Bacteremia from streptococcus constellatus revealing a gastrointestinal stromal tumor.

BACKGROUND: Pyogenic Liver Abscesses (PLA) are the most common type of visceral abscess. They generally develop in a context of biliary disease or hematogenous seeding, but a complete diagnostic work-up is always required in order not to miss other important causes, including above all malignancies of the gastro-intestinal tract. CASE PRESENTATION: Herein, we report a particular case of a 80 years-old immunocompetent woman hospitalized for sepsis. At the end of the diagnostic process, Streptococcus constellatus (Sc) was identified as the cause of sepsis, multiple PLA were found together with a previous unknown ileal malignancy. We speculated about a possible correlation among these three entities (i.e. sepsis from Sc, PLA and tumors). CONCLUSIONS: Detection of Sc in blood should raise red flags in clinicians as aggressive clinical presentation are possible.

Glucose-6-phosphate dehydrogenase deficiency accelerates arterial aging in diabetes.

AIMS: High glucose levels and Glucose-6-Phosphate Dehydrogenase deficiency (G6PDd) have both tissue inflammatory effects. Here we determined whether G6PDd accelerates arterial aging (information linked stiffening) in diabetes. METHODS: Plasma glucose, interleukin 6 (IL6), and arterial stiffness (indexed as carotid-femoral Pulse Wave Velocity, PWV) and red blood cell G6PD activity were assessed in a large (4448) Sardinian population. RESULTS: Although high plasma glucose in diabetics, did not differ by G6DP status (178.2 ± 55.1 vs 169.0 ± 50.1 mg/dl) in G6DPd versus non-G6PDd subjects, respectively, IL6, and PWV (adjusted for age and glucose) were significantly increased in G6PDd vs non-G6PDd subjects (PWV, 8.0 ± 0.4 vs 7.2 ± 0.2 m/sec) and (IL6, 6.9 ± 5.0 vs 4.2 ± 3.0 pg/ml). In non-diabetics, neither fasting plasma glucose, nor IL6, nor PWV were impacted by G6PDd. CONCLUSION: G6PDd in diabetics is associated with increased inflammatory markers and accelerated arterial aging.

Effectiveness of a randomized intervention by a geriatric team in frail hospital inpatients in non-geriatric settings: FRAILCLINIC project.

BACKGROUND: Little research has been undertaken on the benefits of frailty management within different hospital settings. The objective of this study is to provide evidence on the viability and effectiveness of frailty management in non-geriatric hospital settings on mortality and functional decline after discharge. METHODS: Data from the FRAILCLINIC (NCT02643069) study were used. FRAILCLINIC is a randomized controlled trial developed in non-geriatric hospital inpatient settings (emergency room, cardiology and surgery) from Spain (2), Italy (2) and the United Kingdom (1). Inpatients must met frailty criteria (according to the Frailty Phenotype and/or FRAIL scale), ≥75 years old. The control group (CG) received usual care. The intervention group (IG) received comprehensive geriatric assessment (CGA) and a coordinated intervention consisting in recommendations to the treating physician about polypharmacy, delirium, falls, nutrition and physical exercise plus a discharge plan. The main outcomes included functional decline (worsening ≥5 points in Barthel Index) and mortality at 3 months. We used multivariate logistic regression models adjusted by age, gender and the Charlson index. Intention-to-treat (ITT) and per-protocol (PP) analyses were used. RESULTS: Eight hundred twenty one participants (IG: 416; mean age 83.00 ± 4.91; 51.44% women; CG: 405; mean age 82.46 ± 6.03; 52.35% women) were included. In the IG, 77.16% of the participants followed the geriatric team's recommendations as implemented by the treating physicians. The intervention showed a benefit on functional decline and mortality [OR: 0.67(0.47-0.96), P-value 0.027 and 0.29(0.14-0.57), P-value < 0.001, respectively) when fully followed by the treating physician. A trend to benefit (close to statistical significance) in functional decline and mortality were also observed when any of the recommendations were not followed [OR (95% CI): 0.72 (0.51-1.01), P-value: 0.055; and 0.64 (0.37-1.10), P-value: 0.105, respectively]. CONCLUSIONS: An individualized intervention in frail in-patients reduces the risk of functional deterioration and mortality at 3 months of follow-up when a care management plan is designed and followed.

Pancytopenia Secondary to Vitamin B12 Deficiency in Older Subjects.

BACKGROUND: Vitamin B12 (cobalamin CBL) is a water-soluble vitamin required to form hematopoietic cells (red blood cells, white blood cells, and platelets). It is involved in the process of synthesizing DNA and myelin sheath. Deficiencies of vitamin B12 and/or folate can cause megaloblastic anemia (macrocytic anemia with other features due to impaired cell division). Pancytopenia is a less frequent exordium of severe vitamin B12 deficiency. Vitamin B12 deficiency can also cause neuropsychiatric findings. In addition to correcting the deficiency, an essential aspect of management is determining the underlying cause because the need for additional testing, the duration of therapy, and the route of administration may differ depending on the underlying cause. METHODS: Here, we present a series of four patients hospitalized for megaloblastic anemia (MA) in pancytopenia. All patients diagnosed with MA were studied for a clinic-hematological and etiological profile. RESULTS: All the patients presented with pancytopenia and megaloblastic anemia. Vitamin B12 deficiency was documented in 100% of cases. There was no correlation between the severity of anemia and deficiency of the vitamin. Overt clinical neuropathy was present in none of the cases of MA, while subclinical neuropathy was seen in one case. The etiology of vitamin B12 deficiency was pernicious anemia in two cases and low food intake in the remaining cases. CONCLUSION: This case study emphasizes the role of vitamin B12 deficiency as a leading cause of pancytopenia among adults.

Differential utility of various frailty diagnostic tools in non-geriatric hospital departments of several countries: A longitudinal study.

BACKGROUND: There is limited knowledge on the performance of different frailty scales in clinical settings. We sought to evaluate in non-geriatric hospital departments the feasibility, agreement and predictive ability for adverse events after 1 year follow-up of several frailty assessment tools. METHODS: Longitudinal study with 667 older adults recruited from five hospitals in three different countries (Spain, Italy and United Kingdom). Participants were older than 75 years attending the emergency room, cardiology and surgery departments. Frailty scales used were Frailty Phenotype (FP), FRAIL scale, Tilburg and Groningen Frailty Indicators, and Clinical Frailty Scale (CFS). Analyses included the prevalence of frailty, degree of agreement between tools, feasibility and prognostic value for hospital readmission, worsening of disability and mortality, by tool and setting. RESULTS: Emergency Room and cardiology were the settings with the highest frailty prevalence, varying by tool between 40.4% and 67.2%; elective surgery was the one with the lowest prevalence (between 13.2% and 38.2%). The tools showed a fair to moderate agreement. FP showed the lowest feasibility, especially in urgent surgery (35.6%). FRAIL, CFS and FP predicted mortality and readmissions in several settings, but disability worsening only in cardiology. CONCLUSIONS: Frailty is a highly frequent condition in older people attending non-geriatric hospital departments. We recommend that based upon their current feasibility and predictive ability, the FRAIL scale, CFS and FP should be preferentially used in these settings. The low concordance among the tools and differences in prevalence reported and predictive ability suggest the existence of different subtypes of frailty.

The appropriateness of antiplatelet and anticoagulant drug prescriptions in hospitalized patients in an internal medicine ward.

BACKGROUND: Polypharmacy increases the risk of potentially inappropriate prescribing. STOPP&START criteria identify a group of drugs representing inappropriate medication and a group of drugs representing potential prescribing omissions. AIMS: To evaluate the appropriateness of prescription of antiplatelet and anticoagulant drugs in a sample of patients admitted to an internal medicine ward and their impact on three different outcomes: length of hospitalization, intra-hospital death, and risk of re-admission in the hospital. METHODS: We analyzed a cohort of 485 inpatients followed for 1 year after discharge from the hospital. RESULTS: The study sample had a mean age of 70.4 ± 17.6 years, and 48.9% were female. Clinical indication for antiplatelet was not appropriate in 41.2% of the subjects. Anticoagulant therapy was not appropriate in 22.8% of the subjects: there was incorrect clinical indication in 5/33 and inappropriate dosing in 28/33. START criteria for antiplatelet drug, but neither STOPP criteria for antiplatelet nor for anticoagulant was positively associated with the length of hospitalization (t = 3.08, p < 0.01). START criteria for anticoagulant medication were associated with greater odds of intra-hospital mortality (OR 5.16, 95% CI 1.92-13.85, p < 0.0001) and with lower odds of re-admission to the hospital within 12 months (OR 0.38, 95% CI 0.18-0.80, p < 0.01). DISCUSSION: The non-prescription of antiplatelet is associated with longer length of hospitalization. The presence of START criteria for anticoagulant is associated with increased risk of intra-hospital death. CONCLUSIONS: The appropriateness of prescription is a global burden especially in older subjects, while it increases the risk of fatal and non-fatal complications, side effects, and, consequently, higher health-care costs.

Is Arterial Stiffness a Determinant of Hypotension?

INTRODUCTION: Previous observation identified both hypotension and arterial aging, indexed as Pulse Wave Velocity (PWV), as significant determinants of cognitive decline in older subjects. AIM: To investigate the role of PWV as a determinant of hypotension in older patients. METHODS: A cohort of 344 subjects came to our Outpatient Clinic, free of cancer, acute myocardial infarction or stroke, atrial fibrillation, renal, hepatic or cardiac failure, secondary hypertension, or thyroid disease. RESULTS: Hypotension occurred in 49% of participants. SBP levels (OR 0.79, 95% CI 0.67-0.84, p < 0.01), PWV (OR 0.86, 95% CI 0.77-0.94, p < 0.01), and use of beta-blockers (OR 2.42, 95% CI 1.09-5.36, p < 0.05), were independent determinants of the risk of hypotension. CONCLUSIONS: Hypotension is a quite common phenomenon in older subjects. Its prevention requires a more accurate management of hypertension aimed at better identifying which older subjects in whom intensive BP control may be harmful and those who may benefit from it.

Thyroid Hormone Diseases and Osteoporosis.

Thyroid hormones are essential for normal skeletal development and normal bone metabolism in adults but can have detrimental effects on bone structures in states of thyroid dysfunction. Untreated severe hyperthyroidism influences the degree of bone mass and increases the probability of high bone turnover osteoporosis. Subclinical hyperthyroidism, defined as low thyrotropin (TSH) and free hormones within the reference range, is a subtler disease, often asymptomatic, and the diagnosis is incidentally made during screening exams. However, more recent data suggest that this clinical condition may affect bone metabolism resulting in decreased bone mineral density (BMD) and increased risk of fracture, particularly in postmenopausal women. The main causes of exogenous subclinical hyperthyroidism are inappropriate replacement dose of thyroxin and TSH suppressive L-thyroxine doses in the therapy of benign thyroid nodules and thyroid carcinoma. Available data similarly suggest that a long-term TSH suppressive dose of thyroxin may decrease BMD and may induce an increased risk of fracture. These effects are particularly observed in postmenopausal women but are less evident in premenopausal women. Overt hypothyroidism is known to lower bone turnover by reducing both osteoclastic bone resorption and osteoblastic activity. These changes in bone metabolism would result in an increase in bone mineralization. At the moment, there are no clear data that demonstrate any relationship between BMD in adults and hypothyroidism. Despite these clinical evidences, the cellular and molecular actions of thyroid hormones on bone structures are not complete clear.

Effect of rhTSH on Lipids.

BACKGROUND: Subclinical hypothyroidism is associated with increased blood lipid levels. However, the exact role of thyrotropin (TSH) alone is not clear. In order to clarify this point, we analysed the acute effect of recombinant human TSH (rhTSH) administration on lipid levels. METHODS: Sera of 27 premenopausal women with well-differentiated thyroid cancer were analysed. Patients that underwent a total thyroidectomy, ablation with 131I (Iodine 131) and rhTSH administration as a part of routine follow-up American Thyroid Association guidelines were included. The protocol consists of 2 intramuscular injections of 0.9 mg of rhTSH, performed on day 1 day and day 2, with blood collection on day 1 (before rhTSH administration), and day 5. TSH, free thyroxine, total cholesterol, low-density lipoprotein cholesterol (LDLc), high density lipoprotein cholesterol (HDLc), and triglycerides were assessed in all the samples, before and four days after the first administration of rhTSH. RESULTS: Total cholesterol and triglycerides significantly increased after stimulation of rhTSH (respectively, 192 ± 33 vs. 207 ± 26, p = 0.036 and 72 ± 23 vs. 85 ± 23, p = 0.016). LDLc and HDLc showed comparable concentrations before and after the test (respectively, 115 ± 27 vs. 126 ± 22, p = 0.066, and 62 ± 15 vs. 64 ± 15, p = 0.339), while non-HDLc increased after stimulation (130 ± 30 vs. 143 ± 25, p = 0.045). CONCLUSION: TSH has a direct effect on total cholesterol, triglycerides, and nonHDLc. Explanation of these phenomena will require additional studies.

Arterial stiffness and multiple organ damage: a longitudinal study in population.

AIMS: Previous cross-sectional observation identified arterial aging, indexed as pulse-wave velocity (PWV), as a key determinant of the simultaneous multiple organ damage (heart, carotid artery, and kidney). The aim of the present cohort study is to investigate trajectories of repeated measures of PWV and traditional CV risk factors in subjects who eventually presented clinical evidence of multiple organ damage in the SardiNIA study. METHODS AND RESULTS: Organ damage was measured in the heart (left ventricular hypertrophy, LVH), the common carotid artery (intima-media thickness > 0.9 mm and/or plaque), and the kidney (eGFR < 60 ml/min/1.73 m2) of 2130 men and women of a broad age range participating the SardiNIA study. SHATS was defined as the simultaneous occurrence of all the three-organ damages. Trajectory in traditional CV risk factors and PWV was analyzed retrospectively (four observations over 9 years) according to the number of organ damage (from 0 to 3). Compared to subjects with no organ damage, after controlling for traditional CV risk factors, each 1 m/s increase in baseline PWV was accompanied by a 93% higher odds of developing SHATS; and each 1 cm/s (0.01 m/s) annual increase in PWV by a 31% greater odds of developing SHATS. CONCLUSIONS: Arterial stiffness, a proxy of arterial aging that can be measured clinically as PWV, is an integrated predictive marker of multiple age-associated organ damage recognized as clinical diseases.

Declaración de posición del Grupo de la Comisión Lancet de Hipertensión con respecto a la mejora mundial de las normas de exactitud para los dispositivos de medición de la presión arterial / Lancet Commission on Hypertension Group position statement on the global improvement of accuracy standards for devices that measure blood pressure / Posicionamento do Grupo da Lancet Commission on Hypertension sobre a melhoria global dos padrões de acurácia para aparelhos que medem a pressão arterial

Objetivos. El boletín de notas de México correspondiente al 2018 evalúa las oportunidades a disposición de la población infantil y joven mexicana para que puedan desarrollar niveles adecuados de actividad física y sueño, y disminuyan el sedentarismo.Métodos. El boletín es un sistema de vigilancia que recopila los datos obtenidos en las encuestas nacionales, censos, documentos gubernamentales, sitios web, literatura gris y estudios publicados con respecto al análisis de 16 indicadores en 4 categorías: comportamientos diarios, estado físico, entornos y fuentes influyentes, y estrategias e inversión. Los datos fueron cotejados con los puntos de referencia establecidos. A cada indicador se le asignó una calificación entre 1 y 10 (< 6 significa reprobado) o fue marcado como "incompleto" si los datos eran nulos o insuficientes. Resultados. Las calificaciones obtenidas para los comportamientos diarios fueron: actividad física en general: 4; participación en actividades deportivas organizadas: 5; juego activo: 3; modalidades de transporte activas: 5; sueño: 7; y sedentarismo: 3. El estado físico obtuvo un 7. Las calificaciones para los entornos y fuentes influyentes fueron: familiares y pares: "incompleto"; escuela: 3; comunidad y entorno: 4. Para las estrategias e inversión: estrategias gubernamentales: 6; entidades no gubernamentales: 2.Conclusiones. Las bajas calificaciones obtenidas en 11 de los 16 indicadores demuestran que las escuelas, las familias, las comunidades y el gobierno tienen que aunar esfuerzos para mejorar las oportunidades que tiene la población infantil y joven en México para desarrollar niveles de actividad física satisfactorios.(AU)

ABSTRACT The Lancet Commission on Hypertension identified that a key action to address the worldwide burden of high blood pressure (BP) was to improve the quality of BP measurements by using BP devices that have been validated for accuracy. Currently, there are over 3 000 commercially available BP devices, but many do not have published data on accuracy testing according to established scientific standards. This problem is enabled through weak or absent regulations that allow clearance of devices for commercial use without formal validation. In addition, new BP technologies have emerged (e.g. cuffless sensors) for which there is no scientific consensus regarding BP measurement accuracy standards. Altogether, these issues contribute to the widespread availability of clinic and home BP devices with limited or uncertain accuracy, leading to inappropriate hypertension diagnosis, management and drug treatment on a global scale. The most significant problems relating to the accuracy of BP devices can be resolved by the regulatory requirement for mandatory independent validation of BP devices according to the universally-accepted International Organization for Standardization Standard. This is a primary recommendation for which there is an urgent international need. Other key recommendations are development of validation standards specifically for new BP technologies and online lists of accurate devices that are accessible to consumers and health professionals. Recommendations are aligned with WHO policies on medical devices and universal healthcare. Adherence to recommendations would increase the global availability of accurate BP devices and result in better diagnosis and treatment of hypertension, thus decreasing the worldwide burden from high BP.(AU)

RESUMO A Comissão Lancet sobre Hipertensão Arterial identificou que uma iniciativa central para enfrentar a carga mundial da hipertensão arterial seria a melhoria na qualidade da mensuração da pressão arterial pelo uso aparelhos de pressão arterial validados quanto à acurácia. Atualmente, existem mais de 3 000 aparelhos de pressão arterial disponíveis comercialmente; entretanto, muitos não têm dados publicados sobre testes de acurácia realizados de acordo com padrões científicos estabelecidos. Este problema resulta de regulamentação fraca ou inexistente, o que permite a aprovação para uso comercial de dispositivos sem validação formal. Além disso, surgiram novas tecnologias de mensuração da pressão arterial (por exemplo, sensores sem algemas) sem consenso científico quanto aos padrões de acurácia. No conjunto, essas questões contribuem para a oferta generalizada de dispositivos de pressão arterial clínica e domiciliar com acurácia limitada ou incerta, levando a diagnóstico, gerenciamento e tratamento inadequados da hipertensão em escala global. Os problemas mais significativos relacionados com a acurácia dos dispositivos de pressão arterial podem ser resolvidos por regulamentação que imponha a obrigatoriedade de validação independente dos aparelhos de pressão arterial, de acordo com a norma universalmente aceita pela Organização Internacional de Normalização. Esta é uma recomendação fundamental para a qual existe uma necessidade internacional urgente. Outras recomendações essenciais incluem o desenvolvimento de padrões de validação especificamente para novas tecnologias de mensuração da pressão arterial e listas on-line de aparelhos com acurácia adequada que sejam acessíveis aos consumidores e profissionais de saúde. As recomendações estão alinhadas com as políticas da Organização Mundial da Saúde (OMS) sobre dispositivos médicos e atenção universal à saúde. A adesão às recomendações aumentaria a oferta global de dispositivos de pressão arterial com acurácia adequada e resultaria em melhor diagnóstico e tratamento da hipertensão arterial, diminuindo assim a carga mundial dessa doença.(AU)

Frequency of early vascular aging and associated risk factors among an adult population in Latin America: the OPTIMO study.

The main objective was to estimate the frequency of early vascular aging (EVA) in a sample of subjects from Latin America, with emphasis in young adults. We included 1416 subjects from 12 countries in Latin America who provided information about lifestyle, cardiovascular risk factors (CVRF), and anthropometrics. We measured pulse wave velocity (PWV) as a marker of arterial stiffness, and blood pressure (BP) using an oscillometric device (Mobil-O-Graph). To determine the frequency of EVA, we used multiple linear regression to estimate each subject's PWV expected for his/her age and systolic BP, and compared with observed values to obtain standardized residuals (z-scores). We defined EVA when z-score was ≥1.96. Finally, a multivariable logistic regression analysis was performed to determine baseline characteristics associated with EVA. Mean age was 49.9 ± 15.5 years, male gender was 50.3%. Mean PWV was 7.52 m/s (SD 1.97), mean systolic BP was 125.3 mmHg (SD 16.7) and mean diastolic BP was 78.9 mmHg (SD 12.2). The frequency of EVA was 5.7% in the total population, 9.8% in adults of 40 years or less and 18.7% in those 30 years or less. In these young adults, multiple logistic regression analyses demonstrated that dyslipidemia and hypertension showed an independent association with EVA, and smoking a borderline association (p = 0.07). In conclusion, the frequency of EVA in a sample from Latin America was around 6%, with higher rates in young adults. These results would support the search of CVRF and EVA during early adulthood.

The relationship between the metabolic syndrome and arterial wall thickness: A mosaic still to be interpreted.

BACKGROUND AND AIMS: We aimed to identify clusters of metabolic syndrome (MetS) components, risky for extremely high intima-media thickness. METHODS: We studied 41,513 volunteers (men and women) from eleven cohorts worldwide, participating in the MARE (Metabolic syndrome and Artery REsearch) Consortium. RESULTS: Specific clusters of MetS components - high triglycerides-high blood pressure-abdominal obesity (TBW), low HDL cholesterol-high blood pressure-abdominal obesity (HBW), high glucose-high blood pressure-abdominal obesity (GBW) - were accompanied by a 50-90% significantly greater likelihood of presenting extremely high intima-media thickness (via ultrasound of carotid artery, CCA IMT), after controlling for age, sex, smoking, non-HDL cholesterol, and presence of diabetes mellitus. This likelihood is comparable to the effect of being 7-8 years older or of being a cigarette smoker or of having non-HDL cholesterol 50 mg/dl higher. CONCLUSIONS: The consistent association of specific clusters of MetS components with extremely thick (older) large artery cross-culturally suggests that identification of those clusters in clinical practice will facilitate a personalized health care and a better - i.e. more healthy and cost-effective - prevention of major cardiovascular (CV) events.

Arterial stiffness and influences of the metabolic syndrome: a cross-countries study.

Specific clusters of metabolic syndrome (MetS) components impact differentially on arterial stiffness, indexed as pulse wave velocity (PWV). Of note, in several population-based studies participating in the MARE (Metabolic syndrome and Arteries REsearch) Consortium the occurrence of specific clusters of MetS differed markedly across Europe and the US. The aim of the present study was to investigate whether specific clusters of MetS are consistently associated with stiffer arteries in different populations. We studied 20,570 subjects from 9 cohorts representing 8 different European countries and the US participating in the MARE Consortium. MetS was defined in accordance with NCEP ATPIII criteria as the simultaneous alteration in ≥3 of the 5 components: abdominal obesity (W), high triglycerides (T), low HDL cholesterol (H), elevated blood pressure (B), and elevated fasting glucose (G). PWV measured in each cohort was "normalized" to account for different acquisition methods. MetS had an overall prevalence of 24.2% (4985 subjects). MetS accelerated the age-associated increase in PWV levels at any age, and similarly in men and women. MetS clusters TBW, GBW, and GTBW are consistently associated with significantly stiffer arteries to an extent similar or greater than observed in subjects with alteration in all the five MetS components--even after controlling for age, sex, smoking, cholesterol levels, and diabetes mellitus--in all the MARE cohorts. In conclusion, different component clusters of MetS showed varying associations with arterial stiffness (PWV).

High prevalence of poor quality drug prescribing in older individuals: a nationwide report from the Italian Medicines Agency (AIFA).

BACKGROUND: Poor quality of drug prescribing in older persons is often associated with increased drug-related adverse events, hospitalization, and mortality. The present study describes a set of prescribing quality indicators developed by the Geriatrics Working Group of the Italian Medicines Agency (AIFA) and estimates their prevalence in the entire elderly (≥ 65 years) population in Italy. METHODS: We performed a cross-sectional study using 2011 data from the OsMed (Osservatorio dei Medicinali) database, which comprises all prescribed drugs that are reimbursed by the Italian National Healthcare System. Yearly prevalence of drug prescribing quality indicators in the Italian older population (n = 12,301,537) was determined. RESULTS: Overall, 13 quality indicators addressing polypharmacy, adherence to treatment of chronic diseases, prescribing cascade, undertreatment, drug-drug interactions, and drugs to be avoided were identified. Polypharmacy was common, with more than 1.3 million individuals taking greater than or equal to 10 drugs (11.3% of the study population). The prevalence of low adherence and undertreatment was also elevated and increased with advancing age, with highest prevalence occurring in individuals aged 85 years and older. Prevalence was less than 3% for quality indicators assessing the prescribing cascade, drug-drug interactions, and drugs to be avoided. CONCLUSIONS: These results confirm the high frequency of suboptimal drug prescribing in older adults, using a database that covers the whole Italian population. In general, this descriptive study may help in prioritizing strategies aimed at improving the quality of prescribing in elderly population.

Common genetic variation in the 3'-BCL11B gene desert is associated with carotid-femoral pulse wave velocity and excess cardiovascular disease risk: the AortaGen Consortium.

BACKGROUND: Carotid-femoral pulse wave velocity (CFPWV) is a heritable measure of aortic stiffness that is strongly associated with increased risk for major cardiovascular disease events. METHODS AND RESULTS: We conducted a meta-analysis of genome-wide association data in 9 community-based European ancestry cohorts consisting of 20 634 participants. Results were replicated in 2 additional European ancestry cohorts involving 5306 participants. Based on a preliminary analysis of 6 cohorts, we identified a locus on chromosome 14 in the 3'-BCL11B gene desert that is associated with CFPWV (rs7152623, minor allele frequency=0.42, ß=-0.075±0.012 SD/allele, P=2.8×10(-10); replication ß=-0.086±0.020 SD/allele, P=1.4×10(-6)). Combined results for rs7152623 from 11 cohorts gave ß=-0.076±0.010 SD/allele, P=3.1×10(-15). The association persisted when adjusted for mean arterial pressure (ß=-0.060±0.009 SD/allele, P=1.0×10(-11)). Results were consistent in younger (<55 years, 6 cohorts, n=13 914, ß=-0.081±0.014 SD/allele, P=2.3×10(-9)) and older (9 cohorts, n=12 026, ß=-0.061±0.014 SD/allele, P=9.4×10(-6)) participants. In separate meta-analyses, the locus was associated with increased risk for coronary artery disease (hazard ratio=1.05; confidence interval=1.02-1.08; P=0.0013) and heart failure (hazard ratio=1.10, CI=1.03-1.16, P=0.004). CONCLUSIONS: Common genetic variation in a locus in the BCL11B gene desert that is thought to harbor 1 or more gene enhancers is associated with higher CFPWV and increased risk for cardiovascular disease. Elucidation of the role this novel locus plays in aortic stiffness may facilitate development of therapeutic interventions that limit aortic stiffening and related cardiovascular disease events.

Independent and additive effects of cytokine patterns and the metabolic syndrome on arterial aging in the SardiNIA Study.

OBJECTIVE: Metabolic syndrome (MetS) and its components accelerate age-associated increases in arterial stiffness and thickness. We investigated whether specific proinflammatory cytokines contribute to arterial aging, independent of age, sex, MetS, and other traditional CV risk factors. RESEARCH DESIGN AND METHODS: MetS components (ATP III criteria) and arterial properties were assessed in 6148 subjects, aged 14-102 in Sardinia, Italy. Common carotid artery (CCA) diameter, intima-media thickness (IMT), and aortic pulse wave velocity (PWV), adiponectin, leptin, high-sensitivity C reactive protein (hsCRP), monocyte chemoattractant protein 1 (MCP1), and interleukin 6 (IL6) were measured. RESULTS: While cytokine levels - except for MCP1 - were significantly higher (lower for adiponectin) in MetS than in control subjects, and the increased PWV and CCA IMT with aging were associated with MetS, this association was independent of cytokine levels (p<0.001 for both PWV and CCA IMT). Specific cytokines, however, were significantly associated with arterial stiffness (higher leptin, p<0.001, and higher hsCRP, p<0.001) or thickness (lower adiponectin, p<0.05, and higher IL6, p<0.001) - independent of age, sex, MetS and other traditional CV risk factors. The co-occurrence of both MetS and higher cytokines levels was associated with greater increases in arterial stiffness and thickness. CONCLUSION: While MetS and specific cytokine patterns associated with arterial aging, the increases in arterial stiffness and thickness are greater when both MetS and higher cytokine levels are present, suggesting a possible synergistic effect of MetS and inflammation on the arterial wall.

Common variants at ten loci modulate the QT interval duration in the QTSCD Study.

The QT interval, a measure of cardiac repolarization, predisposes to ventricular arrhythmias and sudden cardiac death (SCD) when prolonged or shortened. A common variant in NOS1AP is known to influence repolarization. We analyze genome-wide data from five population-based cohorts (ARIC, KORA, SardiNIA, GenNOVA and HNR) with a total of 15,842 individuals of European ancestry, to confirm the NOS1AP association and identify nine additional loci at P < 5 x 10(-8). Four loci map near the monogenic long-QT syndrome genes KCNQ1, KCNH2, SCN5A and KCNJ2. Two other loci include ATP1B1 and PLN, genes with established electrophysiological function, whereas three map to RNF207, near LITAF and within NDRG4-GINS3-SETD6-CNOT1, respectively, all of which have not previously been implicated in cardiac electrophysiology. These results, together with an accompanying paper from the QTGEN consortium, identify new candidate genes for ventricular arrhythmias and SCD.