Structural alterations in subcutaneous small resistance arteries predict changes in the renal function of hypertensive patients

Boari, Gianluca E.M.; Rizzoni, Damiano; Ciuceis, Carolina De; Porteri, Enzo; Avanzi, Daniele; Platto, Caterina; Mazza, Monica; Brignani, Alida; Rosei, Claudia Agabiti; Ricotta, Doris; Caimi, Luigi; Rosei, Enrico Agabiti

doi:10.1097/hjh.0b013e32833c2177

Cited by 19 publications

(15 citation statements)

References 41 publications

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“…Regardless of the underlying mechanism, a loss of large artery function also results in a reduced capacity of the system to buffer pulsatile changes in BP, with vulnerable end organs at risk of microvascular damage, particularly in the kidney and brain (36). Microvasculature damage results in altered capillary proliferation, increased thrombosis, and vasomotor dysfunction (8), all of which are characteristic features of aging (2). In addition, capillary rarefaction in peripheral beds could further increase peripheral resistance, contributing to hypertension and arterial stiffness (3), as well as being related to efficacy of antihypertensive treatment (14).…”

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confidence: 99%

Aortic stiffness is associated with vascular calcification and remodeling in a chronic kidney disease rat model

Hildreth

Phillips

et al. 2011

American Journal of Physiology-Renal Physiology

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Increased aortic pulse-wave velocity (PWV) reflects increased arterial stiffness and is a strong predictor of cardiovascular risk in chronic kidney disease (CKD). We examined functional and structural correlations among PWV, aortic calcification, and vascular remodeling in a rodent model of CKD, the Lewis polycystic kidney (LPK) rat. Hemodynamic parameters and beat-to-beat aortic PWV were recorded in urethane-anesthetized animals [12-wk-old hypertensive female LPK rats (n = 5)] before the onset of end-stage renal disease and their age- and sex-matched normotensive controls (Lewis, n = 6). Animals were euthanized, and the aorta was collected to measure calcium content by atomic absorption spectrophotometry. A separate cohort of animals (n = 5/group) were anesthetized with pentobarbitone sodium and pressure perfused with formalin, and the aorta was collected for histomorphometry, which allowed calculation of aortic wall thickness, medial cross-sectional area (MCSA), elastic modulus (EM), and wall stress (WS), size and density of smooth muscle nuclei, and relative content of lamellae, interlamellae elastin, and collagen. Mean arterial pressure (MAP) and PWV were significantly greater in the LPK compared with Lewis (72 and 33%, respectively) animals. The LPK group had 6.8-fold greater aortic calcification, 38% greater aortic MCSA, 56% greater EM/WS, 13% greater aortic wall thickness, 21% smaller smooth muscle cell area, and 20% less elastin density with no difference in collagen fiber density. These findings demonstrate vascular remodeling and increased calcification with a functional increase in PWV and therefore aortic stiffness in hypertensive LPK rats.

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confidence: 99%

Aortic stiffness is associated with vascular calcification and remodeling in a chronic kidney disease rat model

Hildreth

Phillips

et al. 2011

American Journal of Physiology-Renal Physiology

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“…Another proposed mechanism is the progressive reduction in renal blood flow in patients with LVH, particularly in those with concentric geometry, accompanying a hemodynamic pattern with reduced stroke volume and increased peripheral resistance. Recent data indicate that the media-to-lumen ratio of small resistance arteries in hypertensive patients is not only related with indices of renal function, but also predicts changes in renal function over time [58]. …”

Section: Pathophysiologic Mechanisms Underlying Preclinical Cardiorenmentioning

confidence: 99%

Preclinical Cardiorenal Interrelationships in Essential Hypertension

et al. 2013

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A diseased heart causes numerous adverse effects on kidney function, and vice versa renal disease can significantly impair cardiac function. Beyond these heart-kidney interrelationships at the clinical level, a reciprocal association has been suggested to exist even in the early stages of those organs' dysfunction. The aim of the present review is to provide evidence of the presence of a preclinical cardiorenal syndrome in the particular setting of essential hypertension, focusing on the subsequent hypertensive sequelae on heart and kidneys. In particular, a plethora of studies have demonstrated not only the predictive role of kidney damage, as expressed by either decreased glomerular filtration or increased urine albumin excretion, for adverse left ventricular functional and structural adaptations but also preclinical heart disease, i.e. left ventricular hypertrophy that is associated with deterioration of renal function. Notably, these reciprocal interactions seem to exist even at the level of microcirculation, since both coronary flow reserve and renal hemodynamics are strongly related with clinical and preclinical renal and cardiac damage, respectively. In this preclinical setting, common pathophysiological denominators, including the increased hemodynamic load, sympathetic and renin-angiotensin system overactivity, increased subclinical inflammatory reaction, and endothelial dysfunction, account not only for the reported associations between overt cardiac and renal damage but also for the parallel changes that occur in coronary and renal microcirculation.

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“…The most novel information provided by the study of Boari et al [11] is the evidence that at the baseline evaluation, media-to-lumen ratio of small resistance arteries in subcutaneous tissue correlates not only with blood pressure values but also with indices of renal function such as serum creatinine and blood urea nitrogen. An inverse correlation was found with estimated glomerular filtration rate (calculated with the Modification of Diet Renal in Disease formulae).…”

Section: Media-to-lumen Ratio: a New Marker Of Renal Function?mentioning

confidence: 99%

“…Another result of the study deserving a comment is the evidence that in both patients with diabetes (about 45% of the entire population enrolled in the study) and nondiabetic patients, percentage and mean yearly changes in estimated glomerular filtration rate did not correlate with media-to-lumen ratio [11]. This indicates that the two phenomena develop at different rates, resulting in different temporal patterns.…”

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confidence: 93%

“…In the present issue of the Journal, Boari et al [11] report a study in which they evaluated retrospectively the behavior of the media-to-lumen ratio of small arteries in normotensive and hypertensive patients in relation to changes in renal function during follow-up. The data provide evidence that patients who exhibit a reduced media-to-lumen ratio are at greater risk of developing reduced renal function.…”

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confidence: 99%

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Media-to-lumen ratio as predictor of renal abnormalities in hypertension: new findings, new questions

Schiffrin

2010

Journal of Hypertension

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An important condition for a marker of subclinical organ damage to be considered for the assessment of patients' cardiovascular risk profile and as a surrogate endpoint in hypertension is its ability to predict future cardiovascular events. This requirement is fulfilled by several markers of end-organ damage, such as electrocardiographic or echocardiographic left ventricular mass, left ventricular diastolic dysfunction, carotid intima-media thickness, arterial stiffness, ankle-brachial index, endothelial dysfunction, glomerular filtration rate and microalbuminuria [1]. Similar evidence, albeit less consistently, has also been shown for another marker of target-organ damage affecting microcirculation, that is, the media-to-lumen ratio of small resistance arteries with a lumen diameter measuring less than 400 mm. Studies [2-4] performed by different investigators have shown that structural alterations of subcutaneous small resistance arteries of humans with essential or secondary hypertension are able, during a follow-up ranging from 6 to 10 years, to independently predict fatal and nonfatal cerebrovascular and coronary events. Structural alterations of small resistance arteries may precede and, with time, be associated with the development and progression of hypertension-related target-organ damage in different vascular beds, such as the brain, the heart and large arteries [5][6][7]. Taken together, these findings indicate that small artery remodelling is linked to cardiovascular prognosis and targetorgan damage in different areas of the cardiovascular system ( Figure 1). Surprisingly, the prognostic relevance played by the small resistance artery network appears to be confined to changes in structure of these vessels, although this remains controversial. In a study published a few years ago by Rizzoni et al.[8] with a follow-up averaging 5.5 years, endothelium-dependent vasodilatation was similarly impaired in hypertensive patients who developed or did not develop cardiovascular events, indicating that endothelial dysfunction in the microcirculation appeared unrelated to cardiovascular events. This is, however, in contrast with the evidence that endothelial dysfunction assessed in large-size and medium-size arteries may indeed represent a marker of future coronary events [9,10].In the present issue of the Journal, Boari et al.[11] report a study in which they evaluated retrospectively the behavior of the media-to-lumen ratio of small arteries in normotensive and hypertensive patients in relation to changes in renal function during follow-up. The data provide evidence that patients who exhibit a reduced media-to-lumen ratio are at greater risk of developing reduced renal function. The predictive value of microvascular alterations was confirmed by stepwise multivariate regression analysis, which identified the mediato-lumen ratio as the variable most closely related to time-dependent changes in renal function. Media-to-lumen ratio: a new marker of renal function?The most novel information provided by the study of B...

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Structural alterations in subcutaneous small resistance arteries predict changes in the renal function of hypertensive patients

Abstract: Our data suggest that structural alterations in subcutaneous small arteries may predict the time course of changes in renal function during a follow-up period of about 9 years.

Cited by 19 publications

References 41 publications

Aortic stiffness is associated with vascular calcification and remodeling in a chronic kidney disease rat model

Aortic stiffness is associated with vascular calcification and remodeling in a chronic kidney disease rat model

Preclinical Cardiorenal Interrelationships in Essential Hypertension

Media-to-lumen ratio as predictor of renal abnormalities in hypertension: new findings, new questions

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