Clinical Significance of Altered Vascular Morphology and Function in Normotension

Abstract

Purpose of review: To review current literature examining the presence of subclinical micro- and macrovascular alterations in normotensive individuals and their clinical significance in terms of hypertension prediction. Emphasis is placed on alterations that can be detected in peripheral vascular beds using non-invasive, easily applicable methodology, as these are in general easier to capture and evaluate in clinical practice compared to more complex invasive or functional tests.

Recent findings: Arterial stiffness, increased carotid intima-media thickness, and altered retinal microvascular diameters predict the progression from the normotensive to the hypertensive state. By contrast, there is substantial lack of relevant prospective studies for skin microvascular alterations. Although conclusions regarding causality cannot be safely deduced from available studies, detection of morphological and functional vascular alterations in normotensive individuals emerges as a sensitive indicator of progression to hypertension and hence increased CVD risk. An increasing amount of evidence suggests that early detection of subclinical micro- and macrovascular alterations would be clinically useful for the early identification of individuals at high risk for future hypertension onset. Methodological issues and gaps in knowledge need to be addressed before detection of such changes could guide the development of strategies to prevent new-onset hypertension in normotensive individuals.

Keywords: Albuminuria; Arterial stiffness; Atherosclerosis; Capillary rarefaction; Macrocirculation; Microcirculation; Normotension; Retinopathy.

Fig. 1

Easily accessible vascular beds for the non-interventional, in vivo study of micro- and macrocirculation. Arterial stiffness and carotid intima-media thickness, secondary to changes in the mechanical and anatomical properties of the arterial wall, are the most widely applied, well-established markers of macroangiopathy. The retina, kidney, and the skin may be used as windows to the heart for the study of microcirculation. While measurement of urinary albumin excretion has long been used as an early indicator of generalized microvascular impairment, methodological advances facilitate the extraction of valuable information on microcirculation from images capturing the retinal microvasculature and the skin capillary network

Fig. 2

Subtle alterations of the retinal arteriolar and venular width can be calculated from digital retinal photography by use of appropriately designed software and have been associated with increased risk of future hypertension onset in multitudinal prospective studies. a Obtained from a 38-year-old normotensive male, arteriolar and venular widths are almost equal corresponding to arteriovenous ratio (AVR) of 1.04. b Obtained from a 32-year-old healthy normotensive female, retinal arteriolar narrowing is evident (AVR 0.69). These changes are remarkably similar to those observed in established hypertension, as shown in c from a 32-year-old hypertensive male (AVR 0.725). Figure obtained and provided by authors (ESH Excellent Center: Hypertension Division of the Third Department of Internal Medicine, Aristotle University of Thessaloniki, Papageorgiou General Hospital, Thessaloniki)

Fig. 3

Nailfold capillaroscopy provides valuable information on capillary rarefaction as an index of peripheral microangiopathy. Skin capillary network appears dense in a 48-year-old normotensive female in Fig. 1a. By contrast, capillary rarefaction is evident in a 46-year-old normotensive male presented in Fig. 1b, despite the absence of established hypertension, as is the case in Fig. 1c (48-year-old hypertensive male). Figure obtained and provided by authors (ESH Excellent Center: Hypertension Division of the Third Department of Internal Medicine, Aristotle University of Thessaloniki, Papageorgiou General Hospital, Thessaloniki)