Showing papers by "Giuseppe Mancia published in 2011"

Reappraisal of European guidelines on hypertension management:: A European Society of Hypertension Task Force document

Abstract: ACEangiotensin-converting enzymeBPblood pressureDBPdiastolic blood pressureeGFRestimated glomerular filtration rateESCEuropean Society of CardiologyESHEuropean Society of HypertensionETendothelinIM...

Early Sympathetic Activation in the Initial Clinical Stages of Chronic Renal Failure

Abstract: Direct and indirect indices of neuroadrenergic function have shown that end-stage renal disease is characterized by a marked sympathetic overdrive. It is unknown, however, whether this phenomenon r...

Effects of intensive blood pressure reduction on myocardial infarction and stroke in diabetes: a meta-analysis in 73,913 patients.

Abstract: ObjectiveGuidelines generally recommend intensive lowering of blood pressure (BP) in patients with type 2 diabetes. There is uncertainty about the impact of this strategy on case-specific events. Thus, we generated estimates of the effects of BP reduction on the risk of myocardial infarction (MI) an

Better compliance to antihypertensive medications reduces cardiovascular risk.

Abstract: ObjectiveThe effect of compliance with antihypertensive medications on the risk of cardiovascular outcomes in a population without a known history of cardiovascular disease has been addressed by a large population-based prospective, cohort study carried out by linking Italian administrative database

Changes in Albuminuria Predict Mortality and Morbidity in Patients with Vascular Disease

Abstract: The degree of albuminuria predicts cardiovascular and renal outcomes, but it is not known whether changes in albuminuria also predict similar outcomes. In two multicenter, multinational, prospective observational studies, a central laboratory measured albuminuria in 23,480 patients with vascular disease or high-risk diabetes. We quantified the association between a greater than or equal to twofold change in albuminuria in spot urine from baseline to 2 years and the incidence of cardiovascular and renal outcomes and all-cause mortality during the subsequent 32 months. A greater than or equal to twofold increase in albuminuria from baseline to 2 years, observed in 28%, associated with nearly 50% higher mortality (HR 1.48; 95% CI 1.32 to 1.66), and a greater than or equal to twofold decrease in albuminuria, observed in 21%, associated with 15% lower mortality (HR 0.85; 95% CI 0.74 to 0.98) compared with those with lesser changes in albuminuria, after adjustment for baseline albuminuria, BP, and other potential confounders. Increases in albuminuria also significantly associated with cardiovascular death, composite cardiovascular outcomes (cardiovascular death, myocardial infarction, stroke, and hospitalization for heart failure), and renal outcomes including dialysis or doubling of serum creatinine (adjusted HR 1.40; 95% CI 1.11 to 1.78). In conclusion, in patients with vascular disease, changes in albuminuria predict mortality and cardiovascular and renal outcomes, independent of baseline albuminuria. This suggests that monitoring albuminuria is a useful strategy to help predict cardiovascular risk.

Blood Pressure Targets Recommended by Guidelines and Incidence of Cardiovascular and Renal Events in the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET)

Abstract: Background—Hypertension treatment guidelines recommend that blood pressure (BP) be lowered to 75%) in which BP was reduced to <140/90 or <130/80 mm Hg. After adjustment for demographic and clinical variables, a progressive increase in the proportion of visits in which BP was reduced to <140/90 or <130/80 mm Hg was associated with a progressive reduction in the risk of stroke, new onset of microalbuminuria or macroalbuminuria, and return to normoalbuminuria in albuminuric patients. An increased frequency of BP control to either target did not have an...

Cardiovascular Protection by Initial and Subsequent Combination of Antihypertensive Drugs in Daily Life Practice

Abstract: Guidelines recommend a combination of 2 drugs to be used as first-step treatment strategy in high-risk hypertensive individuals to achieve timely blood pressure control and avoid early events. The evidence that this is associated with cardiovascular (CV) benefits compared with initial monotherapy is limited, however. The objective of this study was to assess whether, compared with antihypertensive monotherapy, a combination of antihypertensive drugs provides a greater CV protection in daily clinical practice. A population-based, nested case-control study was carried out by including the cohort of 209 650 patients from Lombardy (Italy) aged 40 to 79 years who were newly treated with antihypertensive drugs between 2000 and 2001. Cases were the 10 688 patients who experienced a hospitalization for CV disease from initial prescription until 2007. Three controls were randomly selected for each case. Logistic regression was used to model the CV risk associated with starting on and/or continuing with combination therapy. A Monte-Carlo sensitivity analysis was performed to account for unmeasured confounders. Patients starting on combination therapy had an 11% CV risk reduction with respect to those starting on monotherapy (95% CI: 5% to 16%). Compared with patients who maintained monotherapy also during follow-up, those who started on combination therapy and kept it along the entire period of observation had 26% reduction of CV risk (95% CI: 15% to 35%). In daily life practice, a combination of antihypertensive drugs is associated with a great reduction of CV risk. The indication for using combination of blood pressure drugs should be broadened.

Impact of Body Mass Index and Waist Circumference on the Long-Term Risk of Diabetes Mellitus, Hypertension, and Cardiac Organ Damage

Abstract: Obesity is associated with a higher risk of developing diabetes mellitus (DM), hypertension (HT), and left ventricular hypertrophy (LVH). The present study assessed in the general population the impact of body weight and visceral obesity on the development of alterations in glucose metabolism and cardiac structure, as well as of elevation in blood pressure. In 1412 subjects randomly selected and representative of the general population of Monza, we assessed twice (in 1990/1991 and 2000/2001) body mass index (BMI); waist circumference; office, home, and 24-hour ambulatory (24-hour) blood pressure, fasting glycemia, and left ventricular mass (echocardiography). New-onset high-risk conditions were DM; impaired fasting glucose; office, home, and 24-hour HT; and LVH. The incidence of new-onset DM; impaired fasting glucose; office, home, and 24-hour HT; and LVH increased progressively from the quintile with the lowest to the quintile with the highest BMI values. Adjusting for confounders, the risk of developing new-onset DM; impaired fasting glucose; office, home, and 24-hour HT; and LVH increased significantly for an increase of 1 kg/m 2 of BMI and 1 cm of waist circumference (respectively, 8.4% [ P P P P P P P P P P P P

Blood pressure control and cardiovascular risk profile in hypertensive patients from central and eastern European countries: results of the BP-CARE study.

Abstract: Aims Limited information is available on office and ambulatory blood pressure (BP) control as well as on cardiovascular (CV) risk profile in treated hypertensive patients living in central and eastern European countries. Methods and results In 2008, a survey on 7860 treated hypertensive patients followed by non-specialist or specialist physicians was carried out in nine central and eastern European countries (Albania, Belarus, Bosnia, Czech Republic, Latvia, Romania, Serbia, Slovakia, and Ukraine). Cardiovascular risk assessment was based on personal history, clinic BP values, as well as target organ damage evaluation. Patients had a mean (±SD) age of 60.1 ± 11 years, and the majority of them (83.5%) were followed by specialists. Average clinic BP was 149.3 ± 17/88.8 ± 11 mmHg. About 70% of patients displayed a very high-risk profile. Electrocardiogram was performed in 99% of patients, echocardiography in 65%, carotid ultrasound in 24%, fundoscopy in 68%, and search for microalbuminuria in 10%. Ambulatory BP monitoring was performed in about one-fifth of the recruited patients. Despite the widespread use of combination treatment (87% of the patients), office BP control (<140/90 mmHg) was achieved in 27.1% only, the corresponding control rate for ambulatory BP (<130/80 mmHg) being 35.7%. Blood pressure control was (i) variable among different countries, (ii) worse for systolic than for diastolic BP, (iii) slightly better in patients followed by specialists than by non-specialists, (iv) unrelated to patients’ age, and (v) more unsatisfactory in high-risk hypertensives and in patients with coronary heart disease, stroke, or renal failure. Conclusion These data provide evidence that in central and eastern European countries office and ambulatory BP control are unsatisfactory, particularly in patients at very high CV risk, and not differ from that seen in Western Europe. They also show that assessment of subclinical organ damage is quite common, except for microalbuminuria, and that combination drug treatment is frequently used.

Diagnosis and management of patients with white-coat and masked hypertension

Abstract: White-coat hypertension is characterized by an elevation in clinic blood pressure but normal home or ambulatory blood-pressure values, whereas patients with masked hypertension have normal clinic blood pressure and elevated ambulatory or home blood-pressure load. Both white-coat and masked hypertension are frequent clinical entities that need appropriate recognition and a close diagnostic follow-up. White-coat and masked hypertension seem to be associated with organ damage and increased cardiovascular risk, although not invariably. In addition, patients with masked or white-coat hypertension have an increased risk of abnormalities affecting their glucose and lipid profiles. Therefore, the diagnosis of these conditions should be accurate and include the assessment of cardiovascular as well as of metabolic risk. Once diagnosed, first-line therapeutic interventions should be nonpharmacological and aim at lifestyle changes, but drug treatment can be indicated, particularly when the patient's cardiovascular risk profile is elevated or when target-organ damage is detected.

Hypertension and sexual dysfunction: time to act.

Abstract: Abbreviations ACE: angiotensin-converting enzyme; ARBs: angiotensin receptor blockers; ESH: European Society of Hypertension; PDE: phosphodiesterase.Rationale for developing a working group on sexual dysfunctionSexual dysfunction is a common clinical problem that severely affects the quality of life

Sympathetic Mechanisms, Organ Damage, and Antihypertensive Treatment

Abstract: Sympathetic activation characterizes essential hypertension, contributing to the development and progression of the high blood pressure state. Throughout the years, evidence has been accumulated to show that adrenergic overdrive also participates in the pathogenesis of the end-organ damage associated with hypertension, including cardiac hypertrophy, left ventricular diastolic dysfunction, and heart failure, as well as the vascular structural and functional alterations that frequently can be detected in large, medium-size, and small arteries. Adrenergic overdrive also participates in the renal insufficiency and failure that may accompany the clinical course of the hypertensive state. This paper reviews evidence collected over the past few years documenting the importance of neurogenic factors in the development and progression of end-organ damage. The therapeutic implications of this evidence are also highlighted.

Prognostic Value of Long-Term Blood Pressure Variability: The Evidence Is Growing

Abstract: See related article, pp 160–166 For many years, interest in blood pressure (BP) variability has been limited to the BP variations that occur within a 24-hour period and make BP values often markedly different between and within different periods of the day and night. Evidence has been obtained that some of these variations (eg, the daily BP peaks and the morning BP rise) are independently related to organ damage and the risk of cardiovascular events.1,2 Further, it has been shown that this is also the case for markers of overall BP variability, the values of which (that increase with mean BP and age3) are also related to organ damage and cardiovascular risk.4 A recent example was provided by the data obtained in the general population of the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study, in which 24-hour erratic BP variations (ie, the variations unexplained by the systematic BP oscillations induced by sleep and digestion) showed a positive relationship with the 12-year incidence of cardiovascular mortality, independently of the 24-hour mean BP values.5 For many years, the attention devoted to 24-hour BP variability has marginalized the interest in other types of BP variability, such as those occurring between days or months. On the descriptive side, evidence has been largely limited to the observation that there are clear-cut seasonal BP variations (ie, that BP is several mm Hg lower in summer than in winter)6 that are attributable to, at least in part, the vasodilator effect of higher temperatures.7 With regard to prognosis, the conclusion was drawn that long-term BP …

Sympathetic Nerve Traffic and Asymmetric Dimethylarginine in Chronic Kidney Disease

Abstract: Summary Background and objectives Sympathetic overactivity and high levels of the endogenous inhibitor of NO synthase asymmetric dimethylarginine (ADMA) are prevalent risk factors in chronic kidney disease (CKD). Design, setting, participants, & measurements In 48 stage 2 to 4 CKD patients, we investigated the relationship between efferent postganglionic muscle sympathetic nerve traffic (microneurography) and circulating ADMA and analyzed the links between these risk factors and estimated GFR (eGFR), proteinuria, and different parameters of left ventricular (LV) geometry. Results CKD patients characterized by sympathetic nerve traffic values in the third tertile showed the highest ADMA levels, and this association was paralleled by a continuous, positive relationship between these two risk factors (r 0.32, P 0.03) independent of other confounders. Both sympathetic nerve traffic and ADMA were inversely related to eGFR and directly to proteinuria and LV geometry. Remarkably, the variance of eGFR, proteinuria, and LV geometry explained by sympathetic nerve traffic and ADMA largely overlapped because sympathetic nerve traffic but not ADMA was retained as a significant correlate of the eGFR (P 0.001) and of the relative wall thickness or the left ventricular mass index/LV volume ratio (P 0.05) in models including both risk factors. ADMA, but not sympathetic nerve traffic, emerged as an independent correlate of proteinuria (P 0.003) in a model including the same covariates. Conclusions Sympathetic activity and ADMA may share a pathway leading to renal disease progression, proteinuria, and LV concentric remodeling in CKD patients. Clin J Am Soc Nephrol 6: 2620–2627, 2011. doi: 10.2215/CJN.06970711

Blood pressure control by the nifedipine GITS-telmisartan combination in patients at high cardiovascular risk: the TALENT study

Abstract: BackgroundGuidelines on hypertension regard combinations between two antihypertensive drugs to be the most important treatment strategy. Because of the complementary mechanism of action and the evidence of cardiovascular protective effects they include the combination of a calcium antagonist and an

High-altitude exposure of three weeks duration increases lung diffusing capacity in humans

Abstract: Background: high-altitude adaptation leads to progressive increase in arterial PaO2. In addition to increased ventilation, better arterial oxygenation may reflect improvements in lung gas exchange....

Heterogeneity in antihypertensive treatment discontinuation between drugs belonging to the same class

Abstract: ObjectivesDiscontinuation of antihypertensive treatment is known to be different for different classes of antihypertensive drugs. No information is available on whether this phenomenon differs for drugs belonging to the same class. This is clinically relevant because treatment discontinuation is mai

Effects of selective and nonselective beta-blockade on 24-h ambulatory blood pressure under hypobaric hypoxia at altitude

Abstract: BackgroundLittle is known about the effects of cardiovascular drugs at high altitude.ObjectiveTo assess 24-h blood pressure (BP) and heart rate (HR) during short-term altitude exposure in healthy normotensive persons treated with carvedilol or nebivolol.MethodsParticipants were randomized in double-

Gender differences in the association between education and the incidence of cardiovascular events in Northern Italy

Abstract: Background : The educational differences in the incidence of major cardiovascular events are under-studied in Southern Europe and among women. Methods : The study sample includes n = 5084 participants to 4 population-based Northern Italian cohorts, aged 35–74 at baseline and with no previous cardiovascular events. The follow-up to ascertain the first onset of coronary heart disease (CHD) or ischaemic stroke ended in 2002. At baseline, major cardiovascular risk factors were investigated adopting the standardized MONICA procedures. Two educational classes were obtained from years of schooling. Age- and risk factors-adjusted hazard ratios of first CHD or ischaemic stroke were estimated through sex-specific separate Cox models (high education as reference). Results: Median follow-up time was 12 years. Event rates were 6.38 (CHD) and 2.12 (ischaemic stroke) per 1000 person-years in men; and 1.59 and 0.94 in women. In men, low education was associated with higher mean Body Mass Index and prevalence of diabetes and cigarette smokers; but also with higher HDL cholesterol and a more favourable alcohol intake pattern. Less-educated women had higher mean systolic blood pressure, Body Mass Index and HDL cholesterol and were more likely to have diabetes. Men and women in the low educational class had a 2-fold increase in ischaemic stroke and CHD incidence, respectively, after controlling for major risk factors. Education was not associated with CHD incidence in men. Higher ischaemic stroke rates were observed among more educated women. Conclusion : In this northern Italian population, the association between education and cardiovascular risk seems to vary by gender.

Hypertension and migraine comorbidity: prevalence and risk of cerebrovascular events: evidence from a large, multicenter, cross-sectional survey in Italy (MIRACLES study).

Abstract: Objectives To estimate the prevalence of hypertension-migraine comorbidity; to determine their demographic and clinical characteristics versus patients with hypertension or migraine alone; and to see whether a history of cerebrovascular events was more common in the comorbidity group. Methods The MIRACLES, multicenter, cross-sectional, survey included 2973 patients with a known diagnosis of hypertension or migraine in a general practitioner setting in Italy. Results Five hundred and seventeen patients (17%) suffered from hypertension-migraine comorbidity, whereas 1271 (43%) suffered from hypertension only, and 1185 (40%) from migraine only. In the comorbidity group, the onset of comorbidity occurred at about 45 years of age, with migraine starting significantly later than in the migraine-only group, and hypertension significantly before than in the hypertension-only group; a familial history of both hypertension and migraine had a significantly higher frequency as compared with the hypertension and migraine group. Compared to hypertension (3.1%) and migraine (0.7%), the comorbidity group had a higher prevalence (4.4%) of history of cerebrovascular events, with an odds ratio of a predicted history of stroke/transient ischemic attack (TIA) of 1.76 [95% confidence interval (CI) 1.01-3.07] compared to the hypertension group. In patients without other recognized risk factors for stroke, stroke/TIA occurred more frequently in the comorbidity group, compared to the hypertension group. In the age range 40-49 years, prevalence of history of stroke/TIA was five-fold greater (4.8% in comorbidity vs. 0.9% in hypertension group). Conclusion This cross-sectional study indicates that the prevalence of comorbidity hypertension-migraine is substantial and that patients with comorbidity have a higher probability of history of cerebrovascular events, compared to hypertensive patients.

Antihypertensive treatment and blood pressure in diabetic and nondiabetic patients: The lower, the better?

Abstract: International guidelines on hypertension recommend maintaining blood pressure (BP) below 140 mmHg systolic and 90 mmHg diastolic in the general hypertensive population up to the age of 80 years. A more aggressive BP target is recommended when the hypertensive patient has an additional risk for cardiovascular disease, such as if the patient has diabetes, renal disease, or a prior history of cardiovascular disease. In these situations, guidelines encourage decreasing BP below 130/80 mmHg to grant additional cardiovascular protection (1–3). In the last 2 years, the target BP values recommended by guidelines have been the object of some dissenting views (4,5), based on the argument that these targets are often not supported by evidence from prospective randomized trials (4) and that lowering BP too aggressively may do harm rather than ensuring protection. This article addresses this issue by examining three sets of relevant studies: randomized trials, post hoc analysis of prospective studies, and studies on organ damage. Because of space limitations, the References do not include all single trials mentioned; the reader can refer to a recent document of the European Society of Hypertension for this information (5). This is the case also for the acronym of the trials quoted in Fig. 1. As shown in Fig. 1 (4,5), there is little question that the target BP values recommended by guidelines are not consistently based on trials that compared an actively treated group with placebo or patients treated with less aggressive target BP. To-date trial evidence supports the recommendation to lower systolic BP below 140 mmHg in grade I uncomplicated low cardiovascular risk hypertensive patients, based on the fact that in most trials that involved these patients (although often their “uncomplicated low-risk hypertension category” was questionable [4]), a reduction in cardiovascular …

Nocturnal blood pressure in untreated essential hypertensives

Abstract: AIM. Prevalence, correlates and reproducibility of nocturnal hypertension (NH) as defined by fixed cut-off limits in uncomplicated essential hypertension are poorly defined. Therefore, we assessed such issue in a cohort of 658 untreated hypertensives. METHODS. All subjects underwent procedures including cardiac and carotid ultrasonography, 24-h urine collection for microalbuminuria, ambulatory blood pressure monitoring (ABPM), over two 24-h periods within 4 weeks. NH was defined according to current guidelines (i.e. night-time blood pressure, BP ? 120/70 mmHg) and non-dipping status as a reduction in average systolic (SBP) and diastolic BP (DBP) at night lower than 10% compared with daytime values. RESULTS. A total of 477 subjects showed NH during the first and second ABPM period; 62 subjects had normal nocturnal BP (NN) in both ABPM sessions. Finally, 119 subjects changed their pattern from one ABPM session to the other. Overall, 72.5% of subjects had reproducible NH, 18% variable pattern (VP) and 9.5% reproducible NN. In the same group, figures of reproducible non-dipping, variable dipping and reproducible dipping pattern were 24%, 24% and 52%, respectively. Among NH patients, 56% of whom were dippers, subclinical cardiac organ damage was more pronounced than in their NN counterparts. CONCLUSIONS. In uncomplicated essential hypertensives, NH is a more frequent pattern than non-dipping; NH is associated with organ damage, independently of dipping/non-dipping status. This suggests that options aimed at restoring a blunted nocturnal BP fall may be insufficient to prevent cardiovascular complications unless night-time BP values are fully normalized.

Index measured at an intermediate altitude to predict impending acute mountain sickness

Abstract: Purpose: Acute mountain sickness (AMS) is a neurological disorder that may be unpredictably experienced by subjects ascending at a high altitude. The aim of the present study was to develop a predictive index, measured at an intermediate altitude, to predict the onset of AMS at a higher altitude. Methods: In the first part, 47 subjects were investigated and blood withdrawals were performed before ascent, at an intermediate altitude (3440 m), and after acute and chronic exposition to high altitude (Mount Everest Base Camp, 5400 m (MEBC1 and MEBC2)). Parameters independently associated to the Lake Louise scoring (LLS) system, including the self-reported and the clinical sections, and coefficients estimated from the model obtained through stepwise regression analysis were used to create a predictive index. The possibility of the index, measured after an overnight stay at intermediate altitude (Gnifetti hut, 3647 m), to predict AMS (defined as headache and LLS = 4) at final altitude (Capanna Margherita, 4559 m), was then investigated in a prospective study performed on 44 subjects in the Italian Alps. Results: During the expedition to MEBC, oxygen saturation, hematocrit, day of expedition, and maximum velocity of clot formation were selected as independently associated with LLS and were included in the predictive index. In the Italian Alps, subjects with a predictive index value = 5.92 at an intermediate altitude had an odds ratio of 8.1 (95% confidence limits = 1.7-38.6, sensitivity = 85%, specificity = 59%) for developing AMS within 48 h of reaching high altitude. Conclusion: In conclusion, a predictive index combining clinical and hematological parameters measured at an intermediate step on the way to the top may provide information on impending AMS.

Effect of somatostatin infusion on peptide YY secretion: Studies in the acute and recovery phase of anorexia nervosa and in obesity

Abstract: Objective: Changes in many gastrointestinal peptides, including the anorexigenic peptide YY (PYY), which is produced by L cells, occur in both anorexia nervosa (AN) and obesity (OB) High PYY levels are present in AN, whereas in morbid OB fasting and postprandial PYY secretion is blunted Somatostatin (somatotropin release-inhibiting factor (SRIF)) reportedly inhibits plasma PYY concentrations in animals and healthy humans, but the effect of a SRIF infusion on spontaneous PYY secretion in AN and OB is unknown Methods: A total of 18 young women, seven with acute AN (A-AN), four with AN in the recovery phase (R-AN), and seven with morbid OB, were studied All subjects underwent an infusion of SRIF (9 mg/kg iv/h, over 60 min), with blood samples drawn before and at different time intervals after SRIF administration Plasma PYY levels were measured at each time point Results: SRIF significantly inhibited plasma PYY concentrations in R-AN and OB, without affecting PYY titers in A-AN In OB, the inhibitory effect of SRIF also persisted at 90 min Withdrawal of SRIF infusion in R-AN resulted in a prompt restoration of basal plasma PYY levels, whereas termination of SRIF infusion in OB was followed by a slower increase of PYY titers toward baseline levels After infusion, PYY D area under the curve (DAUC) in R-AN was significantly higher than those in A-AN and OB patients A significant difference in PYY DAUC between A-AN and OB was present Conclusions: These results suggest the existence of a hypo- and hyper-sensitivity of L cells to the inhibitory effect of SRIF in A-AN and OB respectively

Cardiovascular consequences of poor compliance to antihypertensive therapy.

Abstract: Despite the proven efficacy of current strategies for cardiovascular (CV) risk reduction, a considerable gap remains between the risk reductions achieved in clinical trials and those seen in clinical practice. A major reason for this is poor compliance to medication, which has been extensively documented for antihypertensive therapy. Low adherence results in suboptimal blood pressure control, which is associated with adverse CV outcomes and increased treatment costs. Adverse effects of medication are an important cause of diminished adherence. Angiotensin II receptor blockers (ARBs) may offer better long-term tolerability than other classes of antihypertensive agent, and this is likely to be a major factor in the high levels of adherence and persistence seen with these agents. This could have implications for CV protection, as confirmed by the results of recent clinical trials. Thus, ARBs should be considered as an alternative to angiotensin-converting enzyme inhibitors in patients at risk of low ...

GH deficiency in adult B-thalassemia major patients and its relationship with IGF-1 production.

Abstract: Endocrine complications in Β-thalassemia represent a prominent cause of morbidity. Above all, dysfunction of GH-IGF-1 axis is of a major concern because of its pathogenic role on cardiac and bone disease, frequently described in this clinical setting. The aim of this paper is to analyze GH-IGF-1 axis in a cohort of 25 adult patients affected by Β-thalassemia. We found that GH deficiency was present in only 8% of our patients if diagnosis was based on GH peak below 9μg/L to two GH provocative tests instead of only one, and was mainly related to iron overload. On the contrary, IGF-1 production was impaired in a higher percentage of patients (72%), without significant correlation with iron burden. Of note, patients with hepatitis C virus infection showed lower IGF-1 concentrations than uninfected subjects despite a normal GH reserve, suggesting that partial GH insensitivity at the post-receptor level may play a key role in IGF-1 deficiency described in thalassemic patients.

Association between ADRA1A gene and the metabolic syndrome: candidate genes and functional counterpart in the PAMELA population.

Abstract: Objectives There is currently uncertainty about whether metabolic syndrome has a common underlying process We performed a gene-centric association study of metabolic syndrome in 98 major cardiometabolic genes in the large, well phenotyped Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study We followed this with functional studies to elucidate a possible mechanism for the top association signal Methods From the PAMELA cohort, we sampled 1407 individuals with information on the metabolic syndrome (ATPIII criteria) We analyzed 1324 tagging single-nucleotide polymorphisms (SNPs) in 98 candidate genes selected, based on known pathways involved in sympathetic nervous system, oxidative stress, renin-angiotensin system and sodium balance Results The SNP rs17055869 near the alpha-1A-adrenoreceptor gene (ADRA1A) showed the strongest association with metabolic syndrome (odds ratio 17, CI 13-22; P=000007, P=0000098 after permutation) In order to determine a functional basis for this association, we examined in a subgroup of metabolic syndrome patients whether the allelic distribution of the above mentioned gene is different according to the different degree of the metabolic syndrome-related sympathetic activation, directly assessed by the gold standard method to assess neuroadrenergic drive, that is microneurographic recording of efferent postganglionic muscle sympathetic nerve traffic All metabolic syndrome patients with a lesser degree of sympathetic activation were homozygous for the major allele (C), whereas those with a very pronounced sympathetic overdrive had an over-representation of the minor T allele (P<00001) Conclusion Thus, the rs17055869 SNP near the 3' end of ADRA1A is significantly associated with metabolic syndrome and it may be involved in determining a greater level of sympathetic activation in metabolic syndrome patients