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Biomedical subjects

Ronald Klein

Publications and source records attributed to Ronald Klein.

At least 91 records · Page 5Linked to original sources
PubMed2005

Estrogen replacement therapy and retinal vascular caliber.

OBJECTIVE: It is unclear if estrogen replacement therapy (ERT) has an effect on the retinal circulation. In the current study, we examine the association of ERT, female reproductive factors, and retinal vascular caliber. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Women participants aged 43 to 84 years living in Beaver Dam, Wisconsin. METHODS: Retinal photographs of participants taken at the baseline examination were digitized, and the diameters of arterioles and venules were measured using a well-established technique. Estrogen replacement therapy and female reproductive factors were ascertained by interview. MAIN OUTCOME MEASURES: Retinal arteriolar and venular diameters. RESULTS: Of the 2469 women participants with data for analysis, 10.5% were current users of ERT and 7.4% were past users. After adjusting for age, blood pressure (BP), body mass index, smoking, and other factors, women who were current users of ERT had narrower retinal arteriolar and venular diameters than those who were past users or never used, with mean arteriolar diameters of 167.6 microm for current users, 170.8 microm for past users, and 170.9 microm for those who never used (P = 0.009) and mean venular diameters of 239.9 microm for current users, 244.0 microm for past users, and 243.9 microm for those who never used (P = 0.02). There was a significant trend of increasing narrowing for both arterioles (P trend, 0.01) and venules (P trend, 0.007) with increasing duration of ERT. Associations were somewhat stronger in younger women and women without a history of hypertension and cigarette smoking. Female reproductive factors (e.g., age of menarche and pregnancy) were not associated with retinal vessel diameters. CONCLUSIONS: Estrogen replacement therapy is associated with narrower retinal vessel diameters, independent of BP and other vascular factors.

Adult↗
PubMed2005

The association between cardiovascular disease and cochlear function in older adults.

The purpose of this research was to evaluate the relation between self-reported cardiovascular disease (CVD) and cochlear function in older adults. The Epidemiology of Hearing Loss Study (EHLS) is an ongoing population-based study of hearing loss and its risk factors in Beaver Dam, Wisconsin. As part of the EHLS questionnaire, participants were asked about their cardiovascular medical history. CVD history was determined from questions regarding history of angina, myocardial infarction (MI), and stroke. Questions about the use of antihypertensive medication and blood pressure measurements determined the presence or absence of hypertension. Among the audiologic measures completed were distortion product otoacoustic emissions (DPOAEs). Cochlear function was measured using DPOAEs and participants were categorized as having (a) cochlear impairment, (b) possible cochlear impairment, or (c) no cochlear impairment. There were 1,501 participants with complete CVD and DPOAE data from the 1998-2000 examination phase. Women with a self-reported history of MI were twice as likely (age-adjusted odds ratio [OR] = 2.00, 95% confidence interval [CI] = 1.15-3.46) to have cochlear impairment than women without a history of MI. This association was not significant in men (age-adjusted OR = 0.98, 95% CI = 0.61-1.58). Additionally, no other CVD variables were associated with cochlear impairment. This study provides data on a possible sex-specific association between CVD and DPOAEs in older adults.

Adult↗
PubMed2005

Associations between retinal microvascular abnormalities and declining renal function in the elderly population: the Cardiovascular Health Study.

BACKGROUND: Microvascular abnormalities in the kidney are common histopathologic findings in individuals with chronic kidney disease or renal failure. These abnormalities may represent one manifestation of ongoing systemic microvascular damage. We hypothesized that retinal microvascular abnormalities, when present, would be associated with progressive renal dysfunction in elderly individuals. METHODS: The Cardiovascular Health Study (CHS) is a prospective, multicenter, cohort study initiated in 1989 designed to examine cardiovascular risk factors, morbidity, and mortality in elderly Americans. As part of an ancillary study, CHS participants underwent retinal photography in 1997 and 1998. Retinal microvascular abnormalities were assessed and graded by using standardized measures. Retinal microvascular abnormalities were defined as retinopathy (hard and soft exudates, hemorrhages, or microaneurysms) and/or retinal arteriolar abnormalities (arteriovenous nicking, focal arteriolar narrowing, or lowest quartile arteriole-venule ratio). Associations between these abnormalities and observed 4-year changes in serum creatinine levels and estimated glomerular filtration rates (eGFRs) from study years 5 to 9 (encompassing years 1994 to 2001) were examined by using regression modeling. RESULTS: A total of 1,394 CHS participants had retinal and serum creatinine data. After adjustments for age, race, sex, weight, diabetes, hypertension, angiotensin-converting enzyme inhibitor use, and proteinuria, participants with retinopathy showed a significant increase in serum creatinine level and decline in eGFR compared with those without retinopathy during the 4-year study period (+0.24 mg/dL [+21 micromol/L] versus -0.21 mg/dL [-19 micromol/L] and -0.48 mL/min/1.73 m2 [-0.01 mL/s/1.73 m2] versus +1.74 mL/min/1.73 m2 [+0.03 mL/s/1.73 m2], respectively). Participants with retinopathy also were significantly more likely to have an observed significant deterioration in renal function, defined as a 0.3-mg/dL (27-micromol/L) increase in serum creatinine level or 20% or greater decline in eGFR (odds ratio, 3.20; 95% confidence interval, 1.58 to 6.50; and odds ratio, 2.84; 95% confidence interval, 1.56 to 5.16, respectively). These associations remained in separate stratified analyses of patients with and without diabetes. The presence of retinal arteriolar abnormalities was not associated with deteriorating renal function. CONCLUSION: Retinal microvascular abnormalities defined as retinopathy were significantly associated with renal function deterioration. The observed findings were independent of effects of any associated diabetes or hypertension. These findings suggest that systemic microvascular disease may be associated with progressive renal dysfunction in the elderly population.

Black or African American↗
PubMed2005

Factors related to vision care in an older adult cohort.

PURPOSE: This study provides cross-sectional data on eye care utilization in a community-based adult population. METHODS: Data are from a questionnaire administered during the 7-year follow-up of the Epidemiology of Hearing Loss Study in 2000 to 2002. Participants in the population-based Beaver Dam Eye Study were eligible for the Epidemiology of Hearing Loss Study, which began in 1997. The primary outcome was self-reported vision testing within the past year. RESULTS: Subject ages ranged from 55 to 99 years (n = 2433), and 60.4% were female. Fifty-three percent of subjects reported they had their vision tested in the past year. Diabetes was self-reported by 11.5% of subjects, and 70.9% of diabetic participants had their vision tested in the past year. A current hospitalization or health insurance plan was reported by 98.6% of subjects. In multivariate analyses, self-reported factors significantly associated with having a vision test in the past year were female gender (odds ratio [OR] = 1.27; 95% confidence interval [CI] 1.06-1.52), current use of refractive correction for distance (OR = 1.98; 95% CI 1.56-2.52), glaucoma (OR = 3.52; 95% CI 2.37-5.24), cataract surgery (OR = 1.57; 95% CI 1.21-2.03), age-related macular degeneration (ARMD) (OR = 1.74; 95% CI 1.22-2.47), diabetes (OR = 2.46; 95% CI 1.83-3.31), visiting a primary care practitioner for any reason in the past year (OR = 1.72; 95% CI 1.32-2.25), having a hearing test in the past year (OR = 1.79; 95% CI 1.40-2.28), and the cessation of driving because of poor vision (OR = 1.64; 95% CI 1.16-2.52). In participants 65 years of age or older, having private insurance was associated with increased odds (OR = 3.39, 95% CI 1.82-6.31) of vision testing in the past year. CONCLUSION: This study suggests that chronic ocular conditions, diabetes, health insurance beyond government entitlements, and the use of other healthcare services are associated with increased eye care utilization.

Aged↗
PubMed2005

Detecting progression of nuclear sclerosis by using human grading versus semiautomated computer grading.

PURPOSE: To assess indices of nuclear sclerosis derived from digitized images made from color (slide) photographs. METHODS: Film-based slit lamp images taken at baseline and at 5- and 10-year follow-up examinations of the Beaver Dam Eye Study cohort were digitized, and optical traces were taken along an axis through the center of the cornea and lens. Four indices of the severity of sclerosis were calculated based on the optical densities. The associations of the original Beaver Dam grades and these indices to age, vision, and change in severity of sclerosis over two subsequent visits were compared. RESULTS: At baseline photographs, the Spearman correlation between age and severity was 0.65 for the original film-based grading (n = 4518 right eyes) and varied between 0.46 and 0.71 for the measures from digitized images. Correlations of the indices to visual acuity were 0.38 for the film-based grading and ranged from 0.32 to 0.38 for the other indices. The authors assume that nuclear sclerosis does not regress and the percentage of regression is a reflection of error in grading. The percentage of regression and progression of sclerosis over 5- and 10-year intervals was determined for each index. After 5 years, 48.2% progressed and 4.9% regressed, using the Beaver Dam grades; progression occurred in 4.9% to 9.9%, and regression occurred in 4.5% to 7.0% for the other indices. After 10 years, 61.9% progressed and 3.2% regressed using the Beaver Dam grades; progression occurred in 8.0% to 19.7%, and regression occurred in 2.6% to 9.7% for the other indices. CONCLUSIONS: Semiautomated grading of the digitized images can be used to process thousands of images with little oversight by a trained grader. Indices of sclerosis that closely parallel human grading in their relationships to age and visual acuity can be easily computed. However, the indices appear to identify significantly less progression of nuclear sclerosis than does human grading. Further development to define a useful metric for identifying severity and progression of nuclear sclerosis is needed.

Adult↗
PubMed2005

A genetic contribution to intraocular pressure: the beaver dam eye study.

PURPOSE: To investigate a potential genetic contribution to intraocular pressure (IOP), we performed a complex segregation analysis on 2337 individuals in 620 extended pedigrees ascertained through a population-based cohort, the Beaver Dam Eye Study (BDES). IOP is a principal risk factor for primary open-angle glaucoma (POAG) a leading cause of blindness worldwide. METHODS: Segregation analysis is an analytical method that provides statistical evidence supporting the involvement of a major gene or polygenes in a particular phenotype. Detailed medical histories and eye examinations were performed on all participants. From the two eyes, the higher IOP measurement was used as a continuous trait after adjustment for covariates. A genome-wide scan (GWS) using affected sib pair linkage analysis was performed on 218 sibling pairs. RESULTS: In this segregation analysis the model that allowed for an unmeasured major environmental effect plus a polygenic/multifactorial effect provided the best fit and was the most parsimonious model. The lack of an adequate fit for the Mendelian single-gene models is consistent with a multifactorial model of inheritance that may include multiple genes and environmental factors that contribute to IOP. The results of the GWS yielded two novel loci as potential linkage regions for IOP on chromosomes 6 (P = 0.008) and 13 (P = 0.0007). Neither of these regions has previously been identified in GWS of POAG. CONCLUSIONS: The segregation and familial correlation analyses of IOP suggest a polygenetic component with environmental influences. The pilot linkage study further confirms the heterogeneity of IOP with the identification of two novel genetic loci.

Adult↗
PubMed2005

Support for polygenic influences on ocular refractive error.

PURPOSE: Refractive errors, myopia, and hyperopia are common conditions requiring corrective lenses. The familial clustering of myopia has been well established. Several chromosomal regions have been linked to high myopia (12q, 17q, and 18q), to quantitative refraction among twins (3q, 4q, 8p, and 11p), and to families with moderate myopia (22q). This study examined the familial aggregation and pattern of inheritance of ocular refraction in an adult population, by using data from the Beaver Dam Eye Study. METHODS: Familial correlations were examined and segregation analysis was performed on the average refractive error measurements in the right and left eyes after adjustment for age, sex, and education. Analyses were based on 2138 individuals in 620 extended pedigrees with complete data on age, sex, education, and spherical equivalent. RESULTS: Substantial positive correlation was found between siblings (0.33), parents and offspring (0.17), and cousins (0.10) and lower correlation among avuncular pairs (0.08) after adjustment for age, sex, and years of education. The results of this segregation analysis do not support the involvement of a single major locus throughout the entire range of refractive error. However, models allowing for familial correlation, attributable in part to polygenic effects, provided a better fit to the observed data than models without a polygenic component, suggesting that several genes of modest effect may influence refractive error, possibly in conjunction with environmental factors. CONCLUSIONS: These results support the involvement of genetic factors in the etiology of refractive error and are consistent with reports of linkage to multiple regions of the genome.

Family Health↗
PubMed2005

Genome-wide analyses demonstrate novel loci that predispose to drusen formation.

PURPOSE: To test whether genes for drusen formation are independent of age-related macular degeneration (AMD) pathogenesis. METHODS: A genome-wide model-free linkage analysis was performed, using two semiquantitative drusen traits, size and type, on two sets of data: (1) 325 individuals (225 sib pairs) from the Beaver Dam Eye Study (BDES), and (2) 297 individuals (346 sib pairs) from the Family Age Related Maculopathy Study (FARMS). Apolipoprotein E (APOE) genotypes were used as a covariate in a multipoint sibpair analysis. RESULTS: The authors found evidence of linkage on 19q13.31 (D19S245), with size of drusen in both the BDES (P = 0.0287) and the FARMS (P = 0.0013; P = 0.0005, combined). In the BDES, type showed linkage evidence on 3p24.3 (D3S1768; P = 0.0189) and 3q25.1 (D3S2404; P = 0.0141); the linkage on 3p24.3 was also found with size (D3S1768; P = 0.0264). In the FARMS, size showed evidence of linkage at 5q33.3 (D5S820; P = 0.0021), 14q32.33 (D14S1007; P = 0.0013), and 16p13.13 (D16S2616; P = 0.0015) and type at 21q21.2 (D21S2052; P = 0.0070). For size in the FARMS, there was a small increase in P-value at marker D19S245 from 0.0044 to 0.0111, and from 0.0044 to 0.0064, when the epsilon4-carrier and the epsilon3-carrier genotype were the covariates, respectively. CONCLUSIONS: The results show that APOE effects may be mediated early in the progression of ARM to AMD and thus may not be detected by standard genome scans for more severe disease.

Adult↗
PubMed2005

The relationship of diabetic retinopathy to preclinical diabetic glomerulopathy lesions in type 1 diabetic patients: the Renin-Angiotensin System Study.

Few epidemiological data exist regarding the correlation of anatomic measures of diabetic retinopathy and nephropathy, especially early in the disease processes. The aim of this study was to examine the association of severity of diabetic retinopathy with histological measures of diabetic nephropathy in normoalbuminuric patients with type 1 diabetes. The study included participants (n = 285) in the Renin-Angiotensin System Study (RASS; a multicenter diabetic nephropathy primary prevention trial) who were aged >/=16 years and had 2-20 years of type 1 diabetes with normal baseline renal function measures. Albumin excretion rate (AER), blood pressure, serum creatinine, and glomerular filtration rate (GFR) were measured using standardized protocols. Diabetic retinopathy was determined by masked grading of 30 degrees color stereoscopic fundus photographs of seven standard fields using the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. Baseline renal structural parameters, e.g., fraction of the glomerulus occupied by the mesangium or mesangial fractional volume [Vv(Mes/glom)] and glomerular basement membrane width, were assessed by masked electron microscopic morphometric analyses of research percutaneous renal biopsies. No retinopathy was present in 36%, mild nonproliferative diabetic retinopathy in 53%, moderate to severe nonproliferative diabetic retinopathy in 9%, and proliferative diabetic retinopathy in 2% of the cohort. Retinopathy was not related to AER, blood pressure, serum creatinine, or GFR. All renal anatomical end points were associated with increasing severity of diabetic retinopathy, while controlling for other risk factors. These data demonstrate a significant association between diabetic retinopathy and preclinical morphologic changes of diabetic nephropathy in type 1 diabetic patients.

Adult↗
PubMed2005

A computer simulation model of diabetes progression, quality of life, and cost.

OBJECTIVE: To develop and validate a comprehensive computer simulation model to assess the impact of screening, prevention, and treatment strategies on type 2 diabetes and its complications, comorbidities, quality of life, and cost. RESEARCH DESIGN AND METHODS: The incidence of type 2 diabetes and its complications and comorbidities were derived from population-based epidemiologic studies and randomized, controlled clinical trials. Health utility scores were derived for patients with type 2 diabetes using the Quality of Well Being-Self-Administered. Direct medical costs were derived for managed care patients with type 2 diabetes using paid insurance claims. Monte Carlo techniques were used to implement a semi-Markov model. Performance of the model was assessed using baseline and 4- and 10-year follow-up data from the older-onset diabetic population studied in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). RESULTS: Applying the model to the baseline WESDR population with type 2 diabetes, we predicted mortality to be 51% at 10 years. The prevalences of stroke and myocardial infarction were predicted to be 18 and 19% at 10 years. The prevalences of nonproliferative diabetic retinopathy, proliferative retinopathy, and macular edema were predicted to be 45, 16, and 18%, respectively; the prevalences of microalbuminuria, proteinuria, and end-stage renal disease were predicted to be 19, 39, and 3%, respectively; and the prevalences of clinical neuropathy and amputation were predicted to be 52 and 5%, respectively, at 10 years. Over 10 years, average undiscounted total direct medical costs were estimated to be USD $53,000 per person. Among survivors, the average utility score was estimated to be 0.56 at 10 years. CONCLUSIONS: Our computer simulation model accurately predicted survival and the cardiovascular, microvascular, and neuropathic complications observed in the WESDR cohort with type 2 diabetes over 10 years. The model can be used to predict the progression of diabetes and its complications, comorbidities, quality of life, and cost and to assess the relative effectiveness, cost-effectiveness, and cost-utility of alternative strategies for the prevention and treatment of type 2 diabetes.

Computer Simulation↗
PubMed2005

Familial aggregation of severity of diabetic retinopathy in Mexican Americans from Starr County, Texas.

OBJECTIVE: Diabetic retinopathy is a major cause of blindness. To determine whether retinopathy itself or only its severity aggregates in families, we examined the occurrence and severity of diabetic retinopathy in Mexican-American siblings with type 2 diabetes. RESEARCH DESIGN AND METHODS: Using stereoscopic fundus photography of seven standard fields, we measured retinopathy in 656 type 2 diabetic patients from 282 Mexican-American families from Starr County, Texas. Retinopathy severity was scored using the Early Treatment of Diabetic Retinopathy Study system and classified as no retinopathy, early nonproliferative diabetic retinopathy (NPDR-E), moderate-to-severe nonproliferative diabetic retinopathy (NPDR-S), or proliferative diabetic retinopathy (PDR). RESULTS: Of 249 siblings of randomly selected probands with retinopathy, 169 (67.9%) had retinopathy, compared with 95 of 125 siblings of unaffected probands (76.0%; P = 0.11). Proband retinopathy class was associated (P = 0.03) with sibling retinopathy class, with significant odds ratios (ORs) for NPDR-E versus no retinopathy (OR 0.57 [95% CI 0.35-0.93]) and PDR versus NPDR-E (2.02 [1.13-3.63]); the contrast of NPDR-S versus NPDR-E approached significance (1.78 [0.99-3.20]). With the more severe classes (PDR and NPDR-S) combined in one group and the less severe ones (none and NPDR-E) in another, more severe proband retinopathy was associated with more severe sibling retinopathy (1.72 [1.03-2.88]). CONCLUSIONS: More severe diabetic retinopathy showed evidence of familial aggregation, but the occurrence of diabetic retinopathy per se did not. The factors involved in the onset of diabetic retinopathy may differ from those involved in its progression to more severe forms.

Aged↗
PubMed2005

Ethnicity, race, and baseline retinopathy correlates in the veterans affairs diabetes trial.

OBJECTIVE: The Veterans Affairs Diabetes Trial (VADT) cohort is enriched with approximately 20% Hispanics and 20% African Americans, affording a unique opportunity to study ethnic differences in retinopathy. RESEARCH DESIGN AND METHODS: Cross-sectional analyses on the baseline seven-field stereo fundus photos of 1,283 patients are reported here. Diabetic retinopathy scores are grouped into four classes of increasing severity: none (10-14), minimal nonproliferative diabetic retinopathy (NPDR) (15-39), moderate to severe NPDR (40-59), and proliferative diabetic retinopathy (60+). These four groups have also been dichotomized to none or minimal (10-39) and moderate to severe diabetic retinopathy (40+). RESULTS: The prevalence of diabetic retinopathy scores >40 was higher for Hispanics (36%) and African Americans (29%) than for non-Hispanic whites (22%). The difference between Hispanics and non-Hispanic whites was significant (P < 0.05). Similarly, the prevalence of diabetic retinopathy scores >40 was significantly higher in African Americans than in non-Hispanic whites (P < 0.05). These differences could not be accounted for by an imbalance in traditional risk factors such as age, duration of diagnosed diabetes, HbA(1c) (A1C), and blood pressure. Diabetic retinopathy severity scores were also significantly associated with increasing years of disease duration, A1C, systolic and diastolic blood pressure, the degree of microalbuminuria, fibrinogen, and the percentage of patients with amputations. There was no relationship between retinopathy severity and the percentage of people who had strokes or cardiac revascularization procedures. There was an inverse relationship between retinopathy severity and total cholesterol, triglycerides, and plasminogen activator inhibitor-1 as well as with smoking history. Diabetic retinopathy scores were not associated with age. CONCLUSIONS: In addition to many well-known associations with retinopathy, a higher frequency of severe diabetic retinopathy was found in the Hispanic and African-American patients at entry into the VADT that is not accounted for by traditional risk factors for diabetic retinopathy, and these substantial ethnic differences remain to be explained.

Adult↗
PubMed2005

The DIabetic REtinopathy Candesartan Trials (DIRECT) Programme: baseline characteristics.

Renin-angiotensin system blockade has been shown to be superior to other antihypertensive therapy in slowing progression of renal disease in diabetic patients, but questions remain regarding diabetic retinopathy. The primary objective of the DIabetic REtinopathy Candesartan Trials (DIRECT) Programme is to examine primary (incidence) and secondary (progression) prevention of diabetic retinopathy when blocking angiotensin II type 1-receptors with candesartan in normoalbuminuric, normotensive Type 1 diabetic patients, and secondary prevention only in normoalbuminuric, normotensive or treated hypertensive Type 2 diabetic patients. The secondary objectives include examining the effect of candesartan treatment on urinary albumin excretion rate (UAER) in each of the three studies and to examine the incidence of proliferative retinopathy in all three populations combined. Standardised investigations for patients at enrolment include blood pressure measurement, analysis of HbA1C and serum lipids, and a detailed ophthalmological examination. Retinopathy and UAER outcomes are assessed yearly. Retinopathy is graded centrally, based on seven-field stereo photographs using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Randomisation was performed when the results of retinal gradings were available, and treatment with 16 mg candesartan cilexetil or matching placebo was initiated; the dose was increased to 32 mg after one month. Calculations of UAER are based on two timed overnight urine collections. A sample size re-assessment was carried out when approximately 70% of the patients had been randomised in the DIRECT Programme to ensure the results to be conclusive. In total, 5,231 patients were randomised in the DIRECT Programme in 30 countries. One thousand, four hundred and twenty one and 1,905 patients are evaluated in the primary and secondary prevention studies in Type 1 diabetes, respectively and 1,905 patients in the secondary prevention study in Type 2 diabetes. HbA1C showed mean values of 8.1, 8.5 and 8.2% for the Type 1 primary, Type 1 secondary and Type 2 secondary prevention studies, respectively. In the Type 1 secondary prevention study, 49% of the patients had mild nonproliferative retinopathy (level 20) in at least one eye, and 9% had moderate-moderately severe non-proliferative retinopathy (level 43-47). In Type 2 patients, 17% had level 43-47 and the remainder less severe retinopathy.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2004

Cardiovascular disease, mortality, and retinal microvascular characteristics in type 1 diabetes: Wisconsin epidemiologic study of diabetic retinopathy.

BACKGROUND: Diabetic retinopathy and proteinuria, manifestations of microvascular abnormalities, occur early in the course of diabetes mellitus; in contrast, macrovascular cardiovascular complications usually occur later. Retinal vessel characteristics may be informative about risk of cardiovascular disease in persons with diabetes. We evaluated this in a longitudinal cohort study of persons with type 1 diabetes. METHODS: The population consisted of persons with type 1 diabetes who were receiving care in 11 counties in Wisconsin. Subjects (n = 996) were examined at baseline (1980-1982), and 4, 10, 14, and 20 years later. Evaluations included medical history and measurements of height, weight, blood pressure, and glycosylated hemoglobin. Fundus photographs were graded for diabetic retinopathy at baseline, and the same photographs were graded later for the diameters of retinal blood vessels. At each examination, a history of cardiovascular disease events since the last examination (and prior to baseline) was obtained. Mortality was monitored yearly. RESULTS: The 20-year age-adjusted cumulative incidences were 18.1% for angina, 14.8% for myocardial infarction, and 5.9% for stroke. Severity of diabetic retinopathy was associated with angina and stroke. Arteriovenous ratio was associated with myocardial infarction. Of 273 deaths, 176 involved heart disease. The severity of retinopathy and arteriovenous ratio was associated with heart disease mortality. Nephropathy was more informative about the cardiovascular end points than were the blood vessel characteristics. CONCLUSIONS: Incidences of cardiovascular disease, including mortality, were common in people with type 1 diabetes during a 20-year interval. Retinal vascular characteristics were associated with these end points, but this association was confounded by nephropathy.

Adolescent↗
PubMed2004

Identification of a major locus for age-related cortical cataract on chromosome 6p12-q12 in the Beaver Dam Eye Study.

Age-related cataracts are one of the leading causes of visual impairment and blindness among the elderly worldwide. Among age-related cataracts, cortical opacities rank as the second most common type; however, little is known about their molecular pathogenesis or genetics. To identify susceptibility loci for cortical cataracts, we genotyped a subset of families (102 families; n = 224 sib pairs) from the Beaver Dam Eye Study and performed a model-free genome-wide linkage analysis for markers linked to a quantitative measure of cortical opacity. We obtained evidence for linkage at marker D1S1622 on chromosome 1p35 (P < 0.0002) and at marker D6S1053 on 6q12 (P < 0.00008) in the initial scan. Five additional regions on 1q31, 2p24, 2q11, 4q28, and 15q13 that are suggestive of linkage (P < or = 0.01 or logarithm of the likelihood ratio > or = 1.18) were observed. The region on chromosomes 6p12-q12 was selected for fine mapping, and the intermarker distance was reduced to 3 cM by adding 11 markers in the interval between D6S1017 and D6S1021. After fine mapping, significant evidence of linkage remained on chromosome 6p12-q12 at D6S1053 (P < 0.00005). The current genome scan for age-related cortical cataracts may lead to identification of novel genes, because few regions identified in the current scan have previously been implicated in congenital or age-related cataracts.

Age Factors↗