Research ArticleAccumulation of microvascular target organ damage in newly diagnosed hypertensive patients
Introduction
Hypertension represents the leading cause of morbidity and mortality worldwide, exerting its deleterious effects through its cardiovascular complications. Given that hypertension has been acknowledged as the most important reversible risk factor for cardiovascular diseases,1 early identification of hypertensive target organ damage (TOD) and assessment of global cardiovascular risk emerge as extremely important in terms of life prolongation, quality-of-life improvement, and health-care resources sparing.
A well-promising concept for assessing global cardiovascular risk in hypertension is implementation of quantitative microcirculation measures in everyday clinical practice. Structural and functional changes in small vessels of the retina, skin, and kidney are now considered inherent to hypertension. In particular, several qualitative and quantitative alterations, including arteriolar narrowing and decrease of the arteriovenous ratio (AVR), are observed in the hypertensive fundus,2 and a decreased number of capillaries per area of measurement, described as capillary rarefaction, is typically observed in the skin.3 Both measures are used for the identification of structural changes of the microvasculature, although increased excretion of albumin in urine is traditionally used as an early and reliable index of functional microvascular kidney damage in hypertension.4
Despite the mutual presence of hypertension and microvascular abnormalities, the prevalence of the previously mentioned microvascular changes in the very early stages of essential hypertension is not precisely known. Given that hypertensive retinopathy, capillary rarefaction, and microalbuminuria have been identified as different forms of TOD in hypertensive patients, estimation of their prevalence compared with normotensives emerges as an unbridged gap in the relevant literature. Recently, we showed for the first time that quantitative, more accurately, measured retinal vascular alterations are present even in untreated, otherwise healthy, recently diagnosed hypertensives,5 but whether they frequently coexist with capillary rarefaction and microalbuminuria and to what extent remains unknown.
Furthermore, although the predictive value of each microcirculation index (early-stage hypertensive retinopathy, microalbuminuria) in terms of cardiovascular morbidity and mortality has been validated in several studies,6, 7 not a single study has so far addressed the hypothesis that accumulating microvascular damage indicated by the previously mentioned measures may as well denote increasing cardiovascular risk.
In addition, there is lack of data regarding the identification of potential factors inducing accumulation of multiple microvascular organ damage. Whether activation of the renin-angiotensin-aldosterone system, which is primarily involved in the pathogenesis of hypertensive vascular disease, is associated with the development of multiple microvascular TOD, has not yet been addressed.
Of note, identification of microvascular TOD largely lies on the development of the essential technology that will allow the clinician to visualize retinal and skin vessels routinely, rapidly, and non-invasively and obtain robust microcirculation quantitative measures.
Therefore, the aim of the present study was to examine (1) the prevalence of functional and structural microcirculatory changes in early-stage hypertension compared with normotension, through the simultaneous investigation of the status of small vessels of the kidney, eye, and skin; (2) whether combined microcirculatory damage represents a predictor of increased cardiovascular risk, estimated by the Framingham Risk Score (FRS), even in these early stages and long before the development of cardiovascular complications; and (3) whether an association exists between accumulating microvascular damage and activation of the renin-angiotensin-aldosterone system, in a group of meticulously selected, naïve, never-treated, hypertensive patients and normotensive individuals, confirmed by 24-hour ambulatory blood pressure monitoring (ABPM).
Section snippets
Participant Characteristics
Consecutive patients attending the Hypertension Unit of the 2nd Propedeutic Department of Internal Medicine, Aristotle University, Thessaloniki, were included in the study. All subjects were Caucasian and gave written informed consent. The study was approved by the ethics committee of our University and was conducted in accordance with the principles of the Helsinki declaration. Participants had never been treated with antihypertensive agents and had no other known health problems. Only
Results
In total, 103 subjects with a mean age of 41.8 ± 11.2 years were included in the study. According to their office and ABPM, 66 participants were classified as hypertensives and 37 comprised the normotensive–control group. Baseline demographic and clinical characteristics of the study population are depicted in Table 1.
Discussion
To our knowledge, this is the first study investigating the concomitant presence of different forms of microvascular TOD, both structural (capillary rarefaction, impaired retinal diameter calibers) and functional (microalbuminuria), in a series of “naïve”, never-treated, true, hypertensive patients with only recently established hypertension, compared with their normotensive healthy individuals. This was achieved using easily applicable in the everyday clinical setting methods and specifically
Conclusions
We showed that newly diagnosed patients with recent onset of hypertension exhibit a significantly greater number of affected target organs compared with normotensives, with early-stage hypertensive retinopathy and capillary rarefaction being the most common forms of TOD among hypertensives compared with their normotensive counterparts. Accumulation of multiple microvascular TOD was associated with an aggravated cardiovascular risk profile, underlining the significance of quantifying and
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Disclosure: none.
Conflicts of interest: none.
Grant from the Hellenic Society of Hypertension.