This Article Abstract Full Text (PDF) All Versions of this Article: 42/4/534    most recent 01.HYP.0000090122.38230.41v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, J. J. Articles by Klein, R. Search for Related Content PubMed PubMed Citation Articles by Wang, J. J. Articles by Klein, R. Pubmed/NCBI databases Medline Plus Health Information High Blood Pressure Related Collections Other hypertension Epidemiology

(Hypertension. 2003;42:534.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Hypertensive Retinal Vessel Wall Signs in a General Older Population

The Blue Mountains Eye Study

Jie Jin Wang; Paul Mitchell; Harry Leung; Elena Rochtchina; Tien Yin Wong; Ronald Klein

From the Centre for Vision Research, Department of Ophthalmology and the Westmead Millennium and Save Sight Institutes, the University of Sydney (J.J.W., P.M., H.L., E.R.), Australia; Singapore National Eye Center and National University of Singapore (T.Y.W.), Singapore; and the Department of Ophthalmology and Visual Science, University of Wisconsin-Madison (R.K.), Wis.

Correspondence to Jie Jin Wang, MMed, PhD, Centre for Vision Research, Department of Ophthalmology, University of Sydney, Westmead Hospital, Hawkesbury Road, Westmead, NSW Australia, 2145. E-mail jiejin_wang{at}wmi.usyd.edu.au

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
To describe cross-sectional relations between hypertension and retinal vessel wall signs in an older white population. These signs were defined from fundus photographs in 3654 Blue Mountains Eye Study participants 49 years of age. Focal arteriolar narrowing and arteriovenous nicking were graded through the use of standard protocol. Photographs were digitized to measure retinal vessel diameters. Average arteriolar diameter, summarized as central retinal arteriolar equivalent and arteriole-to-venule ratio, were used as indexes of generalized arteriolar narrowing. Blood pressure was measured with the use of a mercury sphygmomanometer. Hypertension was defined through the use of antihypertensive medications, systolic blood pressure 160 mm Hg, or diastolic blood pressure 95 mm Hg. Hypertension was categorized as controlled (using medication, normal blood pressure), uncontrolled (using medication, high blood pressure), or untreated (not using medication). Hypertensive subjects had higher prevalence of all retinal microvascular signs. After adjusting for age, gender, body mass index, and smoking, persons with controlled (18.2%), uncontrolled (13.8%), or untreated hypertension (13.8%) were significantly more likely than normotensive subjects (54.2%) to have (a) lower central retinal arteriolar equivalent: adjusted odds ratios 1.5, (95% CI, 1.1 to 1.9), 2.1 (1.6 to 2.7), and 2.1 (1.6 to 2.7), respectively, and lower arteriole-to-venule ratio: 1.3 (1.0 to 1.6), 1.4 (1.1 to 1.8), and 1.7 (1.3 to 2.2), respectively; (b) focal arteriolar narrowing: 1.3 (0.9 to 1.9), 2.2 (1.5 to 3.2), and 2.5 (1.8 to 3.6), respectively; and (c) arteriovenous nicking: 1.3 (0.9 to 1.8), 2.3 (1.6 to 3.2), and 1.9 (1.3 to 2.7), respectively. Our findings demonstrate a strong relation between presence and severity of hypertension and retinal microvascular structural changes.

Key Words: age • antihypertensive therapy • arterioles • blood pressure • microcirculation • cross-sectional studies

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Hypertensive retinal microvascular signs include a spectrum of lesions, such as generalized¹ and focal retinal arteriolar narrowing,^1,2 arteriovenous (AV) nicking,³ and retinopathy.^4,5 These signs are important markers of microvascular damage from elevated blood pressure. Previous studies on hypertensive retinal microvascular disease have been mainly conducted on highly selected, clinic-based patients and have used clinical ophthalmoscopy to define vessel wall changes, a method that has poor reproducibility. Recent developments in grading these structural changes from photographs have allowed a more precise documentation of hypertensive retinal microvascular signs in the general population.^3–7

In the Beaver Dam Eye Study (4926 participants, 43 to 86 years of age), nondiabetic subjects with uncontrolled hypertension despite use of antihypertensive medications were more frequently found to have nondiabetic retinopathy lesions, focal arteriolar narrowing, or AV nicking at baseline than those who were normotensive or hypertensive but controlled.³ Incident focal arteriolar narrowing or retinopathy was more likely to develop in these subjects over a 5-year period.⁸

In the Atherosclerosis Risk in Communities (ARIC) Study population (11 114 participants, 48 to 73 years of age at the third examination round), mean arterial blood pressure was significantly associated with focal arteriolar narrowing, AV nicking, and retinopathy, independent of age, gender, race, and smoking.⁶

However, the assessment of early signs of hypertensive retinopathy such as generalized retinal arteriolar narrowing has remained problematic because of limited precision in these largely qualitative grading methods. In the ARIC study, a semiautomated, computer-based technique was developed to measure retinal vessel diameters from digitized photographs. Using this technique, the ARIC Study reported that generalized arteriolar narrowing was strongly associated not only with current blood pressure but also with blood pressure measured 3 years and 6 years before the retinal assessment.⁷ Similar findings were observed in the Cardiovascular Health Study (CHS) population (2056 nondiabetic participants, 69 to 97 years of age).⁹ These data therefore suggest that generalized retinal arteriolar narrowing reflect previously elevated blood pressure and may be a useful indicator of hypertensive severity and control.

In the Blue Mountains Eye Study (BMES), a population-based survey of older white Australians, we previously reported the association of more severe retinopathy lesions (microaneurysms and hemorrhages) and the presence and severity of hypertension in persons without diabetes.⁵ We have now applied the quantitative methods used in the ARIC Study to measure retinal vessel diameters in the BMES.¹⁰ In the current study, we examined the association between hypertension control and presence of retinal vessel wall signs (structural microvascular changes), including generalized retinal arteriolar narrowing, focal arteriolar narrowing, and AV nicking.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
The Blue Mountains Eye study is a population-based cohort study of vision, common eye diseases, and other health outcomes in an urban population 49 years of age. Baseline participants (n=3654) represented 82.4% of those eligible living in two postcodes of the Blue Mountains, west of Sydney, Australia. The study was approved by the Western Sydney Area Human Ethics Committee, and written informed consent was obtained from all participants.¹¹

At the baseline examinations (1992 to 1994), blood pressure (BP) was measured once, using a single mercury sphygmomanometer with an appropriate cuff size, after participants had been seated for at least 10 minutes. Systolic and diastolic blood pressures (SBP and DBP) were recorded from the first and fifth Korotkoff sounds. Mean arterial blood pressure (MABP) was calculated as 0.33 (SBP)+0.67 (DBP). Because this is an older population, we defined hypertension as present in persons who were currently using antihypertensive medications or were found to have SBP 160 mm Hg or DBP 95 mm Hg at the time of the examination. Hypertensive subjects were divided into 3 groups: controlled (using medication, normal BP at examination), uncontrolled (using medication, elevated BP at examination), and untreated (elevated BP at examination but not using medication). Isolated systolic hypertension was defined as present in persons with normal diastolic BP (<95 mm Hg) but with elevated systolic BP (160 mm Hg). Diabetes was diagnosed by either medical history or fasting blood glucose 7.0 mmol/L at the baseline examination. Body weight and height were measured and body mass index (BMI) was calculated as weight (kg)/height (m)².

Dilated 30° stereoscopic retinal photographs of the macula, optic disc, and other retinal fields of both eyes were taken with the use of a Zeiss FF3 fundus camera (Carl Zeiss). Retinal photographs of both eyes were taken in 98% of study participants. Focal arteriolar narrowing and arteriovenous (AV) nicking were graded from 35-mm slides of both eyes by one grader, using a light box (Kelvin rating 6200°) and a Donaldson stereo-viewer with x5 magnification. Only arterioles located at least one half-disc diameter away from the optic disc margin were assessed for focal arteriolar narrowing. Standard photographs for retinal microvascular signs were selected by a retinal specialist from the standard photographic set developed for the Modified Airlie House Classification of Diabetic Retinopathy¹² and the Wisconsin Age-related Maculopathy Grading System.¹³ Focal arteriolar narrowing was graded as absent/questionable (none/less severe than the standard photograph) or present (equal to or more severe than the standard). AV nicking (nipping) was defined as a decrease in venular width on both sides of the venule where crossed by an arteriole and was graded as absent/questionable, mild (less than the standard), or moderate to severe (equal to or greater than the standard). The intragrader reliability for detecting focal arteriolar narrowing and AV nicking were ( statistic) 0.80 and 0.87, respectively. Lesions in the worse eye were chosen to classify the person.

A computer-assisted grading method with high reproducibility was used to measure retinal vessel width. Details of this method have been described previously.^10,14,15 Average retinal arteriolar or venular width (diameter) was calculated by means of the Parr-Hubbard formula^6,16 and is presented as the central retinal arteriolar equivalent (CRAE) or central retinal venular equivalent (CRVE). Arteriovenous ratio (AVR) was calculated from CRAE and CRVE. Generalized retinal arteriolar narrowing was defined as CRAE or AVR within the lowest quintile in the population. Intragrader and intergrader reliability of this method was high,¹⁴ with quadratic weighted values of 0.85 (CRAE) and 0.90 (CRVE) found for intergrader reliability and between 0.80 to 0.93 and 0.80 to 0.92 for intragrader reliability of graders 1 and 2, respectively. Since good correlation in the measurements between right and left eyes was found in our study population previously,¹⁵ we believe that measurement of vessel diameters from one eye is adequate.

Statistical Methods
The Statistical Analysis System (SAS, SAS Institute) was used for statistical analysis. Study variables included MABP (in quintiles) and presence of hypertension. Subjects with controlled, uncontrolled, or untreated hypertension were compared with the normotensive group. Subjects with isolated systolic hypertension were compared with normotensive subjects, after excluding those using antihypertensive medications or with elevated diastolic BP. Logistic regression analysis was performed to assess associations between the hypertension status, MABP, and each of the retinal vessel outcome variables, adjusting for age, gender, BMI, and smoking. Similar analyses were also performed separately for subjects with and without diabetes. Adjusted means of the CRAE and AVR were obtained by covariance analysis (general linear model). Odds ratios, 95% confidence intervals, and adjusted P values for trend are presented.

	Results

Top Abstract Introduction Methods Results Discussion References

 
Of the 3654 BMES baseline participants, 3541 (96.9%) had photographs gradable in at least one eye for focal arteriolar narrowing and AV nicking by means of the manual grading method and 3355 (91.8%) had photographs of at least one eye (mainly the right eye) gradable for generalized arteriolar narrowing by means of the computer-assisted method. There were 40 participants with missing or incomplete blood pressure or hypertension data. Of the 3614 remaining participants, 1858 (54.2%) were normotensive, 659 (18.2%) had controlled hypertension, 498 (13.8%) had uncontrolled hypertension, and 499 (13.8%) had untreated hypertension. Of the 3541 participants with gradable photographs, focal retinal arteriolar narrowing was detected in 280 (7.9%). Mild and moderate to severe AV nicking (nipping) was found in 1415 (40.0%) and 316 (8.9%) of participants, respectively. Diabetes was diagnosed in 281 participants (7.8%). Table 1 shows the proportion of the population with hypertension and retinal vessel wall signs by age group. Prevalence of both uncontrolled and untreated hypertension increased with age. All retinal microvascular signs also demonstrated significant age-related trends except for AVR.

View this table: [in this window] [in a new window]   TABLE 1. Frequency Distribution (%) of Hypertension and Retinal Vessel Wall Signs by Age in the Blue Mountains Eye Study Population

Tables 2 and 3 show the relation between MABP and retinal vessel wall signs in persons with and those without diabetes. After adjusting for age, gender, BMI and smoking, MABP was strongly associated with the presence of all retinal vascular wall signs in persons without diabetes. Compared with subjects with the lowest quintile of MABP, nondiabetic subjects with each higher quintile of MABP had an increasing likelihood of presenting with each of the retinal vessel wall signs. The increasing likelihood (odds ratios) showed a dose-response pattern corresponding to increasing MABP quintiles (P values for trend <0.0001) for all retinal vessel wall signs in subjects without diabetes. Among persons with diabetes, however, only the highest quintile of MABP was significantly associated with the narrowest quintile of central retinal arteriolar equivalent.

View this table: [in this window] [in a new window]   TABLE 2. Retinal Vessel Wall Signs by Quintiles of MAP in the Blue Mountains Eye Study Population, Stratified by Diabetes

View this table: [in this window] [in a new window]   TABLE 3. Generalized Retinal Arteriolar Narrowing by Quintiles of MAP in the Blue Mountains Eye Study Population, Stratified by Diabetes

Tables 4 and 5 show the relations between hypertension and retinal vessel wall signs in persons with and without diabetes. The age- and gender-adjusted mean central retinal arteriolar equivalent was 189, 186, 184, and 183 µm, respectively, among persons with normal blood pressure and controlled, uncontrolled, and untreated hypertension. The age- and gender-adjusted mean arteriole-to-venule ratio was 0.84, 0.83, 0.83, and 0.82, respectively, in the same groups.

View this table: [in this window] [in a new window]   TABLE 4. Retinal Vessel Wall Signs by Hypertension Group in the Blue Mountains Eye Study Population, Stratified by Diabetes

View this table: [in this window] [in a new window]   TABLE 5. Generalized Retinal Arteriolar Narrowing by Hypertension Group in the Blue Mountains Eye Study Population, Stratified by Diabetes

After further adjustment for BMI, smoking, and blood glucose level, the decreasing pattern in mean CRAE, CRVE, and AVR associated with hypertension remained and was similar for women and men (Figures 1, 2, and 3). Table 4 shows that after adjusting for age, gender, BMI, and smoking, nondiabetic subjects with uncontrolled or untreated hypertension were significantly more likely than normotensive subjects to have focal arteriolar narrowing and AV nicking. Table 5 shows that nondiabetic subjects with controlled, uncontrolled, and untreated hypertension were all significantly more likely than normotensive subjects to have generalized arteriolar narrowing. Tables 4 and 5 also demonstrate that nondiabetic persons with isolated systolic hypertension had a similar increased likelihood of having focal or generalized arteriolar narrowing and AV nicking. Among diabetic subjects, only persons with untreated hypertension were significantly more likely to have generalized arteriolar narrowing, as shown in Table 5.

View larger version (17K): [in this window] [in a new window]   Figure 1. Mean (±SE) CRAE by hypertension status and gender after adjusting for age, BMI, smoking, and blood glucose level.

View larger version (18K): [in this window] [in a new window]   Figure 2. Mean (±SE) CRVE by hypertension status and gender after adjusting for age, BMI, smoking, and blood glucose level.

View larger version (18K): [in this window] [in a new window]   Figure 3. Mean (±SE) AVR by hypertension status and gender after adjusting for age, BMI, smoking, and blood glucose level.

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
We previously reported an association between retinopathy lesions and hypertension in persons without diabetes.⁵ In the current report, we investigate retinal vessel wall signs, including focal arteriolar narrowing and AV nicking (assessed using manual grading) and generalized arteriolar narrowing (assessed using a quantitative computer-based method).¹⁴ We have also explored the dose-relation between MABP levels and the likelihood of finding these retinal microvascular signs in persons with and without diabetes, after adjusting for age, gender, smoking, and BMI.

We demonstrated a strong association in this population between elevated blood pressure and the presence of each retinal microvascular sign, as previously reported in participants of the Beaver Dam Eye Study,^3,8 the ARIC study,^6,7 and the CHS.⁹ As in the CHS population, we found a dose-response relation between quintiles of blood pressure and the magnitude of association with each retinal microvascular sign.

In the Beaver Dam Eye Study, persons with uncontrolled or untreated hypertension were more likely to have focal arteriolar narrowing, and persons with untreated hypertension were significantly more likely to have AV nicking.³ Among persons without diabetes in the CHS population, those with uncontrolled or untreated hypertension were more likely to have focal arteriolar narrowing, whereas persons with uncontrolled hypertension were significantly more likely to have AV nicking or retinopathy.⁹ Our data support the findings from both of these studies, with a similar magnitude, a 2-fold higher prevalence of retinal microvascular signs among persons with uncontrolled or untreated hypertension compared with those without hypertension. Furthermore, our study indicates consistent associations across the whole spectrum of retinal microvascular signs for persons with either untreated or uncontrolled hypertension. Although controlled hypertension was not significantly associated with focal arteriolar narrowing or AV nicking, it was significantly associated with generalized arteriolar narrowing in our study. A recent report from the ARIC study documented that blacks have a higher prevalence of hypertensive retinopathy than whites and that the excess prevalence in blacks was partially explained by blood pressure and the severity of hypertension.¹⁷ Since retinal microvascular lesions are correlated with end-organ damage elsewhere^18–25 and independently predict stroke,^26,27 these data further support the importance of adequate control of elevated blood pressure in reducing the morbidity from hypertension.

Our data suggest that the association is strongest among persons without diabetes. The findings are very much in line with the recent report from the CHS.⁹ Among persons with diabetes, both our study and the CHS found weaker associations between blood pressure and most retinal microvascular signs. Both studies, however, had relatively low study power to investigate these associations in persons with diabetes. It is possible that slightly different processes masked the occurrence of retinal microvascular signs in persons with diabetes. For example, retinopathy in persons with diabetes may be more strongly related to blood glucose level and to the duration of diabetes, whereas retinopathy in persons without diabetes appears principally related to blood pressure level.⁵

Although we used standard photographs to grade focal arteriolar narrowing and AV nicking, the methodology in assessing these retinal microvascular signs is relatively subjective, with greater interobserver and intraobserver variability compared with the semiobjective assessment of generalized arteriolar narrowing.⁶ Despite this limitation, however, findings from our study (data not provided) and from the earlier ARIC report indicate that assessment of focal arteriolar narrowing and AV nicking can provide stroke risk information independent of other microvascular risk factors.²⁶

Although our data are cross-sectional, there are a number of biologically plausible mechanisms for the relation between elevated blood pressure or hypertension and retinal arteriolar caliber changes. In response to elevated BP, retinal arteriolar tone can increase through the process of autoregulation, leading to generalized arteriolar narrowing.¹ Persistent BP elevation can lead to hyperplasia, intimal thickening, and hyalinization of the tunica media, thereby reducing the lumen or internal diameter of retinal vessels.²⁸

Recently published longitudinal findings from the ARIC study^22,24–27 and a clinical cohort study²⁹ indicate that retinal microvascular signs carry prognostic information not only for subsequent strokes^26,27 but also for subsequent development of coronary heart disease^22,29 and diabetes.²⁴ In the ARIC study population, a positive association between retinal microvascular signs and cognitive impairment was also documented.²⁵ Retinal microvascular signs may thus predict subsequent development of these end-organ diseases, independent of other vascular risk factors. This is probably due to the unique value of retinal vessel images in providing information on microvascular structural change resulting from elevated blood pressure and other vascular risk factors.²⁰

Perspectives
Data from the Australian Blue Mountains Eye Study support and strengthen recent findings from older US populations (the Beaver Dam Eye Study, ARIC, and CHS) that retinal microvascular signs are strongly related to blood pressure levels or hypertension. The consistency of the findings from population-based studies, including the dose-response relations reported herein, suggest that elevated blood pressure may be involved in the pathogenesis of these lesions. Adequate control of elevated blood pressure in hypertensive subjects is needed to minimize such microvascular damage. The usefulness of careful fundus examination and the potential for quantitative digital imaging of retinal vessels as an independent measure of microvascular damage as well as risk of cerebrovascular, cardiovascular, and other important systemic outcomes merits further exploration.

	Acknowledgments

 
This study was supported by the Australian National Health and Medical Research Council, Canberra Australia (grant No. 153948] and US grants to Klein and coworkers, NIH-EY06594 and HL-59259.

Received June 16, 2003; first decision July 2, 2003; accepted July 28, 2003.

	References

Top Abstract Introduction Methods Results Discussion References

 
1. Parr JC. Hypertensive generalised narrowing of retinal arteries. Trans Ophthalmol Soc N Z. 1974; 26: 55–60.[Medline] [Order article via Infotrieve]

2. Stokoe NL, Turner RW. Normal retinal vascular pattern: arteriovenous ratio as a measure of arterial calibre. Br J Ophthalmol. 1966; 50: 21–40.[Free Full Text]

3. Klein R, Klein BE, Moss SE, Wang Q. Hypertension and retinopathy, arteriolar narrowing, and arteriovenous nicking in a population. Arch Ophthalmol. 1994; 112: 92–98.[Abstract/Free Full Text]

4. Klein R, Klein BE, Moss SE, Wang Q. Blood pressure, hypertension and retinopathy in a population. Trans Am Ophthalmol Soc. 1993; 91: 207–222.[Medline] [Order article via Infotrieve]

5. Yu T, Mitchell P, Berry G, Li W, Wang JJ. Retinopathy in older persons without diabetes and its relationship to hypertension. Arch Ophthalmol. 1998; 116: 83–89.[Abstract/Free Full Text]

6. Hubbard LD, Brothers RJ, King WN, Clegg LX, Klein R, Cooper LS, Sharrett AR, Davis MD, Cai J. Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the Atherosclerosis Risk in Communities Study. Ophthalmology. 1999; 106: 2269–2280.[CrossRef][Medline] [Order article via Infotrieve]

7. Sharrett AR, Hubbard LD, Cooper LS, Sorlie PD, Brothers RJ, Nieto FJ, Pinsky JL, Klein R. Retinal arteriolar diameters and elevated blood pressure: the Atherosclerosis Risk in Communities Study. Am J Epidemiol. 1999; 150: 263–270.[Abstract/Free Full Text]

8. Klein R, Klein BE, Moss SE. The relation of systemic hypertension to changes in the retinal vasculature: the Beaver Dam Eye Study. Trans Am Ophthalmol Soc. 1997; 95: 329–348.[Medline] [Order article via Infotrieve]

9. Wong TY, Hubbard LD, Klein R, Marino EK, Kronmal R, Sharrett AR, Siscovick DS, Burke G, Tielsch JM. Retinal microvascular abnormalities and blood pressure in older people: the Cardiovascular Health Study. Br J Ophthalmol. 2002; 86: 1007–1013.[Abstract/Free Full Text]

10. Leung H, Wang JJ, Rochtchina E, Tan AG, Wong TY, Klein R, Hubbard LD, Mitchell P. Relationships between Age, blood pressure and retinal vessel diameters in an older population. Invest Ophthalmol Vis Sci. 2003; 44: 2900–2904.[Abstract/Free Full Text]

11. Attebo K, Mitchell P, Smith W. Visual acuity and the causes of visual loss in Australia: the Blue Mountains Eye Study. Ophthalmology. 1996; 103: 357–364.[Medline] [Order article via Infotrieve]

12. Diabetic Retinopathy Study Research Group. DRS Report No. 7: a modification of the Airlie House classification of diabetic retinopathy. Invest Ophthalmol Vis Sci. 1981; 21: 210–226.[Medline] [Order article via Infotrieve]

13. Klein R, Davis MD, Magli YL, Segal P, Klein BE, Hubbard L. The Wisconsin age-related maculopathy grading system. Ophthalmology. 1991; 98: 1128–1134.[Medline] [Order article via Infotrieve]

14. Sherry LM, Wang JJ, Rochtchina E, Wong T, Klein R, Hubbard L, Mitchell P. Reliability of computer-assisted retinal vessel measurement in a population. Clin Exp Ophthalmol. 2002; 30: 179–182.[CrossRef][Medline] [Order article via Infotrieve]

15. Leung H, Wang JJ, Rochtchina E, Tan AG, Wong TY, Hubbard LD, Klein R, Mitchell P. Computer-assisted retinal vessel measurement in an older population: correlation between right and left eyes. Clin Exp Ophthalmol. 2003; 31: 326–330.[CrossRef][Medline] [Order article via Infotrieve]

16. Parr JC, Spears GF. General caliber of the retinal arteries expressed as the equivalent width of the central retinal artery. Am J Ophthalmol. 1974; 77: 472–477.[Medline] [Order article via Infotrieve]

17. Wong TY, Klein R, Duncan BB, Nieto FJ, Klein BE, Couper DJ, Hubbard LD, Sharrett AR. Racial differences in the prevalence of hypertensive retinopathy. Hypertension. 2003; 41: 1086–1091.[Abstract/Free Full Text]

18. Wong TY, Klein R, Klein BE, Tielsch JM, Hubbard L, Nieto FJ. Retinal microvascular abnormalities and their relationship with hypertension, cardiovascular disease, and mortality. Surv Ophthalmol. 2001; 46: 59–80.[CrossRef][Medline] [Order article via Infotrieve]

19. Svardsudd K, Wedel H, Aurell E, Tibblin G. Hypertensive eye ground changes: prevalence, relation to blood pressure and prognostic importance: the study of men born in 1913. Acta Med Scand. 1978; 204: 159–167.[Medline] [Order article via Infotrieve]

20. Klein R, Sharrett AR, Klein BE, Chambless LE, Cooper LS, Hubbard LD, Evans G. Are retinal arteriolar abnormalities related to atherosclerosis? The Atherosclerosis Risk in Communities Study. Arterioscler Thromb Vasc Biol. 2000; 20: 1644–1650.[Abstract/Free Full Text]

21. Gillum RF. Retinal arteriolar findings and coronary heart disease. Am Heart J. 1991; 122: 262–263.Editorial.[CrossRef][Medline] [Order article via Infotrieve]

22. Wong TY, Klein R, Sharrett AR, Duncan BB, Couper DJ, Tielsch JM, Klein BE, Hubbard LD. Retinal arteriolar narrowing and risk of coronary heart disease in men and women: the Atherosclerosis Risk in Communities Study. JAMA. 2002; 287: 1153–1159.[Abstract/Free Full Text]

23. Schouten EG, Vandenbroucke JP, Heide-Wessel C, van der Heide RM. Retinopathy as an independent indicator of all-causes mortality. Int J Epidemiol. 1986; 15: 234–236.[Abstract/Free Full Text]

24. Wong TY, Klein R, Sharrett AR, Schmidt MI, Pankow JS, Couper DJ, Klein BE, Hubbard LD, Duncan BB. Retinal arteriolar narrowing and risk of diabetes mellitus in middle-aged persons. JAMA. 2002; 287: 2528–2533.[Abstract/Free Full Text]

25. Wong TY, Klein R, Sharrett AR, Nieto FJ, Boland LL, Couper DJ, Mosley TH, Klein BE, Hubbard LD, Szklo M. Retinal microvascular abnormalities and cognitive impairment in middle-aged persons: the Atherosclerosis Risk in Communities Study. Stroke. 2002; 33: 1487–1492.[Abstract/Free Full Text]

26. Wong TY, Klein R, Couper DJ, Cooper LS, Shahar E, Hubbard LD, Wofford MR, Sharrett AR. Retinal microvascular abnormalities and incident stroke: the Atherosclerosis Risk in Communities Study. Lancet. 2001; 358: 1134–1140.[CrossRef][Medline] [Order article via Infotrieve]

27. Wong TY, Klein R, Sharrett AR, Couper DJ, Klein BE, Liao DP, Hubbard LD, Mosley TH. Cerebral white matter lesions, retinopathy, and incident clinical stroke. JAMA. 2002; 288: 67–74.[Abstract/Free Full Text]

28. Tso MO, Jampol LM. Pathophysiology of hypertensive retinopathy. Ophthalmology. 1982; 89: 1132–1145.[Medline] [Order article via Infotrieve]

29. Duncan BB, Wong TY, Tyroler HA, Davis CE, Fuchs FD. Hypertensive retinopathy and incident coronary heart disease in high risk men. Br J Ophthalmol. 2002; 86: 1002–1006.[Abstract/Free Full Text]

This article has been cited by other articles:

				C. Cuspidi, F. Negri, V. Giudici, and C. Sala Retinal changes and cardiac remodelling in systemic hypertension Therapeutic Advances in Cardiovascular Disease, June 1, 2009; 3(3): 205 - 214. [Abstract] [PDF]

				S. Kaushik, J. J. Wang, T. Y. Wong, V. Flood, A. Barclay, J. Brand-Miller, and P. Mitchell Glycemic Index, Retinal Vascular Caliber, and Stroke Mortality Stroke, January 1, 2009; 40(1): 206 - 212. [Abstract] [Full Text] [PDF]

				G. Liew, A. R. Sharrett, J. J. Wang, R. Klein, B. E. K. Klein, P. Mitchell, and T. Y. Wong Relative Importance of Systemic Determinants of Retinal Arteriolar and Venular Caliber: The Atherosclerosis Risk in Communities Study Arch Ophthalmol, October 1, 2008; 126(10): 1404 - 1410. [Abstract] [Full Text] [PDF]

				J. J. Wang, E. Rochtchina, G. Liew, A. G. Tan, T. Y. Wong, S. R. Leeder, W. Smith, A. Shankar, and P. Mitchell The Long-term Relation among Retinal Arteriolar Narrowing, Blood Pressure, and Incident Severe Hypertension Am. J. Epidemiol., July 1, 2008; 168(1): 80 - 88. [Abstract] [Full Text] [PDF]

				C. Cheng, C. Daskalakis, and B. Falkner Original Research: Capillary rarefaction in treated and untreated hypertensive subjects Therapeutic Advances in Cardiovascular Disease, April 1, 2008; 2(2): 79 - 88. [Abstract] [PDF]

				R Kawasaki, J M Tielsch, J J Wang, T Y Wong, P Mitchell, Y Tano, M Tominaga, T Oizumi, M Daimon, T Kato, et al. The metabolic syndrome and retinal microvascular signs in a Japanese population: the Funagata study Br. J. Ophthalmol., February 1, 2008; 92(2): 161 - 166. [Abstract] [Full Text] [PDF]

				T. T. Nguyen, J. J. Wang, and T. Y. Wong Retinal Vascular Changes in Pre-Diabetes and Prehypertension: New findings and their research and clinical implications Diabetes Care, October 1, 2007; 30(10): 2708 - 2715. [Full Text] [PDF]

				J. J. Wang, G. Liew, R. Klein, E. Rochtchina, M. D. Knudtson, B. E.K. Klein, T. Y. Wong, G. Burlutsky, and P. Mitchell Retinal vessel diameter and cardiovascular mortality: pooled data analysis from two older populations Eur. Heart J., August 2, 2007; 28(16): 1984 - 1992. [Abstract] [Full Text] [PDF]

				G. Liew, A. Shankar, J. J. Wang, R. Klein, M. S. Bray, D. J. Couper, A. R. Sharrett, and T. Y. Wong Apolipoprotein E Gene Polymorphisms and Retinal Vascular Signs: The Atherosclerosis Risk in Communities (ARIC) Study Arch Ophthalmol, June 1, 2007; 125(6): 813 - 818. [Abstract] [Full Text] [PDF]

				P. Mitchell, N. Cheung, K. de Haseth, B. Taylor, E. Rochtchina, F. M. A. Islam, J. J. Wang, S. M. Saw, and T. Y. Wong Blood Pressure and Retinal Arteriolar Narrowing in Children Hypertension, May 1, 2007; 49(5): 1156 - 1162. [Abstract] [Full Text] [PDF]

				S. Kaushik, A. Kifley, P. Mitchell, and J. J. Wang Age, Blood Pressure, and Retinal Vessel Diameter: Separate Effects and Interaction of Blood Pressure and Age Invest. Ophthalmol. Vis. Sci., February 1, 2007; 48(2): 557 - 561. [Abstract] [Full Text] [PDF]

				G. Liew, A. R. Sharrett, R. Kronmal, R. Klein, T. Y. Wong, P. Mitchell, A. Kifley, and J. J. Wang Measurement of Retinal Vascular Caliber: Issues and Alternatives to Using the Arteriole to Venule Ratio Invest. Ophthalmol. Vis. Sci., January 1, 2007; 48(1): 52 - 57. [Abstract] [Full Text] [PDF]

				J J Wang, G Liew, T Y Wong, W Smith, R Klein, S R Leeder, and P Mitchell Retinal vascular calibre and the risk of coronary heart disease-related death Heart, November 1, 2006; 92(11): 1583 - 1587. [Abstract] [Full Text] [PDF]

				N. C. B. B. Taarnhoj, M. Larsen, B. Sander, K. O. Kyvik, L. Kessel, J. L. Hougaard, and T. I. A. Sorensen Heritability of retinal vessel diameters and blood pressure: a twin study. Invest. Ophthalmol. Vis. Sci., August 1, 2006; 47(8): 3539 - 3544. [Abstract] [Full Text] [PDF]

				T. Y. Wong, F. M. A. Islam, R. Klein, B. E. K. Klein, M. F. Cotch, C. Castro, A. R. Sharrett, and E. Shahar Retinal Vascular Caliber, Cardiovascular Risk Factors, and Inflammation: The Multi-Ethnic Study of Atherosclerosis (MESA). Invest. Ophthalmol. Vis. Sci., June 1, 2006; 47(6): 2341 - 2350. [Abstract] [Full Text] [PDF]

				S. Cugati, J. J. Wang, E. Rochtchina, and P. Mitchell Ten-year incidence of retinal vein occlusion in an older population: the blue mountains eye study. Arch Ophthalmol, May 1, 2006; 124(5): 726 - 732. [Abstract] [Full Text] [PDF]

				S. Cugati, J. J. Wang, E. Rochtchina, and P. Mitchell Ten-Year Incidence of Retinal Emboli in an Older Population Stroke, March 1, 2006; 37(3): 908 - 910. [Abstract] [Full Text] [PDF]

				A Grosso, F Veglio, M Porta, F M Grignolo, and T Y Wong Hypertensive retinopathy revisited: some answers, more questions Br. J. Ophthalmol., December 1, 2005; 89(12): 1646 - 1654. [Abstract] [Full Text] [PDF]

				P. Mitchell, J. J. Wang, T. Y. Wong, W. Smith, R. Klein, and S. R. Leeder Retinal microvascular signs and risk of stroke and stroke mortality Neurology, October 11, 2005; 65(7): 1005 - 1009. [Abstract] [Full Text] [PDF]

				T. Y. Wong and R. McIntosh Hypertensive retinopathy signs as risk indicators of cardiovascular morbidity and mortality Br. Med. Bull., September 7, 2005; 73-74(1): 57 - 70. [Abstract] [Full Text] [PDF]

				B.-J. H van den Born, C. A A Hulsman, J. B L Hoekstra, R. O Schlingemann, and G. A van Montfrans Value of routine funduscopy in patients with hypertension: systematic review BMJ, July 9, 2005; 331(7508): 73. [Abstract] [Full Text] [PDF]

				T. Y. Wong and P. Mitchell Hypertensive Retinopathy N. Engl. J. Med., November 25, 2004; 351(22): 2310 - 2317. [Full Text] [PDF]

				W. Smith, J. J. Wang, T. Y. Wong, E. Rochtchina, R. Klein, S. R. Leeder, and P. Mitchell Retinal Arteriolar Narrowing Is Associated With 5-Year Incident Severe Hypertension: The Blue Mountains Eye Study Hypertension, October 1, 2004; 44(4): 442 - 447. [Abstract] [Full Text] [PDF]

				M. K. Ikram, F. J. de Jong, J. R. Vingerling, J. C. M. Witteman, A. Hofman, M. M. B. Breteler, and P. T. V. M. de Jong Are Retinal Arteriolar or Venular Diameters Associated with Markers for Cardiovascular Disorders? The Rotterdam Study Invest. Ophthalmol. Vis. Sci., July 1, 2004; 45(7): 2129 - 2134. [Abstract] [Full Text] [PDF]

				A. V. Chobanian, G. L. Bakris, H. R. Black, W. C. Cushman, L. A. Green, J. L. Izzo Jr, D. W. Jones, B. J. Materson, S. Oparil, J. T. Wright Jr, et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Hypertension, December 1, 2003; 42(6): 1206 - 1252. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) All Versions of this Article: 42/4/534    most recent 01.HYP.0000090122.38230.41v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, J. J. Articles by Klein, R. Search for Related Content PubMed PubMed Citation Articles by Wang, J. J. Articles by Klein, R. Pubmed/NCBI databases Medline Plus Health Information High Blood Pressure Related Collections Other hypertension Epidemiology