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Objective: In this analysis of the telehealth-based Vascular health ASsessment Of The hypertENSive patients Registry, we checked how 24-h central and peripheral hemodynamics compare with hypertension-mediated organ damage (HMOD)., Methods: In 646 hypertensive patients (mean age 52 ± 16 years, 54% males, 65% treated) we obtained ambulatory brachial and central SBP and pulse pressure (PP), SBP, and PP variability, pulse wave velocity and augmentation index with a validated cuff-based technology. HMOD was defined by an increased left ventricular mass index (cardiac damage, evaluated in 482 patients), an increased intima-media thickness (vascular damage, n = 368), or a decreased estimated glomerular filtration rate or increased urine albumin excretion (renal damage, n = 388)., Results: Ambulatory SBP and PPs were significantly associated with cardiac damage: the largest odds ratio was observed for 24-h central SBP [1.032 (1.012, 1.051), P = 0.001] and PP [1.042 (1.015, 1.069), P = 0.002], the weakest for brachial estimates. The association was less strong for vascular damage with a trend to the superiority of 24-h central [1.036 (0.997, 1.076), P = 0.070] over brachial PP [1.031 (1.000, 1.062), P = 0.052]. No statistically significant association was observed for renal damage. SBP and PP variabilities, pulse wave velocity and augmentation index were not associated with any form of HMOD. In the multivariate analysis, age was associated with any type of HMOD, whereas central SBP and PP were predictive of an increased risk of cardiac damage., Conclusion: In hypertensive patients a variable association exists between peripheral and central hemodynamics and various types of HMOD, with the most predictive power being observed for central SBP and PP for cardiac damage.

The choroid is the most vascularized structure of the eye and plays a central role in the development of the retinal vascular changes that occur in arterial hypertension. Changes of choroidal thickness (ChT) assessed by optical coherence tomography (OCT) technology could reflect the vascular complications of hypertension. Also, intrarenal hemodynamic damage, associated with endothelial dysfunction, demonstrated to be a good indicator of systemic morphofunctional arterial impairment. The aim of this study is to assess the relationship between ChT and renal hemodynamics in subjects with essential hypertension. Routine laboratory tests, clinical history, and physical examination, including blood pressure assessment, were performed in 90 subjects with essential hypertension. All patients underwent Doppler ultrasonographic evaluation of intra-renal hemodynamics and OCT imaging to assess ChT. When subjects were divided in two groups based on renal resistive index (RRI), group I (RRI ≥ 75% percentile) showed significantly lower values of ChT than group II (RRI < 75% percentile) (P < .001). When divided in two groups based on the ChT median values, patients with lower ChT had significantly higher RRI values than those with ChT above the median values (P < .05). In multivariate model including age, eGFR, and other variables as confounding factors, RRI ≥ 75% was independently associated with ChT. ChT was significantly correlated with renal resistive index in subjects with essential hypertension, confirmed in multivariate analyses. This result could be referred to changes in vascular elastic properties that occur in retinal and intrarenal vascular system probably due to oxidative stress and endothelial dysfunction commonly found in early complications of hypertension., (© 2020 Wiley Periodicals, Inc.)

The kidney is one of the major target organs of hypertension.Kidney damage represents a frequent event in the course of hypertension and arterial hypertension is one of the leading causes of end-stage renal disease (ESRD).ESRD has long been recognized as a strong predictor of cardiovascular (CV) morbidity and mortality. However, over the past 20 years a large and consistent body of evidence has been produced suggesting that CV risk progressively increases as the estimated glomerular filtration rate (eGFR) declines and is already significantly elevated even in the earliest stages of renal damage. Data was supported by the very large collaborative meta-analysis of the Chronic Kidney Disease Prognosis Consortium, which provided undisputable evidence that there is an inverse association between eGFR and CV risk. It is important to remember that in evaluating CV disease using renal parameters, GFR should be assessed simultaneously with albuminuria.Indeed, data from the same meta-analysis indicate that also increased urinary albumin levels or proteinuria carry an increased risk of all-cause and CV mortality. Thus, lower eGFR and higher urinary albumin values are not only predictors of progressive kidney failure, but also of all-cause and CV mortality, independent of each other and of traditional CV risk factors.Although subjects with ESRD are at the highest risk of CV diseases, there will likely be more events in subjects with mil-to-moderate renal dysfunction, because of its much higher prevalence.These findings are even more noteworthy when one considers that a mild reduction in renal function is very common in hypertensive patients.The current European Society of Hypertension (ESH)/European Society of Cardiology (ESC) guidelines for the management of arterial hypertension recommend to sought in every patient signs of subclinical (or asymptomatic) renal damage. This was defined by the detection of eGFR between 30 mL/min/1.73 m 2 and 60 mL/min/1.73 m 2 or the presence of microalbuminuria (MAU), that is an amount of albumin in the urine of 30-300 mg/day or an albumin/creatinine ratio, preferentially on morning spot urine, of 30-300 mg/g.There is clear evidence that urinary albumin excretion levels, even below the cut-off values used to define MAU, are associated with an increased risk of CV events. The relationships of MAU with a variety of risk factors, such as blood pressure, diabetes and metabolic syndrome and with several indices of subclinical organ damage, may contribute, at least in part, to explain the enhanced CV risk conferred by MAU. Nonetheless, several studies showed that the association between MAU and CV disease remains when all these risk factors are taken into account in multivariate analyses. Therefore, the exact pathophysiological mechanisms explaining the association between MAU and CV risk remain to be elucidated. The simple search for MAU and in general of subclinical renal involvement in hypertensive patients may enable the clinician to better assess absolute CV risk, and its identification may induce physicians to encourage patients to make healthy lifestyle changes and perhaps would prompt to more aggressive modification of standard CV risk factors.

The role of systemic vascular involvement in mediating the association between serum uric acid (SUA) and renal function in hypertension has not been explored. Main purpose of our study was to investigate whether morphofunctional vascular changes, assessed as carotid intima-media thickness (cIMT) and aortic pulse wave velocity (aPWV), might mediate the association between SUA and renal damage. We enrolled 523 hypertensive subjects with or without chronic kidney disease and divided population into tertiles of SUA based on sex-specific cutoff values. cIMT and aPWV were higher in uppermost SUA-tertile patients when compared to those in the lowest ones (all P < .001). Uricemia strongly correlated with cIMT and aPWV at univariate analysis (P < .001) and with cIMT after adjustment for confounders (P < .001). Adjustment for cIMT attenuated the relationship between SUA and estimated glomerular filtration rate (P = .019). Systemic vascular changes seem partially to mediate the association between SUA and renal function in hypertensive patients, regardless of kidney function., (Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Background: Structural atherosclerotic damage, arterial stiffness, pulse pressure (PP), and renal hemodynamics may interact and influence each other. Renal resistance index (RRI) appears as a good indicator of systemic vascular changes. The aim of our study was to assess the independent relationships of carotid intima-media thickness (cIMT), aortic pulse wave velocity (aPWV), and peripheral PP with RRI in hypertensives with various degrees of renal function., Methods: We enrolled 463 hypertensive patients (30-70 years) with normal renal function (group 0; n = 280) and with chronic kidney disease (groups I-V; n = 183). All subjects underwent ultrasonographic examination of intrarenal and carotid vasculature, as well as a 24-h ambulatory blood pressure monitoring., Results: A statistically significant difference in RRI, cIMT, aPWV, and clinic PP was observed in the different 6 groups (all P < 0.001), even after adjustment for age. RRI correlated with cIMT (r = 0.460, P < 0.001), aPWV (r = 0.386, P < 0.001), clinic PP (r = 0.279, P < 0.001), and 24-h PP (r = 0.229, P < 0.001) in the entire study population. These correlations were similar in subjects with and without renal dysfunction. In the overall study population, the association between RRI, cIMT, and clinic PP remained statistically significant even after adjustment for various confounding factors, whereas the relationship between RRI and aPWV was lost in multivariate analysis., Conclusions: cIMT and clinic PP rather than directly aPWV are associated with intrarenal hemodynamics. Our results confirm that in hypertensives RRI not only detects derangement of intrarenal circulation but may also be considered as a sensor of systemic vascular changes, independently of level of renal function., (© American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Recent data suggest that renal haemodynamic parameters obtained by duplex Doppler sonography, especially the intrarenal resistive index (RI), may be associated with systemic vascular changes. However, conflicting data exist about the independent relationship between aortic stiffness and RI. The aim of this study was to evaluate the relationship between RI and arterial stiffness, assessed by aortic pulse wave velocity (aPWV), in hypertensive patients., Design: Cross-sectional study., Methods: We enrolled 264 hypertensive subjects aged between 30 and 70 years. They were divided into two groups, either with normal renal function (n = 140) or with chronic kidney disease (CKD) (n = 124). Each patient underwent assessment of ultrasonographic renal RI and measurement of aPWV through oscillometric device., Results: Patients with renal RI>0.7 showed higher values of aPWV, both in the overall population (p < 0.001) and in the subgroups with (p < 0.01) and without CKD (p < 0.01). Moreover, statistically significant correlations were observed between aPWV and RI in the whole population (r = 0.38, p < 0.001) and in the subgroups with (r = 0.35, p < 0.001) and without CKD (r = 0.31, p < 0.001). These correlations held even after adjustment for several confounding factors in multivariate analyses., Conclusions: Our results seem to corroborate the concept that the RI may be considered as a marker of systemic vascular changes and therefore a predictor of cardiovascular risk., (© The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background and Aim: Renal resistance index (RRI), assessed by Duplex-Doppler sonography, has been classically considered as a mere expression of intrarenal vascular resistance. Recent studies, however, have showed that RRI is also influenced by upstream factors, especially arterial compliance, confirming its possible role as a marker of systemic vascular alterations. Several studies have shown that carotid intima-media thickness (cIMT) and carotid plaques (cP), assessed by ultrasonography, are documented markers of subclinical organ damage as well as expression of progressive atherosclerotic disease, and that they get worse with the progressive deterioration of renal function. The study was aimed to evaluate the relationship between RRI and severity of carotid atherosclerosis in hypertensive subjects with and without impaired renal function., Methods and Results: The study population, including 263 hypertensive patients (30-70 years), was split into 3 groups based on cIMT and presence of cP (cIMT ≤ 0.9 mm and no cP; cIMT > 0.9 mm and no cP; cP). All patients were also divided into 2 subgroups (normal renal function; CKD stage I-IV). A stepwise increase in RRI corresponding to the groups of progressive severity of carotid atherosclerosis was observed (respectively 0.61 ± 0.07, 0.65 ± 0.06, 0.68 ± 0.06; p < 0.001). A strong positive correlation was observed between RRI and cIMT in the whole population (r = 0.43; p < 0.001) and in the subgroups with (r = 0.42; p < 0.001) and without (r = 0.39; p < 0.001) CKD. These associations remained statistically significant even after adjustment for various confounding factors., Conclusion: Showing a close association between RRI and severity of carotid atherosclerosis, our results strengthen the concept that RRI is a marker of systemic vascular changes., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Introduction: Cardiovascular diseases are highly prevalent in patients with chronic kidney disease (CKD), and represent the major hazard for mortality in this population. Anomalies of left ventricular (LV) structure and function are very frequent too among CKD patients, and show a negative impact on cardiovascular prognosis., Methods: We searched PubMed for manuscripts regarding left ventricular hypertrophy (LVH) in CKD. Definition of LVH was different according to different studies., Results: In patients with end-stage renal disease, the prevalence of LVH is higher than 70%. Studies in patients with less advanced CKD have reported increasing prevalence of LVH along with declining renal function. However, there is relatively wide heterogeneity in the prevalence of LVH in different studies, according to the characteristics of the population studied, the method chosen to estimate glomerular filtration rate and the definition of LVH., Conclusions: Hypertension, alterations of fluid and electrolyte balance and anemia are identified as the major determinants of LVH in CKD. However, beyond hemodynamic factors, other factors, such as an inappropriate activation of the renin-angiotensin-aldosterone system, oxidative stress, inflammation and collagen and muscle cell growth factors may have a relevant role. LV diastolic dysfunction is also very frequent among CKD patients and is associated with risk of heart failure and with mortality; impairment of diastolic function in patients with CKD may occur very early, even in the absence of LVH. Early detection of LVH and LV dysfunction in CKD could yield an improvement in the adverse cardiovascular outcomes of CKD patients.

Aim: Left ventricular hypertrophy (LVH) is an independent predictor of cardiovascular (CV) morbidity and mortality. The aim of the present study was to evaluate the relationship between LV mass and mild-to-moderate renal dysfunction in a group of non-diabetic hypertensives, free of CV diseases, participating in the Renal Dysfunction in Hypertension (REDHY) study., Methods: Patients with diabetes, a body mass index (BMI) of more than 35 kg/m(2), secondary hypertension, CV diseases and a glomerular filtration rate (GFR) of less than 30 mL/min per 1.73 m(2) were excluded. The final sample included 455 patients, who underwent echocardiographic examination and ambulatory blood pressure monitoring., Results: There was a significant trend for a stepwise increase in LV mass, indexed by both body surface area (LVMI) and height elevated to 2.7 (LVMH(2.7)), with the declining renal function, that remained statistically significant after correction for potential confounders. The prevalence of LVH, defined either as LVMI of 125 g/m(2) or more or as LVMH(2.7) of 51 g/m(2.7) or more, was higher in subjects with lower values of GFR than in those with normal renal function (P < 0.001 in both cases). The multiple regression analysis confirmed that the inverse association between GFR and LVM was independent of confounding factors., Conclusion: The present study confirms the high prevalence of LVH in patients with mild or moderate renal dysfunction. In the patients studied (all with a GFR of 30 mL/min per 1.73 m(2)), the association between LVM and GFR was independent of potential confounders, including 24 h blood pressure load. Taking into account the negative prognostic impact of LVH, further studies focusing on a deeper comprehension of the mechanisms underlying the development of LVH in chronic kidney disease patients are needed.

Background: Hypertension and additional non-traditional risk factors can damage the kidney directly and by promoting atherogenesis. Evidence indicates that increased oxidative stress and inflammation may mediate a large part of the effects of risk factors on the kidney. We hypothesized that in hypertensive patients (HT), oxidative stress, measured as 8-ISO-prostaglandin F2alpha (8-ISO-PGF2alpha), should raise paralleling decreasing renal function and should correlate with estimated glomerular filtration rate (eGFR)., Methods: In 626 HT with renal function ranging from stages 1 to 5 and 100 healthy controls, plasma levels of 8-ISO-PGF2alpha, high-sensitivity C-reactive protein (CRP), transforming growth factor-beta (TGF-beta) and endothelin-1 (ET-1) were measured. GFR was estimated by the Modification of Diet in Renal Disease study equation., Results: When HT were stratified according to renal function stages, 8-ISO-PGF2alpha, CRP, TGF-beta and ET-1 increased progressively and significantly with decreasing eGFR. The multiple regression analysis, considering eGFR as a dependent variable, showed that 8-ISO-PGF2alpha (beta = -0.361, P < 0.000001), ET-1 (beta = -0.197, P < 0.0001) and TGF-beta (beta = -0.170, P < 0.0004) correlated independently with eGFR. All biomarkers were good predictors of eGFR <60 ml/min/1.73 m(2) [receiver-operator-curve (ROC) areas]. ET-1 was shown to be the best predictor with a ROC area = 0.938; with a threshold of 4 pg/ml, 91% sensitivity and 85% specificity were observed, whereas 8-ISO had a ROC area = 0.931, and for a threshold of 329 pg/ml, sensitivity and specificity were 89%, respectively. In contrast, CRP showed the lower predictive value with a ROC area = 0.917; with a threshold of 2.52 mg/l, an 87% sensitivity and an 83% specificity were obtained., Conclusions: Our findings are a clear-cut demonstration of a strong and negative correlation of both oxidative stress and ET-1 with renal function stages in HT. ET-1 and 8-isoprostane are predictive of eGFR.

Aims: We assessed the prevalence of kidney dysfunction evaluated by different methods to estimate glomerular filtration rate (GFR) in a wide group of nondiabetic hypertensive patients, without cardiovascular (CV) complications and without known renal disease, participating in the Renal Dysfunction in Hypertension (REDHY) study., Methods: A total of 1,856 hypertensive individuals (mean age 47 +/- 14 years; men 53%), free from diabetes mellitus and CV complications, and consecutively attending our outpatient hypertension center, were enrolled. Patients with a body mass index >35 (calculated as kg/m(2)) were excluded. The GFR was estimated by the creatinine clearance rate (CrCl), the simplified Modification of Diet in Renal Disease Study prediction equation (MDRD), the Cockcroft-Gault formula (CG) and the Mayo Clinic quadratic equation (Mayo). A 24-hour urine sample was collected to evaluate CrCl and albumin excretion rate (AER). Albuminuria was defined as an AER greater than 20 microg/min., Results: The prevalence of albuminuria was 23.4% (22.7% microalbuminuria and 0.7% macroalbuminuria). Mild renal dysfunction (defined as 24-hour AER >20 microg/min in presence of eGFR > or =60 ml/min per 1.73 m(2)) was found in a proportion of patients ranging from 20.3% using CrCl, to 18.4% using the MDRD equation. The prevalence of overt renal insufficiency (estimated GFR <60 ml/min per 1.73 m(2)) was higher when CrCl (10.8%) or the MDRD equation (10%) was used to estimate the GFR, instead of the CG (7.4%) or Mayo equation (5.4%) (p<0.0001)., Conclusions: Mild renal dysfunction and overt renal insufficiency are highly prevalent among subjects with nonmalignant arterial hypertension without CV complications. However, the prevalence of moderate-to-severe renal function impairment is strongly influenced by the method used to estimate the GFR.

Objective: To analyse the relationships between 24 h blood pressure load (the percentage of systolic/diastolic blood pressures exceeding 140/90 mmHg while awake and 120/80 mmHg during sleep) and some indices of hypertensive target organ involvement, independently of the mean level of 24 h blood pressure., Methods: One hundred and thirty patients with mild-to-moderate hypertension underwent 24 h ambulatory blood pressure monitoring, ocular fundus examination, microalbuminuria assay and two-dimensional guided M-mode echocardiography. The study population was divided into subsets according to the systolic and diastolic 24 h blood pressure load values predicted from the regression equation relating 24 h blood pressure load to 24 h mean blood pressure. The subjects with an observed load above this predicted value were included in the higher blood pressure load groups, the remaining ones being included in the lower groups., Results: Relative myocardial wall thickness and total peripheral resistance were greater, and mid-wall fractional shortening, end-systolic stress-corrected mid-wall fractional shortening and cardiac index lower, in the subjects with a higher systolic blood pressure load. Moreover, the stroke index:pulse pressure ratio was reduced, and a greater prevalence of hypertensive retinopathy was observed in the higher systolic load group. On the contrary, no statistically significant difference was found for any of the cardiac, renal and funduscopic parameters examined when the two groups with a higher and lower 24 h diastolic blood pressure load were compared., Conclusions: Our results seem to suggest that, in mild-to-moderate arterial hypertension, a high 24 h systolic blood pressure load may be associated, independently of the average level of 24 h systolic ambulatory blood pressure, with an adverse cardiovascular risk profile.