Myocardial performance is impaired in patients with branch retinal vein occlusion

Abstract

Objective

To investigate whether the Tei index, which is an indicator of global myocardial function and an independent predictor of cardiac death, is increased in patients with branch retinal vein occlusion (BRVO).

Methods

The Tei index was used to evaluate myocardial performance, in addition to conventional echocardiographic evaluation of myocardial structural and functional changes, in patients with BRVO, patients with hypertension and healthy controls.

Results

Out of 36 patients with BRVO (18 female, 18 male; 17 hypertensive, 19 normotensive), 29 patients with hypertension (15 female, 14 male) and 28 healthy controls (15 female, 13 male), there were no significant between-group differences in age and sex. The mitral A wave was higher and mitral E/A ratio, mitral E wave and ejection time were lower, in patients with BRVO than in healthy controls. Mean Tei index was significantly higher in the BRVO group than in patients with hypertension or healthy controls. Compared with healthy controls, the Tei index was significantly higher in hypertensive and normotensive patients with BRVO.

Conclusion

Myocardial performance is decreased in patients with BRVO, independent of whether or not they have hypertension.

Keywords

Branch retinal vein occlusion echocardiography myocardial performance Tei index

Introduction

Branch (B) retinal vein occlusion (RVO) is the most common type of RVO, with RVOs being the second main cause (after diabetic retinopathy) of retinal vascular-associated moderate or severe visual loss.^1–3 The exact reason for BRVO remains unclear, however, it may be due to a combination of three primary pathological mechanisms: compression of the venous wall by an adjacent sclerotic retinal arteriole;⁴ degeneration of the vessel wall;⁵ thrombosis of the retinal vein.¹ Classic cardiovascular risk factors (such as diabetes mellitus, hypertension, dyslipidaemia, obesity and haemostatic factors) are reported to play a role in the development of RVOs.⁶ Various medical conditions known to cause atherosclerosis have been associated with BRVO.^7,8 Moreover, some studies with long-term follow-up have reported an increased risk of cardiovascular diseases and associated mortality in patients with BRVO.^8–10 These reports suggest that careful cardiovascular assessment and determination of the factors that help to predict the risk of cardiovascular morbidity and mortality may be useful in the management of patients with retinal vascular disorders such as BRVO.

The Tei index, a noninvasive Doppler-derived myocardial performance index,¹¹ combines both systolic and diastolic function, and may give a better reflection of the global left ventricle function than an isolated evaluation of either ejection or relaxation. The method for obtaining the Tei index is also easily applied, repeatable, and heart-rate independent. An increased Tei index has been shown to be a prognostic index and independent predictor of cardiac death in various heart diseases.^12–16 To the best of our knowledge, however, there have been no reports on the application of these methods in the assessment of patients with BRVO. The aim of the present study was to evaluate myocardial performance using the Tei index in patients with BRVO, and compare findings with evaluations in healthy controls and patients with hypertension.

Patients and methods

Study population

This study, conducted at the Department of Ophthalmology, Faculty of Medicine, Uludag University, Bursa, Turkey, included patients with BRVO, patients with hypertension and healthy control volunteers who were sequentially enrolled between July 2011 and November 2012. Age, sex, body mass index (BMI), systolic and diastolic blood pressure (BP), history of smoking and total cholesterol levels were noted for all study participants. All participants with a history of not smoking for the previous 5 years were determined as nonsmokers. Patients with systolic BP ≥140 mmHg and diastolic BP ≥90 mmHg were classified as hypertensive. Patients who were taking antihypertensive drugs for ≥6 months prior to the start of the study were also defined as hypertensive. Healthy controls comprised volunteers who applied for routine ophthalmic examination in the Department of Ophthalmology, Faculty of Medicine, Uludag University. The same ophthalmologist (B.K.) evaluated all patients with BRVO. Participants in the healthy control and hypertensive groups underwent ophthalmic examination in order to exclude such participants with any retinal vascular occlusion. The same cardiologist (T.S.) systemically evaluated all study participants. Patients and controls meeting the inclusion criteria were included in the study.

Exclusion criteria comprised participants with inflammatory BRVO, a history of BRVO >3 months, retinal vascular disease other than BRVO, and those with abnormalities in any of the following laboratory parameters: glycosylated haemoglobin, fasting blood glucose, erythrocyte sedimentation rate, serum creatinine and urea, computerized blood count, homocysteine, factor V Leiden mutation, thyroxine, parathyroid hormone and antiphospholipid antibodies. Patients with heart failure, systolic left ventricle dysfunction (ejection fraction <55%), moderate or severe valvular heart disease, atrial fibrillation, coronary artery disease, diabetes mellitus, renal failure, connective tissue disease and thyroid or parathyroid dysfunction were also excluded. Another cardiologist (A.A.K.), who was blind to the diagnosis of patients, performed all measurements and echocardiographic examinations.

The procedures used in the present study complied with tenets of the Declaration of Helsinki and approval was obtained from the Uludag University Ethical Committee, Bursa, Turkey. All participants provided written informed consent prior to their participation in the study.

Echocardiographic measurements

Transthoracic echocardiographic evaluation was performed using a GE-Vingmed Vivid 7 system (GE-Vingmed Ultrasound AS, Horten, Norway) with a 2.5–3.5 MHz transducer. Patients lay in the left lateral decubitus position; M-mode traces were recorded at a speed of 50 mm/s and Doppler signals at 100 mm/s. Each representative value was obtained from the mean of three consecutive measurements. Standard two- and four-chamber apical views were used to assess the left ventricular wall motions. Left ventricle diastolic filling patterns were determined by the mitral inflow pulsed-wave Doppler examination. Peak early (E) and late (A) transmitral filling velocities, E/A ratio, and the deceleration time of the E wave velocity (DT) were calculated. The isovolumic relaxation time was measured from closure of the aortic valve to opening of the mitral valve. The isovolumic contraction time was measured from closure of the mitral valve to opening of the aortic valve. Both isovolumic relaxation time and isovolumic contraction time were assessed by simultaneously measuring the flow into the left ventricle outflow tract and mitral inflow by Doppler echocardiography. Ejection time was measured from opening to closure of the aortic valve on the left ventricle outflow velocity profile. The Tei index was equal to the sum of the isovolumic relaxation time and isovolumic contraction time divided by the ejection time.¹⁷ Left ventricle diameters and wall thicknesses were measured with two-dimensional targeted M-mode echocardiography, using the criteria of the American Society of Echocardiography.¹⁸ The left ventricle ejection fraction was computed using the Teicholtz formula.¹⁹

Statistical analyses

Continuous variables were presented as mean ± SD. Normality of data distribution was assessed with Shapiro–Wilk test. Between-group differences in continuous variables were compared with independent-samples t-test and one-way analysis of variance testing (Tukey tests). Nonparametric Mann–Whitney U-test was used to compare variables between subgroups within the BRVO group. Between-group differences in categorical variables were compared with χ²-test. A P value <0.05 was considered to be statistically significant. Statistical analyses were performed with SPSS® statistical software package, version 13.0 (SPSS Inc., Chicago, IL, USA).

Results

The present study comprised 36 patients with BRVO (18 female, 18 male), 29 patients with hypertension (15 female, 14 male) and 28 healthy controls (15 female, 13 male). Age, sex and smoking were similar in all groups (Table 1). BMI, systolic BP and diastolic BP were significantly higher in patients with BRVO and hypertension compared with the healthy controls (P = 0.033 and P = 0.047 for BMI, respectively; P < 0.001 and P = 0.003 for systolic BP and diastolic BP, respectively). There were no significant differences between patients with BRVO and hypertension with regard to BMI, systolic BP and diastolic BP: 21/36 patients (58%) with BRVO had hypertension. Total cholesterol was significantly higher in the hypertension group compared with the BRVO and healthy control groups (P = 0.013 and P = 0.001, respectively). There was no statistically significant difference in total cholesterol between the BRVO group and healthy controls.

Table 1.

Demographic and clinical characteristics of patients with branch retinal vein occlusion (BRVO), patients with hypertension and healthy controls included in a study investigating whether the Tei index is increased in patients with BRVO.

Characteristic	BRVO group n = 36	Hypertension group n = 29	Healthy control group n = 28
Age, years	55.4 ± 8.1	56.7 ± 7	53.8 ± 9.4
Sex, female/male	18/18	15/14	15/13
BMI, kg/m²	29.3 ± 4.3^a	29.2 ± 4.2^b	26.7 ± 3.6
Systolic BP, mmHg	153 ± 28^a	145 ± 23^b	123 ± 14
Diastolic BP, mmHg	91 ± 17^a	87 ± 14^b	74 ± 10
Smoking	9 (25)	9 (31)	7 (25)
Total cholesterol, mg	212.7 ± 34^c	238 ± 25^b	195.5 ± 28

Data presented as mean ± SD, n incidence or n (%).

BMI, body mass index; BP, blood pressure.

P < 0.05, BRVO group versus healthy controls (Tukey’s HSD post hoc test).

P < 0.05, Hypertension group versus healthy controls (Tukey’s HSD post hoc test).

P < 0.05, BRVO group versus hypertension group (Tukey’s HSD post hoc test).

Left-ventricle dimensions, left ventricle ejection fraction and left ventricle wall motions were all within normal limits (Table 2). Thicknesses of interventricular septum and posterior wall were significantly lower in healthy controls than in patients with BRVO (P = 0.047 and P = 0.001, respectively). The hypertension group had significantly thicker posterior walls than healthy controls (P = 0.001). The BRVO and hypertension groups had significantly lower E/A ratios (P < 0.001 for both) and significantly higher mitral A velocities, compared with healthy controls (P < 0.001 and P = 0.001, respectively). Ejection time and mitral E velocity were lower in the BRVO group compared with healthy controls (P < 0.001 and P = 0.031, respectively). Deceleration time, isovolumic relaxation time and isovolumic contraction time were all higher in the BRVO and hypertension groups compared with the healthy controls (P = 0.004 and P = 0.045 for deceleration time, respectively; P < 0.001 and P = 0.001 for isovolumic relaxation time, respectively; P = 0.001 and P = 0.015 for isovolumic contraction time, respectively). The Tei index was significantly higher in the BRVO and hypertension groups compared with the healthy controls (P < 0.001 and P = 0.007, respectively), and significantly higher in the BRVO group compared with the hypertension group (P = 0.007). The Tei index was significantly higher in hypertensive and normotensive BRVO patients compared with healthy controls (P < 0.001 and P = 0.001, respectively).

Table 2.

Echocardiographic parameters in patients with branch retinal vein occlusion (BRVO), patients with hypertension and healthy controls included in a study investigating whether the Tei index is increased in patients with BRVO.

Echocardiographic parameter	BRVO group n = 36	Hypertension group n = 29	Healthy control group n = 28
Left ventricle end diastolic diameter, mm	47.8 ± 4.3	46.5 ± 5.1	47 ± 5.6
Left ventricle end systolic diameter, mm	30.3 ± 4.3	29.6 ± 4.6	31 ± 7.2
Interventricular septum diastolic thickness, mm	14 ± 2.7^a	13.9 ± 2^b	9.5 ± 1.2
Posterior wall diastolic thickness, mm	10.7 ± 2^a	10.7 ± 1.2^b	9.1 ± 1.3
Ejection fraction, %	70 ± 13.9	71.6 ± 7.9	72.9 ± 6.4
Mitral E wave, cm/s	74.5 ± 15.9^a	78.8 ± 15.5	85.1 ± 16.8
Mitral A wave, cm/s	83 ± 17.8^a	81.9 ± 12.4^b	67.4 ± 12.1
E/A ratio	0.95 ± 0.3^a	0.99 ± 0.2^b	1.3 ± 0.4
Deceleration time, ms	215 ± 59^a	205 ± 56^b	171 ± 35
Isovolumic relaxation time, ms	106 ± 25^a	102 ± 14^b	81 ± 14
Isovolumic contraction time, ms	64 ± 23^a	60 ± 17^b	44 ± 20
Ejection time, ms	272 ± 41^a	289 ± 34	307 ± 16
Tei index	0.65 ± 0.2^a,c	0.53 ± 0.1^b	0.40 ± 0.1

Data presented as mean ± SD.

P < 0.05, BRVO group versus healthy controls (Tukey’s HSD post hoc test).

P < 0.05, Hypertension group versus healthy controls (Tukey’s HSD post hoc test).

P < 0.05, BRVO group versus hypertension group (Tukey’s HSD post hoc test).

Discussion

Patients with RVO are known to be at increased risk of cardiovascular disease.^9,10 There is no evidence of cardiovascular disease in the majority of patients with RVO at the time of presentation, however, RVO can be the first sign of developing atherosclerosis. One study showed that patients with RVO had significantly higher generalized cardiovascular disease than would be expected for age matched individuals (standardized risk) and that their coronary heart disease risk was much higher than the observed 10-year incidence of coronary heart disease.²⁰ The absolute risk of coronary heart disease and generalized cardiovascular disease was found to be increased in patients with BRVO compared with patients with central RVO in a subgroup of patients <50 years old.²⁰ Likewise, two-thirds of deaths in RVO patients were due to cardiovascular disease and the incidence of death from myocardial infarction was twice the expected level.¹⁰

A study using carotid artery duplex scanning and echocardiography to evaluate atherosclerosis in patients with central RVO reported that echocardiography revealed a significantly increased prevalence of left ventricular hypertrophy in patients with central RVO (30.8%) compared with controls (5.1%) and concluded that the increased prevalence of hypertension was the responsible factor.²¹ The echocardiographic evaluation consisted of left ventricle diameters, mass, regional wall motions and aortic and mitral valve calcification, which mainly show the morphological changes in the myocardium.²¹ According to the authors’ knowledge, the current study is the first that presents functional impairment of myocardial performance (by means of increased Tei index) in patients with BRVO using pulsed wave Doppler echocardiography.

The Tei index is a prognostic index and an independent predictor of cardiac death due to various diseases.^12–16 In the present study, the Tei index and mitral A velocity were significantly higher, and E/A ratio significantly lower, in BRVO and hypertensive groups compared with healthy controls. Additionally, ejection time was lower in the BRVO group compared with healthy controls. These findings indicate a global decrease of myocardial performance in patients with BRVO. It is well known that hypertension is an independent factor for deteriorating myocardial performance and Tei index.²² Systemic hypertension is an agreed predisposing factor for BRVO, however, some patients with BRVO are normotensive.⁶ Compared with healthy controls, the Tei index was higher in the hypertensive and normotensive patients with BRVO, in the present study. Cardiovascular abnormalities in patients with BRVO have been attributed to hypertension.^6,21 The results of the present study, however, suggest that some systemic abnormalities other than hypertension (such as deterioration of myocardial performance) may play role in the development of cardiovascular diseases in patients with BRVO. Left ventricular dysfunction has been reported in patients with metabolic syndrome, and in patients with normotensive metabolic syndrome or isolated metabolic syndrome (e.g. hyperglycaemia or elevated blood pressure without diabetes mellitus or hypertension).^23,24 In these studies, patients in the isolated metabolic group without diabetes or hypertension had a BMI significantly lower than the metabolic syndrome group, and it was hypothesized that the decreased global ventricular performance may be mediated by other potential mechanisms such as insulin resistance, hypertriglyceridaemia with subsequent impaired endothelial dysfunction, abnormalities in myocardial perfusion and/or metabolic substrate utilization, inflammation and oxidative stress, interstitial fibrosis, and impaired ventricular-vascular interaction.²³ Although patients in the present study were not classified according to the criteria of metabolic syndrome, the BMI in the BRVO (29.3 kg/m²) and hypertensive (29.3 kg/m²) patients was similar to those reported for metabolic syndrome (27.6–31.8 kg/m²) and isolated metabolic syndrome (28.7 kg/m²) in published studies.^23,24 Thus, similar pathogenic mechanisms may apply to the patients in the present study. An evaluation of comorbidities 10 years and 1 year prior to diagnosis of BRVO and the incident comorbidity in a mean period of 7 years following diagnosis in 1168 patients with BRVO, compared results with 118 800 live controls aged ≥40 years.²⁵ Diabetes, hypertension, and peripheral artery disease were associated with an increased risk of developing BRVO up to a decade later. Moreover, BRVO was associated with an increased risk of subsequently developing hypertension, diabetes, congestive heart failure and cerebrovascular disease. The authors stated that the results support the assumption that BRVO is a consequence of arterial thickening and that the arteriovenous crossing signs that precede it are hallmarks of arterial disease.²⁵

Atherosclerosis is an end-stage pathological pathway for many cardiovascular risk factors such as hypertension, hyperlipidaemia, diabetes mellitus, cigarette smoking and obesity.^20,26,27 Evaluation of atherosclerosis may, therefore, provide additional information regarding BRVO pathogenesis and risk factors. Evaluation of a large population of middle-aged healthy subjects,²⁸ showed that greater stiffness of the carotid arteries (which is a marker of early atherosclerosis), is related to generalized narrowing of the retinal arterioles independent of BP and other vascular factors. Retinal arterial narrowing is a marker of arteriolosclerosis, which is one of the probable pathological mechanisms in BRVO.²⁸ In a series of 10 BRVO and 18 age-matched hypertensive patients,²⁹ arterial stiffness was demonstrated to be increased in patients with BRVO. In another study, arterial stiffness (aortic distensibility) and radial artery pulse-wave velocity were found to be impaired in cases of BRVO compared with hypertensive and healthy control participants.³⁰ In addition, the elastic properties of the aorta, pulse-wave velocity and aortic distensibility were shown to be related to increased cardiovascular morbidity and mortality in atherosclerosis, diabetes mellitus and hypertension.^31–34 All these findings suggest that BRVO is associated with cardiovascular risk factors and morbidities, and hypertension is not the only aetiopathological factor for BRVO or impaired myocardial function in patients with BRVO.

Hypercholesterolaemia is another factor associated with increased risk of developing BRVO.^6,35–37 In the present study, patients with hypertension had higher total cholesterol levels than the healthy controls and patients with BRVO. Although the total cholesterol level was numerically higher in the BRVO group compared with healthy controls, the difference was not statistically significant. The relatively low total cholesterol levels in the BRVO group may be related to the relatively small sample size in the present study.

Another risk factor for BRVO is cigarette smoking.^2,38 In the present study there was no difference in smoking rates between the study groups, and this finding concurred with the results of large population-based studies, which reported no association between smoking and the prevalence of RVO.^6,39

A major limitation of the present study was the low number of patients analysed. The medication history, including antihypertensive treatment, was different between patients with hypertension and BRVO, and although not significantly different for antihypertensive drugs, may have influenced the results of the present study.

The results of the present study show that patients with BRVO have decreased global myocardial performance (increased Tei index) independent of the presence of hypertension. An increased Tei index is associated with an increased risk of cardiovascular events in some disorders such as systemic hypertension, metabolic syndrome, diabetes mellitus, chronic obstructive lung diseases and sarcoidosis.^{12–16,22–24} It is possible that a similar relationship might occur in BRVO. General practitioners and ophthalmologists, both of whom are involved in the management of patients with BRVO, should be aware of the importance of BRVO as a marker of progressive cardiovascular disease and focus on prevention, identification and treatment of modifiable risk factors such as hypertension, hyperlipidemia and diabetes.²⁵ Further studies are needed, to confirm the results of the present study and to determine the overall prognostic significance of impaired myocardial performance in patients with BRVO.

Footnotes

Declaration of conflicting interest

The authors declare that there are no conflicts of interest.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for profit sectors.

References

Rehak

. Branch retinal vein occlusion: pathogenesis, visual prognosis, and treatment modalities. Curr Eye Res 2008; 33: 111–131.

Klein

Moss

. The epidemiology of retinal vein occlusion: the Beaver Dam Eye Study. Trans Am Ophthalmol Soc 2000; 98: 133–141.

Mitchell

Smith

Chang

. Prevalence and associations of retinal vein occlusion in Australia. The Blue Mountains Eye Study. Arch Ophthalmol 1996; 114: 1243–1247.

Zhao

Sastry

Sperduto

. Arteriovenous crossing patterns in branch retinal vein occlusion. The Eye Disease Case-Control Study Group. Ophthalmology 1993; 100: 423–428.

Frangieh

Green

Barraquer-Somers

. Histopathologic study of nine branch retinal vein occlusions. Arch Ophthalmol 1982; 100: 1132–1140.

Wong

Larsen

Klein

. Cardiovascular risk factors for retinal vein occlusion and arteriolar emboli: the Atherosclerosis Risk in Communities & Cardiovascular Health studies. Ophthalmology 2005; 112: 540–547.

Dodson

Galton

Hamilton

. Retinal vein occlusion and the prevalence of lipoprotein abnormalities. Br J Ophthalmol 1982; 66: 161–164.

Martin

Rauz

Marr

. Plasma total homocysteine and retinal vascular disease. Eye (Lond) 2000; 14(Pt. 4): 590–593.

Rubinstein

Jones

. Retinal vein occlusion: long-term prospects: 10 years' follow-up of 143 patients. Br J Ophthalmol 1976; 60: 148–150.

10.

Tsaloumas

Kirwan

Vinall

. Nine year follow-up study of morbidity and mortality in retinal vein occlusion. Eye (Lond) 2000; 14(Pt. 6): 821–827.

11.

Tei

Nishimura

Seward

. Noninvasive Doppler-derived myocardial performance index: correlation with simultaneous measurements of cardiac catheterization measurements. J Am Soc Echocardiogr 1997; 10: 169–178.

12.

Poulsen

Jensen

Nielsen

. Serial changes and prognostic implications of a Doppler-derived index of combined left ventricular systolic and diastolic myocardial performance in acute myocardial infarction. Am J Cardiol 2000; 85: 19–25.

13.

Orem

Küçükosmanoğlu

Hacihasanoğlu

. Association of Doppler-derived myocardial performance index with albuminuria in patients with diabetes. J Am Soc Echocardiogr 2004; 17: 1185–1190.

14.

Yeo

Dujardin

Tei

. Value of a Doppler-derived index combining systolic and diastolic time intervals in predicting outcome in primary pulmonary hypertension. Am J Cardiol 1998; 81: 1157–1161.

15.

Moyssakis

Gialafos

Tentolouris

. Impaired aortic elastic properties in patients with systemic sarcoidosis. Eur J Clin Invest 2008; 38: 82–89.

16.

Yilmaz

Gencer

Ceylan

. Impact of chronic obstructive pulmonary disease with pulmonary hypertension on both left ventricular systolic and diastolic performance. J Am Soc Echocardiogr 2005; 18: 873–881.

17.

Tei

Ling

Hodge

. New index of combined systolic and diastolic myocardial performance: a simple and reproducible measure of cardiac function – a study in normals and dilated cardiomyopathy. J Cardiol 1995; 26: 357–366.

18.

Sahn

DeMaria

Kisslo

. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978; 58: 1072–1083.

19.

Teichholz

Kreulen

Herman

. Problems in echocardiographic volume determinations: echocardiographic-angiographic correlations in the presence of absence of asynergy. Am J Cardiol 1976; 37: 7–11.

20.

Martin

Butcher

Martin

. Cardiovascular risk assessment in patients with retinal vein occlusion. Br J Ophthalmol 2002; 86: 774–776.

21.

Rauh

Fischereder

Nasemann

. Evaluation of atherosclerosis in patients with central retinal vein occlusion by carotid artery duplex scanning and echocardiography: a prospective case-control study. Eur J Med Res 1996; 1: 429–432.

22.

Masugata

Senda

Goda

. Independent determinants of the Tei index in hypertensive patients with preserved left ventricular systolic function. Int Heart J 2009; 50: 331–340.

23.

Sliem

Nasr

Ibrahiem

. Global left ventricular performance in non-diabetic non-hypertensive metabolic syndrome adults. World J Cardiol 2011; 3: 48–53.

24.

Voulgari

Moyssakis

Papazafiropoulou

. The impact of metabolic syndrome on left ventricular myocardial performance. Diabetes Metab Res Rev 2010; 26: 121–127.

25.

Bertelsen

Linneberg

Rosenberg

. Comorbidity in patients with branch retinal vein occlusion: case-control study. BMJ 2012; 345: e7885–e7885.

26.

Hayreh

. Prevalent misconceptions about acute retinal vascular occlusive disorders. Prog Retin Eye Res 2005; 24: 493–519.

27.

O’Mahoney

Wong

Ray

. Retinal vein occlusion and traditional risk factors for atherosclerosis. Arch Ophthalmol 2008; 126: 692–699.

28.

Liao

Wong

Klein

. Relationship between carotid artery stiffness and retinal arteriolar narrowing in healthy middle-aged persons. Stroke 2004; 35: 837–842.

29.

Nakazato

Watanabe

Kawana

. Evaluation of arterial stiffness in patients with branch retinal vein occlusion. Ophthalmologica 2005; 219: 334–337.

30.

Kaderli

Gullulu

. Impaired aortic stiffness and pulse wave velocity in patients with branch retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol 2010; 248: 369–374.

31.

O’Rourke

Nichols

. Aortic diameter, aortic stiffness, and wave reflection increase with age and isolated systolic hypertension. Hypertension 2005; 45: 652–658.

32.

Laurent

Boutouyrie

Asmar

. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension 2001; 37: 1236–1241.

33.

Hodes

Lakatta

McNeil

. Another modifiable risk factor for cardiovascular disease? Some evidence points to arterial stiffness. J Am Geriatr Soc 1995; 43: 581–582.

34.

Blacher

Asmar

Djane

. Aortic pulse wave velocity as a marker of cardiovascular risk in hypertensive patients. Hypertension 1999; 33: 1111–1117.

35.

Lim

Cheung

Wang

. Prevalence and risk factors of retinal vein occlusion in an Asian population. Br J Ophthalmol 2008; 92: 1316–1319.

36.

Zhou

Wang

. The 10-year incidence and risk factors of retinal vein occlusion: the Beijing eye study. Ophthalmology 2013; 120: 803–808.

37.

Salaun

Delyfer

Rougier

. Assessment of risk factors for retinal vein occlusions in patients under 60 years of age. J Fr Ophtalmol 2007; 30: 918–923 [in French, English abstract].

38.

Turello

Pasca

Daminato

. Retinal vein occlusion: evaluation of “classic” and “emerging” risk factors and treatment. J Thromb Thrombolysis 2010; 29: 459–464.

39.

You

Liu

. Smoking and retinal vein occlusions. The Beijing Eye Study. Graefes Arch Clin Exp Ophthalmol 2010; 248: 1045–1046.