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Unsatisfactory blood pressure (BP) control so often described in treated hypertensive populations is also explained by insufficient physicians' awareness of experts' guidelines. We assessed awareness of current recommendations about hypertension management in a general practice setting, using the World Health Organization/International Society of Hypertension (WHO/ISH) 1999 guidelines as reference. In a regionwide survey, a total of 5133 physicians (three-quarters of all active general practitioners in Lombardy, a region of north-western Italy) were contacted by letter and received a multiple choice 10-item questionnaire. Data on physicians' demographic characteristics, information on hypertension prevalence and their perception of BP control among their patients were also requested in an additional form. The number of answers in agreement with WHO/ISH guidelines was used as an awareness measure. This was considered adequate if correct answers to six out of 10 questions, including an appropriate definition of hypertension, were provided. Of the 1256 returned questionnaires (a 24.5% response rate), 1162 were suitable for analysis. The mean score of correct answers was 5.3 points and only 20.1% of the study population correctly answered at least six of the questions (including that on the definition of hypertension in the elderly). Guidelines awareness was negatively related to increase in physicians' age and duration of clinical practice and by the male gender. Finally, the physicians reported a high rate of achieved BP control, and those who were considered to have achieved highest rates (>75%) of control in their patients had a lower rate of adequate knowledge than those who reported less-successful therapeutic results (18 vs 25%, P<0.01), suggesting that they ignored or disregarded the goal BP recommended by the guidelines. This large regional survey shows that a sufficient degree of guidelines awareness is present in a minority of primary-care physicians in... [ABSTRACT FROM AUTHOR]

Extreme longevity is the paradigm of healthy aging as individuals who reached the extreme decades of human life avoided or largely postponed all major age-related diseases. In this study, we sequenced at high coverage (90X) the whole genome of 81 semi-supercentenarians and supercentenarians [105+/110+] (mean age: 106.6 ± 1.6) and of 36 healthy unrelated geographically matched controls (mean age 68.0 ± 5.9) recruited in Italy. The results showed that 105+/110+ are characterized by a peculiar genetic background associated with efficient DNA repair mechanisms, as evidenced by both germline data (common and rare variants) and somatic mutations patterns (lower mutation load if compared to younger healthy controls). Results were replicated in a second independent cohort of 333 Italian centenarians and 358 geographically matched controls. The genetics of 105+/110+ identified DNA repair and clonal haematopoiesis as crucial players for healthy aging and for the protection from cardiovascular events., Competing Interests: PG, MD, CP, EM, KK, VI, LX, DM, BA, MC, EF, DM, BN, SS, DL, DP, GC, CS, GP, FD, PD, LB, NM, DG, OO, CG, CF No competing interests declared, JM, AV, JC, FR, SC, PD is affiliated with Nestlé Research, Société des Produits Nestlé SA. The author has no other competing interests to declare. MB s affiliated with Nestlé Research, Société des Produits Nestlé SA. The author has no other competing interests to declare. AF is affiliated with Menarini Silicon Biosystems SpA. The author has no other competing interests to declare., (© 2021, Garagnani et al.)

The impact of tuberculosis and of anti-tuberculosis therapy on composition and modification of human lung microbiota has been the object of several investigations. However, no clear outcome has been presented so far and the relationship between M. tuberculosis pulmonary infection and the resident lung microbiota remains vague. In this work we describe the results obtained from a multicenter study of the microbiota of sputum samples from patients with tuberculosis or unrelated lung diseases and healthy donors recruited in Switzerland, Italy and Bangladesh, with the ultimate goal of discovering a microbiota-based biomarker associated with tuberculosis. Bacterial 16S rDNA amplification, high-throughput sequencing and extensive bioinformatic analyses revealed patient-specific flora and high variability in taxon abundance. No common signature could be identified among the individuals enrolled except for minor differences which were not consistent among the different geographical settings. Moreover, anti-tuberculosis therapy did not cause any important variation in microbiota diversity, thus precluding its exploitation as a biomarker for the follow up of tuberculosis patients undergoing treatment., Competing Interests: The authors have declared that no competing interests exist.

Background: The impact of the 2017 American College Cardiology/American Heart Association guidelines on reclassification of white coat hypertension (WCH) and white coat uncontrolled hypertension (WUCH) phenotypes has not been thoroughly investigated, so far. The aim of the present analysis was to compare the prevalence rates of WCH and WUCH according to either 2018 European Society Hypertension/European Society Cardiology and 2017 ACC/AHA hypertension guidelines., Methods: A large database of individual 24-hour ambulatory blood pressure (BP) recordings from untreated and treated hypertensive individuals with office BP ≥140 and/or 90 mm Hg was analyzed., Results: As many as 3,223 (39% men) out of 7,353 (47% men) fulfilled diagnostic criteria for WCH (n = 1,281) and WUCH (n = 1,942) according to the 2018 ESH/ESC guidelines (mean 24-hour BP <130/80 mm Hg), the prevalence rate being 17.4% and 26.4%, respectively. The corresponding figures according to the 2017 ACC/AHA guidelines (mean 24-hour BP <125/75 mm Hg) were 15.6 and 9.4%, respectively. Thus, a total of 1,378 patients (42.7%) either defined as WCH and WUCH by ESH/ESC guidelines, were classifiable as untreated sustained and uncontrolled sustained hypertensives by ACC/AHA guidelines., Conclusions: The ACC/AHA reclassification of patients with office BP ≥140/90 mm Hg leads to a marked decrease in the prevalence of WCH/WUCH. This may have relevant clinical implications because the prognostic significance of these phenotypes is often ignored in clinical practice and, consequently, contributes to the high burden of cardiovascular diseases worldwide., (© The Author(s) 2020. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.)

Aim: Although nocturnal hypotension is considered the key factor responsible for the increased cardiovascular risk associated with the extreme dipping (ED) pattern, no information is available on its prevalence in this setting. Therefore, we have assessed this topic in a cohort of patients referred to a single out-patient hypertension center., Methods: A large database of individual 24-hour ambulatory BP recordings from untreated individuals with a history of hypertension and treated individuals with hypertension was analyzed., Results: A total of 339 of 7,074 patients (4.5%) exhibited an ED pattern (207 had a nighttime reduction in both systolic and diastolic BP ≥ 20% compared to daytime values and 132 a nighttime reduction in diastolic BP ≥ 20%). Among patients with ED, the prevalence of nocturnal hypotension varied from 9.1% to 45.0% depending on the criteria used (i.e., mean nighttime BP < 90/50 mm Hg or < 100/60 mm Hg), and the prevalence of nocturnal hypertension (i.e., mean nighttime BP ≥ 120/70 mm Hg) was 19.5%. Compared with untreated patients, those taking antihypertensive drugs were more likely to have nocturnal hypotension and less likely to have nocturnal hypertension., Conclusions: Our findings support the view that ED pattern is a condition not always associated with nocturnal hypotension because a large fraction of ED patients has normal or elevated mean BP nocturnal values., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

In the PAMELA study (Pressioni Arteriose Monitorate e Loro Associazioni), clinical variables, an echocardiogram, as well as office and ambulatory blood pressure (ABP) were simultaneously measured at baseline and after a 10-year follow-up. The study design allowed us to assess the value of masked hypertension (MH) as a predictor of new-onset left ventricular hypertrophy (LVH). The present analysis included 803 participants without LVH at baseline (left ventricular mass index <115 g/m 2 in men and <100 g/m 2 in women). Based on office and 24-hour mean ABP values, subjects were divided into 3 groups: normal subjects (normotensive, office blood pressure [BP] <140/90 mm Hg and 24-hour mean ABP <130/80 mm Hg), MH (office BP, normal, and 24-hour mean ABP, elevated), and sustained hypertension (office and 24-hour BP, both elevated). At entry, 57 of 803 subjects fulfilled diagnostic criteria for MH (7.1%); 182 participants developed LVH (22.6%). Compared with subjects with normal in-office and out-of-office BP, the risk of new-onset LVH was greater in MH (odds ratio, 2.22; CI, 1.11-4.46, P=0.0250) after adjustment for potential confounders. This was also the case for the absolute increase of left ventricular mass index. Our study provides a new piece of evidence that MH, identified by office and ABP values, is associated with an increased risk of new-onset LVH. Moreover, our findings convey the notion that office BP may inaccurately estimate the risk of incident LVH in the general population.

Cross-sectional and longitudinal data analysis of the PAMELA (Pressioni Monitorate E Loro Associazioni) population was performed to assess the association between prehypertension and left ventricular hypertrophy (LVH) at entry and the risk of new-onset LVH associated to this condition in the subset of participants with normal LV mass index (LVMI). A total of untreated 1397 participants with measurable echocardiographic parameters at baseline were considered in the cross-sectional analysis. The longitudinal analysis included 880 participants without LVH at baseline and with measurable LVMI at follow-up examination performed 10 years later. At entry, after adjustment for major confounders LVH prevalence rates (LVM/body surface area) showed a significant, progressive increase from the normotensive (2.1%), to prehypertension (6.7%), and hypertension group (18.3%). The incidence of LVH increased progressively from the normotensive to prehypertension and hypertension group (9.0%, 23.2%, and 36.5%, respectively). The risk of new LVH was significantly greater in prehypertension who progressed to sustained hypertension (odds ratio, 4.21; CI, 1.64-10.83; P=0.003) than in those with persistent prehypertension (odds ratio, 1.89; CI, 0.77-5.11; P=0.21) compared with persistent normotensive participants after adjustment for age, sex, baseline LVMI, obesity, glucose, creatinine, total cholesterol and the use of antihypertensive drugs at follow-up. Further adjustments for changes in body mass index, metabolic variables, and creatinine during the follow-up did not modify the strength of association between prehypertension and new-onset LVH. Our findings offer a new piece of evidence on the association of prehypertension with LVH and support the view that preventive actions for this condition affecting a large fraction of the general population should be intensified.

Aim: In the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study, clinical and metabolic variables as well as office, home and ambulatory blood pressure (BP) values were simultaneously measured at baseline and after a 10-year follow-up. The study design allowed us to assess the value of selective and combined elevation of different BP phenotypes in predicting new-onset metabolic syndrome (MetS)., Methods: The present analysis included 1182 participants without MetS at baseline, as defined by the APT III criteria. On the basis of office, 24-h ambulatory BP and home values, participants were divided into four groups: normal, white-coat hypertension (WCH), masked hypertension and sustained hypertension., Results: Compared with participants with in-office and out-of-office normal BP, a greater incidence of new-onset age-adjusted and sex-adjusted MetS was observed in WCH (OR = 1.75, CI 1.01-3.04, P = 0.0046), masked hypertension (OR = 2.58, CI 1.26-5.30; P = 0.009) and sustained hypertension (OR = 2.14, CI 1.20-3.79, P = 0.009)) when out-of-office BP was defined by ambulatory criteria. This was not the case when out-of-office BP was defined by home criteria, as only the WCH group showed a greater risk (OR 2.16, CI 1.28-3.63, P = 0.003). Similar findings were obtained for single components of the MetS such as abdominal obesity and hyperglycemia., Conclusion: Our study provides evidence that either isolated or combined BP elevations identified by office/ambulatory measurements, carry an increased risk of new-onset MetS, whereas, only WCH is associated with a greater risk of incident MetS whenever BP phenotypes are identified by office/home measurements. In a clinical perspective, a comprehensive evaluation of BP status based on office/ambulatory measurements may improve diagnosis of new-onset MetS and activate measures for its prevention.

Aim: To evaluate the effects of canrenone as add-on therapy in patients already treated with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARBs) and hydrochlorothiazide at the maximum dosage (25 mg/d)., Method: In this randomized, open-label, controlled trial, we enrolled 175 Caucasian patients with essential hypertension not well controlled by concomitant ACE-I or ARBs and hydrochlorothiazide. At baseline, 87 patients (57 males and 30 females) were randomized to add canrenone 50 mg, and 88 (56 males and 32 females) patients to canrenone 100 mg, once a day, for 3 months. At baseline and after 3 months, we evaluated blood pressure (BP), pulse pressure (PP), heart rate (HR), fasting plasma glucose (FPG), homeostasis model assessment insulin (HOMA Index), lipid profile, electrolytes, uric acid, estimated glomerular filtration rate (eGFR), plasma urea, aldosterone, B-type natriuretic peptide (BNP), and galectin-3., Results: Blood pressure decreased with both dosages of canrenone, with a better effect with canrenone 100 mg (-20.26 vs -23.68 mm Hg for SBP, and -10.58 vs -12.38 mm Hg for DBP), without a clinically relevant increase in potassium levels. We did not observe any differences regarding FPG or HOMA Index, nor of lipid profile, with the exception of triglycerides, which increased compared to baseline with canrenone 50 mg (+0.25 vs +0.34 mEq/L). Creatinine slightly increased with canrenone 100 mg (+0.02 vs +0.05 mg/dL), although no variations of eGFR were observed in neither groups. There was an increase in aldosterone levels with canrenone 50 mg. No changes in BNP or galectin-3 were recorded., Conclusion: Both canrenone dosages gave a decrease in blood pressure, with a better effect with the higher dose, with only a slight increase in potassium and creatinine levels, which were not clinically relevant. Clinical Trials Registration Eudract number: 2010-023606-13; ClinicalTrials.gov NCT02687178., (© 2016 The Authors. Cardiovascular Therapeutics Published by John Wiley & Sons Ltd.)

Aim: We estimated the risk of cardiovascular and all-cause mortality associated with left ventricular hypertrophy (LVH) as assessed by left ventricular mass (LVM), normalized by various indexation methods in 1716 representatives of the general population of Monza, enrolled in the Pressioni Arteriose Monitorate E Loro Associazioni study., Methods: LVH was defined according to four sex-specific criteria derived from the upper limits of normality for LVM index in the healthy normotensive fraction of the Pressioni Arteriose Monitorate E Loro Associazioni population. Death certificates were collected over an average 211 months of follow-up., Results: During follow-up, 89 fatal cardiovascular events and 264 all-cause deaths were observed. LVH prevalence rates in the whole population ranged from 14.2% [LVM/body surface area (BSA)] to 18.0% (LVM/height). Adjusted risk (for baseline covariates, including ambulatory blood pressure) of cardiovascular mortality was increased in patients with LVH, regardless of the indexation type: LVH/BSA [hazard ratio 3.19, 95% confidence interval (CI) 2.02-5.06, P < 0.0001], LVH/height (hazard ratio 2.39, 95% CI 1.51-3.78, P = 0.0002), LVH/height (hazard ratio 2.38, 95% CI 1.50-3.76, P = 0.0002), LVH/height (hazard ratio 2.28, 95% CI 1.44-3.60 P = 0.0004). Similar findings were observed for all-cause mortality and when LVM was assessed as a continuous variable. The fraction of patients (5%) classified into the LVH group by height, but not by BSA, had a mild increased LVM index and showed no increased risk., Conclusions: LVH, irrespective of indexation methods for LVM, confers an increased risk of cardiovascular and all-cause mortality in the general population. LVH, detected by height-based indexes, but not by BSA-based criteria, was not associated with increased mortality; this finding, however, was based on a small group of patients and will deserve further investigations.

Aim: We assessed the value of three electrocardiographic (ECG) voltage criteria in detecting left ventricular hypertrophy (LVH) and in predicting cardiovascular events and all-cause mortality in the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) population., Methods: At entry, 1549 individuals (age 50 ± 13 years, 50.5% men) underwent diagnostic tests including laboratory investigations, 24-h ambulatory blood pressure monitoring, and standard ECG and echocardiography., Results: The sensitivity of ECG criteria for LVH was lowest for Sokolow-Lyon voltage (1.5 and 0.78%), intermediate for Cornell voltage (20.5 and 19.0%), and highest for RaVL wave amplitude (26.0 and 36.2%), independently of whether left ventricular mass was indexed to body surface area or height, respectively. After adjustment for age, sex, night-time SBP, low-density lipoprotein and high-density lipoprotein cholesterol, serum glucose, BMI, smoking, and previous cardiovascular events, only Cornell voltage index [hazard ratio for a 0.1  mV increase: 1.050, 95% confidence interval (CI): 1.017-1.083, P < 0.003] predicted an increased risk of cardiovascular events as well as all-cause mortality. Furthermore, when the categorical relationship between ECG-graphic LVH and cardiovascular outcomes was investigated in multiple models, only LVH identified by the Cornell voltage index remained an independent predictor of cardiovascular events (hazard ratio = 2.466, CI 1.459-4.168, P = 0.0008) and all-cause deaths (hazard ratio = 2.984, CI 1.380-6.449, P = 0.005)., Conclusion: Despite the limited sensitivity of ECG voltage criteria in detecting LVH, our results show that Cornell voltage index may improve cardiovascular risk stratification in a general population independently of several confounding factors.

The red blood cell related traits are highly heritable but their genetics are poorly defined. Only 5-10% of the total observed variance is explained by the genetic loci found to date, suggesting that additional loci should be searched using approaches alternative to large meta analysis. GWAS (Genome Wide Association Study) for red blood cell traits in a founder population cohort from Northern Italy identified a new locus for mean corpuscular hemoglobin concentration (MCHC) in the TAF3 gene. The association was replicated in two cohorts (rs1887582, P = 4.25E-09). TAF3 encodes a transcription cofactor that participates in core promoter recognition complex, and is involved in zebrafish and mouse erythropoiesis. We show here that TAF3 is required for transcription of the SPTA1 gene, encoding alpha spectrin, one of the proteins that link the plasma membrane to the actin cytoskeleton. Mutations in SPTA1 are responsible for hereditary spherocytosis, a monogenic disorder of MCHC, as well as for the normal MCHC level. Based on our results, we propose that TAF3 is required for normal erythropoiesis in human and that it might have a role in controlling the ratio between hemoglobin (Hb) and cell volume and in the dynamics of RBC maturation in healthy individuals. Finally, TAF3 represents a potential candidate or a modifier gene for disorders of red cell membrane.

Population isolates are a valuable resource for medical genetics because of their reduced genetic, phenotypic and environmental heterogeneity. Further, extended linkage disequilibrium (LD) allows accurate haplotyping and imputation. In this study, we use nuclear and mitochondrial DNA data to determine to what extent the geographically isolated population of the Val Borbera valley also presents features of genetic isolation. We performed a comparative analysis of population structure and estimated effective population size exploiting LD data. We also evaluated haplotype sharing through the analysis of segments of autozygosity. Our findings reveal that the valley has features characteristic of a genetic isolate, including reduced genetic heterogeneity and reduced effective population size. We show that this population has been subject to prolonged genetic drift and thus we expect many variants that are rare in the general population to reach significant frequency values in the valley, making this population suitable for the identification of rare variants underlying complex traits.

Background and Objectives: Although several studies demonstrated that platelet count is higher in women, decreases with age, and is influenced by genetic background, most clinical laboratories still use the reference interval 150-400×10(9) platelets/L for all subjects. The present study was to identify age- and sex-specific reference intervals for platelet count., Methods: We analysed electronic records of subjects enrolled in three population-based studies that investigated inhabitants of seven Italian areas including six geographic isolates. After exclusion of patients with malignancies, liver diseases, or inherited thrombocytopenias, which could affect platelet count, reference intervals were estimated from 40,987 subjects with the non parametric method computing the 2.5° and 97.5° percentiles., Results: Platelet count was similar in men and women until the age of 14, but subsequently women had steadily more platelets than men. The number of platelets decreases quickly in childhood, stabilizes in adulthood, and further decreases in oldness. The final result of this phenomenon is that platelet count in old age was reduced by 35% in men and by 25% in women compared with early infancy. Based on these findings, we estimated reference intervals for platelet count ×10(9)/L in children (176-452), adult men (141-362), adult women (156-405), old men (122-350) and, old women (140-379). Moreover, we calculated an "extended" reference interval that takes into account the differences in platelet count observed in different geographic areas., Conclusions: The age-, sex-, and origin-related variability of platelet count is very wide, and the patient-adapted reference intervals we propose change the thresholds for diagnosing both thrombocytopenia and thrombocytosis in Italy.

Background and Aim: Upper reference values of echocardiographic left-ventricular mass in the European population are based on scanty data mostly derived from northern European population-based samples. Furthermore, data in apparently healthy populations have included individuals with conditions affecting left-ventricular mass such as obesity, diabetes and masked hypertension. Thus, from 1051 individuals with normal office blood pressure (BP) belonging to the PAMELA (Pressioni Arteriose Monitorate E Loro Associazioni) study population, we selected a group of 675 sustained normotensive individuals in order to provide reliable echocardiographic reference values for defining the criteria of left-ventricular hypertrophy (LVH)., Methods: The study group (women 58%, mean age 42 ± 11 years) was identified after excluding individuals with isolated home or ambulatory hypertension, obesity, diabetes, cardiovascular diseases and echocardiographic examinations of insufficient quality to evaluate left-ventricular mass., Results: Sex-specific upper limits of normality [mean + 1.96 standard deviation (SD)] for left-ventricular mass, left-ventricular mass indexed to body surface area, heightand height were the following: 213 g, 114 g/m, 51 g/h, 123 g/h in men and 161 g, 99  g/m, 47 g/h, 101 g/h in women. In multivariate analyses, body size measures and ambulatory BP levels were the most important correlates of left-ventricular mass., Conclusions: Our investigation by providing upper reference limits of left-ventricular mass in a southern European population sample, carefully selected after exclusion of a large number of conditions affecting left-ventricular mass, may offer a contribution for revising diagnostic criteria of echocardiographic LVH currently recommended by European hypertension guidelines.

This paper describes a software tool that reconstructs entire genealogies from data collected from different and heterogeneous sources, including municipal and parish records archived over centuries. The tool exploits a record linkage algorithm relying on a rule-based data matching approach. It applies a general strategy for managing the ambiguities due to missing, imprecise or erroneous input data. The process follows an iterative approach that combines automatic pedigree reconstruction with software-empowered human data revision to improve the quality and the accuracy of the results and to optimize the matching rules. The paper discusses the results obtained by reconstructing the entire genealogy of the population of the Val Borbera, a geographically isolated valley in Northern Italy. The genealogy could be reconstructed from data going back as far as the XVI century. The resulting pedigree includes 75,994 trios, 58.9% of which belonging to a unique big family, reconstructed over 13 generations., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Large-scale population studies have established that genetic factors contribute to individual differences in smoking behavior. Linkage and genome-wide association studies have shown many chromosomal regions and genes associated with different smoking behaviors. One study was the association of single-nucleotide polymorphisms (SNPs) in the CHRNA5-A3-B4 gene cluster to nicotine addiction. Here, we report a replication of this association in the Italian population represented by three genetically isolated populations. One, the Val Borbera, is a genetic isolate from North-Western Italy; the Cilento population, is located in South-Western Italy; and the Carlantino village is located in South-Eastern Italy. Owing to their position and their isolation, the three populations have a different environment, different history and genetic structure. The variant A of the rs1051730 SNP was significantly associated with smoking quantity in two populations, Val Borbera and Cilento, no association was found in Carlantino population probably because difference in LD pattern in the variant region.

Background and Aim: Weight and height are two major determinants of left ventricular mass (LVM); the anthropometric parameter to which LVM should be normalized remains, however, debated. In a population of hypertensives, we compared the prevalence of left ventricular hypertrophy (LVH) defined by two indexation criteria of LVM in different subgroups of body mass index (BMI)., Methods: A total of 4468 essential hypertensives included in the Evaluation of Target Organ Damage in Hypertension (ETODH), were divided in four groups according to BMI thresholds: lean (BMI<20 kg/m(2), 4.5%), normal (20-24.9 kg/m(2), 36.5%), overweight (25-29.9 kg/m(2), 41.9%) and obese (≥ 30 kg/m(2), 17.1%). All patients underwent quantitative echocardiography; LVH was defined by two criteria of LVM indexation: (A) ≥ 116 g/m(2) in men and ≥ 96 g/m(2) in women; (B) ≥ 49 g/m(2.7) in men and ≥ 45 g/m(2.7) in women., Results: Overall, 44.9% of the patients were found to have LVH by criterion A, 48.2% by criterion B and 37.0% by both criteria. Prevalence rates of LVH in the four BMI groups were 34.3%, 40.5%, 47.3%, 53.9% by criterion A, 19.8%, 37.0%, 53.6%, 69.7% by criterion B, and 14.2%, 30.9%, 41.5%, 47.8% by both criteria, respectively (p at least <0.05 for all)., Conclusions: Our findings show that LVH prevalence in both overweight and obese hypertensives is higher when LVM is normalized to height(2.7) compared with body surface area (BSA), whereas the opposite trend occurs in normal weight/lean hypertensives. Thus, the risk related to LVH is underestimated when the LVH/height(2.7) criterion is applied to lean/normal weight individuals and the LVH/BSA criterion in overweight/obese individuals.

Background: Isolated populations are a useful resource for mapping complex traits due to shared stable environment, reduced genetic complexity and extended Linkage Disequilibrium (LD) compared to the general population. Here we describe a large genetic isolate from the North West Apennines, the mountain range that runs through Italy from the North West Alps to the South., Methodology/principal Findings: The study involved 1,803 people living in 7 villages of the upper Borbera Valley. For this large population cohort, data from genealogy reconstruction, medical questionnaires, blood, anthropometric and bone status QUS parameters were evaluated. Demographic and epidemiological analyses indicated a substantial genetic component contributing to each trait variation as well as overlapping genetic determinants and family clustering for some traits., Conclusions/significance: The data provide evidence for significant heritability of medical relevant traits that will be important in mapping quantitative traits. We suggest that this population isolate is suitable to identify rare variants associated with complex phenotypes that may be difficult to study in larger but more heterogeneous populations.

Background: The Age-Period-Cohort (APC) analysis is routinely used for time trend analysis of cancer incidence or mortality rates, but in veterinary epidemiology, there are still only a few examples of this application. APC models were recently used to model the French epidemic assuming that the time trend for BSE was mainly due to a cohort effect in relation to the control measures that may have modified the BSE exposure of cohorts over time. We used a categorical APC analysis which did not require any functional form for the effect of the variables, and examined second differences to estimate the variation of the BSE trend. We also reanalysed the French epidemic and performed a simultaneous analysis of Italian data using more appropriate birth cohort categories for comparison., Results: We used data from the exhaustive surveillance carried out in France and Italy between 2001 and 2007, and comparatively described the trend of the epidemic in both countries. At the end, the shape and irregularities of the trends were discussed in light of the main control measures adopted to control the disease. In Italy a decrease in the epidemic became apparent from 1996, following the application of rendering standards for the processing of specific risk material (SRM). For the French epidemic, the pattern of second differences in the birth cohorts confirmed the beginning of the decrease from 1995, just after the implementation of the meat and bone meal (MBM) ban for all ruminants (1994)., Conclusion: The APC analysis proved to be highly suitable for the study of the trend in BSE epidemics and was helpful in understanding the effects of management and control of the disease. Additionally, such an approach may help in the implementation of changes in BSE regulations.

In the revised National Cancer Institute Working Group (NCI-WG)/International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines for CLL, CLL-like monoclonal B lymphocytosis (MBL) is defined as the presence of less than 5 x 10(9)/L B lymphocytes in the peripheral blood. However, the concentration of MBL in the blood is extremely variable. MBL in subjects with lymphocytosis require treatment at a rate of 1.1% per year and present immunoglobulin (IG) gene features and similar to good prognosis CLL. Little is known about low-count MBL cases, accidentally found in the general population. We analyzed IGHV-D-J rearrangements in 51 CLL-like MBL cases from healthy individuals, characterized by few clonal B cells. Seventy percent of the IGHV genes were mutated. The most frequent IGHV gene was IGHV4-59/61, rarely used in CLL, whereas the IGHV1-69 gene was lacking and the IGHV4-34 gene was infrequent. Only 2 of 51 (3.9%) MBL cases expressed a CLL-specific stereotyped HCDR3. Therefore, the IG gene repertoire in low-count MBL differs from both mutated and unmutated CLL, suggesting that the detection of MBL in an otherwise healthy subject is not always equivalent to a preleukemic state. Detailed IG analysis of individual MBL may help to identify cases that necessitate continuous clinical monitoring to anticipate disease progression.

Normal hemoglobin levels vary greatly according to genetic and acquired factors. As a consequence there is no general agreement on the definition of anemia in terms of hemoglobin levels. Here we compare the hemoglobin levels of subjects recruited from normal genetically isolated Italian populations whose medical history, life style habits and results of laboratory tests are available. After the exclusion of pathological samples we analyzed the hemoglobin levels of 3,849 subjects (1,661 males and 2,188 females) and evaluated the hemoglobin heritability. Normal subjects of different age groups from a northern Italian isolate have significantly higher hemoglobin levels when compared to matched subjects of southern Italian isolates. The estimated heritability of hemoglobin levels ranges from 0.34 to 0.42 in the different isolates. Our study provides a dataset of hemoglobin levels for normal subjects of different geographical origin and indicate that hemoglobin levels are substantially influenced by heritable components.

Background: It is still undefined whether serum uric acid (SUA) is an independent risk factor for target organ damage (TOD) and cardiovascular events in human hypertension. We sought to investigate the association of SUA with subclinical cardiac, vascular, and renal alterations in never-treated uncomplicated essential hypertensives., Methods: A total of 580 subjects with recently diagnosed (<1 year) grade 1 and 2 hypertension, categorized by sex and tertiles of SUA levels, were considered for this analysis. All subjects underwent extensive clinical, laboratory, and ultrasonographic investigations searching for cardiac and extracardiac TOD., Results: Hyperuricemia (SUA >7.0 mg/dL in men and >6 mg/dL in women) was present in 8.3% of the patients. The overall prevalence of left-ventricular hypertrophy (LVH), carotid alterations, and microalbuminuria was 28%, 27%, and 8%, respectively. No differences in the prevalence rates of these TOD markers were present across all SUA tertiles in the entire population, as well as in both sexes. The SUA levels were similar in patients with and without LVH, carotid alterations, or microalbuminuria. When patients were classified according to the number of organs involved, those with multiple TOD (2 or 3 organs) had significantly higher SUA levels (5.1 +/- 1.3 or 5.2 +/- 1.4 mg/dL), as compared with those with a single or no organ involvement (4.9 +/- 1.3 or 4.9 +/- 1.4 mg/dL, P < .05). The association, however, between SUA levels and multiple TOD was not confirmed in a logistic regression analysis., Conclusions: Our findings do not support the role of SUA as an independent risk factor for subclinical TOD in a selected population of recently diagnosed uncomplicated hypertensives at low prevalence of hyperuricemia.

Objective: We sought to investigate the association of the metabolic syndrome (MS) with cardiovascular alterations in essential hypertensives in relation to age., Methods: A total of 3266 untreated and treated hypertensive patients categorized in three age groups (I: 17 to 40 years; II: 41 to 64 years; III: >64 years) were considered for this analysis. All patients underwent extensive investigations searching for target organ damage (TOD). The MS was defined according to Advanced Technology Laboratories (ATP) III criteria., Results: In the entire population, the risk of left ventricular hypertrophy (LVH), carotid abnormalities, and microalbuminuria increased by 2.5 (P = .003), 2.2 (P = .005), and 1.5 times (P = .01), respectively, in the presence of MS after adjusting for several confounders. Prevalence of LVH (group I: 39% v 22%; group II: 53% v 35%; group III: 69% v 52%, P < .01 for all), carotid thickening (group I: 8% v 2%; group II 29% v 19%; group III: 69% v 52%, P < .05 for all) and microalbuminuria (group I: 20% v 11%; group II: 16% v 8%; group III: 18% v 11%, P

Background: Echocardiography is more accurate than electrocardiography in the assessment of cardiac target organ damage related to hypertension, thus leading to a more precise stratification of total cardiovascular risk. However, ultrasound examination of the heart on a routine basis remains a matter of debate., Objective: To evaluate the impact and cost-effectiveness of echocardiographic examination on global risk stratification in low and medium-risk hypertensive patients in relation to age and sex., Methods: A total of 580 untreated hypertensive individuals (355 men and 225 women, mean age 47.8 +/- 11.4 years), classified at low to medium risk, according to routine clinical work-up suggested by the 2003 European Society of Hypertension/European Society of Cardiology guidelines, were included in the study. Total risk was reassessed by adding the results of ultrasound examination of the heart. Left ventricular hypertrophy (LVH) was defined as a left ventricular mass index of 125 g/m2 or more in men and 110 g/m2 or more in women. The impact of LVH in stratifying risk was assessed according to age (< 50 and > or = 50 years) and sex., Results: According to routine classification, 16.3% (n = 93) of the 580 patients were considered to be at low added risk and 83.7% (n = 487) at medium added risk. In the whole population, echocardiographic LVH was found in 86 patients (14.8%) who were then reclassified in the high-risk stratum. The prevalence rates of patients reclassified in the high-risk class as a consequence of LVH detection, according to age and sex, were as follows: 8.9% in men under 50 years, 12.3% in women under 50 years, 26.7% in men aged 50 years and over and 15.3% in women aged 50 years and over. The cost per detected case of LVH was 595 euros in patients under 50 years of age and 290 euros in those 50 years of age and older., Conclusions: Our findings indicate that the prevalence of LVH, and consequently the probability of upgrading the total cardiovascular risk profile, is highest in the group of old hypertensive men; echocardiography has a limited impact on the risk reclassification in younger patients and an unfavourable cost-effectiveness profile. Our data thus do not support the systematic ultrasound assessment of the heart in all uncomplicated hypertensive individuals.