8-Hydroxy-2-deoxyguanosine levels and heart failure: A systematic review and meta-analysis of the literature.

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.

In vivo prostacyclin biosynthesis and effects of different aspirin regimens in patients with essential thrombocythaemia.

Essential thrombocythaemia (ET) is characterised by enhanced platelet generation and thrombosis. Once daily (od) aspirin incompletely inhibits platelet thromboxane (TX)A2 production in ET. A twice daily (bid) dosing is necessary to fully inhibit TXA2. Whether this dosing regimen affects in vivo prostacyclin (PGI2) biosynthesis is unknown. PGI2 biosynthesis was characterised in 50 ET patients on enteric-coated (EC) aspirin 100 mg od, by measuring its urinary metabolite, 2,3-dinor-6-keto-PGF1α (PGI-M). Moreover, in a crossover study 22 patients poorly responsive to standard aspirin based on serum TXB2 levels (≥4 ng/ml) were randomised to different seven-day aspirin regimens: EC aspirin 100 mg od, 100 mg bid, 200 mg od, or plain aspirin 100 mg od. PGI-M measured 24 hours after the last aspirin intake (EC, 100 mg od) was similar in patients and healthy subjects both on (n=10) and off (n=30) aspirin. PGI-M was unrelated to in vivo TXA2 biosynthesis, and not affected by EC aspirin 100 mg bid or 200 mg od as compared to EC 100 mg od. PGI2 biosynthesis in aspirin-treated ET patients appears unrelated to TXA2 biosynthesis, and not affected by an improved aspirin regimen, demonstrating its vascular safety for future trials.

Effects of smoking regular or light cigarettes on brachial artery flow-mediated dilation.

BACKGROUND AND PURPOSE: To compare the effects of regular cigarettes (RCs) and light cigarettes (LCs) on brachial artery flow-mediated dilation (FMD) and sublingual glyceryl trinitrate-induced dilation (GTN), markers of endothelial dependant and independent function, respectively. METHODS: 206 subjects (age 51.5 ± 12.8 yr, 122 men) had their smoking habits recorded and FMD and GTN measured by B-mode ultrasound. Cigarettes were categorized as RCs or LCs according to their content of tar, nicotine and CO. The chronic effect was assessed in current smokers of RCs (n = 85) or LCs (n = 53) and in never smokers (NS; n = 68). The acute effect was assessed in current smokers by measuring FMD before and 10-min after smoking a single regular (n = 29) or light (n = 51) cigarette. RESULTS: FMD was significantly lower in consumers of RCs (6.26%, 95% C.I. 5.58, 6.94) or LCs (5.59%, 95% C.I. 4.74, 6.45) compared to NS (8.68%, 95% C.I. 7.92, 9.44) (both P < 0.0001), but did not differ (P > 0.05) when compared to each other. GTN was similar in the three groups. Analyses adjusted for clinical confounders and for markers involved in oxidative stress, arginine/nitric oxide pathway, and inflammation provided identical results. Smoking a single cigarette, either regular or light, reduced FMD (-0.88% and -1.17%, respectively, both P < 0.05), without significant difference between cigarette type. RCs and LCs produced analogous chronic and acute effects when FMD was calculated with respect to the last 60 s of the low-flow phase (FMD60s). CONCLUSIONS: LCs impair endothelial-dependant vasodilation as much as RCs. Thus, smoking LCs cannot be considered an alternative to the only safe choice of a complete and permanent smoking cessation.

Glutathione, vitamin E and oxidative stress in coronary artery disease: relevance of age and gender.

BACKGROUND: Observational studies suggest that low levels of antioxidants are associated with high risk for coronary artery disease (CAD). We investigated whether the biomarkers of oxidative balance undergo the same modifications in all CAD patient groups, regardless of gender and age. MATERIALS AND METHODS: One hundred sixty-eight CAD patients and 107 healthy controls were assayed for plasma levels of reduced glutathione (GSH), alpha- and gamma-tocopherol (alpha- and gamma-T) as endogenous antioxidants. A damage score (DS), representative of oxidative stress status, was calculated. ANCOVA models were used to test the association between antioxidants, DS and CAD and its modulation by age and gender. RESULTS: The DS was higher in CAD than in controls. GSH levels, were lower in CAD patients (mean +/- SEM: 57.61 +/- 1.87 micromol 10 g(-1) haemoglobin vs. 68.55 +/- 2.23 in controls, P < 0.0006) in males and in older subjects. Levels of other antioxidants exhibited a complex pattern. Overall, no difference was found in alpha- and gamma-T contents between CAD and controls, but lower alpha-T values were observed in CAD females. A significant interaction between CAD status and gender was observed (P = 0.003). CONCLUSIONS: Our study shows that the involvement of antioxidants in CAD is related to patients' characteristics. These findings may be relevant in planning antioxidant therapies.