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Severity of Diabetic Retinopathy and the Risk of Future Cerebrovascular Disease, Cardiovascular Disease, and All-Cause Mortality

Published:December 24, 2020DOI:https://doi.org/10.1016/j.ophtha.2020.12.019

      Purpose

      To determine the relationship between the severity of diabetic retinopathy and the future risk of cerebrovascular accident (CVA), myocardial infarction (MI), congestive heart failure (CHF), and all-cause mortality in patients with type 2 diabetes mellitus.

      Design

      Retrospective cohort study.

      Participants

      Patients with type 2 diabetes who underwent diabetic retinopathy screening via fundus photography.

      Methods

      The relationship between retinopathy status and the 5-year risk of first-time CVA, MI, CHF, and all-cause mortality was investigated using multivariate Cox proportional hazards regressions that controlled for age, gender, race or ethnicity, hemoglobin A1c, duration of diabetes, high-density lipoprotein level, low-density lipoprotein level, history of hypertension, systolic blood pressure, diastolic blood pressure, tobacco use, statin use, body mass index, urine microalbumin-to-creatinine ratio, and estimated glomerular filtration rate.

      Main Outcome Measures

      Five-year risk of first-time CVA, MI, CHF, and all-cause mortality.

      Results

      Seventy-seven thousand three hundred seventy-six patients were included in this study. The average age was 59.8 years with 53.6% male, 31.2% non-Hispanic White, and 41.4% Hispanic patients. Diabetic retinopathy was significantly associated with all outcomes on multivariate analysis. Compared with patients with no retinopathy, those with minimal nonproliferative diabetic retinopathy (NPDR) had a higher risk of CVA (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.18–1.46), MI (HR, 1.30; 95% CI, 1.15–1.46), CHF (HR, 1.29; 95% CI, 1.19–1.40), and death (HR, 1.15; 95% CI, 1.05–1.25). Similarly, patients with moderate to severe NPDR had a higher risk of each outcome (CVA: HR, 1.56; 95% CI, 1.29–1.89; MI: HR, 1.92; 95% CI, 1.57–2.34; CHF: HR, 1.90; 95% CI, 1.66–2.18, and death: HR, 1.55; 95% CI, 1.32–1.82), as did patients with proliferative diabetic retinopathy (CVA: HR, 2.53; 95% CI, 1.84–3.48; MI: HR, 1.89; 95% CI, 1.26–2.83; CHF: HR, 1.96; 95% CI, 1.47–2.59; and death: HR, 1.87; 95% CI, 1.36–2.56).

      Conclusions

      Diabetic retinopathy is significantly associated with future risk of CVA, MI, CHF, and death, with higher degrees of retinopathy appearing to carry a heightened risk for each outcome. Retinal information may provide valuable insights into patients’ risk of future vascular disease and death.

      Keywords

      Abbreviations and Acronyms:

      BMI (body mass index), BP (blood pressure), CHF (congestive heart failure), CI (confidence interval), CVA (cerebrovascular accident), eGFR (estimated glomerular filtration rate), HDL (high-density lipoprotein), HR (hazard ratio), IQR (interquartile range), KPSC (Kaiser Permanente Southern California), LDL (low-density lipoprotein), MI (myocardial infarction), NPDR (nonproliferative diabetic retinopathy), PDR (proliferative diabetic retinopathy), SD (standard deviation)
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      References

        • Cho N.H.
        • Shaw J.E.
        • Karuranga S.
        • et al.
        IDF Diabetes Atlas: global estimates of diabetes prevalence for 2017 and projections for 2045.
        Diabetes Res Clin Pract. 2018; 138: 271-281
        • Almdal T.
        • Scharling H.
        • Jensen J.S.
        • Vestergaard H.
        The independent effect of type 2 diabetes mellitus on ischemic heart disease, stroke, and death: a population-based study of 13,000 men and women with 20 years of follow-up.
        Arch Intern Med. 2004; 164: 1422-1426
        • Sasaki A.
        • Horiuchi N.
        • Hasegawa K.
        • Uehara M.
        Mortality from coronary heart disease and cerebrovascular disease and associated risk factors in diabetic patients in Osaka District, Japan.
        Diabetes Res Clin Pract. 1995; 27: 77-83
        • Glovaci D.
        • Fan W.
        • Wong N.D.
        Epidemiology of diabetes mellitus and cardiovascular disease.
        Curr Cardiol Rep. 2019; 21: 21
        • Guo V.Y.
        • Chan J.C.
        • Chung H.
        • et al.
        Retinal information is independently associated with cardiovascular disease in patients with type 2 diabetes.
        Sci Rep. 2016; 6: 19053
        • Hayden J.M.
        • Reaven P.D.
        Cardiovascular disease in diabetes mellitus type 2: a potential role for novel cardiovascular risk factors.
        Curr Opin Lipidol. 2000; 11: 519-528
        • Chamnan P.
        • Simmons R.K.
        • Sharp S.J.
        • et al.
        Cardiovascular risk assessment scores for people with diabetes: a systematic review.
        Diabetologia. 2009; 52: 2001-2014
        • Garg N.
        • Muduli S.K.
        • Kapoor A.
        • et al.
        Comparison of different cardiovascular risk score calculators for cardiovascular risk prediction and guideline recommended statin uses.
        Indian Heart J. 2017; 69: 458-463
        • Brownrigg J.R.
        • Hughes C.O.
        • Burleigh D.
        • et al.
        Microvascular disease and risk of cardiovascular events among individuals with type 2 diabetes: a population-level cohort study.
        Lancet Diabetes Endocrinol. 2016; 4: 588-597
        • Cheung N.
        • Mosley T.
        • Islam A.
        • et al.
        Retinal microvascular abnormalities and subclinical magnetic resonance imaging brain infarct: a prospective study.
        Brain. 2010; 133: 1987-1993
        • Cheung N.
        • Rogers S.
        • Couper D.J.
        • et al.
        Is diabetic retinopathy an independent risk factor for ischemic stroke?.
        Stroke. 2007; 38: 398-401
        • Davis T.M.
        • Millns H.
        • Stratton I.M.
        • et al.
        Risk factors for stroke in type 2 diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS) 29.
        Arch Intern Med. 1999; 159: 1097-1103
        • Kawasaki R.
        • Cheung N.
        • Islam F.M.
        • et al.
        Is diabetic retinopathy related to subclinical cardiovascular disease?.
        Ophthalmology. 2011; 118: 860-865
        • Klein R.
        • Klein B.E.
        • Moss S.E.
        Epidemiology of proliferative diabetic retinopathy.
        Diabetes Care. 1992; 15: 1875-1891
        • Klein R.
        • Klein B.E.
        • Moss S.E.
        • Cruickshanks K.J.
        Association of ocular disease and mortality in a diabetic population.
        Arch Ophthalmol. 1999; 117: 1487-1495
        • Targher G.
        • Bertolini L.
        • Tessari R.
        • et al.
        Retinopathy predicts future cardiovascular events among type 2 diabetic patients: the Valpolicella Heart Diabetes Study.
        Diabetes Care. 2006; 29: 1178
        • Xie J.
        • Ikram M.K.
        • Cotch M.F.
        • et al.
        Association of diabetic macular edema and proliferative diabetic retinopathy with cardiovascular disease: a systematic review and meta-analysis.
        JAMA Ophthalmol. 2017; 135: 586-593
        • Zhu X.R.
        • Zhang Y.P.
        • Bai L.
        • et al.
        Prediction of risk of diabetic retinopathy for all-cause mortality, stroke and heart failure: Evidence from epidemiological observational studies.
        Medicine (Balt). 2017; 96e5894
        • Targher G.
        • Bertolini L.
        • Zenari L.
        • et al.
        Diabetic retinopathy is associated with an increased incidence of cardiovascular events in type 2 diabetic patients.
        Diabet Med. 2008; 25: 45-50
        • Rosenson R.S.
        • Fioretto P.
        • Dodson P.M.
        Does microvascular disease predict macrovascular events in type 2 diabetes?.
        Atherosclerosis. 2011; 218: 13-18
        • Kramer C.K.
        • Rodrigues T.C.
        • Canani L.H.
        • et al.
        Diabetic retinopathy predicts all-cause mortality and cardiovascular events in both type 1 and 2 diabetes: meta-analysis of observational studies.
        Diabetes Care. 2011; 34: 1238-1244
        • Reaven P.D.
        • Emanuele N.
        • Moritz T.
        • et al.
        Proliferative diabetic retinopathy in type 2 diabetes is related to coronary artery calcium in the Veterans Affairs Diabetes Trial (VADT).
        Diabetes Care. 2008; 31: 952-957
        • Gerstein H.C.
        • Ambrosius W.T.
        • Danis R.
        • et al.
        Diabetic retinopathy, its progression, and incident cardiovascular events in the ACCORD trial.
        Diabetes Care. 2013; 36: 1266-1271
        • Miettinen H.
        • Haffner S.M.
        • Lehto S.
        • et al.
        Retinopathy predicts coronary heart disease events in NIDDM patients.
        Diabetes Care. 1996; 19: 1445-1448
        • Cusick M.
        • Meleth A.D.
        • Agron E.
        • et al.
        Associations of mortality and diabetes complications in patients with type 1 and type 2 diabetes: Early Treatment Diabetic Retinopathy Study report no. 27.
        Diabetes Care. 2005; 28: 617-625
        • Koebnick C.
        • Langer-Gould A.M.
        • Gould M.K.
        • et al.
        Sociodemographic characteristics of members of a large, integrated health care system: comparison with US Census Bureau data.
        Perm J. 2012; 16: 37-41
        • Hudson S.M.
        • Contreras R.
        • Kanter M.H.
        • et al.
        Centralized reading center improves quality in a real-world setting.
        Ophthalmic Surg Lasers Imaging Retina. 2015; 46: 624-629
        • Modjtahedi B.S.
        • Theophanous C.
        • Chiu S.
        • et al.
        Two-year incidence of retinal intervention in patients with minimal or no diabetic retinopathy on telemedicine screening.
        JAMA Ophthalmol. 2019; 137: 445-448
        • Chen W.
        • Yao J.
        • Liang Z.
        • et al.
        Temporal trends in mortality rates among Kaiser Permanente Southern California Health Plan enrollees, 2001–2016.
        Perm J. 2019; 23: 18-213
        • Nguyen T.T.
        • Wong T.Y.
        Retinal vascular manifestations of metabolic disorders.
        Trends Endocrinol Metab. 2006; 17: 262-268
        • Targher G.
        • Bertolini L.
        • Zoppini G.
        • et al.
        Increased plasma markers of inflammation and endothelial dysfunction and their association with microvascular complications in type 1 diabetic patients without clinically manifest macroangiopathy.
        Diabet Med. 2005; 22: 999-1004
        • van Hecke M.V.
        • Dekker J.M.
        • Nijpels G.
        • et al.
        Inflammation and endothelial dysfunction are associated with retinopathy: the Hoorn Study.
        Diabetologia. 2005; 48: 1300-1306
        • Doehner W.
        • Frenneaux M.
        • Anker S.D.
        Metabolic impairment in heart failure: the myocardial and systemic perspective.
        J Am Coll Cardiol. 2014; 64: 1388-1400
        • Udell J.A.
        • Cavender M.A.
        • Bhatt D.L.
        • et al.
        Glucose-lowering drugs or strategies and cardiovascular outcomes in patients with or at risk for type 2 diabetes: a meta-analysis of randomised controlled trials.
        Lancet Diabetes Endocrinol. 2015; 3: 356-366
        • Vinik A.I.
        • Ziegler D.
        Diabetic cardiovascular autonomic neuropathy.
        Circulation. 2007; 115: 387-397