Research Article
Accumulation of microvascular target organ damage in newly diagnosed hypertensive patients

https://doi.org/10.1016/j.jash.2014.04.008Get rights and content

Abstract

Early identification of hypertensive target organ damage (TOD) emerges as important for global cardiovascular risk assessment. Retinal vascular alterations, capillary rarefaction, and microalbuminuria represent different forms of microvascular TOD. However, data regarding their concomitant presence in the early stages of hypertension, the association of the number of affected organs with cardiovascular risk, and aldosterone effect on multiple TOD are lacking. We studied naïve, never-treated patients with recent duration of hypertension and healthy volunteers. Innovative software was developed to estimate retinal vascular diameters and capillary density. Biochemical parameters including microalbuminuria and serum aldosterone were derived. Framingham Risk Score was used to determine cardiovascular risk. In total 103 subjects, 66 hypertensives and 37 normotensives, were included. Hypertensive patients exhibited a greater number of affected target organs compared with normotensives (P = .014), with retinopathy and capillary rarefaction (40.9%) representing the most common TOD among hypertensives. The number of affected organs was linearly correlated with increased Framingham score and serum aldosterone, analyzed with univariate (P < .001 and P = .002) and multivariate analysis (P = .025 and P = .004), respectively. Physicians dealing with hypertensive patients should be aware of the possibility of diffuse microvascular impairment and seek multiple TOD even in the early stages of hypertension.

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

References (27)

  • T. Sairenchi et al.

    Mild retinopathy is a risk factor for cardiovascular mortality in Japanese with and without hypertension: the Ibaraki Prefectural Health Study

    Circulation

    (2011)
  • A.V. Chobanian et al.

    Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure

    Hypertension

    (2003)
  • G. Mancia et al.

    2013 ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)

    Eur Heart J

    (2013)
  • Cited by (37)

    • Nailfold capillary changes in newly diagnosed hypertensive patients: An observational analytical study

      2021, Microvascular Research
      Citation Excerpt :

      They also reported an improvement in MCD consequent upon treatment. Yet another study by the same group found capillary rarefaction to be significantly associated with an increased Framingham risk score and cardiovascular mortality (Triantafyllou et al., 2014). We did not evaluate these parameters in our study.

    • Early Prediction of Cardiovascular Risk after Hematopoietic Cell Transplantation: Are We There Yet?

      2019, Biology of Blood and Marrow Transplantation
      Citation Excerpt :

      Similarly, ischemic microvascular retinopathy has been recognized as a non-GVHD ocular complication in HCT recipients that needs to be prevented by treating CV risk factors [47]. However, earlier markers of retinal vascular changes with a prognostic value for future CV disease have not been studied [48–51]. Microalbuminuria and left ventricular (LV) mass indicating LV hypertrophy may be easier to access in the clinical setting.

    • Experimental study of blood pressure and its impact on spontaneous hypertension in rats with Xin Mai Jia

      2019, Biomedicine and Pharmacotherapy
      Citation Excerpt :

      As indicated in Fig. 5A, the microvascular diastolic rate induced by 10 mol Ach in the SG was significantly lower than in the WG. XMJ significantly improved the endothelium-dependent microvascular diastolic function of the SHR [24]. The retinal vascular diameter is also an important index to evaluate microvascular remodelling.

    • Obesity-Related Heart Failure With a Preserved Ejection Fraction: The Mechanistic Rationale for Combining Inhibitors of Aldosterone, Neprilysin, and Sodium-Glucose Cotransporter-2

      2018, JACC: Heart Failure
      Citation Excerpt :

      Moreover, adipocytes synthesize aldosterone directly (43), and the increased neprilysin activity in obesity minimizes the influence of natriuretic peptides that can inhibit aldosterone secretion (44). Hyperaldosteronism not only causes sodium retention, but also promotes the accumulation and inflammation of epicardial adipose tissue and the development of microvascular rarefaction and fibrosis in the underlying cardiac muscle (45–50). The transformation of perivisceral fat to a maladaptive proinflammatory phenotype may depend on mineralocorticoid receptor signaling (46–48).

    View all citing articles on Scopus

    Disclosure: none.

    Conflicts of interest: none.

    Grant from the Hellenic Society of Hypertension.

    View full text