Relationship of fetuin-A with glomerular filtration rate and endothelial dysfunction in moderate-severe chronic kidney disease.

BACKGROUND: In end-stage renal disease, fetuin-A has been demonstrated to be reduced and inversely related to cardiovascular mortality. This study had 2 distinct aims. The first was to verify if circulating concentration of fetuin-A may depend on renal function in patients with chronic kidney disease (CKD). Furthermore, we analyzed the correlation of fetuin-A with the biomarker of endothelial dysfunction endothelin-1 (ET-1), and with the inflammatory cytokine interleukin-6 (IL-6). METHODS: In 108 subjects with stage 3-5 CKD, plasma levels of fetuin-A, ET-1 and IL-6 were assayed. Patients were studied first as a whole group and then were divided according to stages of CKD and fetuin-A tertiles. RESULTS: Fetuin-A concentration decreased in parallel with the increase in ET-1 and IL-6 levels as renal function declined. Multiple regression analysis showed that fetuin-A was independently associated with estimated glomerular filtration rate (beta=0.386; p<0.001), IL-6 (beta=-0.393; p=0.001) and ET-1 (beta=-0.219; p=0.02), in a multivariate model including also sex, parathyroid hormone and the calcium x phosphorus product. CONCLUSIONS: These results seem to indicate that in CKD, even when not severe, inflammatory processes are increased and linked to endothelial dysfunction, worsening progressively with the decline of renal function.

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. 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.

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.

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.

Inverse relationship between ambulatory arterial stiffness index and glomerular filtration rate in arterial hypertension.

BACKGROUND: Arterial stiffness and mild-to-moderate renal dysfunction are predictors of cardiovascular (CV) morbidity and mortality. Recently, the ambulatory arterial stiffness index (AASI) has been proposed as a surrogate index of arterial stiffness. It has been associated with an enhanced risk of stroke. The aim of our study was to assess the relationship between AASI and glomerular filtration rate (GFR) in a group of hypertensive patients with no CV complications. METHODS: A total of 143 untreated hypertensive subjects (mean age: 44 +/- 12 years; men 57%), with serum creatinine <1.5 mg/dl, were enrolled. AASI was calculated as one minus the regression slope of diastolic on systolic blood pressure (BP) obtained by individual 24-h BP recordings. GFR was computed from the scintigraphic determination of the technetium-99m diethylenetriaminepentaacetic acid uptake within the kidneys, by the Gates' method. RESULTS: Hypertensive patients with AASI above the median value (n = 71) had lower GFR than those with AASI below the median (n = 72) (98.3 +/- 31 vs. 122.4 +/- 32 ml/min/1.73 m(2); P < 0.001). This difference held even after adjustment for age and gender. The linear regression analysis disclosed a significant inverse correlation between GFR and AASI (r = -0.30; P < 0.001), that was replicated (beta = -0.19; P = 0.02) in a multiple regression model including, as independent variables (besides AASI), age, gender, high-density lipoprotein cholesterol, body mass index, 24-h pulse pressure (PP) and nocturnal reduction in BP. CONCLUSIONS: AASI is inversely related to GFR in arterial hypertension. This may help to explain the increased CV risk associated with mild-to-moderate renal dysfunction.

Relationship of transforming growth factor-beta(1) with tumour necrosis factor-alpha and endothelial activation in patients with stable renal transplantation.

AIM: To evaluate whether or not transforming growth factor-beta(1) is related to inflammation markers and to intercellular and vascular cell adhesion molecules in patients with stable renal transplantation. METHODS: Serum concentrations of transforming growth factor-beta(1), tumour necrosis factor-alpha, C-reactive protein and adhesion molecules were analysed in 33 renal transplanted patients, 33 patients with chronic renal insufficiency (matched to the transplanted group for level of renal function), and 33 hypertensives with normal renal function. anova, Student's t-test and simple regression analysis were used to analyse the data. RESULTS: Transplanted patients showed higher values than hypertensives of transforming growth factor-beta(1), tumour necrosis factor-alpha, C-reactive protein and adhesion molecules (P < 0.0001 for all). Renal insufficiency group exhibited higher concentrations of transforming growth factor-beta(1), tumour necrosis factor-alpha, C-reactive protein and adhesion molecules than hypertensives (P < 0.0001 for all). Transplanted and renal insufficiency patients had similar blood pressure and renal function levels, and transforming growth factor-beta(1), tumour necrosis factor-alpha, C-reactive protein and adhesion molecules were not significantly different. In transplanted and in renal insufficiency groups transforming growth factor-beta(1), adhesion molecules and tumour necrosis factor-alpha correlated significantly each other and with glomerular filtration rate (P < 0.001 for all). CONCLUSION: In long-term renal transplantation inflammation and endothelial activation biomarkers, the pro-fibrotic cytokine transforming growth factor-beta(1) and kidney function are interrelated. Because of the relevant role that inflammation, organ fibrosis and graft dysfunction may play against renal and cardiovascular survival of graft recipients, a better comprehension of the interactions between these variables is needed.

Parathyroid hormone is inversely related to endothelin-1 in patients on haemodialysis.

AIM: Parathyroid hormone secretion is mainly influenced by hypocalcaemia, hyperphosphataemia and vitamin D deficiency. However, previous in vitro and in vivo studies showed that endothelin-1 can influence parathyroid hormone secretion. This study was aimed at evaluating this relationship in vivo in uraemic patients. METHODS: Parathyroid hormone and endothelin-1 plasma concentrations were measured in 67 haemodialysed patients. Patients with history of cardiovascular diseases and those with parathyroid adenoma were excluded. RESULTS: Plasma levels of endothelin-1 were found to be inversely related to those of parathyroid hormone (P < 0.04) The multiple regression analysis, carried out considering parathyroid hormone as a dependent variable, and including age, sex, blood pressure, calcium x phosphorus product, and endothelin-1, demonstrated that the independent correlates of parathyroid hormone were endothelin-1 (beta = -0.276; P = 0.015), and calcium x phosphorus product (beta = 0.417; P < 0.0001). CONCLUSION: For the first time in vivo, we demonstrated an inverse independent relationship between endothelin-1 and parathyroid hormone in haemodialysed patients. Because both endothelin-1 and parathyroid hormone are endowed with well-known harmful actions on cardiovascular apparatus, whether such inverse relation may really influence the natural history of cardiovascular damage due to secondary hyperparathyroidism remains to be elucidated.

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 F2alpha (8-iso-PGF2alpha), and its relationship with inflammation markers C-reactive protein (CRP) and tumour necrosis factor-alpha (TNFalpha), 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 TNFalpha, 8-iso-PGF2alpha, 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-PGF2alpha (P < 0.0001), high-sensitivity CRP, TNFalpha, ICAM-1 and VCAM-1 (P < 0.001, respectively) than control individuals. In control individuals, 8-iso-PGF2alpha correlated only with high-sensitivity CRP (P < 0.001). In essential hypertensive patients, 8-iso-PGF2alpha correlated with high-sensitivity CRP (P < 0.000001), TNFalpha (P < 0.0001), ICAM-1 (P < 0.000001), VCAM-1 (P < 0.0001) and blood pressure. The multiple regression analysis considering 8-iso-PGF2alpha as the dependent variable showed that in essential hypertensive patients the independent predictors of 8-iso-PGF2alpha were ICAM-1, high-sensitivity CRP (P < 0.00001, respectively), and TNFalpha (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.

Relationship of metabolic syndrome with pulse pressure in patients with essential hypertension.

BACKGROUND: Pulse pressure is largely dependent on arterial stiffness. Recent studies have documented reduced large artery compliance in nondiabetic subjects with metabolic syndrome (MS). The aim of our study was to analyze, in a group of patients with essential hypertension and without diabetes mellitus, the influence of MS on clinic and 24-h pulse pressures. METHODS: A total of 528 hypertensive subjects, aged 18 to 72 years, who were free of cardiovascular and renal diseases were enrolled. Of the subjects, 41% had MS. In all subjects routine blood chemistry, echocardiographic examination, and 24-h ambulatory blood pressure monitoring were performed. RESULTS: When compared with subjects without MS, hypertensive patients with MS exhibited more elevated clinic pulse pressures (66 +/- 16 v .58 +/- 14 mm Hg; P < .00001) and 24-h (51 +/- 9 v .48 +/- 7 mm Hg; P = .00001). These results held even after correction for age, sex, stroke volume, mean pressures, and total cholesterol. The regression line relating PP with age was steeper in patients with MS than in those without MS. Multivariate regression models confirmed that the relationships of MS with clinic (beta = 0.12; P = .003) and 24-h PP (beta = 0.11; P = .01) were independent from several confounding factors. CONCLUSIONS: The elevated levels of clinic and 24-h PP observed in hypertensive patients with MS may reflect increased large arteries stiffness and may therefore contribute to explain the enhanced cardiovascular risk associated with MS.

Influence of chronic renal insufficiency on left ventricular diastolic function in hypertensives without left ventricular hypertrophy.

BACKGROUND: Patients with chronic renal insufficiency (CRI) have a much greater cardiovascular risk than the general population. Moreover, hypertension is common in these patients, as is left ventricular hypertrophy (LVH) and diastolic dysfunction, which contribute to a worse prognosis. While these findings are well established for end-stage renal disease, fewer data are available in mild to moderate CRI. Furthermore, little is known about diastolic function in CRI patients without LVH. METHODS: We performed a cross-sectional study to evaluate LV structure and function in hypertensives with CRI, compared with hypertensives with normal renal function (EH), by means of mitral inflow and tissue Doppler echocardiography. Patients with LVH were excluded from both groups. RESULTS: CRI patients had higher left ventricular end-diastolic diameter, end-systolic diameter (p<0.0001 and p=0.0001, respectively) and left ventricular mass index (LVMI) (p<0.0001) than EH patients. The CRI group also showed greater alterations of the diastolic function indexes than hypertensives: lower E-wave peak velocity (p=0.02), E-wave peak velocity to A-wave peak velocity ratio (p=0.03) and early diastolic myocardial velocity (p=0.04), higher A-wave peak velocity (p=0.07), E-deceleration time (p=0.02) and isovolumic relaxation time (p=0.0001). Multiple regression analysis demonstrated that renal function was a predictor of LVMI and diastolic function independently of age, sex, pulse pressure, body mass index and duration of hypertension. CONCLUSIONS: Our data showed a greater alteration of diastolic function in the CRI group, in part independent of LVMI. In CRI, factors other than LVMI and blood pressure seem to play an important role in causing early diastolic dysfunction.

Relation of C-reactive protein to oxidative stress and to endothelial activation in essential hypertension.

BACKGROUND: C-reactive protein (CRP) predicts cardiovascular outcome. Oxidative stress is considered to be involved in endothelial alteration. We hypothesized that in essential hypertension (EH), oxidative stress, as measured by 8-iso-prostaglandin-F(2alpha) (8-iso-PGF(2alpha)), should be associated with increased CRP and endothelial activation, as evaluated by soluble intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) plasma levels. METHODS: In 83 subjects with mild EH and in 50 healthy control subjects we measured, in basal conditions, plasma levels of hs-CRP, 8-iso-PGF(2alpha), ICAM-1 and VCAM-1, and tumor necrosis factor-alpha (TNF-alpha). RESULTS: Subjects with EH had higher levels of 8-iso-PGF(2alpha) (P < .0001), CRP (P < .001), ICAM-1 and VCAM-1 (P < .001), and TNF-alpha (P < .001) than did control subjects. We divided successively EH according to CRP values (<1, 1-3, >3 mg/L), and we observed increasing and significantly different levels of the endothelial parameters and of TNF-alpha along with increasing CRP. Linear analysis of correlation pointed out significant correlation of CRP with 8-iso-PGF(2alpha) (r = 0.730, P < .001), ICAM-1 and VCAM-1 (r = 0.642 and 0.468, P < .001 respectively), and TNF-alpha (r = 0.609, P < .001). Multiple regression analysis using CRP as a dependent variable confirmed the relationship of CRP with systolic blood pressure (beta 0.216, P = 0.039) and with 8-iso-PGF(2alpha) (beta 0.602, P = .0001). CONCLUSIONS: Our data demonstrate that in EH, inflammatory molecules such as CRP and TNF-alpha are increased and related to both oxidative stress and endothelial activation.

[Screening for depression in hemodialysis]. / Utilità di questionari di screening ultrabrevi per la stima della prevalenza di sintomi depressivi in pazienti anziani in emodialisi.

Prevalence of depression symptoms, which is high among geriatric individuals, it is even higher in hemodialysis patients. In this study we performed a screening for depression symptoms in 82 elderly hemodialysis patients, by means of 3 different ultra-brief questionnaires, proposed for geriatric population by the American Geriatric Society Guide-Lines. At the beginning, patients were requested to fill out the ultra-brief Patient Health Questionnaire (PHQ), which consists of only 2 questions. A score of 3 or greater prompted the administration of the brief version of the Geriatric Depression Scale (GDS-5) and of the full PHQ-9. A GDS-5 score of 2 or greater was considered as positive for depression screening. PHQ-9 scores of 5, 10, 15 and 20 represented the cutpoints for mild, moderate, moderately severe and severe depression, respectively. PHQ-2 score was 3 or greater in 43.9% of patients (n= 36), in which GDS-5 resulted as positive in all of the patients. Further, PHQ-9 scores stratified depression symptoms as follows: mild 22.2%, moderate 16.6%, moderately severe 39% and severe 22.2%. Our sample showed high prevalence of depression symptoms, which were relevant (moderate or worse) in almost 80% of patients. PHQ-2 appeared to be extremely useful, since 100% of patients with PHQ-2 score of 3 or greater had positive GDS-5 score. In conclusion, screening of depression symptoms by ultra-brief self-administered questionnaires may be very simple and useful in hemodialysis patients, therefore it should be encouraged.

Prevalence and predictors of left ventricular hypertrophy in patients with hypertension and normal electrocardiogram.

BACKGROUND: Electrocardiography (ECG) has low sensitivity for detecting left ventricular hypertrophy (LVH), while echocardiography cannot be routinely performed. DESIGN/METHODS: In this study we evaluate the prevalence of LVH and diastolic dysfunction in hypertensive patients with normal ECG. We excluded patients with cardiovascular (CV) diseases, diabetes, chronic kidney disease, or presenting ECG-LVH or other ECG anomalies. The enrolled 440 hypertensive patients underwent echocardiographic examination (Acuson Sequoia 512); LV mass was indexed by body surface area (LVMI) and LVH was defined as LVMI >125 g/m(2) in men and >110 g/m(2) in women. Diastolic function was evaluated by mitral inflow and tissue Doppler imaging (TDI). RESULTS: The prevalence of LVH was 8.18% (95% confidence interval [CI] 5.97-11.1%). Multiple regression analysis showed that the only variable independently associated with LVH was duration of hypertension (p < 0.001). The receiver operating characteristic (ROC) curve showed that duration of hypertension was a powerful predictor of LVH, with an area under the curve (AUC) of 0.878 and p < 0.0001. Further, in patients with LVH the mean difference of LVMI from the cut-off value for LVH was 12.3 ± 9.19 g/m(2). Diastolic dysfunction, defined as early diastolic myocardial velocity (Em) <0.08 m/s, was detected only in 3.2% of patients. CONCLUSIONS: The prevalence of LVH among hypertensive patients with normal ECG, free of diabetes and of CV diseases is low; moreover, patients with echocardiographic LVH presented LVMI values that identified mild LVH. Few cases of impaired diastolic function were registered. We suggest that in hypertensive patients with such characteristics the echocardiographic examination should be reserved to those who present with higher duration of hypertension.

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.

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.

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 (beta -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.

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.

Impact of the metabolic syndrome on total arterial compliance in essential hypertension patients.

The aim of the study was to cross-sectionally analyze, in a group of essential hypertension patients without diabetes mellitus, the influence of the metabolic syndrome (MS) on the stroke volume index to pulse pressure (SVi/PP) ratio, a measure of total arterial compliance. A total of 528 essential hypertension patients, aged 18 to 72 years, free from cardiovascular and renal disease (41% of whom had MS) were enrolled. All participants underwent routine blood chemistry, echocardiographic examination, and 3 blood pressure measurements at the end of echocardiographic examination. When compared with participants who did not have MS, hypertensive patients with MS exhibited lower SVi/PP ratio (0.65+/-0.22 vs 0.73+/-0.21 mm Hg; P=.0003). The independent association of MS with SVi/PP ratio (beta=0.10; P=.02) was confirmed in a multivariate regression model including age, sex, and other potential confounders as covariates. The authors' finding may help to explain the enhanced cardiovascular risk associated with MS.

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 (TNFalpha) 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 TNFalpha (P < 0.0001), ICAM-1 (P < 0.0001), and VCAM-1 (P < 0.0001). CRI group as well exhibited higher concentrations than controls of TNFalpha (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 TNFalpha, ICAM-1, and VCAM-1 were not significantly different in the two groups. In transplanted group ICAM-1, VCAM-1, and TNFalpha correlated negatively and independently with glomerular filtration rate (GFR) -P < 0.00001 for all. TNFalpha as well correlated with ICAM-1 and VCAM-1 (P < 0.001, respectively). In CRI group, TNFalpha 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.