To investigate the association between osteoarthritis (OA) and microvascular pathology, we examined the relationship between retinal microvascular caliber and osteoarthritis of the hand and knee in an elderly population. The AGES-Reykjavik is a population-based, multidisciplinary longitudinal cohort study of aging. Retinal vessel caliber, hand osteoarthritis and total knee joint replacements due to OA were examined in 4757 individuals (mean age 76 ± 5 years; 57% female). Incident knee joint replacements during 5-year follow-up (n = 2961, mean age 75 ± 5 years; 58% female) were also assessed. Logistic regression analysis, adjusting for age, sex, and body mass index, showed an association between narrow arteriolar caliber and hand OA, as well as knee replacement. After adjustment for other covariates, including statin therapy, this association was significant for both hand OA in men and women [OR 1.10(1.03–1.17), p < 0.01] (per unit standard deviation decrease in CRAE) and TKR prevalence [OR 1.15 (1.01–1.32), p = 0.04], especially for men [OR 1.22 (1.00–1.51) p = 0.04] and also for incident TKRs in men [OR 1.50 (1.07–2.10), p = 0.04]. Narrow venular caliber was associated with hand OA in women [OR 1.10 (1.01–1.21), p = 0.03]. Retinal arterial narrowing in hand and knee OA is present in males as well as females. Venular narrowing in hand OA in women was an unexpected finding and is in contrast with the venular widening usually observed in cardiovascular diseases.
Osteoarthritis Retinal vessel diameters
This is a preview of subscription content, log in to check access.
All authors have: (1) made substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data; (2) been involved in drafting the manuscript or revising it critically for important intellectual content; (3) given final approval of the version to be published; and (4) agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
This work was supported by the National Institutes of Health (Intramural Research Programs of the National Institute of Aging and the National Eye Institute, ZIAEY000401), National Institutes of Health contract number N01-AG-1-2100, the Icelandic Heart Association, and the Icelandic Parliament. The funders had no role in data collection, management, analysis and interpretation of the data, preparation, writing and approval of the manuscript, and decision to submit the manuscript for publication.
Compliance with ethical standards
Conflict of interest
The authors have no proprietary or commercial interest in any materials discussed in this article.
All procedures performed were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments. Both studies were approved by the Icelandic National Bioethics Committee, (VSN: 00-063, and VSN 09_098_S1) and the Data Protection Authority.
Both studies were approved by the Icelandic National Bioethics Committee, (VSN: 00–063, and VSN 09_098_S1) and the Data Protection Authority.
All participants signed an informed consent declaration.
Consent to publish
The study is approved by the AGES-Reykjavik steering committee.
All data are from the AGES-Reykjavik study and can be obtained upon application.
Jonsson H, Helgadottir GP, Aspelund T, Eiriksdottir G, Sigurdsson S, Ingvarsson T et al (2009) Hand osteoarthritis in older women is associated with carotid and coronary atherosclerosis: the AGES Reykjavik study. Ann Rheum Dis 68:1696–1700CrossRefPubMedGoogle Scholar
Jonsson H, Helgadottir GP, Aspelund T, Eiriksdottir G, Sigurdsson S, Siggeirsdottir K et al (2011) The presence of total knee or hip replacements due to osteoarthritis enhances the positive association between hand osteoarthritis and atherosclerosis in women: the AGES-Reykjavik study. Ann Rheum Dis 70:1087–1090CrossRefPubMedPubMedCentralGoogle Scholar
Hoeven TA, Kavousi M, Clockaerts S, Kerkhof HJ, van Meurs JB, Franco O et al (2013) Association of atherosclerosis with presence and progression of osteoarthritis: the Rotterdam Study. Ann Rheum Dis 72:646–651CrossRefPubMedGoogle Scholar
Koutroumpas A, Giannoukas A, Zintzaras E, Exarchou E, Baliakos A, Makaritsis K et al (2013) Erosive hand osteoarthritis is associated with subclinical atherosclerosis and endothelial dysfunction. Int J Biomed Sci 9:217–223PubMedPubMedCentralGoogle Scholar
Liew G, Wang JJ, Mitchell PP, Wong TY (2008) Retinal vascular imaging: a new tool in microvascular disease research. Circ Cardiovasc Imaging 1:156–161CrossRefPubMedGoogle Scholar
Ding J, Wai KL, McGeechan K, Ikram MK, Kawasaki R, Xie J et al (2014) Retinal vascular caliber and the development of hypertension: a meta-analysis of individual participant data. J Hypertens 32:207–215CrossRefPubMedPubMedCentralGoogle Scholar
McClintic BR, McClintic JI, Bisognano JD, Block RC (2010) The relationship between retinal microvascular abnormalities and coronary heart disease: a review. Am J Med123:374.e1-374.e7Google Scholar
McGeechan K, Liew G, Macaskill P, Irwig L, Klein R, Klein BE et al (2009) Meta-analysis: retinal vessel caliber and risk for coronary heart disease. Ann Intern Med 151:404–413CrossRefPubMedPubMedCentralGoogle Scholar
Hussain SM, Wang Y, Shaw JE, Magliano DJ, Wong TY, Wluka AE et al (2015) Retinal arteriolar narrowing and incidence of knee replacement for osteoarthritis: a prospective cohort study. Osteoarthritis Cartil 23:589–593CrossRefGoogle Scholar
Harris TB, Launer LJ, Eiriksdottir G, Kjartansson O, Jonsson PV, Sigurdsson G et al (2007) Age, gene/environment susceptibility-Reykjavik study: multidisciplinary applied phenomics. Am J Epidemiol 165:1076–1087CrossRefPubMedPubMedCentralGoogle Scholar
Klein R, Meuer SM, Moss SE, Klein BE, Neider MW, Reinke J (2004) Detection of age-related macular degeneration using a nonmydriatic digital camera and a standard film fundus camera. Arch Ophthalmol 122:1642–1646CrossRefPubMedGoogle Scholar
Knudtson MD, Lee KE, Hubbard LD, Wong TY, Klein R, Klein BE (2003) Revised formulas for summarizing retinal vessel diameters. Curr Eye Res 27:143–149CrossRefPubMedGoogle Scholar
Jonsson H, Helgadottir GP, Aspelund T, Sverrisdottir JE, Eiriksdottir G, Sigurdsson S et al (2012) The use of digital photographs for the diagnosis of hand osteoarthritis: the AGES-Reykjavik study. BMC Musculoskelet Disord 13:20CrossRefPubMedPubMedCentralGoogle Scholar
Jonsson H, Olafsdottir S, Sigurdardottir S, Aspelund T, Eiriksdottir G, Sigurdsson S et al (2016) Incidence and prevalence of total joint replacements due to osteoarthritis in the elderly: risk factors and factors associated with late life prevalence in the AGES-Reykjavik study. BMC Musculoskelet Disord 17:14CrossRefPubMedPubMedCentralGoogle Scholar
Davies-Tuck ML, Kawasaki R, Wluka AE, Wong TY, Hogdson L, English DR et al (2012) The relationship between retinal vessel calibre and knee cartilage and BMLs. BMC Musculoskelet Disord 13:255–265CrossRefPubMedPubMedCentralGoogle Scholar
Liew G, Campbell S, Klein R, Klein BE, Sharrett AR, Cotch MF et al (2011) Ten-year longitudinal changes in retinal microvascular lesions: the atherosclerosis risk in communities study. Ophthalmology 118:1612–1618CrossRefPubMedPubMedCentralGoogle Scholar
Myers CE, Klein R, Knudston MD, Lee KE, Gangnon R, Wong TY et al (2012) Determinants of retinal venular diameter: the Beaver Dam Eye Study. Ophthalmology 199:2563–2571CrossRefGoogle Scholar
Sasaki M, Gan WL, Kawasaki R, Hodgson L, Lee KY, Wong TY et al (2013) Effect of simvastatin on retinal vascular caliber: the Age-Related Maculopathy Statin Study. Acta Ophthalmol 91:e418–e419CrossRefPubMedGoogle Scholar
Bierma-Zeinstra SMA, Hoeven TA, Waarsing JH (2017) Is having OA an independent risk factor for cardiovascular events? Osteoarthritis Cartil 25:997–999CrossRefGoogle Scholar
Liu R, Kwok WY, Vliet Vlieland TP, Kroon HM, Meulenbelt I, Houwing-Duistermaat JJ et al (2015) Mortality in osteoarthritis patients. Scand J Rheumatol 44:70–73CrossRefPubMedGoogle Scholar
Haugen IK, Ramachandran VS, Misra D, Neogi T, Niu J, Yang T et al (2015) Hand osteoarthritis in relation to mortality and incidence of cardiovascular disease: data from the Framingham heart study. Ann Rheum Dis 74:74–81CrossRefPubMedGoogle Scholar
Courties A, Sellam J, Berenbaum F (2017) Metabolic syndrome-associated osteoarthritis. Curr Opin Rheumatol 29:214–222CrossRefPubMedGoogle Scholar
de Munter W, van der Kraan PM, van den Berg WB, van Lent PL (2016) High systemic levels of low-density lipoprotein cholesterol: fuel to the flames in inflammatory osteoarthritis? Rheumatology 55:16–24CrossRefPubMedGoogle Scholar
Tootsi K, Kals J, Zilmer M, Paapstel K, Märtson A (2016) Severity of osteoarthritis is associated with increased arterial stiffness. Int J Rheumatol. 2016:6402963Google Scholar
Hoeven TA, Kavousi M, Ikram MA, van Meurs JB, Bindels PJ, Hofman A et al (2015) Markers of atherosclerosis in relation to presence and progression of knee osteoarthritis: a population-based cohort study. Rheumatology 54:1692–1698CrossRefPubMedGoogle Scholar
Styrkarsdottir U, Thorleifsson G, Helgadottir HT, Bomer N, Metrustry S, Bierma-Zeinstra S et al (2014) Severe osteoarthritis of the hand associates with common variants within the ALDH1A2 gene and with rare variants at 1p31. Nat Genet 46:498–502CrossRefPubMedGoogle Scholar
Krivospitskaya O, Elmabsout AA, Sundman E, Söderström LA, Ovchinnikova O, Gidlöf AC et al (2012) A CYP26B1 polymorphism enhances retinoic acid catabolism and may aggravate atherosclerosis. Mol Med 18:712–718CrossRefPubMedPubMedCentralGoogle Scholar
Marshall M, Jonsson H, Helgadottir GP, Nicholls E, van der Windt D, Myers H, Dziedzic K (2014) Reliability of assessing hand osteoarthritis on digital photographs and associations with radiographic and clinical findings. Arthritis Care Res 66:828–836CrossRefGoogle Scholar
Dougados M, Hawker G, Lohmander S, Davis AM, Dieppe P, Maillefert JF, Gossec L (2009) OARSI/OMERACT criteria of being considered a candidate for total joint replacement in knee/hip osteoarthritis as an endpoint in clinical trials evaluating potential disease modifying osteoarthritic drugs. J Rheumatol 36:2097–2099CrossRefPubMedGoogle Scholar