Showing papers by "Ronald Klein published in 1999"

Retinal arteriolar diameters and elevated blood pressure: the Atherosclerosis Risk in Communities Study.

Abstract: Narrowing and other changes in retinal arterioles may reflect damage due to hypertension, which may predict stroke and other cardiovascular diseases independently of blood pressure level. Newly developed quantitative methods of assessing retinal narrowing are used to determine whether this sign is related only to current blood pressure or whether it also independently reflects the effects of previous blood pressure. Retinal photography was performed at the third examination of Atherosclerosis Risk in Communities (ARIC) Study in 1993-1995, and results are presented for the 9,300 nondiabetic participants aged 50-71 years. Generalized narrowing of smaller arterioles was strongly and monotonically related to current blood pressure in men and women, whether they were taking antihypertensive medications or not, and, independent of current blood pressure, was consistently and monotonically related to blood pressure levels measured 3 and 6 years before the retinal assessment. Arteriovenous nicking was also independently related to both current and previous blood pressures. The patterns of association suggested that these signs reflect both transient and persisting structural effects of elevated blood pressure, in agreement with the scant pathologic literature available. The findings suggest that retinal assessment may be useful for research on the microvascular contributions to clinical cardiovascular diseases.

Association of ocular disease and mortality in a diabetic population

Abstract: Objective To investigate the association of ocular disease with all-cause and cause-specific mortality in a diabetic population. Design Geographically defined population-based cohort study. Setting An 11-county area in Wisconsin. Study Population Participants were all younger-onset diabetic persons (diagnosed as having diabetes at Main Outcome Measure All-cause and cause-specific mortality as determined from death certificates. Results In the younger-onset group, after controlling for age and sex, retinopathy severity, macular edema, cataract, history of cataract surgery, and history of glaucoma at baseline were associated with all-cause and ischemic heart disease mortality. In the older-onset group, after controlling for age and sex, retinopathy and visual impairment were related to all-cause, ischemic heart disease, and stroke mortality. No ocular variable under study was related to cancer mortality in the older-onset group. After controlling for systemic risk factors, visual impairment was associated with all-cause and ischemic heart disease mortality in the younger-onset group. In the older-onset group, retinopathy severity was related to all-cause and stroke mortality, and visual impairment was related to all-cause, ischemic heart disease, and stroke mortality. Conclusions Presence of more severe retinopathy or visual impairment in diabetic patients is a risk indicator for increased risk of ischemic heart disease death. Presence of these ocular conditions may identify individuals who should be under care for cardiovascular disease.

Antioxidant Intake and Risk of Incident Age-related Nuclear Cataracts In the Beaver Dam Eye Study

Abstract: The relation of antioxidant nutrients to the incidence of nuclear cataracts was investigated in a cohort of adults aged 43-84 years in the Beaver Dam Eye Study (Beaver Dam, Wisconsin). Nuclear opacity was assessed on a five-point ordinal scale using lens photographs taken at baseline (1988-1990) and at follow-up (1993-1995). Of the 1,354 persons eligible, 246 developed a nuclear cataract (level 4 or 5 opacity) in at least one eye. Antioxidant intakes were assessed using a food frequency questionnaire administered at baseline for time points corresponding to intake during the year preceding baseline and 10 years before baseline (the distant past). Lutein-zeaxanthin was the only carotenoid, out of five examined, that was associated with nuclear cataracts. Persons in the highest quintile of lutein intake in the distant past were half as likely to have an incident cataract as persons in the lowest quintile of intake (95% confidence interval 0.3-0.8). In the overall group, nuclear cataracts were not significantly related to intake of vitamin C or vitamin E. However, vitamins C and E were inversely associated with opacities in persons who had some other risk factors for cataracts. While results of this short term follow-up study are consistent with a possible protective influence of lutein and vitamins E and C on the development of nuclear cataracts, the evidence in the present study provides weak support for these associations.

The 14-year incidence of lower-extremity amputations in a diabetic population. The Wisconsin Epidemiologic Study of Diabetic Retinopathy.

Abstract: OBJECTIVE: To estimate the cumulative 14-year incidence of lower-extremity amputations (LEAs) and evaluate risk factors for LEA. RESEARCH DESIGN AND METHODS: Study subjects consisted of population-based cohorts of younger-onset (diagnosed before age 30 years and taking insulin, n = 906) and older-onset (diagnosed after age 30 years, n = 984) individuals with diabetes. Subjects participated in baseline (1980-1982), 4-year, 10-year, and 14-year examinations or interviews. LEAs were determined by history. RESULTS: The cumulative 14-year incidence of LEA was 7.2% in younger- and 9.9% in older-onset patients. In multivariable analyses based on the discrete linear logistic model, LEA in the younger-onset group was more likely for males (odds ratio [OR] 5.21 [95% CI 2.50-10.88]), older age (OR for 10 years 1.71 [1.30-2.24]), higher glycosylated hemoglobin (OR for 1% 1.39 [1.22-1.59]), higher diastolic blood pressure (OR for 10 mmHg 1.58 [1.20-2.07]), history of ulcers of the feet (3.19 [1.71-5.95]), and more severe retinopathy (OR for one step 1.16 [1.08-1.24]). In younger-onset patients aged > or = 18, pack-years smoked (OR for 10 years 1.20 [1.03-1.41]) was also associated with LEAs, and daily aspirin use was inversely associated (OR 0.11 [0.01-0.83]). In the older-onset group, LEA was more likely for men (2.66 [1.49, 4.76]) and if the subject had higher glycosylated hemoglobin (OR for 1% 1.25 [1.09-1.43]), higher pulse pressure (OR for 10 mmHg 1.19 [1.04-1.37]), history of ulcers (3.56 [1.84-6.89]), and more severe retinopathy (OR for one step 1.07 [1.00-1.13]). CONCLUSIONS: There are several risk factors for LEA with potential for modification and preventive strategies.

Alcohol intake and the risk of coronary heart disease mortality in persons with older-onset diabetes mellitus.

Abstract: ContextDespite nutrition information and guidelines that advise against depriving diabetic patients of the potential benefit of moderate alcohol intake against cardiovascular events, the association between alcohol consumption and risk of cardiovascular outcomes in diabetic individuals has not been determined.ObjectiveTo examine the relationship between alcohol intake and coronary heart disease (CHD) mortality in persons with older-onset diabetes.DesignPopulation-based, prospective cohort study conducted from 1984 through 1996, with a follow-up of up to 12.3 years.Setting and ParticipantsA total of 983 older-onset diabetic individuals (mean [SD] age, 68.6 [11.0] years; 45.2% male; 98.5% white) were interviewed about their past-year intake of alcoholic beverages during the 1984-1986 follow-up examination of a population-based study of diabetic persons in southern Wisconsin.Main Outcome MeasureTime to mortality from CHD by category alcohol intake.ResultsAlcohol use was inversely associated with risk of CHD mortality in older-onset diabetic subjects. The CHD mortality rates for never and former drinkers were 43.9 and 38.5 per 1000 person-years, respectively, while the rates for those with alcohol intakes of less than 2, 2 to 13, and 14 or more g/d were 25.3, 20.8, and 10.0 per 1000 person-years, respectively. Compared with never drinkers and controlling for age, sex, cigarette smoking, glycosylated hemoglobin level, insulin use, plasma C-peptide level, history of angina or myocardial infarction, digoxin use, and the presence and severity of diabetic retinopathy, former drinkers had a relative risk (RR) of 0.69 (95% confidence interval [CI], 0.43-1.12); for those who drank less than 2 g/d (less frequent than 1 drink a week), the RR was 0.54 (95% CI, 0.33-0.90); for 2 to 13 g/d, it was 0.44 (95% CI, 0.23-0.84); and for 14 or more g/d (about 1 drink or more a day), it was 0.21 (95% CI, 0.09-0.48). Further adjustments for blood pressure, body mass index, education, physical activity, diabetes duration, hypertension history, overt nephropathy, peripheral neuropathy, lipid measures, or intake of medications such as aspirin and antihypertensive agents did not change the associations observed.ConclusionOur results suggest an overall beneficial effect of alcohol consumption in decreasing the risk of death due to CHD in people with older-onset diabetes.

Prevalence of age-related maculopathy in the Atherosclerosis Risk in Communities Study.

Abstract: Objective To describe the prevalence of age-related maculopathy (ARM) in blacks and whites and its relation to macrovascular disease and risk factors thereof in a population studied for cardiovascular disease risk factors and outcomes. Population A biracial population of 11,532 adults (ranging from 48-72 years of age; 8984 whites and 2548 blacks) living in 4 US communities (Forsyth County, North Carolina; the city of Jackson, Miss; selected suburbs of Minneapolis, Minn; and Washington County, Maryland) were examined during the interval from 1993 to 1995. Methods Drusen and other lesions typical of ARM were identified by examining a 45° color fundus photograph of 1 eye of each participant and classified by means of a modification of the Wisconsin Age-Related Maculopathy Grading System. Results The overall prevalence of any ARM was lower in blacks (3.7%) than whites (5.6%). After controlling for age and sex, the odds ratio for any ARM in blacks compared with whites was 0.73 (95% confidence interval, 0.58-0.91; P =.006). Few associations between atherosclerosis and its risk factors and the presence of early ARM or its component lesions were found. After adjusting for age, race, and sex, carotid artery plaque (odds ratio, 1.77; 95% confidence interval, 1.18-2.65) and focal retinal arteriolar narrowing (odds ratio, 1.79; 95% confidence interval, 1.07-2.98) were associated with retinal pigment epithelial depigmentation. Conclusions This population-based study documents the higher prevalence of early ARM in whites compared with blacks. Measures of atherosclerosis and its risk factors were generally unrelated to ARM and do not explain these racial differences.

The 10-year incidence of renal insufficiency in people with type 1 diabetes.

Abstract: OBJECTIVE: To describe the 10-year decrease in estimated creatinine clearance and the incidence of renal insufficiency and end-stage renal disease in a cohort of people with type 1 diabetes. RESEARCH DESIGN AND METHODS: A population-based cohort of individuals with younger-onset diabetes (diagnosed at or = 3 ml.min-1.1.73 m-2.year-1. Renal insufficiency was defined by the development of a serum creatinine of 2.0 mg/dl or greater after the 1984-1986 examination. RESULTS: The 10-year estimated incidence of an annual decrease in the creatinine clearance of > or = 3 ml.min-1.1.73 m-2 for the cohort was 52.5%, and the cumulative 10-year incidence of renal insufficiency and end-stage renal failure was 14.4%. In univariate analyses, incidence of a decrease in the estimated creatinine clearance of > or = 3 ml.min-1.1.73 m-2.year-1 and the incidence of renal insufficiency were both related to higher glycosylated hemoglobin; higher diastolic blood pressure; the presence of microalbuminuria and gross proteinuria; more severe retinopathy; and a history of loss of tactile sensation or temperature sensitivity at baseline. In logistic regression analysis, after adjusting for the presence of microalbuminuria and gross proteinuria at baseline, higher glycosylated hemoglobin and higher diastolic blood pressure were associated with decreasing estimated creatinine clearance. In logistic regression analyses, after adjusting for the presence of microalbuminuria and gross proteinuria at baseline, the incidence of renal insufficiency was independently associated with age, glycosylated hemoglobin, hypertension, and serum HDL cholesterol. CONCLUSIONS: These data suggest that a public health approach aimed at controlling glycemia, blood pressure, and serum lipids might result in reducing the rate of decline in renal function and development of renal insufficiency in people with type 1 diabetes.

Retinal emboli and stroke: the Beaver Dam Eye Study.

Abstract: Objective To describe the prevalence at baseline and the 5-year incidence of retinal emboli, associated risk factors, and the relationship of retinal emboli at baseline to stroke and ischemic heart disease mortality. Methods The Beaver Dam Eye Study is a large (N=4926) population-based study of persons aged 43 to 86 years at the baseline examination. Retinal emboli were detected at baseline (1988-1990) and at a 5-year follow-up (1993-1995) by grading of stereoscopic 30° color fundus photographs using standardized protocols. Cause-specific mortality was determined from death certificates. Results The prevalence of retinal arteriolar emboli was 1.3%, and the 5-year incidence was 0.9%. After adjustments were made for age and sex, the prevalence of retinal emboli was associated with higher pulse pressure, hypertension, diabetes mellitus, past and current smoking, cardiovascular disease, and the presence of retinopathy. After adjustments were made for age and sex, the incidence of retinal emboli was associated with past and current smoking and a history of coronary artery bypass surgery. After age, sex, and systemic factors were controlled for, people with retinal emboli had a significantly higher hazard of dying with a mention of stroke on the death certificate (hazard ratio=2.61, 95% confidence interval=1.12-6.08) than those without retinal emboli. Conclusions Persons with retinal emboli are at an increased risk of stroke-related death. Data also show an association of smoking, hypertension, and cardiovascular disease with the prevalence of retinal emboli. Clinical Relevance Data from this population-based study suggest that after discovery of retinal emboli in the asymptomatic patient, referral for possible medical intervention to control hypertension, if present, may be beneficial.

Changes in refractive error over a 5-year interval in the Beaver Dam Eye Study.

Abstract: PURPOSE. To examine changes in spherical equivalent over a 5-year period in persons 43 to 84 years of age. METHODS. All people 43 to 84 years of age and living in Beaver Dam, Wisconsin, in 1988 were invited for a baseline examination (1988-1990) and a 5-year follow-up examination (1993-1995). Refractions were determined according to the same protocol at both examinations. Aphakic and pseudophakic eyes were excluded as well as eyes with best corrected Snellen visual acuity of 20/40 and worse. After exclusions, refraction was obtained on 3007 right eyes and 3012 left eyes of the 3684 people participating in both examinations. RESULTS. Right and left eyes behaved similarly. Spherical equivalent became more positive in the youngest subjects and more negative in older subjects. After adjusting for other factors, the 5-year change in spherical equivalent of those 45, 55, 65, and 75 years of age was +0.15, +0.18, +0.10, and -0.07 D, respectively. Severity of nuclear sclerosis was related to the amount of change. Those with mild nuclear sclerosis at baseline had a change of +0.2 D, whereas those with severe nuclear sclerosis had a change of -0.5 D. The amount of change was also related to gender, diabetes, and age at onset of myopia. It was unrelated to education and baseline spherical equivalent. CONCLUSIONS. Changes in spherical equivalent over a 5-year period were small. Before the age of 70, people became more hyperopic. After the age of 70, people became more myopic. Much of the myopic change may be related to increasing nuclear sclerosis.

Risk factors for hospitalization in people with diabetes.

Abstract: Objective To determine factors predicting hospitalization in people with diabetes. Methods Two population-based groups with diabetes were examined at baseline (1980-1982), 4 years (1984-1986), and 10 years (1990-1992). The younger-onset group (n=777) consisted of all persons diagnosed as having diabetes before age 30 years who were taking insulin, and the older-onset group (n=542) consisted of a sample of persons diagnosed after age 30 years. At the 10-year examination, participants were asked if they had been hospitalized in the previous year. Factors from the 4-year examination were examined for their ability to predict hospitalization at the 10-year examination. Results In the younger-onset group, 25.5% reported being hospitalized. In logistic models, glycosylated hemoglobin level (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.16-1.39 for a 1% increment) and hypertension (OR, 1.60; 95% CI, 1.08-2.38) predicted hospitalization. Factors that were not significant included age, sex, systolic and diastolic blood pressures, body mass, smoking status, and alcohol consumption. In the older-onset group, 30.8% reported being hospitalized. In logistic models, only glycosylated hemoglobin level (OR, 1.16; 95% CI, 1.06-1.29 for a 1% increment) predicted hospitalization. Conclusions Glycemic control is subject to intervention. Better control may decrease hospitalization among people with diabetes. Thus, there is considerable potential for reducing health care costs.

Associations of performance-based and self-reported measures of visual function. The Beaver Dam Eye Study.

Abstract: Objective : To describe and compare performance-based and self-reported measures of visual function and to evaluate how each varied with age and how the performance-based measures were associated with the responses to self-reported questions about visual function. Design : Population-based epidemiologic study. Participants : Adults participating in the first follow-up of the Beaver Dam Eye Study (n=3,722). Main outcome measures : Performance-based measures of vision including current binocular, best-corrected and near visual acuities, sensitivity to light as measured by an automated perimeter, contrast sensitivity, and self-reported measures from a standardized interview. Results : All performance-based and self-reported visual functions decreased with increasing age (p<0.0001 for each). On average, women did more poorly than men on all the performance-based measures (p<0.0001 for each), and on some of the self-reported measures. For both genders, correlations among the performance-based measures ra...

Incident cataract after a five-year interval and lifestyle factors: the Beaver Dam eye study.

Abstract: CONTEXT: A population-based study to investigate risk factors for age-related eye disease was begun in 1987 in a representative American community. Incidence of cataract was subsequently evaluated. SPECIFIC OBJECTIVES: To examine the relationships of cigarette smoking, alcohol, and caffeine intakes to incidence of age-related cataracts five years later. DESIGN: Observational epidemiologic incidence study of an adult population. PARTICIPANTS AND INTERVENTION: Adults 43-84 years of age were identified during a census in 1987-1988, and examined at baseline (1988-1990) and after a five-year interval (1993-1995). MAIN OUTCOME MEASURE: Standardized protocols were used at the baseline and follow-up evaluations for exposures and for objective identification of cataracts. RESULTS: Cumulative incidence of nuclear cataract in right eyes was about 12%, cortical cataract about 8%, and posterior subcapsular cataract about 3%. In multivariable analyses of the general estimating equations type, there were significant ass...

A Bayesian approach to modelling the natural history of a chronic condition from observations with intervention

Abstract: To assess the costs and benefits of screening and treatment strategies, it is important to know what would have happened had there been no intervention. In today's ethical climate, however, it is almost impossible to observe this directly and therefore must be inferred from observations with intervention. In this paper, we illustrate a Bayesian approach to this situation when the observations are at separated and unequally spaced time points and the time of intervention is interval censored. We develop a discrete-time Markov model which combines a non-homogeneous Markov chain, used to model the natural progression, with mechanisms that describe the possibility of both treatment intervention and death. We apply this approach to a subpopulation of the Wisconsin Epidemiologic Study of Diabetic Retinopathy, a population-based cohort study to investigate prevalence, incidence, and progression of diabetic retinopathy. In addition, posterior predictive distributions are discussed as a prognostic tool to assist researchers in evaluating costs and benefits of treatment protocols. While we focus this approach on diabetic retinopathy cohort data, we believe this methodology can have wide application.

Exogenous estrogen exposures and changes in diabetic retinopathy. The Wisconsin Epidemiologic Study of Diabetic Retinopathy.

Abstract: OBJECTIVE: To investigate whether the use of exogenous estrogen is associated with changes in the severity of diabetic retinopathy and the incidence of macular edema. RESEARCH DESIGN AND METHODS: The study design involved observation of two well-defined cohorts of women with diabetes. One group was diagnosed with diabetes at or = 30 years of age with no criteria regarding therapy (older-onset group). Subjects received standard examinations, medical interviews, and retinal photography in 1980-1982. Specific questions about exogenous hormone exposure were added to the study questionnaire at the first follow-up examination 4 years after the baseline examination. Change in the severity of retinopathy 6 and 10 years after the 4-year follow-up examination were examined regarding the use of oral contraceptives at the first follow-up examination in the younger-onset group and at 6 years after the first follow-up examination regarding hormone replacement therapy in the older-onset group. RESULTS: Changes in the severity of retinopathy and incidence of macular edema were unrelated to either type of estrogen exposure in univariable and multivariable analyses. CONCLUSIONS: These data are compatible with the hypothesis that the medications used by our population do not affect the severity of diabetic retinopathy or macular edema.

Prevalence of self-rated visual impairment among adults with diabetes.

Abstract: OBJECTIVES: This study estimated the prevalence of self-rated visual impairment among US adults with diabetes and identified correlates of such impairment. METHODS: Self-reported data from the 1995 Behavioral Risk Factor Surveillance System survey of adults 18 years and older with diabetes were analyzed. Correlates of visual impairment were examined by multiple logistic regression analysis. RESULTS: The prevalence of self-rated visual impairment was 24.8% (95% confidence interval [CI] = 22.3%, 27.3%). Among insulin users, multivariable-adjusted odds ratios were 4.9 (95% CI = 2.6, 9.2) for those who had not completed high school and 1.8 (95% CI = 1.0, 2.8) for those who had completed high school compared with those with higher levels of education. Comparable estimates of odds ratios for nonusers of insulin were 2.2 (95% CI = 1.4, 3.4) and 1.3 (95% CI = 0.9, 2.0), respectively. Among nonusers, the adjusted odds for minority adults were 2.4 (95% CI = 1.0, 3.7) times the odds for non-Hispanic Whites. CONCLUSI...

Mortality and hormone-related exposures in women with diabetes.

Abstract: OBJECTIVE: Hormone-related events and exposures are related to mortality and especially to cardiovascular disease in women. We evaluated whether such exposures influenced risk in a well-defined group of women with diabetes. RESEARCH DESIGN AND METHODS: Women with younger- and older-onset diabetes who were identified during a population-based study were queried about number of pregnancies, age at menarche, use of oral contraceptives, use of estrogen replacement therapy, and menopausal status at examinations in 1984-1986. Analyses are limited to women aged > or = 18 years (n = 398 and 542 in those with younger- and older-onset diabetes, respectively). Cohort mortality was monitored carefully, and causes of death were abstracted from death certificates. RESULTS: There were 58 deaths in the first group and 338 deaths in the second group since the 1984-1986 examination. The number of pregnancies was significantly associated with all-cause mortality (hazard ratio, 0.96 [95% CI 0.92-1.00]) in older-onset women only. CONCLUSIONS: These data suggest and are compatible with the notion that the hormone exposures examined are unrelated to cardiovascular mortality in women with diabetes, with the exception of a minimal effect of the number of pregnancies in older-onset women. Whether there is a difference in these exposure-outcome relationships between women with diabetes and those without diabetes is uncertain and requires further investigation.

Diabetic retinopathy: an end of the century perspective.

Abstract: In 1978 the late Kelly West wrote: 'The extent to which the level of hyperglycemia determines the risk of retinopathy is not all that clear.d At that time, the 55% of persons with type 1 diabetes in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) took only one injection of long-acting insulin a day, essentially none did self blood glucose monitoring at least once per day, and the mean glycosylated haemoglobin Ale level for this group was 10.1%.2 The level of glycosylated haemoglobin in persons with type 2 disease, 9.0%, was also high. In addition, despite data from the Diabetic Retinopathy Study that showed panretinal photocoagulation resulted in a 50% reduction in severe visual loss (5/200 or worse) in eyes with severe proliferative retinopathy compared with eyes that were randomized to no treatment, only 54% of eyes with severe proliferative retinopathy in those with type 1 diabetes and 32% of those with type 2 diabetes had had such treatment.3,4 Only 67% of those with type 1 diabetes and 50% of those with type 2 diabetes in the WESDR had been seen by an ophthalmologist within 2 years of the time they were studied in 1980-2.5 Twenty years later, the pathogenesis of diabetic retinopathy has become better understood, leading to new approaches to its treatment and prevention.6,7 Epidemiological data from population-based studies8 and clinical trials9-11 have provided an answer to Kelly West's question. Data from the Diabetes Control and Complications Trial (DCCT) showed that in persons with type 1 diabetes, intensive treatment with insulin significantly reduced the risk of progression of retinopathy by 63%, of macular oedema by 26%, and the need for laser treatment by 51 % compared with conventional treatment.9 The WESDR showed that after adjusting for other risk factors in persons with type 2 diabetes a 1% decrease in glycosylated haemoglobin levels over the first 4 years of the study was associated with a 22% decrease in the odds of developing proliferative retinopathy and a 15% decrease in the odds of developing macular oedema at the 10-year follow-up.s In patients with type 2 diabetes, data from the United Kingdom Diabetes Prospective Study (UKPDS) showed that compared with the conventional group, the risk RONALD KLEIN