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ABSTRACT: The intima-media thickness (IMT) is considered as a surrogate marker for atherosclerotic disease. The aim of this study was to analyze the relationship of carotid IMT with fetuin-A in patients with essential hypertension (EH) and normal renal function. The plasma levels of fetuin-A, interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) and the biomarker of oxidative stress 8-iso-PGF2alpha were assayed in samples from 105 untreated EH patients. Carotid IMT measurements were also performed. EH was studied overall and after dividing in EH with IMT and <0.9 mm. All of the biomarkers were significantly different between the two subgroups, in particular, the fetuin-A level was lower in the patients with an IMT 0.9 mm. In the overall group, the linear analysis of correlation demonstrated that the IMT was significantly inversely correlated with the fetuin-A level (r=-0.40, P<0.0001) and directly with TNF-α (r=0.39, P<0.0001), IL-6 (r=0.38, P<0.0001) and 8-iso-PGF2alpha (r=0.356, P<0.0003). The multiple regression analysis performed that assigned IMT as a dependent variable showed that fetuin-A (β=-0.268, P<0.0001) was independently correlated with the IMT. Receiver-operator curves demonstrated that fetuin-A levels have a predictive power of IMT>0.9 mm (AUC (area under the curve) 0.738, P<0.0001). Our results suggest that in EH, fetuin-A is associated with the IMT independently of oxidative stress and renal function, thus predicting increases in the IMT.Hypertension Research advance online publication, 13 September 2012; doi:10.1038/hr.2012.136.
Hypertension Research 09/2012; · 2.58 Impact Factor
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ABSTRACT: 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.
European journal of preventive cardiology. 05/2012;
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Journal of hypertension 03/2011; 29(3):621-2; author reply 622. · 4.02 Impact Factor
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ABSTRACT: There is clear evidence that urinary albumin excretion levels, even below the cut-off values currently used to diagnose microalbuminuria, are associated with an increased risk of cardiovascular events. The relationships of microalbuminuria with a variety of risk factors, such as hypertension, diabetes and metabolic syndrome and with several indices of subclinical organ damage, may contribute, at least in part, to explain the enhanced cardiovascular risk conferred by microalbuminuria. Nonetheless, several studies showed that the association between microalbuminuria and cardiovascular disease remains when all these risk factors are taken into account in multivariate analyses. Therefore, the exact pathophysiological mechanisms explaining the association between microalbuminuria and cardiovascular risk remain incompletely understood. The simple search for microalbuminuria in hypertensive patients may enable the clinician to better assess absolute cardiovascular 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 cardiovascular risk factors.
Journal of hypertension 12/2010; 28(12):2357-69. · 4.02 Impact Factor
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Silvio Buscemi,
John A Batsis,
Salvatore Verga,
Tommasa Carciola,
Alessandro Mattina,
Salvatore Citarda,
Andrea Re,
Mariangela Arnone,
Leonardo D'Orio,
Serena Belmonte,
Angela D'Angelo, Giovanni Cerasola
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ABSTRACT: Obesity is associated with well-known cardiovascular risk factors and a lower life expectancy. This study investigated whether nonoperative nutritional treatment of obesity without comorbidities influenced the carotid intima-media thickness (c-IMT) in the long run. Fifty-four subjects of an original cohort of 251 subjects were re-evaluated 10 years after a medical nutritional treatment (MNT) with cognitive-behavioral approach for uncomplicated obesity. Forty subjects were classified as failure (10-year body weight change > 0.5 kg) and 14 (body weight change ≤ 0.5 kg) as a success of the MNT. Ten years after MNT, c-IMT significantly increased (0.06 ± 0.02 mm; P = 0.004) in the failure group and significantly decreased (-0.07 ± 0.03 mm; P = 0.027) in the success group. Ten-year change in c-IMT correlated significantly with 10-year change in body weight (r = 0.28; P = 0.040). Multiple stepwise linear regression analysis demonstrated that age, final BMI, and group (success or failure) influenced independently the 10-year c-IMT. In conclusion, this study is in agreement with the possibility that the successful MNT of obesity may be an effective choice in the long run and seems to indicate that it may be able to reduce the cardiovascular risk as reflected by the change in c-IMT.
Obesity 12/2010; 19(6):1187-92. · 4.28 Impact Factor
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ABSTRACT: Introduction Evidence suggests that decreased haemoglobin plasma concentration may be a predictor of adverse cardiovascular events in patients with chronic kidney disease (CKD). We hypothesized that in CKD patients, oxidative stress could influence the development of cardiovascular damage via a relationship with haemoglobin levels.Methods We assayed plasma levels of the biomarker of oxidative stress 8-ISO-prostaglandin F2α (8-ISO-PGF2α) and of haemoglobin in 193 stage 2-5 CKD patients, investigating their relationship. Eighty healthy subjects and 80 patients with primary hypertension having normal renal function were enrolled as controls.Results The CKD group was divided according to 8-ISO-PGF2α quartiles, and decreasing levels of both haemoglobin and estimated glomerular filtration rate (eGFR) along with increasing quartiles were observed. In the 193 CKD patients, the linear analysis of correlation showed inverse correlations of 8-ISO-PGF2α with both haemoglobin and eGFR (r = −0.47; r = −0.81; p < 0.00001, respectively). In the control groups, no correlation between haemoglobin and 8-ISO-PGF2α was found. The multiple regression analysis carried out in CKD patients, by a model with 8-ISO-PGF2α as the dependent variable, and including haemoglobin and all confounding factors, confirmed the inverse relationship between haemoglobin and 8-ISO-PGF2α (β = −0.50; p < 0.00001). In this model, only when eGFR was added did the relationship between haemoglobin and 8-ISO-PGF2α lose statistical significance. In this final multivariate model, 8-ISO-PGF2α correlated independently with eGFR (β = −0.82; p < 0.0001).Conclusions In CKD, haemoglobin plasma level is inversely related to oxidative stress, depending on GFR. It remains to be elucidated whether or not the biochemistry of nitric oxide and haemoglobin interaction has a role in causing this relationship.Received for publication 20 August 2010; accepted for publication 3 October 2010.
High Blood Pressure & Cardiovascular Prevention 11/2010; 17(4):227-233.
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American Journal of Hypertension 10/2010; 23(10):1050. · 3.18 Impact Factor
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ABSTRACT: Aerobic capacity, as indicated by maximal oxygen uptake (VO(2) max) has an important role in contrasting the traditional cardiovascular risk factors and preventing cardiovascular morbidity and mortality. It is known that endothelial function, measured as flow-mediated dilation (FMD) of the brachial artery, is strictly linked to atherogenesis and cardiovascular risk. However, the relationship between VO(2) max and FMD has not been fully investigated especially in healthy non-obese subjects. This preliminary study cross-sectionally investigated the relationship between VO(2) max and FMD in 22 non-obese, healthy sedentary male subjects. Dividing the cohort in two subgroups of 11 subjects each according to the median value of VO(2) max, the FMD was significantly lower in the subgroup with lower VO(2) max (mean ± sem: 7.1 ± 0.7 vs. 9.5 ± 0.8 %; P = 0.035). Absolute VO(2) max (mL min(-1)) was significantly and independently correlated with body fat mass (r = -0.50; P = 0.018) and with FMD (r = 0.44; P = 0.039). This preliminary study suggests that maximal oxygen uptake is independently correlated with endothelial function in healthy non-obese adults. These results are also in agreement with the possibility that improving maximal oxygen uptake may have a favorable effect on endothelial function and vice versa.
Acta Diabetologica 10/2010; · 2.78 Impact Factor
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Ettore Ambrosioni,
Michele Bombelli, Giovanni Cerasola,
Francesco Cipollone,
Claudio Ferri,
Irene Grazioli,
Cristiana Leprotti,
Giuseppe Mancia,
Gabriella Melzi,
Amedeo Mugellini,
Giuseppe Mulè,
Giuseppe Palasciano,
Antonio Salvetti,
Bruno Trimarco
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ABSTRACT: Systolic hypertension is very common in the elderly and is strongly associated with the risk of cardiovascular and cerebrovascular events. The control of systolic hypertension is difficult and most patients require combination antihypertensive therapy. Few data are available regarding the efficacy of angiotensin II receptor antagonists on systolic hypertension of the elderly. The aim of this double-blind, double-dummy, randomized, parallel-group, multicenter study was to assess the efficacy of eprosartan 600 mg in combination with hydrochlorothiazide (HCTZ) 12.5 mg in comparison with losartan 50 mg in combination with HCTZ 12.5 mg, in reducing blood pressure in elderly patients with grade 2 systolic hypertension who did not optimally respond to eprosartan or losartan monotherapy.
After a 3-week placebo wash-out, 155 patients with an Office trough sitting systolic blood pressure (Office sitSBP) >or=160 mmHg and <180 mmHg were randomized to eprosartan 600 mg (n=78) or losartan 50 mg (n=77) once daily for 6 weeks. In patients not optimally responding to monotherapy (Office sitSBP>or=130 mmHg) 12.5 mg HCTZ was added as fixed combination once daily for 6 weeks. A 24-hour ambulatory blood pressure monitoring (ABPM) was performed at the end of wash-out and at the end of the fixed-combination period.
No statistically significant difference was found between eprosartan/HCTZ and losartan/HCTZ on the primary endpoint (24-hour ABPM SBP) with an adjusted mean difference between treatments of 3.1 mmHg (95% CI: -0.32-6.59). However, the mean 24-hour ABPM SBP significantly decreased by 16.7 mmHg with eprosartan/HCTZ and 20.3 mmHg with losartan/HCTZ (P<0.001 vs. baseline). The mean Office sitSBP significantly decreased by 28.7 mmHg and 29.6 mmHg respectively, with eprosartan/HCTZ and losartan/HCTZ (P<0.001 vs.baseline and vs. monotherapy).
In this study, eprosartan/HCTZ did not demonstrate to be superior to losartan/HCTZ in reducing ABPM systolic hypertension in the elderly.
Advances in Therapy 06/2010; 27(6):365-80. · 2.11 Impact Factor
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ABSTRACT: 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.
We searched PubMed for manuscripts regarding left ventricular hypertrophy (LVH) in CKD. Definition of LVH was different according to different studies.
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.
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.
Journal of nephrology 05/2010; 24(1):1-10. · 1.65 Impact Factor
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ABSTRACT: 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 (β=0.22; p<0.001 and β=-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.
International journal of cardiology 03/2010; 145(2):372-5. · 7.08 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Nephrology 03/2010; 15(2):203-10. · 1.31 Impact Factor
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ABSTRACT: Metabolic syndrome (MetS) is associated with increased cardiovascular risk. We hypothesize that early vascular changes are already present at the time of diagnosis of MetS. The relationship of different measures of early vascular impairment with body fat distribution and the natural progression of MetS was examined in newly diagnosed subjects non-pharmacologically treated.
246 consecutively enrolled subjects were categorized according to the presence of MetS and type 2 diabetes (T2D). Intra-renal Doppler flow was used to ascertain resistive (RI) and pulsatility (PI) indices as markers of vascular resistance. Carotid intima-media thickness (IMT), cutis-rectis (CR) and rectis-aorta (RA) thicknesses were measured by ultrasonography; RA/CR ratio was used as measure of body fat distribution. Pro-inflammatory cytokines, C-reactive protein, oxidative markers insulin and adiponectin blood concentrations were also measured.
Baseline characteristics demonstrated increasing trends in biochemical, inflammatory, and oxidative parameters from MetS-, MetS+, to MetS+/T2D (p<0.001). After adjusting for age, the same increasing trends across the groups were observed in both sexes in IMT (p<0.001), RI (p<0.001) and PI (p<0.001). IMT correlated with RI (r=0.25; p<0.001), PI (r=0.26; p<0.001), and RA/CR ratio (r=0.43; p<0.001).
Carotid IMT and intra-renal resistances are elevated at an early stage in MetS and are associated with a dysregulated production of fat-derived hormones and cytokines.
Diabetes research and clinical practice 10/2009; 86(3):177-85. · 2.16 Impact Factor
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ABSTRACT: 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.
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).
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).
Our results suggest that in patients with essential hypertension, MAU and CRP are independently associated with an increased aortic stiffness.
American Journal of Hypertension 08/2009; 22(10):1041-7. · 3.18 Impact Factor
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ABSTRACT: Metabolic syndrome (MS) may be associated with the presence of an energy-sparing metabolism that predisposes to the excess accumulation of body fat. This study examined the relationship between reported energy intake and obesity in individuals with and without MS.
Ninety consecutive non-diabetic obese subjects were divided into 2 groups based on the presence (MS+: no.=50) or absence (MS-: no.=40) of MS. The study design was cross-sectional. The 3-day food record method was used to assess the subjects' usual energy intake and the Diet Readiness Test (DRT) was also administered. Compared to the MS- group, the MS+ group had a significantly higher body weight, body mass index (mean+/-SEM: 39.1+/-1.3 vs 31.5+/-0.9, p<0.001) and fat mass. The absolute energy intake of the MS+ group (8629+/-331 kJ/24h) did not differ from that of the MS- group (8571+/-515 kJ/24h; p=ns). The daily energy intake normalized for the fat-free mass (FFM) size was higher in the MS- group (163+/-8 kJ/kg-FFM x 24h) than in the MS+ group (138+/-4 kJ/kg-FFM x 24h; p<0.03). The DRT test results were similar in both groups except that section 6 (exercise patterns and attitudes) score was lower in the MS+ group (10.0+/-0.5) than in the MS- group (11.9+/-0.5; p<0.01).
The results of this study support the hypothesis that subjects with MS have an energy-sparing metabolism.
Journal of endocrinological investigation 05/2009; 32(6):538-41. · 1.57 Impact Factor
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ABSTRACT: 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.
All patients underwent echocardiographic examination. Patients on stage 1 CKD, dialysis treatment, or with cardiovascular diseases were excluded.
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.
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.
Journal of hypertension 03/2009; 27(3):633-41. · 4.02 Impact Factor
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ABSTRACT: 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.
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.
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).
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.
Nephrology 12/2008; 13(6):467-71. · 1.31 Impact Factor
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ABSTRACT: Subjects who develop diabetes have an increased cardiovascular risk even before the appearance of diabetes. The aim of this study was to investigate the glycaemic variability measured by continuous glucose monitoring (CGM CV%) in nondiabetic subjects with metabolic syndrome (MS) and to explore if glycaemic variability was associated with circulating levels of interleukin-6 (IL-6), a proinflammatory cytokine, or with an anti-inflammatory factor like adiponectin. Three groups of obese subjects with (MS+: 6m, 8f; BMI 33.1+/-1.4 mean+/-SEM) or without metabolic syndrome (MS-: 2m, 4f; BMI 29.2+/-2.2) and with MS associated with type 2 diabetes (MS/T2D: 3m, 5f; BMI 32.9+/-1.4) were investigated. The glycaemic variability was measured in all subjects in terms of CV% of the glycaemic values obtained every 3 min during the course of a 48 h CGM performed using a subcutaneous glucose sensor. The average CGM CV% increased from MS- group (21.1%) to the MS+ group (23.9%) and to the MS+/T2D group (27.4%) but it was not correlated to the CGM mean glycaemia (r=0.20; P=ns). In some instances, CGM CV% was found higher in MS+ subjects than in some MS+ T2D ones. Stepwise multiple correlation analysis showed that IL-6 predicted CGM CV% (R(2)=0.35, beta=0.13; P<0.05) independently from BMI, waist circumference, adiponectin and insulin concentrations. In conclusion, the CGM CV% may contribute to better describe the individual metabolic state and to understand the pathogenesis of endothelial dysfunction in non diabetic subjects with MS.
Acta Diabetologica 10/2008; 46(1):55-61. · 2.78 Impact Factor
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Santina Cottone,
Giuseppe Mulè,
Marco Guarneri,
Alessandro Palermo,
Maria C Lorito,
Raffaella Riccobene,
Rosalia Arsena,
Francesco Vaccaro,
Anna Vadalà,
Emilio Nardi,
Paola Cusimano, Giovanni Cerasola
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ABSTRACT: 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).
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.
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.
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.
Nephrology Dialysis Transplantation 09/2008; 24(2):497-503. · 3.40 Impact Factor
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Enrico Agabiti Rosei,
Giovanni de Simone,
Gian Francesco Mureddu,
Bruno Trimarco,
Paolo Verdecchia,
Massimo Volpe,
Maria Lorenza Muiesan,
Ettore Ambrosioni,
Giampaolo Bernini, Giovanni Cerasola, [......],
Giuseppe Mancia,
Dario Manfellotto,
Andrea Mezzetti,
Carlo Palombo,
Stefano Perlini,
Achille Pessina,
Alessandro Rappelli,
Gianpaolo Rossi,
Antonio Salvetti,
Franco Veglio
Giornale italiano di cardiologia (2006) 07/2008; 9(6):427-54.
