Abstract
The retinal vasculature can be viewed directly and noninvasively, offering an easily accessible window through which to study the human microcirculation in vivo and, therefore, early processes and pathways in cardiovascular disease (CVD) development. Recent advances in digital retinal photography and image analysis have allowed reliable and objective evaluation of retinal vascular pathologies (eg, retinopathy signs) as well as quantitative assessment of other topographic retinal vascular parameters, including retinal vascular caliber. An expanding series of clinical and epidemiologic studies now show that retinal vascular changes are associated with cardiovascular and metabolic diseases, including hypertension, diabetes, obesity, stroke, coronary heart disease, and heart failure. These data indicate that structural alterations in the retinal vasculature may mirror pathologic processes occurring in the systemic circulation and may represent novel biomarkers for CVD risk. This review summarizes the systemic cardiovascular associations of retinal vascular changes and discusses their clinical and research implications.
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References and Recommended Reading
Cheung N, Wong TY: Diabetic retinopathy and systemic vascular complications. Prog Retin Eye Res 2008, 27:161–176.
Nguyen TT, Wong TY: Retinal vascular manifestations of metabolic disorders. Trends Endocrinol Metab 2006, 17:262–268.
Wong TY, Mitchell P: Hypertensive retinopathy. N Engl J Med 2004, 351:2310–2317.
Wong TY, Mitchell P: The eye in hypertension. Lancet 2007, 369:425–435.
Leung H, Wang JJ, Rochtchina E, et al.: Impact of current and past blood pressure on retinal arteriolar diameter in an older population. J Hypertens 2004, 22:1543–1549.
Sharrett AR, Hubbard LD, Cooper LS, et al.: Retinal arteriolar diameters and elevated blood pressure: the Atherosclerosis Risk in Communities Study. Am J Epidemiol 1999, 150:263–270.
Wang JJ, Rochtchina E, Liew G, et al.: The long-term relation among retinal arteriolar narrowing, blood pressure, and incident severe hypertension. Am J Epidemiol 2008, 168:80–88.
Wong TY, Klein R, Sharrett AR, et al.: Retinal arteriolar diameter and risk for hypertension. Ann Intern Med 2004, 140:248–255.
Wong TY, Shankar A, Klein R, et al.: Prospective cohort study of retinal vessel diameters and risk of hypertension. BMJ 2004, 329:79.
Nguyen TT, Wang JJ, Wong TY: Retinal vascular changes in pre-diabetes and prehypertension: new findings and their research and clinical implications. Diabetes Care 2007, 30:2708–2715.
Nguyen TT, Wang JJ, Amirul Islam F, et al.: Retinal arteriolar narrowing predicts incidence of diabetes: the Australian Diabetes, Obesity and Lifestyle (AusDiab) Study. Diabetes 2007, 57:536–539.
Wong TY, Klein R, Sharrett AR, et al.: Retinal arteriolar narrowing and risk of diabetes mellitus in middle-aged persons. JAMA 2002, 287:2528–2533.
Wong TY, Shankar A, Klein R, et al.: Retinal arteriolar narrowing, hypertension, and subsequent risk of diabetes mellitus. Arch Intern Med 2005, 165:1060–1065.
Rajala U, Laakso M, Qiao Q, Keinanen-Kiukaanniemi S: Prevalence of retinopathy in people with diabetes, impaired glucose tolerance, and normal glucose tolerance. Diabetes Care 1998, 21:1664–1669.
Singleton JR, Smith AG, Russell JW, Feldman EL: Microvascular complications of impaired glucose tolerance. Diabetes 2003, 52:2867–2873.
Tapp RJ, Tikellis G, Wong TY, et al.: Longitudinal association of glucose metabolism with retinopathy: results from the Australian Diabetes Obesity and Lifestyle (AusDiab) study. Diabetes Care 2008, 31:1349–1354.
Wong TY, Barr EL, Tapp RJ, et al.: Retinopathy in persons with impaired glucose metabolism: the Australian Diabetes Obesity and Lifestyle (AusDiab) study. Am J Ophthalmol 2005, 140:1157–1159.
Wong TY, Mohamed Q, Klein R, Couper DJ: Do retinopathy signs in non-diabetic individuals predict the subsequent risk of diabetes? Br J Ophthalmol 2006, 90:301–303.
Klein R, Klein BE, 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, 104:98–107.
Cheung N, Wong TY: Obesity and eye diseases. Surv Ophthalmol 2007, 52:180–195.
Sun C, Liew G, Wang JJ, et al.: Retinal vascular caliber, blood pressure, and cardiovascular risk factors in an Asian population: the Singapore Malay Eye Study. Invest Ophthalmol Vis Sci 2008, 49:1784–1790.
Wong TY, Islam FM, Klein R, et al.: Retinal vascular caliber, cardiovascular risk factors, and inflammation: the Multi-Ethnic Study of Atherosclerosis (MESA). Invest Ophthalmol Vis Sci 2006, 47:2341–2350.
Wong TY, Duncan BB, Golden SH, et al.: Associations between the metabolic syndrome and retinal microvascular signs: the Atherosclerosis Risk In Communities study. Invest Ophthalmol Vis Sci 2004, 45:2949–2954.
Wang JJ, Taylor B, Wong TY, et al.: Retinal vessel diameters and obesity: a population-based study in older persons. Obesity (Silver Spring) 2006, 14:206–214.
Kawasaki R, Tielsch JM, Wang JJ, et al.: The metabolic syndrome and retinal microvascular signs in a Japanese population: the Funagata study. Br J Ophthalmol 2008, 92:161–166.
Kifley A, Liew G, Wang JJ, et al.: Long-term effects of smoking on retinal microvascular caliber. Am J Epidemiol 2007, 166:1288–1297.
Ikram MK, de Jong FJ, Vingerling JR, et al.: Are retinal arteriolar or venular diameters associated with markers for cardiovascular disorders? The Rotterdam Study. Invest Ophthalmol Vis Sci 2004, 45:2129–2134.
Klein R, Klein BE, Knudtson MD, et al.: Are inflammatory factors related to retinal vessel caliber? The Beaver Dam Eye Study. Arch Ophthalmol 2006, 124:87–94.
Cheung N, Wong TY: Fenofibrate and diabetic retinopathy. Lancet 2008, 371:721–722.
Wong TY: Is retinal photography useful in the measurement of stroke risk? Lancet Neurol 2004, 3:179–183.
Patton N, Aslam T, Macgillivray T, et al.: Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures. J Anat 2005, 206:319–348.
Baker ML, Hand PJ, Wang JJ, Wong TY: Retinal signs and stroke: revisiting the link between eye and brain. Stroke 2008, 39:1371–1379.
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.
Cheung N, Rogers S, Couper DJ, et al.: Is diabetic retinopathy an independent risk factor for ischemic stroke? Stroke 2007, 38:398–401.
Wong TY, Klein R, Sharrett AR, et al.: Cerebral white matter lesions, retinopathy, and incident clinical stroke. JAMA 2002, 288:67–74.
Klein R, Klein BE, 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, 114:1884–1892.
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.
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.
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.
Wang JJ, Liew G, Wong TY, et al.: Retinal vascular calibre and the risk of coronary heart disease-related death. Heart 2006, 92:1583–1587.
Cheung N, Wang JJ, Klein R, et al.: Diabetic retinopathy and the risk of coronary heart disease: the Atherosclerosis Risk in Communities Study. Diabetes Care 2007, 30:1742–1746.
Liew G, Wong T, Mitchell P, et al.: Retinopathy predicts coronary heart disease mortality. Heart 2008 Aug 12 (Epub ahead of print).
Wong TY, Rosamond W, Chang PP, et al.: Retinopathy and risk of congestive heart failure. JAMA 2005, 293:63–69.
Cheung N, Wang JJ, Rogers S, et al.: Diabetic retinopathy and risk of heart failure. J Am Coll Cardiol 2008, 51:1573–1578.
Klein R, Sharrett AR, Klein BE, et al.: Are retinal arteriolar abnormalities related to atherosclerosis?: The Atherosclerosis Risk in Communities Study. Arterioscler Thromb Vasc Biol 2000, 20:1644–1650.
Wong TY, Cheung N, Islam FM, et al.: Relation of retinopathy to coronary artery calcification: the Multi-Ethnic Study of Atherosclerosis. Am J Epidemiol 2008, 167:51–58.
Rema M, Mohan V, Deepa R, Ravikumar R: Association of carotid intima-media thickness and arterial stiffness with diabetic retinopathy: the Chennai Urban Rural Epidemiology Study (CURES-2). Diabetes Care 2004, 27:1962–1967.
Cheung N, Sharret AR, Klein R, et al.: Aortic distensibility and retinal arteriolar narrowing: the Multi-Ethnic Study of Atherosclerosis. Hypertension 2007, 50:617–622.
Cheung N, Islam AFM, Jacobs DR, et al.: Arterial compliance and retinal vascular caliber in cerebrovascular disease. Ann Neurol 2007, 62:618–624.
Tikellis G, Arnett DK, Skelton TN, et al.: Retinal arteriolar narrowing and left ventricular hypertrophy in African Americans: the Atherosclerosis Risk in Communities (ARIC) study. Am J Hypertens 2008, 21:352–359.
Cheung N, Bluemke DA, Klein R, et al.: Retinal arteriolar narrowing and left ventricular remodeling: the Multi-Ethnic Study of Atherosclerosis. J Am Coll Cardiol 2007, 50:48–55.
Wang L, Wong TY, Sharrett AR, et al.: Relationship between retinal arteriolar narrowing and myocardial perfusion: Multi-Ethnic Study of Atherosclerosis. Hypertension 2008, 51:119–126.
Brindle P, Beswick A, Fahey T, Ebrahim S: Accuracy and impact of risk assessment in the primary prevention of cardiovascular disease: a systematic review. Heart 2006, 92:1752–1759.
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.
Cheung N, Wong TY, Liew G, Saw SM: Low birth weight and retinal vascular caliber in young children. Pediatrics 2008, 121:862–863.
Cheung N, Islam FM, Saw SM, et al.: Distribution and associations of retinal vascular caliber with ethnicity, gender, and birth parameters in young children. Invest Ophthalmol Vis Sci 2007, 48:1018–1024.
Cheung N, Saw SM, Islam FM, et al.: BMI and retinal vascular caliber in children. Obesity (Silver Spring) 2007, 15:209–215.
Mitchell P, Cheung N, de Haseth K, et al.: Blood pressure and retinal arteriolar narrowing in children. Hypertension 2007, 49:1156–1162.
Mitchell P, Liew G, Rochtchina E, et al.: Evidence of arteriolar narrowing in low-birth-weight children. Circulation 2008, 118:518–524.
Taylor B, Rochtchina E, Wang JJ, et al.: Body mass index and its effects on retinal vessel diameter in 6-year-old children. Int J Obes (Lond) 2007, 31:1527–1533.
Xing C, Klein BE, Klein R, et al.: Genome-wide linkage study of retinal vessel diameters in the Beaver Dam Eye Study. Hypertension 2006, 47:797–802.
Ikram MK, De Jong FJ, Van Dijk EJ, et al.: Retinal vessel diameters and cerebral small vessel disease: the Rotterdam Scan Study. Brain 2006, 129:182–188.
Ikram MK, Janssen JA, Roos AM, et al.: Retinal vessel diameters and risk of impaired fasting glucose or diabetes: the Rotterdam study. Diabetes 2006, 55:506–510.
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Cheung, N., Wong, T.Y. Microvascular changes in the retina as a risk marker for cardiovascular disease. Curr Cardio Risk Rep 3, 51–58 (2009). https://doi.org/10.1007/s12170-009-0009-8
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DOI: https://doi.org/10.1007/s12170-009-0009-8