Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21
Filtrar
Mais filtros










Tipo de estudo
Intervalo de ano de publicação
1.
PLoS One ; 14(5): e0217620, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31150472

RESUMO

Oxidatively modified low-density lipoproteins (oxLDL) play an important role in the occurrence and progression of atherosclerosis. To identify the genetic factors influencing the oxLDL levels, we have genotyped 776 DNA samples of Russian individuals for 196,725 single-nucleotide polymorphisms (SNPs) using the Cardio-MetaboChip (Illumina, USA) and conducted genome-wide association study (GWAS). Fourteen common variants in the locus including APOB gene were significantly associated with the oxLDL levels (P < 2.18 × 10-7). These variants explained only 6% of the variation in the oxLDL levels. Then, we assessed the contribution of rare coding variants of APOB gene to the oxLDL levels. Individuals with the extreme oxLDL levels (48 with the lowest and 48 with the highest values) were selected for targeted sequencing of the region including APOB gene. To evaluate the contribution of the SNPs to the oxLDL levels we used various statistical methods for the association analysis of rare variants: WST, SKAT, and SKAT-O. We revealed that both synonymous and nonsynonymous SNPs affected the oxLDL levels. For the joint analysis of the rare and common variants, we conducted the SKAT-C testing and found a group of 15 SNPs significantly associated with the oxLDL levels (P = 2.14 × 10-9). Our results indicate that the oxLDL levels depend on both common and rare variants of the APOB gene.

2.
Obes Facts ; 12(1): 103-114, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30844809

RESUMO

OBJECTIVE: To evaluate the prevalence and geographic distribution of overweight and obesity in Russian adults aged 25-64 years as well as the association between chronic risk factors and obesity. METHODS: Data were obtained from the survey "Epidemiology of Cardiovascular Diseases and Its Risk Factors in Some Regions of the Russian Federation" (ESSE-RF). This is a large cross-sectional multicenter population-based study that included interviews and medical examination (anthropometry, blood pressure [BP] measurement, and laboratory analysis) applied in 2012-2014. RESULTS: The sample included 20,190 adults (response rate 79.4%) aged 25-64 years. Approximately one third of participants (30.3%) had obesity and another third (34.3%) were classified as overweight. BMI increased with age in both sexes. The prevalence of obesity between regions ranged from 24.4 to 35.5%. Overweight and obesity levels decreased with higher education (men only). Overall obesity rates were higher in rural than urban populations, but rates of overweight were similar in rural and urban populations. Participants with obesity were more likely to have BP > 160/100 mm Hg (odds ratio > 2.0) and also > 140/90 mm Hg, raised blood glucose, and high triglycerides. CONCLUSION: The prevalence of overweight and obesity in Russian adults aged 25-64 years is not evenly distributed geographically, but it is comparable to that of other European countries. Individuals with obesity were also more likely to have indicators of poor cardiovascular and metabolic health.

3.
Eur Respir J ; 53(1)2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30545974

RESUMO

Pulmonary hypertension (PH) is frequent in left heart disease (LHD), as a consequence of the underlying condition. Significant advances have occurred over the past 5 years since the 5th World Symposium on Pulmonary Hypertension in 2013, leading to a better understanding of PH-LHD, challenges and gaps in evidence. PH in heart failure with preserved ejection fraction represents the most complex situation, as it may be misdiagnosed with group 1 PH. Based on the latest evidence, we propose a new haemodynamic definition for PH due to LHD and a three-step pragmatic approach to differential diagnosis. This includes the identification of a specific "left heart" phenotype and a non-invasive probability of PH-LHD. Invasive confirmation of PH-LHD is based on the accurate measurement of pulmonary arterial wedge pressure and, in patients with high probability, provocative testing to clarify the diagnosis. Finally, recent clinical trials did not demonstrate a benefit in treating PH due to LHD with pulmonary arterial hypertension-approved therapies.

4.
Lung ; 196(6): 745-753, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30182153

RESUMO

PURPOSE: To evaluate the influence of riociguat on World Health Organization functional class (WHO FC), 6-min walk distance (6MWD), right heart remodeling, and right ventricular-pulmonary arterial (RV-PA) coupling in patients with idiopathic pulmonary arterial hypertension (IPAH) who are treatment-naïve or who have failed to achieve treatment goals with sildenafil therapy. METHODS: Twenty patients with IPAH were enrolled: 12 had not previously received PAH-targeted therapy (treatment-naïve subgroup) and 8 had been receiving sildenafil therapy but failed to achieve treatment goals; on entering this pilot study these 8 patients were switched from sildenafil to riociguat therapy (treatment-switch subgroup). Patients received riociguat individually dose-adjusted up to a maximum of 2.5 mg three times daily. After 12 weeks, patients were assessed for WHO FC, 6MWD, right heart remodeling, and RV-PA coupling. RESULTS: Riociguat significantly improved WHO FC in treatment-naïve patients (from 0/4/8/0 patients in WHO I/II/III/IV at baseline to 1/6/5/0 at week 12) and in treatment-switch patients (from 0/4/4/0 patients in WHO I/II/III/IV at baseline to 1/4/3/0 at week 12). Additionally, treatment-naïve and treatment-switch patients showed significant improvements at week 12 versus baseline in 6MWD (increases of + 76.8 m and + 71.6 m, respectively), RV systolic function, and RV-PA coupling. CONCLUSION: These results support the proven efficacy of riociguat in patients with IPAH, including treatment-naïve patients and those switching to riociguat following failure to achieve treatment goals with sildenafil, and suggest that it may be possible to delay disease progression in this patient group.

5.
Eur J Epidemiol ; 32(3): 251-254, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28039558

RESUMO

INTRODUCTION: The aim of the study was to estimate the prevalence of metabolically healthy obese (MHO) and metabolically unhealthy non-obese (MUNO) phenotypes in Russian population. DESIGN AND METHODS: In cross-sectional epidemiology survey "Epidemiology of cardiovascular diseases and its risk factors in some regions of the Russian Federation" a random sampling of 21,121 subjects (25-65 years), stratified by age and sex was involved. Anthropometry, blood pressure (BP) measurement and fasting blood-tests (glucose, lipids) were performed according to standard protocols. Criteria for MHO-body mass index (BMI) ≥30 kg/m2 and ≤2 of markers: HDL < 1.30 (females)/1.04 (males) mmol/l; triglycerides ≥1.7 mmol/l; glucose ≥5.6 mmol/l or treatment; waist >88 (females)/102 (males) cm and BP ≥ 130/85 mm Hg or therapy. Criteria for MUNO was BMI < 30 kg/m2 and ≥2 markers listed above. Simple tabulations, descriptive statistics, post-stratification weights and logistic regression were used for analyses. RESULTS: MHO phenotype was detected in 2856 (41.5%) obese people; MUNO phenotype-in 4762 (34.4%) non-obese subjects. Aging was negatively associated with MHO and positively with MUNO prevalence. Gender was registered as determinant only of MUNO probability. No dramatic differences in lifestyle risk factors between 3 BMI groups (lean, overweight, obese) were found out. CONCLUSION: Half of obese Russian inhabitants are metabolically healthy. At the same time, metabolic abnormalities were detected in one third of non-obese participants with a shift to male gender.


Assuntos
Glicemia , Nível de Saúde , Obesidade/sangue , Obesidade/epidemiologia , Triglicerídeos/sangue , Adulto , Fatores Etários , Idoso , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Federação Russa/epidemiologia , Fatores Sexuais
6.
Kardiol Pol ; 75(1): 55-64, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27714718

RESUMO

BACKGROUND AND AIM: The aim of the trial was to establish the efficacy and safety of Valsacor® (valsartan) and Valsacombi® (combination of valsartan and hydrochlorothiazide) in a wide variety of patient populations with mild to moderate arterial hypertension. METHODS: We performed an international, multicentre, open-label, prospective trial. After one week of washout in previously treated patients, the patients were treated for 16 weeks according to the protocol. Naïve patients entered the treatment period immediately. During the active treatment, four visits were planned for each patient to obtain the data for the primary and secondary efficacy endpoints analysis. The principal methods were blood pressure (BP) measurement, additionally in a subgroup of patients, assessment of erectile function. The initial dosage of valsartan 80 mg/day was titrated up to 320 mg/day to achieve the BP goal, with the addition of hydrochlorothiazide (HCTZ) in a fixed-dose combination (FDC), if needed. RESULTS: Mean ± standard deviation changes from baseline at week 16 were -26.6 ± 10.4 mm Hg (systolic BP) and -14.8 ± 7.6 mm Hg (diastolic BP). A total of 91% of the patients treated with either valsartan or valsartan FDC achieved the BP goal. Adverse reactions were experienced by 7.1% of the patients, with the most common being headache (1.9%), palpitation (1.6%), dizziness (1.6%), and fatigue (1.6%), during the whole trial. CONCLUSIONS: The results of the VICTORY trial show that valsartan and valsartan FDC effectively reduce the BP in patients with mild to moderate arterial hypertension and have a good tolerability profile.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Valsartana/uso terapêutico , Adulto , Idoso , Anti-Hipertensivos/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Hidroclorotiazida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Estudos Prospectivos , Resultado do Tratamento , Valsartana/efeitos adversos
7.
N Engl J Med ; 374(21): 2021-31, 2016 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-27040132

RESUMO

BACKGROUND: Previous trials have shown that the use of statins to lower cholesterol reduces the risk of cardiovascular events among persons without cardiovascular disease. Those trials have involved persons with elevated lipid levels or inflammatory markers and involved mainly white persons. It is unclear whether the benefits of statins can be extended to an intermediate-risk, ethnically diverse population without cardiovascular disease. METHODS: In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants in 21 countries who did not have cardiovascular disease and were at intermediate risk to receive rosuvastatin at a dose of 10 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included revascularization, heart failure, and resuscitated cardiac arrest. The median follow-up was 5.6 years. RESULTS: The overall mean low-density lipoprotein cholesterol level was 26.5% lower in the rosuvastatin group than in the placebo group. The first coprimary outcome occurred in 235 participants (3.7%) in the rosuvastatin group and in 304 participants (4.8%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.64 to 0.91; P=0.002). The results for the second coprimary outcome were consistent with the results for the first (occurring in 277 participants [4.4%] in the rosuvastatin group and in 363 participants [5.7%] in the placebo group; hazard ratio, 0.75; 95% CI, 0.64 to 0.88; P<0.001). The results were also consistent in subgroups defined according to cardiovascular risk at baseline, lipid level, C-reactive protein level, blood pressure, and race or ethnic group. In the rosuvastatin group, there was no excess of diabetes or cancers, but there was an excess of cataract surgery (in 3.8% of the participants, vs. 3.1% in the placebo group; P=0.02) and muscle symptoms (in 5.8% of the participants, vs. 4.7% in the placebo group; P=0.005). CONCLUSIONS: Treatment with rosuvastatin at a dose of 10 mg per day resulted in a significantly lower risk of cardiovascular events than placebo in an intermediate-risk, ethnically diverse population without cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; HOPE-3 ClinicalTrials.gov number, NCT00468923.).


Assuntos
Doenças Cardiovasculares/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hipercolesterolemia/tratamento farmacológico , Rosuvastatina Cálcica/administração & dosagem , Idoso , Doenças Cardiovasculares/etnologia , Doenças Cardiovasculares/mortalidade , LDL-Colesterol/sangue , Método Duplo-Cego , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Fatores de Risco , Rosuvastatina Cálcica/efeitos adversos
8.
N Engl J Med ; 374(21): 2009-20, 2016 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-27041480

RESUMO

BACKGROUND: Antihypertensive therapy reduces the risk of cardiovascular events among high-risk persons and among those with a systolic blood pressure of 160 mm Hg or higher, but its role in persons at intermediate risk and with lower blood pressure is unclear. METHODS: In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to receive either candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; the second coprimary outcome additionally included resuscitated cardiac arrest, heart failure, and revascularization. The median follow-up was 5.6 years. RESULTS: The mean blood pressure of the participants at baseline was 138.1/81.9 mm Hg; the decrease in blood pressure was 6.0/3.0 mm Hg greater in the active-treatment group than in the placebo group. The first coprimary outcome occurred in 260 participants (4.1%) in the active-treatment group and in 279 (4.4%) in the placebo group (hazard ratio, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P=0.40); the second coprimary outcome occurred in 312 participants (4.9%) and 328 participants (5.2%), respectively (hazard ratio, 0.95; 95% CI, 0.81 to 1.11; P=0.51). In one of the three prespecified hypothesis-based subgroups, participants in the subgroup for the upper third of systolic blood pressure (>143.5 mm Hg) who were in the active-treatment group had significantly lower rates of the first and second coprimary outcomes than those in the placebo group; effects were neutral in the middle and lower thirds (P=0.02 and P=0.009, respectively, for trend in the two outcomes). CONCLUSIONS: Therapy with candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day was not associated with a lower rate of major cardiovascular events than placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.).


Assuntos
Anti-Hipertensivos/administração & dosagem , Benzimidazóis/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Hidroclorotiazida/administração & dosagem , Hipertensão/tratamento farmacológico , Tetrazóis/administração & dosagem , Idoso , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Hipotensão/induzido quimicamente , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Fatores de Risco
9.
N Engl J Med ; 374(21): 2032-43, 2016 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-27039945

RESUMO

BACKGROUND: Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase the risk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events substantially. METHODS: In a trial with 2-by-2 factorial design, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to rosuvastatin (10 mg per day) or placebo and to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day) or placebo. In the analyses reported here, we compared the 3180 participants assigned to combined therapy (with rosuvastatin and the two antihypertensive agents) with the 3168 participants assigned to dual placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included heart failure, cardiac arrest, or revascularization. The median follow-up was 5.6 years. RESULTS: The decrease in the LDL cholesterol level was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo. The first coprimary outcome occurred in 113 participants (3.6%) in the combined-therapy group and in 157 (5.0%) in the dual-placebo group (hazard ratio, 0.71; 95% confidence interval [CI], 0.56 to 0.90; P=0.005). The second coprimary outcome occurred in 136 participants (4.3%) and 187 participants (5.9%), respectively (hazard ratio, 0.72; 95% CI, 0.57 to 0.89; P=0.003). Muscle weakness and dizziness were more common in the combined-therapy group than in the dual-placebo group, but the overall rate of discontinuation of the trial regimen was similar in the two groups. CONCLUSIONS: The combination of rosuvastatin (10 mg per day), candesartan (16 mg per day), and hydrochlorothiazide (12.5 mg per day) was associated with a significantly lower rate of cardiovascular events than dual placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.).


Assuntos
Anti-Hipertensivos/administração & dosagem , Benzimidazóis/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Hidroclorotiazida/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hipertensão/tratamento farmacológico , Rosuvastatina Cálcica/administração & dosagem , Tetrazóis/administração & dosagem , Idoso , Anti-Hipertensivos/efeitos adversos , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol/sangue , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Fatores de Risco , Rosuvastatina Cálcica/efeitos adversos
10.
Can J Cardiol ; 32(3): 311-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26481083

RESUMO

BACKGROUND: Cholesterol and blood pressure (BP) can be effectively and safely lowered with statin drugs and BP-lowering drugs, reducing major cardiovascular (CV) events by 20%-30% within 5 years in high-risk individuals. However, there are limited data in lower-risk populations. The Heart Outcomes Prevention Evaluation-3 (HOPE-3) trial is evaluating whether cholesterol lowering with a statin drug, BP lowering with low doses of 2 antihypertensive agents, and their combination safely reduce major CV events in individuals at intermediate risk who have had no previous vascular events and have average cholesterol and BP levels. METHODS: A total of 12,705 women 65 years or older and men 55 years or older with at least 1 CV risk factor, no known CV disease, and without any clear indication or contraindication to the study drugs were randomized to rosuvastatin 10 mg/d or placebo and to candesartan/hydrochlorothiazide 16/12.5 mg/d or placebo (2 × 2 factorial design) and will be followed for a mean of 5.8 years. The coprimary study outcomes are the composite of CV death, nonfatal myocardial infarction (MI), and nonfatal stroke and the composite of CV death, nonfatal MI, nonfatal stroke, resuscitated cardiac arrest, heart failure, and arterial revascularization. RESULTS: Participants were recruited from 21 countries in North America, South America, Europe, Asia, and Australia. Mean age at randomization was 66 years and 46% were women. CONCLUSIONS: The HOPE-3 trial will provide new information on cholesterol and BP lowering in intermediate-risk populations with average cholesterol and BP levels and is expected to inform approaches to primary prevention worldwide (HOPE-3 ClinicalTrials.gov NCT00468923).


Assuntos
Benzimidazóis/administração & dosagem , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/sangue , Hidroclorotiazida/administração & dosagem , Prevenção Primária/métodos , Rosuvastatina Cálcica/administração & dosagem , Tetrazóis/administração & dosagem , Idoso , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , LDL-Colesterol/efeitos dos fármacos , Diuréticos/administração & dosagem , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Saúde Global , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Vigilância da População , Fatores de Risco , Resultado do Tratamento
11.
J Hypertens ; 34(1): 139-48, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26630216

RESUMO

OBJECTIVE: To compare a combination of a dihydropyridine calcium-channel blocker with an angiotensin converting enzyme inhibitor vs. monotherapy with one or the other drug and placebo for their effects on home blood pressure (HBP). METHODS: After a 2-week placebo wash-out, patients with an elevated office blood pressure (BP) (diastolic 100-109 and systolic <180 mmHg) and HBP (diastolic ≥85 mmHg) were randomized double-blind to a 10-week treatment with placebo, lercanidipine, 10 or 20 mg daily, enalapril, 10 or 20 mg daily, or the four possible combinations. In addition to office BP, HBP was self-measured via a validated semiautomatic device twice in the morning and twice in the evening during the 7 days before randomization and at the end of treatment. Baseline and treatment HBP values were separately averaged for each day, morning, evening or the whole monitoring period, excluding the first day. Day-by-day HBP variability was defined as the SD or the variation coefficient of the daily BP averages. RESULTS: Eight hundred and fifty-four patients with valid HBP recordings at baseline and at the end of treatment were analyzed (intention-to-treat population). From the baseline value (147.0±11.6 mmHg) systolic/diastolic HBP showed a small reduction (average baseline-adjusted change: -1.8/-1.6 mmHg) with placebo, a more marked significant fall with monotherapies (-8.8/-5.9 mmHg, P < 0.001/<0.001 vs. placebo) and even more with combination treatment (11.6/-7.6 mmHg, P < 0.001/ < 0.001 vs. placebo and P < 0.01/ < 0.05 vs. monotherapy). A similar pattern was observed for each of the days of the BP self-monitoring period as well as for either morning or evening values, although the difference between mono and combination treatment appeared to be consistently significant for the morning values only. Day-by-day systolic BP-SD was unaffected by placebo and slightly reduced by drug treatments, with no, however, significant changes in SBP-variation coefficient. Baseline and end of treatment HBP values showed a limited correlation with office BP values, this being particularly the case for treatment-induced changes (correlation coefficients: 0.37 for systolic and 0.45 for diastolic BP). CONCLUSION: This large HBP database shows that the lercanidipine-enalapril combination lowers HBP more effectively than the corresponding monotherapies and placebo, and that this greater effect is consistent between days. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01093807.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Di-Hidropiridinas/uso terapêutico , Enalapril/uso terapêutico , Hipertensão/tratamento farmacológico , Adulto , Idoso , Determinação da Pressão Arterial , Bases de Dados Factuais , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Hipertensão/fisiopatologia , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Visita a Consultório Médico , Autocuidado
12.
N Engl J Med ; 374(21): 2009-2020, 2016.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: ses-34743

RESUMO

BACKGROUND: Antihypertensive therapy reduces the risk of cardiovascular events among high-risk persons and among those with a systolic blood pressure of 160 mm Hg or higher, but its role in persons at intermediate risk and with lower blood pressure is unclear. METHODS: In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to receive either candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; the second coprimary outcome additionally included resuscitated cardiac arrest, heart failure, and revascularization. The median follow-up was 5.6 years. RESULTS: The mean blood pressure of the participants at baseline was 138.1/81.9 mm Hg; the decrease in blood pressure was 6.0/3.0 mm Hg greater in the active-treatment group than in the placebo group. The first coprimary outcome occurred in 260 participants (4.1%) in the active-treatment group and in 279 (4.4%) in the placebo group (hazard ratio, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P=0.40); the second coprimary outcome occurred in 312 participants (4.9%) and 328 participants (5.2%), respectively (hazard ratio, 0.95; 95% CI, 0.81 to 1.11; P=0.51). In one of the three prespecified hypothesis-based subgroups, participants in the subgroup for the upper third of systolic blood pressure (>143.5 mm Hg) who were in the active-treatment group had significantly lower rates of the first and second coprimary outcomes than those in the placebo group; effects were neutral in the middle and lower thirds (P=0.02 and P=0.009, respectively, for trend in the two outcomes)...(AU)


Assuntos
Pressão Sanguínea , Pressão Arterial , Risco , Doenças Cardiovasculares
13.
J Hypertens ; 33(3): 653-61; discussion 662, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25479022

RESUMO

OBJECTIVE: To evaluate perindopril 3.5 mg/amlodipine 2.5 mg once daily, a novel fixed-dose combination adapted for first-step treatment in patients with hypertension. This fixed dose had to be equivalent to amlodipine 5 mg in terms of blood pressure efficacy, but with an expected better tolerability profile. We selected two drugs with complementary modes of action, with doses chosen so that each drug would contribute similarly to the overall blood pressure-lowering effect METHODS: : An international, randomized, double-blind, placebo-controlled study with six equal parallel treatment arms and an 8-week randomized treatment period, whose design, clinical significance and non-inferiority criteria were in accordance with European guidelines. RESULTS: In all, 1581 patients with mild-to-moderate uncomplicated hypertension (mean age 51.7 years) were randomized and 94.7% completed the study. The combination was statistically and clinically superior to placebo (between-group differences: SBP: -7.22 mmHg, DBP: -4.12 mmHg, P < 0.001 for both). Rates of response and normalization of blood pressure were greater with the combination (P < 0.001 for both) and numerical differences relative to placebo were apparent at 2 weeks. The combination was superior to either component given singly (P < 0.001 for both drugs, for SBP and DBP), and was non-inferior to both component drugs given singly at their lowest clinically-approved doses. The components of the combination had similar effects on SBP (perindopril 3.5 mg: -16.3 mmHg; amlodipine 2.5 mg: -16.0 mmHg). Adverse events relating to peripheral oedema were less frequent with the combination than with amlodipine 5 mg. CONCLUSIONS: The observed blood pressure-lowering efficacy, rapidity of onset of effect and favourable safety profile of the combination perindopril 3.5 mg/amlodipine 2.5 mg indicate its potential suitability for use as first-step treatment in hypertension.


Assuntos
Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Perindopril/uso terapêutico , Adolescente , Adulto , Idoso , Anlodipino/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Perindopril/administração & dosagem , Resultado do Tratamento , Adulto Jovem
14.
J Hypertens ; 33(2): 401-11, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25380149

RESUMO

OBJECTIVES: An international double-blind, parallel-group, randomized controlled trial was performed to determine the efficacy and safety of a new first-line strategy in mild to moderate hypertension based on a single-pill combination of perindopril/amlodipine versus a validated stepped-care strategy (initiation with valsartan monotherapy, up-titrating to valsartan/amlodipine after 2 months). METHODS: At inclusion, patients received perindopril/amlodipine 3.5/2.5 mg or valsartan 80 mg. At 1, 2, and 3 months, patients were up-titrated if they had uncontrolled hypertension (≥140/90 mmHg). The up-titration steps were: perindopril/amlodipine 7/5 mg, 14/10 mg, and 14/10 mg + indapamide sustained release 1.5 mg; or valsartan 160 mg, valsartan/amlodipine 160/5 mg, and 160/10 mg. The two groups were similar at baseline (55.5 years, 53% men, blood pressure 163.5/100.2 mmHg); 881 perindopril/amlodipine and 876 valsartan/amlodipine patients were analyzed for efficacy. RESULTS: After 1 month, the rate of controlled hypertension was 33% with perindopril/amlodipine versus 27% with valsartan/amlodipine (estimate of difference, +6.1%; P = 0.005); this between-strategy difference remained significant at every visit (P < 0.05). After 3 months, blood pressure was 137.8 ±â€Š12.4/83.3 ±â€Š8.7 and 139.7 ±â€Š13.3/84.8 ±â€Š9.0 mmHg, respectively, with greater reductions from baseline with perindopril/amlodipine (primary endpoint -2.0/-1.5 mmHg; both P < 0.001). Similar results were observed at all other visits (all P ≤ 0.001). The safety of the two strategies was equivalent. CONCLUSIONS: The three-step strategy of initiation with single-pill perindopril/amlodipine produces greater reductions in blood pressure, and better and quicker rates of control of hypertension. This can be expected to be associated with benefits beyond blood pressure control, notably improved compliance and better cardioprotection.


Assuntos
Combinação Anlodipino e Valsartana/uso terapêutico , Anlodipino/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Hipertensão/tratamento farmacológico , Perindopril/uso terapêutico , Adulto , Idoso , Pressão Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Indapamida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Valsartana/administração & dosagem
15.
Journal of Hypertension ; 33(02): 401-411, 2015. ilus
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: ses-31266

RESUMO

An international double-blind, parallel-group,randomized controlled trial was performed to determinethe efficacy and safety of a new first-line strategy in mildto moderate hypertension based on a single-pillcombination of perindopril/amlodipine versus a validatedstepped-care strategy (initiation with valsartanmonotherapy, up-titrating to valsartan/amlodipine after2 months).Methods: At inclusion, patients received perindopril/amlodipine 3.5/2.5mg or valsartan 80 mg. At 1, 2, and3 months, patients were up-titrated if they haduncontrolled hypertension ( 140/90 mmHg). The uptitrationsteps were: perindopril/amlodipine 7/5 mg,14/10 mg, and 14/10mg R indapamide sustained release1.5 mg; or valsartan 160 mg, valsartan/amlodipine160/5 mg, and 160/10 mg. The two groups were similarat baseline (55.5 years, 53% men, blood pressure163.5/100.2 mmHg); 881 perindopril/amlodipine and876 valsartan/amlodipine patients were analyzed forefficacy.Results: After 1 month, the rate of controlledhypertension was 33% with perindopril/amlodipine versus27% with valsartan/amlodipine (estimate of difference,R6.1%; P¼0.005); this between-strategy differenceremained significant at every visit (P<0.05). After 3months, blood pressure was 137.8 12.4/83.3 8.7 and139.7 13.3/84.8 9.0 mmHg, respectively, with greaterreductions from baseline with perindopril/amlodipine(primary endpoint 2.0/ 1.5 mmHg; both P<0.001).Similar results were observed at all other visits (allP 0.001). The safety of the two strategies wasequivalent.Conclusions: The three-step strategy of initiation withsingle-pill perindopril/amlodipine produces greaterreductions in blood pressure, and better and quicker ratesof control of hypertension. This can be expected to beassociated with benefits beyond blood pressure control,notably improved compliance and better cardioprotection.Keywords: amlodipine, hypertension, perindopril, singlepillcombination, valsartan...(AU)


Assuntos
Hipertensão , Perindopril , Morbidade
16.
J Hypertens ; 32(8): 1700-7; discussion 1707, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24906174

RESUMO

OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of combinations of lercanidipine (L) and enalapril (E) at different doses on office and home blood pressure (BP) in patients with Stage 2 hypertension. STUDY DESIGN: This was a randomized, double-blind, placebo-controlled, factorial study conducted in 100 centres from seven countries. Patients with office DBP 100-109 mmHg and home DBP at least 85 mmHg at the end of a 2-week placebo run-in period were randomized to a 10-week treatment with placebo, L (10 or 20 mg), E (10 or 20 mg) or the four L-E combinations. The efficacy parameters were office DBP at trough (primary), SBP at trough and home SBP and DBP. Office BP was measured at each visit in both the sitting and the standing position, while home BP was measured twice in the morning and twice in the evening for at least 3 days before treatment and at study end. Safety parameters included adverse events, laboratory tests and 12-lead ECG. RESULTS: A total of 1039 patients were randomized (48% men, mean age 54 years, mean BMI 30 kg/m, 40% obese patients). Baseline BP was similar in all groups and lower for home than for office values (149/95 and 159/103 mmHg, respectively). A marked placebo effect was observed on office but not on home BP. Combination therapy was superior to placebo at all doses for both office and home BP. The greatest effect was observed in the L20/E20 group, in which the SBP/DBP fall amounted to -19.2/-15.2 and -13.2/-7.5 mmHg for sitting office and home BP, respectively. Similar reductions were observed on standing office BP. The L20/E20 combination was associated with less cough, palpitations and leg oedema than monotherapies, with no increased rate of dizziness or hypotension. CONCLUSION: In Stage 2 hypertension, a fixed-dose combination of L and E ensures a control of both office and out-of-office BP, with a favourable tolerability profile.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/administração & dosagem , Di-Hidropiridinas/administração & dosagem , Enalapril/administração & dosagem , Hipertensão/tratamento farmacológico , Adulto , Idoso , Di-Hidropiridinas/efeitos adversos , Método Duplo-Cego , Combinação de Medicamentos , Enalapril/efeitos adversos , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Adesão à Medicação , Pessoa de Meia-Idade
17.
Int J Hypertens ; 2013: 541689, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23533713

RESUMO

This study was designed to assess the effects of moxonidine on blood pressure and aspects of the metabolic syndrome in racially diverse population of patients encountered in routine medical practice. Physicians collected data on a minimum of three consecutive patients with uncontrolled essential hypertension and criteria for metabolic syndrome, eligible to receive moxonidine (0.2-0.4 mg once daily) for 6 months, either as monotherapy or as adjunct therapy to current antihypertensive treatment. Systolic and diastolic blood pressure (BP) declined by an average of 24.5 + 14.3 mmHg and 12.6 + 9.1 mmHg, respectively. BP responder rates defined as attaining BP < 140/90 mmHg were significantly (P < 0.001) and substantially higher among younger patients, nonpostmenopausal women, and patients receiving monotherapy. While potentially relevant improvements in the entire cohort were observed in regard to body weight (-2.1 ± 5.4 kg), fasting plasma glucose (from 6.8 to 6.2 mmol/L), and triglycerides (2.4 to 2.0 mmol/L), statistically significant changes in metabolic parameters could only be detected in subgroup analyses. Moxonidine therapy reduced blood pressure and improved rates of blood pressure control in this group of patients. While the observed trend towards improvement in various metabolic parameters merits further investigation, the overall effect of moxonidine treatment is consistent with a reduction of total cardiovascular risk in this hypertensive metabolic syndrome cohort.

18.
J Hypertens ; 30(5): 1004-14, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22495138

RESUMO

BACKGROUND: Evidence on new-onset atrial fibrillation in high-risk vascular patients without heart failure is limited. New-onset atrial fibrillation was a prespecified secondary objective of the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET)/Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) studies. METHODS: We studied 30 424 ONTARGET/TRANSCEND patients (mean age ±â€ŠSD, 66.4 ±â€Š7.0) with vascular disease or complicated diabetes who were in sinus rhythm at entry. A copy of ECG was sent to central office every time new atrial fibrillation was detected by investigators. RESULTS: During a median follow-up period of 4.7 years, new atrial fibrillation occurred in 2092 patients (15.1 per 1000  patient-years). Risk of atrial fibrillation increased with age, SBP and pulse pressure, left ventricular hypertrophy, BMI, serum creatinine and history of hypertension, coronary artery disease and cerebrovascular disease (all P < 0.01). After adjustment for BMI and other variables, atrial fibrillation risk increased with hip circumference. History of hypertension was associated with a 34% higher risk of new atrial fibrillation. New atrial fibrillation portended an increased risk of congestive heart failure [hazard ratio 2.89, 95% confidence interval (CI) 2.45-3.40, P < 0.01] and cardiovascular death (hazard ratio 1.22, 95% CI 1.05-1.41, P < 0.01). Risk of stroke was unaffected (hazard ratio 1.14, 95% CI 0.93-1.40), whereas that of myocardial infarction was reduced (hazard ratio 0.64, 95% CI 0.50-0.82). Patients with new atrial fibrillation were more likely to receive vitamin K antagonists (P < 0.01), statins (P < 0.05) and ß-blockers (P < 0.01) than those in sinus rhythm. CONCLUSION: New atrial fibrillation is common in high-risk vascular patients and is associated with several risk factors including history of hypertension. Hip circumference was the strongest anthropometric predictor. Despite extensive use of modern therapies, new atrial fibrillation carries a high risk of congestive heart failure and death over a relatively short term.


Assuntos
Fibrilação Atrial/diagnóstico , Benzimidazóis/farmacologia , Benzoatos/farmacologia , Doenças Cardiovasculares/diagnóstico , Ramipril/farmacologia , Idoso , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Antropometria , Índice de Massa Corporal , Doenças Cardiovasculares/complicações , Complicações do Diabetes/diagnóstico , Método Duplo-Cego , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipertrofia Ventricular Esquerda/patologia , Masculino , Pessoa de Meia-Idade , Placebos , Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Telmisartan , Vitamina K/antagonistas & inibidores
19.
Adv Ther ; 28(2): 134-49, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21240661

RESUMO

INTRODUCTION: The aim of our study was to evaluate the safety and effectiveness of the free combination of amlodipine/valsartan in patients with arterial hypertension in a real-life setting. METHODS: This was a multicenter, open-label, observational, noninterventional, postmarketing surveillance study conducted in 298 centers in China, Malaysia, Pakistan, Bangladesh, Egypt, and Russia. We evaluated changes in heart rate, systolic and diastolic office blood pressure (BP), as well as BP control rate (<140/90 mmHg) overall, and in clinically relevant subgroups of hypertensive patients (BP >140/90 mmHg) after 12 weeks of treatment with 5/10 mg amlodipine and 80/160 mg valsartan combination. RESULTS: Two thousand seven hundred and eighty-five patients with arterial hypertension were enrolled, 52 discontinued (eight due to adverse events), and four patients' data were missing. In total, 2729 patients completed the study: mean age 57.9 years, 54.5% men, 54.2% Asian, 44.6% Caucasian; 86.5% had prior hypertension treatment (which was discontinued), baseline BP was 163.1/96.2 mmHg. The significant reduction in BP (-33.2/-16.9 mmHg, P<0.0001) was achieved with amlodipine/valsartan treatment resulting in a final BP of 129.9/79.3 mmHg. A dose-dependent effect was observed with the least BP reduction for 5/80 mg (-29.2/-15.1 mmHg, P<0.0001) and the greatest for the 10/160 mg dose regimen (-43.6/-22.4 mmHg, P<0.0001). Treatment response increased with increasing initial severity of hypertension with the least BP reduction in patients with baseline grade 1 hypertension BP level (SBP 140-159 mmHg): -20.0/-13.4 mmHg, P<0.0001, and the greatest BP drops observed in grade 3 hypertensive patients with baseline systolic BP over 200 mmHg: -73.1/-26.3 mmHg, P<0.0001. Patients with isolated systolic hypertension had BP reductions of -24.2/-4.8 mmHg, P<0.0001. CONCLUSION: An optimal BP reduction was achieved for all hypertension grades as well as isolated systolic hypertension, providing evidence that most hypertensive patients may benefit from amlodipine/valsartan combination treatment.


Assuntos
Anlodipino , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Tetrazóis , Valina/análogos & derivados , Administração Oral , Anlodipino/administração & dosagem , Anlodipino/efeitos adversos , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Bangladesh , Monitorização Ambulatorial da Pressão Arterial , China , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Sinergismo Farmacológico , Egito , Feminino , Humanos , Hipertensão/fisiopatologia , Malásia , Masculino , Pessoa de Meia-Idade , Paquistão , Vigilância de Produtos Comercializados , Federação Russa , Índice de Gravidade de Doença , Tetrazóis/administração & dosagem , Tetrazóis/efeitos adversos , Resultado do Tratamento , Valina/administração & dosagem , Valina/efeitos adversos , Valsartana
20.
Lancet Neurol ; 10(1): 43-53, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20980201

RESUMO

BACKGROUND: cardiovascular risk factors are associated with dementia and cognitive decline. We investigated the effects of renin-angiotensin system blockade on cognitive function in patients aged 55 years and older with established atherosclerotic cardiovascular disease or diabetes with end-organ damage in two clinical trials. METHODS: in the main study, ONTARGET, a double-blind, double-dummy, randomised controlled trial, the effects on cardiovascular outcomes of standard doses of an angiotensin-converting enzyme (ACE) inhibitor (ramipril), an angiotensin-receptor blocker (telmisartan), and a combination of the drugs were evaluated in 25 620 participants. In the parallel TRANSCEND trial, the effects of telmisartan were compared with those of placebo in 5926 participants intolerant to ACE inhibitors. Secondary outcomes included cognitive impairment (defined by investigator-reported diagnosis of dementia or significant cognitive dysfunction, or a score of ≤ 23 on the Mini-Mental State Examination [MMSE]) and cognitive decline (a decrease of ≤ 3 points on the MMSE from baseline during follow-up). Analyses were by intention to treat. We pooled data from these studies to identify baseline predictors of cognitive impairment and its frequency according to mean systolic blood pressure during follow-up. These studies were registered with ClinicalTrials.gov, number NCT00153101. FINDINGS: During a median duration of 56 months (IQR 51-64) of follow-up in ONTARGET, cognitive impairment occurred in 652 (8%) of 7865 patients allocated ramipril, 584 (7%) of 7797 allocated telmisartan, and 618 (8%) of 7807 allocated combination treatment (combination vs ramipril, odds ratio [OR] 0·95, 95% CI 0·85-1·07, p= 0·39; telmisartan vs ramipril, OR 0·90, 0·80-1·01, p = 0·06). Corresponding figures for cognitive decline were 1314 (17%), 1279 (17%), and 1240 (17%) in each of the groups, respectively (telmisartan vs ramipril, OR 0·97, 0·89-1·06, p= 0·53; combination vs ramipril, OR 0·95, 0·88-1·04, p=0·28). In TRANSCEND, cognitive impairment occurred in 239 (9%) of 2694 participants allocated telmisartan compared with 245 (9%) of 2689 allocated placebo (OR 0·97, 0·81-1·17, p= 0·76). The corresponding figures for cognitive decline were 454 (17%) and 412 (16%; OR 1·10, 0·95-1·27, p= 0·22). INTERPRETATION: In patients with cardiovascular disease or diabetes, different approaches to blocking of the renin-angiotensin system had no clear effects on cognitive outcomes. Although patients with the lowest systolic blood pressure had the greatest preservation of cognitive function, meta-regression analyses did not show any benefits of blood-pressure lowering on cognition over several years of treatment.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Benzimidazóis/uso terapêutico , Benzoatos/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Ramipril/uso terapêutico , Sistema Renina-Angiotensina/fisiologia , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Benzimidazóis/efeitos adversos , Benzoatos/efeitos adversos , Transtornos Cognitivos/induzido quimicamente , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Testes Neuropsicológicos , Razão de Chances , Ramipril/efeitos adversos , Sistema Renina-Angiotensina/efeitos dos fármacos , Telmisartan , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA