A view from Reykjavik.
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Biomedical subjects
Publications and source records attributed to Karl Andersen.
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OBJECTIVE: Supervised cardiac rehabilitation programs have been offered to patients following myocardial infarct (MI), coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) for many years. However, limited information is available on the usefulness of rehabilitation programs in chronic heart failure (CHF). The aim of our study was to evaluate the outcome of supervised physical training on CHF patients by measuring both central and peripheral factors. MATERIAL AND METHODS: This was a prospective randomized study, including 43 patients with CHF, New York Heart Association (NYHA) class II or III, mean age 68 years. After initial measurements of V02peak, 6 minute walk distance, muscle strength, plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), echocardiogram, measurements of pulmonary function and quality of life questionnaire, patients were randomized to either a training group (n=21) or a control group (n=22). The training group had supervised aerobic and resistance training program twice a week for five months. After the training program was completed, all measurements were repeated in both groups. RESULTS: No training related adverse events were reported. Significant improvement was found between groups in the six minute walk test (+37.1 m vs. +5.3 m, p=0.01), work load on the bicycle exercise test (+6.1W vs. +2.1 W, p=0.03), time on the bicycle exercise test (+41 s vs +0 s, p=0.02) and quadriceps muscle strength test (+2.8 kg vs +0.2 kg, 0.003). Quality of life factors that reflect exercise tolerance and general health, improved significantly in the training group compared to the control group. No other significant changes were found between the two groups. CONCLUSION: Supervised physical training as used in this study appears safe for CHF patients in NYHA class II or III. The improvement in functional capacity observed in the training group seems to be related more to increased muscle performance rather than central cardiovascular conditioning.
CONTEXT: Myocardial infarction (MI) is the leading cause of death in the world. Variants in the 5-lipoxygenase-activating protein (FLAP) gene are associated with risk of MI. OBJECTIVE: To determine the effect of an inhibitor of FLAP on levels of biomarkers associated with MI risk. DESIGN, SETTING, AND PATIENTS: A randomized, prospective, placebo-controlled, crossover trial of an inhibitor of FLAP (DG-031) in MI patients who carry at-risk variants in the FLAP gene or in the leukotriene A4 hydrolase gene. Of 268 patients screened, 191 were carriers of at-risk variants in FLAP (87%) or leukotriene A4 hydrolase (13%). Individuals were enrolled in April 2004 and were followed up by designated cardiologists from a university hospital in Iceland until September 2004. INTERVENTIONS: Patients were first randomized to receive 250 mg/d of DG-031, 500 mg/d of DG-031, 750 mg/d of DG-031, or placebo. After a 2-week washout period, patients received DG-031 if they had received placebo first or placebo if they had received DG-031 first. Treatment periods lasted for 4 weeks. MAIN OUTCOME MEASURES: Changes in levels of biomarkers associated with risk of MI. RESULTS: In response to 750 mg/d of DG-031, production of leukotriene B4 was significantly reduced by 26% (95% confidence interval [CI], 10%-39%; P = .003) and myeloperoxidase was significantly reduced by 12% (95% CI, 2%-21%; P = .02). The higher 2 doses of DG-031 produced a nonsignificant reduction in C-reactive protein (16%; 95% CI, -2% to 31%; P = .07) at 2 weeks. However, there was a more pronounced reduction (25%; 95% CI, 5%-40%; P = .02) in C-reactive protein at the end of the washout period that persisted for another 4 weeks thereafter. The FLAP inhibitor DG-031 was well tolerated and was not associated with any serious adverse events. CONCLUSION: In patients with specific at-risk variants of 2 genes in the leukotriene pathway, DG-031 led to significant and dose-dependent suppression of biomarkers that are associated with increased risk of MI events.
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