The Relationship between Age-Related Macular Degeneration and Cardiovascular Disease: A Meta-Analysis
Abstract
Background: Age-related macular degeneration (AMD) and cardiovascular disease (CVD) share pathogenic mechanisms, and their lead-lag relationship remains unclear. We performed a meta-analysis of data from longitudinal studies to evaluate the interactive association between age-related macular degeneration (AMD) and cardiovascular disease (CVD).
Methods: A literature search was performed in PubMed, Embase, and Cochrane Library up to Feb 2019. Estimates were pooled by study quality and type of AMD and CVD. Publication bias was assessed by Begg’s test.
Results: We identified nine studies for the risk of AMD in CVD and ten studies for the risk of CVD in AMD. Overall, evidence for the risk of CVD in AMD patients was most robust. Both early and late AMD preceded CVD, but more solid significance existed in late AMD. Among the types of CVD, stroke was more tightly associated with AMD than coronary heart disease. Publication bias was not significant in either direction.
Conclusion: AMD is a risk factor for CVD, which is primarily driven by the increased risk of stroke in patients with late AMD. Moreover, these results suggested that AMD treatment and screening for CVD in AMD patients may have unexplored clinical benefits.
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2. Wong WL, Su X, Li X, Cheung CM, et al (2014). Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health, 2(2):e106-16.
3. Nevitt MC, Cummings SR, Kidd S, Black D (1989). Risk factors for recurrent nonsyncopal falls. A prospective study. JAMA, 261(18):2663-8.
4. Cummings SR, Nevitt MC, Browner WS, et al (1995). Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med, 332(12):767-73.
5. Wang X, Lamoureux E, Zheng Y, et al (2014). Health burden associated with visual impairment in Singapore: the Singapore epidemiology of eye disease study. Ophthalmology, 121(9):1837-42.
6. Chiang PP, Zheng Y, Wong TY, Lamoureux EL (2013). Vision impairment and major causes of vision loss impacts on vision-specific functioning independent of socioeconomic factors. Ophthalmology, 120(2):415-22.
7. Rein DB, Zhang P, Wirth KE, et al (2006). The economic burden of major adult visual disorders in the United States. Arch Ophthalmol, 124(12):1754-60.
8. Cheung CM, Wong TY (2014). Is age-related macular degeneration a manifestation of systemic disease? New prospects for early intervention and treatment. J Intern Med, 276(2):140-53.
9. Seddon JM (2017). Macular Degeneration Epidemiology: Nature-Nurture, Lifestyle Factors, Genetic Risk, and Gene-Environment Interactions - The Weisenfeld Award Lecture. Invest Ophthalmol Vis Sci, 58(14):6513-6528.
10. Snow KK, Seddon JM (1999). Do age-related macular degeneration and cardiovascular disease share common antecedents? Ophthalmic Epidemiol, 6(2):125-43.
11. Wu J, Uchino M, Sastry SM, Schaumberg DA (2014). Age-related macular degeneration and the incidence of cardiovascular disease: a systematic review and meta-analysis. PLoS One, 9(3):e89600.
12. Wang J, Xue Y, Thapa S, et al (2016). Relation between Age-Related Macular Degeneration and Cardiovascular Events and Mortality: A Systematic Review and Meta-Analysis. Biomed Res Int, 2016:8212063.
13. Chakravarthy U, Wong TY, Fletcher A, et al (2010). Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis. BMC Ophthalmol, 10:31.
14. Fernandez AB, Panza GA, Cramer B, et al (2015). Age-Related Macular Degeneration and Incident Stroke: A Systematic Review and Meta-Analysis. PLoS One, 10(11):e0142968.
15. Voutilainen-Kaunisto RM, Terasvirta ME, Uusitupa MI, Niskanen LK (2000). Age-related macular degeneration in newly diagnosed type 2 diabetic patients and control subjects: a 10-year follow-up on evolution, risk factors, and prognostic significance. Diabetes Care, 23(11):1672-8.
16. Lee WA, Cheng CL, Lee CH, et al (2017). Risks of newly onset hemorrhagic stroke in patients with neovascular age-related macular degeneration. Pharmacoepidemiol Drug Saf, 26(10):1277-1285.
17. Ikram MK, Mitchell P, Klein R, et al (2012). Age-related macular degeneration and long-term risk of stroke subtypes. Stroke, 43(6):1681-3.
18. Stroup DF, Berlin JA, Morton SC, et al (2000). Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA, 283(15):2008-12.
19. Klein R, Davis MD, Magli YL, et al (1991). The Wisconsin age-related maculopathy grading system. Ophthalmology, 98(7):1128-34.
20. Bird AC, Bressler NM, Bressler SB, et al (1995). An international classification and grading system for age-related maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group. Surv Ophthalmol, 39(5):367-74.
21. Higgins JP, Thompson SG (2002). Quantifying heterogeneity in a meta-analysis. Stat Med, 21(11):1539-58.
22. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003). Measuring inconsistency in meta-analyses. BMJ, 327(7414):557-60.
23. Liao D, Mo J, Duan Y, et al (2008). Is age-related macular degeneration associated with stroke among elderly americans? Open Ophthalmol J, 2:37-42.
24. Duan Y, Mo J, Klein R, et al (2007). Age-related macular degeneration is associated with incident myocardial infarction among elderly Americans. Ophthalmology, 114(4):732-7.
25. Wieberdink RG, Ho L, Ikram MK, et al (2011). Age-related macular degeneration and the risk of stroke: the Rotterdam study. Stroke, 42(8):2138-42.
26. Nguyen-Khoa BA, Goehring EL Jr, Werther W, et al (2008). Hospitalized cardiovascular diseases in neovascular age-related macular degeneration. Arch Ophthalmol, 126(9):1280-6.
27. Fernandez AB, Ballard KD, Wong TY, et al (2018). Age-related macular degeneration and progression of coronary artery calcium: The Multi-Ethnic Study of Atherosclerosis. PLoS One, 13(7):e0201000.
28. Klein R, Cruickshanks KJ, Myers CE, et al (2013). The relationship of atherosclerosis to the 10-year cumulative incidence of age-related macular degeneration: The beaver dam studies. Ophthalmology, 120(5):1012-9.
29. Friedman E (2000). The role of the atherosclerotic process in the pathogenesis of age-related macular degeneration. Am J Ophthalmol, 130(5):658-63.
30. Wong TY (2010). Age-related macular degeneration: why should stroke physicians care? Stroke, 41(4):575-6.
31. Di Napoli M (2001). Systemic complement activation in ischemic stroke. Stroke, 32(6):1443-8.
32. Edwards AO, Ritter R 3rd, Abel KJ, et al (2005). Complement factor H polymorphism and age-related macular degeneration. Science, 308(5720):421-4.
33. Yip JL, Khawaja AP, Chan MP, et al (2015). Cross Sectional and Longitudinal Associations between Cardiovascular Risk Factors and Age Related Macular Degeneration in the EPIC-Norfolk Eye Study. PLoS One, 10(7):e0132565.
34. Wang X, Dong Y, Qi X, et al (2013). Cholesterol levels and risk of hemorrhagic stroke: a systematic review and meta-analysis. Stroke, 44(7):1833-9.
35. Rempe RG, Hartz AMS, Bauer B (2016). Matrix metalloproteinases in the brain and blood-brain barrier: Versatile breakers and makers. J Cereb Blood Flow Metab, 36(9):1481-507.
36. Zeng S, Whitmore SS, Sohn EH, et al (2016). Molecular response of chorioretinal endothelial cells to complement injury: implications for macular degeneration. J Pathol, 238(3):446-56.
37. Yan T, Chopp M, Chen J (2015). Experimental animal models and inflammatory cellular changes in cerebral ischemic and hemorrhagic stroke. Neurosci Bull, 31(6):717-34.
38. Zhou F, Chen B, Chen C, et al (2015). Elevated homocysteine levels contribute to larger hematoma volume in patients with intracerebral hemorrhage. J Stroke Cerebrovasc Dis, 24(4):784-8.
39. Kim AS, Johnston SC (2011). Global variation in the relative burden of stroke and ischemic heart disease. Circulation, 124(3):314-23.
40. Wong CW, Yanagi Y, Lee WK, et al (2016). Age-related macular degeneration and polypoidal choroidal vasculopathy in Asians. Prog Retin Eye Res, 53:107-139.
41. Glasziou PP, Sanders SL (2002). Investigating causes of heterogeneity in systematic reviews. Stat Med, 21(11):1503-11.
42. Sobrin L, Seddon JM (2014). Nature and nurture- genes and environment- predict onset and progression of macular degeneration. Prog Retin Eye Res, 40:1-15.
43. Holz FG, Schmitz-Valckenberg S, Fleckenstein M (2014). Recent developments in the treatment of age-related macular degeneration. J Clin Invest, 124(4): 1430–1438.
44. Foo VHX, Yanagi Y, Nguyen QD, et al (2018). Six-Year Incidence and Risk Factors of Age-Related Macular Degeneration in Singaporean Indians: The Singapore Indian Eye Study. Sci Rep, 8(1):8869.
45. Vassilev ZP, Ruigomez A, Soriano-Gabarro M, Garcia Rodriguez LA (2015). Diabetes, cardiovascular morbidity, and risk of age-related macular degeneration in a primary care population. Invest Ophthalmol Vis Sci, 56(3):1585-92.
46. Thomas J, Mohammad S, Charnigo R, et al (2015). Age-Related Macular Degeneration and Coronary Artery Disease in a VA Population. South Med J, 108(8): 502–506.
47. Tan JS, Mitchell P, Smith W, Wang JJ (2007). Cardiovascular risk factors and the long-term incidence of age-related macular degeneration: the Blue Mountains Eye Study. Ophthalmology, 114(6):1143-50.
48. Leske MC, Wu SY, Hennis A, et al (2006). Nine-year incidence of age-related macular degeneration in the Barbados Eye Studies. Ophthalmology, 113(1):29-35.
49. Buch H, Vinding T, la Cour M, et al (2005). Risk factors for age-related maculopathy in a 14-year follow-up study: the Copenhagen City Eye Study. Acta Ophthalmol Scand, 83(4):409-18.
50. Tomany SC, Wang JJ, Van Leeuwen R, et al (2004). Risk factors for incident age-related macular degeneration: pooled findings from 3 continents. Ophthalmology, 111(7):1280-7.
51. Klein R, Klein BE, Tomany SC, Cruickshanks KJ (2003). The association of cardiovascular disease with the long-term incidence of age-related maculopathy: the Beaver Dam eye study. Ophthalmology, 110(6):1273-80.
52. Fernandez AB, Wong TY, Klein R, et al (2012). Age-related macular degeneration and incident cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis. Ophthalmology, 119(4):765-70.
53. Golan S, Shalev V, Goldstein M, et al (2011). The rate of myocardial infarction events among patients with age-related macular degeneration: a population-based study. Graefes Arch Clin Exp Ophthalmol, 249(2):179-82.
54. Sun C, Klein R, Wong TY (2009). Age-related macular degeneration and risk of coronary heart disease and stroke: the Cardiovascular Health Study. Ophthalmology, 116(10):1913-9.
55. Wong TY, Tikellis G, Sun C, et al (2007). Age-related macular degeneration and risk of coronary heart disease: the Atherosclerosis Risk in Communities Study. Ophthalmology, 114(1):86-91.
2. Wong WL, Su X, Li X, Cheung CM, et al (2014). Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health, 2(2):e106-16.
3. Nevitt MC, Cummings SR, Kidd S, Black D (1989). Risk factors for recurrent nonsyncopal falls. A prospective study. JAMA, 261(18):2663-8.
4. Cummings SR, Nevitt MC, Browner WS, et al (1995). Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med, 332(12):767-73.
5. Wang X, Lamoureux E, Zheng Y, et al (2014). Health burden associated with visual impairment in Singapore: the Singapore epidemiology of eye disease study. Ophthalmology, 121(9):1837-42.
6. Chiang PP, Zheng Y, Wong TY, Lamoureux EL (2013). Vision impairment and major causes of vision loss impacts on vision-specific functioning independent of socioeconomic factors. Ophthalmology, 120(2):415-22.
7. Rein DB, Zhang P, Wirth KE, et al (2006). The economic burden of major adult visual disorders in the United States. Arch Ophthalmol, 124(12):1754-60.
8. Cheung CM, Wong TY (2014). Is age-related macular degeneration a manifestation of systemic disease? New prospects for early intervention and treatment. J Intern Med, 276(2):140-53.
9. Seddon JM (2017). Macular Degeneration Epidemiology: Nature-Nurture, Lifestyle Factors, Genetic Risk, and Gene-Environment Interactions - The Weisenfeld Award Lecture. Invest Ophthalmol Vis Sci, 58(14):6513-6528.
10. Snow KK, Seddon JM (1999). Do age-related macular degeneration and cardiovascular disease share common antecedents? Ophthalmic Epidemiol, 6(2):125-43.
11. Wu J, Uchino M, Sastry SM, Schaumberg DA (2014). Age-related macular degeneration and the incidence of cardiovascular disease: a systematic review and meta-analysis. PLoS One, 9(3):e89600.
12. Wang J, Xue Y, Thapa S, et al (2016). Relation between Age-Related Macular Degeneration and Cardiovascular Events and Mortality: A Systematic Review and Meta-Analysis. Biomed Res Int, 2016:8212063.
13. Chakravarthy U, Wong TY, Fletcher A, et al (2010). Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis. BMC Ophthalmol, 10:31.
14. Fernandez AB, Panza GA, Cramer B, et al (2015). Age-Related Macular Degeneration and Incident Stroke: A Systematic Review and Meta-Analysis. PLoS One, 10(11):e0142968.
15. Voutilainen-Kaunisto RM, Terasvirta ME, Uusitupa MI, Niskanen LK (2000). Age-related macular degeneration in newly diagnosed type 2 diabetic patients and control subjects: a 10-year follow-up on evolution, risk factors, and prognostic significance. Diabetes Care, 23(11):1672-8.
16. Lee WA, Cheng CL, Lee CH, et al (2017). Risks of newly onset hemorrhagic stroke in patients with neovascular age-related macular degeneration. Pharmacoepidemiol Drug Saf, 26(10):1277-1285.
17. Ikram MK, Mitchell P, Klein R, et al (2012). Age-related macular degeneration and long-term risk of stroke subtypes. Stroke, 43(6):1681-3.
18. Stroup DF, Berlin JA, Morton SC, et al (2000). Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA, 283(15):2008-12.
19. Klein R, Davis MD, Magli YL, et al (1991). The Wisconsin age-related maculopathy grading system. Ophthalmology, 98(7):1128-34.
20. Bird AC, Bressler NM, Bressler SB, et al (1995). An international classification and grading system for age-related maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group. Surv Ophthalmol, 39(5):367-74.
21. Higgins JP, Thompson SG (2002). Quantifying heterogeneity in a meta-analysis. Stat Med, 21(11):1539-58.
22. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003). Measuring inconsistency in meta-analyses. BMJ, 327(7414):557-60.
23. Liao D, Mo J, Duan Y, et al (2008). Is age-related macular degeneration associated with stroke among elderly americans? Open Ophthalmol J, 2:37-42.
24. Duan Y, Mo J, Klein R, et al (2007). Age-related macular degeneration is associated with incident myocardial infarction among elderly Americans. Ophthalmology, 114(4):732-7.
25. Wieberdink RG, Ho L, Ikram MK, et al (2011). Age-related macular degeneration and the risk of stroke: the Rotterdam study. Stroke, 42(8):2138-42.
26. Nguyen-Khoa BA, Goehring EL Jr, Werther W, et al (2008). Hospitalized cardiovascular diseases in neovascular age-related macular degeneration. Arch Ophthalmol, 126(9):1280-6.
27. Fernandez AB, Ballard KD, Wong TY, et al (2018). Age-related macular degeneration and progression of coronary artery calcium: The Multi-Ethnic Study of Atherosclerosis. PLoS One, 13(7):e0201000.
28. Klein R, Cruickshanks KJ, Myers CE, et al (2013). The relationship of atherosclerosis to the 10-year cumulative incidence of age-related macular degeneration: The beaver dam studies. Ophthalmology, 120(5):1012-9.
29. Friedman E (2000). The role of the atherosclerotic process in the pathogenesis of age-related macular degeneration. Am J Ophthalmol, 130(5):658-63.
30. Wong TY (2010). Age-related macular degeneration: why should stroke physicians care? Stroke, 41(4):575-6.
31. Di Napoli M (2001). Systemic complement activation in ischemic stroke. Stroke, 32(6):1443-8.
32. Edwards AO, Ritter R 3rd, Abel KJ, et al (2005). Complement factor H polymorphism and age-related macular degeneration. Science, 308(5720):421-4.
33. Yip JL, Khawaja AP, Chan MP, et al (2015). Cross Sectional and Longitudinal Associations between Cardiovascular Risk Factors and Age Related Macular Degeneration in the EPIC-Norfolk Eye Study. PLoS One, 10(7):e0132565.
34. Wang X, Dong Y, Qi X, et al (2013). Cholesterol levels and risk of hemorrhagic stroke: a systematic review and meta-analysis. Stroke, 44(7):1833-9.
35. Rempe RG, Hartz AMS, Bauer B (2016). Matrix metalloproteinases in the brain and blood-brain barrier: Versatile breakers and makers. J Cereb Blood Flow Metab, 36(9):1481-507.
36. Zeng S, Whitmore SS, Sohn EH, et al (2016). Molecular response of chorioretinal endothelial cells to complement injury: implications for macular degeneration. J Pathol, 238(3):446-56.
37. Yan T, Chopp M, Chen J (2015). Experimental animal models and inflammatory cellular changes in cerebral ischemic and hemorrhagic stroke. Neurosci Bull, 31(6):717-34.
38. Zhou F, Chen B, Chen C, et al (2015). Elevated homocysteine levels contribute to larger hematoma volume in patients with intracerebral hemorrhage. J Stroke Cerebrovasc Dis, 24(4):784-8.
39. Kim AS, Johnston SC (2011). Global variation in the relative burden of stroke and ischemic heart disease. Circulation, 124(3):314-23.
40. Wong CW, Yanagi Y, Lee WK, et al (2016). Age-related macular degeneration and polypoidal choroidal vasculopathy in Asians. Prog Retin Eye Res, 53:107-139.
41. Glasziou PP, Sanders SL (2002). Investigating causes of heterogeneity in systematic reviews. Stat Med, 21(11):1503-11.
42. Sobrin L, Seddon JM (2014). Nature and nurture- genes and environment- predict onset and progression of macular degeneration. Prog Retin Eye Res, 40:1-15.
43. Holz FG, Schmitz-Valckenberg S, Fleckenstein M (2014). Recent developments in the treatment of age-related macular degeneration. J Clin Invest, 124(4): 1430–1438.
44. Foo VHX, Yanagi Y, Nguyen QD, et al (2018). Six-Year Incidence and Risk Factors of Age-Related Macular Degeneration in Singaporean Indians: The Singapore Indian Eye Study. Sci Rep, 8(1):8869.
45. Vassilev ZP, Ruigomez A, Soriano-Gabarro M, Garcia Rodriguez LA (2015). Diabetes, cardiovascular morbidity, and risk of age-related macular degeneration in a primary care population. Invest Ophthalmol Vis Sci, 56(3):1585-92.
46. Thomas J, Mohammad S, Charnigo R, et al (2015). Age-Related Macular Degeneration and Coronary Artery Disease in a VA Population. South Med J, 108(8): 502–506.
47. Tan JS, Mitchell P, Smith W, Wang JJ (2007). Cardiovascular risk factors and the long-term incidence of age-related macular degeneration: the Blue Mountains Eye Study. Ophthalmology, 114(6):1143-50.
48. Leske MC, Wu SY, Hennis A, et al (2006). Nine-year incidence of age-related macular degeneration in the Barbados Eye Studies. Ophthalmology, 113(1):29-35.
49. Buch H, Vinding T, la Cour M, et al (2005). Risk factors for age-related maculopathy in a 14-year follow-up study: the Copenhagen City Eye Study. Acta Ophthalmol Scand, 83(4):409-18.
50. Tomany SC, Wang JJ, Van Leeuwen R, et al (2004). Risk factors for incident age-related macular degeneration: pooled findings from 3 continents. Ophthalmology, 111(7):1280-7.
51. Klein R, Klein BE, Tomany SC, Cruickshanks KJ (2003). The association of cardiovascular disease with the long-term incidence of age-related maculopathy: the Beaver Dam eye study. Ophthalmology, 110(6):1273-80.
52. Fernandez AB, Wong TY, Klein R, et al (2012). Age-related macular degeneration and incident cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis. Ophthalmology, 119(4):765-70.
53. Golan S, Shalev V, Goldstein M, et al (2011). The rate of myocardial infarction events among patients with age-related macular degeneration: a population-based study. Graefes Arch Clin Exp Ophthalmol, 249(2):179-82.
54. Sun C, Klein R, Wong TY (2009). Age-related macular degeneration and risk of coronary heart disease and stroke: the Cardiovascular Health Study. Ophthalmology, 116(10):1913-9.
55. Wong TY, Tikellis G, Sun C, et al (2007). Age-related macular degeneration and risk of coronary heart disease: the Atherosclerosis Risk in Communities Study. Ophthalmology, 114(1):86-91.
| Files | ||
| Issue | Vol 50 No 2 (2021) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v50i2.5334 | |
| PMCID | PMC7956087 | |
| PMID | 33747986 | |
| Keywords | ||
| Age-related macular degeneration Cardiovascular disease Meta-analysis Stroke | ||
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How to Cite
1.
LEE J, SUH HS, HWANG IC. The Relationship between Age-Related Macular Degeneration and Cardiovascular Disease: A Meta-Analysis. Iran J Public Health. 2021;50(2):219-231.
