Publications (12) View all
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Article: Do calcium channel blockers increase the diagnosis of heart failure in patients with hypertension?
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ABSTRACT: Calcium channel blockers (CCBs) are widely used to control hypertension. Previous work suggested that their use could increase heart failure (HF), which is 1 of the consequences of uncontrolled hypertension. Information about the effect of CCBs on incident HF in patients with hypertension is scarce. A systematic review was conducted to evaluate patients with hypertension treated with CCBs and incident HF. An electronic search of publications was conducted using 8 major databases. Studies were eligible if they (1) were randomized clinical trials, (2) performed comparisons of CCBs versus active control, (3) randomized >200 patients, (4) had follow-up periods >6 months, and (5) provided data regarding incident HF. Trials of renal transplantation patients, placebo-controlled trials, and HF trials were excluded. A total of 156,766 patients were randomized to CCBs or control, with a total of 5,049 events. The analysis indicated a significant increase in the diagnosis of HF in patients allocated to CCBs (odds ratio 1.18, 95% confidence interval 1.07 to 1.31). The effect observed was independent of incident myocardial infarction. Subgroup analyses indicated that patients with diabetes were at higher risk for developing HF (odds ratio 1.71, 95% confidence interval 1.21 to 2.41). In conclusion, the results suggest that patients with hypertension treated with CCBs have increased incident HF.The American journal of cardiology 07/2010; 106(2):228-35. · 3.58 Impact Factor -
Article: Activation and modulation of 72kDa matrix metalloproteinase-2 by peroxynitrite and glutathione.
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ABSTRACT: Matrix metalloproteinase-2 (MMP-2) has emerged as a key protease in various pathologies associated with oxidative stress, including myocardial ischemia-reperfusion, heart failure or inflammation. Peroxynitrite (ONOO(-)), an important effector of oxidative stress, was reported to activate some full length MMP zymogens, particularly in the presence of glutathione (GSH), but whether this occurs for MMP-2 is unknown. Treating MMP-2 zymogen with ONOO(-) resulted in a concentration-dependent regulation of MMP-2, with 0.3-1 microM ONOO(-) increasing and 30-100 microM ONOO(-) attenuating enzyme activity. The enzyme's V(max) was also significantly increased by 1 microM ONOO(-). Comparable responses to ONOO(-) treatment were observed using the intracellular target of MMP-2, troponin I (TnI). GSH at 100 microM attenuated the effects of ONOO(-) on MMP-2. Mass spectrometry revealed that ONOO(-) can oxidize and, in the presence of GSH, S-glutathiolate the MMP-2 zymogen or a synthetic peptide containing the cysteine-switch motif in the enzyme's autoinhibitory domain. These results suggest that ONOO(-) and GSH can modulate the activity of 72 kDa MMP-2 by modifying the cysteine residue in the autoinhibitory domain of the zymogen, a process that may be relevant to pathophysiological conditions associated with increased oxidative stress.Biochemical pharmacology 12/2008; 77(5):826-34. · 4.25 Impact Factor -
Article: Effect of fish oil on arrhythmias and mortality: systematic review.
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ABSTRACT: To synthesise the literature on the effects of fish oil-docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)-on mortality and arrhythmias and to explore dose response and formulation effects. Systematic review and meta-analysis. Medline, Embase, the Cochrane Library, PubMed, CINAHL, IPA, Web of Science, Scopus, Pascal, Allied and Complementary Medicine, Academic OneFile, ProQuest Dissertations and Theses, Evidence-Based Complementary Medicine, and LILACS. Studies reviewed Randomised controlled trials of fish oil as dietary supplements in humans. The primary outcomes of interest were the arrhythmic end points of appropriate implantable cardiac defibrillator intervention and sudden cardiac death. The secondary outcomes were all cause mortality and death from cardiac causes. Subgroup analyses included the effect of formulations of EPA and DHA on death from cardiac causes and effects of fish oil in patients with coronary artery disease or myocardial infarction. 12 studies totalling 32 779 patients met the inclusion criteria. A neutral effect was reported in three studies (n=1148) for appropriate implantable cardiac defibrillator intervention (odds ratio 0.90, 95% confidence interval 0.55 to 1.46) and in six studies (n=31 111) for sudden cardiac death (0.81, 0.52 to 1.25). 11 studies (n=32 439 and n=32 519) provided data on the effects of fish oil on all cause mortality (0.92, 0.82 to 1.03) and a reduction in deaths from cardiac causes (0.80, 0.69 to 0.92). The dose-response relation for DHA and EPA on reduction in deaths from cardiac causes was not significant. Fish oil supplementation was associated with a significant reduction in deaths from cardiac causes but had no effect on arrhythmias or all cause mortality. Evidence to recommend an optimal formulation of EPA or DHA to reduce these outcomes is insufficient. Fish oils are a heterogeneous product, and the optimal formulations for DHA and EPA remain unclear.BMJ (Clinical research ed.). 02/2008; 337:a2931. -
Chapter: Turmoil in the Cardiac Myocyte: Acute Intracellular Activation of Matrix Metalloproteinases
12/2004: pages 213-237; -
Article: Cardiovascular autonomic function testing in asymptomatic T. cruzi carriers: a sensitive method to identify subclinical Chagas' disease.
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ABSTRACT: Although impaired cardio-vagal response characterizes full-blown Chagas' disease, this feature among otherwise healthy T. cruzi serology carriers (SERO[+]) requires confirmation. The purpose of this study was to determine whether abnormal cardio-vagal responses were different among SERO[+] subjects with varying ECG alterations. We assessed cardio-vagal reflex response in 57 randomly selected healthy blood donors (36 SERO[+], 15 with ECG rhythm/conduction abnormalities). The following cardiac autonomic tests were performed: (1) short-term heart rate variability (HRV), (2) Deep breathing test (DBT), (3) cold face test, (4) cold pressor test (CPT), (5) Valsalva maneuver, and (6) baroreflex sensitivity after administration of nitroprusside (BRS-NTP) and phenylephrine (BRS-PNP). Overall, SERO[+] subjects had 161/324 (49.7%) abnormal responses, compared to 41/189 (21.7%) in SERO[-] (p<0.001). Similar rates were found in SERO[+] according to ECG status (68/135, 50.4% in ECG[+] and 93/189, 49.2% in ECG[-], p=0.836). Covariate-adjusted pooled odd ratios (95%CI) for abnormal responses compared to SERO[-] were: 2.73 (1.71-4.35) for SERO[+], and 2.63 (1.63-4.34) for SERO[+]/ECG[-] (p<0.001). BRS-NTP, CPT and DBT individually showed significant differences between SERO[-] and SERO[+] groups. Conversely, ECG changes among SERO[+] were not associated with a significant excess of autonomic abnormality either overall (OR=1.09, 95%CI: 0.67-1.78, p=0.719) or by any individual test. Early cardio-vagal dysfunction was documented in SERO[+] subjects regardless of ECG status. Cardiac autonomic evaluation may be useful for identification of subclinical disease in SERO[+] subjects.International Journal of Cardiology 02/2004; 93(2-3):189-95. · 7.08 Impact Factor
