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Meta-analysis finds lipids and lipid genes do not influence incidence, progression of AMD
Study confirms weak or inverse associations of high-density lipoprotein cholesterol and total cholesterol to AMD found in previous reports.
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No statistically significant association was found between the incidence or progression of age-related macular degeneration and cholesterol measures, history of statin use or lipid pathway genes, according to a meta-analysis of three population-based cohorts.
The 6,950 subjects, who were followed for 20 years and examined every 5 years, were from the Beaver Dam Eye Study, Blue Mountains Eye Study and Rotterdam Study.
Inconsistent relationships
“Atherosclerosis has been hypothesized to be one of the pathogenetic pathways for the development of age-related macular degeneration,” lead author Ronald Klein, MD, MPH, a professor of Ophthalmology and Visual Sciences at the University of Wisconsin School of Medicine and Public Health in Madison, said. “In fact, we had found an association of carotid intima-media thickness as measured by ultrasound, a marker of atherosclerosis to be associated with the incidence of AMD, in earlier analyses of the [Beaver Dam] cohort.”
Klein said serum lipids — serum high-density lipoprotein cholesterol and total cholesterol levels, for instance — and lipid pathway genes had been found in some studies to be associated with the incidence of AMD, whereas other studies have found a protective effect of statins.
“However, data from some studies have not shown these relationships,” Klein told Ocular Surgery News. “We felt that by studying the relationships of serum lipids, lipid pathway genes and history of statin use, in the large consortium we would be able to determine whether these factors were related to the incidence of AMD.”
The major findings of the meta-analysis, which appeared in the American Journal of Ophthalmology, did not come as a surprise to Klein.
“Earlier analysis of data from each of the three large cohorts had shown inconsistent relationships when the associations of serum lipids and AMD had been studied in the specific study,” he said. “Also, none of the three studies had shown a protective effect of statins for AMD.”
Generalizable results
Because the consortium of the three large population-based studies used the same methodology and provided enough statistical power to examine the relationships, the results are generalizable to aging white populations at risk for AMD, Klein said. However, because the three studies consisted mainly of individuals of Northern and Western European descent, the results may not be applicable to other races or white subjects of different descent.
After adjusting for age, sex and other covariates, patients with higher serum high-density lipoprotein cholesterol were 10% more likely to have a large drusen area in the macula, whereas lipoprotein lipase rs281 was linked with a decreased risk of soft indistinct drusen and large drusen area in the macula.
Considerable heterogeneity was also common when data from the three studies were combined. This may be due in part to biological differences among patients, including variations in cholesterol levels and in rates of smoking and diabetes. To minimize these and other differences, the meta-analysis was performed at a single center using the same modeling process. The risk factors, covariates and AMD outcome were also harmonized.
The authors said that other lipids, such as low-density lipoprotein cholesterol, triglycerides, fatty acids and oxidized lipids, were not measured in all three studies, and thus the current study could not determine if they were associated with the incidence of large soft drusen and late AMD.
Klein said the meta-analysis sheds further new light on how clinicians should counsel their patients about the use of statins for treatment of AMD “in that the study results suggest that physicians should not be giving statins to patients to prevent AMD, as was based on data from earlier studies that suggested a beneficial effect.” – by Bob Kronemyer
Reference:
Klein R, et al. Am J Ophthalmol. 2014;doi:10.1016/j.ajo.2014.05.027.For more information:
Ronald Klein, MD, MPH, can be reached at University of Wisconsin School of Medicine and Public Health, Department of Ophthalmology and Visual Sciences, 610 N. Walnut St., 4th Floor WARF, Madison, WI 53726-2336; 608-263-7758; email: kleinr@epi.ophth.wisc.edu.Disclosure: Klein has no relevant financial disclosures.