CC BY 4.0 · TH Open 2022; 06(04): e429-e436
DOI: 10.1055/s-0042-1758713
Original Article

Evaluation of Risk Scores as Predictive Tools for Stroke in Patients with Retinal Artery Occlusion: A Danish Nationwide Cohort Study

Marie Ørskov
1   Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark
2   Department of Clinical Medicine, Aalborg Thrombosis Research Unit, Faculty of Health, Aalborg University, Aalborg, Denmark
,
Henrik Vorum
3   Department of Ophthalmology, Aalborg University Hospital, Aalborg, Denmark
,
Torben Bjerregaard Larsen
1   Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark
2   Department of Clinical Medicine, Aalborg Thrombosis Research Unit, Faculty of Health, Aalborg University, Aalborg, Denmark
,
Flemming Skjøth
2   Department of Clinical Medicine, Aalborg Thrombosis Research Unit, Faculty of Health, Aalborg University, Aalborg, Denmark
4   Unit for Clinical Biostatistics, Aalborg University Hospital, Aalborg, Denmark
› Author Affiliations
Funding This study was partly funded by an unrestricted grant from The Obel Family Foundation and Lions Club Bannerslund. The sponsor did not influence the design or execution of the study.

Abstract

Purpose We investigated the 1-year risk of stroke in patients with retinal artery occlusion and evaluated the predictive and discriminating abilities of contemporary risk stratification models for embolic stroke.

Methods This register-based cohort study included 7,906 patients with retinal artery occlusion from Danish nationwide patient registries between 1995 and 2018. The study population was stratified according to the number of points obtained in the stroke risk scores: the CHA2DS2-VASc score and the ESSEN Stroke Risk score. The 1-year risk of stroke within strata was evaluated and compared using the cox proportional hazards model. Furthermore, the discrimination of the risk scores as predictive tools for stroke risk assessment was investigated using C-statistics, Brier score, and the index of prediction accuracy.

Results The stroke event rate in patients with retinal artery occlusion increased as the score increased for both risk scores, ranging from 3.62 (95% confidence interval [CI]: 2.46–5.31) per 100 person-years to 13.25 (95% CI: 11.78––14.89) per 100-person-years for increasing levels of the CHA2DS2-VASc score and from 3.97 (95% CI: 2.97–5.32) per 100 person-years to 16.43 (95% CI: 14.01–19.27) per 100 person-years for increasing levels of the ESSEN Stroke Risk score. Using a risk score of 0 as a reference, the difference was statistically significant for retinal artery occlusion patients with a CHA2DS2-VASc score of 2 or above and for all levels of the ESSEN Stroke Risk score. The C-statistics for the risk scores was 61% (95% CI: 58%–63%) and 62% (95% CI: 59–64%) for the CHA2DS2-VASc score and ESSEN Stroke Risk score, respectively.

Conclusion The results suggested that the use of the CHA2DS2-VASc score and the ESSEN Stroke Risk score was applicable for risk stratification of stroke in patients with retinal artery occlusion, but discrimination was poor due to low specificity.

Supplementary Material



Publication History

Received: 08 July 2022

Accepted: 28 September 2022

Article published online:
30 November 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Rim TH, Han J, Choi YS. et al. Retinal artery occlusion and the risk of stroke development: twelve-year nationwide cohort study. Stroke 2016; 47 (02) 376-382
  • 2 Lavin P, Patrylo M, Hollar M, Espaillat KB, Kirshner H, Schrag M. Stroke risk and risk factors in patients with central retinal artery occlusion. Am J Ophthalmol 2018; 196: 96-100
  • 3 Biousse V, Nahab F, Newman NJ. Management of acute retinal ischemia: follow the guidelines!. Ophthalmology 2018; 125 (10) 1597-1607
  • 4 Callizo J, Feltgen N, Pantenburg S. et al; European Assessment Group for Lysis in the Eye. Cardiovascular risk factors in central retinal artery occlusion: results of a prospective and standardized medical examination. Ophthalmology 2015; 122 (09) 1881-1888
  • 5 Hayreh SS, Podhajsky PA, Zimmerman MB. Retinal artery occlusion: associated systemic and ophthalmic abnormalities. Ophthalmology 2009; 116 (10) 1928-1936
  • 6 Savino PJ, Glaser JS, Cassady J. Retinal stroke. Is the patient at risk?. Arch Ophthalmol 1977; 95 (07) 1185-1189
  • 7 Wilson LA, Warlow CP, Russell RW. Cardiovascular disease in patients with retinal arterial occlusion. Lancet 1979; 1 (8111): 292-294
  • 8 Egan RA, Biousse V. Update on ischemic stroke. Curr Opin Ophthalmol 2000; 11 (06) 395-402
  • 9 Chang Y-S, Jan R-L, Weng S-F. et al. Retinal artery occlusion and the 3-year risk of stroke in Taiwan: a nationwide population-based study. Am J Ophthalmol 2012; 154 (04) 645-652.e1
  • 10 Furie KL, Kasner SE, Adams RJ. et al; American Heart Association Stroke Council, Council on Cardiovascular Nursing, Council on Clinical Cardiology, and Interdisciplinary Council on Quality of Care and Outcomes Research. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42 (01) 227-276
  • 11 Sacco RL, Kasner SE, Broderick JP. et al; American Heart Association Stroke Council, Council on Cardiovascular Surgery and Anesthesia, Council on Cardiovascular Radiology and Intervention, Council on Cardiovascular and Stroke Nursing, Council on Epidemiology and Prevention, Council on Peripheral Vascular Disease, Council on Nutrition, Physical Activity and Metabolism. An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013; 44 (07) 2064-2089
  • 12 Kernan WN, Ovbiagele B, Black HR. et al; American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014; 45 (07) 2160-2236
  • 13 Easton JD, Saver JL, Albers GW. et al; American Heart Association, American Stroke Association Stroke Council, Council on Cardiovascular Surgery and Anesthesia, Council on Cardiovascular Radiology and Intervention, Council on Cardiovascular Nursing, Interdisciplinary Council on Peripheral Vascular Disease. Definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists. Stroke 2009; 40 (06) 2276-2293
  • 14 Hughes S, Yang H, Chan-Ling T. Vascularization of the human fetal retina: roles of vasculogenesis and angiogenesis. Invest Ophthalmol Vis Sci 2000; 41 (05) 1217-1228
  • 15 Purves D, Augustine GJ, Fitzpatrick D. et al. Neuroscience. 2nd ed.. Sunderland, MA: Sinauer Associates; 2001
  • 16 Runkle EA, Antonetti DA. The blood-retinal barrier: structure and functional significance. Methods Mol Biol 2011; 686: 133-148
  • 17 O'Brown NM, Pfau SJ, Gu C. Bridging barriers: a comparative look at the blood-brain barrier across organisms. Genes Dev 2018; 32 (7-8): 466-478
  • 18 Singh S, Dass R. The central artery of the retina. I. Origin and course. Br J Ophthalmol 1960; 44: 193-212
  • 19 Avery MB, Magal I, Kherani A, Mitha AP. Risk of stroke in patients with ocular arterial occlusive disorders: a retrospective Canadian study. J Am Heart Assoc 2019; 8 (03) e010509
  • 20 Kim JS, Caplan LR. Clinical stroke syndromes. Front Neurol Neurosci 2016; 40: 72-92
  • 21 Park SJ, Choi N-K, Seo KH, Park KH, Woo SJ. Nationwide incidence of clinically diagnosed central retinal artery occlusion in Korea, 2008 to 2011. Ophthalmology 2014; 121 (10) 1933-1938
  • 22 Park SJ, Choi N-K, Yang BR. et al. Risk and risk periods for stroke and acute myocardial infarction in patients with central retinal artery occlusion. Ophthalmology 2015; 122 (11) 2336-2343.e2
  • 23 Rothwell PM, Giles MF, Chandratheva A. et al; Early use of Existing Preventive Strategies for Stroke (EXPRESS) study. Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison. Lancet 2007; 370 (9596): 1432-1442
  • 24 Olsen TW, Pulido JS, Folk JC, Hyman L, Flaxel CJ, Adelman RA. Retinal and ophthalmic artery occlusions Preferred Practice Pattern®. Ophthalmology 2017; 124 (02) 120 –P143
  • 25 Atkins EJ, Bruce BB, Newman NJ, Biousse V. Translation of clinical studies to clinical practice: survey on the treatment of central retinal artery occlusion. Am J Ophthalmol 2009; 148 (01) 172-173
  • 26 Abel AS, Suresh S, Hussein HM, Carpenter AF, Montezuma SR, Lee MS. Practice patterns after acute embolic retinal artery occlusion. Asia Pac J Ophthalmol (Phila) 2017; 6 (01) 37-39
  • 27 Dattilo M, Biousse V, Newman NJ. Update on the management of central retinal artery occlusion. Neurol Clin 2017; 35 (01) 83-100
  • 28 Lawlor M, Perry R, Hunt BJ, Plant GT. Strokes and vision: the management of ischemic arterial disease affecting the retina and occipital lobe. Surv Ophthalmol 2015; 60 (04) 296-309
  • 29 Pedersen CB. The Danish Civil Registration System. Scand J Public Health 2011; 39 (7, Suppl): 22-25
  • 30 Lynge E, Sandegaard JL, Rebolj M. The Danish National Patient Register. Scand J Public Health 2011; 39 (7, Suppl): 30-33
  • 31 Kildemoes HW, Sørensen HT, Hallas J. The Danish National Prescription Registry. Scand J Public Health 2011; 39 (7, Suppl): 38-41
  • 32 Lip GYH, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest 2010; 137 (02) 263-272
  • 33 January CT, Wann LS, Alpert JS. et al; ACC/AHA Task Force Members. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 2014; 130 (23) e199-e267
  • 34 Boulanger M, Li L, Lyons S. et al. Essen risk score in prediction of myocardial infarction after transient ischemic attack or ischemic stroke without prior coronary artery disease. Stroke 2019; 50 (12) 3393-3399
  • 35 Cox DR. Regression models and life-tables. J R Stat Soc B 1972; 34: 187-202
  • 36 Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc Taylor & Francis 1999; 94: 496-509
  • 37 Caetano SJ, Sonpavde G, Pond GR. C-statistic: a brief explanation of its construction, interpretation and limitations. Eur J Cancer 2018; 90: 130-132
  • 38 Brier GW. Verification of forecasts expressed in terms of probability. Mon Weather Rev 1950; 78: 1-3
  • 39 Gerds TA, Kattan MW. Medical Risk Prediction: With Ties to Machine Learning. 1st ed.. London, United Kingdom: Chapman and Hall/CRC; 2021
  • 40 Kattan MW, Gerds TA. The index of prediction accuracy: an intuitive measure useful for evaluating risk prediction models. Diagn Progn Res 2018; 2: 7
  • 41 Feigin VL, Forouzanfar MH, Krishnamurthi R. et al; Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) and the GBD Stroke Experts Group. Global and regional burden of stroke during 1990-2010: findings from the Global Burden of Disease Study 2010. Lancet 2014; 383 (9913): 245-254
  • 42 Wang JJ, Cugati S, Knudtson MD. et al. Retinal arteriolar emboli and long-term mortality: pooled data analysis from two older populations. Stroke 2006; 37 (07) 1833-1836
  • 43 Klein R, Klein BEK, Jensen SC. et al. Retinal emboli and stroke. 1999; 117: 1063-1068
  • 44 Klein R, Klein BEK, Moss SE, Meuer SM. Retinal emboli and cardiovascular disease: the Beaver Dam Eye Study. Arch Ophthalmol 2003; 121 (10) 1446-1451
  • 45 Chen J-Y, Zhang A-D, Lu H-Y, Guo J, Wang FF, Li ZC. CHADS2 versus CHA2DS2-VASc score in assessing the stroke and thromboembolism risk stratification in patients with atrial fibrillation: a systematic review and meta-analysis. J Geriatr Cardiol 2013; 10 (03) 258-266
  • 46 Lip GYH, Lin H-J, Chien K-L. et al. Comparative assessment of published atrial fibrillation stroke risk stratification schemes for predicting stroke, in a non-atrial fibrillation population: the Chin-Shan Community Cohort Study. Int J Cardiol 2013; 168 (01) 414-419
  • 47 Van Staa TP, Setakis E, Di Tanna GL, Lane DA, Lip GY. A comparison of risk stratification schemes for stroke in 79,884 atrial fibrillation patients in general practice. J Thromb Haemost 2011; 9 (01) 39-48
  • 48 Assel M, Sjoberg DD, Vickers AJ. The Brier score does not evaluate the clinical utility of diagnostic tests or prediction models. Diagn Progn Res 2017; 1: 19
  • 49 Arboix A, Alió J. Cardioembolic stroke: clinical features, specific cardiac disorders and prognosis. Curr Cardiol Rev 2010; 6 (03) 150-161
  • 50 Arboix A, García-Eroles L, Massons JB, Oliveres M, Pujades R, Targa C. Atrial fibrillation and stroke: clinical presentation of cardioembolic versus atherothrombotic infarction. Int J Cardiol 2000; 73 (01) 33-42
  • 51 Varma DD, Cugati S, Lee AW, Chen CS. A review of central retinal artery occlusion: clinical presentation and management. Eye (Lond) 2013; 27 (06) 688-697
  • 52 Ørskov M, Vorum H, Larsen TB, Lip GYH, Bek T, Skjøth F. Clinical risk factors for retinal artery occlusions: a nationwide case-control study. Int Ophthalmol 2022; 42 (08) 2483-2491
  • 53 Hayreh SS. Acute retinal arterial occlusive disorders. Prog Retin Eye Res 2011; 30 (05) 359-394
  • 54 Schmidt M, Schmidt SAJ, Sandegaard JL, Ehrenstein V, Pedersen L, Sørensen HT. The Danish National Patient Registry: a review of content, data quality, and research potential. Clin Epidemiol 2015; 7: 449-490
  • 55 Yoon M, Yang P-S, Jang E. et al. Dynamic changes of CHA2DS2-VASc score and the risk of ischaemic stroke in Asian patients with atrial fibrillation: a nationwide cohort study. Thromb Haemost 2018; 118 (07) 1296-1304