1953; 49: 117-138
        • Moritz AR
        • Oldt MR
        Arteriolar sclerosis in hypertensive and non-hypertensive individuals.
        Am J Pathol. 1937; 13: 679
        • Sun C
        • Wang JJ
        • Mackey DA
        • Wong TY
        Retinal vascular caliber: systemic, environmental, and genetic associations.
        Surv Ophthalmol. 2009; 54: 74-95
        • McGeechan K
        • Liew G
        • Macaskill P
        • et al.
        Meta-analysis: retinal vessel caliber and risk for coronary heart disease.
        Ann Intern Med. 2009; 151: 404-413
        • McClintic BR
        • McClintic JI
        • Bisognano JD
        • Block RC
        The relationship between retinal microvascular abnormalities and coronary heart disease: a review.
        Am J Med. 2010; 123: 374.e1-374.e7
        • Dumitrescu AG
        • Voinea L
        • Badarau IA
        • Paun VA
        • Schowe M
        • Ciuluvica R
        Update on retinal vascular caliber.
        Rom J Ophthalmol. 2017; 61: 171
        • Santos CM da C
        • Pimenta CA de M
        • Nobre MRC
        The PICO strategy for the research question construction and evidence search.
        Rev Lat Am Enfermagem. 2007; 15: 508-511
        • Wong TY
        • Klein R
        • Sharrett AR
        • et al.
        Retinal arteriolar narrowing and risk of coronary heart disease in men and women: the Atherosclerosis Risk in Communities Study.
        JAMA. 2002; 287: 1153-1159
        • McGeechan K
        • Liew G
        • Macaskill P
        • et al.
        Risk prediction of coronary heart disease based on retinal vascular caliber (from the Atherosclerosis Risk In Communities [ARIC] Study).
        Am J Cardiol. 2008; 102: 58-63
        • Seidelmann SB
        • Claggett B
        • Bravo PE
        • et al.
        Retinal vessel calibers in predicting long-term cardiovascular outcomes: the atherosclerosis risk in communities study.
        Circulation. 2016; 134: 1328-1338
        • Wang JJ
        • Liew G
        • Wong TY
        • et al.
        Retinal vascular calibre and the risk of coronary heart disease-related death.
        Heart. 2006; 92: 1583-1587https://doi.org/10.1136/hrt.2006.090522
        • Miller RG
        • Prince CT
        • Klein R
        • Orchard TJ
        Retinal vessel diameter and the incidence of coronary artery disease in type 1 diabetes.
        Am J Ophthalmol. 2009; 147: 653-660
        • Liew G
        • Mitchell P
        • Chiha J
        • et al.
        Retinal microvascular changes in microvascular angina: findings from the Australian Heart Eye Study.
        Microcirculation. 2019; : e12536
        • Wong TY
        • Kamineni A
        • Klein R
        • et al.
        Quantitative retinal venular caliber and risk of cardiovascular disease in older persons: the cardiovascular health study.
        Arch Intern Med. 2006; 166: 2388-2394
        • Wang JJ
        • Liew G
        • Klein R
        • et al.
        Retinal vessel diameter and cardiovascular mortality: pooled data analysis from two older populations.
        Eur Heart J. 2007; 28: 1984-1992
        • Øhrn AM
        • Schirmer H
        • von Hanno T
        • et al.
        Small and large vessel disease in persons with unrecognized compared to recognized myocardial infarction: The TromsøStudy 2007-2008.
        Int J Cardiol. 2018; 253: 14-19
        • Klein R
        • Klein BEK
        • Moss SE
        • Wong TY
        Retinal vessel caliber and microvascular and macrovascular disease in type 2 diabetes: XXI: the Wisconsin Epidemiologic Study of Diabetic Retinopathy.
        Ophthalmology. 2007; 114: 1884-1892https://doi.org/10.1016/j.ophtha.2007.02.023
        • Grunwald JE
        • Ying G-S
        • Maguire M
        • et al.
        Association between retinopathy and cardiovascular disease in patients with chronic kidney disease (from the Chronic Renal Insufficiency Cohort [CRIC] Study).
        Am J Cardiol. 2012; 110: 246-253
        • 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
        • Lam A
        • Bunya VY
        • Piltz‐Seymour JR
        Cardiovascular risk factors and events in glaucoma patients with peripapillary focal arteriolar narrowing.
        Acta Ophthalmol Scand. 2006; 84: 69-73
        • Liew G
        • Mitchell P
        • Rochtchina E
        • et al.
        Fractal analysis of retinal microvasculature and coronary heart disease mortality.
        Eur Heart J. 2010; 32: 422-429
        • Wong TY
        • Klein R
        • Sharrett AR
        • et al.
        The prevalence and risk factors of retinal microvascular abnormalities in older persons: The Cardiovascular Health Study.
        Ophthalmology. 2003; 110: 658-666https://doi.org/10.1016/S0161-6420(02)01931-0
        • Wong TY
        • Klein R
        • Nieto FJ
        • et al.
        Retinal microvascular abnormalities and 10-year cardiovascular mortality: a population-based case-control study.
        Ophthalmology. 2003; 110: 933-940
        • Kralev S
        • Zimmerer E
        • Buchholz P
        • et al.
        Microvascular retinal changes in patients presenting with acute coronary syndromes.
        Microvasc Res. 2010; 79: 150-153
        • Witt N
        • Wong TY
        • Hughes AD
        • et al.
        Abnormalities of retinal microvascular structure and risk of mortality from ischemic heart disease and stroke.
        Hypertension. 2006; 47: 975-981
        • Kreis AJ
        • Nguyen TT
        • Wang JJ
        • et al.
        Are retinal microvascular caliber changes associated with severity of coronary artery disease in symptomatic cardiac patients?.
        Microcirculation. 2009; 16: 177-181
        • Cheng L
        • Barlis P
        • Gibson J
        • et al.
        Microvascular retinopathy and angiographically-demonstrated coronary artery disease: a cross-sectional, observational study.
        PLoS One. 2018; 13e0192350
        • Wong TY
        • Cheung N
        • Islam FMA
        • et al.
        Relation of retinopathy to coronary artery calcification: the multi-ethnic study of atherosclerosis.
        Am J Epidemiol. 2007; 167: 51-58
        • Josef P
        • Ali I
        • Ariel P
        • Alon M
        • Nimer A
        Relationship between retinal vascular caliber and coronary artery disease in patients with non-alcoholic fatty liver disease (NAFLD).
        Int J Environ Res Public Health. 2013; 10: 3409-3423
        • Gopinath B
        • Chiha J
        • Plant AJH
        • et al.
        Associations between retinal microvascular structure and the severity and extent of coronary artery disease.
        Atherosclerosis. 2014; 236: 25-30
        • Wang L
        • Wong TY
        • Sharrett AR
        • Klein R
        • Folsom AR
        • Jerosch-Herold M
        Relationship between retinal arteriolar narrowing and myocardial perfusion: multi-ethnic study of atherosclerosis.
        Hypertension. 2008; 51: 119-126
        • Wightman A
        • Barlis P
        • MacBain M
        • et al.
        Small vessel disease and intracoronary plaque composition: a single centre cross-sectional observational study.
        Sci Rep. 2019; 9: 4215
        • Motoyama S
        • Ito H
        • Sarai M
        • et al.
        Plaque characterization by coronary computed tomography angiography and the likelihood of acute coronary events in mid-term follow-up.
        J Am Coll Cardiol. 2015; 66: 337-346
        • Xu BL
        • Zhou WL
        • Zhu TP
        • et al.
        A full-width half-maximum method to assess retinal vascular structural changes in patients with ischemic heart disease and microvascular anginga.
        Sci Rep. 2019; 9: 11019https://doi.org/10.1038/s41598-019-47194-5
        • Wang SB
        • Mitchell P
        • Liew G
        • et al.
        A spectrum of retinal vasculature measures and coronary artery disease.
        Atherosclerosis. 2018; 268: 215-224
        • Wong TY
        • McIntosh R
        Systemic associations of retinal microvascular signs: a review of recent population‐based studies.
        Ophthalmic Physiol Opt. 2005; 25: 195-204
        • Merz CNB
        • Shaw LJ
        • Reis SE
        • et al.
        Insights from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study: Part II: gender differences in presentation, diagnosis, and outcome with regard to gender-based pathophysiology of atherosclerosis and macrovascular and microvascular cor.
        J Am Coll Cardiol. 2006; 47: S21-S29
        • Dean J
        • Cruz S Dela
        • Mehta PK
        • Merz CNB
        Coronary microvascular dysfunction: sex-specific risk, diagnosis, and therapy.
        Nat Rev Cardiol. 2015; 12: 406
        • Gillum RF
        Retinal arteriolar findings and coronary heart disease.
        Am Heart J. 1991; 122: 262
        • Wong TY
        • Klein R
        • Klein BEK
        • Meuer SM
        • Hubbard LD
        Retinal vessel diameters and their associations with age and blood pressure.
        Invest Ophthalmol Vis Sci. 2003; 44: 4644-4650
        • Kifley A
        • Wang JJ
        • Cugati S
        • Wong TY
        • Mitchell P
        Retinal vascular caliber and the long‐term risk of diabetes and impaired fasting glucose: the Blue Mountains Eye Study.
        Microcirculation. 2008; 15: 373-377
        • Klein R
        • Klein BEK
        • Moss SE
        • Wong TY
        The relationship of retinopathy in persons without diabetes to the 15-year incidence of diabetes and hypertension: Beaver Dam Eye Study.
        Trans Am Ophthalmol Soc. 2006; 104: 98
        • Wong TY
        • Klein R
        • Couper DJ
        • et al.
        Retinal microvascular abnormalities and incident stroke: the Atherosclerosis Risk in Communities Study.
        Lancet. 2001; 358: 1134-1140
        • Arbab-Zadeh A
        • Fuster V
        The myth of the “vulnerable plaque”: transitioning from a focus on individual lesions to atherosclerotic disease burden for coronary artery disease risk assessment.
        J Am Coll Cardiol. 2015; 65: 846-855
        • Pletcher MJ
        • Tice JA
        • Pignone M
        • Browner WS
        Using the coronary artery calcium score to predict coronary heart disease events: a systematic review and meta-analysis.
        Arch Intern Med. 2004; 164: 1285-1292
        • Bamberg F
        • Sommer WH
        • Hoffmann V
        • et al.
        Meta-analysis and systematic review of the long-term predictive value of assessment of coronary atherosclerosis by contrast-enhanced coronary computed tomography angiography.
        J Am Coll Cardiol. 2011; 57: 2426-2436
        • Cheung CY
        • Zheng Y
        • Hsu W
        • et al.
        Retinal vascular tortuosity, blood pressure, and cardiovascular risk factors.
        Ophthalmology. 2011; 118: 812-818
        • Vorobtsova N
        • Chiastra C
        • Stremler MA
        • Sane DC
        • Migliavacca F
        • Vlachos P
        Effects of vessel tortuosity on coronary hemodynamics: an idealized and patient-specific computational study.
        Ann Biomed Eng. 2016; 44: 2228-2239
        • Stanton AV
        • Wasan B
        • Cerutti A
        • et al.
        Vascular network changes in the retina with age and hypertension.
        J Hypertens. 1995; 13: 1724-1728
        • Chapman N
        • Dell'Omo G
        • Sartini MS
        • et al.
        Peripheral vascular disease is associated with abnormal arteriolar diameter relationships at bifurcations in the human retina.
        Clin Sci. 2002; 103: 111-116
        • Habib MS
        • Al-Diri B
        • Hunter A
        • Steel DHW
        The association between retinal vascular geometry changes and diabetic retinopathy and their role in prediction of progression—an exploratory study.
        BMC Ophthalmol. 2014; 14: 89
        • Griffith TM
        • Edwards DH
        • Davies RL
        • Harrison TJ
        • Evans KT
        EDRF coordinates the behaviour of vascular resistance vessels.
        Nature. 1987; 329: 442
        • Sng CCA
        • Sabanayagam C
        • Lamoureux EL
        • et al.
        Fractal analysis of the retinal vasculature and chronic kidney disease.
        Nephrol Dial Transplant. 2010; 25: 2252-2258https://doi.org/10.1093/ndt/gfq007
        • McGrory S
        • Ballerini L
        • Doubal FN
        • et al.
        Retinal microvasculature and cerebral small vessel disease in the Lothian Birth Cohort 1936 and Mild Stroke Study.
        Sci Rep. 2019; 9: 6320
        • Kawasaki R
        • Azemin MZC
        • Kumar DK
        • et al.
        Fractal dimension of the retinal vasculature and risk of stroke: a nested case-control study.
        Neurology. 2011; 76: 1766-1767
        • Cheung CY
        • Tay WT
        • Ikram MK
        • et al.
        Retinal microvascular changes and risk of stroke: the Singapore Malay Eye Study.
        Stroke. 2013; 44: 2402-2408
        • Doubal FN
        • MacGillivray TJ
        • Patton N
        • Dhillon B
        • Dennis MS
        • Wardlaw JM
        Fractal analysis of retinal vessels suggests that a distinct vasculopathy causes lacunar stroke.
        Neurology. 2010; 74: 1102-1107
        • Cheung N
        • Liew G
        • Lindley RI
        • et al.
        Retinal fractals and acute lacunar stroke.
        Ann Neurol. 2010; 68: 107-111
        • Grauslund J
        • Green A
        • Kawasaki R
        • Hodgson L
        • Sjolie AK
        • Wong TY
        Retinal vascular fractals and microvascular and macrovascular complications in type 1 diabetes.
        Ophthalmology. 2010; 117: 1400-1405https://doi.org/10.1016/j.ophtha.2009.10.047
        • Cheung N
        • Donaghue KC
        • Liew G
        • et al.
        Quantitative assessment of early diabetic retinopathy using fractal analysis.
        Diabetes Care. 2009; 32: 106-110
        • Lim LS
        • Chee ML
        • Cheung CY
        • Wong TY
        Retinal vessel geometry and the incidence and progression of diabetic retinopathy.
        Invest Ophthalmol Vis Sci. 2017; 58: BIO200-BIO205
        • Newman AR
        • Andrew NH
        • Casson RJ
        Review of paediatric retinal microvascular changes as a predictor of cardiovascular disease.
        Clin Experiment Ophthalmol. 2017; 45: 33-44