Alessandro Palermo

Left ventricular hypertrophy and geometry in hypertensive patients with chronic kidney disease.

Objective To evaluate the prevalence of left ventricular hypertrophy (LVH) and left ventricular geometry in a group of 293 hypertensive patients with stage 2–5 chronic kidney disease (CKD), compared with 289 essential hypertensive patients with normal renal function. Methods All patients underwent echocardiographic examination. Patients on stage 1 CKD, dialysis treatment, or with cardiovascular diseases were excluded. Results LVH was observed in 47.1% of patients with CKD and in 31.14% of essential hypertensive patients (P < 0.0001). We found increasingly higher left ventricular diameters, thicknesses, and mass from stage 2 to 5 CKD. Distribution of concentric and eccentric LVH was not different between the two groups. However, after introducing mixed hypertrophy, the difference between the two groups group was disclosed (P = 0.027). The prevalence of inappropriate left ventricular mass was 52.6% in patients with CKD vs. 30.5% in essential hypertensive patients (P < 0.0001). Multiple regression analysis confirmed that the association between renal function and left ventricular mass (β −0.287; P < 0.0001) was independent by potential confounders. From stage 4 to 5, the significant increase of left ventricular mass was due to growth in posterior wall thickness rather than end-diastolic diameter. Diastolic function was significantly worse in patients with CKD, especially in more advanced stages. Conclusion Our study confirms that LVH is highly prevalent in patients with CKD; in this population, LVH is often inappropriate and characterized by the simultaneous increase of wall thicknesses and diameters.

Epidemiology and pathophysiology of left ventricular abnormalities in chronic kidney disease: a review

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.

Endothelin-1 and F2-isoprostane relate to and predict renal dysfunction in hypertensive patients

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.

Association between biomarkers of inflammation and left ventricular hypertrophy in moderate chronic kidney disease

AIMS Left ventricular hypertrophy (LVH) is a predictor for cardiovascular mortality, and it is considered to be a surrogate marker of preclinical cardiovascular disease. This study aimed at evaluating whether fetuin-A plasma levels are decreased in patients with moderate chronic kidney disease (CKD) and their linkage to plasma concentrations of hs-C-reactive protein (CRP), cardiotrophyn-1 (CT-1), tumor necrosis factor-ac (TNF-alpha), propeptide of collagen Type I (PIP) and to LVH. MATERIAL AND METHODS We enrolled 64 moderate CKD and 55 essential hypertensives (EH) with normal renal function as controls. All the patients underwent an echocardiographic examination; plasma samples were obtained to measure routine clinical parameters and the molecules listed above (measured by ELISA). RESULTS Among CKD there were 30/64 patients with LVH, and in EH group 14/55 subjects had LVH. Fetuin A was reduced in CKD when compared with EH (p < 0.0001). The comparison between CKD having LVH with those without LVH showed significant differences in plasma levels of fetuin-A (p < 0.002), TNF-alpha (p < 0.01) and hs-CRP (p < 0.001), CT-1 and PIP (p < 0.002). CKD with LVH had lower values of fetuin-A (p < 0.001), and higher values of hs-CRP (p < 0.001) TNF-alpha (p < 0.001), CT-1 (p < 0.001) and PIP (p < 0.001) than EH with LVH. The multivariate analysis of correlation demonstrated that in CKD patients hs-CRP (beta 0.42, p < 0.00006), and systolic blood pressure (beta 0.29, p < 0.02) were independent predictors of LV mass index. The relationship between LV mass index and fetuin-A did not reach statistical significance. CONCLUSIONS For the first time in moderate CKD patients, we demonstrate that fetuin-A is decreased and relates to LVH depending on C-reactive protein.

Left ventricular mass in hypertensive patients with mild‐to‐moderate reduction of renal function

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.

C-reactive protein and intercellular adhesion molecule-1 are stronger predictors of oxidant stress than blood pressure in established hypertension.

Background Oxidant stress is implicated in the pathogenesis of atherosclerosis in cardiovascular diseases. Our aim was to test oxidative stress, as 8-iso-prostaglandin F2α (8-iso-PGF2α), and its relationship with inflammation markers C-reactive protein (CRP) and tumour necrosis factor-α (TNFα), and endothelial activation assayed as soluble intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in essential hypertension. Methods In 216 essential hypertensive patients and 55 healthy control individuals, plasma levels of high-sensitivity CRP and TNFα, 8-iso-PGF2α, ICAM-1 and VCAM-1 were measured in basal conditions. Moreover, basal and 24-h ambulatory blood pressure monitoring measurements were obtained. Results Essential hypertensive patients showed higher levels of 8-iso-PGF2α (P < 0.0001), high-sensitivity CRP, TNFα, ICAM-1 and VCAM-1 (P < 0.001, respectively) than control individuals. In control individuals, 8-iso-PGF2α correlated only with high-sensitivity CRP (P < 0.001). In essential hypertensive patients, 8-iso-PGF2α correlated with high-sensitivity CRP (P < 0.000001), TNFα (P < 0.0001), ICAM-1 (P < 0.000001), VCAM-1 (P < 0.0001) and blood pressure. The multiple regression analysis considering 8-iso-PGF2α as the dependent variable showed that in essential hypertensive patients the independent predictors of 8-iso-PGF2α were ICAM-1, high-sensitivity CRP (P < 0.00001, respectively), and TNFα (P = 0.028). Conclusion Our findings demonstrate that oxidant stress is increased in essential hypertension, and relates to inflammation and endothelial activation. Factors other than blood pressure are stronger predictors of oxidant stress.

Plasma Aldosterone and Its Relationships With Left Ventricular Mass in Essential Hypertensive Patients With the Metabolic Syndrome

BACKGROUND The association of aldosterone with the metabolic syndrome (MetS) has not been fully elucidated. The aim of our study was to evaluate the relationships of plasma aldosterone concentration (PAC) with MetS and left ventricular mass (LVM) in nondiabetic Caucasian patients with essential hypertension. METHODS Measurements were taken with the patients off antihypertensive medications. The measurements included 24-h blood pressure (BP) readings, plasma renin activity (PRA) and aldosterone, and an echocardiogram. RESULTS Subjects with MetS (n = 201) had higher age-adjusted PAC (10.2 +/- 5.8 vs. 11.6 +/- 5.9 ng/dl; P = 0.01) and greater age-adjusted LVM indexed for height2.7 (LVMH2.7) (56 +/- 19 vs. 62 +/- 20 g/m2; P = 0.001) than those without MetS (n = 249). The difference in respect of PAC between the two groups was independent of PRA and was attributable mainly to obesity. After adjusting for potential confounders, LVMH2.7 was associated with MetS as a whole (beta = 0.11; P = 0.02) and with body mass index (BMI) (beta = 0.19; P < 0.0001) in the overall population. The latter relationship was attenuated (beta = 0.15; P = 0.001) after further adjustment for PAC. In the MetS group the association of LVMH2.7 with PAC held (beta = 0.19; P = 0.007) in multivariate analyses. In subjects without MetS, this relationship had only borderline statistical significance. CONCLUSIONS Our results suggest that the elevated PAC related to obesity may help to explain the increased LVM observed in association with MetS, and may contribute to enhancing the cardiovascular risk associated with MetS.

Inflammation and endothelial activation are linked to renal function in long‐term kidney transplantation

The aim of this study was to investigate the relationships between inflammation and adhesion molecules in long‐term kidney transplantation. We measured serum concentrations of tumor necrosis factor‐alpha (TNFα) and intercellular and vascular cell adhesion molecules (ICAM‐1 and VCAM‐1) in 35 renal transplant recipients (mean age of transplantation 5 ± 3 years) and in 35 chronic renal insufficiency (CRI) patients; twenty‐six healthy subjects were enrolled as controls. Transplanted showed higher values than controls of TNFα (P < 0.0001), ICAM‐1 (P < 0.0001), and VCAM‐1 (P < 0.0001). CRI group as well exhibited higher concentrations than controls of TNFα (P < 0.0001), ICAM‐1 (P < 0.0001), and VCAM‐1 (P < 0.0001). Transplanted and CRI patients had similar blood pressure and renal function levels, and TNFα, ICAM‐1, and VCAM‐1 were not significantly different in the two groups. In transplanted group ICAM‐1, VCAM‐1, and TNFα correlated negatively and independently with glomerular filtration rate (GFR) –P < 0.00001 for all. TNFα as well correlated with ICAM‐1 and VCAM‐1 (P < 0.001, respectively). In CRI group, TNFα correlated with serum creatinine, ICAM‐1, and VCAM‐1 (P = 0.01 for all). In conclusion, in long‐term renal transplantation, the level of kidney function and both inflammation and endothelial activation are closely related. In fact, the multiple regression analysis demonstrated that the level of kidney insufficiency and the levels of the studied molecules were independently associated.

Metabolic syndrome in subjects with white-coat hypertension: impact on left ventricular structure and function.

Some reports have suggested that white-coat hypertension (WCH) is associated with some features of the metabolic syndrome (MetS). These metabolic disturbances, instead of WCH per se, may potentially explain the greater extent of end-organ damage sometimes observed in WCH subjects (WCHs) when compared to normotensive individuals (NTs). The aim of the present cross-sectional study was to compare left ventricular (LV) structure and function in three groups of subjects: WCHs with MetS, WCHs without MetS and NTs. A total of 145 WCHs, 35% of whom had MetS, were enrolled. As controls, 35 NTs were also studied. In all subjects, routine blood chemistry, echocardiographic examination and 24-h ambulatory blood pressure monitoring were performed. When compared with WCHs without MetS, those with MetS showed higher LV mass indexed by height elevated by a power of 2.7 (LVMH2.7) (49.6±14.8 vs 38.9±9.8 g/m2.7; P<0.0001). The same parameter was greater in WCHs without MetS than in NTs (32±8 g/m2.7; P=0.004). Moreover, the E-wave deceleration time was longer in WCHs with MetS than in those without it (236.2±66.4 vs 200.5±30.8 ms; P<0.0001). The relationship of MetS with LVMH2.7 was confirmed in multivariate regression models. Our results seem to suggest that MetS may have a deleterious influence on LV structure and function in WCH. However, WCH, being associated with an increased LV mass, also in subjects without MetS, may not be considered as an innocuous phenomenon.

The Association of Microalbuminuria With Aortic Stiffness Is Independent of C-Reactive Protein in Essential Hypertension

BACKGROUND It has not been fully elucidated whether microalbuminuria (MAU) and high-sensitivity C-reactive protein (hsCRP) are associated with aortic distensibility independently of each other. Our study was aimed to evaluate the independent relationships of urinary albumin excretion rate (AER) and hsCRP with aortic stiffness in hypertensive patients. METHODS We enrolled 140 untreated nondiabetic essential hypertensives (mean age: 48 +/- 12 years). In all subjects, 24-hour AER and plasma levels of hsCRP were determined by immunoenzymatic assay. MAU was defined as an AER of 20-200 microg/min. Aortic stiffness was assessed by measurement of carotid-femoral pulse wave velocity (PWV). RESULTS Carotid-femoral PWV, adjusted for age and mean arterial pressure (MAP), was higher in subjects with MAU (n = 41) than in those without it (n = 99) (11.6 +/- 2.3 vs. 9.9 +/- 1.8 m/s; P < 0.001) and in subjects with hsCRP above the median value when compared to those with lower levels of hsCRP (10.8 +/- 2.1 vs. 10 +/- 2.1 m/s; P = 0.026). In multiple regression analysis, AER and hsCPR remained independent predictors of aortic stiffness (beta = 0.24; P < 0.001 and beta = 0.15; P = 0.03, respectively). CONCLUSIONS Our results suggest that in patients with essential hypertension, MAU and CRP are independently associated with an increased aortic stiffness.