Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Characteristics of Japanese Patients with Complex Sleep Apnea Syndrome: A Retrospective Comparison with Obstructive Sleep Apnea Syndrome

Objective The prevalence of complex sleep apnea syndrome (CompSAS) among Asian patients with obstructive sleep apnea syndrome (OSAS) has not yet been reported. Distinguishing CompSAS from pure OSAS is difficult using only diagnostic polysomnography (PSG). We examined the prevalence of CompSAS in Japanese patients with OSAS and the possibility to distinguish CompSAS from pure OSAS by analyzing the severity of respiratory events based on either sleep body position or sleep stage using a diagnostic PSG. Patients and Methods A retrospective chart review of 297 consecutive Japanese patients who were 15 years of age or older with a primary diagnosis of OSAS who were referred for CPAP titration (AHI. 20 events/hr). Results Seventeen patients (5.7%) out of the 297 patients who had an obstructive apnea hypopnea index (AHI) of 20 or higher showed adverse increases in central apnea index (CAI) by the treatment with CPAP whereas obstructive apnea index (OAI) and mixed apnea index (MAI) were significantly decreased. In the results, the AHI on the PSG for CPAP titration reached only approximately half of the values on the diagnostic PSG. In these CompSAS patients, both the total CAI and the CAI in the supine position during NREM sleep on the diagnostic PSG were significantly higher than those in the OSAS group. The sleep body position did not so strongly affect the AHI, OAI and MAI in the CompSAS group. Multiple, stepwise, and logistic regression analyses revealed that the CAI in the supine position during NREM (p=0.026) was a significant variable to distinguish CompSAS from OSAS statistically although the variables were within the normal range. Conclusion The prevalence of CompSAS in Japanese OSAS patients may be lower when compared with Caucasian patients. The increase of CAI in the supine position during NREM sleep on diagnostic PSG may be a characteristic feature in CompSAS.ArticleINTERNAL MEDICINE. 48(6):427-432 (2009)journal articl

Environmental assessment of organic juice imported to Denmark: a case study on oranges (Citrus sinensis) from Brazil

Growing global trade with organic products has given rise to a debate on the environmental impacts during both production and transport. Environmental hotspots of organic orange juice produced by smallholders in Brazil, processed and imported to Denmark were identified in a case study using a life cycle approach. Furthermore, small-scale organic orange production was compared with small-scale conventional and large-scale organic orange production in the case study area in Brazil. Transport was the main contributor (57%) to the global warming potential of organic orange juice from small-scale farmers imported to Denmark, followed by the processing stage (29%), especially the truck transport of fresh oranges in Brazil and of reconstituted orange juice in Europe. Non-renewable energy use per hectare was significantly lower on the organic small-scale farms than on the conventional, with a similar, although not significantly lower, pattern for global warming potential and eutrophication. Including soil carbon sequestration in organic plantations widened the difference in global warming potential between organic and conventional. Organic small-scale farms had a higher crop diversity than conventional, which may have a positive effect on biodiversity along with the spontaneous vegetation between the organic orange trees and the absence of toxic pesticides. Comparing small-scale with large-scale organic orange production, crop diversity was higher on the small-scale farms, while global warming potential, eutrophication potential and the use of copper per hectare were significantly lower, indicating that environmental impacts from small-scale differ from large-scale organic farms