Transient enhancement of oxidant stress and collagen turnover in patients with acute worsening of congestive heart failure.

BACKGROUND: Myocardial remodeling is a crucial step for progression of heart failure (HF). Free radical generation by the failing myocardium has been proposed as linked to myocardial remodeling. The aim of this study was to evaluate the urinary excretion of 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), a reliable marker for oxidant stress in vivo, and collagen turnover in patients with acute worsening of congestive HF. METHODS AND RESULTS: Enrolled were 43 patients with acute worsening of congestive HF of various etiologies. On admission (acute phase) and after approximately 2 weeks of conventional treatment (chronic phase), the following were measured: (1) immunoreactive urinary 8-iso-PGF2alpha, (2) serum total antioxidant status (TAS); and (3) serum levels of procollagen type I carboxyterminal peptide (PIP) and carboxyterminal collagen type I telopeptide (CITP), biochemical markers for collagen synthesis and degradation, respectively. From the acute to the chronic phase the parameters changed as follows: 335.1+/-245.4 to 205.3+/-107.4 pg/mg creatinine for urinary 8-iso-PGF2alpha (p<0.0001); 0.92+/-0.16 to 0.98+/-0.13 mmol/L for TAS (p<0.01); 171.4+/-72.5 to 93.7+/-33.9 ng/ml for PIP (p<0.0001); and 7.2+/-3.6 to 12.6+/-8.4 ng/ml for CITP (p<0.0001). CONCLUSIONS: Acute worsening of congestive HF promotes free radical generation and collagen synthesis.

A Single-Center, Open-Label, Randomized, Parallel-Group Study Assessing the Differences Between an Angiotensin II Receptor Antagonist and an Angiotensin-Converting Enzyme Inhibitor in Hypertensive Patients with Congestive Heart Failure: The Research for Efficacy of Angiotensin II Receptor Antagonist in Hypertensive Patients with Congestive Heart Failure Study.

BACKGROUND: Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) have been used to treat congestive heart failure (CHF). According to a MEDLINE search, however, few studies are available on the clinical differences between ARBs and ACEIs in CHF. OBJECTIVE: To examine the clinical differences between an ARB (candesartan cilexetil) and an ACEI (lisinopril) in the treatment of CHF, we investigated exercise capacity, ventricular function, and neurohormonal levels in hypertensive patients with CHF before and after treatment with these agents. METHODS: Patients with symptoms of CHF (New York Heart Association functional class II-III and left ventricular ejection fraction [LVEF] ≤45%) complicated by hypertension (systolic blood pressure [BP] ≥140 mm Hg or diastolic BP ≥90 mm Hg) were eligible for this single-center, open-label, randomized, parallel-group study. They were given either the ARB or the ACEI for 24 weeks. A cardiopulmonary exercise test and echocardiography were performed. Clinical findings and cardiac events in addition to the CHF symptoms were investigated. Neurohormonal levels were measured before and after 24 weeks of treatment with the study drug. The primary end point of this study was exercise capacity, which was measured using peak oxygen consumption (VO2). RESULTS: Forty-two patients with CHF were enrolled and 38 (28 men, 10 women; mean [SD] age, 69.0 [8.2] years) completed the study. None of these patients had definite progression of the CHF symptoms. In the ARB-treated patients, mean (SD) peak VO2 (mL/min/kg) and LVEF (%) increased from 14.1 (2.9) to 15.3 (3.4) and from 34.4 (9.5) to 41.8 (9.5), respectively. In the ACEI group, the peak VO2 did not change, but the LVEF (%) increased from 34.2 (10.2) to 40.4 (13.0). However, the differences between ARB and ACEI were not clarified because of the possibility of a small sample size. CONCLUSIONS: Although this study was not powered to show differences in efficacy between the ARB and ACEI in this study, our findings suggest that both ARB and ACEI had beneficial effects in hypertensive patients with CHF. Some unidentified differences in hemodynamic characteristics were found between the ARB and the ACEI groups.