RESUMEN
BACKGROUND AND AIMS: The generation of reactive oxygen species (ROS) plays an important role in the etiology of several pathological conditions. High levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), a biomarker of oxidative damage of DNA, have been found in patients with heart failure (HF). We performed a meta-analysis of the literature to investigate the association between 8-OHdG levels and HF. METHODS AND RESULTS: A systematic search was performed in the PubMed, Web of Science, Scopus, EMBASE databases and studies evaluating 8-OHdG levels in HF patients and controls were included. Differences between cases and controls were expressed as standard mean difference (SMD) or mean difference (MD) with pertinent 95% confidence intervals (95%CI). Impact of clinical and demographic features on effect size was assessed by meta-regression. Six studies (446 HF patients and 140 controls) were included in the analysis. We found that HF patients showed higher 8-OHdG levels than controls (SMD:0.89, 95%CI: 0.68, 1.10). The difference was confirmed both in studies in which 8-OHdG levels were assessed in urine (MD:6.28 ng/mg creatinine, 95%CI: 4.01, 8.56) and in blood samples (MD:0.36 ng/ml, 95%CI: 0.04, 0.69). Interestingly, 8-OHdG levels progressively increased for increasing New York Heart Association (NYHA) class. Meta-regression models showed that none of clinical and demographic variables impacted on the difference in 8-OHdG levels among HF patients and controls. CONCLUSIONS: 8-OHdG levels are higher in HF patients HF than in controls, with a progressive increase for increasing NYHA class. However, larger prospective studies are needed to test 8-OHdG as a biomarker of HF severity and progression.
Asunto(s)
Daño del ADN , Desoxiguanosina/análogos & derivados , Insuficiencia Cardíaca/metabolismo , Miocardio/metabolismo , Estrés Oxidativo , 8-Hidroxi-2'-Desoxicoguanosina , Biomarcadores/metabolismo , Distribución de Chi-Cuadrado , Desoxiguanosina/metabolismo , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/fisiopatología , Humanos , Valor Predictivo de las Pruebas , Pronóstico , Factores de Riesgo , Índice de Severidad de la Enfermedad , Volumen Sistólico , Regulación hacia Arriba , Función Ventricular IzquierdaRESUMEN
On-pump cardiac surgery may trigger inflammation and accelerate platelet cyclooxygenase-1 renewal, thereby modifying low-dose aspirin pharmacodynamics. Thirty-seven patients on standard aspirin 100 mg once-daily were studied before surgery and randomized within 36 hours postsurgery to 100 mg once-daily, 100 mg twice-daily, or 200 mg once-daily for 90 days. On day 7 postsurgery, immature and mature platelets, platelet mass, thrombopoietin, glycocalicin, leukocytes, C-reactive protein, and interleukin-6 significantly increased. Interleukin-6 significantly correlated with immature platelets. At day 7, patients randomized to 100 mg once-daily showed a significant increase in serum thromboxane (TX)B2 within the 24-hour dosing interval and urinary TXA2 metabolite (TXM) excretion. Aspirin 100 mg twice-daily lowered serum TXB2 and prevented postsurgery TXM increase (P < 0.01), without affecting prostacyclin metabolite excretion. After cardiac surgery, shortening the dosing interval, but not doubling the once-daily dose, rescues the impaired antiplatelet effect of low-dose aspirin and prevents platelet activation associated with acute inflammation and enhanced platelet turnover.