Retinal vessel narrowing linked to hypertension

People with the lowest arteriole-to-venule ratios were more likely to develop hypertension than those with the largest ratios, researchers found.

People with small retinal arteriolar diameters have a higher long-term risk of hypertension than those with larger arterioles, a review of medical studies suggests. A connection between vessel narrowing and age-related maculopathy is also being investigated, although the current evidence is weak and inconsistent, according to researchers.

“The narrowing of blood vessels is an integral part of the mechanism and consequences of hypertension and elevated blood pressure. Thus, we see narrowing not only in the retina, but in the vessels in the skins, muscles and other systems,” said Tien Yin Wong, MD, MPH, PhD, an associate professor of ophthalmology at the University of Melbourne’s Centre for Eye Research Australia and Singapore National Eye Centre, Singapore, in an e-mail interview with Ocular Surgery News.

“The reason blood vessels narrow is that, in a higher pressure environment, the body compensates by decreasing the excessive amount of flow delivered to the tissue beds by narrowing,” Dr. Wong explained.

A less convincing association between blood vessels and maculopathy was seen, he said.

“The link between vessel narrowing and maculopathy is weak. The hypothesis is that maculopathy may develop due to reduced blood flow in the macula region, principally in the choroidal vessels,” Dr. Wong said.

Mild narrowing of retinal arterioles is difficult to detect and less significant, he said. But clinicians should monitor patients with moderate to severe hypertensive retinopathy and refer them to a cardiologist or internist for further check-up, Dr. Wong said.

Beaver Dam Eye Study

A study published in July in the British Medical Journal reports the findings on risk of hypertension in people with small arteriolar-to-venule ratios. Dr. Wong and colleagues studied the relationships between retinal arteriole diameters and the 10-year incidence of hypertension in a population of 2,451 normotensive people who participated in the Beaver Dam Eye Study.

Subjects were examined at baseline and at 10-year follow-up, performed between 1998 and 2000. Initial health examinations recorded patients’ incidence of hypertension (defined as systolic blood pressure greater than or equal to 140 mm Hg, diastolic blood pressure greater than or equal to 90 mm Hg or use of antihypertensive medication during follow-up).

Blood specimens were obtained to check for diabetes and serum concentrations of total cholesterol and high-density lipoprotein cholesterol. Subjects answered questionnaires about their family income, education, history of smoking, physical exercise and alcohol consumption.

Blood vessel measurement

Retinal arteriole and venule diameters were measured from digital retinal photographs.

The study authors said that 30° color retinal photographs of each subject’s right eye taken at baseline were digitized by a high resolution scanner.

“Graders masked to the characteristics of participants used a computer program to measure diameters of all arterioles and venules in a specified zone surrounding the optic disc,” the authors said.

Measurements were combined into average venule and arteriole diameters, and the difference was expressed as a retinal arteriole-to-venule ratio.

An arteriole-to-venule ratio of 1 indicated that arteriolar diameters were, on average, the same as venular diameters in that eye. A smaller ratio suggested narrower arterioles, the authors explained.

Hypertension development

Over a 10-year period, 721 participants in the study developed hypertension.

“After adjustment for age and sex, those who developed incident hypertension had significantly lower mean baseline arteriole:venule ratio (0.69 vs. 0.72, P < .001)="" and="" smaller="" retinal="" arteriolar="" diameter="" (166="" µm="" vs.="" 172.5="" µm,="">P < .001)="" compared="" with="" those="" who="" did="" not="" develop="" hypertension,”="" the="" researchers="" reported.="" in="" contrast,="" they="" noted,="" retinal="" venular="" diameters="" at="" baseline="" did="" not="" differ="" between="" subjects="" who="" developed="" hypertension="" and="" those="" who="" did="">

Patients with arteriole-to-venule ratios in the lowest quarter were three times more likely to develop hypertension than those with a ratios in the highest quarter, the researchers found.

The data provide support for the hypothesis that arteriolar narrowing precedes the development of hypertension in a normal population, the researchers said.

“Our results may have potential clinical implications,” the study authors said. “There is increasing recognition of the value of specifically targeting the microcirculation in the prevention and treatment of hypertension and its complications.” Specifically, they said, angiotensin-converting enzyme inhibitors have beneficial effects on the microvascular structure, and these compounds may have a therapeutic value beyond the lowering of blood pressure.

	Computer imaging (top left) to quantify retinal vessel diameters. Bottom left photo shows narrowed retinal vessels (smaller AV ratio) associated with higher risk of stroke, hypertension and diabetes. Narrowed vessels (AV ratio = 0.59). And photo on the bottom right shows normal-size vessels (AV ratio = 1.1). All images courtesy of Tien Yin Wong, MD, MPH, PhD.

Another study

Another study by Dr. Wong and colleagues, published in February in Annals of Internal Medicine, found a similar link between retinal vessel narrowing and hypertension in a different population.

In the Atherosclerosis Risk in Communities Study, conducted in four U.S. communities, the researchers found a 60% higher risk of developing hypertension in patients with the lowest arteriole-to-venule ratios compared to those with the highest ratios.

“Smaller retinal arteriolar diameters are independently associated with incident hypertension, which suggests that arteriolar narrowing may be linked to the occurrence and development of hypertension,” the authors said in the study abstract.

In the multicenter study, incidence of hypertension in 5,628 participants age 49 to 73 years was assessed at 3-year follow-up. Hypertension was defined by parameters of the Beaver Dam Eye Study. Diameters of retinal vessels were measured according to protocol of the Beaver Dam Eye Study.

By the 36-month follow-up, 811 (14.4%) patients had developed hypertension.

“The incidence of hypertension was higher in persons with lower arteriole-to-venule ratios (incidence of 8.9%, 12.3%, 13.7%, 14.3% and 22.3%, comparing decreasing quintiles of the ratio) and in persons with focal arteriolar narrowing than in those without focal arteriolar narrowing (25.1% vs. 13.0%),” the study authors said.

Maculopathy link

The Beaver Dam researchers also studied the relationship of vessel narrowing to age-related eye disease.

Ronald Klein, MD, and colleagues, including Dr. Wong, examined the relationships between microvascular characteristics associated with systemic hypertension and ocular diseases, including age-related maculopathy.

The microvascular characteristics they studied included arteriole-to-venule ratio, focal retinal arteriolar narrowing, arteriovenous (AV) nicking, retinopathy, central retinal vein equivalent (CRVE) and central retinal artery equivalent (CRAE).

Fundus photographs of 4,926 participants in the Beaver Dam studies were graded. Patients were examined for signs of maculopathy, cataract and glaucoma at baseline and again at 5- and 10-year examinations.

Follow-up markers showed that CRAE narrowing and AV nicking were associated with the incidence of retinal pigment epithelium depigmentation. An additional association was found between CRAE narrowing and AV nicking and nuclear cataract.

The researchers, however, called the associations between microvascular characteristics and eye disease “weak and inconsistent.”

Dr. Wong and colleagues continue their investigations into the relationships among retinal vessel narrowing and hypertension.

“We are developing better computer-based techniques to quantify retinal vessel narrowing and look at how narrowing will provide clues to the risk of stroke, heart disease, diabetes and other diseases,” he said.

For Your Information:

• Tien Yin Wong, MD, MPH, PhD, is an associate professor of ophthalmology at the University of Melbourne, Centre for Eye Research Australia, and Singapore National Eye Centre, Singapore. He can be reached at 32 Gisborne St., East Melbourne 3002, Australia; 61-3-99298352; fax: 61-3-9662-3859; e-mail: ophwty@nus.edu.sg.

References:

• Klein R, Klein BEK, et al. The relation of retinal microvascular characteristics to age-related eye disease: the Beaver Dam eye study. Am J Ophthalmol. 2004;137(3):435-444.
• Wong TY, Klein R, et al. Retinal arteriolar diameter and risk for hypertension. Ann Intern Med. 2004;140(4):248-255.
• Wong TY, Shankar A, et al. Prospective cohort study of retinal vessel diameters and risk of hypertension. BMJ. 2004;329(7457):79-82.

• OSN Staff Writer Nicole Nader covers pediatrics and strabismus and neuro-ophthalmology, in addition to cataract and refractive surgery.