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Original Research: Cardiovascular Disease |

The Impact of Associated Diabetic Retinopathy on Stroke and Severe Bleeding Risk in Diabetic Patients With Atrial FibrillationDiabetic Retinopathy and Atrial Fibrillation: The Loire Valley Atrial Fibrillation Project FREE TO VIEW

Gregory Y. H. Lip, MD; Nicolas Clementy, MD; Bertrand Pierre, MD; Mathieu Boyer, MSc; Laurent Fauchier, MD, PhD
Author and Funding Information

From the University of Birmingham Centre for Cardiovascular Sciences (Prof Lip), City Hospital, Birmingham, England; Thrombosis Research Unit (Prof Lip), Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; and Service de Cardiologie, Pôle Coeur Thorax Vasculaire (Drs Clementy, Pierre, and Fauchier and Mr Boyer), Centre Hospitalier Universitaire Trousseau et Faculté de Médecine, Université François Rabelais, Tours, France.

CORRESPONDENCE TO: Gregory Y. H. Lip, MD, University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Dudley Rd, Birmingham, B18 7QH, England; e-mail: g.y.h.lip@bham.ac.uk


FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;147(4):1103-1110. doi:10.1378/chest.14-2096
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BACKGROUND:  Diabetes mellitus is recognized as a stroke risk factor in atrial fibrillation (AF). Patients with diabetes with retinopathy have an increased risk for systemic cardiovascular complications, and severe diabetic retinopathy predisposes to ocular bleeding. We hypothesized that patients with diabetes, retinopathy, and AF have increased stroke/thromboembolism (TE) and severe bleeding risks when compared with patients with diabetes and AF who do not have retinopathy or to patients with AF and without diabetes.

METHODS:  We tested our hypothesis in a large “real-world” cohort of individuals with AF from the Loire Valley Atrial Fibrillation project.

RESULTS:  Of 8,962 patients with AF in our dataset, 1,409 (16%) had documented diabetes mellitus. Of these, 163 (1.8% of the whole cohort) were patients with diabetic retinopathy. After a follow-up of 31 ± 36 months, when compared with patients without diabetes, the risk of stroke/TE in patients with diabetes with no retinopathy increased 1.3-fold (relative risk [RR], 1.30; 95% CI, 1.07-1.59; P = .01); in patients with diabetes with retinopathy, the risk of stroke/TE was increased 1.58-fold (RR, 1.58; 95% CI, 1.07-2.32; P = .02). There was no significant difference when patients with diabetes with no retinopathy were compared with patients with diabetes with retinopathy (RR, 1.21; 95% CI, 0.80-1.84; P = .37). A similar pattern was seen for mortality and severe bleeding. On multivariate analysis, the presence of diabetic retinopathy did not emerge as an independent predictor for stroke/TE or severe bleeding.

CONCLUSIONS:  Crude rates of stroke/TE increased in a stepwise fashion when patients without diabetes and with AF were compared with patients with diabetes with no retinopathy and patients with diabetes with retinopathy. However, we have shown for the first time, to our knowledge, that the presence of diabetic retinopathy did not emerge as an independent predictor for stroke/TE or severe bleeding on multivariate analysis.

Figures in this Article

Atrial fibrillation (AF) confers a fivefold increase in stroke overall, but this risk is not homogeneous and is dependent upon the presence of one or more risk factors in combination with AF.1 Individual stroke risk factors do not necessarily carry a uniform risk weight, and the presence of more “severe” disease with a particular stroke risk factor may confer added weight to stroke risk. For example, hypertension contributes to stroke risk in patients with AF, and the risk is increased with higher quartiles of BP such that those patients with uncontrolled BP have higher risks for stroke and thromboembolism (TE).2

Diabetes mellitus is recognized as a stroke risk factor in AF, scoring one point on the CHADS2 (congestive heart failure, hypertension, age ≥ 75 years, diabetes, prior stroke, or transient ischemic attack) or CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years [doubled], diabetes, stroke [doubled], vascular disease, age 65 to 74 years, and sex category [female]) scores.3 However, diabetes is not a homogeneous entity, and the presence of associated target-organ damage (eg, retinopathy, nephropathy, or neuropathy) indicates more advanced or severe disease.4,5 Given the association with visual loss, patients with diabetes with significant retinopathy are often managed by ophthalmologists, and, indeed, many such patients have an increased risk for systemic cardiovascular complications.4,5 Also, diabetic retinopathy predisposes to ocular bleeding, and one concern is the increased risk of severe bleeding among patients with AF, especially GI bleedings, if oral anticoagulation therapy is used.6

We hypothesized that patients with diabetes with retinopathy and AF have added stroke/TE and severe bleeding risks in AF, when compared with patients with diabetes and AF but no retinopathy or to patients with AF and without diabetes. We tested the hypothesis in a large “real-world” cohort of individuals with AF from the Loire Valley Atrial Fibrillation project.

Study Population

The methods of the Loire Valley Atrial Fibrillation Project, which is based at the Centre Hospitalier Régional et Universitaire in Tours, France, have been previously reported.7 The institution includes four hospitals covering all medical and surgical specialties and is the only public institution in an area of around 4,000 km2, serving approximately 400,000 inhabitants. All patients diagnosed with nonvalvular AF or atrial flutter by the Cardiology Department between 2000 and 2010 were identified.7 Patients with valvular AF were excluded. Treatment at discharge was obtained by screening hospitalization reports, and information on comorbidities was obtained from the computerized coding system. Patients were followed from the first record of nonvalvular AF after January 1, 2000 (ie, index date) up to the latest data collection at the time of study (December 2010).

Diabetes mellitus, with and without retinopathy, was defined from clinical history or medical records. For each patient, the CHADS28 and CHA2DS2-VASc9 scores were calculated. The CHADS2 score was the sum of points obtained after adding one point for congestive heart failure, hypertension, age ≥ 75 years, and diabetes, and two points for previous stroke or TE.9 The CHA2DS2-VASc score was the sum of points after adding one point for congestive heart failure, hypertension, diabetes, vascular disease (including history of coronary, cerebrovascular or peripheral vascular disease), age 65 to 74 years, and female sex, and two points for previous stroke or TE and age ≥ 75 years.9 According to the two risk scores, patients with a score of 0 on either schema were considered as at low risk, 1 as at intermediate risk, and ≥ 2 as at high risk for stroke and TE.

The HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly [> 65 years], drugs [antiplatelet drugs or nonsteroidal antiinflammatory drugs]/alcohol excess concomitantly) score is a validated scoring system for bleeding risk stratification in patients with AF.10 For each patient, the HAS-BLED score was also calculated as the sum of the points obtained after adding one point for the presence of each individual factor. Patients with HAS-BLED score of 0 to 2 were deemed to have low bleeding risk and those with a HAS-BLED score of ≥ 3 were classified as at high bleeding risk.

During follow-up, information on outcomes of TE, that is, stroke (ischemic or hemorrhagic), transient ischemic attack, severe bleeding, and mortality, were recorded. Severe bleeding was defined as a decrease in the blood hemoglobin level of > 5.0 g/dL (including the period around the coronary interventional procedure), the need for transfusion of one or more unit of blood, the need for corrective surgery, the occurrence of an intracranial or retroperitoneal hemorrhage, or any combination of these events.

Statistical Analysis

Risk factors were investigated by Cox regression. Baseline characteristics were determined based on the presence of diabetic retinopathy or not, and differences were investigated using the χ2 test for categorical covariates and Kruskal-Wallis test for continuous covariates.

Event rates of stroke/TE were calculated for all patients. The risk associated with diabetes with or without retinopathy was estimated in Cox proportional-hazard models. Both univariate and multivariate (including all the CHA2DS2-VASc risk factors) Cox regression models were applied. A two-sided P value < .05 was considered statistically significant. All analyses were performed with SPSS statistical software, version 18.0 (IBM Corp).

Ethics Approval

The study was approved by the institutional review board of the Pole Coeur Thorax Vaisseaux from the Trousseau University Hospital (Tours, France) on December 7, 2010, and registered as a clinical audit. Ethical review, therefore, was not required. Patient consent was not sought. Patient data were used only to facilitate the cross referencing of data sources and records were otherwise anonymous. The study was conducted retrospectively, patients were not involved in its conduct, and there was no impact on their care.

Of 8,962 patients with AF in our dataset, 1,409 (16%) had documented diabetes mellitus. As expected, patients with diabetes were older and had more comorbidities, with higher mean CHA2DS2-VASc and HAS-BLED scores (Table 1). Some drug therapies were also more common in patients with diabetes, including antiplatelet drugs, but use of oral anticoagulation therapy was similar between patients with diabetes and patients without diabetes.

Table Graphic Jump Location
TABLE 1 ]  Characteristics of the Patients With Atrial Fibrillation

Data given as No. (%) unless otherwise indicated. ACEI = angiotensin-converting enzyme inhibitor; AF = atrial fibrillation; AT2 = angiotensin 2; CABG = coronary artery bypass grafting; CHA2DS2-VASc = congestive heart failure, hypertension, age ≥ 75 y (doubled), diabetes, stroke/transient ischemic attack/thromboembolism (doubled), vascular disease (prior myocardial infarction, peripheral artery disease, or aortic plaque), age 65 to 74 y, sex category (female); ESC = European Society of Cardiology; HAS-BLED = hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly (> 65 y), drugs (antiplatelet drugs or nonsteroidal antiinflammatory drugs)/alcohol excess concomitantly); ICD = implantable cardioverter defibrillator; LVEF = left ventricular ejection fraction; MI = myocardial infarction.

Of the patients with diabetes, 163 (1.8% of the whole cohort) had diabetic retinopathy (Fig 1). For the risk of stroke/transient ischemic attack/TE, patients with diabetes and diabetic retinopathy were compared with 1,246 patients (13.9%) with diabetes without retinopathy and the 7,553 patients (84.2%) with AF and without diabetes. When patients with diabetes with no retinopathy were compared with those with retinopathy, the latter group had more heart failure (P = .04), renal insufficiency (P < .0001), and COPD (P = .01), with higher mean HAS-BLED score (P = .03) and less antiplatelet therapy use (P = .01). The mean CHA2DS2-VASc score and oral anticoagulation use was not significantly different between the two subgroups with diabetes.

Figure Jump LinkFigure 1 –  Flowchart of study population.Grahic Jump Location
Stroke/TE and Mortality

Rates of adverse events (stroke/TE, mortality, and the composite of stroke and mortality) per 100 person-years according to diabetes status, after a follow-up of 31 months (SD, ± 36 months), are shown in Tables 2-5. Crude event rates increased in a stepwise fashion when patients with AF and without diabetes were compared with patients with diabetes with no retinopathy and patients with diabetes with retinopathy.

Table Graphic Jump Location
TABLE 2 ]  Rates of Adverse End Points per 100 Person-y According to Diabetes Status: Stroke/TE

TE = thromboembolism.

Table Graphic Jump Location
TABLE 3 ]  Rates of Adverse End Points per 100 Person-y According to Diabetes Status: Mortality
Table Graphic Jump Location
TABLE 4 ]  Rates of Adverse End Points per 100 Person-y According to Diabetes Status: Stroke and Mortality
Table Graphic Jump Location
TABLE 5 ]  Rates of Adverse End Points per 100 Person-y According to Diabetes Status: Severe Bleeding

Kaplan-Meier curves showing event rates for stroke/TE in patients with AF and without diabetes, diabetes and no retinopathy, and diabetic retinopathy are shown in Figure 2. When patients without diabetes were compared with patients with diabetes with no retinopathy, the risk for stroke/TE was increased 1.3-fold (relative risk [RR], 1.30; 95% CI, 1.07-1.59; P = .01); when compared with patients with diabetes with retinopathy, the risk for stroke/TE was increased 1.58-fold (RR, 1.58; 95% CI, 1.07-2.32; P = .02). There was no significant difference when patients with diabetes with no retinopathy were compared with patients with diabetes with retinopathy (RR, 1.21, 95% CI, 0.80-1.84; P = .37).

Figure Jump LinkFigure 2 –  Event rates in patients without diabetes, patients with diabetes and no retinopathy, and patients with diabetes with retinopathy. A, Stroke/thromboembolism. B, Mortality. C, Stroke/thromboembolism/death. D, Severe bleeding. RR = relative risk.Grahic Jump Location

When patients without diabetes were compared with patients with diabetes with no retinopathy, mortality was increased 1.37-fold (RR, 1.37; 95% CI, 1.17-1.60; P < .0001), and when compared with patients with diabetes with retinopathy, the risk was nonsignificantly increased 1.25-fold (RR, 1.25; 95% CI, 0.89-1.75; P = .20). There was no significant difference when patients with diabetes with no retinopathy were compared with patients with diabetes with retinopathy (RR, 0.91, 95% CI, 0.64-1.31; P = .62).

Composite of Stroke and TE and Mortality

When patients without diabetes were compared with patients with diabetes with no retinopathy, the combined risk for stroke/TE or death was increased 1.32-fold (RR, 1.32; 95% CI, 1.16-1.51; P < .0001). When compared with patients with diabetes with retinopathy, the risk for stroke/TE was increased 1.39-fold (RR, 1.39; 95% CI, 1.05-1.83; P = .02). There was no significant difference when patients with diabetes with no retinopathy were compared with patients with diabetes with retinopathy (RR, 1.05; 95% CI, 0.78-1.41; P = .76).

Using Cox regression analysis, we calculated the hazard ratios for stroke/TE, with diabetic retinopathy adjusted for CHA2DS2VASc score and concomitant medications. Results are shown in Figure 3. The CHA2DS2VASc score remained a significant predictor for stroke/TE in the whole cohort, if oral anticoagulation therapy was used. The presence of diabetic retinopathy did not emerge as an independent predictor for stroke/TE. Results were similar when renal impairment was added in the model for adjustment (Fig 3). The presence of diabetic retinopathy did not emerge as an independent predictor for mortality (RR, 0.81; 95% CI, 0.57-1.16; P = .25) or for the combined end point of stroke and TE and mortality (RR, 0.92; 95% CI, 0.69-1.23; P = .58) after adjustment for CHA2DS2VASc score and concomitant medications.

Figure Jump LinkFigure 3 –  A, Hazard ratios for stroke/thromboembolism, with diabetic retinopathy adjusted on CHA2DS2VASc score, renal impairment, and concomitant medication. B, Hazard ratios for severe bleeding, with diabetic retinopathy adjusted on HASBLED score, renal impairment, and concomitant medication. CHA2DS2VASc = congestive heart failure, hypertension, age ≥ 75 y (doubled), diabetes, stroke (doubled), vascular disease, age 65 to 74 y, and sex category (female); HASBLED = hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly (> 65 y), drugs (antiplatelet drugs or nonsteroidal antiinflammatory drugs)/alcohol excess concomitantly); VKA = vitamin K antagonist.Grahic Jump Location
Severe Bleeding

Crude rates for severe bleeding according to diabetes status are shown in Table 5. When patients without diabetes were compared with patients with diabetes with no retinopathy, the risk for severe bleeding was increased 1.37-fold (RR, 1.37; 95% CI, 1.13-1.65; P = .001), and when compared with patients with diabetes with retinopathy, the risk for stroke/TE was increased 1.78-fold (RR, 1.78; 95% CI, 1.26-2.52; P = .001). There was no significant difference when patients with diabetes with no retinopathy were compared with patients with diabetes with retinopathy (RR, 1.31; 95% CI, 0.89-1.90; P = .17).

The hazard ratios for severe bleeding with diabetic retinopathy adjusted for HAS-BLED score and concomitant medications, by Cox regression analysis, are shown in Figure 3. The HAS-BLED score remained a significant predictor for severe bleeding in the whole cohort, if oral anticoagulation therapy was used. The presence of diabetic retinopathy did not emerge as an independent predictor for severe bleeding.

To our knowledge, this is the first analysis that has examined the impact of associated diabetic retinopathy on stroke/TE, mortality, and severe bleeding in a large, real-world cohort of patients with AF. First, we show that crude rates of stroke/TE increased in a stepwise fashion when patients with AF but not diabetes were compared with patients with diabetes with no retinopathy and patients with diabetes with retinopathy. Second, the CHA2DS2VASc and HAS-BLED scores in this diabetic cohort remained significant independent predictors for stroke/TE and severe bleeding, respectively, if oral anticoagulation therapy was used. Finally, the presence of diabetic retinopathy did not emerge as an independent predictor for stroke/TE or severe bleeding on multivariate analysis.

AF and diabetes are intimately related, both pathophysiologically and clinically. Patients with diabetes have an approximately 30% to 40% greater risk of developing AF compared with unaffected patients.11 Among patients with diabetes in the Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROactive) trial, the incidence of new-onset AF was 0.87%/y among patients with diabetes with macrovascular disease.12 In contrast, the Women’s Health Study reported that while there was a significant relationship between baseline type 2 diabetes and incident AF, the increased risk was mainly mediated by changes of other AF risk factors over time.13 Both AF or diabetes mellitus individually contribute to stroke risk,14 and when both are present, this is additive to the risk for stroke and TE. Nonetheless, stroke risk stratification schemes such as the CHADS2 and CHA2DS2-VASc scores assume diabetes as a homogeneous risk factor, scoring one point irrespective of disease severity or evidence of diabetes-related target-organ damage.

Diabetic retinopathy has been related to a higher prevalence of diabetes-related target-organ damage.5,15 Indeed, subclinical vascular disease may be a common denominator; while the presence of diabetic nephropathy, neuropathy, retinopathy, left ventricular hypertrophy, left bundle-branch block, and AF were all associated with a subclinical vascular disease (eg, low ankle-brachial index), but only renal disease remained significant after adjusting for age, duration of diabetes, and cardiovascular risk factors.16

In the present analysis, we investigated the incremental impact of diabetic retinopathy (a measure of disease severity in diabetes) on stroke, TE, and/or mortality in a contemporary cohort of real-world patients with AF from a well-established and validated prospective dataset, the Loire Valley AF study. Our findings suggest that we may not need to give extra weight to diabetes-related target-organ damage (eg, retinopathy, renal impairment, vascular disease) when using the CHA2DS2-VASc score for stroke-risk stratification in AF. Also, diabetic retinopathy did not emerge as an independent predictor for severe bleeding, nor did renal impairment. Nonetheless, we did not have unequivocal information about the quality of diabetes control, a fact that could have an impact on stroke and major hemorrhagic events but, on the other hand, reflects the reality of real-life clinical management of these patients, whereby strict control of diabetes may be suboptimal. It is also possible that physicians succeed in equalizing risks and benefits in different patients with diabetes and retinopathy by closer medical management, including those of other risk factors. In any case, the clinician may confidently use the CHA2DS2-VASc and HAS-BLED scores for stroke and bleeding risk assessment, respectively, independent of the presence of diabetic retinopathy or other complications related to diabetes, such as renal impairment.

Study Limitations

This study is based on a real-world registry with a prospective cohort design, but with the well-recognized inherent limitations of diagnostic coding and case ascertainment. Nonetheless, the reliability of the French codification system using diagnosis-related groups (PMSI) has been well validated, and by tracing the trajectory of the patient, we were able to detect and correct inaccuracies, errors, and missing values. For incidence studies, we were able to correct incident cases by removing prevalent cases.17 The study population was also hospital based and, therefore, may not be representative of all patients with AF (especially those nonhospitalized patients) but a high rate of hospitalizations among patients with AF is well recognized.18

Despite adjustment for various risk factors, the nonrandomized design of the study has the potential for residual confounding or confounding by indication.19 For example, the data regarding oral anticoagulant use only regard baseline therapy and do not reflect any changes in prescribed therapy or adherence to therapy. Also, data regarding the time in therapeutic range are not available for our study population. If a resident moved away from the area or died or had a stroke diagnosed elsewhere, information on the event was not available, but the relatively high number of deaths in our study suggests a high proportion of ascertainment of events. Our study was not ethnically diverse and, thus, our observations may not be generalizable to other ethnic populations. Finally, the study had a power to detect a 32% increase in ORs in patients with retinopathy, but the actual ORs were very close to 1.0; hence, beyond statistical power considerations, the difference, if any, would probably not be clinically relevant. Also, we did not assess the severity of retinopathy per se, given the limitations of our observational cohort design.

In this large, real-world cohort of patients with AF, crude rates of stroke/TE increased in a stepwise fashion when patients with AF and without diabetes were compared with patients with diabetes with no retinopathy and patients with diabetes with retinopathy. To our knowledge, we have shown for the first time that the presence of diabetic retinopathy did not emerge as an independent predictor for stroke/TE or severe bleeding on multivariate analysis.

Author contributions: G. Y. H. L. and L. F. had full access to all of the data in the study, and take responsibility for the integrity of the data and the accuracy of the data analysis. G. Y. H. L. contributed to the study concept and drafting the manuscript, and served as principal author; L. F. contributed to data collection and analysis; G. Y. H. L., N. C., B. P., M. B., and L. F. contributed to data interpretation and revising the manuscript, and approved the final manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Prof Lip has served as a consultant for Bayer AG, Astellas Pharma Inc, Merck & Co Inc, AstraZeneca plc, Sanofi SA, Biotronik SE & CoKG, Bristol-Myers Squibb Co/Pfizer Inc, and Boehringer Ingelheim GmbH and has been on the speakers bureau for Bayer AG, Bristol-Myers Squibb Co/Pfizer Inc, Boehringher Ingelheim GmbH, and Sanofi Aventis LLC. Dr Fauchier has served as a consultant for Bayer AG, Medtronic Inc, and Sanofi Aventis LLC, and has received funding for conference travel and educational symposia from Boehringher Ingelheim GmbH, Bayer AG, Medtronic Inc, and Sanofi Aventis LLC. Drs Clementy, Pierre, and Fauchier and Mr Boyer have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

AF

atrial fibrillation

CHADS2

congestive heart failure, hypertension, age ≥ 75 years, diabetes, prior stroke, or transient ischemic attack

CHA2DS2-VASc

congestive heart failure, hypertension, age ≥ 75 years (doubled), diabetes, stroke (doubled), vascular disease, age 65 to 74 years, and sex category (female)

HAS-BLED

hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly (> 65 years), drugs (antiplatelet drugs or nonsteroidal antiinflammatory drugs)/alcohol excess concomitantly)

RR

relative risk

TE

thromboembolism

Lip GY. Stroke and bleeding risk assessment in atrial fibrillation: when, how, and why? Eur Heart J. 2013;34(14):1041-1049. [CrossRef] [PubMed]
 
Lip GY, Frison L, Grind M; SPORTIF Investigators. Effect of hypertension on anticoagulated patients with atrial fibrillation. Eur Heart J. 2007;28(6):752-759. [CrossRef] [PubMed]
 
Pisters R, Lane DA, Marin F, Camm AJ, Lip GY. Stroke and thromboembolism in atrial fibrillation. Circ J. 2012;76(10):2289-2304. [CrossRef] [PubMed]
 
Rydén L, Grant PJ, Anker SD, et al; Authors/Task Force Members; ESC Committee for Practice Guidelines (CPG); Document Reviewers. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur Heart J. 2013;34(39):3035-3087. [CrossRef] [PubMed]
 
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Pfister R, Michels G, Cairns R, Schneider CA, Erdmann E. Incidence of new onset bundle branch block and atrial fibrillation in patients with type 2 diabetes and macrovascular disease: an analysis of the PROactive study. Int J Cardiol. 2011;153(2):233-234. [CrossRef] [PubMed]
 
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Figures

Figure Jump LinkFigure 1 –  Flowchart of study population.Grahic Jump Location
Figure Jump LinkFigure 2 –  Event rates in patients without diabetes, patients with diabetes and no retinopathy, and patients with diabetes with retinopathy. A, Stroke/thromboembolism. B, Mortality. C, Stroke/thromboembolism/death. D, Severe bleeding. RR = relative risk.Grahic Jump Location
Figure Jump LinkFigure 3 –  A, Hazard ratios for stroke/thromboembolism, with diabetic retinopathy adjusted on CHA2DS2VASc score, renal impairment, and concomitant medication. B, Hazard ratios for severe bleeding, with diabetic retinopathy adjusted on HASBLED score, renal impairment, and concomitant medication. CHA2DS2VASc = congestive heart failure, hypertension, age ≥ 75 y (doubled), diabetes, stroke (doubled), vascular disease, age 65 to 74 y, and sex category (female); HASBLED = hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly (> 65 y), drugs (antiplatelet drugs or nonsteroidal antiinflammatory drugs)/alcohol excess concomitantly); VKA = vitamin K antagonist.Grahic Jump Location

Tables

Table Graphic Jump Location
TABLE 1 ]  Characteristics of the Patients With Atrial Fibrillation

Data given as No. (%) unless otherwise indicated. ACEI = angiotensin-converting enzyme inhibitor; AF = atrial fibrillation; AT2 = angiotensin 2; CABG = coronary artery bypass grafting; CHA2DS2-VASc = congestive heart failure, hypertension, age ≥ 75 y (doubled), diabetes, stroke/transient ischemic attack/thromboembolism (doubled), vascular disease (prior myocardial infarction, peripheral artery disease, or aortic plaque), age 65 to 74 y, sex category (female); ESC = European Society of Cardiology; HAS-BLED = hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly (> 65 y), drugs (antiplatelet drugs or nonsteroidal antiinflammatory drugs)/alcohol excess concomitantly); ICD = implantable cardioverter defibrillator; LVEF = left ventricular ejection fraction; MI = myocardial infarction.

Table Graphic Jump Location
TABLE 2 ]  Rates of Adverse End Points per 100 Person-y According to Diabetes Status: Stroke/TE

TE = thromboembolism.

Table Graphic Jump Location
TABLE 3 ]  Rates of Adverse End Points per 100 Person-y According to Diabetes Status: Mortality
Table Graphic Jump Location
TABLE 4 ]  Rates of Adverse End Points per 100 Person-y According to Diabetes Status: Stroke and Mortality
Table Graphic Jump Location
TABLE 5 ]  Rates of Adverse End Points per 100 Person-y According to Diabetes Status: Severe Bleeding

References

Lip GY. Stroke and bleeding risk assessment in atrial fibrillation: when, how, and why? Eur Heart J. 2013;34(14):1041-1049. [CrossRef] [PubMed]
 
Lip GY, Frison L, Grind M; SPORTIF Investigators. Effect of hypertension on anticoagulated patients with atrial fibrillation. Eur Heart J. 2007;28(6):752-759. [CrossRef] [PubMed]
 
Pisters R, Lane DA, Marin F, Camm AJ, Lip GY. Stroke and thromboembolism in atrial fibrillation. Circ J. 2012;76(10):2289-2304. [CrossRef] [PubMed]
 
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