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1.
Artigo em Inglês | MEDLINE | ID: mdl-32639326

RESUMO

: Cardiovascular diseases (CVDs) are the main cause of mortality worldwide. Risk factors of CVD can be classified into modifiable (smoking, hypertension, diabetes, hypercholesterolemia) through lifestyle changes or taking drug therapy and not modifiable (age, ethnicity, sex and family history). Elevated total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels have a lead role in the development of coronary heart disease (CHD), while high levels of high-density lipoprotein-cholesterol (HDL-C) seem to have a protective role.The current treatment for dyslipidemia consists of lifestyle modification or drug therapy even if not pharmacological treatment should be always considered in addition to lipid-lowering medications.The use of lipid-lowering nutraceuticals alone or in association with drug therapy may be considered when the atherogenic cholesterol goal was not achieved.These substances can be classified according to their mechanisms of action into natural inhibitors of intestinal cholesterol absorption, inhibitors of hepatic cholesterol synthesis and enhancers of the excretion of LDL-C. Nevertheless, many of them are characterized by mixed or unclear mechanisms of action.The use of these nutraceuticals is suggested in individuals with borderline lipid profile levels or with drug intolerance, but cannot replace standard lipid-lowering treatment in patients at high, or very high CVD risk.Nutraceuticals can also have vascular effects, including improvement in endothelial dysfunction and arterial stiffness, as well as antioxidative properties. Moreover, epidemiological and clinical studies reported that in patients intolerant of statins, many nutraceuticals with demonstrated hypolipidemic effect are well tolerated.

2.
Biomarkers ; 25(2): 201-211, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32063068

RESUMO

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome for which clear evidence of effective therapies is lacking. Understanding which factors determine this heterogeneity may be helped by better phenotyping. An unsupervised statistical approach applied to a large set of biomarkers may identify distinct HFpEF phenotypes.Methods: Relevant proteomic biomarkers were analyzed in 392 HFpEF patients included in Metabolic Road to Diastolic HF (MEDIA-DHF). We performed an unsupervised cluster analysis to define distinct phenotypes. Cluster characteristics were explored with logistic regression. The association between clusters and 1-year cardiovascular (CV) death and/or CV hospitalization was studied using Cox regression.Results: Based on 415 biomarkers, we identified 2 distinct clusters. Clinical variables associated with cluster 2 were diabetes, impaired renal function, loop diuretics and/or betablockers. In addition, 17 biomarkers were higher expressed in cluster 2 vs. 1. Patients in cluster 2 vs. those in 1 experienced higher rates of CV death/CV hospitalization (adj. HR 1.93, 95% CI 1.12-3.32, p = 0.017). Complex-network analyses linked these biomarkers to immune system activation, signal transduction cascades, cell interactions and metabolism.Conclusion: Unsupervised machine-learning algorithms applied to a wide range of biomarkers identified 2 HFpEF clusters with different CV phenotypes and outcomes. The identified pathways may provide a basis for future research.Clinical significanceMore insight is obtained in the mechanisms related to poor outcome in HFpEF patients since it was demonstrated that biomarkers associated with the high-risk cluster were related to the immune system, signal transduction cascades, cell interactions and metabolismBiomarkers (and pathways) identified in this study may help select high-risk HFpEF patients which could be helpful for the inclusion/exclusion of patients in future trials.Our findings may be the basis of investigating therapies specifically targeting these pathways and the potential use of corresponding markers potentially identifying patients with distinct mechanistic bioprofiles most likely to respond to the selected mechanistically targeted therapies.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Fenótipo , Idoso , Biomarcadores/análise , Análise por Conglomerados , Feminino , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Proteômica , Volume Sistólico
3.
Diabetes Metab Res Rev ; 36(1): e3219, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31642581

RESUMO

BACKGROUND: To evaluate if the positive effects recorded on glycaemic control with continuous subcutaneous insulin infusion (CSII) were maintained on the long-term compared with multiple daily injection (MDI). The secondary objective was to evaluate if there is a reduction of type and number of cardiovascular events (CV). METHODS: This retrospective, observational study evaluated glycaemic control and the number of CV in 104 patients with type 1 or 2 diabetes previously treated with MDI and initiating CSII therapy with tubed insulin pumps compared with 109 patients previously treated with MDI continuing MDI. RESULTS: After 8 years, the glycaemic control including glycated haemoglobin (HbA1c ), fasting plasma glucose (FPG), and prandial plasma glucose (PPG) improved with both CSII and MDI compared with baseline; however, HbA1c , FPG, and PPG recorded with CSII were lower than data recorded with MDI. During the 8 years, there were fewer CV events with CSII, compared with MDI, and in particular, there were fewer cases of atrial fibrillation, premature ventricular contractions, acute coronary infarction, angina pectoris, heart failure, and peripheral vascular ischemia. We did not record any reduction of ischemic stroke events. CONCLUSION: Our preliminary data suggest that CSII treatment seems to reduce the rates of CV compared with MDI therapy. Moreover, CSII also improved glycaemic control, without increasing the number of hypoglycaemia. However, given the observational design of this trial, our data should be validated in a randomized clinical trial; if they will be confirmed, CSII could be chosen for fully informed and motivated patients at higher risk of developing CV.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31596464

RESUMO

AIMS: Right ventricular free wall longitudinal strain (RVFWLS) has been proposed as an accurate and sensitive measure of right ventricular function that could integrate other conventional parameters such as tricuspid annulus plane systolic excursion (TAPSE) and fractional area change (FAC%). The aim of the present study was to evaluate the relationship between RVFWLS and outcomes in stable asymptomatic outpatients with left-sided structural heart disease. METHODS AND RESULTS: We enrolled 458 asymptomatic patients with left-side heart diseases and any ejection fraction who were referred for echocardiography to two Italian centres. The composite endpoint of death for any cause and heart failure hospitalization was used as primary outcome of this analysis. After a mean follow-up of 5.4 ± 1.2 years, 145 patients (31%) reached the combined endpoint. Most of echocardiographic parameters were related to outcomes, including right ventricular functional parameters. Mean value of RVFWLS in our cohort was -21 ± 8% and it was significantly related to the combined endpoint and in multivariable Cox-regression model; when tested with other echocardiographic parameters that were significantly related to outcome at univariate analysis, RVFWLS maintained its independent association with outcome (hazard ratio 0.963, 95% confidence interval 0.948-0.978; P = 0.0001). The best cut-off value of RVFWLS to predict outcome was -22% (area under the curve 0.677; P < 0.001; sensitivity 70%; 65% specificity). CONCLUSION: RVFWLS may help clinicians to identify patients with left-sided structural heart disease at higher risk for first heart failure hospitalization and death for any cause.

5.
Eur J Pharmacol ; 838: 85-90, 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30201379

RESUMO

Patients who experienced cardiovascular side effects during cancer therapy with carfilzomib for multiple myeloma had relapsed multiple myeloma, so have be previously treated with other cancer therapies. The present is a single center cohort study to evaluate early cardiovascular effects of administration of irreversible proteasome inhibitor carfilzomib in naïve patients. We included 24 patients and collected cardiovascular side effects, echocardiographic parameters and endothelial function at baseline and after 4 cycles. At early follow up we observed increase in blood arterial pressure values (mean change in systolic pressure of 10 mmHg (P-value < 0.01; diastolic arterial pressure and mean arterial pressure of 3.3 mmHg and 5.4 mmHg, both P-value < 0.01). Reactive hyperemia PAT index was reduced in the whole cohort by a mean of 0.46 points (P-value < 0.01); diastolic function was changed: E-wave-deceleration-time (EDT) was reduced by 49,96 ±â€¯31 ms, P-value < 0.05 and early diastolic tissue Doppler velocity (e') by a mean value of 1.46 cm/s, P - value 0.04. At early follow up we did not observe events of grade 3 or 4. We observe correlation between events and endothelial dysfunction at baseline and age (OR 1.9, CI 95% 0.05-5.804, P- value: 0.038 for RHI<1.67; OR 1,4, CI 95%0.99-2.56, P- value: 0.04 for age). Our results suggest that therapy with carfilzomib when used as first line therapy is responsible for increase in systemic blood pressure, alteration of endothelium-mediated vascular dilatation and early myocardial diastolic dysfunction.


Assuntos
Antineoplásicos/efeitos adversos , Mieloma Múltiplo/tratamento farmacológico , Oligopeptídeos/efeitos adversos , Inibidores de Proteassoma/efeitos adversos , Fatores Etários , Pressão Sanguínea/efeitos dos fármacos , Estudos de Coortes , Diástole/efeitos dos fármacos , Ecocardiografia Doppler , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Feminino , Coração/diagnóstico por imagem , Coração/efeitos dos fármacos , Coração/fisiopatologia , Humanos , Hiperemia/induzido quimicamente , Hiperemia/diagnóstico por imagem , Hiperemia/epidemiologia , Hiperemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Vasodilatação/efeitos dos fármacos
6.
Phytomedicine ; 42: 75-82, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29655700

RESUMO

BACKGROUND: In literature, there are several studies about the effects of nutraceutical combinations at fasting, but data in post-prandial phase are lacking. PURPOSE: We planned a study to evaluate the efficacy and safety of a nutraceutical agent containing fermented red rice, phytosterols and olive polyphenols compared to placebo in a sample of Caucasian patients with low cardiovascular risk, both at fasting and after an oral fat load. STUDY DESIGN: Eighty patients were randomized to receive, as addition to diet and physical activity, a nutraceutical combination containing fermented red rice, sterol esters and stanols, curcumin, and olive polyphenols or placebo (control group), once a day. METHODS: We evaluated at baseline, and after 3 months: body mass index, fasting plasma glucose, lipid profile, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and soluble endothelial-leukocyte adhesion molecule-1. We evaluated these parameters both at fasting, and after an oral fat load. RESULTS: Nutraceutical combination gave a reduction of total cholesterol, triglycerides, and low-density lipoprotein cholesterol, both compared to baseline (p < 0.05 for all), and to placebo (p < 0.05 for all). We recorded a reduction of soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and sE-selectin in the group treated with nutraceutical combination, both compared to baseline (p < 0.05 for all), and to placebo (p < 0.05 for all). Parameters recorded during oral fat load improved compared to the oral fat load performed at baseline with the nutraceutical combination. CONCLUSIONS: The nutraceutical combination of fermented red rice, sterol esters and stanols, curcumin, and olive polyphenols seems to be effective in improving lipid profile and markers of endothelial damage in dyslipidemic patients in primary prevention at low risk for developing cardiovascular disease. The true novelty of this study, however, is the improvement of endothelial damage after an oral fat load compared to placebo.


Assuntos
Curcumina/farmacologia , Suplementos Nutricionais , Lipídeos/sangue , Oryza , Fitosteróis/farmacologia , Biomarcadores/sangue , Índice de Massa Corporal , LDL-Colesterol/sangue , Dislipidemias/prevenção & controle , Selectina E/sangue , Feminino , Humanos , Molécula 1 de Adesão Intercelular/sangue , Masculino , Pessoa de Meia-Idade , Olea/química , Polifenóis/farmacologia , Triglicerídeos/sangue
7.
Eur J Pharmacol ; 828: 80-88, 2018 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-29550338

RESUMO

Proteasome Inhibitors (PI) have now become the cornerstone of treatment of multiple myeloma (MM). Carfilzomib has been demonstrated to cause more frequent cardiovascular side effects such as dyspnea, hypertension, and heart failure. Recent pre-clinical studies have investigated the effects of proteasome on myocardial and vascular cells, but the pathogenic mechanism underlying the effects of proteasome inhibition on these cells is poorly understood. We reviewed the evidence from clinical trials, post-hoc analysis and small observational studies currently available and summarized the data from experimental, focusing on the pathogenic mechanisms potentially implicated in the cardiovascular toxicity of proteasome inhibitor, particularly of carfilzomib that is most responsible for cardiovascular side effects. Finally, we tried to suggest future perspectives for diagnostic and therapeutic approach to this type of cardiovascular damage.


Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Inibidores de Proteassoma/efeitos adversos , Animais , Humanos , Complexo de Endopeptidases do Proteassoma/metabolismo , Segurança , Ubiquitina/metabolismo
8.
Drug Des Devel Ther ; 11: 3425-3434, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29270001

RESUMO

Background and aim: Clinical benefits of early high-dose statin therapy after acute coronary syndromes are widely known; however, there is poor evidence on the specific setting of ST-elevation myocardial infarction (STEMI) and dose-dependent effects of this therapy on endothelial function and inflammatory biomarkers in the most vulnerable phase after acute coronary syndromes: the postdischarge period. In our study, we compared the short-term effects of high (80 mg) vs moderate doses of atorvastatin (20 mg) in patients with STEMI undergoing primary percutaneous coronary intervention on endothelial function and vascular inflammation. The aim of our study was the evaluation of dose-dependent short-term effects. Subjects and methods: We enrolled 52 patients within 48 hours of a STEMI to atorvastatin 80 mg (n=26) or 20 mg (n=26). Every patient underwent endothelial function evaluation by the reactive hyperemia-peripheral arterial tonometry (RH-PAT) index on the first day and 1 month after the STEMI. At the same time, we measured lipid profile and serum levels of high-sensitivity CRP, IL6, TNFα, and oxidized LDL. Results: After 1 month of therapy, we observed differences in high-sensitivity CRP levels (0.04±0.02 mg/dL vs 0.36±0.3 mg/dL, P=0.001), IL6 (1.12±0.93 pg/mL vs 3.13±2.84 pg/mL, P=0.03), and improvement in RH-PAT index (1.96±0.16 vs 1.72±0.19, P=0.002) in the group treated with high-dose vs moderate-dose atorvastatin. There was no significant difference in levels of TNFα or oxidized LDL with atorvastatin 20 mg, while there was a reduction in these variables in the group treated with atorvastatin 80 mg. We observed a correlation between high-sensitivity polymerase chain reaction and RH-PAT index on the 30th day after STEMI (r=0.5, P=0.001). Conclusion: Higher dose statin therapy in patients with STEMI undergoing primary percutaneous coronary intervention showed early greater vascular protective effects that moderate dose.


Assuntos
Anticolesterolemiantes/farmacologia , Atorvastatina/farmacologia , Endotélio Vascular/efeitos dos fármacos , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticolesterolemiantes/administração & dosagem , Atorvastatina/administração & dosagem , Relação Dose-Resposta a Droga , Método Duplo-Cego , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Feminino , Humanos , Inflamação/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Adulto Jovem
9.
EBioMedicine ; 21: 206-212, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28587834

RESUMO

BACKGROUND: Carfilzomib (CFZ) is a new proteasome inhibitor used for the treatment of multiple myeloma. Besides heart failure, angina and myocardial ischemia occurred following administration of CFZ, which is not contraindicated in patients with recent myocardial infarction/unstable angina excluded from the safety trials. AIM OF STUDY: To test the effects of CFZ (10-9 to 10-7mol/L) on vascular tone and reactivity in the isolated rabbit heart and aorta. METHODS AND RESULTS: CFZ administered by bolus injection to the isolated heart increased coronary perfusion pressure (CPP) at all tested concentrations and mildly raised left ventricular pressure and heart rate, only at the highest concentration. Addition of CFZ directly into the organ bath increased the basal tone of isolated aortic strips with contraction plateau reached after 10min. This spasmogenic effect doubled following ablation of the endothelium. Pretreatment with CFZ amplified the vasospastic action exerted by KCl, noradrenaline (NA) and angiotensin II (A) on aortic strips, and impaired vasodilation following administration of nitroglycerin (NTG) and nifedipine (NFP) on the contraction plateau induced by KCl, NA and A. Aortic strips pretreated with CFZ exhibited impaired relaxation, as compared to untreated strips, following administration of acetylcholine (Ach), an endothelium-dependent vasodilating agent, on the plateau of NA contraction (p<0.05). CONCLUSIONS: CFZ increased CPP, resting vasoconstricting tone and the spasmogenic effect of different agents. Preincubation with CFZ decreased the anti-spasmogenic activity of NTG and NFP, as well as reduced by over 50% the vasodilating effect of Ach, suggesting that CFZ can impair vasodilation via an endothelium dependent mechanism. Further studies are warranted to establish its clinical safety in patients with known CAD and prior history of coronary spasm.


Assuntos
Pressão Arterial/efeitos dos fármacos , Vasos Coronários/efeitos dos fármacos , Oligopeptídeos/farmacologia , Inibidores de Proteassoma/farmacologia , Resistência Vascular/efeitos dos fármacos , Acetilcolina/farmacologia , Animais , Frequência Cardíaca/efeitos dos fármacos , Nitroglicerina/farmacologia , Coelhos
10.
J Cardiovasc Med (Hagerstown) ; 17(8): 547-55, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27168142

RESUMO

AIMS: Cardiovascular diseases affect adult population but risk factors develop as a result of known or assumed behavior since childhood. In Italy, up to 22.2% of children are overweight, 10.6% are obese, and 2.5% have severe obesity. METHODS: We performed a systematic review of the literature to identify studies and initiatives addressing health promotion among children in Italy. Given the high heterogeneity of interventions and outcomes assessed we opted to perform a qualitative synthesis of the results. We described also nonrandomized trial where the intervention of primary prevention was very innovative, explained in detail, and reached an improving outcome for participants. RESULTS: We identified 11 projects since 1983, only five were randomized control trials. Three involved children and teachers of primary and secondary schools and were based on specific curricular lectures about health. One was based on a game developed for high schools with the purpose to promote healthy lifestyle and physical activity. The fifth project was based on an enhanced physical activity program. CONCLUSION: Our results show that school and family should be considered as the privileged places for health promotion. In Italy, the development of scientific-validated lifestyle interventions for children is still an unmet need.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Promoção da Saúde/métodos , Estilo de Vida Saudável , Obesidade/epidemiologia , Prevenção Primária/métodos , Adolescente , Criança , Exercício Físico , Família , Humanos , Itália/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Instituições Acadêmicas
12.
Food Funct ; 5(8): 1881-90, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24942553

RESUMO

BACKGROUND AND AIMS: Recent data suggest that n-3 PUFA exert beneficial effects on endothelial progenitor cell (EPC) biology. We sought to investigate whether these effects might be mediated by enhanced EPC in vitro function and/or in vivo bioavailability. METHODS AND RESULTS: CACs and late-outgrowth EPCs were isolated from peripheral blood mononuclear cells obtained from 12 donor buffy-coats. The effect of n-3 PUFA (EPA:DHA = 0.9:1.5; 9 µM EPA plus 15 µM DHA) was tested on CAC/EPC viability, function (tube-formation) and pro-inflammatory molecule expression. Circulating EPC (cells positive for CD34, CD133 and kinase insert domain receptor - KDR cell-surface antigens by flow cytometry) number was evaluated in 20 healthy subjects (10 F/10 M, 32 ± 5 years), randomized to receive 4 mackerel or sardine portions per week for 6 weeks followed by a 6 week free-diet period. N-3 PUFA improved CAC and late-outgrowth EPC viability (p < 0.05) and the capacity to form tube-like structures in CACs (+38%; p < 0.05) and late-outgrowth EPCs (+15%; p < 0.05). ICAM-1 expression was reduced in both CACs (p < 0.05) and late-outgrowth EPCs (p < 0.05) and VCAM-1 in late-outgrowth EPCs (p < 0.005). N-3 PUFA significantly decreased TNF-α and MCP-1 expression in CACs and IL-8, TNF-α and MCP-1 in late-outgrowth EPCs (p < 0.05). Circulating EPC number significantly improved after 6 weeks of a fish-enriched diet (p < 0.01) and returned to baseline levels after a 6 week free-diet period (p < 0.01). Plasma EPA levels were independently and positively associated with EPC levels (p < 0.005). CONCLUSION: Our findings support the case of a beneficiary role played by n-3 PUFA in EPC function and bioavailability.


Assuntos
Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/sangue , Células Progenitoras Endoteliais/efeitos dos fármacos , Adulto , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Células Progenitoras Endoteliais/metabolismo , Feminino , Peixes , Humanos , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Leucócitos Mononucleares/metabolismo , Masculino , NF-kappa B/genética , NF-kappa B/metabolismo , Alimentos Marinhos , Fator de Necrose Tumoral alfa/metabolismo , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
13.
J Investig Med ; 62(6): 856-64, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24945081

RESUMO

The combination of risk stratification by assessment of conventional risk factors for cardiovascular disease (CVD) with not only a morphological assessment of vascular damage (such as carotid ultrasound examination) but also vascular function tests may be a useful strategy for the management of CVD and its related risk factors. Endothelial dysfunction is present in a great variety of pathological conditions: it is considered the first alteration of vascular function in atherosclerosis and one of the phenomena involved in the progression of heart failure. Assessing endothelial function with noninvasive methods could have a central role for evaluation of treatment, prognostic stratification, and pharmacological studies in CVD. In this review, we focus on noninvasive techniques that have recently become available to assess endothelial function and express the possible clinical role in different clinical settings.


Assuntos
Endotélio Vascular/fisiologia , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Animais , Artérias/fisiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Humanos , Manometria/tendências , Microcirculação/fisiologia
14.
Artigo em Inglês | MEDLINE | ID: mdl-24915974

RESUMO

The activation and aggregation of platelets at sites of vascular injury or near to implanted stent are pivotal in the development of thrombotic events during and after an acute coronary syndrome (ACS) or a percutaneous coronary intervention (PCI). For that reason, an exclusively oral dual antiplatelet treatment regimen with platelet P2Y12 receptor antagonists in addition to the cyclooxygenase inhibitor aspirin has become the cornerstone of treatment in that contest. However, every trial underlines the same problem: if maximizing antiplatelet therapy significantly attenuates ischemic events in patients with coronary artery disease, on the other side it may also increase bleeding phenomena. These limitations have prompted a search for novel antiplatelet agents with a more favorable risk-benefit ratio. Moreover, an early onset of action is desirable during PCI and an early offset after bleeding events. Two novel antiplatelet agents, Cangrelor and Elinogrel, are available in intravenous form (Elinogrel also in oral form) and expand this context. Recent trials have tested them against Clopidogrel regarding efficacy and safety outcomes.This review aimed at providing an overview on intravenous emerging compounds and recent patents in the setting of ACS and PCI.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Monofosfato de Adenosina/análogos & derivados , Quinazolinonas/uso terapêutico , Sulfonamidas/uso terapêutico , Síndrome Coronariana Aguda/fisiopatologia , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/farmacologia , Monofosfato de Adenosina/uso terapêutico , Hemorragia/induzido quimicamente , Humanos , Patentes como Assunto , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/farmacologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Quinazolinonas/efeitos adversos , Quinazolinonas/farmacologia , Sulfonamidas/efeitos adversos , Sulfonamidas/farmacologia
16.
J Clin Hypertens (Greenwich) ; 16(3): 202-6, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24708382

RESUMO

Arterial stiffness and endothelial dysfunction are important determinants of cardiovascular events in patients with arterial hypertension. There are few data regarding the role of aliskiren on the central hemodynamics and endothelial function in patients with uncontrolled arterial hypertension. The aim of this study was to assess the addition of aliskiren to other antihypertensive drug treatment for arterial stiffness and endothelial function. Thirty uncontrolled hypertensive patients (mean age, 60.4±12.2 years), without any other cardiovascular risk factors, were enrolled. Augmentation index (AIx) and carotid-femoral pulse wave velocity (cfPWV) by applanation tonometry and reactive hyperemia peripheral arterial tonometry (RH PAT) index using peripheral arterious tonometry at baseline and after 6 months of aliskiren titrated to 300 mg once a day was evaluated. The addition of aliskiren had no effect on values of central AIx (33.26±10.74% vs 28.86±10.74%; P=.36) but did significantly improve values of cfPWV (9.36±2.65 m/s vs 8.72±2.48 m/s; P=.04) and RH PAT index (1.64±0.57 vs 1.75±0.45; P=.05). In addition to improving systolic and diastolic blood pressure, the addition of aliskiren to concomitant antihypertensive drugs in uncontrolled hypertensive patients may be effective in improving aortic stiffness and endothelial function. These results encourage further studies to evaluate the use of aliskiren for cardiovascular prevention.


Assuntos
Amidas/farmacologia , Amidas/uso terapêutico , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Endotélio Vascular/efeitos dos fármacos , Fumaratos/farmacologia , Fumaratos/uso terapêutico , Hipertensão/tratamento farmacológico , Rigidez Vascular/efeitos dos fármacos , Idoso , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Índice de Massa Corporal , Quimioterapia Combinada , Endotélio Vascular/fisiologia , Feminino , Hemodinâmica/efeitos dos fármacos , Hemodinâmica/fisiologia , Humanos , Hipertensão/fisiopatologia , Masculino , Manometria , Pessoa de Meia-Idade , Análise de Onda de Pulso , Renina/antagonistas & inibidores , Renina/efeitos dos fármacos , Resultado do Tratamento , Rigidez Vascular/fisiologia
17.
Int J Cardiol Heart Vessel ; 3: 6-14, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29450163

RESUMO

Aldosterone is involved in various deleterious effects on the cardiovascular system, including sodium and fluid retention, myocardial fibrosis, vascular stiffening, endothelial dysfunction, catecholamine release and stimulation of cardiac arrhythmias. Therefore, aldosterone receptor blockade may have several potential benefits in patients with cardiovascular disease. Mineralocorticoid receptor antagonists (MRAs) have been shown to prevent many of the maladaptive effects of aldosterone, in particular among patients with heart failure (HF). Randomized controlled trials have demonstrated efficacy of MRA in heart failure with reduced ejection fraction, both in patients with NYHA functional classes III and IV and in asymptomatic and mildly symptomatic patients (NYHA classes I and II). Recent data in patients with heart failure with preserved ejection fraction are encouraging. MRA could also have anti-arrhythmic effects on atrial and ventricular arrhythmias and may be helpful in patient ischemic heart disease through prevention of myocardial fibrosis and vascular damage. This article aims to discuss the pathophysiological effects of aldosterone in patients with cardiovascular disease and to review the current data that support the use of MRA in heart failure.

18.
Heart Lung Circ ; 23(2): 114-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23972720

RESUMO

INTRODUCTION: Elastic properties of the aorta represent an important determinant of left ventricular function and coronary blood flow but there are few data about aortic stiffness in patients with X syndrome. AIM: To investigate the elastic aortic proprieties (aortic stiffness and distensibility) and arterial wall motion velocities as measured by tissue Doppler imaging (TDI) in patients with cardiac X syndrome. MATERIALS AND METHODS: Fifteen patients with X syndrome (typical chest pain and angiographically normal coronary arteries associated with a positive exercise test) were enrolled in the study. The control group consisted of 15 healthy patients. The aortic elastic indexes, namely distensibility (cm(2) dyne(-1)) and stiffness index (ß index) were calculated from M-mode echocardiographically-derived thoracic aortic diameters using accepted formulae, and TDI parameters were measured on the wall of the ascending aorta 3 cm above the aortic valve. Anterior wall aortic expansion velocity (S), early (E) and late (A) diastolic retraction velocity and peak systolic strain were determined. RESULTS: Aortic elastic proprieties were more impaired in the syndrome X group than in the control group. Aortic distensibility was significantly lower in the syndrome X group (3.2 ± 1.3 vs. 7.95 ± 4 cm(2) dyne(-1), p<0.001), while stiffness index was higher (7.3 ± 2.1 vs. 4.1 ± 1.6, p<0.001) than in the control group. Peak systolic (S) and diastolic waves (E and A waves) of the aortic wall TDI were similar in patients and controls (S wave: 5.7 ± 1.6 cm/s vs. 5.8 ± 1.6 cm/s, E wave: -4.8 ± 2.0 vs. -4.1 ± 2.0 cm/s; A wave: -4.32 ± 2.1 vs. -4.76 ± 1.8 cm/s) while tissue strain of the aortic wall was lower in patients with X syndrome than controls (-12.80 ± 7% vs. -22.3 ± 5.9%, p<0.00001). CONCLUSION: Deterioration in aortic elasticity properties in patients with cardiac syndrome X suggests that this disease may be a more generalised disturbance of the vasculature.


Assuntos
Ecocardiografia Doppler em Cores , Elasticidade , Síndrome Metabólica , Rigidez Vascular , Adulto , Idoso , Feminino , Humanos , Masculino , Síndrome Metabólica/diagnóstico por imagem , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade
19.
Am J Med Sci ; 347(4): 271-6, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24196866

RESUMO

BACKGROUND: The purpose of this study is to evaluate long-term effects of spironolactone, an affordable and widely used aldosterone receptor blocker, in patients with heart failure (HF) and mild or no symptoms. METHODS: The study is a single-blind, placebo-controlled, blinded endpoint, randomized study. Patients with New York Heart Association (NYHA) classes I to II HF and left ventricular ejection fraction < 40% were randomized to spironolactone or placebo in addition to optimal therapy. The primary endpoint was the composite of death from any cause or cardiovascular hospitalization. RESULTS: A total of 130 patients were randomized to spironolactone (n = 65) or placebo (n = 65). Patients on spironolactone had a better event-free survival for cardiovascular death or cardiovascular hospitalizations and for cardiovascular hospitalizations alone. At multivariable analysis, only spironolactone therapy, left ventricular ejection fraction and serum creatinine levels had an independent prognostic value for the combined endpoint, whereas only spironolactone therapy and serum creatinine levels had an independent prognostic value for cardiovascular hospitalizations alone. CONCLUSIONS: Administration of spironolactone reduced the composite of death and cardiovascular hospitalization in patients with NYHA classes I to II HF. These results suggest that spironolactone could be beneficial when administered on top of optimal therapy among patients with HF and mild or no symptoms.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Espironolactona/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Creatinina/sangue , Intervalo Livre de Doença , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Prognóstico , Método Simples-Cego , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos
20.
G Ital Cardiol (Rome) ; 13(10 Suppl 2): 50S-54S, 2012 Oct.
Artigo em Italiano | MEDLINE | ID: mdl-23096376

RESUMO

Major steps have been made in the treatment of ischemic heart disease from the discovery of nitrates as antianginal medication to the techniques of percutaneous angioplasty. This incredible therapeutic progress has resulted in a reduced incidence of ischemic heart disease and related mortality and morbidity. However, statistical and epidemiological data indicate that in ischemic heart disease, despite the achievement of great success, there is a necessity for a further step toward treatment, considering the fact that the characteristics of this population are changing (increased prevalence of subendocardial infarction compared with classic transmural infarction, especially in the elderly population). Furthermore, the need for alternative therapeutic approaches to traditional ones is recognized. Ranolazine is a selective inhibitor of Na channels that prevents pathological extension of late Na current developing in the ischemic myocardial cell. This current is responsible for calcium overload, with consequent impairment of diastolic relaxation. Ranolazine reduces Na overload induced by calcium and improves diastolic relaxation and coronary subendocardial flow, without affecting hemodynamic parameters such as blood pressure, heart rate, or inotropic state of the heart, avoiding undesirable side effects. Efficacy of ranolazine has been evaluated in several trials, using clinical and instrumental endpoints (MARISA and CARISA) or, more recently, using endpoints such as mortality and reinfarction (ERICA and MERLIN-TIMI 36). Ivabradine acts through the inhibition of late Na current (also known as If), which controls the spontaneous diastolic depolarization of sinus node cells. The partial inhibition of these channels reduces the frequency of sinus node action potential initiation, resulting in decreased heart rate without effects on contractility, atrio-ventricular conduction, or repolarization. The BEAUTIFUL trial has tested whether the effect of ivabradine in lowering heart rate is able to reduce mortality and cardiovascular morbidity in patients with coronary artery disease and left ventricular systolic dysfunction. The most significant results were obtained in the subgroup of patients with life-limiting exertional angina. In this group, ivabradine significantly reduced the primary endpoint, a composite of cardiovascular death, hospitalization for fatal and nonfatal acute myocardial infarction (AMI) or heart failure, by 24%, and hospitalizations for AMI by 42%. In the subgroup of patients with baseline heart rate >70 bpm, hospitalizations for AMI and revascularization were reduced by 73% and 59%, respectively.


Assuntos
Acetanilidas/uso terapêutico , Benzazepinas/uso terapêutico , Isquemia Miocárdica/tratamento farmacológico , Piperazinas/uso terapêutico , Humanos , Ivabradina , Ranolazina
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