Diabetic Retinopathy and Risk of Stroke: A Secondary Analysis of the ACCORD Eye Study.
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ABSTRACT: Background and purpose
Diabetic retinopathy (DR) is a common microvascular complication of diabetes, which causes damage to the retina and may lead to rapid vision loss. Previous research has shown that the macrovascular complications of diabetes, including stroke, are often comorbid with DR. We sought to explore the association between DR and subsequent stroke events.Methods
This is a secondary analysis of patients enrolled in the ACCORD Eye study (Action to Control Cardiovascular Risk in Diabetes). The primary outcome was stroke during follow-up. The exposure was presence of DR at study baseline. We fit adjusted Cox proportional hazards models to provide hazard ratios for stroke and included interaction terms with the ACCORD randomization arms.Results
We included 2828 patients, in whom the primary outcome of stroke was met by 117 (4.1%) patients during a mean (SD) of 5.4 (1.8) years of follow-up. DR was present in 874 of 2828 (30.9%) patients at baseline and was more common in patients with than without incident stroke (41.0% versus 30.5%; P=0.016). In an adjusted Cox regression model, DR was independently associated with incident stroke (hazard ratio, 1.52 [95% CI, 1.05-2.20]; P=0.026). This association was not affected by randomization arm in the ACCORD glucose (P=0.300), lipid (P=0.660), or blood pressure interventions (P=0.469).Conclusions
DR is associated with an increased risk of stroke, which suggests that the microvascular pathology inherent to DR has larger cerebrovascular implications. This association appears not to be mediated by serum glucose, lipid, and blood pressure interventions.
SUBMITTER: Wong KH
PROVIDER: S-EPMC7686117 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeTo report additional ocular outcomes of intensive treatment of hyperglycemia, blood pressure, and dyslipidemia in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study.DesignDouble 2×2 factorial, multicenter, randomized clinical trials in people with type 2 diabetes who had cardiovascular disease or cardiovascular risk factors. In the glycemia trial, targets of intensive and standard treatment were: hemoglobin A1c <6.0% and 7.0% to 7.9%, respectively, and in the blood pressure trial: systolic blood pressures of <120 and <140 mmHg, respectively. The dyslipidemia trial compared fenofibrate plus simvastatin with placebo plus simvastatin.ParticipantsOf the 3472 ACCORD Eye Study participants enrolled, 2856 had 4-year data (85% of survivors).MethodsEye examinations and fundus photographs were taken at baseline and year 4. Photographs were graded centrally for retinopathy severity and macular edema using the Early Treatment Diabetic Retinopathy Study (ETDRS) methods.Main outcome measuresThree or more steps of progression on the ETDRS person scale or treatment of retinopathy with photocoagulation or vitrectomy.ResultsAs previously reported, there were significant reductions in the primary outcome in the glycemia and dyslipidemia trials, but no significant effect in the blood pressure trial. Results were similar for retinopathy progression by 1, 2, and 4 or more steps on the person scale and for ≥ 2 steps on the eye scale. In the subgroup of patients with mild retinopathy at baseline, effect estimates were large (odds ratios, ∼0.30; P < 0.001), but did not reach nominal significance for participants with no retinopathy or for those with moderate to severe retinopathy at baseline.ConclusionsSlowing of progression of retinopathy by intensive treatment of glycemia was observed in ACCORD participants, whose average age and diabetes duration were 62 and 10 years, respectively, and who had cardiovascular disease or cardiovascular risk factors. The effect seemed stronger in patients with mild retinopathy. Similar slowing of progression was observed in patients treated with fenofibrate, with no effect observed with intensive blood pressure treatment. This is the second study to confirm the benefits of fenofibrate in reducing diabetic retinopathy progression, and fenofibrate should be considered for treatment of diabetic retinopathy.
| S-EPMC4252767 | biostudies-literature
Project description:PurposeTo report the longitudinal association between use of thiazolidinediones (TZDs), visual acuity (VA) change, and diabetic eye disease incidence and progression.DesignCohort study ancillary to a randomized clinical trial.MethodsWe analyzed baseline and 4-year follow-up data of 2856 ACCORD trial participants with no history of proliferative diabetic retinopathy. Based on stereoscopic fundus photographs, we evaluated diabetic macular edema (DME) progression and DR progression. We also evaluated 10- and 15-letter change on the ETDRS visual acuity chart. Main outcome measures were incidence or progression of DME or DR and change in visual acuity.ResultsTZD use was not associated with DME incidence in either the analysis of any use (adjusted odds ratio [aOR] [95% CI]: 1.22 [0.72-2.05]) or duration of use (aOR: 1.02 [0.99-1.04]). Diabetic retinopathy (DR) incidence/progression was more common in patients with no or mild DR at baseline who were ever treated with TZDs (aOR: 1.68 [1.11-2.55]), but this association disappeared when adjusting for the time on TZD (aOR: 1.02 [1.00-1.04]). DR progression among those with moderate or worse DR at baseline was no different between TZD users and non-users. TZD usage had no effect on the ultimate visual acuity outcome.ConclusionIn this longitudinal study of patients with type 2 diabetes, we found no association between TZD use and visual acuity outcomes or DME progression, and no consistent evidence of increased DR progression in patients ever treated with TZDs vs those never treated with TZDs.
| S-EPMC6381823 | biostudies-literature
Project description:Both the presence of diabetic retinopathy and its severity are significantly associated with future cardiovascular (CV) events. Whether its progression is also linked to incident CV outcomes hasn't been assessed.The relationship between retinopathy, its 4-year progression, and CV outcomes (CV death or nonfatal myocardial infarction or stroke) was analyzed in participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial who also participated in the ACCORD Eye Study. Retinopathy was classified as either none, mild, moderate, or severe, and worsening was classified as a <2-step, 2-3-step, or >3-step change (that included incident laser therapy or vitrectomy).Participants (n = 3,433) of mean age 61 years had baseline retinal photographs (seven stereoscopic fields). Compared with no retinopathy, the adjusted HRs (95% CI) for the CV outcome rose from 1.49 (1.12-1.97) for mild retinopathy to 2.35 (1.47-3.76) for severe retinopathy. A subset of 2,856 was evaluated for progression of diabetic retinopathy at 4 years. The hazard of the primary outcome increased by 38% (1.38 [1.10-1.74]) for every category of change in retinopathy severity. Additional adjustment for the baseline and follow-up levels of A1C, systolic blood pressure, and lipids either individually or together rendered the relationships between worsening and CV outcomes nonsignificant.Both the severity of retinopathy and its progression are determinants of incident CV outcomes. The retina may provide an anatomical index of the effect of metabolic and hemodynamic factors on future CV outcomes.
| S-EPMC3631868 | biostudies-literature
Project description:To assess the cumulative 10-year incidence of diabetic retinopathy (DR) and its associated factors in a population living in Greater Beijing.The population-based longitudinal Beijing Eye Study, which included 4439 subjects (age in 2001: 40+years) in 2001, was repeated in 2011 with 2695 subjects participating (66.4% of the survivors). The study participants underwent a detailed ophthalmic examination. Fundus photographs were examined for the new development of DR.After excluding individuals with DR at baseline (n = 87) or no sufficient fundus photographs in 2011 (n = 6), the study included 2602 subjects with a mean age of 64.6±9.7 years (median: 64.0 years; range: 50 to 93 years). In the 10-year period, 109 subjects (39 men) developed new DR with an incidence of 4.2% (95% confidence interval (CI): 3.45,5.03). In multiple logistic regression analysis, incident DR was significantly associated with higher HbA1c value (P<0.001; Odds Ratio (OR): 1.73; 95% Confidence Interval (CI): 1.35,2.21), longer duration of diabetes mellitus (P<0.001; OR: 1.16; 95% CI: 1.10,1.22), higher serum concentration of creatinine (P = 0.02; OR: 1.01; 95% CI: 1.002,1.022), lower educational level (P = 0.049; OR: 0.74; 95% CI: 0.55,0.99), higher estimated cerebrospinal fluid pressure (P = 0.038; OR: 1.10; 95% CI: 1.01,1.22), and shorter axial length (P<0.001; OR: 0.48; 95% CI: 0.33,0.71).The cumulative 10-year incidence (mean: 4.2%) of DR in a North Chinese population was significantly associated with a higher HbA1c value, longer known duration of diabetes mellitus, higher estimated CSFP and shorter axial length (P<0.001). Shorter axial length (or hyperopia) and, potentially, higher CSFP may be additional risk factors to be taken into account when counseling and treating patients with diabetes mellitus.
| S-EPMC4210166 | biostudies-other
Project description:Research questionThe current population-based study aimed to investigate the prevalence of diabetic retinopathy (DR) and risk factors among residents over 40 years old in the rural area of Dongguan, southern China.Study designThe Dongguan Eye Study was a population-based study from September 2011 to February 2012.SettingThe area was set in the rural area of Dongguan, southern China.ParticipantsAdult rural population aged 40 or older.InterventionParticipants underwent haematological, physical, ophthalmic examinations and completed a questionnaire regarding lifestyles and systemic medical conditions.Primary and secondary outcome measuresThe frequency and risk factors of visual impairment and the major vision-threatening eye diseases.ResultsOf the 8952 Han Chinese, 1500 were diagnosed with type 2 diabetes mellitus (T2DM) with an average age of 59.5±11.1 years, and 1310 participants with fundus photography results were analysed. Standardised prevalence rate of DR was 18.2% for all patients with diabetes, 32.8% for the patients with previously diagnosed diabetes and 12.6% for newly diagnosed patients with T2DM. The prevalence rate of male DR was significantly higher than that of female DR (23.0% vs 14.1%, p<0.001). No significant difference was found in age-specific prevalence of DR. In diabetic patients, the prevalence rates of vision-threatening diabetic retinopathy, diabetic macular oedema and clinically significant macular oedema were 2.5%, 2.8% and 0.9%, respectively. Male gender, higher education level, longer duration of diabetes mellitus (DM), higher systolic blood pressure and glycosylated haemoglobin were independent risk factors for DR development in patients with diabetes.ConclusionA relatively lower prevalence of DR was found among the participants with T2DM in residents over 40 years in the rural area of southern China. Thus, an ophthalmic examination is recommended, especially for individuals with DM and DR risk factors. There is a need to increase awareness and education on DM and DR, especially in subjects with DR risk factors to reduce the incidence of DR and macular oedema.
| S-EPMC6756414 | biostudies-literature
Project description:Background: The population-based studies conducted thus far do not provide conclusive evidence of the link between diabetic retinopathy (DR) and stroke. The aim of the present systematic review was to determine whether DR is specifically associated with stroke. Methods: MEDLINE, Embase, and Web of Science were systematically searched from their inception to July 31, 2020. All cohort studies that reported associations between the presence of DR and incident stroke were included. The pooled hazard ratios (HRs), pooled risk ratios (RRs), and 95% confidence intervals (CIs) were calculated. Results: The meta-analysis included 19 cohort studies involving 81,452 diabetic patients. The pooled effect size of any DR related to stroke was 1.25 for HR (95% CI: 1.12-1.39; P < 0.0001) and 1.96 for RR (95% CI: 1.60-2.39; P < 0.0001). Subgroup analysis for the type of diabetes yielded pooled HR of 1.29 (95% CI: 1.10-1.50; P = 0.001) in patients with type 2 diabetes mellitus (T2DM). The pooled RR was 2.29 (95% CI: 1.77-2.96; P < 0.0001) in patients with T2DM. Two studies addressed the DR-related stroke among type 1 diabetes mellitus (T1DM) patients. One study found a significant association between DR and stroke (OR: 1.6; 95% CI: 1.1-2.3; P < 0.01), while the other did not identify an association between these two conditions (RR: 1.40; 95% CI: 0.62-2.18; P = 0.178). Conclusions: The presence of DR is associated with an increased risk of stroke in diabetic patients. This correlation is robust in T2DM patients but uncertain in T1DM patients. Our findings indicate that DR is an important biomarker for the prediction of stroke. To further validate the role of DR in stroke-risk stratification, additional research is required on the association between the stage of DR and stroke risk, and more studies including T1DM patients are necessary.
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Project description:ImportanceCataracts and diabetic retinopathy (DR) are the leading causes of acquired blindness worldwide. Although extraction is the standard treatment option for cataracts, it is also reported to increase the risk of developing DR among individuals with diabetes. Nevertheless, the association between cataract surgery and risk of DR is still not well understood, and there have been no prior population-based reports in this area.ObjectiveTo assess the risk of developing DR after cataract surgery among individuals with type 2 diabetes.Design, setting, and participantsA population-based prospective cohort study was conducted among participants recruited from the Singapore Epidemiology of Eye Diseases Study. The baseline visit was conducted between June 1, 2004, and March 31, 2009, and the 6-year follow-up visit was conducted between June 1, 2011, and July 31, 2016. Statistical analysis was performed from October 1 to 31, 2019.ExposuresCataract surgery performed before a follow-up visit, determined based on slitlamp evaluation of lens status at baseline and follow-up visits.Main outcomes and measuresEyes with incidence of DR were defined as those with the presence of any DR (level ?15 based on the modified Airlie House classification system, graded from retinal photographs) at 6-year follow-up with no DR at baseline. The association between cataract surgery and incidence of DR was evaluated using a multivariable Poisson regression model with a generalized estimating equation to account for correlation between both eyes.ResultsA total of 1734 eyes from 972 participants with diabetes (392 Malay individuals and 580 Indian individuals; 495 men; mean [SD] age, 58.7 [9.1] years) were included in the analysis. A total of 163 study eyes had already undergone cataract surgery at baseline, and a total of 187 eyes (originally phakic at baseline) underwent cataract surgery any time during the follow-up period. Of these 350 eyes, 77 (22.0%) developed DR. Among the 1384 eyes that never underwent cataract surgery, 195 (14.1%) developed DR. After adjustments for age, sex, race/ethnicity, baseline hemoglobin A1c level, duration of diabetes, random blood glucose level, antidiabetic medication use, hypertension, body mass index, and smoking status, multivariable regression analysis showed that any prior cataract surgery was associated with incidence of DR (relative risk, 1.70; 95% CI, 1.26-2.30; P?=?.001). Subgroup analyses by race/ethnicity showed similar associations in both Malay individuals (relative risk, 1.73; 95% CI, 1.13-2.69; P?=?.02) and Indian individuals (relative risk, 1.93; 95% CI, 1.33-2.80; P?<?.001).Conclusions and relevanceThe findings of this population-based cohort study suggest that prior cataract surgery was associated with a higher risk of developing DR among individuals with diabetes. Further validation is warranted to confirm this association.
| S-EPMC7298610 | biostudies-literature
Project description:Background/aimsTo determine the association between aspirin use and diabetic retinopathy (DR) among persons with diabetes, in a population-based, cross-sectional study.MethodsSubjects with diabetes aged >40 years from the Singapore Epidemiology of Eye Diseases Study were enrolled in this study. Retinal photographs were graded for DR according to the modified Airlie House classification system. Vision threatening diabetic retinopathy (VTDR) was defined as the presence of severe non-proliferative DR, or proliferative DR, or clinically significant macular oedema. The association between aspirin use and the presence of DR or VTDR was assessed using multivariable logistic regression models including age, gender, ethnicity, socioeconomic status, HbA1c, systolic blood pressure, anti-hypertension medicine, total cholesterol, anti-cholesterol medicine, BMI, current smoking status, diabetes duration, history of cardiovascular disease (CVD) and chronic kidney disease (CKD.).ResultsA total of 2,061 participants with diabetes and complete record of relevant systemic and DR data were included. Of these, 711 (34.5%) had any stage of DR, and among these 177 (8.6%) had VTDR. After adjusting for co-variables listed, the association between aspirin use and VTDR was significant (OR = 1.69, P = 0.019), while the association between aspirin use and any DR was borderline (OR = 1.31, P = 0.063). Aspirin use was not associated with either DR or VTDR after additional adjustment of CVD and CKD. Further stratification by history of CVD or CKD showed no association between aspirin use and DR/VTDR in either subgroup.ConclusionAspirin use was not significantly associated with DR but might be an indicator of diabetic complications (CVD, CKD) that were co-present with more severe DR type. Future longitudinal studies are warranted to confirm our findings.
| S-EPMC5409055 | biostudies-literature
Project description:ObjectiveTo identify factors associated with prevalent diabetic retinopathy (DR) among Chinese American adults with type 2 diabetes mellitus (T2DM), and to compare these factors to ones previously described for a population-based sample of Latinos with a higher DR prevalence.DesignPopulation-based cross-sectional study.Participants4582 Chinese Americans aged 50 or older residing in Monterey Park, California.MethodsParticipants completed an in-home questionnaire on socio-demographic status and medical history, and a comprehensive clinical eye examination, using the same protocol implemented in the Los Angeles Latino Eye Study. Fundus photographs from 7 Early Treatment Diabetic Retinopathy fields were graded in a masked manner using a modified Airlie House grading system to assess presence and severity of DR. Logistic regression analyses based on a conceptual model of DR risk identified factors associated with prevalent DR.Main outcome measuresOdds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with DR and vision-threatening DR (VTDR).ResultsIn total, 238 participants were diagnosed with any DR; 27 of these were classified as having VTDR. Both, any DR and VTDR showed statistically significant positive associations with T2DM duration (OR5-9 years = 1.24, OR10-14 years = 2.07, OR15+years = 3.99), glycosylated hemoglobin (HbA1c) (OR6.5-6.9% = 1.33, OR7-7.9% = 1.86, OR8%+ = 3.22), systolic blood pressure (SBP) (ORper 10mmHg+ = 1.19), and insulin treatment (ORinsulin+ = 2.44). For VTDR, we also found novel associations with antihypertensive drugs (OR: 0.18; 95% CI: 0.06-0.61) and statins (OR: 4.96; 95% CI: 1.60-16.41). Chinese Americans and Latinos had a nearly identical DR probability based on HbA1c and SBP. However, Latinos had a higher DR probability at every year of duration of T2DM (≥ 5 years).ConclusionsWhile we observed an overall lower DR prevalence in Chinese Americans than in Latinos (35.8% of individuals with TD2M in Chinese Americans versus 42.0% in Latinos), our data indicate that the impact of increasing HbA1c and SBP on DR probability is incrementally the same in both populations. However, increasing T2DM duration is associated with higher DR probability in Latinos than Chinese Americans, even after controlling for other known predictors. Novel factors associated with VTDR include antihypertensive drugs and statins. However, to determine if these drugs impact VTDR susceptibility, we need longitudinal data and more cases.
| S-EPMC5828248 | biostudies-literature
Project description:ImportanceThe Diabetic Retinopathy Clinical Research Network Protocol S randomized clinical trial results suggest that ranibizumab is a reasonable treatment alternative to panretinal photocoagulation (PRP) when managing proliferative diabetic retinopathy (PDR), with or without concomitant baseline diabetic macular edema (DME). However, ranibizumab injections are costly. Thus, it would be useful to examine the relative cost-effectiveness of these 2 treatment modalities.ObjectiveTo evaluate incremental cost-effectiveness ratios of 0.5-mg ranibizumab therapy vs PRP for PDR.Design, setting, and participantsPreplanned secondary analysis using efficacy, safety, and resource utilization data through 2 years of follow-up at 55 US sites for 213 adults with PDR. Data were collected from February 2012 to January 2015.InterventionsIntravitreous 0.5-mg ranibizumab at baseline and as frequently as every 4 weeks based on a structured retreatment protocol or PRP at baseline for PDR. Eyes in both groups could receive ranibizumab for concomitant DME.Main outcomes and measuresIncremental cost-effectiveness ratios of ranibizumab compared with PRP evaluated within 2 prespecified subgroups for the study eye: with baseline vision-impairing (Snellen equivalent 20/32 or worse) DME and without baseline vision-impairing DME.ResultsThe study included 305 adults with PDR, the mean age was 52 years, 44% were women, and 52% were white. Of the 46 participants with PDR and vision-impairing DME at baseline, 21 were assigned to the ranibizumab group and 25 to the PRP group (plus ranibizumab for DME). Among the remaining participants without baseline vision-impairing DME, 80 and 87 were in the ranibizumab and PRP groups, respectively. For participants with and without baseline vision-impairing DME, the incremental cost-effectiveness ratios of ranibizumab therapy compared with PRP were $55 568/quality-adjusted life-year and $662 978/quality-adjusted life-year, respectively, over 2 years.Conclusions and relevanceOver 2 years, compared with PRP, 0.5-mg ranibizumab as given in this trial is within the $50 000/quality-adjusted life-year to $150 000/quality-adjusted life-year range frequently cited as cost-effective in the United States for eyes presenting with PDR and vision-impairing DME, but not for those with PDR without vision-impairing DME.Trial registrationClinicaltrials.gov Identifier: NCT01489189.
| S-EPMC5540054 | biostudies-literature