Papers

Risk of macular degeneration in users of statins: cross sectional study

Nigel F Hall, Wellcome research fellow, Catharine R Gale, research fellow, Holly Syddall, statistician, David I W Phillips, professor, Christopher N Martyn, epidemiologist. 

MRC Environmental Epidemiology Unit, (University of Southampton), Southampton General Hospital, Southampton SO16 6YD

Correspondence to: C N Martyn cnm{at}mrc.soton.ac.uk

Atherosclerosis and abnormalities of lipid metabolism are associated with an increased risk of age related macular degenerationthe Western world's main cause of blindness.¹ Statins (hydroxymethyl glutaryl coenzyme A reductase inhibitors) modify patients' lipid profile and lower their risk of coronary heart disease.² They also prevent stroke and, possibly, Alzheimer's disease. We report here an association between statin use and lower risk of age related macular degeneration.

	Participants, methods, and results

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We wrote to 660 men and women aged 66-75 who had been traced by the Office for National Statistics using information from their birth record at the Jessop Hospital for Women, Sheffield. Of these, 412 (62%) agreed to take part and were interviewed at home. We recorded their use of drugs, including statins, currently and in the previous five years, and their history of cardiovascular disease. The participants were invited to a clinic at the Northern General Hospital, Sheffield, and 392 (95% of those interviewed) attended, where stereoscopic photos of both fundi were taken. Photographs were graded by one observer (NFH), who was unaware of the participants' drug history, against standard images using the Wisconsin age related maculopathy grading system.³ We excluded 12 participants who had non-age related degenerative macular changes and one participant who was taking part in a trial of statins. The analyses that follow are therefore based on 379 participants.

Of the 379 subjects, 27 (7%) reported taking statins and 77 (20%) had some evidence of macular degeneration. Age related macular degeneration was more common among the participants who did not take statins (see table ): 76/352 (22%) of participants who did not take statins showed signs of macular degeneration, compared with only 1/27 (4%) of participants taking statins (P=0.02, Fisher's exact test). This is equivalent to an odds ratio for macular degeneration among participants who took statins of 0.14 (95% confidence interval 0.02 to 0.83) compared with those who did not.

A history of coronary artery bypass grafting or angioplasty was associated with macular degeneration. Eight of the 77 participants with macular degeneration (10%) had undergone coronary angioplasty or bypass grafting compared with 13 of the 302 participants (4%) without macular degeneration (P=0.05, Fisher's exact test). Not surprisingly, people who had undergone coronary angioplasty or bypass grafting were more likely to have taken statins than those who had not (6/22 (27%) compared with 21/389 (5%) respectively). In a logistic regression modelafter adjustment for age, sex, smoking, and history of coronary angioplasty or bypass graftingthe odds ratio for macular degeneration (early or late) among participants taking statins was 0.09 (0.01 to 0.73) compared with those who did not take the drug.

	Comment

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In this survey of men and women aged 66-75 those who took statins had an eleventh the risk of age related macular degeneration (after adjustment for coronary artery disease and smoking) compared with those not taking the drug. The confidence intervals are wide, however, giving an imprecise estimate of the reduced risk. Bias could lead to this association if people with macular degeneration and taking statins were less likely to participate, or people without macular degeneration and not taking statins were more likely to participate, but this seems unlikely.

We suggest three mechanisms that could link statin use with lower risk of macular degeneration. Firstly, statins might prevent the accumulation of basal linear deposit in Bruch's membrane, which occurs with higher concentrations of plasma cholesterol.⁴ Secondly, antioxidant properties of statins might protect the outer retina from oxidative damage. Thirdly, simvastatin inhibits endothelial cell apoptosis and preserves ischaemic vasculature,⁵ perhaps maintaining a competent vascular supply to the macula.

	Acknowledgments

We thank Sheila Walton and Elizabeth Kelleher, research nurses, for their help with the fieldwork.

Contributors: NFH, CRG, DIWP, and CNM formulated the design of the study. NFH and CRG carried out the fieldwork. HS analysed the data. The paper was written by NFH and CNM, and edited by CNM, CRG, and DIWP. NFH and CNM are guarantors for the paper.

	Footnotes

Funding: This study was funded by the Wellcome Trust and the Medical Research Council.

Competing interests: None declared.

	References

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1.	Bressler NM. Age related macular degeneration. BMJ 2000; 321: 1425-1427[Free Full Text].
2.	Pignone M, Phillips C, Mulrow C. Use of lipid lowering drugs for primary prevention of coronary heart disease: meta-analysis of randomised trials. BMJ 2000; 321: 983-986[Abstract/Free Full Text].
3.	Klein R, Davis MD, Magli YL, Segal P, Klein BEK, Hubbard L. The Wisconsin age-related maculopathy grading system. Ophthalmology 1991; 98: 1128-1131[Medline].
4.	Dithmar S, Curcio CA, Le N-A, Brown S, Grossniklaus HE. Ultrastructural changes in Bruch's membrane of apolipoprotein E-deficient mice. Invest Ophthalmol Vis Sci 2000; 41: 2035-2042[Abstract/Free Full Text].
5.	Kureishi Y, Luo Z, Shiojima I, Bialik A, Fulton D, Lefer DJ, et al. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nature Med 2000; 6: 1004-1010[CrossRef][Medline].

(Accepted 25 June 2001)