Tiziana Di Chiara

Hemostatic function in young subjects with central obesity: relationship with left ventricular function.

This study was designed to evaluate coagulation and fibrinolysis activity and their relationship with left ventricular function in young obese subjects with central fat distribution. We assessed coagulation and fibrinolysis activity by evaluation of factor VII activity, fibrinogen and plasminogen, plasminogen activator inhibitor (PAI), and tissue plasminogen activator antigen basally (tPA1) and after venous occlusion (tPA2). These measures were evaluated in young (< 40 years) obese subjects with central fat distribution (n = 19) and in comparable lean subjects (n = 20). Blood glucose, triglycerides, total and high-density lipoprotein (HDL) cholesterol, apolipoprotein (apo) A1 and apo B, fasting immunoreactive insulin, and lipoprotein(a) levels were also measured by current methods. Left ventricular ejection fraction (LVEF) and peak filling rate (PFR) determined by radionuclide angiocardiography and left ventricular mass (LVM) and LVM indexed for body height (LVM/H) determined by echocardiographic study were calculated. Central obesity was evaluated by the waist to hip ratio (WHR) according to the criteria of the Italian Consensus Conference of Obesity. Factor VII (P < .001), fibrinogen (P < .001), plasminogen (P < .001), PAI activity (P < .001), tPA1 (P < .02), fasting blood glucose (P < .01), apo B (P < .02), and immunoreactive insulin (P < .01) were significantly higher in obese than in lean subjects. In contrast, HDL cholesterol (P < .01), tPA2 (P < .01), LVEF (P < .001), and PFR (P < .02) were significantly lower in obese than in lean subjects. In all subjects, WHR correlated directly with fibrinogen and inversely with tPA2; LVEF correlated inversely with tPA1, PAI, and fibrinogen; and PFR correlated inversely with factor VII activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Visceral obesity and metabolic syndrome: two faces of the same medal?

In this review, we have analyzed the role of visceral obesity in the occurrence of metabolic syndrome (MetS). MetS is a common metabolic disorder that has been related recently to the increasing prevalence of obesity. The disorder is defined in various ways, but in the near future a new definition(s) should be applicable worldwide. The pathophysiology has been largely attributed, in the past years, to insulin resistance, although several epidemiological and pathophysiological data now indicate visceral obesity as a main factor in the occurrence of all the components of MetS. In view of this, relationships among visceral obesity, free fatty acids, dyslipidemia and insulin resistance have been reported. In addition, the effects of some adipocytokines and other proinflammatory factors produced by fat accumulation on the occurrence of MetS have been also emphasized. Accordingly, the “hypoadiponectinemia hypothesis” has been proposed as the most interesting to explain the pathophysiology of MetS. The epidemiologic, pathophysiologic and clinical data reported seem to indicate that MetS might be considered a fatal consequence of visceral obesity.

Heredity and obesity-associated hypertension: impact of hormonal characteristics and left ventricular mass

Objectives: To investigate the influence of heredity on obesity-associated hypertension, we evaluated casual and 24-h blood pressure, left ventricular mass and some metabolic and hormonal measurements in normotensive obese subjects. Design: Healthy, normotensive obese subjects (n=81) with positive or negative family history of hypertension were studied. Both groups were also subdivided according to a positive or a negative family history of obesity. Accordingly, 45 obese subjects had a positive family history of hypertension, 25 of these having a positive (subgroup A) and 20 having a negative family history of obesity (subgroup B). The other 36 obese subjects had a negative family history of hypertension, 19 of these having a positive (subgroup C) and 17 having a negative family history of obesity (subgroup D). Methods: Casual and 24-h systolic (SBP), diastolic (DBP) and mean blood pressure (MBP) were evaluated. Serum fasting blood sugar, total cholesterol and triglycerides levels, urinary excretion of sodium, immunoreactive fasting insulin, plasma ANF levels, plasma renin activity (PRA), plasma aldosterone level, plasma adrenaline and noradrenaline levels and echocardiographic total left ventricular mass (LVM) and LVM: height ratio were also calculated. Results: Twenty-four-hour DBP, 24-h MBP, LVM, LVM:height ratio, total cholesterol and PRA values were significantly higher in normotensive obese offspring of hypertensive parents than in obese offspring of normotensive parents. Twenty-four-hour DBP and MBP, LVM, LVM:height ratio, insulin level, insulin:glucose ratio and PRA were significantly higher in subgroup A than in subgroup B. Fasting blood sugar level, 24-h DBP and MBP, insulin level, insulin:glucose ratio, PRA, noradrenaline, adrenaline and plasma aldosterone levels were significantly higher in subgroup C than in subgroup D. Multivariate analysis also indicated that 24-h MBP and PRA levels were significantly influenced by the association between a positive family history of hypertension and obesity. Conclusions: The present results suggest that a family history of obesity might increase the risk of developing hypertension in obese subjects. An elevated PRA may precede the development of hypertension in obese subjects who are at risk for developing hypertension.

Hypoadiponectinemia: A Link between Visceral Obesity and Metabolic Syndrome

Metabolic syndrome (MetS) represents a combination of cardiometabolic risk factors, including visceral obesity, glucose intolerance or type 2 diabetes, elevated triglycerides, reduced HDL cholesterol, and hypertension. MetS is rapidly increasing in prevalence worldwide as a consequence of the “epidemic” obesity, with a considerable impact on the global incidence of cardiovascular disease and type 2 diabetes. At present, there is a growing interest on the role of visceral fat accumulation in the occurrence of MetS. In this review, the effects of adipocytokines and other proinflammatory factors produced by fat accumulation on the occurrence of the MetS have been also emphasized. Accordingly, the “hypoadiponectinemia” has been proposed as the most interesting new hypothesis to explain the pathophysiology of MetS.

Central obesity and hypertensive renal disease: association between higher levels of BMI, circulating transforming growth factor beta1 and urinary albumin excretion.

Objective: In this study, the relationship between circulating transforming growth factor β1 (TGFβ1) and urinary albumin excretion (UAE) has been investigated in non‐obese and central obese hypertensive patients. Design and Patients: Fifty‐eight consecutive hypertensive outpatients both lean and with central obesity were enrolled and divided in three groups, according to their body mass index (BMI) values. Group A: 16 lean hypertensives (men with BMI <25 kg/m 2 and women with BMI <24.7 kg/m 2 ); Group B: 16 overweight hypertensives (men with BMI ≥25 kg/m 2 and <30 kg/m 2 and women with BMI ≥24.7 kg/m 2 and <27.3 kg/m 2 ); Group C: 26 obese hypertensives (men with BMI ≥30 kg/m 2 and women with BMI ≥27.3 kg/m 2 ). Measures: In all patients, UAE, by immunonephelometric assay, circulating TGFβ1 by a solid‐phase specific sandwich enzyme‐linked immunosorbent assay (ELISA) technique, blood urea nitrogen (BUN) and creatinine, by routine laboratory methods, were determined. In addition, left ventricular telediastolic internal diameter (LVIDd), interventricular septum diastolic (IVSTd), posterior wall thickness (PWT), total and normalized to height 2.7 left ventricular mass (LVM, LVM/h 2.7 ), relative wall thickness (RWT) and left ventricular ejection fraction (EF) by M‐B Mode echocardiography were calculated. Results: Overweight and obese hypertensives had significantly (p < 0.05) higher BMI, waist–hip ratio (WHR), UAE and TGFβ1 than lean hypertensives. Obese hypertensives had significantly (p < 0.05) higher total and indexed LVM values than lean hypertensives. Obese hypertensives had significantly (p < 0.05) higher BMI, UAE and TGFβ1 than overweight hypertensives. In all subjects, TGFβ1 correlated directly with BMI (r = 0.52; p < 0.0001), WHR (r = 0.48; p < 0.003), MBP (r = 0.31; p < 0.02) and UAE (r = 0.57; p < 0.0001). Multiple regression analysis indicated that BMI, MBP and UAE were able to explain the 47.9% TGFβ1 variability (r = 0.69; p < 0.0001), and that TGFβ1 was the best predictor of UAE changes (r = 0.60; p < 0.0001). Conclusion: Our data suggest that TGFβ1 levels are positively associated with BMI, MBP and UAE in hypertensive subjects. This also indicates that TGFβ1 overproduction might be considered a pathophysiology mechanism of progressive renal function impairment in obese hypertensives.

Transforming growth factor beta1 and additional renoprotective effect of combination ACE inhibitor and angiotensin II receptor blocker in hypertensive subjects with minor renal abnormalities: a 24-week randomized controlled trial

Objective To verify the benefit of renin–angiotensin system blockade in hypertension, the effects of 24 weeks’ losartan and ramipril treatment, both alone and in combination, on urinary albumin excretion (UAE) and circulating transforming growth factor β1 (TGFβ1) have been evaluated in hypertensive subjects with minor renal abnormalities. Design and methods Fifty-one patients with stage 1 and 2 essential hypertension and with UAE ≥20 mg/24 h but with maintained renal function have been included. After a 4-week run-in with placebo administration, a randomized double-blind, three-arm double-dummy trial was used. All the hypertensives (HT) were allocated randomly to three treatment arms (17 patients for each group) and they were single-matched for age, gender, body mass index (BMI), systolic and diastolic blood pressure. Active treatment consisted of losartan (50 mg/day), ramipril (5 mg/day) and combined (losartan 50 mg/day plus ramipril 5 mg/day) for 24 weeks. Hydrochlorothiazide 12.5 mg/day was added in HT patients with uncontrolled blood pressure (≥140/90 mmHg) during the active treatment period. In all patients UAE, by immunonephelometric assay; circulating TGFβ1 by a solid-phase specific sandwich enzyme-linked immunosorbent assay (ELISA); and blood urea nitrogen (BUN), creatinine and creatinine clearance and potassium, by routine laboratory methods, were determined after placebo treatment and 24 weeks follow-up. Results The three treatment groups were comparable for gender, age, BMI, blood pressure, UAE and renal function measurements. During the active treatment period it was necessary to add hydrochlorothiazide in five patients – two each of the losartan and ramipril groups and one of the combined group. At the end of treatment, significant (P < 0.05) reductions in systolic, diastolic and mean blood pressure, UAE and TGFβ1 levels were observed in all the groups. No change in renal function measurements were observed. The absolute and percentage reduction in UAE and TGFβ1 were significantly higher in the combined group than in the losartan or ramipril groups. No significant changes in absolute and percentage reduction of systolic, diastolic and mean blood pressure were found. All treatment regimens were well tolerated with few and transient side-effects. Conclusion These data indicate an additional renoprotective effect of dual blockade of the renin–angiotensin system (RAS) in hypertensive patients with minor renal abnormalities. In addition, the contemporaneus and marked decrease in TGFβ1 and UAE levels in hypertensives treated with combined therapy might indicate the presence of a subset of subjects who may benefit from complete RAS blockade.

Relationship between circulating E-selectin, DD genotype of angiotensin-converting-enzyme, and cardiovascular damage in central obese subjects

Fifty-six young central obese patients were investigated to evaluate relationships between soluble E-selectin (sE-S), angiotensin-converting enzyme (ACE) gene polymorphism, left ventricular function and structure, and carotid morphology by determination of sE-S and ACE genotypes. Our results indicated that central obese subjects with concomitant higher levels of sE-S and ACE DD genotype may be characterized by early cardiovascular alterations and then considered a particular subset of subjects at higher risk of cardiovascular disease.

Transforming growth factor β1 T29C gene polymorphism and hypertension : Relationship with cardiovascular and renal damage

Distribution of T29C TGFβ1 gene polymorphism was analysed in 260 hypertensive and 134 normotensive subjects. Circulating TGFβ1 and procollagen type III levels, microalbuminuria, left ventricular geometry and function were evaluated in all the hypertensives subgrouped according to T29C TGFβ1 gene polymorphism. Circulating TGFβ1 by ELISA technique, procollagen type III by a specific radioimmunoassay, microalbuminuria by radioimmunoassay, left ventricular geometry and function by echocardiography were determined. All groups were comparable for gender, age and sex. Regarding T29C TGFβ1 gene polymorphism, prevalence of TC or CC genotypes was significantly (p<0.05) higher in hypertensives than normotensives. TC and CC hypertensives were characterized by a higher prevalence of subjects with microalbuminuria (p<0.001 TC vs TT; p<0.05 CC vs TT), left ventricular hypertrophy (p<0.01 TC and CC vs TT), and by increased levels of procollagen type III (p<0.05 TC and CC vs TT). TC hypertensives were also characterized by a significant increase (p<0.05) of LVM and LVM/h2.7 and of urinary albumin excretion (p<0.05) values than those detectable in TT hypertensives. Our data suggest that T29C TGFβ1 gene polymorphism was associated to clinical characteristics suitable to recognize hypertensives with a higher severity of hypertension.

Association Between Low Education and Higher Global Cardiovascular Risk

This study was designed to evaluate the impact of educational status on global cardiovascular risk in a southern Italian urban population. The study population consisted of 488 consecutive outpatients aged 18 years and older. Educational status was categorized according to the number of years of formal education as follows: (1) low education group (<10 years) and (2) medium‐high education group (10–15 years). In both groups, cardiometabolic comorbidities (obesity, visceral obesity, diabetes, dyslipidemia, metabolic syndrome, microalbuminuria, left ventricular hypertrophy) and global cardiovascular risk, according to international guidelines, were analyzed. Left ventricular mass index and ejection fraction by echocardiography and E/A ratio, by pulsed‐wave Doppler, were calculated. The low education group was characterized by a significantly higher prevalence of patients with visceral obesity (P=.021), hypertension (P=.010), metabolic syndrome (P=.000), and microalbuminuria (P=.000) and greater global cardiovascular risk (P=.000). Significantly increased levels of microalbuminuria (P=.000) and significantly decreased values of E/A ratio (P=.000) were also detected in the low education group. Global cardiovascular risk correlated directly with waist‐to‐hip ratio (P=.010), microalbuminuria (P=.015), and the metabolic syndrome (P>.012) and inversely with educational status (P=.000). Education was independently (P=.000) associated with global cardiovascular risk. These data indicate a strong association between low education and cardiometabolic comorbidities suitable to influence the evolution of chronic degenerative diseases. Preventive strategies need to be more efficient and more effective in this patient population.

A family with various symptomatology suggestive of Anderson-Fabry disease and a genetic polymorphism of alpha galactosidase A gene.

BACKGROUND Anderson/Fabry disease expresses a wide range of clinical variability in patients that it is possible to explain referring to a genetic variability with numerous mutations described in the literature (more than 600). METHODS We report some clinical cases of some members of a Sicilian family to express phenotypical variability of this disease in subjects with the same genetic mutation RESULTS The first case was a 59-year-old female. Brain MRI revealed right frontal periventricular white matter of likely vascular-degenerative origin. The probands alpha galactosidase A activity was 3.7nmol/mL/h. Molecular genetics revealed a polymorphism: -10 C>T; IVS 2-76_80del5; IVS4-16 A>G; IVS6-22 C>T. The second case was a 30year-old male affected by acroparesthesias and hypoidrosis since he was an adolescent. Renal impairment was first detected at age 29; it began with high plasma levels of creatinine and microalbuminuria date. The third case was a 41year-old daughter that presented with acroparesthesias, hypoidrosis since she was very young. The patients alpha galactosidase A activity was 4.1nmol/mL/h, in whole blood, which is compatible with heterozygote subject for Fabrys disease or healthy control. The fourth case was a male grandson of the proband, 9year-old child. He had a classic gastrointestinal involvement. He complained of recurrent abdominal pain, post prandial bloating and pain. This childs enzyme activity was 1.65nmol/mL/h. In cases 2, 3, and 4, molecular genetics revealed a polymorphism: -10 C>T; IVS 2-76_80del5; IVS4-16 A>G; IVS6-22 CG, IVS6-22C>T polymorphisms occurred in 8.9% and 3.7% of the subjects respectively, and the significance of this haplotype in FD pathology remains unknown but possibly suggestive of Anderson/Fabry disease.