Are Narrower or Wider Retinal Venules Associated With Incident Hypertension?
To the Editor:
Ikram et al1 reported recently that both retinal arteriolar and venular narrowing predict incident hypertension. The relationship between retinal arteriolar narrowing and incident hypertension has been clearly demonstrated in previous studies,2–4 but the reported association between retinal venular narrowing and incident hypertension is new. In fact, studies suggest that prehypertensive damage to the microcirculation leads to chronic retinal hypoperfusion, ischemia, and widening of venular caliber.5 We, therefore, sought to replicate these findings in the Blue Mountains Eye Study, hypothesizing that wider venular caliber is associated with incident hypertension.
We measured retinal vessel calibers in the same way as Ikram et al1 but used a higher blood pressure (BP) threshold to define hypertension (systolic BP ≥160 mm Hg, diastolic BP ≥100 mm Hg, or current use of antihypertensive medications).4 We constructed 2 models containing: (1) covariates plus either arteriolar calibers, venular calibers, or the arteriole-to-venule ratio; and (2) covariates plus both arteriolar and venular calibers simultaneously.
Incident hypertension was detected in 390 of 1319 persons without hypertension at baseline (Table). In model 1, narrower arteriolar caliber and smaller arteriole-to-venule ratio were associated with 5-year incident hypertension but not wider venular caliber. In model 2, incident hypertension was independently associated with not only narrower arteriolar caliber (odds ratio, 1.42; 95% CI, 1.20 to 1.67, per SD decrease in arteriolar caliber) but also with wider retinal venular caliber (odds ratio, 1.28; 95% CI, 1.09 to 1.50, per SD increase in venular caliber).
The stronger association found for narrowing of retinal arterioles and widening of retinal venules in model 2 suggests a confounding effect of arteriolar and venular calibers that was not accounted for in model 1. Arteriolar and venular calibers are correlated (r=0.59), and persons with narrower arterioles are more likely to have narrower venules. This confounding effect may explain the counterintuitive association between retinal venular narrowing and hypertension observed by Ikram et al.1 We now show that after controlling for arteriolar caliber, wider retinal venular caliber was associated with incident hypertension, a result consistent with the pathophysiology of retinal vessel caliber changes. Our findings further highlight the need to understand the role of retinal vascular caliber in relation to risk of hypertension and other cardiovascular conditions.
Sources of Funding
Supported by the Australian National Health and Medical Research Council, Canberra Australia (grants 153948 and 302068).
Ikram MK, Witteman JC, Vingerling JR, Breteler MM, Hofman A, de Jong PT. Retinal vessel diameters and risk of hypertension. The Rotterdam Study. Hypertension. 2006; 47: 189–194.
Smith W, Wang JJ, Wong TY, Rochtchina E, Klein R, Leeder SR, Mitchell P. Retinal arteriolar narrowing is associated with 5-year incident severe hypertension: the Blue Mountains Eye Study. Hypertension. 2004; 44: 442–447.
Saldivar E, Cabrales P, Tsai AG, Intaglietta M. Microcirculatory changes during chronic adaptation to hypoxia. Am J Physiol Heart Circ Physiol. 2003; 285: H2064–H2071.