Paola Cusimano

Influence of metabolic syndrome on hypertension‐related target organ damage

Objectives.  The aim of our study was to analyse, in a wide group of essential hypertensive patients without diabetes mellitus, the influence of metabolic syndrome (MS) (defined according to the criteria laid down in the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults) on markers of preclinical cardiac, renal and retinal damage.

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.

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.

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.

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.

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.

Impact of type 2 diabetes on left ventricular geometry and diastolic function in hypertensive patients with chronic kidney disease

Left ventricular hypertrophy (LVH) and diastolic dysfunction are very common in patients with chronic kidney disease (CKD). Aim of this study was to evaluate the impact of type 2 diabetes on LV geometry and diastolic function in hypertensive patients with CKD. We enrolled 288 Caucasian subjects with hypertension and CKD; of them, 112 had diabetes. Patients with cardiovascular (CV) diseases, glomerular filtration rate (GFR) >60 ml min−1 per 1.73 m2, dialysis treatment and other major non-CV diseases were excluded. All patients underwent routine biochemical analyses and echocardiographic examination with tissue Doppler imaging (TDI). Patients with diabetes had significantly higher LV wall thicknesses (P=0.0001), relative wall thickness (RWT) (P=0.0001) and left atrium volume index (P=0.03), when compared with patients without diabetes. Further, diabetic patients had very high prevalence of concentric LVH. Em, evaluated by TDI, was significantly lower in patients with diabetes (P=0.005). However, the difference lost statistical significance after correction by analysis of covariance for RWT. Multiple stepwise linear regression analysis showed that the variables independently associated with Em were: age (β 0.364; P=0.0001), GFR (beta 0.101; P=0.019), and the presence of diabetes (β 0.166; P=0.002). Our study showed that in hypertensive patients with CKD the presence of diabetes is associated with increased LV-wall thicknesses and concentric geometry; further, diabetes together with renal function (GFR) is associated with worse diastolic function, independently of potential confounders, such as age, gender, body mass index and blood pressure.

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 (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.

Relationships between metabolic syndrome and left ventricular mass in hypertensive patients: does sex matter?

Several studies documented an association between metabolic syndrome (MetS) and left ventricular (LV) hypertrophy. However, only in a few of these studies the impact of MetS on left ventricular mass (LVM) was separately analysed by gender, with conflicting results. The aim of our study was to verify, in a wide sample of essential hypertensive patients, the influence of gender, if any, on the relationship between MetS and LVM. We enrolled 475 non-diabetic subjects (mean age: 46±11 years), with mild-to-moderate essential hypertension, of whom 40% had MetS, defined on the basis of Adult Treatment Panel III (ATPIII) criteria. All the patients underwent a 24-h ambulatory blood pressure monitoring and an echocardiogram. LVM indexed for height2.7 (LVMH2.7) was significantly (P<0.001) higher in women with MetS (n=83) than in those without it (n=97; 54±17 vs 42±11 g m−2.7). An equally significant difference in LVMH2.7 was documented also in male gender between the two groups with (n=105) and without MetS (n=190; 51±14 vs 43±11 g m−2.7; P<0.001). The relationship between MetS and LVMH2.7 remained statistically significant (P<0.001) in both sexes, in multiple regression analyses, even after adjustment for potential confounding factors. Our results seem to suggest that the relationship between MetS and LVM is not significantly affected by gender, being LVM increased in both hypertensive women and men with MetS.