Do microvascular retinal changes improve cardiovascular risk estimation?

Abstract

F undoscopic examination is a unique, noninvasive tool allowing the assessment of retinal vessel changes induced by high blood pressure (BP), which, in turn, may reflect cerebral microangiopathic alterations. Mechanical stretch and increased arteriolar transmural pressure combined with metabolic disorders associated with hypertension cause the release from endothelial cells of neurohormonal factors influencing arteriolar smooth muscle and pericyte tone [1]. Locally activated humoral factors, including angiotensin II, endothelin and insulin, induce arteriolar lumen narrowing, apoptosis of vascular smooth muscle cells and vascular fibrosis. Subtle changes in retinal microcirculation, characterized by increased arteriolar wall-to-lumen ratio and venular dilatation, represent an early stage frequently observed in hypertensive retinopathy. More advanced stages of retinopathy, including the 'exudative stage' (i.e. disruption of the blood-retina barrier, exudation of blood and lipids, retinal ischemia) characterized by microaneurysms, hemorrhages, hard exudates, cotton-wool spots and papilloedema, are fortunately rarely found in current hypertension to day [2].Since the pioneering study by Keith et al. [3], showing a strong association between hypertensive retinopathy and incident mortality, a vast amount of data has been accumulated about the clinical and prognostic value of this condition across different clinical settings and ethnicities. In the observational survey by Keith et al.[3], including 219 hypertensive patients, the authors reported a dramatic decline in survival during a 5-year follow-up period from grade 1 to 4 retinopathy. All-cause mortality rate was strongly related to retinopathy, increasing from 30% in grade 1, to 46% in grade 2, 80% in grade 3, up to 99% in grade 4. In the decades from 1950 through 1980, several reports confirmed the association of hypertensive retinal vascular damage with excess cardiovascular morbidity, in particular with stroke [4,5]. These findings, however, have a limited application to contemporary clinical practice, due to a number of limitations. First, retinal alterations were simply defined by fundoscopic examination, a method affected by poor intraobserver and interobserver reproducibility. Second, in older studies, more advanced degrees of retinopathy, including hemorrhages and exudates, were observed in the majority of patients. However, focal or generalized arteriolar narrowing and arteriovenous crossing are the most prevalent retinal alterations observed in contemporary hypertension, more frequently detected than other markers of organ damage with proven prognostic value (i.e. left ventricular hypertrophy, carotid intimamedia thickening or plaques and microalbuminuria). Moreover, the prognostic value of these retinal alterations has been questioned by several cross-sectional studies [6,7]. Thus, the 2007 European Society of Hypertension-European Society of Cardiology guidelines stated that examination of eye grounds is only recommended in patients with severe hyperten...