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1.
2.
Vasc Health Risk Manag ; 15: 539-550, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827327

RESUMO

Background: Left ventricular hypertrophy (LVH), as assessed by measurement of left ventricular mass (LVM), is one of the most important cardiovascular risk factors. It is commonly present in patients with ischemic heart disease (IHD), irrespective of the level of blood pressure; recently, oxidative stress has been shown to be an important factor in its development. The question then arises: can this risk factor be modified by antioxidant treatment (e.g., with allopurinol, a xanthine oxidase inhibitor)? Methods: This is an observational study with a cross-sectional design which explored the association between long-term (>12 months) allopurinol therapy and LV mass index (LVMI) as well as geometry in patients generally receiving standard treatments for IHD. The primary endpoint was LVMI measurement (by 2D-echocardiography) and secondary endpoints included the association of allopurinol use with LV function (ejection fraction), blood pressure, glycemic control, and lipid profile. Results: Ninety-six patients on standard anti-ischemic drug treatment (control group) and 96 patients who were additionally taking allopurinol (minimum dose 100 mg/day) were enrolled. Both groups were matched for age, sex, height, and co-morbidities, but poorer kidney function in the allopurinol group required further sub-group analysis based on renal function. Allopurinol treatment was associated with the lowest LVMI in the patients with normal serum creatinine (median LVMI; 70.5 g/m2): corresponding values were 76.0 and 87.0 in the control group with, respectively, normal and elevated serum creatinine, and 89.5 in the allopurinol group with elevated serum creatinine (P=0.027). In addition, allopurinol was associated with better glycemic control (HbA1c) with a difference of 0.8% (95% CI; 1.3, 0.2) (P=0.004) as compared with control patients. Conclusion: In our population, treatment with allopurinol (presumably because of its anti-oxidant properties) has shown a tendency to be associated with smaller LVM in IHD patients with normal serum creatinine, along with better glycemic control.


Assuntos
Alopurinol/uso terapêutico , Antioxidantes/uso terapêutico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Alopurinol/efeitos adversos , Antioxidantes/efeitos adversos , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Estudos de Casos e Controles , Creatinina/sangue , Estudos Transversais , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/sangue , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
3.
Int J Mol Sci ; 20(13)2019 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-31261886

RESUMO

Chronic heart failure (CHF) is a complex syndrome that results from structural and functional disturbances that affect the ability of the heart to supply oxygen to tissues. It largely affects and reduces the patient's quality of life, socio-economic status, and imposes great costs on health care systems worldwide. Endothelial dysfunction (ED) is a newly discovered phenomenon that contributes greatly to the pathophysiology of numerous cardiovascular conditions and commonly co-exists with chronic heart failure. However, the literature lacks clarity as to which heart failure patients might be affected, its significance in CHF patients, and its reversibility with pharmacological and non-pharmacological means. This review will emphasize all these points and summarize them for future researchers interested in vascular pathophysiology in this particular patient population. It will help to direct future studies for better characterization of these two phenomena for the potential discovery of therapeutic targets that might reduce future morbidity and mortality in this "at risk" population.


Assuntos
Endotélio Vascular/metabolismo , Insuficiência Cardíaca/fisiopatologia , Fármacos Cardiovasculares/uso terapêutico , Endotélio Vascular/fisiopatologia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Humanos , Vasodilatação , Vasodilatadores/uso terapêutico
4.
Clin Med Insights Cardiol ; 12: 1179546818779584, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29899669

RESUMO

Background: The xanthine oxidase inhibitor allopurinol improves endothelial function in different populations, including patients with chronic heart failure (CHF). Its effect on arterial stiffness parameters is less clear. We investigated the effect of short-term low-dose allopurinol therapy on arterial stiffness in Saudi patients with stable mild-moderate CHF. Methods: A prospective, randomized, double-blind, placebo-controlled study was performed on 73 patients with mild-moderate CHF. In all, 36 patients were randomized to allopurinol 300 mg daily for 3 months, while 37 patients were randomized to placebo. Arterial stiffness parameters, aortic pulse wave velocity (Ao-PWV) and heart rate corrected augmentation index (c-AIx), were assessed before and after treatment along with serum uric acid. Results: A total of 66 patients completed the study. Both groups were matched for age, sex, severity of heart failure, and arterial stiffness. Compared with placebo, allopurinol recipients had a significant fall in uric acid concentration from 6.31 ± 1.4 (SD) mg/dL to 3.81 ± 1.2 (P < .001). Despite that, there was no significant change in arterial stiffness parameters between allopurinol and placebo groups. Post-treatment Ao-PWV was 9.79 ± 2.6 m/s in the allopurinol group and 10.07 ± 3.4 m/s in the placebo group, P = .723. Post-treatment c-AIx was 24.0% ± 9.1% and 22.0% ± 9.9%, respectively, P = .403. Conclusions: We have shown that allopurinol significantly reduced uric acid concentration in Saudi patients with CHF but was not associated with a change in arterial stiffness. Our cohort of patients had worse arterial stiffness values at baseline, which might make them more resistant to change using our study regimen.The study has been registered with the International Standard Randomized Controlled Trial Number registry with an identifier number of ISRCTN58980230.

5.
Cardiovasc Ther ; 36(4): e12432, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29673103

RESUMO

AIM: Oxidative stress and endothelial dysfunction are two inter-related conditions commonly seen in patients with cardiovascular risk factors. The enzyme, xanthine oxidase, is an important contributor to these phenomena but to a variable degree in different patient populations. This meta-analysis will summarize the effect of allopurinol, an established xanthine oxidase inhibitor, on endothelial function among patients with different comorbidities. METHODS: Medline Complete, PubMed, ProQuest, ClinicalKey, Wiley Online Library, and Cochrane Central Register of Controlled Trials were searched till July 29, 2017. Meta-analysis was planned for randomized controlled trials (RCTs) that investigated allopurinol effects on endothelial function. A random effect model was used to calculate the standardized mean difference (with 95% confidence intervals: CI) as an estimate of effect size. Heterogeneity was quantified by four types of information: Q statistics, I2 statistic, Tau-squared (T2 ), and Tau (T). RESULTS: Thirty eligible studies were identified; 12 were included in the final analysis and subdivided among 3 patient's groups: patients with chronic heart failure (CHF; 197 patients), patients with chronic kidney disease (CKD; 183 patients), and patients with type 2 diabetes mellitus (DM; 170 patients). Allopurinol was found to have a statistically significant benefit on endothelial function in patients with CHF and CKD but not in type 2 DM. The standardized mean differences and CI in the three patient's groups were 0.776 (0.429, 1.122), 0.350 (0.009, 0.690), and 1.331 (-0.781, 3.444), respectively. CONCLUSION: Allopurinol has an antioxidant property that might partially reverse endothelial dysfunction in patients with certain comorbidities. The importance of this property and the magnitude of the beneficial effect are likely to be related to the relative contribution of xanthine oxidase into the oxidative stress associated with different underlying pathologies.


Assuntos
Alopurinol/uso terapêutico , Antioxidantes/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Inibidores Enzimáticos/uso terapêutico , Idoso , Alopurinol/efeitos adversos , Antioxidantes/efeitos adversos , Doenças Cardiovasculares/enzimologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Comorbidade , Endotélio Vascular/enzimologia , Endotélio Vascular/fisiopatologia , Inibidores Enzimáticos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Resultado do Tratamento , Xantina Oxidase/antagonistas & inibidores , Xantina Oxidase/metabolismo
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