Biomedical subjects

Ronald Klein

Publications and source records attributed to Ronald Klein.

At least 19 recordsLinked to original sources

PubMed2007

Apolipoprotein e gene and age-related maculopathy in older individuals: the cardiovascular health study.

OBJECTIVE: To examine the association between the apolipoprotein E (APOE) gene and age-related maculopathy (ARM) in an older population. METHODS: Two thousand one hundred seventy persons 65 years and older sampled from 4 US communities had ARM signs assessed from retinal photographs using a modified Wisconsin Age-Related Maculopathy Grading System. DNA extracted from blood samples was analyzed for common APOE alleles. RESULTS: After controlling for age, sex, cigarette smoking, and other factors, white participants carrying the epsilon2 allele had an increased risk of late ARM (odds ratio, 2.53 [95% confidence interval, 1.08-5.90]) while carriers of the epsilon4 allele had a lower risk of late ARM (odds ratio, 0.69 [95% confidence interval, 0.19-2.50]). There were too few late ARM cases in African American individuals for analysis. CONCLUSION: APOE polymorphism is associated with late ARM in older white persons 65 years and older. Consistent with previous studies, the APOE epsilon2 allele is associated with a significant increased risk of late ARM development, whereas the epsilon4 allele may confer some protection.

Black or African American↗

PubMed2007

Identification of novel genetic loci for intraocular pressure: a genomewide scan of the Beaver Dam Eye Study.

OBJECTIVE: To identify genetic loci that control intraocular pressure (IOP). METHODS: We performed a genomewide scan of IOP, using 486 pedigrees ascertained through a population-based cohort, the Beaver Dam Eye Study. Linkage analysis was performed using the modified Haseman-Elston regression models and variance components linkage analysis. RESULTS: Seven regions of interest were identified on chromosomes 2, 5, 6, 7, 12, 15, and 19. The novel linkage region on chromosome 19p had an empirical multipoint P value of 6.1 x 10(-5). Two of the regions (2 and 19) were especially interesting since each has been identified as a potential linkage region for blood pressure. CONCLUSIONS: The results of this genomewide scan provide evidence that a quantitative trait locus may influence elevated IOP and may colocalize with blood pressure loci. These loci may control systemic pressure reflected in the eye and vascular system. CLINICAL RELEVANCE: Glaucoma is a leading cause of blindness in the world, and the identification of genes that contribute to this disease is essential. Elevated IOP is a principal risk factor for primary open-angle glaucoma and an intriguing quantitative trait that may strongly influence the development of disease.

Adult↗

PubMed2007

Confirmation of linkage to ocular refraction on chromosome 22q and identification of a novel linkage region on 1q.

OBJECTIVE: To localize genes influencing ocular refraction in subjects in the Beaver Dam Eye Study. Previous studies establish that myopia clusters within families and linkage to myopia has been demonstrated on 2q, 4q, 12q, 17q, 18q, 22q, and Xq. Few studies have examined genetic effects across the entire range of refraction, though linkages to 1p, 3q, 4q, 8p, and 11p have been reported, and our previous analysis of the Beaver Dam Eye Study demonstrated substantial heritability for refraction (68%). METHODS: We conducted nonparametric sibling-pair and genome-wide linkage analyses on spherical equivalent adjusting for age, education, and nuclear sclerosis, in 834 sibling pairs in 486 extended pedigrees. RESULTS: We identified a novel region of suggestive linkage on 1q (multipoint, P<.00019) and replicated the 22q region (multipoint, P = .0033) previously linked to myopia. Additionally, there was some evidence of linkage to 7p (multipoint, P = .0023). CONCLUSION: Refraction is a complex trait influenced by both genes and environment. Our work confirms a previously reported linkage region on 22q and identifies 2 novel regions of linkage on 1q and 7p. CLINICAL RELEVANCE: Further, genetic research is needed to finemap this trait to identify the causative gene. Modifying the actions of such a gene might lead to a reduction in the risk of refractive error.

Adult↗

PubMed2007

Age-related macular degeneration and risk of coronary heart disease: the Atherosclerosis Risk in Communities Study.

OBJECTIVE: To examine the association of age-related macular degeneration (AMD) with incident coronary heart disease (CHD) and all-cause mortality. DESIGN: Population-based prospective cohort study. PARTICIPANTS: From the Atherosclerosis Risk in Communities Study (n = 12 536; age range, 49-73 years). METHODS: Participants had retinal photographs of one eye taken between 1993 and 1995. Photographs were evaluated for the presence of early and late AMD signs according to the Wisconsin grading system. Incident CHD events (acute myocardial infarction, silent myocardial infarction, fatal CHD, and cardiac revascularization procedures) and all-cause mortality were identified prospectively using standardized methods. MAIN OUTCOME MEASURES: Incident CHD events and all-cause mortality. RESULTS: Of 11,414 persons at risk of CHD, there were 555 (4.9%) with AMD at baseline, of whom 540 were early AMD and 15 were late AMD cases. Over a 10-year follow-up, 922 persons developed an incident CHD event. After controlling for age, gender, race, systolic and diastolic blood pressure, pack-years of cigarette smoking, and other variables, early AMD was not associated with incident CHD (relative risk, 1.08; 95% confidence interval, 0.82-1.42). However, individuals with late AMD were significantly more likely to have an incident CHD event, with 4 CHD events among the 15 participants with late AMD at baseline (10-year cumulative incidence, 30.9%) as compared with 918 CHD events among the 11 399 participants without late AMD (incidence of 10.0%; P = 0.049, Fisher exact test). In the full cohort (n = 12 536), early AMD was not significantly associated with all-cause mortality. However, individuals with late AMD were more likely to die (10-year cumulative mortality rate, 23.5%) than those without late AMD (mortality rate, 8.9%; P = 0.088, Fisher exact test). CONCLUSIONS: These data provide no evidence of an association between early AMD signs with incident CHD and all-cause mortality in middle-aged persons. Individuals with late AMD appear to have a higher rate of CHD events than those without late AMD, but due to a small number of late AMD cases, this finding should be interpreted cautiously.

Aged↗

PubMed2007

Association of retinal vessel caliber to optic disc and cup diameters.

PURPOSE: To investigate whether optic disc size is related to retinal venule and arteriole diameters. METHODS: The population of Beaver Dam, Wisconsin, aged 43 to 86 years were invited to participate in a baseline examination from 1988 to 1990. During this examination, photographs, centered on the optic discs, were taken after pupil dilation. Optic discs and cups were measured from stereoscopic photographs, whereas retinal vessel measurements were taken from a single digitized photograph. Central retinal vein and central retinal arterial equivalents were subsequently calculated. Data for 3887 right eyes are included in the analyses. RESULTS: Narrower retinal venules and arterioles were found in the smaller optic discs controlling for optic cup diameter as well as age, systolic and diastolic blood pressure, refraction, and sex. Central retinal artery equivalents ranged from 156.04 +/- 16.82 microm in the smallest optic disc category to 165.93 +/- 15.17 microm in the larger disc category (P < 0.001). Central retinal vein equivalents ranged from 228.93 +/- 21.26 microm in the smallest to 243.18 +/- 22.32 microm in the larger disc categories (P < 0.001). The significant reduction in retinal vessel diameters was only apparent for the smallest optic disc sizes. A reduction in retinal vessel diameters was less consistent and not significant for small optic cup sizes. CONCLUSIONS: Smallest optic discs were associated with smaller central retinal artery and central retinal vein diameters. This anatomic relationship may be useful as an additional associated indicator for nonarteritic anterior ischemic optic neuropathy as well as for retinal vascular events.

Adult↗

PubMed2007

Measurement of retinal vascular caliber: issues and alternatives to using the arteriole to venule ratio.

PURPOSE: The arteriole to venule ratio (AVR) is widely used in studies of the associations of retinal microvascular disease with systemic and ocular outcomes. This is a discussion of the limitations of AVR; a comparison of its predictive information with that of its components, arteriolar and venular caliber; and a description of a suggested alternative method of modeling arteriolar and venular calibers directly. METHODS: Data from the population-based Blue Mountains Eye Study were used to compare the predictive information in models using AVR with models using arteriolar and venular calibers directly. Determination was made of how the apparent relationship between vessel caliber and two systemic outcomes (blood pressure [BP] and white blood cell count [WBC]) was influenced by the choice of regression model. These findings were interpreted with reference to the known biological relationship among vessel calibers, BP, and WBC. RESULTS: Models using arteriolar and venular calibers directly had more predictive information than models using AVR. The apparent relationship of vessel caliber to BP and WBC differed substantially, depending on the model chosen. For example, after adjustment for age, sex, and other covariates, decreasing venular caliber was associated with higher systolic BP when modeled separately, but was associated with lower systolic BP when modeled simultaneously with arteriolar caliber. CONCLUSIONS: The findings suggest AVR provides less information with regards to predicting systemic outcomes than its two components. Modeling arteriolar and venular calibers separately could be biased by confounding, while modeling both simultaneously appears to provide unbiased, biologically plausible results. The use of this approach is recommended in future research relating retinal vascular caliber to systemic or ocular outcomes.

Aged↗

PubMed2006

Is diabetic retinopathy an independent risk factor for ischemic stroke?

BACKGROUND AND PURPOSE: The relationship between diabetic retinopathy and ischemic stroke is uncertain and examined in this study. METHODS: A population-based, prospective cohort study of 1617 middle-aged persons with diabetes. Diabetic retinopathy signs were ascertained from retinal photographs, and incident ischemic stroke events were prospectively identified and validated. RESULTS: Over an average follow-up of 7.8 years, there were 75 ischemic stroke events. After adjustment for age, gender, race, center, 6-year mean arterial blood pressure, anti-hypertensive treatment use, fasting glucose, insulin treatment, duration of diabetes, high-density lipoprotein and low-density lipoprotein cholesterol levels and cigarette smoking status, diabetic retinopathy was associated with an increased risk of ischemic stroke (hazard rate ratio, 2.34; 95% CI, 1.13 to 4.86). CONCLUSIONS: Diabetic retinopathy predicts incident ischemic stroke in people with diabetes, independent of other risk factors.

Brain Ischemia↗

PubMed2006

Age-related macular degeneration is associated with incident myocardial infarction among elderly Americans.

OBJECTIVE: To investigate whether age-related macular degeneration (AMD) is associated with the development of myocardial infarction (MI) among elderly Americans. DESIGN: Population-based cross-sectional and cohort study. PARTICIPANTS: Five percent random sample of 2000 to 2003 Medicare enrollees. METHODS: The cross-sectional study included the first 2-year (2000 and 2001) enrollees who were aged > or =65 years (n = 1,519,086). The cohort study included only baseline MI-free enrollees (n = 1445677). MAIN OUTCOME MEASURES: Chronic conditions (AMD and type, history of MI, hypertension, and diabetes) were defined based on any occurrence of relevant International Classification of Diseases 9 codes in relevant diagnosis fields of the baseline Medicare claim files. A total of 56611 incident MI cases were identified from the follow-up data (2002 and 2003). RESULTS: Baseline mean age was 76 years, with 60% women and 88% whites. The prevalence of neovascular AMD was 2.2% (2.3% in women vs. 1.7% in men and 2.3% in whites vs. 1.2% in blacks; P<0.01 for both gender and race differences). The prevalence of nonneovascular AMD was 8.8% (9.9% in women vs. 7.3% in men and 9.5% in whites vs. 4.3% in blacks; P<0.01 for both gender and race differences). Baseline age-, gender-, and race-adjusted prevalences of hypertension, diabetes, and history of MI were 75%, 33%, and 5.00%, respectively, in the neovascular AMD group. In contrast, they were 73%, 27%, and 4.68% in the nonneovascular AMD group, and 65%, 25%, and 4.54% in the non-AMD group (P<0.01 for comparing the prevalence in neovascular and nonneovascular AMD vs. non-AMD groups). Prospectively, baseline age-, gender-, race-, hypertension-, and diabetes-adjusted 2-year incident odds ratios and 95% confidence intervals of MI associated with AMD are 1.19 (1.16-1.22) for all persons with AMD, 1.26 (1.20-1.33) for neovascular AMD, and 1.18 (1.14-1.21) for nonneovascular AMD. CONCLUSIONS: AMD is associated with older age, female gender, being white, and having a history of MI, hypertension, and diabetes. Furthermore, presence of AMD, especially neovascular AMD, is prospectively associated with a higher risk of incident MI. These findings, if confirmed by other studies that control for smoking and other lifestyle covariables, suggest the possibility of shared common antecedents between MI and AMD.

Age Factors↗

PubMed2006

Retinal vein occlusion and vascular mortality: pooled data analysis of 2 population-based cohorts.

PURPOSE: To assess the association of retinal vein occlusion (RVO) with cardiovascular and cerebrovascular mortality. DESIGN: Pooled data from 2 population-based cohort studies. PARTICIPANTS: At baseline, the Beaver Dam Eye Study (BDES) examined 4926 persons aged 43 to 86 years (from 1988-1990) and the Blue Mountains Eye Study (BMES) examined 3654 persons aged 49 to 97 years (from 1992 to 1994). METHODS: Retinal vein occlusion was assessed from retinal photographs. Vascular deaths were determined using either death certificates (BDES) or the Australian National Death Index (BMES). Cox regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). MAIN OUTCOME MEASURE: Vascular (cardiovascular and cerebrovascular) mortality was determined. RESULTS: Of 8384 baseline participants, 96 (1.14%) had RVO at baseline (BDES, n = 38; BMES, n = 58). Over 12 years, 1312 (15.7%) died of cardiovascular-related conditions and 341 (4.1%) died of cerebrovascular-related conditions. Age-standardized vascular mortality rates were 26.0% and 5.3%, respectively, in persons with RVO and 17.1% and 4.5%, respectively, in those without RVO. After adjusting for age, gender, body mass index, hypertension, diabetes, smoking, glaucoma, and study site, RVO was not associated with cardiovascular-related mortality (HR, 1.2; 95% CI, 0.8-1.8) or cerebrovascular-related mortality (HR, 0.9; 95% CI, 0.4-2.1) among participants of all ages. However, in persons aged less than 70 years, baseline RVO was associated with higher cardiovascular mortality (combined BDES and BMES: HR, 2.5; 95% CI, 1.2-5.2; BDES: HR, 2.5; 95% CI, 0.9-6.9; BMES: HR, 2.1; 95% CI, 0.7-6.8). CONCLUSIONS: Retinal vein occlusion in persons aged 43 to 69 years may signal a doubling of the risk of cardiovascular mortality.

Adult↗

PubMed2006

Quantitative retinal venular caliber and risk of cardiovascular disease in older persons: the cardiovascular health study.

BACKGROUND: Small vessel disease may contribute to the risk of cardiovascular disease in older persons. We describe the relation of retinal vascular caliber to incident coronary heart disease (CHD) and stroke in elderly persons. METHODS: Prospective population-based cohort study composed of 1992 men and women aged 69 to 97 years living in 4 US communities. Retinal arteriolar and venular calibers were measured from retinal photographs using a computer-assisted method. Incident CHD and stroke events were ascertained using standardized methods. RESULTS: After 5 years of follow-up, there were 115 incident CHD events and 113 incident stroke events. Participants with larger retinal venular caliber had a higher incidence of CHD (11.7%; 95% confidence interval [CI], 8.7%-15.8%, vs 8.1%; 95% CI, 5.7%-11.6%), comparing largest with smallest venular caliber quartiles, and stroke (8.4%; 95% CI, 6.0-11.7, vs 5.8%; 95% CI, 3.9-8.4). At multivariable analysis, controlling for age, sex, race, arteriolar caliber, systolic and diastolic blood pressure, diabetes, glucose concentration, cigarette smoking, pack-years of smoking, and high-density-lipoprotein and low-density lipoprotein cholesterol levels, larger retinal venular caliber was associated with incident CHD (rate ratio, 3.0; 95% CI, 1.6-5.7, comparing largest with smallest venular caliber quartiles; P(trend) = .001) and incident stroke (rate ratio, 2.2; 95% CI, 1.1-4.3; P(trend) = .02). Additional adjustment for C-reactive protein and common and internal carotid artery intimal-media thickness had minimal effect on these associations. At multivariable analysis, smaller retinal arteriolar caliber was associated with incident CHD (rate ratio, 2.0; 95% CI, 1.1-3.7, comparing largest with smallest arteriolar caliber quartiles; P = .03) but not stroke (rate ratio,1.1; 95% CI, 0.5-2.2; P = .73). CONCLUSION: Larger retinal venular caliber is independently associated with risk of cardiovascular disease in elderly persons.

Aged↗

PubMed2006

Relationship between low-normal blood pressure and kidney disease in type 1 diabetes.

Current recommendations, largely based on studies in type 2 diabetes, suggest lower target blood pressures (BPs) for individuals with diabetes than for the general population. However, the effect of lower BP on renal outcomes in type 1 diabetes is uncertain. In a population-based cohort of type 1 diabetes adults (mean age: 33.1 years) based in Wisconsin, of which the distribution of baseline BP was in the low-normal range, we examined the relationship between decreasing categories of systolic and diastolic BP and the 16-year incidence of proteinuria (n=232 of 604) and estimated glomerular filtration rate of <60 mL/min/1.73 m(2) (n=158 of 547). Decreasing BP categories had lower relative risk (RR) of developing incident proteinuria (RR comparing decreasing quartiles of systolic BP: 1.00, 0.76, 0.58, 0.73; P for trend=0.03; RR comparing decreasing quartiles of diastolic BP: 1.00, 0.81, 0.66, 0.42; P for trend <0.0001) and incident estimated glomerular filtration rate <60 mL/min/1.73 m(2) (RR comparing decreasing quartiles of systolic BP: 1.00, 0.83, 0.61, 0.65; P for trend=0.03; RR comparing decreasing quartiles of diastolic BP: 1.00, 0.84, 0.82, 0.43; P for trend=0.001). These associations were independent of glycemic control and several putative confounding factors. Subjects with either systolic BP <120 mm Hg or diastolic BP <70 mm Hg had significantly lower RR (95% confidence interval) of incident proteinuria (0.63 [0.48 to 0.82]) and incident estimated glomerular filtration rate <60 mL/min/1.73 m(2) (0.60 [0.43 to 0.82]); corresponding population-attributable risks for these outcomes were 26.7% and 29.5%, respectively. Our study suggests that lower BP levels, even below the accepted normal range, are protective against kidney disease in adults with type 1 diabetes. Interventional trials are desirable to clarify the clinical significance of this association.

Adult↗

PubMed2006

Associations between findings on cranial magnetic resonance imaging and retinal photography in the elderly: the Cardiovascular Health Study.

Associations between findings on cranial magnetic resonance imaging (MRI) and retinal photographs have been described mostly in middle-aged people. In the Cardiovascular Health Study, 1,717 elderly participants underwent MRI and retinal photography between 1991 and 1999. Associations were sought between MRI findings and four findings of retinal microvascular disease: retinopathy, focal arteriolar narrowing, arteriovenous nicking, and the arteriovenous ratio--the last based upon semiautomated measurements of arterioles and venules. After controlling for age and gender, the authors found associations between MRI findings and the smaller arteriovenous ratio (per standard deviation decrease): prevalent infarcts (odds ratio = 1.18, 95% confidence interval: 1.05, 1.34; p = 0.007), white matter grade (regression coefficient, 0.093; p = 0.011), incident infarct (odds ratio = 1.26, 95% confidence interval: 1.09, 1.46; p = 0.002), and worsening white matter grade (odds ratio = 1.12, 95% confidence interval: 0.98, 1.29; p = 0.09). Arteriovenous nicking was also associated with prevalent (odds ratio = 1.84, 95% confidence interval: 1.23, 2.76; p = 0.003) and incident (odds ratio = 1.84, 95% confidence interval: 1.15, 2.94; p = 0.011) infarcts. Adjustment for hypertension and diabetes had minimal effect. Evidence of small vessel disease in the retina increases the likelihood of finding it in the brain. Associations were less prominent in this elderly population than have been described in middle-aged people.

Age Factors↗

PubMed2006

Is early age-related macular degeneration related to carotid artery stiffness? The Atherosclerosis Risk in Communities Study.

BACKGROUND/PURPOSE: Atherosclerosis and vascular stiffness have been implicated in the pathogenesis of age-related macular degeneration (AMD). The association of carotid artery stiffness, a measure of arterial elasticity reflecting early atherosclerosis, with early AMD, was examined in this study. METHODS: A population-based, cross-sectional study of 9954 middle-aged people (age range 51-72 years). The presence of AMD signs was determined from fundus photographs according to the Wisconsin grading protocol. Carotid arterial stiffness was measured from high-resolution ultrasonic echo tracking of the left common carotid artery, and was defined as an adjusted arterial diameter change (AADCmu). A smaller AADC reflects greater carotid artery stiffness. The associations of pulse pressure and carotid artery intima-media thickness (IMT) with early AMD signs were also analysed. RESULTS: In the study population, 454 (4.6%) had early AMD. The mean (SD) AADC was 403 (127) mu. After adjusting for age, sex, race/centre, education, cigarette smoking, fasting glucose, lipid profile and inflammatory markers, a smaller AADC was found to be not associated with early AMD (odds ratio 0.94; 95% confidence interval, 0.71 to 1.25) or its component lesions. Other measures of arterial stiffness (pulse pressure) and atherosclerosis (carotid IMT) were also not associated with early AMD. CONCLUSIONS: Carotid artery stiffness was not associated with signs of early AMD in this middle-aged population. These data provide no evidence of a link between age-related elastoid changes and early atherosclerotic processes in the carotid arteries and early AMD.

Aged↗

PubMed2006

Frailty and age-related cataract.

OBJECTIVE: To determine whether there is an association between age-related cataract and frailty that persists after controlling for visual acuity (VA) and comorbid conditions. DESIGN: Cross-sectional. PARTICIPANTS: Two thousand three hundred seventy Beaver Dam Eye Study cohort members at 10-year (third) examination with cataract information. Ninety-nine percent of the population was Caucasian. METHODS: Medical history, blood pressures, height, weight, measures of frailty, and lens photographs were obtained during the study evaluation. Lens photographs were graded according to standardized protocols. MAIN OUTCOME MEASURES: Four of frailty (gait time, peak expiratory flow rate, handgrip strength, chair stand) and an index combining all 4 measures. RESULTS: After controlling for age, age squared, comorbidity index, pack-years, sedentary lifestyle, education, and VA, nuclear cataract in women was not associated significantly with any frailty measures; in men, nuclear cataract was associated with slower gait time (P = 0.01) and a poorer frailty index score (P = 0.01) in multivariable analyses. Cortical cataract was associated in women with a lower peak expiratory flow rate (P<0.01) and in men with weaker handgrip strength (P = 0.02) and a poorer frailty index score (P</=0.01) in multivariable analyses. Posterior subcapsular cataract in women was associated significantly with a lower peak expiratory flow rate (P = 0.01). Nuclear and cortical cataract add significant information in explaining frailty index scores in men. CONCLUSIONS: Three common types of age-related cataract are associated with some measures of frailty independent of VA and systemic comorbidities. It is possible that age-related cataract may be an indicator of general functional decline in older adults.

Adult↗

PubMed2006

The relation of ambulatory blood pressure and pulse rate to retinopathy in type 1 diabetes mellitus: the renin-angiotensin system study.

PURPOSE: To examine the association of ambulatory blood pressure (ABP) and ambulatory pulse rate (APR) with diabetic retinopathy (DR) in persons with type 1 diabetes in the Renin-Angiotensin System Study (RASS), a multicenter primary diabetic nephropathy (DN) prevention trial. DESIGN: Cross-sectional study. PARTICIPANTS: One hundred ninety-four normotensive RASS participants in 3 centers who are 16 years of age or older with type 1 diabetes mellitus (DM) of 2 to 20 years' duration. METHODS: Ambulatory blood pressure and APR were monitored using standardized protocols. Patients were defined as nondippers if the night-to-day ratios for both systolic and diastolic blood pressures were >0.9. Diabetic retinopathy was determined by masked grading of 30 degrees color stereoscopic fundus photographs of 7 standard fields using the Early Treatment Diabetic Retinopathy Study severity scale. MAIN OUTCOME MEASURE: Severity of DR. RESULTS: No DR was present in 32%, mild nonproliferative DR (NPDR) was present in 55%, and moderate to severe NPDR or proliferative DR was present in 13% of the cohort. Neither 24-hour systolic ABP or diastolic ABP, daytime systolic or diastolic ABP, nor nighttime diastolic ABP were related to severity of DR. Statistically significant associations were found between nighttime systolic ABP and mean ABP and DR. Among those with no DR, 19% were nondippers; for those with mild NPDR, 28% were nondippers; and for those with severe NPDR or proliferative DR, 36% were nondippers (P = 0.08). The ratio of nighttime to daytime APR, but not the 24-hour APR or daytime or nighttime APR, was related positively to the severity of DR. In multivariable analyses, only the nighttime systolic ABP was related to severity of DR (P<0.05). CONCLUSIONS: These data suggest that ABP, especially during the night, may provide a better measure than clinical BP regarding the relationship of BP to the severity of retinopathy in normotensive persons with type 1 DM without clinical DN.

Adult↗

PubMed2006

CFH, ELOVL4, PLEKHA1 and LOC387715 genes and susceptibility to age-related maculopathy: AREDS and CHS cohorts and meta-analyses.

Age-related maculopathy (ARM) is an important cause of visual impairment in the elderly population. It is of crucial importance to identify genetic factors and their interactions with environmental exposures for this disorder. This study was aimed at investigating the CFH, ELOVL4, PLEKHA1 and LOC387715 genes in independent cohorts collected using different ascertainment schemes. The study used a case-control design with subjects originally recruited through the Cardiovascular Health Study (CHS) and the Age-Related Eye Disease Study (AREDS). CFH was significantly associated with ARM in both cohorts (P</=0.00001). A meta-analysis confirmed that the risk allele in the heterozygous or homozygous state (OR, 2.4 and 6.2; 95% CI, 2.2-2.7 and 5.4-7.2, respectively) confers susceptibility. LOC387715 was also significantly associated with ARM in both cohorts (P</=0.00001) and a meta-analysis confirmed that the risk allele in the heterozygous and homozygous state (OR, 2.5 and 7.3; 95% CI, 2.2-2.9 and 5.7-9.4, respectively) confers susceptibility. Both CFH and LOC387715 showed an allele-dose effect on the ARM risk, individuals homozygous at either locus were at more than two-fold risk compared to those heterozygous. PLEKHA1, which is closely linked to LOC387715, was significantly associated with ARM status in the AREDS cohort, but not the CHS cohort and ELOVL4 was not significantly associated with ARM in either cohort. Joint action of CFH and LOC387715 was best described by independent multiplicative effect without significant interaction in both cohorts. Interaction of both genes with cigarette smoking was insignificant in both cohorts. This study provides additional support for the CFH and LOC387715 genes in ARM susceptibility via the evaluation of cohorts that had different ascertainment schemes regarding ARM status and through the meta-analyses.

Aged↗

PubMed2006

Is early age-related macular degeneration associated with cerebral MRI changes? The Atherosclerosis Risk in Communities study.

PURPOSE: To examine the relation of early age-related macular degeneration (AMD) with cerebral magnetic resonance imaging (MRI) changes. DESIGN: Population-based, cross-sectional study. METHODS: A sample of 1,684 persons ages 51 to 72 years with no history of stroke had cerebral MRI and retinal photography. MRI scans were graded for severity of white matter lesions (WML), sulcal widening (SW), and ventricular enlargement (VE). AMD was graded from retinal photographs. RESULTS: After adjustment for age, gender, race, or center, early AMD (5.0% of participants) was not significantly associated with WML (odds ratio [OR] 1.0, 95% confidence intervals [CI], 0.6 to 1.6), SW (OR 0.6, 95% CI, 0.4 to 1.2), or VE (OR 1.0, 95% CI, 0.6 to 1.8). CONCLUSIONS: These data showed no statistically significant association of early AMD with cerebral MRI changes, but the study was limited by a small number of cases with wide CIs. Further studies may clarify these associations.

Aged↗

PubMed2006

Age-related macular degeneration and risk for stroke.

BACKGROUND: Age-related macular degeneration (AMD) affects 7 million persons 40 years of age and older in the United States. Risk factors for the disease are similar to those for stroke. OBJECTIVE: To determine what relationship, if any, exists between AMD and incident clinical stroke. DESIGN: Prospective cohort study. SETTING: The population-based Atherosclerosis Risk in Communities Study, which was conducted in Minnesota, Maryland, Mississippi, and North Carolina. PATIENTS: 10 405 persons between 49 and 73 years of age who had no history of stroke or coronary heart disease. MEASUREMENTS: Participants had retinal photographs taken between 1993 and 1995. A standardized protocol was used to evaluate the photographs for the presence of drusen and other signs of AMD. Incident stroke events were identified and validated by reviewing case records. RESULTS: There were 498 early-stage and 10 late-stage cases of AMD in the cohort (n = 508). Over a 10-year period, 241 persons had an incident stroke event. After adjusting for age, sex, ethnicity, and site, the authors found that persons with early-stage AMD had a higher cumulative incidence of stroke than those without the disease (4.08% vs. 2.14%). The presence of early-stage AMD was associated with a higher adjusted risk for stroke (hazard ratio, 1.87 [95% CI, 1.21 to 2.88]). Further adjustment for systolic blood pressure, diabetes, cigarette smoking, and use of antihypertensive medications did not substantially alter this association (hazard ratio, 1.85 [CI, 1.19 to 2.87]). The authors found that the association between early-stage AMD and stroke varied by study site and patient ethnicity. Multivariable-adjusted hazard ratios were 3.15 and 1.07 in samples of white patients in Minnesota and Maryland, respectively; 3.77 in a sample of African-American patients in Mississippi; and 0.33 in a sample of mostly white patients (91%) in North Carolina. No site included sufficient numbers of both African-American and white patients to determine whether ethnicity contributed to the observed differences by study site. LIMITATIONS: There were few cases of late-stage AMD, and the cohort assembly method prohibited full understanding of variation by ethnicity and site. CONCLUSION: Middle-aged persons with signs of early-stage AMD have a higher risk for stroke independent of traditional stroke risk factors.

Aged↗