A multicenter, open-label study of the efficacy and safety of telmisartan in mild to moderate hypertensive patients

OBJECTIVE: To evaluate the efficacy and tolerability of telmisartan, given once a day to patients with mild to moderate hypertension, as well as to assess the 24-hour blood pressure profile with ABPM. METHODS: Initially, 163 patients over 18 were selected, regardless of sex, with blood pressure levels >140/90mmHg at visit 1, which was confirmed at visit 2. One hundred thirty-four patients completed the study. After a 4-week placebo run-in phase, telmisartan 40mg/daily was given for 6 weeks. In those patients whose blood pressure (BP) levels were lower than 140/90mmHg, the same dosage was kept for an additional period of 6 weeks. For those who had BP higher than 140/90mmHg, the dosage was increased to 80mg/daily. Sixty-two patients were included in a subgroup that underwent ABPM 3 different times during the study. RESULTS: In the overall group, blood pressure reduction ranged from 162.3±14.5/101.3±5.75 mmHg (baseline) to 147.3±20.1/90.8±10.9 mmHg (week 12) (p<0.05). Mean blood pressure decreases were 14.4mmHg for systolic BP and 10.3mmHg for diastolic BP, after 12 weeks of active treatment. A subanalysis showed that 47 (35%) patients took telmisartan 40mg throughout the study and 81 (65%) had the dosage increased to 80mg daily. Using ABPM, an 8-mmHg reduction in systolic BP as well as a 5-mmHg reduction in diastolic BP were observed, when compared with baseline values in the final 6 hours (18-24 hours after the last dose of study medication). CONCLUSION: Our results confirm that telmisartan given once a day is effective in reducing blood pressure levels in mild to moderate hypertensive patients. This reduction occurs in a sustained and gradual manner during a 24-hour period confirmed by ABPM.

Detection of incipient left ventricular hypertrophy in mild to moderate arterial hypertension with normal electrocardiogram and echocardiogram: a new use for signal-averaged electrocardiography

OBJECTIVE: To assess signal-averaged electrocardiogram (SAECG) for diagnosing incipient left ventricular hypertrophy (LVH). METHODS: A study with 115 individuals was carried out. The individuals were divided as follows: GI - 38 healthy individuals; GII - 47 individuals with mild to moderate hypertension and normal findings on echocardiogram and ECG; and GIII - 30 individuals with hypertension and documented LVH. The magnitude vector of the SAECG was analyzed with the high-pass cutoff frequency of 40 Hz through the bidirectional four-pole Butterworth high-pass digital filter. The mean quadratic root of the total QRS voltage (RMST) and the two-dimensional integral of the QRS area of the spectro-temporal map were analyzed between 0 and 30 Hz for the frequency domain (Int FD), and between 40 and 250 Hz for the time domain (Int TD). The electrocardiographic criterion for LVH was based on the Cornell Product. Left ventricular mass was calculated with the Devereux formula. RESULTS: All parameters analyzed increased from GI to GIII, except for Int FD (GII vs GIII) and RMST log (GII vs GIII). Int TD showed greater accuracy for detecting LVH with an appropriate cutoff > 8 (sensitivity of 55%, specificity of 81%). Positive values (> 8) were found in 56.5% of the G II patients and in 18.4% of the GI patients (p< 0.0005). CONCLUSION: SAECG can be used in the early diagnosis of LVH in hypertensive patients with normal ECG and echocardiogram.

Cost-Effectiveness of High, Moderate and Low-Dose Statins in the Prevention of Vascular Events in the Brazilian Public Health System

Background:Statins have proven efficacy in the reduction of cardiovascular events, but the financial impact of its widespread use can be substantial.Objective:To conduct a cost-effectiveness analysis of three statin dosing schemes in the Brazilian Unified National Health System (SUS) perspective.Methods:We developed a Markov model to evaluate the incremental cost-effectiveness ratios (ICERs) of low, intermediate and high intensity dose regimens in secondary and four primary scenarios (5%, 10%, 15% and 20% ten-year risk) of prevention of cardiovascular events. Regimens with expected low-density lipoprotein cholesterol reduction below 30% (e.g. simvastatin 10mg) were considered as low dose; between 30-40%, (atorvastatin 10mg, simvastatin 40mg), intermediate dose; and above 40% (atorvastatin 20-80mg, rosuvastatin 20mg), high-dose statins. Effectiveness data were obtained from a systematic review with 136,000 patients. National data were used to estimate utilities and costs (expressed as International Dollars - Int$). A willingness-to-pay (WTP) threshold equal to the Brazilian gross domestic product per capita (circa Int$11,770) was applied.Results:Low dose was dominated by extension in the primary prevention scenarios. In the five scenarios, the ICER of intermediate dose was below Int$10,000 per QALY. The ICER of the high versus intermediate dose comparison was above Int$27,000 per QALY in all scenarios. In the cost-effectiveness acceptability curves, intermediate dose had a probability above 50% of being cost-effective with ICERs between Int$ 9,000-20,000 per QALY in all scenarios.Conclusions:Considering a reasonable WTP threshold, intermediate dose statin therapy is economically attractive, and should be a priority intervention in prevention of cardiovascular events in Brazil.

Moderate amounts of fructose consumption impair insulin sensitivity in healthy young men: a randomized controlled trial.

OBJECTIVE: Adverse effects of hypercaloric, high-fructose diets on insulin sensitivity and lipids in human subjects have been shown repeatedly. The implications of fructose in amounts close to usual daily consumption, however, have not been well studied. This study assessed the effect of moderate amounts of fructose and sucrose compared with glucose on glucose and lipid metabolism. RESEARCH DESIGN AND METHODS: Nine healthy, normal-weight male volunteers (aged 21-25 years) were studied in this double-blind, randomized, cross-over trial. All subjects consumed four different sweetened beverages (600 mL/day) for 3 weeks each: medium fructose (MF) at 40 g/day, and high fructose (HF), high glucose (HG), and high sucrose (HS) each at 80 g/day. Euglycemic-hyperinsulinemic clamps with [6,6]-(2)H(2) glucose labeling were used to measure endogenous glucose production. Lipid profile, glucose, and insulin were measured in fasting samples. RESULTS: Hepatic suppression of glucose production during the clamp was significantly lower after HF (59.4 ± 11.0%) than HG (70.3 ± 10.5%, P < 0.05), whereas fasting glucose, insulin, and C-peptide did not differ between the interventions. Compared with HG, LDL cholesterol and total cholesterol were significantly higher after MF, HF, and HS, and free fatty acids were significantly increased after MF, but not after the two other interventions (P < 0.05). Subjects' energy intake during the interventions did not differ significantly from baseline intake. CONCLUSIONS: This study clearly shows that moderate amounts of fructose and sucrose significantly alter hepatic insulin sensitivity and lipid metabolism compared with similar amounts of glucose.

Assessing depression outcome in patients with moderate dementia: sensitivity of the HoNOS65+ scale.

To date, there is no widely accepted clinical scale to monitor the evolution of depressive symptoms in demented patients. We assessed the sensitivity to treatment of a validated French version of the Health of the Nation Outcome Scale (HoNOS) 65+ compared to five routinely used scales. Thirty elderly inpatients with ICD-10 diagnosis of dementia and depression were evaluated at admission and discharge using paired t-test. Using the Brief Psychiatric Rating Scale (BPRS) "depressive mood" item as gold standard, a receiver operating characteristic curve (ROC) analysis assessed the validity of HoNOS65+F "depressive symptoms" item score changes. Unlike Geriatric Depression Scale, Mini Mental State Examination and Activities of Daily Living scores, BPRS scores decreased and Global Assessment Functioning Scale score increased significantly from admission to discharge. Amongst HoNOS65+F items, "behavioural disturbance", "depressive symptoms", "activities of daily life" and "drug management" items showed highly significant changes between the first and last day of hospitalization. The ROC analysis revealed that changes in the HoNOS65+F "depressive symptoms" item correctly classified 93% of the cases with good sensitivity (0.95) and specificity (0.88) values. These data suggest that the HoNOS65+F "depressive symptoms" item may provide a valid assessment of the evolution of depressive symptoms in demented patients.

A human MYBPC3 mutation appearing about 10 centuries ago results in a hypertrophic cardiomyopathy with delayed onset, moderate evolution but with a risk of sudden death.

BACKGROUND: Hypertrophic Cardiomyopathy (HCM) is a genetically heterogeneous disease. One specific mutation in the MYBPC3 gene is highly prevalent in center east of France giving an opportunity to define the clinical profile of this specific mutation. METHODS: HCM probands were screened for mutation in the MYH7, MYBPC3, TNNT2 and TNNI3 genes. Carriers of the MYBPC3 IVS20-2A>G mutation were genotyped with 8 microsatellites flanking this gene. The age of this MYBPC3 mutation was inferred with the software ESTIAGE. The age at first symptom, diagnosis, first complication, first severe complication and the rate of sudden death were compared between carriers of the IVS20-2 mutation (group A) and carriers of all other mutations (group B) using time to event curves and log rank test. RESULTS: Out of 107 HCM probands, 45 had a single heterozygous mutation in one of the 4 tested sarcomeric genes including 9 patients with the MYBPC3 IVS20-2A>G mutation. The IVS20-2 mutation in these 9 patients and their 25 mutation carrier relatives was embedded in a common haplotype defined after genotyping 4 polymorphic markers on each side of the MYBPC3 gene. This result supports the hypothesis of a common ancestor. Furthermore, we evaluated that the mutation occurred about 47 generations ago, approximately at the 10th century.We then compared the clinical profile of the IVS20-2 mutation carriers (group A) and the carriers of all other mutations (group B). Age at onset of symptoms was similar in the 34 group A cases and the 73 group B cases but group A cases were diagnosed on average 15 years later (log rank test p = 0.022). Age of first complication and first severe complication was delayed in group A vs group B cases but the prevalence of sudden death and age at death was similar in both groups. CONCLUSION: A founder mutation arising at about the 10th century in the MYBPC3 gene accounts for 8.4% of all HCM in center east France and results in a cardiomyopathy starting late and evolving slowly but with an apparent risk of sudden death similar to other sarcomeric mutations.

Effect of moderate hyperventilation and induced hypertension on cerebral tissue oxygenation after cardiac arrest and therapeutic hypothermia.

AIM: Improving cerebral perfusion is an essential component of post-resuscitation care after cardiac arrest (CA), however precise recommendations in this setting are limited. We aimed to examine the effect of moderate hyperventilation (HV) and induced hypertension (IH) on non-invasive cerebral tissue oxygenation (SctO2) in patients with coma after CA monitored with near-infrared spectroscopy (NIRS) during therapeutic hypothermia (TH). METHODS: Prospective pilot study including comatose patients successfully resuscitated from out-of-hospital CA treated with TH, monitored with NIRS. Dynamic changes of SctO2 upon HV and IH were analyzed during the stable TH maintenance phase. HV was induced by decreasing PaCO2 from ∼40 to ∼30 mmHg, at stable mean arterial blood pressure (MAP∼70 mmHg). IH was obtained by increasing MAP from ∼70 to ∼90 mmHg with noradrenaline. RESULTS: Ten patients (mean age 69 years; mean time to ROSC 19 min) were studied. Following HV, a significant reduction of SctO2 was observed (baseline 74.7±4.3% vs. 69.0±4.2% at the end of HV test, p<0.001, paired t-test). In contrast, IH was not associated with changes in SctO2 (baseline 73.6±3.5% vs. 74.1±3.8% at the end of IH test, p=0.24). CONCLUSIONS: Moderate hyperventilation was associated with a significant reduction in SctO2, while increasing MAP to supra-normal levels with vasopressors had no effect on cerebral tissue oxygenation. Our study suggests that maintenance of strictly normal PaCO2 levels and MAP targets of 70mmHg may provide optimal cerebral perfusion during TH in comatose CA patients.

Could moderate alcohol consumption help prevent the metabolic syndrome and diabetes mellitus ?

Aim and purpose: Moderate alcohol consumption has been associated with lower risk of diabetes mellitus, but few data exist on the metabolic syndrome and on the metabolic impact of heavy drinking. The aim of our study was to investigate the complex relationship between alcohol and the metabolic syndrome and diabetes mellitus in a population-based study in Switzerland with high mean alcohol consumption. Design and methods: In 6188 adults aged 35 to 75, alcohol consumption was categorized as 0, 1-6, 7-13, 14-20, 21-27, 28-34 and >= 35 drinks/week or as nondrinkers, moderate (1-13 drinks), high (14-34 drinks) and very high (>= 35 drinks) alcohol consumption. The metabolic syndrome was defined according to the ATP-III criteria and diabetes mellitus as fasting glycemia >= 7 mmol/l or self-reported medication.We used multivariate analysis adjusted for age, gender, smoking status, physical activity and education level to determine the prevalence of the conditions according to drinking categories. Results: 73% (n = 4502) of the participants consumed alcohol, 16% (n = 993) were high drinkers and 2% (n = 126) very high drinkers. In multivariate analysis, alcohol consumption had a U-shaped relationship with the metabolic syndrome and diabetes mellitus. The prevalence of the metabolic syndrome significantly differed between nondrinkers (24%), moderate (19%), high (20%) and very high drinkers (29%) (P<= 0.005). The prevalence of diabetes mellitus also significantly differed between nondrinkers (6.0%), moderate (3.6%), high (3.8%) and very high drinkers (6.7%) (P<= 0.05). These relationships did not differ according to beverage types. Conclusions: The prevalence of the metabolic syndrome and diabetes mellitus decrease with moderate alcohol consumption and increase with heavy drinking, without differences according to beverage types. Recommending to limit alcohol consumption to 1-2 drinks/day might help prevent these conditions in primary care Metabolic Syndrome and Diabetes Mellitus.

Local moderate magnetically induced hyperthermia using an implant formed in situ in a mouse tumor model.

Purpose: We investigate a new heat delivery technique for the local treatment of solid tumors. The technique involves injecting a formulation that solidifies to form an implant in situ. This implant entraps superparamagnetic iron oxide nanoparticles (SPIONs) embedded in silica microbeads for magnetically induced moderate hyperthermia. Particle entrapment prevents phagocytosis and distant migration of SPIONs. The implant can be repeatedly heated by magnetic induction. Methods: We evaluated heating and treatment efficacies by means of thermometry and survival studies in nude mice carrying subcutaneous human colocarcinomas. At day 1, we injected the formulation into the tumor. At day 2, a single 20-min hyperthermia treatment was delivered by 141-kHz magnetic induction using field strengths of 9 to 12 mT under thermometry. Results: SPIONs embedded in silica microbeads were effectively confined within the implant at the injection site. Heat-induced necro-apoptosis was assessed by histology on day 3. On average, 12 mT resulted in tumor temperature of 47.8 degrees C, and over 70% tumor necrosis that correlated to the heat dose (AUC = 282 degrees C.min). In contrast, a 9-mT field strength induced tumoral temperature of 40 degrees C (AUC = 131 degrees C.min) without morphologically identifiable necrosis. Survival after treatment with 10.5 or 12 mT fields was significantly improved compared to non-implanted and implanted controls. Median survival times were 27 and 37 days versus 12 and 21 days respectively. Conclusion: Five of eleven mice (45%) of the 12 mT group survived one year without any tumor recurrence, holding promise for tumor therapy using magnetically induced moderate hyperthermia through injectable implants.

Substance use behaviours of young people with a moderate learning disability: a longitudinal analysis.

Substance use behaviors of young people attending a special school are reported over a 4-year period from the age of 12-16 years. The article investigated these behaviors by surveying a cohort of young people with a statement for moderate learning disabilities annually during the last 4 years of compulsory schooling. The findings show that these young people consistently reported lower levels of tobacco, alcohol, and cannabis use compared with those attending mainstream school. No other illicit drug use was reported. The potential implications of these findings are discussed in relation to the context and timing of targeted substance education and prevention initiatives for young people with moderate learning disability attending a special school.This resource was contributed by The National Documentation Centre on Drug Use.

Moderate exercise blunts oxidative stress induced by normobaric hypoxic confinement

PURPOSE: Both acute hypoxia and physical exercise are known to increase oxidative stress. This randomized prospective trial investigated whether the addition of moderate exercise can alter oxidative stress induced by continuous hypoxic exposure. METHODS: Fourteen male participants were confined to 10-d continuous normobaric hypoxia (FIO2 = 0.139 +/- 0.003, PIO2 = 88.2 +/- 0.6 mm Hg, approximately 4000-m simulated altitude) either with (HCE, n = 8, two training sessions per day at 50% of hypoxic maximal aerobic power) or without exercise (HCS, n = 6). Plasma levels of oxidative stress markers (advanced oxidation protein products [AOPP], nitrotyrosine, and malondialdehyde), antioxidant markers (ferric-reducing antioxidant power, superoxide dismutase, glutathione peroxidase, and catalase), nitric oxide end-products, and erythropoietin were measured before the exposure (Pre), after the first 24 h of exposure (D1), after the exposure (Post) and after the 24-h reoxygenation (Post + 1). In addition, graded exercise test in hypoxia was performed before and after the protocol. RESULTS: Maximal aerobic power increased after the protocol in HCE only (+6.8%, P < 0.05). Compared with baseline, AOPP was higher at Post + 1 (+28%, P < 0.05) and nitrotyrosine at Post (+81%, P < 0.05) in HCS only. Superoxide dismutase (+30%, P < 0.05) and catalase (+53%, P < 0.05) increased at Post in HCE only. Higher levels of ferric-reducing antioxidant power (+41%, P < 0.05) at Post and lower levels of AOPP (-47%, P < 0.01) at Post + 1 were measured in HCE versus HCS. Glutathione peroxidase (+31%, P < 0.01) increased in both groups at Post + 1. Similar erythropoietin kinetics was noted in both groups with an increase at D1 (+143%, P < 0.01), a return to baseline at Post, and a decrease at Post + 1 (-56%, P < 0.05). CONCLUSIONS: These data provide evidence that 2 h of moderate daily exercise training can attenuate the oxidative stress induced by continuous hypoxic exposure.