AMD risk factors in Latinos
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risk factors for 4-year incidence of age-related macular degeneration
(AMD) in adult Latinos.
Latinos constitute the largest and fastest-growing minority segment of
the US population. If recent trends continue, the US Latino population
is estimated to increase to 102.6 million in 2050, or 24.4% of the
total population. But there is a relative lack of population-based
data regarding ocular health in Latinos, and the factors associated
with AMD incidence and progression among Latinos remain largely
unexplored. Data from the Los Angeles Latino Eye Study (LALES)
demonstrate a lower prevalence and incidence of early and late AMD
compared to other populations. Therefore, it is important to
understand whether different and modifiable factors are operative in
Latinos that influence disease risk and progression and may explain
the differences in rates.
In the LALES, examination of baseline data revealed several
demographic (age, male gender, Native American ancestry, family
history), behavioral (smoking, alcohol consumption), clinical (higher
diastolic blood pressure [DBP], uncontrolled diastolic hypertension,
pulse pressure), and ocular (presence of cataract, cataract surgery,
and myopic refractive error) factors to be associated
cross-sectionally with the prevalence of different AMD lesions in
Latinos.
In the current analysis, the researchers examine the relationships
between these factors and the 4-year incidence and progression of AMD
in the cohort to tease out factors that are associated with disease
development vs those associated with disease duration. While
cross-sectional studies can identify associations between risk factors
and existing AMD, longitudinal incidence studies are required to
determine the indicators that may be associated with the development
of future AMD.
Methods & Results
Latinos (Hispanics, Hispanic Americans, and Latino Americans) are
individuals who are born into or have descended from a
Spanish-speaking community, regardless of race. In the United States,
Latinos are a heterogeneous group, with the majority being of Mexican
ancestry (66%). The Los Angeles Latino Eye Study is a population-based
longitudinal study of eye disease in self-identified Latinos, aged 40
years and older, living in 6 census tracts in the city of La Puente,
Los Angeles County, California. Baseline examination was performed
from 2000 to 2003, with 4-year follow-up examination from 2004 to
2008.
Participants, aged 40 or older, from The Los Angeles Latino Eye Study
(LALES) underwent standardized comprehensive ophthalmologic
examinations at baseline and at 4 years of follow-up. Age-related
macular degeneration was detected by grading 30-degree stereoscopic
fundus photographs using the modified Wisconsin Age-Related
Maculopathy Grading System. Multivariate stepwise logistic regression
was used to examine the independent association of incidence and
progression of AMD and baseline sociodemographic, behavioral,
clinical, and ocular characteristics.
Multivariate analyses revealed that older age (OR per decade of age:
1.52; 95% CI: 1.29, 1.85) and higher pulse pressure (OR per 10 mm Hg:
2.54; 95% CI: 1.36, 4.76) were independently associated with the
incidence of any AMD. The same factors were associated with early AMD,
soft indistinct drusen, and retinal pigmentary abnormalities.
Additionally, presence of clinically diagnosed diabetes mellitus was
independently associated with increased retinal pigment (OR: 1.66; 95%
CI: 1.01, 2.85), and male gender was associated with retinal pigment
epithelial depigmentation (OR 2.50; 95% CI: 1.48, 4.23). Older age (OR
per decade of age: 2.20; 95% CI: 1.82, 2.67) and current smoking (OR:
2.85; 95% CI: 1.66, 4.90) were independently associated with
progression of AMD. (see TABLE)
Discussion & Conclusions
In this longitudinal study, over a 4-year period we found older age,
increased pulse pressure, diabetes mellitus, and male gender to be
associated with incident early AMD in Latinos. Older age and current
smoking were associated with increased risk of progression of AMD.
Some of these findings are consistent with data from other
population-based longitudinal studies, including the Beaver Dam Eye
Study and the Blue Mountains Eye Study, which have used similar
methodologies to detect and define AMD. However, we have found several
novel associations, especially when the outcomes were defined as early
AMD and soft drusen, that were not reported in earlier studies.
Sociodemographic Risk Factors
Numerous studies have demonstrated older age as the strongest risk
factor of AMD prevalence, incidence, and progression. The relationship
between age and prevalence of AMD was demonstrated previously with the
LALES prevalence data. The present analyses demonstrated the increased
risk of AMD incidence and progression with increasing age. It has been
suggested that the ongoing subclinical pathogenetic processes, such as
deposition of lipofuscin and thickening and loss of elasticity of the
Bruch membrane, begin earlier in life. These changes are likely to
manifest as clinical signs of early AMD as people age, due in part to
the inability of the RPE in some individuals to process these
degenerative products.
Gender difference in incident or prevalent AMD has been an
inconsistent finding in most population-based studies. The previous
report from LALES prevalence data was suggestive of an increased risk
of all and early AMD prevalence. In the present report we found an
increased risk in male participants for RPE depigmentation only.
The reasons for increased risk of RPE depigmentation in Latino men are
not known, although several other known risk factors of AMD (eg,
smoking, alcohol use, and cardiovascular disease) are found to be more
prevalent in male subjects. Indeed, in LALES we noted that Latino men
were more likely to smoke (19% vs 9%, P < .001) and drink alcohol
regularly compared to Latino women (22% vs 3%). But even after
adjusting for these variables, men were more likely than women to
develop RPE depigmentation (OR 2.73; 95% CI: 1.52, 4.94).
Behavioral Risk Factors
The results of this study suggest an almost 3-fold increased risk of
progression of AMD in current smokers (P = .0004). There was no such
significant association in former smokers.
Smoking has been the most consistent modifiable behavioral risk factor
in most population-based ocular epidemiologic studies. It has been
found to be associated with all stages of AMD. In particular, the risk
has been found strongest in those who are current smokers. Some
investigators have suggested the effect of cigarette smoking on AMD
may be attributable to its negative effect on antioxidants. In this
report we found smoking to be associated with progression but not with
incidence of AMD in Latinos.
Clinical Risk Factors
The association of blood pressure and AMD has been inconsistent in
epidemiologic population-based studies. Our results suggest increased
risks of all measures of AMD incidence with increased pulse pressure
(see FIGURE). The BDES found a positive association of pulse pressure
with prevalence of RPE depigmentation and increased retinal
pigmentation in male subjects only. However, in the 5-year cumulative
incidence in BDES, higher pulse pressure was significantly associated
with increased incidence of RPE depigmentation (OR per 10 mm Hg: 1.27;
95% CI: 1.14, 1.42) and exudative macular degeneration (OR per 10 mm
Hg: 1.29; 95% CI: 1.02, 1.65), irrespective of gender. However, a
number of other studies did not report this association. Pulse
pressure emerged as the most important modifiable risk factor in this
cohort.
To further evaluate whether the effect of pulse pressure was
independent of hypertension, we restricted the analysis to
normotensive participants and found a similar age-adjusted independent
relationship (OR for AMD: 2.6; 95% CI: 1.4, 4.9). The underlying
mechanism of increased pulse pressure on AMD risk may be attributable
to age-related degenerative changes in collagen and elastin, resulting
in a decrease in distensibility of blood vessels. This in turn results
in higher systolic and lower diastolic blood pressure and widening of
pulse pressure.
Diabetes is a disparate finding as a risk factor for AMD. In this
study, presence of clinically diagnosed diabetes mellitus was
independently associated with incidence of increased retinal
pigmentation. The Blue Mountains Eye Study found an association of
diabetes with geographic atrophy but not with increased retinal
pigment or any other measure of early AMD. In BDES, diabetes was not
associated with early AMD but was associated with neovascular AMD in
persons 75 or older. A large number of studies found no association.
The paucity of literature suggests caution in drawing any inference.
However, diabetes as a risk factor of any disease in Latinos requires
more attention, as diagnosed diabetes is 1.7 times more likely in
Latinos than in non-Hispanic whites. Therefore, timely prevention,
diagnosis, and proper control of diabetes will likely have a positive
impact on the burden of ocular disease in Latinos.
In LALES, there was a relative low rate of AMD progression. In this
analysis we could not identify any protective factors that may affect
AMD progression in Latinos. However, a previous analysis from LALES
was suggestive of a low prevalence of the genetic risk factor of CFH
Tyr402 polymorphism in Latinos. Further analysis of distributions of
genetic risk factors, both protective and deleterious, and their
relationship to AMD may shed more light on factors that are likely to
play a role in progression, or relative lack of it, in this
population.
In conclusion, in Latinos, increasing age, increased pulse pressure,
and diabetes mellitus were associated with higher risks of incidence
of early AMD, and increasing age and current smoking were associated
with the progression of AMD. Some of the findings are similar to those
reported by studies in non-Hispanic whites, suggesting some
similarities in the pathogenesis of the disease between the 2 ethnic
groups. Studies of genetic risk factors may explain the differences in
risk factors for incidence of some early maculopathies like soft
drusen. Because Latinos represent the largest minority group in the
United States and exhibit different patterns of AMD incidence and
progression than other ethnic groups, it is empirical to address the
unique risk factors of AMD in Latinos. The fact that easily modifiable
factors like pulse pressure were associated with Latinos may provide
clinicians with important guidelines for preventive interventions.
Further longitudinal studies of AMD progression in Latinos are needed
for conclusive inferences. It remains to be seen whether interventions
aimed at reducing pulse pressure or stopping smoking would affect the
incidence and progression of AMD in Latinos.
Am J Ophthalmol. 2011 Sep;152(3):385-95
http://www.ncbi.nlm.nih.gov/pubmed/21679916
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