Cardiovasc Prev Pharmacother.  2021 Oct;3(4):95-105. 10.36011/cpp.2021.3.e11.

Relationship between Retinal Nerve Fiber Layer Defects and Coronary Artery Calcium Score in Patients at Risk for Cardiovascular Disease

• Lee CJ
• Shin JY
• Oh J
• Lee SH
• Kang SM
• Park S
• Byeon SH

• KMID: 2536936
• DOI: http://doi.org/10.36011/cpp.2021.3.e11

Abstract

Background
Noninvasive fundus imaging may provide useful information on blood vessels. This study investigated the relationship between localized retinal nerve fiber layer defects (RNFLDs) and vascular biomarkers.
Methods
This study included 1,316 participants without cardiovascular disease who were registered in a cardiovascular high-risk cohort. Examined vascular biomarkers included central hemodynamics, carotid-femoral pulse wave velocity (cfPWV), left ventricular hypertrophy (LVH) on electrocardiogram, and coronary artery calcium score (CACS). Fundus photography and optical coherence tomography were used to evaluate RNFLDs. The associations between RNFLDs and established high-risk cutoff points for each biomarker (central blood pressure [BP] ≥125/80 mmHg, central pulse pressure [PP] ≥50 mmHg, cfPWV ≥10 m/s, presence of LVH, and CACS ≥300) were assessed.
Results
RNFLD was identified in 394 participants (29.9%) who had higher fasting glucose level, lower renal function, and higher BP than those without RNFLDs. Additionally, central BP, central PP, cfPWV, CACS, and the percentage of subjects with LVH were higher in the RNFLD group. After adjusting for confounders, RNFLDs were not associated with LVH or an elevated central BP, central PP, or cfPWV. However, they were associated with an elevated CACS (odds ratio, 1.44; 95% confidence interval, 1.04–2.00; p=0.029).
Conclusions
Non-glaucomatous localized RNFLDs were associated with elevated CACS. Therefore, evaluating RNFLDs using fundus imaging may aid in the assessment of cardiovascular disease risk.

Keyword

Coronary artery disease; Heart disease risk factors; Retina; Retinal neurons; Vascular calcification

Reference

1. Sharrett AR, Hubbard LD, Cooper LS, Sorlie PD, Brothers RJ, Nieto FJ, Pinsky JL, Klein R. Retinal arteriolar diameters and elevated blood pressure: the Atherosclerosis Risk in Communities Study. Am J Epidemiol. 1999; 150:263–70.

2. Ikram MK, Witteman JC, Vingerling JR, Breteler MM, Hofman A, de Jong PT. Retinal vessel diameters and risk of hypertension: the Rotterdam study. Hypertension. 2006; 47:189–94.

3. Kawasaki R, Cheung N, Wang JJ, Klein R, Klein BE, Cotch MF, Sharrett AR, Shea S, Islam FA, Wong TY. Retinal vessel diameters and risk of hypertension: the Multiethnic Study of Atherosclerosis. J Hypertens. 2009; 27:2386–93.

4. Leung H, Wang JJ, Rochtchina E, Tan AG, Wong TY, Klein R, Hubbard LD, Mitchell P. Relationships between age, blood pressure, and retinal vessel diameters in an older population. Invest Ophthalmol Vis Sci. 2003; 44:2900–4.

5. Lindley RI, Wang JJ, Wong MC, Mitchell P, Liew G, Hand P, Wardlaw J, De Silva DA, Baker M, Rochtchina E, Chen C, Hankey GJ, Chang HM, Fung VS, Gomes L, Wong TY; Multi-Centre Retina and Stroke Study (MCRS) Collaborative Group. Retinal microvasculature in acute lacunar stroke: a cross-sectional study. Lancet Neurol. 2009; 8:628–34.

6. Cuspidi C, Meani S, Salerno M, Fusi V, Severgnini B, Valerio C, Catini E, Esposito A, Magrini F, Zanchetti A. Retinal microvascular changes and target organ damage in untreated essential hypertensives. J Hypertens. 2004; 22:2095–102.

7. Xu L, Zhou JQ, Wang S, Wang YX, You QS, Yang H, Zhang YQ, Wu MY, Lu YF, Fan YY, Jonas JB. Localized retinal nerve fiber layer defects and arterial hypertension. Am J Hypertens. 2013; 26:511–7.

8. Kalitzeos AA, Heitmar R, Lip GY. Localized retinal nerve fiber layer defects and arterial hypertension: insights into pathophysiology and perhaps an eye for detail? Am J Hypertens. 2013; 26:454–5.

9. Wang D, Li Y, Wang C, Xu L, You QS, Wang YX, Zhao L, Wei WB, Zhao X, Jonas JB. Localized retinal nerve fiber layer defects and stroke. Stroke. 2014; 45:1651–6.

10. Zhao L, Wang YX, Zhang W, Zhang JS, Chen CX, Xu L, Jonas JB. Localized retinal nerve fiber layer defects detected by optical coherence tomography: the Beijing eye study. PLoS One. 2013; 8:e68998.

11. Ishikawa J, Ishikawa S, Kabutoya T, Gotoh T, Kayaba K, Schwartz JE, Pickering TG, Shimada K, Kario K; Jichi Medical School Cohort Study Investigators Group. Cornell product left ventricular hypertrophy in electrocardiogram and the risk of stroke in a general population. Hypertension. 2009; 53:28–34.

12. Hecht HS. Coronary artery calcium scanning: past, present, and future. JACC Cardiovasc Imaging. 2015; 8:579–96.

13. Mancia G, Fagard R, Narkiewicz K, Redón J, Zanchetti A, Böhm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A, Galderisi M, Grobbee DE, Jaarsma T, Kirchhof P, Kjeldsen SE, Laurent S, Manolis AJ, Nilsson PM, Ruilope LM, Schmieder RE, Sirnes PA, Sleight P, Viigimaa M, Waeber B, Zannad F; Task Force Members. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013; 31:1281–357.

14. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, MacLaughlin EJ, Muntner P, Ovbiagele B, Smith SC Jr, Spencer CC, Stafford RS, Taler SJ, Thomas RJ, Williams KA Sr, Williamson JD, Wright JT Jr. 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. J Am Coll Cardiol. 2018; 71:e127–248.

15. Weber T, O'Rourke MF, Ammer M, Kvas E, Punzengruber C, Eber B. Arterial stiffness and arterial wave reflections are associated with systolic and diastolic function in patients with normal ejection fraction. Am J Hypertens. 2008; 21:1194–202.

16. Rajzer MW, Wojciechowska W, Klocek M, Palka I, Brzozowska-Kiszka M, Kawecka-Jaszcz K. Comparison of aortic pulse wave velocity measured by three techniques: Complior, SphygmoCor and Arteriograph. J Hypertens. 2008; 26:2001–7.

17. Molloy TJ, Okin PM, Devereux RB, Kligfield P. Electrocardiographic detection of left ventricular hypertrophy by the simple QRS voltage-duration product. J Am Coll Cardiol. 1992; 20:1180–6.

18. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 1990; 15:827–32.

19. Nakazato R, Dey D, Gutstein A, Le Meunier L, Cheng VY, Pimentel R, Paz W, Hayes SW, Thomson LE, Friedman JD, Berman DS. Coronary artery calcium scoring using a reduced tube voltage and radiation dose protocol with dual-source computed tomography. J Cardiovasc Comput Tomogr. 2009; 3:394–400.

20. Jonas JB, Schiro D. Localized retinal nerve fiber layer defects in nonglaucomatous optic nerve atrophy. Graefes Arch Clin Exp Ophthalmol. 1994; 232:759–60.

21. Lee J, Kim J, Kee C. Characteristics of patients with a localized retinal nerve fiber layer defect and normal optic disc appearance. Eye (Lond). 2012; 26:1473–8.

22. 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; 164:1285–92.

23. Silverman MG, Harkness JR, Blankstein R, Budoff MJ, Agatston AS, Carr JJ, Lima JA, Blumenthal RS, Nasir K, Blaha MJ. Baseline subclinical atherosclerosis burden and distribution are associated with frequency and mode of future coronary revascularization: multi-ethnic study of atherosclerosis. JACC Cardiovasc Imaging. 2014; 7:476–86.

24. Pletcher MJ, Sibley CT, Pignone M, Vittinghoff E, Greenland P. Interpretation of the coronary artery calcium score in combination with conventional cardiovascular risk factors: the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation. 2013; 128:1076–84.

25. Greenland P, LaBree L, Azen SP, Doherty TM, Detrano RC. Coronary artery calcium score combined with Framingham score for risk prediction in asymptomatic individuals. JAMA. 2004; 291:210–5.

26. Hayreh SS, Jonas JB. Appearance of the optic disk and retinal nerve fiber layer in atherosclerosis and arterial hypertension: an experimental study in rhesus monkeys. Am J Ophthalmol. 2000; 130:91–6.

27. Kim M, Park KH, Kwon JW, Jeoung JW, Kim TW, Kim DM. Retinal nerve fiber layer defect and cerebral small vessel disease. Invest Ophthalmol Vis Sci. 2011; 52:6882–6.

28. Carr JJ, Jacobs DR Jr, Terry JG, Shay CM, Sidney S, Liu K, Schreiner PJ, Lewis CE, Shikany JM, Reis JP, Goff DC Jr. Association of coronary artery calcium in adults aged 32 to 46 years with incident coronary heart disease and death. JAMA Cardiol. 2017; 2:391–9.

29. Kim EJ, Park CG, Park JS, Suh SY, Choi CU, Kim JW, Kim SH, Lim HE, Rha SW, Seo HS, Oh DJ. Relationship between blood pressure parameters and pulse wave velocity in normotensive and hypertensive subjects: invasive study. J Hum Hypertens. 2007; 21:141–8.

30. Miyashita H. Clinical assessment of central blood pressure. Curr Hypertens Rev. 2012; 8:80–90.

31. Wang S, Xu L, Jonas JB, Wang YS, Wang YX, You QS, Yang H, Zhou JQ. Five-year incidence of retinal microvascular abnormalities and associations with arterial hypertension: the Beijing Eye Study 2001/2006. Ophthalmology. 2012; 119:2592–9.