To investigate whether the statin class of drugs reduces the risk of cataract extraction.
setting: Kaiser Permanente Southern California, which provides prepaid healthcare for 3.2 million residents by 6000 physicians. patient population: Eligible patients were those who had 5+ years of continuous enrollment in 2009. Cases were 13 982 patients who underwent cataract surgery in their first eye in 2009. Controls were the 34 049 patients who had an eye examination, but did not undergo cataract surgery or have a diagnosis of cataract in their medical record. observation procedure: The primary source of data to assess cataract surgery, treatment with statins, and other risk factors is the electronic database of Kaiser Permanente. main outcome measure: Use of the statin class of drug.
Patients who had cataract surgery were older, were more likely to be white, and appeared to have more coronary artery disease but less diabetes. The proportion of statin users appeared to be greater among those with cataract surgery (64.3%) compared to those without a diagnosis of cataract or cataract surgery (55.5%). After adjustment for age, sex, race, smoking status, diabetes, and coronary artery disease, longer-term statin use was found to be protective against cataract extraction (OR: 0.93, P = .02), while shorter-term use was associated with cataract surgery (OR: 1.11, P < .0001). Age-stratified logistic regression analysis showed that statin use of 5 years or more was protective against cataract surgery in the younger age group (50-64 years), while shorter-term use (<5 years) was associated with an increased risk of surgery in both the younger and older age groups (60+ years).
The current study finds that recent longer-tem statin use was protective against cataract surgery in younger patients (50-64 years of age), while shorter-term use was associated with an increased risk of surgery. One strength of the current study is information on the large number of incident cases of cataract extraction and the electronic database on drug use. Additional studies will be needed to understand the difference in effect between longer- and shorter-term users of statins.
Cataract is the main cause of low vision and blindness in the world. Estimates indicate that nearly 13 million people in the United States suffer from cataract. A total of 1.2 million Medicare beneficiaries get cataract surgery each year, accounting for $4.7 billion per year cost to Medicare. With the aging of the population, the expanding indications for surgery, and the greater demand for good acuity in older age, the demand for cataract surgery is going to increase.
A number of investigators have suggested that oxidation might play a role in the aging of the lens nucleus and epithelium. Statins are widely prescribed to reduce serum cholesterol and might also have antioxidant effects and anti-inflammatory actions on the lens. The current literature is inconclusive about cataract and statins: A large population-based case-control study (15 479 cases and 15 479 controls) showed no association with statins. The Beaver Dam Eye Study examined 210 persons with incident cataract and found that statin use appeared to be associated with a lower risk of nuclear cataract. The Blue Mountains Eye Study found that statin use reduced the risk of cataract development by 50%. In a retrospective cohort study of 180 000 statin users, statin use was protective against cataract development.
The current study investigates whether the statin class of drugs reduces the risk of cataract extraction.
The study was conducted at Kaiser Permanente Southern, a group-model health maintenance organization that provides care for 3.2 million residents of Southern California with over 7000 physicians working in 12 medical centers. The study is a case-control study to determine whether incident cases of cataract extraction are less likely to be users of statins. Eligible patients were 50 years or older and had been enrolled in Kaiser Permanente Southern California for at least 5 years in 2009. Cases were any patient who had cataract extraction, identified with the CPT (current procedural terminology) code 66982, 66983, or 66984, in the year 2009 and who did not have this procedure in the past. Controls were patients who had an eye examination in 2009 but who had not had cataract extraction and did not have a diagnosis of cataract anywhere in their chart (366.x).
The primary source of data to assess treatment with statins is our electronic database containing outpatient prescriptions filled in Kaiser Permanente pharmacies, called the Pharmacy Information Management System. The Pharmacy Information Management System has been used in Kaiser Permanente Southern California since 1991, with complete data available from January 1992. This system actually consists of several databases, with records linked between databases using medical record numbers and other identifiers. Information available from the Pharmacy Information Management System includes details on known drug allergies as well as the following data for each prescription dispensed: date, place, and person filling the order; the type of medication dispensed, identified by Generic Product Identification code; number of units dispensed; dosage; route of administration; ingredients (if medication mixed by pharmacist); and billing information. About 93% of Kaiser Permanente Southern California Health Plan members have prescription drug coverage as a benefit. It is estimated that more than 97% of all prescriptions written by Kaiser Permanente physicians are filled at Kaiser Permanente Southern California pharmacies and therefore would be included in the Pharmacy Information Management System.
Statin use was defined as use of atorvastin, ezetimibe-simvastatin, lovastatin, pravastatin, and simvastatin. In analyses involving other lipid-lowering agents, cholestyramine, colestipol, ezetimibe, fenofibrate, and gemfibrozil were included. Drug use was defined as use prior to case determination. Recent use was defined as a filled prescription of statins in the year prior to the year of diagnosis and recent longer-term use, a filled prescription in each of the 5 years prior to the diagnosis. Coronary artery disease was defined as: 1) any hospitalization with a diagnosis of myocardial infarction or coronary artery disease; 2) procedure of coronary artery angioplasty or coronary artery bypass grafting; 3) any outpatient encounter with a coronary artery disease–related diagnosis with 3 filled nitrate prescriptions; or 4) 3 outpatient encounters with coronary artery disease–related diagnoses. Diabetes status was confirmed using Kaiser Permanente Southern California’s Diabetes Case Identification Database.
The primary analyses for this study assessed the association between statins and other lipid-lowering agents and cataract. Initial analyses compared, in cases and controls, the distribution of age, race, sex, education , socioeconomic status, and statin use and duration of use. Differences in proportions were tested using the χ 2 tests, supplemented by calculation of odds ratio with associated 95% confidence limits. Means were tested using the t tests. Logistic regression analysis was performed to adjust for potential confounding variables. Odds ratios were tested using the Wald test.
In the calendar year 2009, 13 982 patients underwent cataract surgery in the first eye. A total of 34 049 patients had an eye examination but did not undergo cataract surgery or have the diagnosis of cataract in their record.
Table 1 shows the demographic characteristics of cases and controls. Patients who had cataract surgery were older and more likely to be white. Household income and education were similar between the 2 groups. Patients who underwent cataract surgery also appeared to have more coronary artery disease, but less diabetes.
|No = 34 049||Yes = 13 583||P Value|
|Mean (SD)||60.2 (7.65)||72.1 (9.2)|
|Female % (n)||55.8 (19 004)||56.8 (7714)|
|Ethnicity % (n)||<.0001|
|White||36.8 (12 515)||53.4 (7257)|
|Black||12.2 (4157)||8.8 (1196)|
|Hispanic||22.7 (7725)||18.3 (2481)|
|Native American/Alaskan||0.1 (32)||0.1 (20)|
|Asian||8.1 (2773)||9.5 (1284)|
|Multiple/other||1.6 (544)||0.7 (100)|
|Missing or unknown||18.5 (6303)||9.2 (1245)|
|Median household income||<.0001|
|Mean (SD)||70 651.4 (31 512.6)||68 880.5 (30 301.1)|
|% of population with high school education||<.0001|
|Mean (SD)||20.7 (7.4)||21.2 (7.6)|
|Tobacco use, % (n)||<.0001|
|Never||61.6 (20 918)||51.9 (7050)|
|Passive||0.6 (206)||0.3 (47)|
|Quit||31.4 (10 656)||41.5 (5633)|
|Yes||6.5 (2205)||6.2 (841)|
|Missing||0.0 (64)||0.0 (12)|
|Coronary artery disease||<.0001|
|Yes, % (n)||51 (17 360)||59.1 (8029)|
|Yes, % (n)||37.6 (12 797)||34.4 (4671)|
The proportion of statin users appeared to be greater among those with cataract surgery ( Table 2 ). Longer-term users of statins also appeared to be more common among those who had cataract surgery. There was no difference in the use of other lipid-lowering drugs. Table 3 shows that the prevalence of statin use increased with age. To adjust for the relationship between statin use and age, several analyses were conducted. The first was a multivariate logistic regression analysis ( Table 4 ). After adjusting for age, female sex, race, coronary artery disease, diabetes, and smoking, statin use of 5 or more years was protective against cataract surgery, while statin use of less than 5 years raised the risk of cataract surgery. When compared to white subjects, Asian Americans were more likely, while black and Hispanic Americans were less likely, to undergo cataract surgery. Both coronary artery disease and diabetes reduced the risk of cataract surgery. The second analysis was an age-stratified multivariate analysis ( Table 5 ), in which separate logistic regression analyses were performed for those 50 to 64 years of age and for those 65 years or older. Compared to the unstratified analysis, female sex had a lower risk of cataract surgery in those 50 to 64 years of age and a higher risk in those 65 years or older. Statin use appeared to have a different effect, depending on the age group. Statin use of 5 years or more was protective against cataract surgery in those aged 50 to 64 years. Surprisingly, shorter-term use (<5 years) was associated with an increased risk of surgery in both age groups. The third analysis was a multivariate logistic regression analysis performed on cases and controls that were age-matched ( Table 6 ). In this analysis, controls were found for only 8568 cases. The other 5015 cases could not be matched because no controls could be found that were of the same age but had an eye examination and did not have a diagnosis of cataract or cataract surgery. In this analysis with a limited data set, the protective effect of longer-term statin use was still present but was not statistically significant.
|No = 34 049||Yes = 13 583||P Value|
|Yes, % (n)||55.5 (18893)||64.3 (8739)||<.0001|
|Statin use in days||<.0001|
|Mean (SD)||742.7 (862.5)||906.0 (893.0)|
|Statin use (year), % (n)||<.0001|
|0||44.5 (15 156)||35.7 (4844)|
|1||9.7 (3294)||10.1 (1369)|
|2||5.0 (1686)||5.2 (711)|
|3||5.4 (1825)||5.6 (754)|
|4||5.7 (1939)||6.5 (881)|
|5||29.8 (10 149)||37.0 (5024)|
|Lipid-lowering agent use||.0941|
|Yes, % (n)||10.1 (3454)||10.7 (1448)|
|Lipid-lowering agent use in days||.2679|
|Mean (SD)||88.8 (351.8)||90.0 (351.4)|
|Lipid-lowering agent use in years, % (n)||.0987|
|0||89.9 (30 595)||89.3 (12 135)|
|1||3.8 (1290)||4.1 (561)|
|2||1.5 (503)||1.5 (201)|
|3||1.1 (391)||1.4 (186)|
|4||1 (340)||1.1 (151)|
|5||2.7 (930)||2.6 (349)|
|Statin use, % (n)|
|Never used||48.1 (14 202)||32.9 (6080)|
|>0 − <5 years||33.5 (9898)||33.7 (6226)|
|5+ years||18.4 (5443)||33.4 (6182)|
|Total||100.0 (29 543)||100.0 (18 488)|
|Factor||Odds Ratio||95% Wald||P Value|
|Coronary artery disease||0.88||0.83||0.92||<.0001|
|5 years or more||0.93||0.87||0.99||.0282|
|Less than 5 years||1.11||1.05||1.18||<.0001|
|Factor||50−64 Years||65+ Years|
|95% Wald||95% Wald|
|Odds Ratio||Confidence Interval||P Value||Odds Ratio||Confidence Interval||P Value|
|Coronary artery disease||0.82||0.76||0.89||<.0001||0.92||0.86||0.99||.02|