European Journal of Cardiovascular Medicine

Diabetic retinopathy (DR) is the most common and well-recognized microvascular complication of type 2 diabetes mellitus (T2DM) and remains a leading cause of preventable blindness worldwide. With the global prevalence of diabetes rising sharply, DR has emerged as a major public-health burden, with estimates projecting more than 100 million people currently affected and many more at risk of vision-threatening disease in the coming decades (1, 2). Traditionally regarded as an ocular condition, DR is increasingly understood as a systemic vascular disorder that reflects generalized microvascular injury. Beyond the confines of the retina, DR shares common pathophysiological pathways with macrovascular complications, including coronary artery disease (CAD). Mechanisms such as chronic hyperglycemia, advanced glycation end products, oxidative stress, endothelial dysfunction, low-grade inflammation, and microvascular rarefaction contribute both to retinal microangiopathy and to the development of atherosclerotic vascular disease (3).

Several population-based cohort studies have demonstrated that retinal microvascular changes and DR severity are not only markers of ocular morbidity but also indicators of systemic vascular health. DR severity has been associated with coronary and cerebrovascular disease events, suggesting that the retina can serve as a “window” to systemic vascular pathology (4). Multiple large-scale studies and meta-analyses have further confirmed that the presence and progression of DR predict major adverse cardiovascular events (MACE), cardiovascular disease (CVD) mortality, and coronary heart disease (CHD), even after adjustment for conventional risk factors. Importantly, the risk of adverse outcomes increases stepwise with DR severity, from non-proliferative DR (NPDR) to proliferative DR (PDR), and is further accentuated in the presence of diabetic macular edema (DME) (5).

However, the evidence is not entirely consistent. Some post-hoc analyses of cardiovascular outcome trials have reported attenuated or even null associations between DR and recurrent cardiovascular events, underscoring heterogeneity across study populations, outcome definitions, and confounder adjustments (6). Moreover, interventional trials such as the ACCORD Eye program demonstrated that intensive management of glycemia, blood pressure, and lipids reduced DR progression, indirectly supporting shared mechanisms between microvascular and macrovascular disease. Yet these studies were not designed to establish a causal link between DR and CAD (7).

In India, where the burden of T2DM is among the highest globally and patients often develop complications at an earlier age and lower body mass index, DR is highly prevalent. Hospital-based studies from Indian cohorts suggest that increasing DR severity is associated with greater ischemic heart disease burden, including angiographically confirmed CAD. Still, most of these studies have been limited by small sample sizes, variable diagnostic criteria, and inconsistent adjustment for confounding factors (8). Thus, while international literature strongly suggests that DR may serve as a predictor of systemic vascular disease, there is a paucity of adequately powered, standardized, and rigorously conducted Indian studies directly addressing the DR–CAD association using gold-standard diagnostic tools.

Recent systematic reviews and new observational studies continue to highlight DR as an independent marker of cardiovascular risk, but important uncertainties remain. These include the incremental prognostic value of DR over established cardiovascular risk scores, the specific contribution of vision-threatening DR (VTDR) compared with mild DR, and the modifying effects of modern cardioprotective therapies such as statins, sodium-glucose co-transporter-2 (SGLT2) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists (9).

Taken together, these gaps justify focused investigation into the relationship between DR and CAD in Indian patients with T2DM. The present study was therefore designed to determine whether the presence and severity of DR, as graded by the Early Treatment Diabetic Retinopathy Study (ETDRS) classification, are independently associated with angiography-confirmed CAD. Additionally, this study aimed to evaluate whether DR severity provides incremental predictive value for CAD risk beyond conventional cardiovascular risk factors such as age, sex, duration of diabetes, hypertension, HbA1c, and dyslipidemia.

Study Design and Setting: This was a hospital-based cross-sectional observational study conducted in the Department of General Medicine, Mamata Medical College, Khammam, Telangana.

Study Population and Sample Size: A total of 150 patients with type 2 diabetes mellitus (T2DM) attending the outpatient and inpatient services of the department were recruited consecutively. The sample size was chosen based on feasibility and prevalence data from similar Indian studies evaluating diabetic retinopathy (DR) and coronary artery disease (CAD).

Inclusion and Exclusion Criteria: Patients aged ≥30 years with a confirmed diagnosis of T2DM (as per American Diabetes Association criteria) were included. Patients with type 1 diabetes mellitus, other causes of retinopathy (e.g., hypertensive or vascular retinopathies), history of ocular trauma, prior coronary revascularization, or coexisting systemic illnesses such as chronic kidney disease, severe hepatic disease, or malignancy were excluded to avoid confounding.

Clinical and Biochemical Assessment: Detailed demographic and clinical data including age, sex, duration of diabetes, smoking and alcohol history, and hypertension were recorded. Baseline investigations included fasting plasma glucose, HbA1c, lipid profile, renal function tests, and electrocardiogram.

Ophthalmological Evaluation: All participants underwent a comprehensive ophthalmic examination in collaboration with the Department of Ophthalmology. After pupillary dilatation, fundus evaluation was performed using direct ophthalmoscopy and slit-lamp biomicroscopy with a +90D lens. Where required, fundus photography was taken for documentation. DR was graded according to the Early Treatment Diabetic Retinopathy Study (ETDRS) classification into non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), and diabetic macular edema (DME).

Cardiovascular Evaluation: All patients underwent a baseline electrocardiogram and echocardiography to assess left ventricular function and exclude structural heart disease. Suspicion of ischemic heart disease was further evaluated using treadmill test (TMT) or, when indicated, coronary angiography. CAD was defined as the presence of ≥50% stenosis in at least one major epicardial coronary artery on coronary angiography. Patients were stratified into CAD-positive and CAD-negative groups.

Statistical Analysis: Data were entered into Microsoft Excel and analyzed using SPSS software version 25.0. Continuous variables were expressed as mean ± standard deviation (SD), and categorical variables as proportions. Chi-square test was used for comparison of categorical data, and Student’s t-test for continuous variables. Logistic regression analysis was performed to determine the independent association between DR severity and presence of CAD after adjusting for confounding factors such as age, sex, duration of diabetes, hypertension, HbA1c, and dyslipidemia. A p-value <0.05 was considered statistically significant.

Table 1: Baseline Demographic and Clinical Characteristics of Study Population (n = 150)

Table 1 shows the baseline profile of the 150 patients studied. The mean age was 56.2 ± 9.1 years, with a male predominance (61.3%). The average duration of diabetes was 10.1 ± 5.7 years, reflecting long-standing disease in many patients. Smoking (21.3%) and alcohol use (18.0%) were noted as additional vascular risk factors. Hypertension was highly prevalent (60.7%), underscoring its role as a major comorbidity in this diabetic population.

Table 2: Biochemical and Clinical Investigations of Study Population (n = 150)

Table 2 summarizes the biochemical and clinical investigations of the study population. The mean fasting plasma glucose (162.4 ± 48.6 mg/dL) and HbA1c (8.2 ± 1.4%) indicate suboptimal glycemic control in most patients. Lipid profile revealed diabetic dyslipidemia, with elevated total cholesterol (198.6 ± 36.2 mg/dL), LDL-C (122.8 ± 28.4 mg/dL), triglycerides (176.5 ± 52.7 mg/dL), and reduced HDL-C (40.7 ± 8.9 mg/dL). Renal function was largely preserved, with mean serum creatinine of 1.0 ± 0.3 mg/dL and blood urea of 32.1 ± 8.7 mg/dL. Electrocardiographic abnormalities suggestive of ischemic changes were detected in 58 patients (38.7%), reflecting the high burden of cardiovascular involvement in this cohort.

Table 3: Distribution of Diabetic Retinopathy (n = 150)

Table 3 shows the distribution of diabetic retinopathy in the study group. More than half of the patients (52.0%) had no evidence of DR, while 48.0% demonstrated varying grades of retinopathy. Non-proliferative DR (30.7%) was the most common stage, with mild (12.0%), moderate (11.3%), and severe (7.3%) forms. Proliferative DR was present in 12.0% of patients, and diabetic macular edema in 5.3%, either alone or with other stages. This pattern reflects the progressive spectrum of retinal changes typically seen in long-standing diabetes.

Table 4: Coronary Artery Disease Profile (n = 150)

Table 4 presents the coronary artery disease profile of the study population. Out of 150 patients, 64 (42.7%) were diagnosed with CAD, while 86 (57.3%) had no significant coronary involvement. Among CAD-positive patients, single-vessel disease was the most frequent pattern (43.7%), followed by double-vessel (34.4%) and triple-vessel disease (21.9%). This indicates a substantial burden of CAD in patients with type 2 diabetes mellitus, with nearly half showing angiographically confirmed coronary involvement and a considerable proportion having multi-vessel disease.

Figure 1: Association Between Diabetic Retinopathy Severity and Coronary Artery Disease

The figure 1 illustrates the relationship between diabetic retinopathy (DR) severity and coronary artery disease (CAD) status in the study cohort. CAD prevalence showed a progressive increase with advancing DR. While only 31.2% of patients without DR had CAD, the proportion rose steadily across stages of NPDR, reaching 64.7% in severe NPDR. The highest prevalence was observed in proliferative DR (72.2%) and in those with diabetic macular edema (62.5%). This trend demonstrates a strong association between DR severity and CAD burden, supporting the role of retinopathy as an independent marker of systemic vascular disease in type 2 diabetes mellitus.

Table 6: Logistic Regression Analysis for Association Between DR Severity and CAD

Table 6 shows the results of multivariate logistic regression analysis for predictors of coronary artery disease (CAD) in patients with type 2 diabetes mellitus. Among traditional risk factors, longer duration of diabetes (OR 1.08, p = 0.006) and hypertension (OR 1.74, p = 0.041) were significantly associated with CAD, while age showed only a marginal effect (p = 0.048). HbA1c and dyslipidemia did not reach statistical significance. Importantly, DR severity emerged as a strong independent predictor of CAD. Compared with patients without DR, moderate NPDR (OR 2.35, p = 0.038), severe NPDR (OR 2.98, p = 0.038), proliferative DR (OR 4.12, p = 0.002), and DME (OR 3.54, p = 0.037) were significantly associated with higher odds of CAD. These findings confirm that advanced stages of retinopathy are independent indicators of systemic vascular disease, even after adjusting for major cardiovascular risk factors.

Figure 2: Independent association of diabetic retinopathy (DR) severity with coronary artery disease (CAD) after multivariate logistic regression.

The figure 2 shows odds ratios (blue dots) with 95% confidence intervals (horizontal lines) for clinical variables and DR stages. The vertical red dashed line represents the null value (OR = 1). Advanced DR, including moderate NPDR, severe NPDR, proliferative DR (PDR), and diabetic macular edema (DME), showed significantly increased odds of CAD after adjusting for age, sex, duration of diabetes, hypertension, HbA1c, and dyslipidemia

In this cross-sectional study of adults with type 2 diabetes mellitus (T2DM) from the Department of General Medicine, Mamata Medical College, we found that coronary artery disease (CAD) prevalence rose stepwise with diabetic retinopathy (DR) severity, and that moderate NPDR, severe NPDR, PDR, and DME were independently associated with higher odds of CAD after adjustment for age, sex, duration of diabetes, hypertension, HbA1c, and dyslipidemia. These findings align with prior meta-analyses showing that advanced DR phenotypes particularly PDR and DME confer greater cardiovascular risk, including incident CAD and cardiovascular mortality (10).

Our adjusted effect sizes are concordant with contemporary hospital-based work linking ETDRS severity to angiography-defined CAD. For example, Lingineni et al. reported that DR severity tracks CAD burden in T2DM, supporting the concept that retinal microangiopathy mirrors systemic macrovascular disease (11). In the Indian context, population studies such as CURES and the nationwide IJO analysis have documented the substantial burden of DR and its association with cardiometabolic comorbidities, reinforcing the plausibility that retinopathy marks broader vascular injury in South Asian patients who develop diabetes earlier and at lower BMI (12).

Biologically, shared pathways including chronic hyperglycemia, endothelial dysfunction, low-grade inflammation, and microvascular rarefaction provide a mechanistic bridge between retinal disease and atherosclerosis (13). Intensive multifactorial therapy slows DR progression (ACCORD Eye), which indirectly supports common mechanisms, even though those trials were not designed to establish DR–CAD causality (14). Our data are directionally consistent with these mechanisms: the odds of CAD increased across ETDRS stages despite adjustment for traditional risks, suggesting that DR carries information beyond standard risk factors.

Not all literature is uniform. Some cohorts have shown attenuation of associations after comprehensive adjustment or have emphasized competing risks (e.g., nephropathy) that can confound microvascular–macrovascular links, particularly in long-standing diabetes (13). Still, the weight of evidence—including recent meta-analyses supports DR as an independent marker of adverse cardiovascular outcomes, especially at advanced stages (15).

Clinical implications: In routine practice, a documented ETDRS grade—especially moderate/severe NPDR, PDR, or DME should prompt systematic cardiovascular risk assessment (blood pressure, lipids), ECG review, and consideration of further ischemia testing where indicated. This is particularly relevant in India, where DR and CAD burdens are high and presentation may be earlier (12). Given that intensive risk-factor control reduces DR progression (16), it is reasonable to treat advanced DR as a “red flag” to optimize cardioprotective therapy (statins, ACEi/ARB, SGLT2 inhibitors or GLP-1 receptor agonists as appropriate), while recognizing that randomized evidence specifically targeting DR-guided CAD prevention is still limited (13).

Strengths and limitations: Strengths include standardized ETDRS grading, angiography-based CAD definition (≥50% stenosis), and multivariable adjustment. Limitations include cross-sectional design (precluding temporality), single-center convenience sampling (possible selection bias), and a modest sample size (n=150) that widens confidence intervals for some strata. Residual confounding (e.g., renal function beyond creatinine, inflammatory markers, medication classes) is possible. External validity to primary-care or community settings may be limited

In adults with T2DM evaluated at a tertiary center in South India, DR severity—particularly moderate/severe NPDR, PDR, and DME—was independently associated with angiography-confirmed CAD after adjustment for conventional risk factors. These results, consistent with prior systematic reviews and hospital cohorts, support using DR severity as a practical clinical signal to intensify cardiovascular risk assessment and management in diabetes (1–3,6,11). Prospective, multi-center studies should test whether DR-informed care pathways improve CAD detection and outcomes.

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