Relationships between mild hyperuricaemia and aortic stiffness in untreated hypertensive patients.

BACKGROUND AND AIMS: Clinical studies exploring the relationship between serum uric acid (SUA) and arterial stiffness yielded conflicting results. Only in a few of these studies, arterial distensibility was examined by measuring aortic pulse wave velocity (PWV), which is considered the gold standard for evaluating arterial stiffness. In none of the previous investigations was the influence of SUA on aortic distensibility assessed, taking into account the effect of albuminuria. The purpose of our study was to comprehensively analyse the relationships between SUA and aortic PWV in a group of essential hypertensive patients. METHODS AND RESULTS: We enrolled 222 untreated and uncomplicated hypertensive subjects (mean age: 44 ± 10 years; 60% males), without gout. In all patients, SUA and urinary albumin excretion rate (AER) were determined. Moreover, carotid-femoral (c-f) PWV was measured. C-f PWV was significantly higher in hypertensive patients belonging to the uppermost tertile of SUA distribution, compared to subjects of the lowest tertiles (10.9 ± 2.2 vs. 10 ± 1.8 vs. 9.9 ± 1.7 m s(-1); p = 0.001). In univariate analysis, SUA correlated with c-f PWV (r = 0.24; p < 0.001). This association disappeared when AER was added in a multiple regression model, including SUA, age, mean arterial pressure, gender, metabolic syndrome components and glomerular filtration rate. CONCLUSION: The results of our study showed that, in essential hypertensive subjects, there is a positive relationship between mild hyperuricaemia and aortic stiffness. This association weakened after adjustment for covariates and lost statistical significance after further correction for albuminuria.

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.

Endothelium-derived factors in microalbuminuric and nonmicroalbuminuric essential hypertensives.

Previous evidence has demonstrated a relationship between growth factors and cardiovascular diseases. This study was aimed at evaluating levels of some endothelium-derived growth factors, and their relationship with microalbuminuria (MAU), in essential hypertension. Ninety-nine mild-moderate essential hypertensives (EH) and 25 healthy controls were studied. All patients underwent 24-h blood pressure monitoring, serum endothelin-1 (ET-1), basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF), and 24-h MAU assays. Later, EH were divided into two subsets consisting of microalbuminurics (MAU >11 microg/min) and nonmicroalbuminurics (MAU <11 microg/min). In microalbuminuric EH, circulating ET-1, bFGF, and PDGF were significantly higher than in nonmicroalbuminurics (P < .0001, P < .0001, P < .005, respectively) or in controls. In the group of 99 EH, significant positive correlations of MAU with both ET-1 and bFGF (r = 0.35, P < .001, and r = 0.34, P < .001, respectively) were found. ET-1 and bFGF correlated significantly (r = 0.31, P < .002). Circulating bFGF also correlated significantly with MAU in the microalbuminuric EH subset (r = 0.49, P < .01). Our results show that in microalbuminuric EH circulating levels of certain growth factors are increased. In human essential hypertension these factors are linked with MAU, an early cardiovascular and renal damage marker.

Influence of vascular load on plasma endothelin-1, cytokines and catecholamine levels in essential hypertensives.

In vitro studies demonstrated a relationship between ET-1 and basic Fibroblast Growth Factor (bFGF), and of bFGF with Platelet Derived Growth Factor (PDGF). The present study was carried out to investigate in vivo the behaviour after vascular stress of circulating ET-1, bFGF and PDGF, and catecholamines, and their relationship. In 12 healthy normotensives (NTs) and 15 essential hypertensives (Ehs) venous blood samples to determine circulating ET-1, bFGF and PDGF, and catecholamine (EPI and NE) levels were drawn before and at the third minute of a handgrip test. Blood pressures (BP) and heart rate were automatically recorded before starting, and at 1, 2, and 3 minutes during the test. The NTs showed, in basal condition, lower values than the EHs of all the examined parameters; later, the handgrip test induced significant increases in circulating levels of ET-1, bFGF and catecholamine. In the EHs at the third minute of the exercise significant increases in plasma ET-1 (p < 0.002), bFGF (p < 0.006), and EPI and NE (p < 0.0005) levels were observed. Systolic and diastolic BP significantly increased after handgrip test in NTs and EHs. Plasma ET-1 correlated with bFGF both before (p < 0.01) and at the acme (p < 0.05) of the isometric exercise. Our results show that in EHs plasma ET-1 and bFGF correlate each other, indicating that in human hypertension a linkage between ET-1 and bFGF exists.

Changes of plasma endothelin and growth factor levels, and of left ventricular mass, after chronic AT1-receptor blockade in human hypertension.

The stimulation of autocrine and paracrine factors such as basic fibroblast- (bFGF) and platelet-derived (PDGF) growth factors mediates many of the growth-promoting actions of angiotensin II. The aim of this study was to evaluate the effect of chronic AT1-receptor blockade on plasma endothelin-1 (ET-1) and growth factors levels, and on left ventricular mass, in essential hypertension (EH). The study population consisted of 16 patients with mild-moderate EH, and 25 normotensive controls. In the EH patients under basal conditions, and after 3 and 6 months of chronic therapy with Losartan 50 mg/day, we measured serum levels of ET-1, bFGF and PDGF, and tumor necrosis factor (TNF). At the same time, all patients underwent 24-h ambulatory blood pressure monitoring and an echocardiographic evaluation to measure the thickness of the posterior wall (PWT) of the left ventricle and of the interventricular septum (IVS). The healthy controls underwent the same analyses, under basal conditions, at baseline and after 3 and 6 months of observation. In the EH patients, after 3 months of AT1-receptor blockade bFGF was reduced from 13.6 +/- 0.7 to 10.9 +/- 0.7 pg/mL (P < .004), and both TNF and PDGF were significantly decreased (P < .006 and P < .007, respectively). After 6 months of therapy, ET-1 was significantly diminished in comparison with baseline (6.9 +/- 0.8 v 5.5 +/- 0.1 fmol/mL; P < .05), and the reduction in the levels of growth factors were even more significant than at 3 months of treatment. Both PWT and IVS were significantly changed after 6 months of therapy with losartan after basal evaluation (P < .05, respectively). Systolic and diastolic 24-h blood pressures declined significantly after 3 and 6 months of therapy with losartan (P < .01, respectively). It seems likely that the inhibition of the action of angiotensin II by the specific AT1-receptor blockade, by reducing circulating levels of ET-1 and those of some growth factors, may offer an advantage regarding the effect on hypertensive cardiovascular changes in human hypertension.

Microalbuminuria, renal dysfunction and cardiovascular complication in essential hypertension.

OBJECTIVE: To evaluate the prevalence of microalbuminuria (albumin excretion rate, AER) in a wide hypertensive population, and to evaluate any relationship with cardiovascular damage and renal dysfunction. DESIGN: A transversal study. SUBJECTS AND METHODS: In 383 hospitalized Caucasian essential hypertensives (198 men, 185 women) of mean age 44 +/- 0.5 years and mean clinic blood pressure 170.3 +/- 0.95/ 103.4 +/- 0.47 mmHg, metabolic parameters, serum creatinine level (Cs), creatinine clearance rate (Ccs), 24 AER and plasma renin activity (PRA) were measured. Furthermore, each patient underwent 24 h ambulatory blood pressure monitoring (ABPM) and echocardiography to measure left ventricular mass, which was indexed both by body surface area to obtain left ventricular mass index (LVMI) and by height to obtain the left ventricular mass indexed for height (LVMH). By Doppler echocardiography, the diastolic compliance by early:late peak filling velocity ratio was analysed. The fundus oculi was also observed. Three subsets of hypertensives were obtained by dividing the 383 essential hypertensives on the basis of their AER: < or = 11 (group A), 11 < or = 20 (group B) and > 20 micrograms/min (group C). MAIN OUTCOME MEASURES: Microalbuminuria, creatinine clearance, PRA, ABPM, LVMI, LVMH, early:late peak filling velocity ratio, hypertensive retinopathy. RESULTS: Among the 383 essential hypertensives, AER was < 11 micrograms/min in 55% of the patients (group A), 18% had AER in the range 11-20 micrograms/min (group B) and 27% had AER > 20 micrograms/min (group C). In the entire essential hypertensive population the prevalence of left ventricular hypertrophy was 44.39% and hypertensive retinopathy was observed in 54.83%. Moreover, AER significantly correlated with clinic systolic blood pressure (SBP) and diastolic blood pressure (DBP), with 24 SBP and DBP and with 24 h daytime and night-time mean blood pressure (MBP). AER was correlated also with LVMH and creatinine clearance. The analysis of the three subsets revealed no differences in age, body mass index, serum creatinine level and PRA. Group C in comparison with group A showed higher values of clinic SBP, 24 h SBP, DBP and MBP, and of daytime and night-time MBP. Furthermore, in group C, LVMI and LVMH were significantly greater than in group A, with a prevalence of left ventricular hypertrophy of 55% in the former group. Group C showed a prevalence of hypertensive retinopathy of 69% whereas in group A the prevalence was 48%. In group C, AER was significantly correlated with serum creatinine level. CONCLUSIONS: The transversal phase of our research, performed in a homogeneous population of Caucasian essential hypertensives with no metabolic disturbances, confirms the relationship between blood pressure pattern and early glomerular changes in essential hypertensives without overt proteinuria. Furthermore, these results emphasize the role of microalbuminuria as a marker of early cardiac, renal and retinal structural and functional changes in essential hypertension. The longitudinal study, which is in progress, will confirm the prognostic value of microalbuminuria in essential hypertension.