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.

The Relationship Between Aortic Root Size and Hypertension: An Unsolved Conundrum.

Thoracic aortic aneurysms rupture and dissection are among the most devastating vascular diseases, being characterized by elevated mortality, despite improvements in diagnostic imaging and surgical techniques.An increased aortic root diameter (ARD) represents the main risk factor for thoracic aortic dissection and rupture and for aortic valve regurgitation.Even though arterial hypertension is commonly regarded as a predisposing condition for the development of thoracic aorta aneurysms, the role of blood pressure (BP) as determinant of aortic root enlargement is still controversial. The use of different methods for indexation of ARD may have in part contributed to the heterogeneous findings obtained in the investigations exploring the relationships between ARD and BP. Indeed, the best methods for ARD indexation, as well as the normal values of aortic root size, are still a matter of debate.Several non-hemodynamic factors influence ARD, including age, gender, and anthropometric variables, such as height, weight and their derivatives body surface area (BSA) and body mass index. Of these factors, anthropometric variables have the greatest impact.Several studies documented an association between ARD enlargement, assessed by echocardiography, and some indices of hypertensive target organ damage such as left ventricular hypertrophy, diastolic dysfunction, and carotid intima-media thickening. Recently, we found that ARD, expressed either as absolute values or normalized for BSA (ARD/BSA) or height (ARD/H), was significantly greater in hypertensive subjects with chronic kidney disease (CKD) when compared to their counterparts with normal renal function. Moreover, at univariate analyses estimated glomerular filtration rate (eGFR) showed significant inverse correlations with ARD not indexed and with ARD/BSA and ARD/H. Taking into account the effect of age, sex, duration of hypertension and other potentially confounding factors, in multiple regression analyses, only the association of GFR with ARD/H and that between GFR and ARD/BSA remained statistically significant. The receiver-operating characteristic curve analysis revealed that an estimated GFR of about 50 ml/min/1.73 m2 represents the better threshold to distinguish hypertensive patients with dilated aortic root from those with a normal one.Some population-based studies showed that an enlarged ARD might predict an adverse prognosis, even in absence of aneurysmatic alterations.In the Cardiovascular Health Study, a dilated aortic root was independently associated with an increased risk for stroke, cardiovascular and total mortality in both sexes and with incident congestive heart failure only in men. The relationship between ARD and heart failure has been observed also in the Framingham Heart Study. More recently, the PAMELA (Pressioni Arteriose Monitorate E Loro Associazioni) study demonstrated an independent relationship of ARD/H with incident cardiovascular morbidity and mortality.Although the relationship between BP and aortic root size is still a matter of debate, increasing evidence seems to support the notion that aortic root dilatation, even in absence of aneurysmatic alterations, may be regarded as an hypertensive organ damage paralleling other preclinical markers whose unfavourable prognostic significance is firmly established. Future studies are needed to assess whether or not antihypertensive therapy is able to reduce aortic root dimension and the increased risk associated with its enlargement.

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 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 m2 and 60 mL/min/1.73 m2 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.

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 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.

Unfavourable interaction of microalbuminuria and mildly reduced creatinine clearance on aortic stiffness in essential hypertension.

The aim of our study was to assess the independent relationships of urinary albumin excretion rate (AER), of creatinine clearance (CrCl) and of their interaction with aortic stiffness in hypertensive patients without overt renal insufficiency. We studied 222 untreated nondiabetic essential hypertensives. In patients with reliable 24-h urine collections, AER and CrCl were determined. Microalbuminuria (MAU) was defined as an AER of 20 to 200 µg/min. Aortic stiffness was assessed by measurement of carotid-femoral pulse wave velocity (c-f PWV). C-f PWV was higher in subjects with MAU than in those without it (p<0.001, even after adjustment for age, sex and mean arterial pressure) and in subjects with CrCl below 90 ml/min/1.73 m(2) when compared to those with greater values of CrCl (p=0.04 after correction for age, sex and mean arterial pressure). There was a significant interaction of MAU and reduced CrCl regarding c-f PWV (p=0.04). In multiple regression analysis, AER and CrCl remained independently associated with aortic stiffness (ß=0.22; p<0.001 and ß=-0.13; p=0.02, respectively). In essential hypertensive patients microalbuminuria and mildly reduced CrCl are related independently of each other with increased c-f PWV and exert a synergistic unfavourable effect on aortic stiffness.