Santina Cottone

Association of renal resistive index with aortic pulse wave velocity in hypertensive patients.

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 (nu2009=u2009140) or with chronic kidney disease (CKD) (nu2009=u2009124). 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 (pu2009<u20090.001) and in the subgroups with (pu2009<u20090.01) and without CKD (pu2009<u20090.01). Moreover, statistically significant correlations were observed between aPWV and RI in the whole population (ru2009=u20090.38, pu2009<u20090.001) and in the subgroups with (ru2009=u20090.35, pu2009<u20090.001) and without CKD (ru2009=u20090.31, pu2009<u20090.001). 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.

Plasma aldosterone and its relationship with left ventricular mass in hypertensive patients with early-stage chronic kidney disease

Plasma aldosterone concentrations (PACs) are often increased in the advanced stages of chronic kidney disease (CKD); however, PAC has not been fully investigated in early CKD. Moreover, little is known about the relationship between aldosteronemia and left ventricular (LV) mass in subjects with mild-to-moderate CKD. The study objectives were to analyze PAC, LV mass (LVM), LV geometry and their relationships, in a group of hypertensive patients with stage I–III CKD. One hundred ninety-five hypertensive patients with stage I–III CKD were enrolled and compared with a control group of 82 hypertensive patients without renal dysfunction. LVM was higher in subjects with CKD than in the control group and increased progressively with advancing stages of CKD (P=0.004). A similar trend was observed for PAC (P<0.0001), in which PAC was greater in CKD subjects with LV concentric geometry than in those with eccentric LV hypertrophy (P=0.01). Furthermore, in CKD patients, PAC was directly and significantly correlated with LVM (r=0.29; P<0.0001) and with relative wall thickness (RWT; r=0.36; P<0.0001). These associations remained significant even after adjustment for various confounding factors in multiple regression analyses (P<0.001). In summary, the results demonstrated that in CKD hypertensive patients, LVM, RWT and PAC are increased and related to each other from the earliest stages of renal dysfunction. Furthermore, it seems biologically plausible to speculate that aldosterone may promote a concentric geometry of the left ventricle and increase LVM in hypertensive patients with early CKD.

Association Between Uric Acid and Renal Hemodynamics: Pathophysiological Implications for Renal Damage in Hypertensive Patients

The role of vascular renal changes in mediating the association between serum uric acid (SUA) and renal damage is unclear. The purposes of this study were to investigate the relationship between SUA and renal resistive index (RRI), assessed by duplex Doppler ultrasonography, and to assess whether hemodynamic renal changes may explain the association between SUA and renal damage in hypertensive patients. A total of 530 hypertensive patients with and without chronic kidney disease were enrolled and divided into SUA tertiles based on sex‐specific cutoff values. RRI and albuminuria were greater and glomerular filtration rate (GFR) was lower in the uppermost SUA tertile patients when compared with those in the lowest tertiles (all P<.001). Moreover, SUA strongly correlated with RRI (P<.001) in all patients. However, RRI did not seem to explain the relationship between SUA and renal damage, and GFR significantly related with SUA in the overall population (P<.001) even after adjustment for RRI.

Relationship Between Carotid Atherosclerosis and Pulse Pressure with Renal Hemodynamics in Hypertensive Patients.

BACKGROUNDnStructural 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.nnnMETHODSnWe 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.nnnRESULTSnA 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.nnnCONCLUSIONSncIMT 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.

Average real variability of 24-h systolic blood pressure is associated with microalbuminuria in patients with primary hypertension

Limited and conflicting data are available about the association between short-term blood pressure (BP) variability and urinary albumin excretion rate (uAER). The objective of our study was to analyze the relationships between microalbuminuria (MAU), defined as an uAER between 20 and 200u2009μgu2009min−1, and short-term BP variability (BPV), assessed as average real variability (ARV), weighted s.d. of 24-h BP and as s.d. of daytime and night-time BP. The study population consisted of 315 untreated essential hypertensives with normal estimated glomerular filtration rate (>60u2009mlu2009min−1 per 1.73u2009m2), who underwent 24-h ambulatory BP monitoring and 24-h uAER determination. MAU was detected in 82 (26%) patients. ARV of 24-h systolic BP (SBP) was significantly higher in patients with MAU (9.8 (8.5–11.1) mmu2009Hg) when compared with those without it (9.1 (8–10.2) mmu2009Hg; P=0.007). This difference held (P=0.026) after adjustment for age, mean levels of BP and other potential confounders by analysis of covariance. A statistically significant correlation was also found between ARV of 24-h SBP and uAER (r=0.17; P=0.003). This association remained significant (β=0.15; P=0.01), also taking into account the effect of 24-h average systolic and diastolic BP, age, gender, diabetes, serum uric acid, triglycerides, estimated glomerular filtration rate in multiple regression analyses. All the other indices of short-term BPV tested were not independently associated with MAU. Our results seem to suggest that in essential hypertension, short-term BPV, only when estimated by ARV of 24-h SBP, is independently associated with MAU.

Association between uric acid and renal function in hypertensive patients: which role for systemic vascular involvement?

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 Pxa0<xa0.001). Uricemia strongly correlated with cIMT and aPWV at univariate analysis (Pxa0<xa0.001) and with cIMT after adjustment for confounders (Pxa0<xa0.001). Adjustment for cIMT attenuated the relationship between SUA and estimated glomerular filtration rate (Pxa0=xa0.019). Systemic vascular changes seem partially to mediate the association between SUA and renal function in hypertensive patients, regardless of kidney function.

Subclinical Kidney Damage in Hypertensive Patients: A Renal Window Opened on the Cardiovascular System. Focus on Microalbuminuria

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 20xa0years 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 30xa0mL/min/1.73xa0m2 and 60xa0mL/min/1.73xa0m2 or the presence of microalbuminuria (MAU), that is an amount of albumin in the urine of 30-300xa0mg/day or an albumin/creatinine ratio, preferentially on morning spot urine, of 30-300xa0mg/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 changing landscape of thromboprophylaxis for atrial fibrillation: insights from the ISPAF-2 survey

Atrial fibrillation is the most common sustained cardiac dysrhythmia. It represents a major public health problem due to increased mortality risk, reduced quality of life, and increased health costs [1, 2]. The prevalence of nonvalvular atrial fibrillation (AF) continues to increase worldwide, largely affecting the elderly, but also occurring in younger patients as a result of structural heart disease, autonomic imbalance, genetic abnormality, or previous cardiac surgery [3]. The rise in prevalence of AF is largely due to the increasing age of the population. About 1–2% of the total population is affected by AF, but the prevalence of this condition rises to ≈ 10% in individuals aged > 75 years [1–3]. In Europe, the number of adults with AF is rising markedly, with 9 million affected individuals in 2010, and 17 million expected patients in 2050, with an alarming impact on morbidity and mortality [4]. The associated fivefold risk of stroke is one of the most feared complications of AF. It is worth noting that AF accounts for at least 25% of the one million strokes that occur every year in Europe [4]. The true prevalence of AF is probably higher than that indicated by current statistics because prolonged electrocardiographic monitoring may detect clinically silent AF in a variable proportion of subjects who present in sinus rhythm [5]. Despite major advances in the understanding of the diverse pathogenesis, electrophysiological mechanisms, and triggering factors contributing to AF, the management of this dysrhythmia is still palliative in most cases. It consists of pharmacological therapy aimed at either maintenance of sinus rhythm or merely ventricular rate control and lifelong anticoagulation prophylaxis [1, 2]. In particular, oral anticoagulation (OAC) is recommended to reduce the risk of stroke associated with nonvalvular atrial fibrillation (NVAF) in patients at moderate to high risk of thromboembolism [1, 2]. Vitamin K antagonists (VKA), such as warfarin, have been regarded as the standard of care to reduce this increased risk of stroke [1, 2] and subsequent morbidity and mortality. However, prescribing physicians and patients using VKA are well aware of its many limitations, such as delayed onset of action, narrow therapeutic window, need for frequent and regular blood monitoring, frequent dose adjustments, and myriad drug and food interactions, all of which may contribute to underuse of VKA therapy, thereby exposing patients to risk of thromboembolic complications [1, 2, 6, 7]. Even in the monitored setting of randomized trials, anticoagulation with VKA has been unreliable. The ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial reports the VKA arm to be within the therapeutic range of the international normalized ratio only 55% of the time [8]. OAC therapy for NVAF has been revolutionized by the introduction in clinical practice of direct or new oral anticoagulants (DOACs or NOACs), such as dabigatran, rivaroxaban, apixaban and edoxaban, as alternatives to dose-adjusted VKA [9–12]. Meta-analyses of randomized controlled trials [9] as well as observational data [10] document the efficacy and real-life effectiveness of these agents. NOACs, although more expensive than VKA, have the added benefit of favourable pharmacology resulting in convenience for patients, with rapid onset of action, fixed dosing, no laboratory monitoring, and fewer food and drug interactions [1, 2, 11, 12]. It is conceivable that DOAC availability may increase the rate of OAC use for NVAF. A few studies address this issue, reporting almost invariably an increase in the overall numbers of OAC prescriptions, * Giuseppe Mulè’ giuseppe.mule@unipa.it

Serum uric acid is not independently associated with plasma renin activity and plasma aldosterone in hypertensive adults

BACKGROUND AND AIMSnIn experimental investigations conducted in rats, raising serum uric acid (SUA) levels resulted in the stimulation of intrarenal renin expression. Studies in humans exploring the association of SUA with plasma renin activity (PRA) yielded conflicting results. Moreover, little is known about the relationship of SUA with plasma aldosterone concentration (PAC). The study aimed to assess the relationship between SUA levels, PRA, and PAC and the influence of age, gender, body mass index (BMI), and hyperuricemia on these relationships in subjects with essential hypertension (EH).nnnMETHODS AND RESULTSnWe enrolled 372 hypertensive patients (mean age 45xa0±xa012 years, men 67%) with uncomplicated EH that was not pharmacologically treated. The study population was divided in tertiles according to SUA levels. While PRA did not differ significantly across the three tertiles, PAC was higher in subjects belonging to the uppermost tertile of SUA than those in the lower ones (pxa0=xa00.0429); however, this difference lost statistical significance after adjustment for age, sex, BMI, and serum creatinine. Univariate correlation analyses showed significant associations of SUA with PRA (rxa0=xa00.137; pxa0=xa00.008) and PAC (rxa0=xa00.179; pxa0<xa00.001). However, these relationships were not significant after correcting for confounding factors in multiple linear regression analyses. We did not observe statistically significant effect modification by gender, age, BMI, and hyperuricemia.nnnCONCLUSIONnSUA levels are weakly associated with PRA and PAC in adults with untreated EH. These relationships were lost after adjustment for age, sex, BMI, and serum creatinine.

Relationship between kidney findings and systemic vascular damage in elderly hypertensive patients without overt cardiovascular disease

Few studies have investigated the influence of age on the relationships between systemic vascular damage, kidney dysfunction, and intrarenal hemodynamic changes in patients with hypertension without overt cardiovascular disease. The authors enrolled 126 elderly patients with hypertension (aged ≥65 years) and 350 nonelderly patients with hypertension (aged <65 years). Carotid intima‐media thickness, renal resistive index, and aortic pulse wave velocity were performed in all patients. Elderly patients with hypertension had lower estimated glomerular filtration rates and higher albuminuria, renal resistive index, carotid intima‐media thickness, and aortic pulse wave velocity compared with nonelderly patients with hypertension (P < .001). Carotid intima‐media thickness independently correlated with renal resistive index and estimated glomerular filtration rate in nonelderly patients with hypertension, whereas it was significantly related to renal resistive index only in elderly patients with hypertension. Aortic pulse wave velocity was independently associated with albuminuria in nonelderly patients with hypertension, whereas it did not independently correlate with any indexes of renal damage in elderly patients with hypertension. Age is an important modifier of the relationships between renal function and renal hemodynamics with subclinical vascular involvement in elderly persons without cardiovascular disease.