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1.
Cardiovasc Diabetol ; 20(1): 219, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34753480

RESUMO

BACKGROUND: Recent studies indicated that sodium glucose cotransporter (SGLT)2 inhibition increases levels of ketone bodies in the blood in patients with type 1 and 2 diabetes. Other studies suggested that in patients with chronic heart failure (CHF), increased myocardial oxygen demand can be provided by ketone bodies as a fuel substrate. Experimental studies reported that ketone bodies, specifically beta-hydroxybutyrate (ß-OHB) may increase blood pressure (BP) by impairing endothelium-dependant relaxation, thereby leading to increased vascular stiffness. In our study we assessed whether the SGLT 2 inhibition with empagliflozin increases ketone bodies in patients with stable CHF and whether such an increase impairs BP and vascular function. METHODS: In a prospective, double blind, placebo controlled, parallel-group single centre study 75 patients with CHF (left ventricular ejection fraction 39.0 ± 8.2%) were randomised (2:1) to the SGLT-2 inhibitor empagliflozin 10 mg orally once daily or to placebo, 72 patients completed the study. After a run-in phase we evaluated at baseline BP by 24 h ambulatory blood pressure (ABP) monitoring, vascular stiffness parameters by the SphygmoCor system (AtCor Medical, Sydney, NSW, Australia) and fasting metabolic parameters, including ß-OHB by an enzymatic assay (Beckman Coulter DxC 700 AU). The same measurements were repeated 12 weeks after treatment. In 19 of the 72 patients serum levels of ß-OHB were beneath the lower border of our assay (< 0.05 mmol/l) therefore being excluded from the subsequent analysis. RESULTS: In patients with stable CHF, treatment with empagliflozin (n = 36) was followed by an increase of ß-OHB by 33.39% (p = 0.017), reduction in 24 h systolic (p = 0.038) and diastolic (p = 0.085) ABP, weight loss (p = 0.003) and decrease of central systolic BP (p = 0.008) and central pulse pressure (p = 0.008). The increase in ß-OHB was related to an attenuated decrease of empagliflozin-induced 24 h systolic (r = 0.321, p = 0.069) and diastolic (r = 0.516, p = 0.002) ABP and less reduction of central systolic BP (r = 0.470, p = 0.009) and central pulse pressure (r = 0.391, p = 0.033). No significant changes were seen in any of these parameters after 12 weeks of treatment in the placebo group (n = 17). CONCLUSION: In patients with stable CHF ketone bodies as assessed by ß-OHB increased after treatment with empagliflozin. This increase led to an attenuation of the beneficial effects of empagliflozin on BP and vascular parameters. Trial registration The study was registered at http://www.clinicaltrials.gov (NCT03128528).

2.
Internist (Berl) ; 60(4): 424-430, 2019 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-30770942

RESUMO

Arterial hypertension represents one of the most frequent chronic diseases that can lead to complications, such as stroke, dementia, heart attack, heart failure and renal failure. By 2025 the number of hypertensive patients will increase to approximately 1.6 billion people worldwide. The new guidelines of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH) on the management of arterial hypertension replace the guidelines of the ESC/ESH from 2013. The 2018 guidelines of the ESC/ESH were adopted by the German Cardiac Society and the German Hypertension League. In these comments national characteristics are worked out and the essential new aspects of the guidelines are critically discussed. These include, for example, the definition of hypertension, the importance of out of office blood pressure measurements, revised blood pressure targets, the modified algorithm for drug treatment and the relevance of device-based hypertension treatments. Important aspects for the management of hypertensive emergencies are also presented.


Assuntos
Cardiologia , Hipertensão , Anti-Hipertensivos , Pressão Sanguínea , Determinação da Pressão Arterial , Humanos
3.
Internist (Berl) ; 60(2): 202-208, 2019 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-30649580

RESUMO

BACKGROUND: In November 2017, the latest American guidelines for the management of arterial hypertension were published. With these guidelines lowering the threshold for hypertension to 130/80 mm Hg, the latest European guidelines were expected with excitement. OBJECTIVES: This article gives an overview on the European Society of Cardiology (ESC) and European Society of Hypertension (ESH) 2018 guidelines for the management of arterial hypertension, thereby identifying the most relevant changes in comparison to previous guidelines. CURRENT DATA: The latest 2018 ESC/ESH guidelines adhere to the previous definition of hypertension, in which a blood pressure of 140/90 mm Hg is considered as threshold for diagnosis. In contrast, there was a change in blood pressure treatment target from below 140/90 to between 120-129/70-79 mm Hg in patients < 65 years if well tolerated. Among patients ≥ 65 years, a systolic blood pressure between 130 and 139 mm Hg is recommended, whereas a diastolic blood pressure between 70 and 79 mm Hg should be targeted. Additionally the guidelines recommend the use of fixed dose combinations as first choice instead of monotherapy to improve adherence. Interventional treatment strategies should only be applied in carefully selected patients at experienced centers and are not recommended outside of clinical studies and registers. Furthermore, the chapters regarding initiation of blood pressure-lowering therapy and clinical evaluation as well as management of hypertension emergencies have been outlined. CONCLUSIONS: The latest European guidelines for the management of hypertension include several changes. One of the most important aspects is that-in contrast to the American guidelines-the threshold for diagnosis remains at 140/90 mm Hg, whereas treatment target range has been lowered by roughly 10 mm Hg and single pill fixed dose combinations are recommended.


Assuntos
Anti-Hipertensivos/uso terapêutico , Cardiologia/normas , Hipertensão/tratamento farmacológico , Guias de Prática Clínica como Assunto/normas , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/fisiologia , Determinação da Pressão Arterial/normas , Monitorização Ambulatorial da Pressão Arterial , Cardiologia/tendências , Europa (Continente) , Humanos , Hipertensão/diagnóstico , Rim/inervação , Artéria Renal/inervação , Artéria Renal/cirurgia
4.
Cardiovasc Diabetol ; 17(1): 5, 2018 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-29301520

RESUMO

BACKGROUND AND AIMS: Sodium tissue content by 23Na magnetic resonance imaging (Na-MRI) has been validated in experimental and human studies. SGLT-2 inhibition blocks the reabsorption of glucose and of sodium in the proximal tubular cells in a 1:1 fashion. We hypothesized that SGLT-2 inhibition in patients with type 2 diabetes characterized by sodium retention leads to decreased tissue sodium content due to its pharmacological action. MATERIALS AND METHODS: In a prospective double blind, placebo controlled, cross-over trial 59 patients (61 ± 7.6 years) with type 2 diabetes were randomized to either dapagliflozin 10 mg or placebo once daily for 6 weeks each. In addition to metabolic parameters and ambulatory blood pressure (BP) we analysed the sodium content in the skin and muscles of the lower leg by Na-MRI. RESULTS: Compared to baseline 6 weeks treatment with the SGLT-2 inhibitor dapagliflozin decreased fasting (132 ± 28 vs. 114 ± 19 mg/dl, p < 0.001), postprandial blood glucose (178 ± 66 mg/dl vs. 153 ± 46 mg/dl, p < 0.001), body weight (87.6 vs. 86.6 kg, p < 0.001) and systolic (129 ± 12 vs. 126 ± 11 mmHg, p = 0.010), and diastolic (77.4 ± 9 vs. 75.6 ± 8 mmHg, p = 0.024), 24-h ambulatory BP. Tissue sodium content in the skin was reduced after 6 weeks treatment with dapagliflozin compared to baseline [24.1 ± 6.6 vs. 22.7 ± 6.4 A.U.(arbitrary unit) p = 0.013]. No significant reduction of tissue sodium content was observed in the muscle (M. triceps surae: 20.5 ± 3.5 vs. 20.4 ± 3.7 A.U. p = 0.801). No clear significant difference in tissue water content of muscle and skin was observed after 6 weeks of treatment with dapagliflozin, compared to baseline. CONCLUSION: SGLT-2 inhibition with dapagliflozin resulted in a significant decrease in tissue sodium content of the skin after 6 weeks. This observation point to a decrease of total sodium content in patients with type 2 diabetes prone to cardiovascular complications, that might be mitigated by SGLT-2 inhibition. Trial registration The study was registered at http://www.clinicaltrials.gov (NCT02383238) retrospectively registered.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Músculo Esquelético/efeitos dos fármacos , Pele/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Transportador 2 de Glucose-Sódio/efeitos dos fármacos , Sódio/metabolismo , Idoso , Compostos Benzidrílicos/efeitos adversos , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Estudos Cross-Over , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Método Duplo-Cego , Feminino , Alemanha , Glucosídeos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Estudos Prospectivos , Pele/metabolismo , Transportador 2 de Glucose-Sódio/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
6.
J Intern Med ; 278(3): 303-12, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25872921

RESUMO

BACKGROUND: Elevated systolic blood pressure (SBP) and high resting heart rate (HR) are associated with cardiovascular end-points. Although the association between atrial fibrillation (AF) and SBP is well established, the relation between AF and HR remains unclear. METHODS: In patients from the ONTARGET and TRANSCEND studies with high cardiovascular disease risk (n = 27 064), new-onset AF was evaluated in relation to mean SBP, visit-to-visit variation in SBP (SBP-CV; i.e. SD/mean × 100%), mean HR and visit-to-visit variation in HR (HR-CV). RESULTS: Low mean HR (P < 0.0001) and high SBP (P = 0.0021) were associated with incident AF. High SBP-CV (P = 0.031) and HR-CV (P < 0.0001) were also associated with incident AF. After adjustment for confounders, SBP and SBP-CV were no longer significantly associated with AF. The detrimental effect of low HR was particularly evident in subjects who were not receiving treatment with beta-blockers (P = 0.014 for interaction between beta-blocker use and mean HR). In addition to low HR, high HR-CV and high SBP had additive effects on incident AF. CONCLUSIONS: Low mean HR (<60 beats min(-1) ) is independently associated with incident AF, and low HR-CV and high SBP further increase the incidence of new-onset AF in patients at high risk of cardiovascular disease.


Assuntos
Fibrilação Atrial/fisiopatologia , Frequência Cardíaca/fisiologia , Doenças Vasculares/complicações , Antagonistas Adrenérgicos beta/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Pressão Sanguínea , Humanos , Pessoa de Meia-Idade
8.
Eur J Health Econ ; 16(1): 65-72, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24390212

RESUMO

The financial burden for EU health systems associated with cardiovascular disease (CV) has been estimated to be nearly €110 billion in 2006, corresponding to 10% of total healthcare expenditure across EU or a mean €223 annual cost per capita. The main purpose of this study is to estimate the costs related to hypertension and the economic impact of increasing adherence to anti-hypertensive therapy in five European countries (Italy, Germany, France, Spain and England). A probabilistic prevalence-based decision tree model was developed to estimate the direct costs of CV related to hypertension (CV defined as: stroke, heart attack, heart failure) in five European countries. Our model considered adherence to hypertension treatment as a main driver of blood pressure (BP) control (BP < 140/90 mmHg). Relative risk of CV, based on controlled or uncontrolled BP group, was estimated from the Framingham Heart Study and national review data. Prevalence and cost data were estimated from national literature reviews. A national payer (NP) perspective for 10 years was considered. Probabilistic sensitivity analysis was performed in order to evaluate uncertainty around the results (given as 95% confidence intervals). The model estimated a total of 8.6 million (1.4 in Italy, 3.3 in Germany, 1.2 in Spain, 1.8 in France and 0.9 in England) CV events related to hypertension over the 10-year time horizon. Increasing the adherence rate to anti-hypertensive therapy to 70% (baseline value is different for each country) would lead to 82,235 fewer CV events (24,058 in Italy, 7,870 in Germany, 18,870 in Spain, 24,855 in France and 6,553 in England). From the NP perspective, the direct cost associated with hypertension was estimated to be 51.3 billion (8.1 in Italy, 17.1 in Germany, 12.2 in Spain, 8.8 in France and 5.0 in England). Increasing adherence to anti-hypertensive therapy to 70% would save a total of 332 million (CI 95%: €319-346 million) from the NPs perspective. This study is the first attempt to estimate the economic impact of non-adherence amongst patients with diagnosed hypertension in Europe, using data from five European countries (Italy, France, Germany, Spain and England).


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão/economia , Adesão à Medicação/estatística & dados numéricos , Adulto , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea , Doenças Cardiovasculares/economia , Árvores de Decisões , Europa (Continente)/epidemiologia , Feminino , Gastos em Saúde/estatística & dados numéricos , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Método de Monte Carlo , Prevalência , Medicina Estatal/estatística & dados numéricos
9.
J Nephrol ; 28(2): 165-72, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24990164

RESUMO

BACKGROUND: Hyperkalemia is a common and life-threatening complication frequently seen in patients with acute kidney injury, end-stage renal disease and chronic heart failure. Cardiac arrest and ventricular fibrillation are possible consequences. Biosensors are currently being developed to measure serum potassium under ambulatory conditions and trigger an alarm if the potassium concentration exceeds normal limits. Only few studies exist on the circadian rhythm of potassium; and its dependence on age and kidney function is less clear. METHODS: Our observational monocentric exploratory study included 30 subjects of which 15 had impaired renal function (RF) (GFR <60 ml/min/1.73 m(2)). Subjects were further categorized into three age groups: 18-39 years (N normal RF = 5, N impaired RF = 4), 40-59 years (N normal RF = 5, N impaired RF = 6), 60-80 years (N normal RF = 5, N impaired RF = 5). Serum potassium levels were measured every 2 h during a 24 h period and repeated once after 2, 4, or 6 days. RESULTS: In the 15 subjects with normal RF, the lowest mean potassium level (3.96 ± 0.14 mmol/l) was observed at 9 p.m. and the greatest (4.23 ± 0.23 mmol/l) at 1 p.m. In patients with impaired RF the lowest mean potassium level (4.20 ± 0.32 mmol/l) was observed at 9 p.m. and the highest (4.57 ± 0.46 mmol/l) at 3 p.m. The range between the mean of minimum and maximum was greater in patients with impaired RF (0.71 ± 0.45 mmol/l) than in subjects with normal RF (0.53 ± 0.14 mmol/l) [p < 0.001]. No difference in the circadian rhythm was found between the first and second examination. CONCLUSION: Our results indicate that patients with normal and impaired RF have comparable circadian patterns of serum potassium concentrations, but higher fluctuations in patients with impaired RF. These results have clinical relevance for developing an automatic biosensor to measure the potassium concentration in blood under ambulatory conditions in patients at high risk for potassium fluctuations.


Assuntos
Ritmo Circadiano , Potássio/sangue , Insuficiência Renal Crônica/sangue , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Adulto Jovem
10.
J Intern Med ; 278(1): 38-49, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25431275

RESUMO

BACKGROUND: Resting heart rate (RHR) is associated with cardiovascular disease outcomes in high-risk patients. It is not known whether RHR is predictive of renal outcomes such as albuminuria, end-stage renal disease (ESRD) or doubling of creatinine. We evaluated whether RHR could predict renal endpoints in patients at a high risk of cardiovascular disease. We also tested the effects of RHR at different levels of systolic blood pressure (SBP). METHODS: We analysed data from 28 757 patients in the ONTARGET and TRANSCEND trials. RHR and SBP were available for a mean of 4.9 ± 0.4 visits (range 3-5) within the first 2 years of the studies. Albuminuria was determined at baseline, at 2 years and at study end. RESULTS: Mean RHR was predictive of incident micro-albuminuria [hazard ratio (HR) for RHR ≥80 vs. <60 beats min(-1) 1.49, 95% confidence interval (CI) 1.29-1.71, P < 0.0001], incident macro-albuminuria (HR 1.84, 95% CI 1.39-2.42, P < 0.0001), doubling of creatinine (HR 1.47, 95% CI 1.00-2.17, P = 0.050) and ESRD (HR 1.78, 95% CI 1.00-3.16, P = 0.050), and the combined renal end-point (HR 1.51, 95% CI 1.32-1.74, P < 0.0001). Associations were robust at SBPs from <120 to ≥150 mmHg, with the lowest risk at a SBP of 130-140 mmHg. CONCLUSION: Resting heart rate is a potent predictor of these renal outcomes, as well as their combination, in patients with cardiovascular disease. RHR at all SBP levels should be considered as a possible renal disease risk predictor and should be investigated as a treatment target with RHR-reducing agents.


Assuntos
Albuminúria/fisiopatologia , Doenças Cardiovasculares/fisiopatologia , Frequência Cardíaca , Falência Renal Crônica/fisiopatologia , Idoso , Pressão Sanguínea , Doenças Cardiovasculares/complicações , Creatinina/sangue , Feminino , Humanos , Falência Renal Crônica/complicações , Masculino , Prognóstico , Fatores de Risco
11.
J Hum Hypertens ; 29(5): 316-23, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25273857

RESUMO

We aimed to analyze benefits and risks of aliskiren treatment in older adults (⩾ 65 years) in clinical practice. Patients (n = 14,986) were assigned to either aliskiren (ALIS), an angiotensin-converting-enzyme inhibitor or angiotensin receptor blocker (ACEi/ARB), or an agent not blocking the renin-angiotensin system (non-RAS). Older adults (n = 7396) had a longer history of hypertension (8.7 vs 4.7 years; P < 0.0001), lower mean diastolic blood pressure (DBP; 87.7 ± 11.0 vs 92.1 ± 11.0 mm Hg) and more renal (12.0 vs 5.6%; P < 0.0001) or cardiovascular disease (44.0 vs 18.9%; P < 0.0001); 4548 received aliskiren (68.8%), 1215 ACEi/ARBs (18.4%) and 850 non-RAS treatments (12.9%). Office BP at 1 year was reduced by 18.4 ± 21.5/7.2 ± 12.0 mm Hg. BP reductions were greater (19.5 ± 21.7/7.6 ± 12.1 mm Hg) in the aliskiren group than in the ACEi/ARB (15.6 ± 20.9/6.4 ± 11.9) and non-RAS groups (16.1 ± 20.7/6.5 ± 11.7 mm Hg), respectively (P<0.0001 for systolic BP (SBP) and <0.01 for DBP). After multivariable adjustment, differences in SBP reductions were clinically irrelevant and no differences were noted for DBP. Adverse effects were higher in older adults with no differences between treatment groups. In conclusion, the present analysis of a large, unselected cohort of patients in clinical practice from the 3A study, offers real-life evidence of the effectiveness and safety of aliskiren for the treatment of hypertension in older adults.


Assuntos
Amidas , Fumaratos , Hipertensão , Fatores Etários , Idoso , Amidas/administração & dosagem , Amidas/efeitos adversos , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Fumaratos/administração & dosagem , Fumaratos/efeitos adversos , Alemanha/epidemiologia , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/metabolismo , Masculino , Pessoa de Meia-Idade , Renina/antagonistas & inibidores , Sistema Renina-Angiotensina/efeitos dos fármacos , Medição de Risco , Resultado do Tratamento
12.
J Hum Hypertens ; 27(12): 715-20, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23636009

RESUMO

It is well known that 24-h ambulatory blood pressure monitoring (ABPM) provides a more accurate picture of a patient's blood pressure (BP) compared with clinic BP measurement. Twenty-four-hour ABPM better predicts hypertension-related risks such as end-organ damage including left ventricular hypertrophy, cardiovascular (CV) events and mortality. Threshold BP values for hypertension based on 24-h ABPM results have been established, including daytime and night-time averages. Nevertheless, the relationship between 24-h ABPM and clinic BP measurement in patients on antihypertensive therapy, and in particular how each may change in response to antihypertensive therapy, is less clear. This review will provide an overview of current knowledge on the relation between clinic BP and ambulatory BP reductions in clinical trials on antihypertensive therapies. Reduction in CV risk and its correlation with the magnitude of reduction in both clinic and ambulatory BP are explored. The most striking result is that reduction in clinic BP and ambulatory BP do not correspond in a 1:1 fashion, that is, smaller changes in 24-h ABPM correspond to significantly larger changes in clinic BP.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea , Hipertensão/terapia , Humanos , Hipertensão/mortalidade
13.
Int J Cardiol ; 168(3): 2255-63, 2013 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-23474245

RESUMO

OBJECTIVE: Twenty-four hour ambulatory blood pressure (ABP) is superior to office blood pressure (BP) in predicting cardiovascular events. However, its use to optimise BP control in treated hypertensive patients is less well examined. DESIGN AND METHOD: In this observational study conducted in 899 general practitioners' offices, 4078 hypertensive patients with uncontrolled office BP were included. Antihypertensive therapy was intensified and after 1 year office BP and 24-hour ABP were measured to categorise patients according to the ESC/ESH 2007 guidelines. RESULTS: In this cohort (mean office BP 156/90 mmHg, mean ABP 146/85 mmHg), 2059 out of 4078 patients (50.5%) had controlled office BP (<140/90 mmHg) at 1 year examination. Of these apparently controlled patients (N=2059), 1339 (65.8%) had 24-hour ABP ≥ 130/80 mmHg, indicating masked hypertension (32.9% of all treated patients). In the prespecified subgroups the prevalence of masked hypertension was the following: diabetes 28.2%, CVD 29.1%, and CKD 32.1%. White coat hypertension (24h-ABP<130/80 mmHg and office BP ≥ 140/90 mmHg) was found in 12.4% (N=233) of patients with elevated office BP (6.1% of all treated patients), and in 5.7% of the diabetic subgroup, 5.6% CVD and 7.1% CKD. Discrepancies in BP categorisation between office BP and 24-hour ABP were high; all subjects 52.8%, diabetes 50.0%, CVD 49.0% and CKD 50.4%. CONCLUSION: In hypertensive patients on therapy, 2 out of 3 with apparently controlled office BP had masked hypertension, suggesting a more aggressive therapy, and 1 out of 8 with elevated office BP had white coat hypertension potentially falsely forcing physicians to intensify therapy. The 3A Registry is listed under clinicaltrials.gov, NCT01454583.


Assuntos
Anti-Hipertensivos/uso terapêutico , Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea/fisiologia , Hipertensão/diagnóstico , Idoso , Feminino , Seguimentos , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Tempo
16.
Microvasc Res ; 84(1): 60-4, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22484031

RESUMO

One of the major indicators of intact endothelial function is basal nitric oxide (NO) activity. Further, it seems to be likely that statin therapy exerts beneficial effects on vascular function, at least in part via an improvement of NO bioavailability. In the present double-blind crossover study 29 hypercholesterolemic patients were randomly assigned to receive rosuvastatin and placebo for 42days. Pulse wave analysis was assessed after 30min of rest (baseline) and after infusion of N(G)-monomethyl-l-arginine (l-NMMA) at the end of 42days treatment period. The magnitude of the increase in central augmentation index (cAIx) in response to inhibition of NO synthase (NOS) by l-NMMA is indicative of basal NO activity. CAIx was significantly lower (18.3±10 versus 21.9±12%, p=0.027) with rosuvastatin compared to placebo. There was no increment of cAIx in response to l-NMMA in placebo group. In contrast, cAIx increased significantly in response to l-NMMA (20.5±11 versus 25.7±10mm Hg, p=0.001) in rosuvastatin group. The percentage of increase of cAIx tended to be more pronounced after treatment with rosuvastatin compared to placebo (53.7±92 versus 14.1±36%, p=0.087). Pulse pressure amplification (PPA) improved (1.31±0.2 versus 1.26±0.2%, p=0.016) after rosuvastatin compared to placebo. Regression analyses revealed that both LDL-cholesterol and CRP-levels are independent determinants of basal NO activity improvement, which itself is an independent determinant of vascular function, expressed by an improvement of pulse wave reflection and PPA. In this placebo controlled study, treatment with rosuvastatin improved vascular and endothelial function. Determinants for improved NO production in patients with hypercholesterolemia were the achieved levels of LDL-cholesterol and CRP. Overall, in patients without CV disease, rosuvastatin exerted beneficially effect on vascular dysfunction, one of the earliest manifestation of atherosclerosis.


Assuntos
Endotélio Vascular/efeitos dos fármacos , Fluorbenzenos/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipercolesterolemia/tratamento farmacológico , Microcirculação/efeitos dos fármacos , Fluxo Pulsátil/efeitos dos fármacos , Pirimidinas/farmacologia , Sulfonamidas/farmacologia , Angiografia , Pressão Sanguínea , Estudos Cross-Over , Elasticidade , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Hipercolesterolemia/fisiopatologia , Masculino , Microvasos/efeitos dos fármacos , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo III , Rosuvastatina Cálcica , ômega-N-Metilarginina
17.
Dtsch Med Wochenschr ; 137(7): 317-21, 2012 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-22318846

RESUMO

Arterial blood pressure is subject to a circadian rhythm that results in a fall of blood pressure during the night. In patients with diabetes, renal insufficiency, left-ventricular hypertrophy, sleep apnea, hypertension of pregnancy, and different forms of secondary hypertension a nocturnal fall of blood pressure is even abandoned or reverted. Diagnosis is made using 24-h blood pressure measurement, which is however used not frequently enough for a clinical assessment or adjustment of therapy. An adaption of the selection or the time of administration of antihypertensive drugs with respect to the circadian rhythm is beneficial to control blood pressure and reduce cardiovascular morbidity. This is particularly true for patients with an a non- or inverted dipping blood pressure pattern, in which the bedtime dosing may result in a normalization of blood pressure and restoration of a normal circadian rhythm. The present manuscript reviews the chronopharmacotherapy of arterial hypertension and grant practical recommendations for their translation into clinical practice.


Assuntos
Anti-Hipertensivos/uso terapêutico , Ritmo Circadiano/fisiologia , Cronoterapia Farmacológica , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Fatores Etários , Animais , Monitorização Ambulatorial da Pressão Arterial , Humanos , Hipertensão/tratamento farmacológico
18.
J Intern Med ; 271(5): 463-71, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21812843

RESUMO

OBJECTIVES: Risk factors of mortality in patients with haemodialysis (HD) have been identified in several studies, but few prognostic models have been developed with assessments of calibration and discrimination abilities. We used the database of the Assessment of Survival and Cardiovascular Events study to develop a prognostic model of mortality over 3-4 years. METHODS: Five factors (age, albumin, C-reactive protein, history of cardiovascular disease and diabetes) were selected from experience and forced into the regression equation. In a 67% random try-out sample of patients, no further factors amongst 24 candidates added significance (P < 0.01) to mortality outcome as assessed by Cox regression modelling, and individual probabilities of death were estimated in the try-out and test samples. Calibration was explored by calculating the prognostic index with regression coefficients from the try-out sample to patients in the 33% test sample. Discrimination was assessed by receiver operating characteristic (ROC) areas. RESULTS: The strongest prognostic factor in the try-out sample was age, with small differences between the other four factors. Calibration in the test sample was good when the calculated number of deaths was multiplied by a constant of 1.33. The five-factor model discriminated reasonably well between deceased and surviving patients in both the try-out and test samples with an ROC area of about 0.73. CONCLUSIONS: A model consisting of five factors can be used to estimate and stratify the probability of death for individuals The model is most useful for long-term prognosis in an HD population with survival prospects of more than 1 year.


Assuntos
Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus/epidemiologia , Falência Renal Crônica/epidemiologia , Diálise Renal , Fatores Etários , Idoso , Proteína C-Reativa/análise , Comorbidade , Feminino , Unidades Hospitalares de Hemodiálise/estatística & dados numéricos , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Diálise Renal/mortalidade , Diálise Renal/estatística & dados numéricos , Fatores de Risco , Albumina Sérica/análise
19.
J Med Econ ; 15(1): 155-65, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22035215

RESUMO

OBJECTIVE: This retrospective patient data analysis was initiated to describe current treatment patterns of patients in Germany with arterial hypertension, with a special focus on compliance, persistence, and medication costs of fixed-dose and unfixed combinations of angiotensin receptor blockers (ARBs), amlodipine (AML) and hydrochlorothiazide (HCT) in Germany. METHODS: The study analyzed prescription data collected by general practitioners, using the IMS Disease Analyzer database. The database was searched for patients with the diagnosis hypertension (ICD-10 code I10) and treatment data in the period 09/2009 to 08/2010. Compliance was measured indirectly based on the medication possession ratio (MPR), and persistence was defined as the duration of time from initiation to discontinuation of therapy. Medication costs were assessed from the statutory health insurance perspective in Germany. RESULTS: In the IMS DA 406,888 observable patients in Germany were encoded with the diagnosis I10 essential hypertension. In total, 88,716 patients received prescriptions including ARBs, monotherapy (18.6%) or unfixed combinations with other anti-hypertensives (19.3%). The compliance with fixed-dose combinations of ARB with HCT, either dual or with one other anti-hypertensive drug, was significantly better, compared to unfixed combinations (mean compliance 78.1% for fixed-dose vs 71.5% for unfixed combinations of ARB with HCT, p < 0.0001; mean compliance 79.4% vs 72.0%, p < 0.0001 if an additional anti-hypertensive medication was added). Fixed-dose combinations of ARB with HCT, ARB with AML, dual only or prescribed with another anti-hypertensive medication resulted in a substantial increase of persistence, especially for patients on fixed-dose dual combinations (225.7 vs 163.6 days for ARB with HCT; 232.9 vs 178.4 days for ARB with AML, respectively). Fixed-dose combinations (varying from €1.38 to €2.20 per patient and day) were on average cheaper than unfixed combinations. LIMITATIONS: Persistence and compliance could be under- or over-estimated because their assessment was based on prescription information. For two thirds of 69,060 patients, data on compliance and persistence was missing. CONCLUSION: The study shows considerable variations in ARB treatment patterns among patients, with the majority of patients treated with fixed-dose or semi-fixed combination therapy. Fixed-dose combinations of ARBs with HCT and/or AML seem to result in better compliance and persistence compared to unfixed regimes of these drug classes, leading to reduction in all-cause hospitalizations, emphasizing the benefit and potential cost-savings of using fixed-dose regimes in a real-life general practice setting in Germany.


Assuntos
Anti-Hipertensivos/economia , Custos de Medicamentos , Hidroclorotiazida/economia , Hipertensão/tratamento farmacológico , Cooperação do Paciente , Idoso , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Custos de Medicamentos/estatística & dados numéricos , Feminino , Alemanha , Humanos , Hidroclorotiazida/administração & dosagem , Hidroclorotiazida/uso terapêutico , Hipertensão/economia , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente/estatística & dados numéricos
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