Adverse association between diabetic retinopathy and cardiac structure and function

doi:10.1016/j.ahj.2008.10.019

American Heart Journal

Volume 157, Issue 3, March 2009, Pages 563-568

https://doi.org/10.1016/j.ahj.2008.10.019 Get rights and content

Background

Recent work has demonstrated a link between retinopathy, a marker of microvascular disease, and the development of heart failure, a finding particularly relevant in individuals with diabetes. Our objective was to assess the relationship between retinopathy and cardiac structure and function in a cohort of individuals with type 2 diabetes mellitus.

Methods

Stereoscopic fundus photography of 7 standard fields was obtained in 531 Mexican American adults with type 2 diabetes mellitus recruited as sibships from Starr County, Texas. Retinopathy was centrally scored and classified as no retinopathy, early nonproliferative diabetic retinopathy, moderate to severe nonproliferative diabetic retinopathy, or proliferative diabetic retinopathy. Echocardiography was used to assess cardiac structure and function. Multilevel mixed models were used to assess associations of clinical and echocardiographic variables with retinopathy while accounting for correlations among siblings.

Results

More severe diabetic retinopathy was associated with the presence of hypertension, previous cardiovascular disease, longer duration of diabetes, elevated glycosylated hemoglobin, and greater albuminuria. With worsening severity of diabetic retinopathy, left ventricular (LV) mass and left atrial dimension increased, and LV ejection fraction and LV fractional shortening decreased, independent of potential confounding variables.

Conclusions

More severe diabetic retinopathy was associated with worse cardiac structure and function by echocardiography independent of potential confounding variables. These data suggest a possible microvascular contribution to the development of diabetes-associated cardiac enlargement and dysfunction. Alternatively, common pathways may be leading to both disorders.

Section snippets

Study design and sample

Individuals for this study were recruited in Starr County, Texas, a community located on the Texas-Mexico border in which 97% of residents are Mexican American,¹⁴ and enrolled in the Family Blood Pressure Program, as previously described.¹⁵ Briefly, subjects were recruited as members of families in which at least 2 siblings had type 2 diabetes mellitus, which was originally defined as onset of diabetes at age ≥30 years and either 2 elevated fasting blood glucose values ≥140 mg/dL, use of

Results

Clinical and retinal gradings were available for 531 participants. Baseline characteristics based on retinopathy classification are described in Table I. There were 126 (23.7%) individuals without diabetic retinopathy, 231 (43.5%) with early nonproliferative diabetic retinopathy, 107 (20.2%) with moderate to severe nonproliferative diabetic retinopathy, and 67 (12.6%) with proliferative diabetic retinopathy. Significant differences in gender, cigarette smoking, and serum total cholesterol were

Discussion

In this cohort of individuals with type 2 diabetes mellitus, more severe diabetic retinopathy was associated with worse echocardiographic indices of cardiac structure, including increased LV mass and increased left atrial dimension, independent of potential confounding variables such as hypertension and previous cardiovascular disease. In addition, parameters of LV systolic function also worsened with increasing severity of retinopathy.

Previous studies have linked the presence of retinopathy

Conclusions

This study demonstrates an association between more severe diabetic retinopathy and worse echocardiographic indices of cardiac structure, including increased LV mass and increased left atrial dimension, independent of potential confounding variables. This association between diabetic retinopathy and abnormalities of cardiac structure and function in this study and the previously demonstrated association between adverse clinical cardiovascular events and retinopathy12, 13, 23, 24 highlight need

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Cited by (20)

Left ventricular systolic dysfunction predicts long-term major microvascular complication outcomes in type 1 diabetes. The Pittsburgh Epidemiology of Diabetes Complications (EDC) study of childhood onset diabetes
2018, Journal of Diabetes and its Complications
Citation Excerpt :
Recently, Bonapace et al. reported cross-sectional associations between increased left atrial volume index and microvascular complications (albuminuria, overt nephropathy, diabetic retinopathy and peripheral sensory neuropathy), whether individually or in combination9 in patients with type 2 diabetes. Similarly, in a cohort of 531 Mexican Americans with type 2 diabetes, a dose-dependent relation was observed between the severity of retinopathy and abnormal myocardial structure and function, including decreased LVEF.8 Of note, relevant data in type 1 diabetes are still very limited and the sample sizes in existing studies were small.
We aimed to assess association between abnormal LVEF, in the absence of coronary artery disease (CAD), and 25-year incidence of major outcomes of diabetes (MOD) in a cardiology substudy of the Pittsburgh Epidemiology of Diabetes Complications cohort of childhood-onset type 1 diabetes.
115 normotensive type 1 diabetes individuals without known CAD, underwent a baseline exercise radionuclide ventriculography. Abnormal LVEF was defined as a resting ejection fraction <50% or a failure to increase ejection fraction with exercise by >5% (men) or a fall in ejection fraction with exercise (women). Cox proportional hazards models were used to predict the composite endpoint of MOD (first instance of major CAD, stroke, end-stage renal disease, blindness, amputation or diabetes-related death).
Mean baseline age was 28 and diabetes duration 19 years. In a mean follow-up of 19 years, 50 MOD events were identified. Allowing for established risk factors at baseline, abnormal LVEF (n = 22) independently predicted MOD incidence (HR = 2.12, 95% CI: 1.12–4.00, p = 0.022) but not major CAD (HR = 1.33, 95% CI: 0.53–3.33, p = 0.539).
An abnormal LVEF may identify diabetic cardiomyopathy and predict long term risk of MOD (but not CAD alone) in type 1 diabetes individuals, consistent with it reflecting microvascular disease.
Retinopathy and left ventricular hypertrophy in patients with chronic kidney disease: Interrelationship and impact on clinical outcomes
2017, International Journal of Cardiology
Retinopathy and left ventricular hypertrophy (LVH) are representative markers of microvascular and cardiac dysfunction in patients with chronic kidney disease (CKD). However, their relationship and their combined effects on clinical outcomes are unknown.
We included 401 patients with nondialysis-dependent CKD stage 3–5 who had been examined with fundus photography for diabetic or hypertensive retinopathy. The presence of LVH was identified by echocardiography. The clinical significance of retinopathy and LVH was evaluated in terms of the rate of renal function decline and for any cardiovascular event (CVE)/death.
CKD patients with retinopathy had a higher prevalence of LVH than those without retinopathy (38.9% vs. 27.6%, P = 0.017). The presence of retinopathy was independently associated with LVH (odds ratio 1.69, 95% confidence interval [CI] 1.02, 2.80). Compared with subjects without either retinopathy or LVH, the coexistence of retinopathy and LVH was independently associated with rapid renal function decline (β = − 3.28; 95% CI − 6.52, − 0.04), whereas retinopathy or LVH alone were not. Patients with both retinopathy and LVH had a higher risk of CVE/death (adjusted hazard ratio 2.75; 95% CI 1.44, 5.26) than patients with either factor alone. A significant synergistic interaction was observed between retinopathy and LVH to predict CVE/death (P for interaction = 0.049).
Retinopathy was independently associated with LVH. The coexistence of retinopathy and LVH was associated with higher risks of CKD progression and CVE/death than was either factor alone, and their combined effects synergized to predict the risk of CVE/death.
Evaluation of the association between diabetic retinopathy and the incidence of atrial fibrillation: A nationwide population-based study
2016, International Journal of Cardiology
Citation Excerpt :
Diabetes is associated with LA enlargement and dysfunction independent of hypertension or diastolic dysfunction [14]. Furthermore, a more severe grade of DR is associated with worse cardiac structural changes, including an increased LA dimension and increased left ventricular mass [13,15]. Considering that atrial structural remodeling is a well-known substrate for AF development, the presence and severity of DR can increase the risk of AF by LA structural remodeling.
Atrial fibrillation (AF) is prevalent among type 2 diabetic patients. However, the association between diabetic retinopathy (DR) and AF is controversial.
We included 40,500 patients with type 2 diabetes (≥ 40 years, mean age 62 ± 11 years, 53% men) without AF from the Korean National Insurance Service-National Sample Cohort (2002–2007). Subjects were classified without DR (non-DR, n = 30,178), with DR (DR, n = 8920), and with proliferative DR (PDR, n = 1402).
During a mean 5.9-year follow-up, 1261 (3.1%) patients were newly diagnosed as having AF (4.9, 6.0, and 8.3 per 1000 person-years in the non-DR, DR, and PDR groups, respectively). In multivariate Cox proportional hazard models, patients in the DR and PDR groups had a significantly higher risk of AF than those in the non-DR group (DR group: hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.00–1.30; PDR group: HR 1.46, 95% CI 1.13–1.87); p for trend < 0.001). The risk of AF increased in patients with DR and end-stage renal disease (ESRD) (HR 2.39, 95% CI 1.31–3.96, p < 0.001) and in those with PDR and ESRD (HR 3.59, 95% CI 1.96–5.97, p < 0.001) compared to those without DR and ESRD.
The presence and severity of DR was significantly associated with the incidence of AF. Also, the presence of ESRD had an impact on the incidence of AF in patients with DR.
Association between retinal vein occlusion and risk of heart failure: A 12-year nationwide cohort study
2016, International Journal of Cardiology
Citation Excerpt :
Our results confirm that RVO, a small to medium-sized vessel disease in the eye, is also associated with an increased risk of cardio/cerebrovascular diseases, including HF. The associations of the retina with HF have been studied in patients with DM, considering the importance of microvascular dysfunction in the pathogenesis of diabetic complications [19,20]. In our study, we found a greater HR for HF by RVO among patients without DM (HR = 1.56) than those with DM (HR = 1.30, Fig. 1).
Retinal vein occlusion (RVO) is one of the major causes of visual impairment in elderly people. Risk factors for RVO are also common risk factors for cardiovascular disease, including heart failure (HF). However, the association between RVO and HF has not been evaluated.
A retrospective propensity-score matched cohort study was conducted using national representative 1 million samples from the Korea National Health Insurance Service. The RVO group included patients with a first diagnosis of either central or branch RVO (n = 1754) and the comparison group included randomly selected patients (n = 8749) who were matched to sociodemographic factors and the year of RVO diagnosis. In the longitudinal cohort, HF developed in 11.6% and 8.0% of patients in the RVO and comparison groups, respectively, (p < 0.001) during the 11-year follow-up period (median, 7.6 years). RVO was significantly associated with an increased risk of HF after multivariable adjustment (HR = 1.36; 95% CI, 1.16–1.60). In terms of HF subtypes, RVO was associated with the risk of ischemic HF but not with the risk of non-ischemic HF. The effect size (~ HR) for HF by RVO was larger in patients without each comorbidity than in patients with each comorbidity.
Our observational study on nationwide data suggests that RVO is associated with an increased risk of the incidence of HF, especially ischemic HF. An optimal surveillance strategy and referring from ophthalmologists to cardiologists should be considered in the presence of one or more additional HF risk factors in patients with RVO.
Relationship between macular and retinal diseases with prevalent atrial fibrillation - An analysis of the Australian Heart Eye Study
2015, International Journal of Cardiology
Relationship between increased left atrial volume and microvascular complications in patients with type 2 diabetes
2015, Journal of Diabetes and its Complications
We assessed whether left atrial volume index (LAVI) was associated with the presence of microvascular complications in patients with type 2 diabetes, and whether this association was independent of hemodynamic and non-hemodynamic factors.
We studied 157 consecutive outpatients with type 2 diabetes with no previous history of ischemic heart disease, chronic heart failure and valvular diseases. A transthoracic echocardiography and myocardial perfusion scintigraphy were performed in all participants. Presence of microvascular complications was also recorded.
Overall, 51 patients had decreased estimated glomerular filtration rate and/or abnormal albuminuria, 24 had diabetic retinopathy, 22 had lower-extremity sensory neuropathy, and 67 (42.7%) patients had one or more of these microvascular complications (i.e., combined endpoint). After stratifying patients by LAVI, those with LAVI ≥ 32 ml/m² had a greater prevalence of microvascular complication, lower left ventricular (LV) ejection fraction, higher LV mass index and higher E/e’ ratio than those with LAVI < 32 ml/m². Logistic regression analyses revealed that microvascular complications (singly or in combination) were associated with increased LAVI, independently of age, sex, diabetes duration, hemoglobin A1c, hypertension, LV-ejection fraction, LV mass index and the E/e’ ratio.
These results indicate that microvascular diabetic complications are associated with increased LAVI in well-controlled type 2 diabetic patients with preserved systolic function and free from ischemic heart disease, independently of multiple potential confounders.

View all citing articles on Scopus

: This study was supported in part by the National Heart, Lung, and Blood Institute Family Blood Pressure Program (HL54504), the National Eye Institute (EY12386), and an NIH Mentored Clinical Investigator Award (5K12RR017665-05) to Dr Aguilar.

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Clinical InvestigationDiabetes and MetabolismAdverse association between diabetic retinopathy and cardiac structure and function

Background

Methods

Results

Conclusions

Section snippets

Study design and sample

Results

Discussion

Conclusions

Am J Cardiol

Am J Med

J Am Coll Cardiol

J Am Soc Echocardiogr

Am J Cardiol

Am J Cardiol

Am J Hypertens

J Am Coll Cardiol

Diabetes Res Clin Pract

J Am Soc Echocardiogr

Prog Cardiovasc Dis

J Am Coll Cardiol

Am Heart J

Risk factors for congestive heart failure in US men and women: NHANES I epidemiologic follow-up study

Arch Intern Med

Diabetes and cardiovascular disease. The Framingham study

JAMA

The incidence of congestive heart failure in type 2 diabetes: an update

Diabetes Care

Impact of diabetes on cardiac structure and function: the strong heart study

Circulation

Clinical Investigation
Diabetes and Metabolism
Adverse association between diabetic retinopathy and cardiac structure and function